Haemophilus

An Esp Pediatr, 2002 Nov, 57(5), 427 - 31
{Acute mastoiditis: an increasing entity}; Ruiz Diaz AI et al.; BACKGROUND: Mastoiditis used to be the most common complication of acute otitis media . However, once antibiotics became widely available, it was rarely reported . Recently, this complication has become more frequent . OBJECTIVES: To determine the frequency of acute mastoiditis in our center in the last few years and to analyze the clinical and bacteriologic characteristics of the patients with this diagnosis . METHODS: Retrospective analysis of all patients admitted to our hospital with a diagnosis of acute mastoiditis from 1994-2001 . RESULTS: One hundred patients were diagnosed with acute mastoiditis during the study period . The mean age was 2 years and 10 months (range: 2 months-13 years) and the median age was 15 months . The mean number of episodes was 12.5 cases of acute mastoiditis per year, but 52 % of the cases occurred from 1999-2001 . Culture of middle ear effusions was performed in 47 patients, revealing Streptococcus pneumoniae in 17, Haemophilus influenzae in 3, and other pathogens in 10 children . Cultures were sterile in 17 patients . Three children did not respond to medical therapy and required mastoidectomy . CONCLUSIONS: In the last few years, the incidence of acute mastoiditis in our population has increased considerably . This complication is more common in children aged less than 2 years.

Genome Res, 2002 Dec, 12(12), 1889 - 900
Extreme pathway lengths and reaction participation in genome-scale metabolic networks; Papin JA et al.; Extreme pathways are a unique and minimal set of vectors that completely characterize the steady-state capabilities of genome-scale metabolic networks . A framework is provided to mathematically characterize extreme pathway length and to study how individual reactions participate in the extreme pathway structure of a network . The length of an extreme pathway is the number of reactions that comprise it . Reaction participation is the percentage of extreme pathways that utilize a given reaction . These properties were computed for the production of individual amino acids and protein production in Helicobacter pylori and individual amino acid production in Haemophilus influenzae . Reaction participation classifies the reactions into groups that are always, sometimes, or never utilized for the production of a target product . The utilized reactions can be further grouped into correlated subsets of reactions, some of which are non-obvious, and which may, in turn, suggest regulatory structure . The length of the extreme pathways did not correlate with product yield or chemical complexity . The distributions of extreme pathway lengths in H . pylori were also very different from those in H . influenzae, showing a distinct systemic difference between the two organisms, despite overall similar metabolic networks . Reaction participation and extreme pathway lengths thus serve to elucidate systemic biological features.

Clin Pediatr (Phila), 2002 Nov-Dec, 41(9), 681 - 6
Reasons hospitals give for not offering hepatitis B vaccine to low-risk newborns; Aiken KD et al.; After a temporary suspension of hepatitis B vaccination (HBV) for low-risk newborns in July 1999, some hospitals still do not offer HBV to these infants . A semi-structured telephone survey of medical directors from a national random sample of 296 hospital nurseries was completed from August 2000 to April 2001 and analyzed using qualitative techniques . Directors of 201 of 290 eligible nurseries (71%) participated . Twenty-ight nurseries have never offered HBV to low-risk newborns ("Never Offered HBV") and 37 nurseries had offered HBV to low-risk newborns before July 1999, but discontinued this practice after the temporary suspension ("Discontinued HBV") . Common reasons for not offering HBV to low-risk newborns were difficulty with reimbursement and convenience of outpatient administration . In addition, directors of "Never Offered HBV" nurseries cited low disease incidence in their patient population, whereas directors of "Discontinued HBV" cited preference for the combination hepatitis B-Haemophilus influenza type b vaccine as important factors . Multi-faceted interventions may be necessary to increase HBV use in the nursery.

J Clin Pathol, 2002 Dec, 55(12), 961 - 4
Clinical and microbiological features of Haemophilus influenzae vulvovaginitis in young girls; Cox RA et al.; AIMS: To define the clinical and microbiological features of vulvovaginitis in prepubertal girls whose genital swabs yielded Haemophilus influenzae . METHODS: Laboratory based study and retrospective collection of clinical data from the requesting doctors . RESULTS: Thirty eight isolates of non-capsulate Haemophilus influenzae and one of H parainfluenzae were isolated from 32 girls aged 18 months to 11 years . No other pathogens, such as beta haemolytic streptococci or yeasts, were present with H influenzae . The most common biotype was biotype II, comprising 57% of the 26 isolates biotyped . Six children had more than one episode of vulvovaginitis caused by H influenzae and a total of 14 children had recurrent vaginal symptoms . CONCLUSION: Children who have H influenzae vulvovaginitis are at risk of recurrent symptoms . Biotype II is the one most commonly associated with this condition.

J Antimicrob Chemother, 2002 Dec, 50(6), 903 - 6
Comparison of the antibacterial activities of ampicillin, ciprofloxacin, clarithromycin, telithromycin and quinupristin/dalfopristin against intracellular non-typeable Haemophilus influenzae; Ahren IL et al.; Non-typeable Haemophilus influenzae, which is a cause of disease in the upper and lower respiratory tract, can survive intracellularly in human epithelial cells and macrophages . We studied the in vitro activity of five antibiotics against intracellular non-typeable H . influenzae in human type II alveolar epithelial cells . The eukaryotic cells were loaded with bacteria, and extracellular bacteria were killed by gentamicin . After the cells were washed, antibiotics were added at concentrations of 0.12-64 mg/L for 18 h before the numbers of viable intracellular bacteria were determined . Of the antibiotics tested, ciprofloxacin and quinupristin/dalfopristin were the most potent agents, followed by clarithromycin and telithromycin . Ampicillin was not active against intracellularly localized, non-typeable H . influenzae.

J Pediatr Adolesc Gynecol, 2002 Aug, 15(4), 213 - 6
Vaginal discharge due to undiagnosed bilateral duplicated collecting system with ectopic ureters in a three-year-old female: an initial high index of suspicion for sexual abuse; Moon TD et al.; In prepubertal girls with vaginal discharge, consideration of the etiology must be given to respiratory pathogens (Streptococcus pyogenes, Haemophilus influenzae, Staphylococcus aureus, Streptococcus pneumoniae, and Neisseria meningitidis), enteric pathogens (Escherichia coli, Shigella, and Yersinia), poor hygiene, foreign body, nonabsorbent undergarments, irritants, vulvar skin disease, anatomic abnormalities (double vagina with fistula, pelvic abscess, and ectopic ureter), and sexual abuse . Prepubertal girls, outside the newborn period, with suspected gonococcal infection should be strongly considered to be victims of sexual abuse, once congenital and other newborn acquired forms of gonorrhea are excluded . We present a case of a three-year-old female with vaginal discharge and fever with a clouded social history, disproportionate distress on physical exam, and initial laboratory gram stain suggestive of gonococcus.

Med Microbiol Immunol (Berl), 2002 Dec, 191(3-4), 191 - 5 Epub 2002 Sep 13.
Conceptional considerations for a German influenza pandemic preparedness plan; Fock R et al.; A pandemic appearance of influenza A virus must be expected at any time . The limitations of health preserving and life-saving resources, which will inevitably be reached in the event of a pandemic, will be accompanied by ethical and possibly social conflicts, which can be lessened or resolved only through precautionary planning, clearly specified competencies and transparent decisions within a social consensus . In case of a shortage of vaccines and virostatic agents, decisions will have to be made with regard to the segment of the population that absolutely must be vaccinated . It is currently estimated that a (monovalent) vaccine developed for a new pandemic strain would only suffice for the single vaccination of approximately half of the German population after a year; only 10-14 million vaccine dosages would be available to provide basic immunization and single boosters to personnel required to maintain basic medical care and essential infrastructure after half a year . In the event of local influenza outbreaks, antiviral chemotherapeutic agents could be used to close the gap until a vaccine can become effective . Even if suitable influenza vaccines and virostatic agents are not sufficiently available at the start of a pandemic, it is still possible to at least prevent an outbreak of two of the most feared secondary infections that accompany influenza: pneumococcal pneumonia or meningitis and illnesses resulting from Haemophilus influenzae . Agreement still needs to be reached with manufacturers for guaranteeing the necessary vaccine production or ensuring that they have a sufficient stock to meet the minimum demand for antiviral agents and agents for symptomatic treatment.

J Chromatogr B Analyt Technol Biomed Life Sci, 2002 Dec 25, 782(1-2), 219 - 26
Proteomic study of non-typable Haemophilus influenzae; Thoren K et al.; Non-typable Haemophilus influenzae (NTHi) are small, gram-negative bacteria and are strictly human pathogens, causing acute otitis media, sinusitis and community-acquired pneumonia . There is no vaccine available for NTHi, as there is for H . influenzae type b . Recent advances in proteomic techniques are finding novel applications in the field of vaccinology . There are several protein separation techniques available today, each with inherent advantages and disadvantages . We employed a combined proteomics approach, including sequential extraction and analytical two-dimensional polyacrylamide electrophoresis (2D PAGE), and two-dimensional semi-preparative electrophoresis (2D PE), in order to study protein expression in the A4 NTHi strain . Although putative vaccine candidates were identified with both techniques, 11 of 15 proteins identified using the 2D PE approach were not identified by 2D PAGE, demonstrating the complementarily of the two methods.

Pediatrics, 2002 Dec, 110(6), 1064 - 70
Diagnostic accuracy, tympanocentesis training performance, and antibiotic selection by pediatric residents in management of otitis media; Pichichero ME; OBJECTIVE: To assess the accuracy of pediatric residents in recognizing the physical examination findings of acute otitis media (AOM) and otitis media with effusion (OME), technical competence to perform tympanocentesis, and knowledge of guideline-recommended antibiotic management of AOM . METHODS: A total of 383 pediatric residents from various programs in the United States viewed 9 different video-recorded pneumatic otoscopic examinations of tympanic membranes during a continuing medical education course . The ability to differentiate AOM, OME, and normal was ascertained . A mannequin of a child was used to assess technical proficiency of performing tympanocentesis on artificial tympanic membranes . A series of questions was posed regarding appropriate, pathogen-directed, second-line antibiotic selection for AOM . RESULTS: The average +/- standard deviation correct diagnosis on the otoscopic video examination was 41% +/- 16% (range: 19%-70%; median: 38%) by pediatric residents, tympanocentesis was optimally performed by 89%, and appropriate antibiotic therapy for drug-resistant Streptococcus pneumoniae was selected by 78% and appropriate therapy for beta-lactamase-producing Haemophilus influenzae was selected by 74% . CONCLUSIONS: According to this video-based examination, pediatric residents misdiagnose OME frequently . Pediatric residents have the skills to be trained to perform tympanocentesis . Approximately 75% of pediatric residents have knowledge of the appropriate antibiotics to select for treatment of resistant AOM pathogens . Interactive instruction with simulation technology may enhance skills and lead to improved diagnostic accuracy and treatment paradigms.

Curr Drug Targets Infect Disord, 2001 Nov, 1(3), 325 - 34
Vaccines against polysaccharide antigens; Lesinski GB et al.; Encapsulated bacteria such as Streptococcus pneumoniae, Neisseria meningitidis, and Haemophilus influenzae serogroup B (Hib) are a major cause of disease worldwide . Vaccine development against these organisms has targeted their capsular polysaccharides (CPS), as anti-capsular antibodies often protect against disease . The capsular polysaccharide vaccines that have been available against these organisms are neither immunogenic nor protective in young children and certain immunocompromised individuals . In general, polysaccharide (PS) antigens elicit a T-independent immune response, characterized by lack of memory, and poor immunogenicity at the extremes of life . Efforts to overcome the poor immunogenicity of CPS vaccines have led to development of conjugate vaccines . By conjugating CPS to carrier proteins it is possible to induce a T-dependent immune response against these antigens . Although conjugate vaccines have been successful against Hib disease, their applicability to multi-serotype/serogroup pathogens like the pneumococcus or the meningococcus is questioned . As a result, alternative vaccines including (1) surface proteins conserved across serotypes/serogroups, (2) peptides that mimic PS antigens and (3) DNA vaccines are presently under investigation . This review will highlight the potential and limitations of both CPS and CPS-conjugate vaccines against encapsulated bacteria as well as alternative strategies against PS antigens.

Inhal Toxicol, 2002 Dec, 14(12), 1215 - 29
Pulmonary effects of ultrafine and fine ammonium salts aerosols in healthy and monocrotaline-treated rats following short-term exposure; Cassee FR et al.; In the present study the effects of a 3-day inhalation exposure to model compounds for ambient particulate matter were investigated: ammonium bisulfate, ammonium ferrosulfate, and ammonium nitrate, all components of the secondary aerosol fraction of ambient particulate matter (PM), and carbon black (CB, model aerosol for primary PM) . The objective of this study was to test the hypothesis that secondary model aerosols exert acute pulmonary adverse effects in rats, and that rats with pulmonary hypertension (PH), induced by monocrotaline (MCT), are more sensitive to these components than normal healthy animals . An additional aim was to test the hypothesis that fine particles exert more effects than ultrafines . Healthy and PH rats were exposed to ultrafine (mass median diameter {MMD} approximate, equals 0.07-0.10 microm; 4 x 10(5) particles/cm(3)) and fine (MMD approximate, equals 0.57-0.64 micro;m; 9 x 10(3) particles/cm(3)) ammonium aerosols during 4 h/day for 3 consecutive days . The mean mass concentrations ranged from 70 to 420 microg/m(3), respectively, for ultrafine ammonium bisulfate, nitrate, and ferrosulfate and from 275 to 410 microg/m(3) for fine-mode aerosols . In an additional experiment, simultaneous exposure to a fine CB aerosol (0.6 microm; 2-9 mg/m(3)) and ammonium nitrate (0.4-18 mg/m(3)) was performed . Bronchoalveolar lavage fluid (BALF) analysis and histopathological examination were performed on animals sacrificed 1 day after the last exposure . Histopathology of the lungs did not reveal test atmosphere-related abnormalities in either healthy or PH rats exposed to the ammonium salts, or to a combination of CB + nitrate . Alveolar macrophages in rats exposed to CB only revealed the presence of black material in their cytoplasm . There were no signs of cytotoxicity due to the aerosol exposures (as measured with lactate dehydrogenase {LDH}, protein, and albumin contents in BALF) . Macrophages were not activated after MCT treatment or the test atmospheres, since no changes were observed in N-acetyl glucosaminidase (NAG) . Cell differentiation profiles were inconsistent, partly caused by an already present infection with Haemophilus sp . However, we believe that the test atmospheres did not affect cell differentiation or total cell counts . The results show that at exposure levels of ammonium salts at least one order of magnitude higher than ambient levels, marked adverse health effects were absent in both healthy and PH rats.

Mol Microbiol, 2002 Dec, 46(5), 1367 - 80
Evolution of the paralogous hap and iga genes in Haemophilus influenzae: evidence for a conserved hap pseudogene associated with microcolony formation in the recently diverged Haemophilus aegyptius and H . influenzae biogroup aegyptius; Kilian M et al.; Certain non-capsulate strains belonging to the Haemophilus influenzae/Haemophilus aegyptius complex show unusually high pathogenicity, but the evolutionary origin of these virulent phenotypes, termed H . influenzae biogroup aegyptius, is as yet unknown . The aim of the present study was to elucidate the mechanisms of evolution of two paralogous genes, hap and iga, which encode the adhesion and penetration Hap protein and the IgA1 protease respectively . Partial sequencing of hap and iga genes in a comprehensive collection of strains belonging to the H . influenzae/H . aegyptius complex revealed considerable genetic polymorphism and pronounced mosaic-like patterns in both genes, but no evidence of intrastrain recombination between the two genes . A conserved hap pseudogene was present in all strains of H . aegyptius and H . influenzae biogroup aegyptius, each of which constituted distinct subpopulations as revealed by phylogenetic analysis . There was no evidence for a second, functional copy of the hap gene in these strains . The perturbed expression of the Hap serine protease appears to be associated with the formation of elongated bacterial cells growing in chains and a distinct colonization pattern on conjunctival cells, previously termed microcolony formation . The fact that individual hap pseudogenes differed from the ancestral sequence by zero to two positions within a 1.5 kb stretch suggests that the silencing event happened approximately 2000-11,000 years ago . Divergence of H . aegyptius and H . influenzae biogroup aegyptius occurred subsequent to this genetic event . The loss of Hap protein expression may be one of the genetic events that facilitated exploitation of the conjunctivae as a new niche.

Ann Otol Rhinol Laryngol, 2002 Nov, 111(11), 1002 - 4
Bacteriology of acute and chronic sphenoid sinusitis; Brook I; Aspirates of 16 acutely infected and 7 chronically infected sphenoid sinuses were processed for aerobic and anaerobic bacteria . A total of 29 isolates were recovered from the 16 cases of acute sphenoid sinusitis (1.8 per specimen): 22 aerobic and facultative (1.4 per specimen), and 7 anaerobic (0.4 per specimen) . Aerobic and facultative organisms alone were recovered in 10 specimens (62%), anaerobes alone were isolated in 3 (19%), and mixed aerobic and anaerobic bacteria were recovered in 3 (19%) . The predominant aerobic and facultative species were Staphylococcus aureus (9 isolates), Streptococcus spp (9), and Haemophilus influenzae (2) . A total of 28 isolates were recovered from the 7 cases of chronic sphenoid sinusitis (4.0 per specimen): 11 aerobic and facultative (1.6 per specimen) and 17 anaerobic (2.4 per specimen) . Aerobic and facultative organisms alone were recovered in I instance (14%), anaerobes alone in 3 instances (43%), and mixed aerobes and anaerobes in 3 instances (43%) . The predominant aerobic bacteria were gram-negative bacilli (Klebsiella pneumoniae, Escherichia coli, and Pseudomonas aeruginosa; 1 each) . The predominant anaerobes included Peptostreptococcus spp (4 isolates), Prevotella spp (5), and Fusobacterium spp (4) . These findings illustrate the unique microbiology of acute and chronic sphenoid sinusitis.

Zh Mikrobiol Epidemiol Immunobiol, 2002 Jul-Aug, (4), 51 - 4
{Diagnostic value of different laboratory methods in the diagnosis of pneumonia caused by Haemophilus influenzae type B}; Gorbunov SG et al.; Comparative analysis of the diagnostic value of different laboratory methods in the diagnosis of H . influenzae b (Hib) pneumonia in children (bacteriological method, latex agglutination, counter immunoelectrophoresis, the passive hemagglutination test and the enzyme immunoassay (EIA) was carried out . EIA proved to be the most informative method for the diagnosing Hib pneumonia . EIA makes it possible to detect specific Hib antigens in different clinical materials in 48.8% of cases, as well as high titers of antibodies to mis infective agent in 61.7% of cases . The authors propose the unified criteria of the laboratory diagnosis of Hib infection in children.

J Bacteriol, 2002 Dec, 184(24), 6906 - 17
Ribosylnicotinamide kinase domain of NadR protein: identification and implications in NAD biosynthesis; Kurnasov OV et al.; NAD is an indispensable redox cofactor in all organisms . Most of the genes required for NAD biosynthesis in various species are known . Ribosylnicotinamide kinase (RNK) was among the few unknown (missing) genes involved with NAD salvage and recycling pathways . Using a comparative genome analysis involving reconstruction of NAD metabolism from genomic data, we predicted and experimentally verified that bacterial RNK is encoded within the 3' region of the nadR gene . Based on these results and previous data, the full-size multifunctional NadR protein (as in Escherichia coli) is composed of (i) an N-terminal DNA-binding domain involved in the transcriptional regulation of NAD biosynthesis, (ii) a central nicotinamide mononucleotide adenylyltransferase (NMNAT) domain, and (iii) a C-terminal RNK domain . The RNK and NMNAT enzymatic activities of recombinant NadR proteins from Salmonella enterica serovar Typhimurium and Haemophilus influenzae were quantitatively characterized . We propose a model for the complete salvage pathway from exogenous N-ribosylnicotinamide to NAD which involves the concerted action of the PnuC transporter and NRK, followed by the NMNAT activity of the NadR protein . Both the pnuC and nadR genes were proven to be essential for the growth and survival of H . influenzae, thus implicating them as potential narrow-spectrum drug targets.

J Bacteriol, 2002 Dec, 184(24), 6893 - 905
Bacteriophage HP2 of Haemophilus influenzae; Williams BJ et al.; Temperate bacteriophages effect chromosomal evolution of their bacterial hosts, mediating rearrangements and the acquisition of novel genes from other taxa . Although the Haemophilus influenzae genome shows evidence of past phage-mediated lateral transfer, the phages presumed responsible have not been identified . To date, six different H . influenzae phages are known; of these, only the HP1/S2 group, which lyosogenizes exclusively Rd strains (which were originally encapsulated serotype d), is well characterized . Phages in this group are genetically very similar, with a highly conserved set of genes . Because the majority of H . influenzae strains are nonencapsulated (nontypeable), it is important to characterize phages infecting this larger, genetically more diverse group of respiratory pathogens . We have identified and sequenced HP2, a bacteriophage of nontypeable H . influenzae . Although related to the fully sequenced HP1 (and even more so to the partially sequenced S2) and similar in genetic organization, HP2 has a few novel genes and differs in host range; HP2 will not infect or lysogenize Rd strains . Genomic comparisons between HP1/S2 and HP2 suggest recent divergence, with new genes completely replacing old ones at certain loci . Sequence comparisons suggest that H . influenzae phages evolve by recombinational exchange of genes with each other, with cryptic prophages, and with the host chromosome.

J Immunol, 2002 Dec 1, 169(11), 6316 - 23
Evolution of the cutaneous immune response to experimental Haemophilus ducreyi infection and its relevance to HIV-1 acquisition; Humphreys TL et al.; Haemophilus ducreyi causes the sexually transmitted disease chancroid, which facilitates HIV-1 transmission . Skin biopsies were obtained from subjects experimentally infected with H . ducreyi to study the evolution of the immune response and immunophenotypes relevant to transmission of HIV-1 . Compared with peripheral blood, there was an enrichment of T cells and macrophages after 48 h of infection in the skin . Neutrophils became the predominant cell type by 7-9 days . By immunohistochemistry, macrophage-inflammatory protein-1alpha was not present early in infection, but was abundant at later stages . RANTES was present throughout the papular and pustular stages of experimental infection, but not present in uninfected control skin . Stromal cell-derived factor-1 was present at low levels in all samples examined . Macrophages in lesions had significantly increased expression of CCR5 and CXCR4 compared with peripheral blood cells, and CD4 T cells had significant up-regulation of CCR5 . The magnitude of increased expression of these receptors was not replicated when PBMCs were incubated with H . ducreyi or H . ducreyi lipooligosaccharide in vitro . Together with the disruption of mucosal and skin barriers, the presence of cells with up-regulated HIV-1 coreceptors in H . ducreyi-infected lesions may provide an environment that facilitates the acquisition of R5 (CCR5), X4 (CXCR4), and dual-tropic HIV-1 strains.

Int J Pediatr Otorhinolaryngol, 2002 Dec 2, 66(3), 227 - 42
Microbiologic findings and risk factors for antimicrobial resistance at myringotomy for tympanostomy tube placement--a prospective study of 601 children in Toronto; Ford-Jones EL et al.; CONTEXT: There is limited information on the identity and antibiotic susceptibility of bacterial pathogens in children with chronic otitis media whose repeated antibiotic use may place them at increased risk of antibiotic-resistant bacteria . OBJECTIVE: To determine, at myringotomy for tympanostomy tube placement, (1) the prevalence of bacteria, (2) the extent and patterns of antibiotic resistance, and (3) the risk factors associated with the presence and resistant status of pathogens . DESIGN: Prospective, multi-site, cohort study . SETTING AND PATIENTS: Children undergoing myringotomy for tympanostomy tube placement between November 1, 1999 and March 31, 2000 in seven hospitals in Toronto, Ontario, were identified . If fluid was present, aspirates were submitted for bacteriologic testing . A follow-up telephone questionnaire was administered to patient caregivers in order to identify risk factors for the presence of (1) culturable pathogens and (2) resistant pathogens . MAIN OUTCOME MEASURES: The identification and prevalence of bacteria cultured from the middle ears of subjects, and the degree of nonsusceptibility to commonly prescribed antibiotics . RESULTS: Among 601 patients (mean age 3.9 years, 60.7% male), both a telephone interview (n=544) and an ear specimen (n=527) were obtained for 478 . Pathogens were found in middle ear effusions of 37% of the children in the study; including at least one 'definite' pathogen in 189 children (31.4%), and a further 32 children (5.3%) with at least one 'possible' pathogen . Definite pathogens included Haemophilus influenzae in 17% of the children, followed by Moraxella catarrhalis (9%) and Streptococcus pneumoniae (6%); ampicillin nonsusceptibility was found in 40, 100 and 24%, respectively . Overall, 123 children (20.5%) were found to have definite pathogens with resistance to ampicillin/penicillin, trimethoprim-sulfamethoxazole, or clarithromycin/erythromycin . Patient characteristics included premature birth and/or long length of stay in the nursery (23%), first infection before the age of 6 months (26%), put to bed with a bottle (28%), household smoker (34%), in out-of-home child care (38%), history of eczema, bronchiolitis and/or asthma (39%), and use of pacifiers (40%) . Household characteristics were smoking (34%), married/common law parents (85%), and 60% had completed college or university; in 26% both parents were born outside of Canada; 73% of children were Caucasian . Of the 75% who responded to the question regarding income, 42% had household income over $60,000 (CAN) . Risk factors for the presence of a pathogen and for a resistant pathogen in multivariate analysis included younger age, lower maternal education, day care centre attendance, no previous adenoidectomy and bilateral, primarily winter infections as well as amoxicillin use in the previous 6 months . CONCLUSION: Modifiable risk factors for otitis media including household smoking and pacifier use are present in many children undergoing tympanostomy tube placement; child care centre attendees are over-represented . Multiple antibiotic courses were commonly prescribed prior to surgery . H . influenzae and M . catarrhalis are important pathogens and therapy in clinical failures should be directed against them . The 7-valent protein conjugate polysaccharide vaccine (Prevnar) would have covered 73% of the serotypes of S . pneumoniae isolated in this study.

Vaccine, 2002 Nov 22, 21(1-2), 53 - 9
Occurrence of adverse events following inadvertent administration of childhood vaccines; Derrough TF et al.; As a service to healthcare professionals, Aventis Pasteur MSD UK Ltd . operates a telephone-based Vaccine Information Service, providing information on all aspects of vaccination . In the UK it is the primary means by which spontaneous adverse drug reaction reports are received by the company.It was brought to the attention of the Pharmacovigilance Department that a significant number of calls related to people seeking advice following inadvertent administration of vaccines . To inform our advice it was decided to collect details of such episodes, to enquire whether an adverse drug reaction had already occurred, and to encourage reporting of adverse drug reaction that may occur subsequently . Inadvertent vaccination during pregnancy was not included in this survey since these data were already being collected separately.During the period from 1 September 1999 to 31 August 2000 the Vaccine Information Service received 124010 enquiries . Of these, 302 (0.2%) concerned inadvertent administration of one or more vaccines (all age groups), 161 (53.2% of total inadvertent administration) of them in children (<18 years) . These 161 reports involved the inadvertent administration of 221 vaccines . In six cases (3.8%) one or more adverse drug reaction were reported following the inadvertent administration . Five of these six cases involved a DTP-containing vaccine: one case where DTP was given instead of diphtheria and tetanus toxoid (DT) vaccine as a pre-school booster, one case where a fourth dose of DTP-Haemophilus influenzae type b conjugate vaccine (Hib) was given at 20 weeks of age and three cases where DTP was mixed with DTP-Hib . The sixth case involved a child given an adult dose of hepatitis B vaccine . Data are available for five of these six cases-all adverse drug reactions were non-serious and resolved without sequelae.Inadvertent administration of vaccines in childhood, although worrying for both the healthcare professionals and the parents involved, seems rarely to result in adverse reactions.

Ann Med Interne (Paris), 2002 Sep, 153(5), 311 - 7
{Epidemiology of bacterial meningitis in France in 1999}; Perrocheau A et al.; In France, two sources of data, the mandatory notification and the laboratory network EPIBAC, allow the health authorities to follow the incidence of bacterial meningitis (BM) and to assess the relative frequency of the micro-organisms responsible for such infection . In 1999, more than 1,000 cases of BM were notified in France . The more common micro-organisms were: Streptococcus pneumoniae 46%, Neisseria meningitidis 32% and Streptococcus agalactiae(or Streptococcus B) 11% . Listeria monocytogenes and Haemophilus influenzae accounted for 6% and 5% of the cases respectively . In 1999, the incidence per 100,000 inhabitants of meningitis due to pneumococci (0.81), to streptococci B (0.19) and tuberculosis meningitis (0.17) were stable since 1995 . The incidence rate of meningitis due to Listeria (0.10) and to H . influenzae (0.08) shows a regular decrease since 1992 . The impact of preventive measures of meningitis due to Listeria and H . influenzae B has been clearly demonstrated through the dramatic decrease of meningitis due to these micro-organisms.

Pediatr Infect Dis J, 2002 Nov, 21(11), 1004 - 7
Immunogenicity after one, two or three doses and impact on the antibody response to coadministered antigens of a nonavalent pneumococcal conjugate vaccine in infants of Soweto, South Africa; Huebner RE et al.; BACKGROUND: Children <6 months of age are at increased risk of pneumococcal disease . The early immunogenicity of conjugate vaccines therefore may be important to prevent disease in young children . OBJECTIVES: To determine the immunogenicity of a nonavalent pneumococcal conjugate vaccine after one dose, two doses and three doses and its impact on the antibody response to coadministered antigens . METHODS: A total of 500 infants from Soweto were immunized at 6, 10 and 14 weeks of age with either placebo (n = 250) or 9-valent pneumococcal conjugate vaccine (n = 250) containing serotypes 1, 4, 5, 6B, 9V, 14, 18C, 19F and 23F conjugated to CRM(197) mutant diphtheria protein . Blood was taken for determination of serotype-specific IgG before the first dose and 1 month after each dose . RESULTS: Before the first dose at 6 weeks of age >80% of infants had >0.15 microg/ml antibody to six of the nine antigens, >70% to serotypes 18C and 23F and >50% to serotype 4 . Geometric mean concentrations (GMCs) after one dose ranged from 0.27 microg/ml for serotype 23F to 2.98 microg/ml for serotype 1; >90% of infants had serotype-specific antibody >0.15 microg/ml except for serotypes 23F (70%) and 6B (80%) . After two doses GMCs ranged from 1.14 microg/ml for serotype 23F to 5.68 microg/ml for serotype 1; >95% of infants had serotype-specific antibody >0.15 microg/ml and >75% had >0.5 microg/ml for all nine serotypes . GMCs after three doses ranged from 2.73 microg/ml for serotype 23F to 6.18 microg/ml for serotype 5; >98% of infants had serotype-specific antibody >0.15 microg/ml and >92% had >0.5 microg/ml for all nine serotypes . Antibody concentrations after three doses were significantly higher to Haemophilus influenzae type b-polyribosylribitol phosphate vaccine in children who received pneumococcal conjugate vaccine, but they had lower antibodies to pertussis toxin than controls . CONCLUSIONS: A single dose of this pneumococcal conjugate vaccine produces a potentially protective antibody response to most serotypes in the majority of children in this population.

Glycoconj J, 2001 Oct, 18(10), 779 - 87
Molecular cloning and functional expression of the rfaE gene required for lipopolysaccharide biosynthesis in Salmonella typhimurium; Jin UH et al.; The rfaE (WaaE) gene of Salmonella typhimurium is known to be located at 76min on the genetic map outside of the rfa gene cluster encoding core oligosaccharide biosynthesis of lipopolysaccharide(LPS) . The rfaE mutant synthesizes heptose-deficient LPS; its LPS consists of only lipid A and 3-deoxy-D-manno-octulosonic acid (KDO), and the rfaE gene is believed to be involved in the formation of ADP-L-glycero-D-manno-heptose . Mutants, which make incomplete LPS, are known as rough mutants . Salmonella typhimurium deep-rough mutants affected in the heptose region of the inner core often show reduced growth rate, sensitivity to high temperature and hypersensitivity to hydrophobic antibiotics . We have cloned the rfaE gene of S . typhimurium . The chromosomal region carrying this gene was isolated by screening a genomic library of S . typhimurium using the complementation of S . typhimurium rfaE mutant . The 2.6-Kb insert in the plasmid pHEPs appears to carry a functional rfaE gene . SL1102 (rfaE543) makes heptose-deficient LPS and has a deep rough phenotype, but pHEPs complement the rfaE543 mutation to give the smooth phenotype . The sensitivity of SL1102 to bacteriophages (P22.c2, Felix-O, Br60) which use LPS as their receptor for adsorption is changed to that of wild-type strain . The permeability barrier of SL1102 to hydrophobic antibiotics (novobiocin) is restored to that of wild-type . LPS produced by SL1102 (rfaE543) carrying pHEPs makes LPS indistinguishable from that of smooth strains . The rfaE gene encoded a polypeptide of 477 amino acid residues highly homologous to the S . enterica rfaE protein (98% identity), E . coli (93% identity), Yersenia pestis (85% identity), Haemophilus influenzae (70% identity) and Helicobacter pyroli (41% identity) with a molecular weight 53 kDa.

Laryngoscope, 2002 Nov, 112(11), 2042 - 5
Effect of 23 valent pneumococcal polysaccharide and Haemophilus influenza conjugated vaccines on the clinical course of otitis media with effusion; Kilic R et al.; OBJECTIVE: To determine if there is any clinical effect of 23-valent pneumococcal and type B conjugate vaccine on prognosis of otitis media with effusion . METHOD: All children who have middle ear effusion despite long-standing antibiotherapy with a beta lactamase stable agent were offered for tympanostomy tube insertion between February 1999 and December 2001 . Patients who accepted the surgical intervention were operated under general anesthesia and a Shepard grommet-type tympanostomy tube was inserted . Those who refused the surgical intervention were vaccinated with 23-valent pneumococcal and type B conjugate vaccine . State of the middle ear effusion was evaluated at the end of the 12th month in the vaccine group and 1 month after the myringotomy site was healed in the tympanostomy tube insertion group . RESULTS: Twenty-six children in the vaccine group and 37 children in the tympanostomy tube insertion group proved the inclusion criteria at the end of study . Complete or partial resolution of middle ear effusion was observed in 73.1% of 26 children in the vaccine group and 59.5% of children in the tympanostomy tube insertion group . There was no significant difference between the two groups . CONCLUSION: Vaccination against and type b seems to aid resolution of middle ear effusion in children with otitis media with effusion.

Infect Immun, 2002 Dec, 70(12), 7161 - 4
Neuraminidase expressed by Streptococcus pneumoniae desialylates the lipopolysaccharide of Neisseria meningitidis and Haemophilus influenzae: a paradigm for interbacterial competition among pathogens of the human respiratory tract; Shakhnovich EA et al.; Both Neisseria meningitidis and Haemophilus influenzae are capable of mimicking host structures by decorating their lipopolysaccharides with sialic acid . We show that a neuraminidase expressed by Streptococcus pneumoniae (NanA) is able to desialylate the cell surfaces of both these species, which reside in and possibly compete for the same host niche.

J Trauma, 2002 Nov, 53(5), 950 - 6
Vaccination practices among North American trauma surgeons in splenectomy for trauma; Shatz DV; BACKGROUND: The purpose of this study was to examine trama surgeons' practice patterns regarding immunization of splenic injury patients . METHODS: Data were analyzed from surgeons responding to a survey sent to 557 adult trauma surgeons in the United States and Canada . The survey queried the timing and use of vaccinations in splenic injury patients . RESULTS: Three hundred four (54.6%) surgeons responded to the survey, with 43 no longer active . Of the 261 active surgeons, 99.2% immunize their splenectomized patients, whereas 15.7% immunize those who undergo splenorrhaphy and 8.4% immunize those managed nonoperatively . Vaccines are administered anywhere from the immediate postoperative period to as long as 6 weeks later . All but two responding surgeons provide the pneumococcal vaccine, 62.8% also advocate meningococcal vaccination, 72.4% add the Haemophilus influenzae vaccine, and 56.7% give all three . Thirteen of the responding surgeons reimplant splenic tissue, most frequently in the omentum, and in quantities varying from two slices to the entire spleen . Revaccination practices are extremely varied-ranging from nothing at all to annually-and seldom follow Centers for Disease Control and Prevention guidelines . CONCLUSION: With the exception of immunizing splenectomized patients against pneumococcal infection, little consensus exists among surgeons regarding the immunization of patients sustaining splenic injury.

Eur J Med Res, 2002 Sep 30, 7(9), 387 - 92
Vaccination against Haemophilus influenzae type b and atopy in east German schoolchildren; Laubereau B et al.; INTRODUCTION: Although routine childhood immunisations are known to prevent severe diseases there is an ongoing discussion on possible side effects in later life . In this paper we investigated the association of Haemophilus influenzae type b (Hib)-vaccination and atopic diseases and allergic sensitisation in children in Eastern Germany . METHODS: From 1998-1999 a cross-sectional survey of school children aged 5 to 14 years on long-term health effects of air pollution was conducted in three regions of Eastern Germany . Atopic outcome was defined by parental reporting of wheezing and doctor's diagnosed asthma (including asthma-like bronchitis), hay fever and eczema . Specific serum IgE against 5 aeroallergens were analysed by RAST-technique . Vaccination status was assessed by vaccination records from the respective local health authorities . Analysis is restricted to 1943 children with complete information on age, gender, place of residence, parental education and 1676 children with available blood data . RESULTS: Lifetime prevalence were 4.9% for asthma, 21.1% for wheezing, 6.6% for hay fever, 11.4% for eczema . 32% of the children had at least one specific IgE RAST>0 . Hib-vaccination coverage was 42 % overall, 93 % in 5-7 yr olds, 59 % in 8-10 yr olds and 11 % in 11-14 yr olds . Odds Ratios adjusted for age, gender, place of residence, and parental education were 1.86 (1.05-3.32) for asthma, 1.55 (0.95-2.54) for hay fever, 1.03 (0.70-1.50) for eczema and 1.25 (0.94-1.67) for at least 1 specific IgE RAST>0 . CONCLUSION: We found little evidence for an association between Hib-vaccination and some atopic outcomes and causality cannot be ascertained . Our findings do not give sufficient support to question the value of Hib vaccination given the substantial contribution of mass immunisations to public health . Specific research on possible long-term effects of vaccines is needed to enable final conclusions on this topic.

Am J Respir Crit Care Med, 2003 Feb 15, 167(4), 587 - 92 Epub 2002 Nov 14.
Adaptive immunity to nontypeable Haemophilus influenzae; King PT et al.; Nontypeable Haemophilus influenzae (NTHi) colonizes the upper respiratory tract of most healthy people and is also a major cause of infection in chronic obstructive lung disease . The immune response to this bacterium has not been well characterized . We tested the hypothesis that recurrent airway infection with NTHi may be associated with nonclearing adaptive immunity . Study subjects were healthy control subjects and patients with idiopathic bronchiectasis who had severe chronic infection with H . influenzae . We established that all subjects in both groups had detectable antibody to NTHi, suggesting that most normal people have developed an adaptive immune response . To characterize the nature of the immune response, we measured antigen-specific production of T helper cell cytokines and CD40 ligand by flow cytometry and immunoglobulin subclass levels in peripheral blood . We found that normal control subjects made Th1 response to NTHi with distinct CD40 ligand production . In contrast, subjects with bronchiectasis had predominant production of Th2 cytokines, decreased expression of CD40 ligand, and different immunoglobulin G subclass production . Therefore, chronic infection with NTHi in bronchiectasis is associated with a change in adaptive immunity that may be important in the pathogenesis of bronchial infection.

J Mol Microbiol Biotechnol, 2002 Nov, 4(6), 515 - 7
Rapid assignment of nucleotide sequence data to allele types for multi-locus sequence analysis (MLSA) of bacteria using an adapted database and modified alignment program; Diggle MA et al.; A novel database and modified alignment program is described which provides a fast and accurate procedure for assigning nucleotide sequences to allele types for multi-locus sequence analysis (MLSA) . The database has between 40 and 160 alleles per organism including Neisseria meningitidis, Streptococcus pneumoniae, Staphylococcus aureus and Haemophilus influenzae . The database directly compares the query nucleotide sequence against all alleles within the database and this system reduces the time taken for the analysis of nucleotide sequence data and assignment of alleles for subsequent sequence analysis.

Rev Panam Salud Publica, 2002 Oct, 12(4), 247 - 57
Primary and booster vaccination with DTPw-HB/Hib pentavalent vaccine in Costa Rican children who had received a birth dose of hepatitis B vaccine; Faingezicht I et al.; OBJECTIVE: The DTPw-HB/Hib pentavalent combination vaccine has been developed following recommendations of the World Health Organization for the introduction of hepatitis B (HB) and Haemophilus influenzae type b (Hib) vaccines into routine childhood vaccination programs . The objectives of this study were to: 1) analyze the immunogenicity and the reactogenicity of the DTPw-HB/Hib pentavalent combination vaccine in comparison to separate injections of DTPw-HB and Hib vaccines as primary vaccination in a group of children who had received a dose of HB vaccine at birth and 2) in the second year of life to assess the antibody persistence as well as the response to a DTPw-HB/Hib or DTPw/Hib booster . METHODS: In the first part of the study (primary-vaccination stage), conducted in 1998-1999, we analyzed the immunogenicity and reactogenicity of the DTPw-HB/Hib combination vaccine in comparison to separate injections of DTPw-HB and Hib vaccines as primary vaccination at 2, 4, and 6 months of age in 207 Costa Rican children who had received a dose of HB vaccine at birth . Later, in the booster-vaccination stage of the study, in 1999-2000, in a subset of the children (69 toddlers, now 15-18 months old), antibody persistence was measured, and response to a DTPw-HB/Hib or DTPw/Hib booster was also assessed . RESULTS: In both primary-vaccination groups, at least 97.5% of the infants reached protective levels of antibodies (seropositivity) against the antigens employed in the vaccines . The DTPw-HB/Hib pentavalent combination vaccine did not result in more local reactions than did the DTPw-HB vaccine alone, and, in terms of general reactions, there was no clinically significant difference between the combination or separate injections, and with the pentavalent vaccine having the benefit of needing one less injection . Nine months after the third dose of the primary-vaccination course, antibody persistence was similar in both groups, with over 93% of children still having protective/seropositive titers for Hib, HB, and tetanus and about 50% for diphtheria and Bordetella pertussis . At 15 months of age, virtually all the toddlers responded with a strong boost response to all the vaccine antigens, whether they received the DTPw-HB/Hib pentavalent vaccine or the DTPw/Hib vaccine as a booster . Both booster regimens were equally well tolerated, indicating that up to five doses of the HB vaccine can be given without impact on safety.CONCLUSIONS: Our study confirms that the DTPw-HB/Hib pentavalent vaccine is highly immunogenic as a primary vaccination in children who received an HB vaccine at birth, with the pentavalent combination inducing both persisting immunity and boostable memory . The pentavalent vaccine was safe both for primary and booster vaccinations . Thus, this study in Costa Rican infants supports the routine use of the pentavalent DTPw-HB/Hib vaccine as part of childhood vaccination programs in Latin America and the Caribbean.

Vet Rec, 2002 Oct 26, 151(17), 502 - 5
Protection of vaccinated pigs against experimental infections with homologous and heterologous Haemophilus parasuis; Bak H et al.; The efficacy of a new Haemophilus parasuis vaccine for pigs was investigated . The vaccine contains H parasuis serotype 5 cells and is adjuvanted with Diluvac Forte (Intervet) . Groups of pigs were vaccinated at five and seven weeks with 2 ml and their littermates served as unvaccinated controls . The vaccinated pigs were protected against a challenge with another strain of Hparasuis serotype 5 at two, eight and 17 weeks after the second vaccination, whereas the controls became very ill . The susceptibility of the pigs to the infection decreased with increasing age . After a heterologous challenge with H parasuis serotypes 1, 12, 13 and 14, two weeks after the second vaccination, the vaccine also gave clear protection . The severity of the illness among the control pigs differed with the different serotypes.

Clin Microbiol Infect, 2002, 8 Suppl 2, 12 - 42
Surveillance of resistance in bacteria causing community-acquired respiratory tract infections; Felmingham D et al.; Bacterial resistance to antibiotics in community-acquired respiratory tract infections is a serious problem and is increasing in prevalence world-wide at an alarming rate . Streptococcus pneumoniae, one of the main organisms implicated in respiratory tract infections, has developed multiple resistance mechanisms to combat the effects of most commonly used classes of antibiotics, particularly the beta-lactams (penicillin, aminopenicillins and cephalosporins) and macrolides . Furthermore, multidrug-resistant strains of S . pneumoniae have spread to all regions of the world, often via resistant genetic clones . A similar spread of resistance has been reported for other major respiratory tract pathogens, including Haemophilus influenzae, Moraxella catarrhalis and Streptococcus pyogenes . To develop and support resistance control strategies it is imperative to obtain accurate data on the prevalence, geographic distribution and antibiotic susceptibility of respiratory tract pathogens and how this relates to antibiotic prescribing patterns . In recent years, significant progress has been made in developing longitudinal national and international surveillance programs to monitor antibiotic resistance, such that the prevalence of resistance and underlying trends over time are now well documented for most parts of Europe, and many parts of Asia and the Americas . However, resistance surveillance data from parts of the developing world (regions of Central America, Africa, Asia and Central/Eastern Europe) remain poor . The quantity and quality of surveillance data is very heterogeneous; thus there is a clear need to standardize or validate the data collection, analysis and interpretative criteria used across studies . If disseminated effectively these data can be used to guide empiric antibiotic therapy, and to support-and monitor the impact of-interventions on antibiotic resistance.

Braz J Med Biol Res, 2002 Nov, 35(11), 1293 - 300
Antimicrobial resistance among invasive Haemophilus influenzae strains: results of a Brazilian study carried out from 1996 through 2000; Casagrande ST et al.; A total of 1712 strains of Haemophilus influenzae isolated from patients with invasive diseases were obtained from ten Brazilian states from 1996 to 2000 . beta-Lactamase production was assessed and the minimum inhibitory concentrations (MIC) of ampicillin, chloramphenicol, ceftriaxone and rifampin were determined using a method for broth microdilution of Haemophilus test medium . The prevalence of strains producing beta-lactamase ranged from 6.6 to 57.7%, with an overall prevalence of 18.4% . High frequency of beta-lactamase-mediated ampicillin resistance was observed in Distrito Federal (25%), Sao Paulo (21.7%) and Parana (18.5%) . Of the 1712 strains analyzed, none was beta-lactamase negative, ampicillin resistant . A total of 16.8% of the strains were resistant to chloramphenicol, and 13.8% of these also presented resistance to ampicillin, and only 3.0% were resistant to chloramphenicol alone . All strains were susceptible to ceftriaxone and rifampin and the MIC90 were 0.015 micro g/ml and 0.25 micro g/ml, respectively . Ceftriaxone is the drug of choice for empirical treatment of bacterial meningitis in pediatric patients who have not been screened for drug susceptibility . The emergence of drug resistance is a serious challenge for the management of invasive H . influenzae disease, which emphasizes the fundamental role of laboratory-based surveillance for antimicrobial resistance.

Eur J Pediatr, 2002 Nov, 161(11), 581 - 7 Epub 2002 Oct 05.
Immunogenicity and reactogenicity of a novel hexavalent DTPa-HBV-IPV/Hib vaccine compared to separate concomitant injections of DTPa-IPV/Hib and HBV vaccines, when administered according to a 3, 5 and 11 month vaccination schedule; Avdicova M et al.; In an open randomised trial, 312 eligible infants were enrolled to receive either a single injection of the hexavalent diphtheria-tetanus-acellular pertussis-hepatitis B virus-inactivated polio/ Haemophilus influenzae b (DTPa-HBV-IPV/Hib) vaccine, or concomitant injections of commercial DTPa-IPV/Hib and HBV vaccines (comparator) . Vaccines were administered at 3, 5 and 11 months of age . The statistical approach for non-inferiority showed that the DTPa-HBV-IPV/Hib vaccine was at least as immunogenic as the comparator vaccines in terms of immunogenicity of all antigens 1 month after the 2nd dose . Non-inferiority criteria were also met immediately before and 1 month after the 3rd dose for all antigens except poliovirus type 3 prior to the 3rd dose . The majority of subjects were seroprotected against diphtheria, tetanus, polyribosyl-ribitol-phosphate, hepatitis B and poliovirus after the 2nd dose and maintained seroprotective antibody levels until the 3rd dose . A marked difference was observed in anti-HBs antibody geometric mean antibody concentrations (GMCs) at 1 month after the 2nd dose (higher GMCs in DTPa-HBV-IPV/Hib group) . Reactogenicity (incidence of solicited local and general symptoms) was similar between the two study groups and no vaccine-related serious adverse events occurred . CONCLUSION: the new diphtheria-tetanus-acellular pertussis-hepatitis B virus-inactivated polio/ Haemophilus influenzae b vaccine administered at 3, 5 and 11 months of age was safe and at least as immunogenic as the comparator vaccines thus providing an effective and more comfortable option for this infant vaccination schedule.

FEMS Immunol Med Microbiol, 2002 Nov 15, 34(3), 221 - 30
The role of licA phase variation in the pathogenesis of invasive disease by Haemophilus influenzae type b; Humphries HE et al.; LicA encodes the enzyme phosphorylcholine kinase which catalyses the incorporation of phosphorylcholine (ChoP) into H . influenzae LPS . Expression of this gene is subject to phase variation, resulting in the spontaneous loss, or gain of phosphorylcholine (ChoP)-decorated LPS structures . To investigate the role of this phenomenon in the pathogenesis of invasive disease an H . influenzae mutant was constructed which lacked the ability to phase vary licA . This was achieved by introducing an in-frame deletion of the 5'-CAAT-3' repeats into licA using polymerase chain reaction . The resultant mutant, licADelta5'-CAAT-3', was unable to switch off expression of licA and constitutively expressed ChoP-decorated LPS structures, as judged by colony immunoblotting with Mabs 12D9 and HAS . This resulted in increased synthesis of high molecular mass LPS structures and the absence of non-ChoP-decorated LPS species as determined by T-SDS-PAGE analysis . Inability to switch off the expression of licA reduced the virulence of H . influenzae in an infant rat model of invasive disease and resulted in increased sensitivity to the bactericidal activity of serum in the presence of CRP . The ability to switch off the expression of licA through phase variation is therefore concluded to enhance the systemic survival of H . influenzae.

FEMS Immunol Med Microbiol, 2002 Nov 15, 34(3), 215 - 9
Interaction of vitronectin with Haemophilus influenzae; Eberhard T et al.; Eight strains of Haemophilus influenzae were tested for binding to human vitronectin . All strains adhered to vitronectin-coated glass slides but no binding was detected using soluble vitronectin, suggesting that surface association of vitronectin is a prerequisite . Vitronectin binding was not likely to be mediated by fimbriae as non-fimbriated and fimbriated isogenic strains adhered equally . Adhesion could be blocked by heparin, which is also known to block vitronectin binding to Staphylococcus aureus . However, no blocking was achieved with sialic acid-rich glycoproteins such as fetuin and mucin contrasting with Helicobacter pylori for which sialic acid seems to play an important role . With Streptococcus pneumoniae binding was detected both with soluble and surface-associated vitronectin and could not be blocked by heparin . Our results suggest that H . influenzae, Streptococcus pneumoniae and Helicobacter pylori all use distinct modes to interact with vitronectin.

Rev Med Brux, 2002 Sep, 23(4), A237 - 46
{Conjugate vaccines}; Swennen B et al.; Conjugate vaccines extend the vaccinal prevention for children to more diseases . Conjugating the capsular polysaccharide to a carrier protein transforms a T-independent antigen in a T-dependent, allowing protection of the children (before 2 years of age) against Haemophilus influenzae type b, meningococcal C and pneumococcal infections . This article reviews the 3 conjugate vaccines and their results with focus on some questions: antigens interference in the immunological response, serological subrogate for protection, herd immunity and replacement of circulating serotypes.

Indian J Pediatr, 2002 Sep, 69(9), 775 - 7
Nasopharyngeal carriage of Haemophilus influenzae; Das BK et al.; OBJECTIVE: Nasopharyngeal colonization of Haemophilus influenzae (H . influenzae) in young children may be important in developing countries . METHOD: In this study, we screened school going children for carriage of H . influenzae . A total of 44 H . influenzae isolates out of a collection of 162 were characterized for biotypes, capsular serotypes and antibiotic resistance . RESULTS: A significant proportion of H . influenzae (25/44) isolates were serotype b . High antibiotic resistance was observed against commonly administered antibiotics like ampicillin (79%), chloramphenicol (20%), trimethoprim sulfamethoxazole (84%) and erythromycin (95%) . Comparison of antibiotic resistance profile of nasopharyngeal isolates was observed to be correlated with those of H . influenzae from disease . CONCLUSION: Multidrug resistant nasopharyngeal H . influenzae in young healthy children may act as reservoir . Monitoring of antibiotic resistance among nasopharyngeal H . influenzae as a surrogate for invasive H . influenzae seems an attractive option.

P N G Med J, 2001 Mar-Jun, 44(1-2), 6 - 16
Safety and immunogenicity of two Haemophilus influenzae type b polysaccharide-tetanus toxoid conjugate vaccines (PRP-T) given with diphtheria-tetanus-pertussis vaccine to young Papua New Guinean children; Lehmann D et al.; BACKGROUND: In view of high mortality and morbidity from Haemophilus influenzae type b (Hib) in young Papua New Guinean children, the incorporation of a Hib conjugate vaccine into a nationwide immunization program would be of major public health benefit . METHODS: We evaluated the safety and immunogenicity of a lyophilized and a liquid form of Hib polysaccharide-tetanus toxoid conjugate vaccines (PRP-T) given in the same syringe as diphtheria-tetanus-pertussis (DTP) vaccine to children in Goroka, Eastern Highlands Province . In Part 1 of the study 209 children were randomized to receive at ages 1, 2 and 3 months either DTP alone or a liquid formulation of DTP/PRP-T or lyophilized PRP-T dissolved in DTP suspension . A further 75 children were given the liquid DTP/PRP-T formulation at ages 2, 3 and 4 months (Part 2) . 54 children aged 15-18 months were given a booster of the same preparation of PRP-T/DTP as they had received during Part 1 . Blood for antibody assays was collected at enrolment, before (Part 1 only) and one month after the third dose, then just before and 3 weeks after the booster dose . RESULTS: Follow-up to age of 12 months showed that PRP-T was safe with no evidence of impaired response to individual vaccine components when combined with DTP . Geometric mean titres (GMTs) of anti-PRP antibody before vaccination (n = 64, mean age 41 days), after 2 doses (mean age 99 days) and after 3 doses (mean age 132 days) of the lyophilized formulation were 0.21, 1.48 and 5.04 microg/ml, respectively, with 58% and 89% having anti-PRP antibody titres > or = 1.0 microg/ml after 2 and 3 doses, respectively . Anti-PRP antibody responses to the liquid Hib vaccine formulation were lower (GMT post-dose 3 = 0.48 microg/ml) than to the lyophilized formulation, but better responses were elicited from older children (Part 2; GMT post-dose 3 = 0.78 microg/ml, with 79% > or = 0.15 microg/ml) . Both PRP-T preparations elicited excellent booster responses suggesting that children are likely to be protected if exposed to Hib infection . CONCLUSIONS: Lyophilized PRP-T given together with DTP is safe and immunogenic when given to young infants . The liquid DTP/PRP-T formulation showed a lower immunogenicity than in earlier studies with this vaccine, which might have been due to exposure to low temperature during shipment or the younger age at immunization.

J Chemother, 2002 Jul, 14 Suppl 3, 17 - 24
What can PROTEKT tell us at a local level?
Inoue M.
Because of increasing antimicrobial resistance in bacterial pathogens causing community-acquired respiratory tract infections (CARTIs), surveillance at local, regional, national and international levels is necessary to provide information to guide empiric antimicrobial therapy . PROTEKT (Prospective Resistant Organism Tracking and Epidemiology for the Ketolide Telithromycin) is a longitudinal, global, multicenter surveillance study designed to monitor the worldwide development of antimicrobial resistance, and disseminate up-to-date information via the internet to assist in the choice of empiric therapy at the local level . In this paper, the results for the first year of PROTEKT are presented from a local perspective . In examples from Japan, USA and Europe, great variation was observed between antimicrobial susceptibility patterns for Streptococcus pneumoniae, Streptococcus pyogenes and Haemophilus influenzae in countries and cities in close proximity to each other . Telithromycin demonstrated excellent in vitro activity against all organisms and is a potential new candidate for the empiric therapy of CARTIs . The first year of PROTEKT has provided valuable information on the prevalence of antimicrobial resistance of bacterial agents causing CARTIs that can be used for guiding empiric therapy and policies . Variation in local resistance observed in this study further emphasizes the need for accurate up-to-date surveillance data at the local level.

J Chemother, 2002 Jul, 14 Suppl 3, 9 - 16
Global surveillance through PROTEKT: the first year; Gruneberg RN; The increasing antimicrobial resistance amongst bacterial pathogens causing community-acquired respiratory tract infections (CARTIs) necessitates surveillance at the local, regional, national and international levels to provide information to guide empiric antimicrobial therapy . PROTEKT (Prospective Resistant Organism Tracking and Epidemiology for the Ketolide Telithromycin) is a longitudinal, global, multicenter surveillance study designed to monitor the worldwide development of antimicrobial resistance and disseminate up-to-date information via the internet to assist in the choice of empiric therapy at the local level . In this paper, the results for the first year of PROTEKT are presented from a global perspective . Streptococcus pneumoniae, followed by Haemophilus influenzae and Moraxella catarrhalis, are the principal organisms responsible for the majority of CARTIs . The global prevalence of penicillin G resistance in S . pneumoniae has risen to an alarming 36.3% (high-level resistance 22.1%, intermediate-level 14.2%) with the highest prevalence found in Asia (68%) . In all regions, macrolide resistance is greater than penicillin G resistance with a global prevalence rate of 31.2% . High resistance rates were also found for tetracycline (30.5%) and co-trimoxazole (43.9%), and multiresistance was found between penicillin G, macrolides, tetracycline and co-trimoxazole . The prevalence of beta-lactamase-producing H . influenzae and M . catarrhalis was found to be similar to previous reports . Macrolide resistance in S . pyogenes was 0.3% overall . Telithromycin demonstrated excellent in vitro activity against all organisms and is a potential new candidate for the empiric therapy of CARTIs . The first year of PROTEKT has provided valuable information on the prevalence of antimicrobial resistance of bacterial agents causing CARTIs that can be used for guiding empiric therapy and policies . The rapidly developing and geographically varying resistance observed in this study further emphasizes the need for accurate up-to-date surveillance data.

Pediatrics . 2002 Nov;110(5):e58.
Reducing geographic, racial, and ethnic disparities in childhood immunization rates by using reminder/recall interventions in urban primary care practices; Szilagyi PG et al.; CONTEXT: An overarching national health goal of Healthy People 2010 is to eliminate disparities in leading health care indicators including immunizations . Disparities in US childhood immunization rates persist, with inner-city, black, and Hispanic children having lower rates . Although practice or clinic-based interventions, such as patient reminder/recall systems, have been found to improve immunization rates in specific settings, there is little evidence that those site-based interventions can reduce disparities in immunization rates at the community level . OBJECTIVE: To assess the effect of a community-wide reminder, recall, and outreach (RRO) system for childhood immunizations on known disparities in immunization rates between inner-city versus suburban populations and among white, black, and Hispanic children within an entire county . SETTING: Monroe County, New York (birth cohort: 10 000, total population: 750 000), which includes the city of Rochester . Three geographic regions within the county were compared: the inner city of Rochester, which contains the greatest concentration of poverty (among 2-year-old children, 64% have Medicaid); the rest of the city of Rochester (38% have Medicaid); and the suburbs of the county (8% have Medicaid) . INTERVENTIONS: An RRO system was implemented in 8 city practices in 1995 (covering 64% of inner-city children) and was expanded to 10 city practices by 1999 (covering 74% of inner-city children, 61% of rest-of-city children, and 9% of suburban children) . The RRO intervention involved lay community-based outreach workers who were assigned to city practices to track immunization rates of all 0- to 2-year-olds, and to provide a staged intervention with increasing intensity depending on the degree to which children were behind in immunizations (tracking for all children, mail, or telephone reminders for most children, assistance with transportation or scheduling for some children, and home visits for 5% of children who were most behind in immunizations and who faced complex barriers) . STUDY PARTICIPANTS: Three separate cohorts of 0- to 2-year-old children were assessed-those residing in the county in 1993, 1996, and 1999 . STUDY DESIGN: Immunization rates were measured for each geographic region in Monroe County at 3 time periods: before the implementation of a systematic RRO system (1993), during early phases of implementation of the RRO system (1996), and after implementation of the RRO system in 10 city practices (1999) . Immunization rates were compared for children living in the 3 geographic regions, and for white, black, and Hispanic children . Immunization rates were measured by the same methodology in each of the 3 time periods . A denominator of children was obtained by merging patient lists from the practice files of most pediatric and family medicine practices in the county (covering 85% to 89% of county children) . A random sample of children (>500 from the suburbs and >1200 from the city for each sampling period) was then selected for medical chart review at practices to determine demographic characteristics (including race and ethnicity) and immunization rates . City children were oversampled to allow detection of effects by geographic region and race . Rates for the 3 geographic regions and for the entire county were determined using Stata to adjust for the clustered sampling . MAIN OUTCOME MEASURES: Immunization rates at 12 and 24 months for recommended vaccines (4 diphtheria-tetanus-pertussis:3 polio:1 measles-mumps-rubella: > or =1 Haemophilus influenzae type b on or after 12 months of age) . RESULTS: DISPARITIES BY GEOGRAPHIC REGION: Baseline immunization rates (1993) for 24-month-olds were as follows: inner city (55%), rest of city (64%), and suburbs (73%), with an 18% difference in rates between the inner city and suburbs . By 1996, immunization rates rose faster in the inner city (+21% points) than in the suburbs (+14% points) so that the difference in rates between the inner city and suburbs had narrowed to 11% . In 1999, rates were similar across geographic regions: inner city (84%), rest of city (81%), and suburbs (88%), with a 4% difference between the inner city and suburbs . DISPARITIES BY RACE AND ETHNICITY: Immunization rates were available in 1996 and 1999 by race and ethnicity . Twenty-four-month immunization rates in 1996 showed disparities: white (89%), black (76%), and Hispanic (74%), with a 13% difference between rates for white and black children and a 15% difference between white and Hispanic children . In 1999, rates were similar across the groups: white (88%), black (81%), and Hispanic (87%), with a 7% difference between rates for white and black children, and a 1% difference between white and Hispanic children . CONCLUSIONS: A community-wide intervention of patient RRO raised childhood immunization rates in the inner city of Rochester and was associated with marked reductions in disparities in immunization rates between inner-city and suburban children and among racial and ethnic minority populations . By targeting a relatively manageable number of primary care practices that serve city children and using an effective strategy to increase immunization rates in each practice, it is possible to eliminate disparities in immunizations for vulnerable children.

Pediatrics, 2002 Nov, 110(5), 935 - 9
Timeliness of childhood immunizations; Luman ET et al.; OBJECTIVE: To examine the timeliness of vaccine administration among infants and young children in the United States . METHODS: We analyzed age at receipt of vaccines among 16 211 children aged 24 to 35 months in the 2000 National Immunization Survey and examined receipt at the recommended time of each dose and selected vaccination series, as well as receipt at 4 additional time frames: acceptably early, late, never by 24 months, and too early to be considered valid . We also examined the relationship between timeliness of vaccinations and characteristics of the child, mother, and immunization provider, using multivariate logistic regression . RESULTS: Only 9% of children received all recommended vaccines at the recommended ages . The rates varied significantly by antigen, ranging from 24% for all Haemophilus influenzae type b doses to 75% for all hepatitis B doses as recommended . Overall, 55% of children did not receive all recommended doses by 24 months of age, and 8% of children received at least 1 vaccination dose too early to be considered valid . Factors associated with not receiving all vaccines as recommended were having more children in the household, mothers younger than 30 years, use of public providers, and multiple vaccination providers . CONCLUSIONS: By 24 months of age, 9 of 10 children received at least 1 vaccine outside the recommended age ranges . High vaccination status of children at 24 months of age does not reflect the reality that many vaccinations are not given at the appropriate ages . Timeliness of vaccination is critical to prevent disease outbreaks, protect children through their first 2 years of life, and minimize the need to repeat doses.

Stroke, 2002 Nov, 33(11), 2581 - 6
Impact of infectious burden on progression of carotid atherosclerosis; Espinola-Klein C et al.; BACKGROUND AND PURPOSE: Recent findings suggest a causative role of infections in the pathogenesis of atherosclerosis . The extent of atherosclerosis and the prognosis of patients with atherosclerosis seem to be increased by the number of infections to which an individual has been exposed . In a prospective study, we evaluated the effect of 8 pathogens and the aggregate pathogen burden on the progression of carotid atherosclerosis . METHODS: In 504 patients (74.9% men; age, 62.9+/-10 years), we measured intima-media thickness and prevalence of carotid artery stenosis . Follow-up measurements after a mean of 2.5 years were available in 427 patients (85%) . Blood samples were taken, and IgG or IgA antibodies to Chlamydia pneumoniae, Helicobacter pylori, Haemophilus influenzae, Mycoplasma pneumoniae, cytomegalovirus, Epstein-Barr virus, and herpes simplex virus types 1 and 2 were measured . Statistical evaluation was performed with logistic regression procedures . RESULTS: Elevated IgA antibodies against C pneumoniae (P<0.04) and IgG antibodies against Epstein-Barr virus (P<0.01) and herpes simplex virus type 2 (P<0.04) were associated with progression of atherosclerosis (increase of intima-media thickness > or =0.1 mm/y or progression of carotid stenosis) after adjustment for age, sex, cardiovascular risk factors, highly sensitive C-reactive protein, and statin intake . Infectious burden, divided into 0 to 3, 4 to 5, and 6 to 8 seropositivities, was significantly associated with progression of atherosclerosis, with odds ratios of 1.8 (95% confidence interval, 1.1 to 2.9) for 4 to 5 and 3.8 (95% CI, 1.6 to 8.8) for 6 to 8 compared with 0 to 3 seropositivities after adjustment . CONCLUSIONS: Our results support the hypothesis that the number of infectious pathogens to which an individual has been exposed independently contributes to the progression of carotid atherosclerosis.

Chin Med J (Engl), 2002 Sep, 115(9), 1415 - 7
Identification of Streptococcus species and Haemophilus influenzae by direct sequencing of PCR products from 16S-23SrDNA intergenic spacer regions; Lu X et al.; OBJECTIVE: To set up a rapid and simple method for identificating bacteria by 16S-23SrDNA intergenic spacer regions (ISRs) . METHODS: Polymorphic products of PCR from ISRs were selected on agarose gel and sequenced directly using purified fragments by excising the gel without cloning . Nucleotide sequences were compared with GenBank databases and analyzed by DNAMAN program . RESULTS: There was only a single product in streptococcus genus after PCR amplification of 16S-23SrDNA ISRs . Five streptococcal species were obtained from 7 strains of streptococcus . Two major amplicons were consistently generated for 8 strains of Haemophilus influenzae (H . influenzae) . The sequence data showed that they all belonged to H . influenzae type b on GenBank databases . CONCLUSION: PCR and direct sequencing of 16S-23SrDNA ISRs were very successful methods for bacterial species identification.

Mol Microbiol, 2002 Nov, 46(3), 731 - 43
The Haemophilus influenzae Hia autotransporter harbours two adhesive pockets that reside in the passenger domain and recognize the same host cell receptor; Laarmann S et al.; Haemophilus influenzae is a human-specific pathogen and a major source of morbidity worldwide . Infection with this organism begins with colonization of the nasopharynx, a process that probably depends on adherence to respiratory epithelium . The Hia autotransporter protein is the major adhesin ex-pressed by a subset of non-typeable H . influenzae strains and promotes high-level adherence to a variety of human epithelial cell lines . In the current study, we discovered that the Hia passenger domain contains two distinct binding pockets, including one at the C-terminal end and a second at the N-terminal end . Competition assays revealed that the two binding pockets interact with the same host cell receptor structure, although with differing affinities . Additional experiments demonstrated that both binding domains are required for full-level bacterial adherence . These observations are reminiscent of eukaryotic cell adhesion molecules and highlight the first example of a bacterial adhesin with two domains that participate in a bivalent interaction with identical host cell receptors . Such an interaction increases avidity, thus stabilizing bacterial adherence to the epithelial surface, despite physical forces such as coughing, sneezing and mucociliary clearance.

Clin Infect Dis, 2002 Nov 15, 35(10), 1205 - 11 Epub 2002 Oct 28.
Nursing home-acquired pneumonia; Mylotte JM; Pneumonia is the most serious of the common infections that occur in nursing homes, with a high case-fatality rate and considerable mortality among survivors . Risk factors for nursing home-acquired pneumonia (NHAP) have been defined, and prediction models for death due to NHAP have been developed . The bacterial etiology of NHAP has been debated, but "typical" bacterial pathogens (Streptococcus pneumoniae, Haemophilus influenzae, and Moraxella catarrhalis) are most important . Clinical presentation of NHAP is said to be "atypical," but this may be confounded by dementia in the nursing home resident . A recent guideline has made recommendations regarding the minimal diagnostic workup when a resident has a suspected case of pneumonia . Until recently, most guidelines for the treatment of pneumonia did not specifically address NHAP; there is some evidence that use of a quinolone alone may be an acceptable first choice of therapy for most cases . Pneumococcal and influenza vaccination have been the primary prevention measures . However, additional methods to prevent NHAP should be evaluated, including improving the oral hygiene of residents and instituting pharmacological interventions.

J Clin Microbiol, 2002 Nov, 40(11), 4340 - 2
Assessment of the nasopharyngeal bacterial flora of rhesus macaques: moraxella, Neisseria, haemophilus, and other genera; Bowers LC et al.; The nasopharyngeal bacterial flora of healthy rhesus macaques was surveyed for the presence of Neisseria and Haemophilus species, as well as Moraxella catarrhalis . M . catarrhalis was found both in healthy rhesus macaques and in possibly immunocompromised rhesus macaques . Several Haemophilus spp . that are part of the normal nasopharyngeal bacterial flora of humans were found in many animals; these Haemophilus species included H . parahaemolyticus, H . segnis, and H . parainfluenzae . While Haemophilus influenzae was not identified, it is possible that the identification of H . influenzae types may have been thwarted by the growth of less fastidious species . A number of animals harbored Neisseria spp . such as N . sicca . However, Neisseria meningitidis was not found . In summary, it appears as though the rhesus macaque may be used as a model for M . catarrhalis infections . Moreover, in view of the susceptibility of macaques to organisms of the Haemophilus and Neisseria genera, it is possible that these animals may also accurately model nontypeable H . influenzae and N . meningitidis infections.

Am J Manag Care, 2002 Oct, 8(14 Suppl), S345 - 52
Strategies for decreasing multidrug antibiotic resistance: role of ototopical agents for treatment of middle ear infections; Klein JO; Change in the susceptibility of bacterial pathogens to antimicrobial agents is constant . The efficacy of a new drug may change as it is used in clinical settings, and resistant bacterial clones result from the encounter of drug and organism . Soon after the introduction of the sulfonamides in the mid-1930s, the first effective agents of the antimicrobial era, resistance of pneumococci and group A streptococci was evident . In each of the following decades, a different problem in multidrug resistance occurred among common bacterial pathogens: beta-lactamase-producing staphylococci in the 1950s; highly resistant gram-negative enteric bacteria in the 1960s; beta-lactamase-producing Haemophilus influenzae and Moraxella catarrhalis in the 1970s; and multidrug-resistant pneumococci in the 1980s . Antimicrobial resistance among respiratory pathogens is now a common clinical problem throughout the world, and its management is a part of routine office practice . Currently in the United States, about 25% of pneumococci are resistant to penicillin, and 25% of H influenzae and 90% of M catarrhalis produce beta-lactamase and would be inactivated by organisms producing the enzyme . The emergence of penicillin and multidrug-resistant pneumococci and beta-lactamase-producing strains of H influenzae and M catarrhalis have special importance for the management of infections of the middle ear . The widespread use of oral and parenteral antimicrobial drugs for appropriate and inappropriate uses has driven the emergence and spread of resistant organisms . This article discusses current susceptibility patterns of organisms involved in middle ear infections, risk factors associated with development of resistant strains, strategies for limiting the incidence and spread of resistant organisms and, as part of the strategy, use of ototopical rather than systemic antimicrobial drugs for chronic suppurative otitis media (CSOM) and acute otitis media (AOM) in children with tympanostomy tubes . Although many ototopical agents are approved by the Food and Drug Administration for the indication of otitis externa, only ofloxacin otic is approved for treatment of CSOM in patients older than 12 years of age and AOM in children with tympanostomy tubes who are 1 year of age or older.

Appl Environ Microbiol, 2002 Nov, 68(11), 5634 - 40
Donor substrate regeneration for efficient synthesis of globotetraose and isoglobotetraose; Shao J et al.; Here we describe the efficient synthesis of two oligosaccharide moieties of human glycosphingolipids, globotetraose (GalNAcbeta1-->3Galalpha1-->4Galbeta1-->4Glc) and isoglobotetraose (GalNAcbeta1-->3Galalpha1-->3Galbeta1-->4Glc), with in situ enzymatic regeneration of UDP-N-acetylgalactosamine (UDP-GalNAc) . We demonstrate that the recombinant beta-1,3-N-acetylgalactosaminyltransferase from Haemophilus influenzae strain Rd can transfer N-acetylgalactosamine to a wide range of acceptor substrates with a terminal galactose residue . The donor substrate UDP-GalNAc can be regenerated by a six-enzyme reaction cycle consisting of phosphoglucosamine mutase, UDP-N-acetylglucosamine pyrophosphorylase, phosphate acetyltransferase, pyruvate kinase, and inorganic pyrophosphatase from Escherichia coli, as well as UDP-N-acetylglucosamine C4 epimerase from Plesiomonas shigelloides . All these enzymes were overexpressed in E . coli with six-histidine tags and were purified by one-step nickel-nitrilotriacetic acid affinity chromatography . Multiple-enzyme synthesis of globotetraose or isoglobotetraose with the purified enzymes was achieved with relatively high yields.

J Trop Pediatr, 2002 Oct, 48(5), 273 - 9
Seven days vs . 10 days ceftriaxone therapy in bacterial meningitis; Singhi P et al.; Ceftriaxone is recommended in children with acute bacterial meningitis (ABM) for 10 days . However, the drug is expensive, and shorter duration of therapy, if equally effective, would cut costs of therapy and hospitalization . The aim of this study was to compare the outcome of 7 days vs . 10 days' ceftriaxone therapy in children with ABM . Seventy-three children aged 3 months to 12 years with ABM, consecutively admitted to hospital were enrolled . Ceftriaxone was given for 7 days to all . Randomization to group I (7 days) and group II (10 days) therapy was done on the seventh day . At the end of 7 days' therapy in group I and 10 days in group II, children were evaluated using a clinical scoring system . Children with a score of more than 10 were labelled as 'treatment failures' and were continued on ceftriaxone . If a score was less than 10, the antibiotic was stopped . Complications were appropriately evaluated and managed . All children were followed-up 1 month after discharge: neurodevelopmental assessment, Denver Development Screening Tests, IQ and hearing assessment were done . After excluding four patients, there were 35 children in group I and 34 in group II . The two groups were comparable with respect to age, sex, nutritional status, presenting clinical features, and CSF parameters . Organism identification was possible in 38 per cent of children: (Streptococcus pneumoniae, 21 per cent; Haemophilus influenzae, 13 per cent; meningococcus, 4 per cent) . Treatment failure rate was comparable in both groups (9 in group I and 8 in group II) as was the sequelae at discharge and at 1 month (9 in group I, 15 in group II,p > 0.1) . Status epilepticus and focal deficits at presentation were significantly associated with treatment failures and sequelae in both the groups (p < 0.05) . Length of hospital stay was shorter in group I (10.8 +/- 6.0 days) as compared with group II (14.4 +/- 7.2 days,p < 0.05) and frequency of nosocomial infection was significantly more in group II (p < 0.05) . It was concluded that clinical outcome of patients treated with 7 days' ceftriaxone therapy is similar to that of 10 days' therapy, and is associated with lesser nosocomial infection and earlier hospital discharge . Seven days ceftriaxone therapy may be recommended for uncomplicated ABM in children in developing countries.

J Med Assoc Thai, 2002 Aug, 85 Suppl 2, S694 - 9
Combination vaccines; Chokephaibulkit K; Recently multiple individual vaccines were put together into one syringe . This is ideal to simplify the administration of vaccines and reduce emotional distress from multiple injections . However, combination of many vaccines may interfere with the properties of each individual antigen and complicate the schedule . From earlier studies, most of the combinations of diphtheria-tetanus-pertussis (whole-cell) vaccine (DTPw), Haemophilus influenzae type b vaccine (Hib), hepatitis B vaccine (HBV), and inactivated polio vaccine (IPV) were safe and adequately immunogenic . On the other hand, there was a notable reduction in anti-PRP when Hib was combined with acellular pertussis vaccine (DTPa) . Combination of hepatitis A vaccine and HBV was safe and effective . Those coming soon in the pipeline are DTPa-Hib-HBV, MMR-varicella, pneumococcal-meningococcal . With the increase in demand, health-care providers need to be acquainted to these combination vaccines . The bottom line is to make sure that the children get vaccination appropriately.

Pharm Res, 2002 Sep, 19(9), 1330 - 6
On technological and immunological benefits of multivalent single-injection microsphere vaccines; Boehm G et al.; PURPOSE: With the aim of developing multivalent vaccines for single-injection, we examined the feasibility of combining antigens in biodegradable microspheres . Such vaccines are expected to improve vaccination coverage by reducing the number of vaccination sessions required to generate immunity . METHODS: Mono- and multivalent vaccines of Haemophilus influenzae type b (Hib) conjugate, diphtheria toxoid (DT), tetanus toxoid (TT), and pertussis toxin (PT) in poly (lactic acid) and poly(lactic-coglycolic acid) microspheres were prepared by spray drying, and the influence of coencapsulated antigens and excipients on antigen loading, release, and stability was examined . Two tetravalent formulations were tested in guinea pigs . RESULTS: Monovalent Hib and PT vaccines showed loading efficiencies of 10% (Hib) and 30% (PT) in both polymers . The loading efficiencies increased upon addition of trehalose and, even more, when the antigens were coencapsulated in di- and trivalent combinations . Highest loading efficiencies (> 80%) were achieved with trivalent formulations (DT + PT + Hib) that also contained coencapsulated albumin . The percentage of antigen released during 24 h of incubation was typically 10-40% and decreased as loading efficiency increased . Enzyme-linked immunosorbent assay (ELISA) data revealed that TT, DT, and PT remained antigenic throughout the encapsulation and subsequent release processes . Finally, all antigens maintained their immunogenicity, since strong and sustained antibody responses were elicited after a single injection of tetravalent microsphere vaccines (DT + TT + PT + Hib) in guinea pigs . CONCLUSIONS: This study reveals technologic benefit as well as an immunological potential of multivalent single-injection microsphere vaccines . The results support our hypothesis that coencapsulation of several antigens may intrinsically improve entrapment of antigenic and immunogenic antigen probably by virtue of increased protein concentration during microencapsulation leading to mutual stabilization of the components.

J Infect Dis, 2002 Nov 1, 186(9), 1358 - 61 Epub 2002 Oct 08.
Combinations of protein polysaccharide conjugate vaccines for intranasal immunization; Ugozzoli M et al.; The ability of 2 mutants of heat-labile Escherichia coli enterotoxin (LTK63 and LTR72) to enhance the immunogenicity of 2 protein polysaccharide conjugate vaccines, Neisseria meningitidis group C (MenC) and Haemophilus influenzae type B (Hib), both of which are conjugated to the nontoxic mutant of diphtheria toxin (CRM197), after intranasal (inl) immunization in mice was evaluated . In addition, the question of whether combining both vaccines in a single formulation with heat-labile E . coli enterotoxin mutants reduced the response to either vaccine was investigated . The results showed that potent serum antibody responses against MenC and Hib could be elicited by inl immunization in combination with the mucosal adjuvants . Moreover, IgA mucosal responses were induced only in animals immunized through the inl route . Finally, the coadministration of 2 conjugate vaccines simultaneously did not adversely affect the responses against either . These studies support the rationale for developing mucosal vaccines, based on combining protein polysaccharide conjugates with heat-labile E . coli enterotoxin mutants, for infants and young children.

Avian Pathol, 2002 Aug, 31(4), 363 - 70
Occurrence of conjunctivitis, sinusitis and upper region tracheitis in Japanese quail (Coturnix coturnix japonica), possibly caused by Mycoplasma gallisepticum accompanied by Cryptosporidium sp . infection; Murakami S et al.; On a farm raising approximately 75,000 Japanese quail (Coturnix coturnix japonica) for egg production, the diseased quail showed clinical signs of swelling of the head, nasal discharge, increased lacrimation, and decreased egg production . The flock experienced a mortality rate of 5.7% per day . Macroscopic observation revealed large, gelatinous masses of caseous exudate in the sinuses, egg peritonitis, and airsacculitis . Microscopically, non-purulent or purulent inflammation accompanied by lymphoid hyperplastic tissue with germinal centers was observed in the oculofacial respiratory mucosa . The developing stage of the lesions was abscess formation . In the investigation of pathogens, antigens to Mycoplasma gallisepticum and Pasteurella multocida serotype D were immunolabeled on and demonstrated in the mucosal membranes . In addition, P . multocida, Escherichia coli, Staphylococcus sp., and Streptococcus sp . were isolated from the infraorbital sinuses, and Mycoplasma isolated from a diseased bird was confirmed as M . gallisepticum by polymerase chain reaction (PCR) . Furthermore, Cryptosporidium sp . was frequently found in the brush border . Serological, bacteriological and PCR examinations, some with negative outcomes, were carried out concerning microbes that are known to cause swollen heads in birds (Haemophilus paragallinarum, Newcastle disease virus and turkey rhinotracheitis virus) . The average concentration of ammonia fumes in the cages was 30.6 parts/106, which suggests that the high levels of ammonia fumes promoted infection and multiplication of M . gallisepticum in the quail, and that the clinical disease then worsened due to mixed infection with M . gallisepticum and Cryptosporidium sp . or other bacteria.

J Comput Chem, 2002 Dec, 23(16), 1656 - 70
Enhanced docking with the mining minima optimizer: acceleration and side-chain flexibility; Kairys V et al.; The ligand-protein docking algorithm based on the Mining Minima method has been substantially enhanced . First, the basic algorithm is accelerated by: (1) adaptively determining the extent of each energy well to help avoid previously discovered energy minima; (2) biasing the search away from ligand positions at the surface of the receptor to prevent the ligand from staying at the surface when large sampling regions are used; (3) quickly testing multiple different ligand positions and orientations for each ligand conformation; and (4) tuning the source code to increase computational efficiency . These changes markedly shorten the time needed to discover an accurate result, especially when large sampling regions are used . The algorithm now also allows user-selected receptor sidechains to be treated as mobile during the docking procedure . The energies associated with the mobile side chains are computed as if they belonged to the ligand, except that atoms at the boundary between side chains and the rigid backbone are treated specially . This new capability is tested for several well-known ligand/protein systems, and preliminary application to an enzyme whose substrate is unknown--the recently solved hypothetical protein YecO (HI0319) from Haemophilus influenzae--indicates that side-chains relaxations allow candidate substrates of various sizes to be accommodated .

Pediatr Infect Dis J, 2002 Oct, 21(10), 940 - 7
Safety and immunogenicity of pneumococcal conjugate vaccine in combination with diphtheria, tetanus toxoid, pertussis and Haemophilus influenzae type b conjugate vaccine; Obaro SK et al.; BACKGROUND: Pneumococcal polysaccharide/protein conjugate vaccines (PnCV) are immunogenic and effective in infancy . However, an addition to the nine currently recommended vaccine injections during the first year of life of African children may be a deterrent to participation in a PnCV program . Thus we have evaluated the safety and immunogenicity of a 9-valent PnCV (Wyeth Lederle Pediatrics and Vaccines) mixed with diphtheria, tetanus toxoid, cell pertussis and type b (TETRAMUNE) . METHODS: Healthy Gambian infants were randomized at the age of 2 months to receive three doses 1 month apart of either (1) placebo reconstituted in TETRAMUNE in the right thigh (control) or (2) PnCV in the left thigh and TETRAMUNE in the right thigh (separate) or (3) PnCV reconstituted in TETRAMUNE as a single injection in the right thigh (combined) . The vaccines were given together with routine Expanded Program on Immunization vaccines . Adverse reactions were recorded after vaccination, and antibody concentrations were measured by enzyme-linked immunosorbent assays . RESULTS: Local induration and tenderness were observed more commonly at the site of injection of TETRAMUNE than at the site of injection with PnCV after each dose of vaccination . Swelling at the site of injection was encountered more frequently at the site of administration of TETRAMUNE than at the site of administration PnCV ( P< 0.00001 for Doses 1 and 2 and P< 0.0009 for Dose 3) . Swelling at the site of administration of TETRAMUNE mixed with PnCV was comparable with that observed for TETRAMUNE alone . Although most mothers reported that the babies "felt hot" 24 h after each injection, febrile reactions (temperature, >or=38 degrees C) were infrequent and resolved with antipyretics . Geometric mean titer for anti-polyribosylribitol phosphate antibody was 11.6 microg/ml {95% confidence limits (95% CI), 9.2, 14.6} in the control group and comparable with 13.3 microg/ml (95% CI 11.0, 16.0) in the combined group and significantly higher at 17.9 microg/ml (95% CI 14.7, 21.9; P= 0.01) in the separate group . Geometric mean concentrations of serotype-specific pneumococcal antibodies were higher in the combined group than the separate group for all nine serotypes . Antibody responses to diphtheria and pertussis antigens were similar in all groups . Anti-tetanus toxoid antibody concentrations were lowest in the combined group (6.66 IU/ml, 95% CI 5.77, 7.68 in the control group; 5.15 IU/ml, 95% CI 4.39, 6.03 in the combined group; P= 0.02) . However, all vaccinees achieved protective antibody values . CONCLUSION: The combination of TETRAMUNE and PnCV is safe and immunogenic.

Genetika, 2002 Sep, 38(9), 1203 - 14
{Purine regulon of gamma-proteobacteria: a detailed description}; Ravcheev DA et al.; The structure of the purine regulon was studied by a comparative genomic approach in seven genomes of gamma-proteobacteria: Escherichia coli, Salmonella typhi, Yersinia pestis, Haemophilus influenzae, Pasteurella multocida, Actinobacillus actinomycetemcomitans, and Vibrio cholerae . The palindromic binding site of the purine repressor (consensus ACGCAAACGTTTGCGT) is fairly well retained of genes encoding enzymes that participate in the synthesis of inosinemonophosphate from phosphoribozylpyrophosphate and in transfer of unicarbon groups, and also upstream of some transport protein genes . These genes may be regarded as the main part of the purine regulon . In terms of physiology, the regulation of the purC and gcvTHP/folD genes seems to be especially important, because the PurR site was found upstream of nonorthologous but functionally replaceable genes . However, the PurR site is poorly retained in front of orthologs of some genes belonging to the E . coli purine regulon, such as genes involved in general nitrogen metabolism, biosynthesis of pyrimidines, and synthesis of AMP and GMP from IMP, and also upstream of the purine repressor gene . It is predicted that purine regulons of the examined bacteria include the following genes: upp participating in synthesis of pyrimidines; uraA encoding an uracil transporter gene; serA involved in serine biosynthesis; folD responsible for the conversion of N5,N10-methenyl tetrahydrofolate into N10-formyltetrahydrofolate; rpiA involved in ribose metabolism; and protein genes with an unknown function (yhhQ and ydiK) . The PurR site was shown to have different structure in different genomes . Thus, the tendency for a decline of the conservatism of site positions 2 and 15 was observed in genomes of bacteria belonging to the Pasteurellaceae and Vibrionaceae groups.

Clin Exp Immunol, 2002 Nov, 130(2), 325 - 30
Humoral immunity and bronchiectasis; Stead A et al.; Bronchiectasis is a common complication of primary antibody deficiency but the incidence of antibody deficiency as an underlying cause of bronchiectasis is largely undefined . In this study the humoral immune status of a cohort of bronchiectatic patients was investigated to detect the frequency of significant antibody deficiency and to determine the extent of immunological investigation which is appropriate for routine assessment of bronchiectasis patients . Fifty-six out-patients (with a mean age of 59.6 years) had serum immunoglobulins, IgG subclasses and specific antibodies to capsular polysaccharides of Haemophilus influenzae and Streptococcus pneumoniae measured . Where specific antibody -levels were low, where possible, appropriate immunization with pneumococcal or conjugated Haemophilus polysaccharide vaccines was offered and the responses quantified . Three of 56 patients had low total serum IgG levels . Thirteen of 56 had deficiencies of either a single IgG subclass or combinations of two or more subclasses, with IgG4 being most frequently implicated (9/56) . Twenty-nine of 56 had low basal specific polysaccharide antibody levels . Test immunization, where performed, produced satisfactory responses in all cases except one, where a specific defect of responsiveness to pneumococcal polysaccharide was identified . This study indicates that antibody deficiency is an uncommon aetiological/underlying factor in the causation of bronchiectasis beyond the fourth decade and that detailed investigation of humoral immune status as a routine in bronchiectasis patients, at least at this age, is not generally justified.

Clin Exp Immunol, 2002 Nov, 130(2), 271 - 8
Risk factors in HIV-1-infected patients developing repetitive bacterial infections: toxicological, clinical, specific antibody class responses, opsonophagocytosis and Fc(gamma) RIIa polymorphism characteristics; Payeras A et al.; The aim of the study was to determine possible factors related to the risk of developing recurrent bacterial respiratory tract infections in HIV-1-infected patients, regardless of the degree of immune cellular impairment . Thirty-three HIV-1 seropositive patients with previous repetitive bacterial respiratory tract infections (case group), 33 HIV-1 seropositive controls (matched by CD4-cell counts) without these antecedents and 27 healthy controls were studied before and after administration of pneumococcal and Haemophilus influenzae type b vaccines . Clinical or toxicological variables, cutaneous tests, complement factors, beta2-microglobulin, serum IgM, IgA, IgG and subclasses, specific antibodies (IgG, IgG2, IgA) against pneumococcal vaccine and polyribosylribitol phosphate (PRP), their avidity, opsonophagocytosis and IgG(2)m and Fc(gamma)RIIa allotypes were determined . A history of drug abuse (P = 0.001), less likelihood of receiving high activity antiretroviral treatment high activity antiretroviral treatment (HAART) (P = 0.01), higher levels of HIV-1 viral load (P < 0.05), serum IgG (P < 0.01) and beta2-microglobulin (P < 0.01) were observed in the case group . Also, a lower increase in specific antibodies to pneumococcal vaccine and PRP was demonstrated in the cases in comparison with the two control groups . No differences were observed in the avidity of antibodies, opsonophagocytic capacity or IgG(2)m and Fc(gamma)RIIa allotypes between the three groups . These data indicate that vaccination strategies against encapsulated bacteria can be unsuccessful in the HIV-1-infected patients presenting repetitive bacterial respiratory tract infections if behavioural aspects or measures to improve adherence to HAART therapies are not considered.

Clin Microbiol Infect, 2002 Oct, 8(10), 646 - 53
Pharmacodynamics of amoxicillin/clavulanic acid against Haemophilus influenzae in an in vitro kinetic model: a comparison of different dosage regimens including a pharmacokinetically enhanced formulation; Lowdin E et al.; OBJECTIVE: To study the pharmacodynamics of amoxicillin/clavulanic acid against different strains of Haemophilus influenzae in an in vitro kinetic model . The concentrations used corresponded to human serum levels obtained after 875 mg amoxicillin/clavulanic acid given b.i.d., 500/125 mg amoxicillin/clavulanic acid given t.i.d . and those obtained with a pharmacokinetically enhanced formulation containing 1125/125 mg amoxicillin/clavulanic acid (immediate release) and 875 mg amoxicillin (sustained release) given b.i.d . METHODS: Bacteria at an initial inoculum of 106 colony-forming units (CFU)/mL were exposed to amoxicillin/clavulanic acid with an initial concentration of approximately 15/3 mg/L, 8/3 mg/L simulating the peak levels in humans achieved after a dose of 875/125 mg and 500/125 mg with a half-life of 1 h . In addition, experiments with a 2000/125 mg pharmacokinetically enhanced formulation of amoxicillin/clavulanic acid given b.i.d . were performed . A repeated dose was given at 12 h after the initial dose of 875/125 mg and the pharmacokinetically enhanced formulation or at 8 and 16 h after the dose of 500/125 mg . The experiments were performed in an in vitro kinetic model, which consists of a spinner flask with a filter membrane fitted in between the upper part and the bottom part in order to prevent bacterial dilution . The medium is removed from the culture flask, through the filter, at a constant rate with a pump . Repeated samples were taken at intervals of 1-2 h up to 24 h during the experiments for viable counting . One of the strains of H . influenzae was also exposed to a constant concentration corresponding to the peak serum levels obtained after a dose of 500/125 mg . RESULTS: The concentrations of amoxicillin in the in vitro kinetic model were as expected . At the end of the experiment (24 h), there was a tendency for a greater bactericidal effect with 500/125 mg t.i.d., as compared to 875/125 b.i.d., with differences in CFUs between the two dosing regimens of 2.6 log10 CFU for H . influenzae LH 2803 and 1.8 log10 CFU for the other clinical strains . However, these differences did not reach statistical significance (P = 0.075 and 0.10, respectively) . A statistically significant higher bactericidal effect was seen in the experiments with the pharmacokinetically enhanced formulation in comparison with the b.i.d . regimen both at 8, 16 and 24 h and at 8 and 16 h with the t.i.d . regimen . With the new formulation, no regrowth was seen at 24 h, similar to the results obtained with a constant concentration . CONCLUSIONS: Neither of the standard dosing regimens of amoxicillin (875/125 mg b.i.d . or 500/125 mg) used in our study, in which the time that the free (non-protein-bound) concentration the MIC (T > MIC) exceeding was less than 50%, was sufficient to achieve a complete bactericidal effect during the first 24 h of treatment . However, a statistically significant difference in bactericidal activity was seen at 8, 16 and 24 h vs . the b.i.d . regimen and at 8 and 16 h vs . the t.i.d . regimen with the pharmacokinetically enhanced formulation . This formulation gave a longer T > MIC (73-79%) of amoxicillin even though the concentration of clavulanic acid was only detectable for 45% of the dosing interval, and complete killing of all strains was obtained after 24 h.

Clin Microbiol Infect, 2002 Oct, 8(10), 623 - 33
The new pneumococcal vaccine; Obaro SK; Pneumococcal disease is now the leading cause of vaccine-preventable bacterial disease in children worldwide . Although a pneumococcal polysaccharide vaccine has been available for over three decades, its use has been limited due to poor immunogenicity in the most vulnerable children, aged less than 2 years . The prevalence of pneumococcal disease worldwide and the alarming global escalation of multiresistant strains of Streptococcus pneumoniae (pneumococcus) during the past decade have provided the impetus for the development and application of a new pneumococcal vaccine . The outstanding success of Haemophilus influenzae type b (Hib) conjugate vaccine in the control of invasive Hib disease is a reason to be optimistic that the pneumococcal conjugate vaccines will achieve similar results for the control of invasive pneumococcal disease . Remarkable efficacy against invasive pneumococcal disease with a seven-valent pneumococcal conjugate vaccine was demonstrated in infants and toddlers in the USA, and in February 2000 the first pneumococcal conjugate vaccine was licensed . Licensure and widespread use is likely to follow in other countries in which there is a need and the means to afford this live-saving vaccine . Active disease surveillance must be sustained globally, while active research, development of other multivalent conjugate formulations and the search for new candidate protein-based vaccines are in progress.

Drugs Aging, 2002, 19(10), 761 - 75
Chronic obstructive pulmonary disease: role of bacteria and guide to antibacterial selection in the older patient; Murphy TF et al.; Chronic obstructive pulmonary disease (COPD) is a common problem in the elderly . The disease is characterised by intermittent worsening of symptoms and these episodes are called acute exacerbations . The best estimate, based on several lines of evidence, is that approximately half of all exacerbations are caused by bacteria . These lines of evidence include studies of lower respiratory tract bacteriology during exacerbations, correlation of airways' inflammation with results of sputum cultures during exacerbations, analysis of immune responses to bacterial pathogens, and the observation in randomised, prospective, placebo-controlled trials that antibacterial therapy is of benefit . The most important bacterial causes of exacerbations of COPD are nontypeable Haemophilus influenzae, Moraxella catarrhalis, Streptococcus pneumoniae and Chlamydia pneumoniae . In approaching the elderly patient with an exacerbation, it is useful to consider the severity of the exacerbation based on three cardinal symptoms: increased sputum volume, increased sputum purulence and increased dyspnoea compared with baseline . Patients experiencing moderate (two symptoms) or severe (all three symptoms) exacerbations benefit from antibacterial therapy . Consideration of underlying host factors allows for a rational choice of antibacterial agent . Patients are considered to have 'simple COPD' or 'complicated COPD' based on: (i) the severity of underlying lung disease; (ii) the frequency of exacerbations; and (iii) the presence of comorbid conditions . It is proposed that patients with simple COPD are treated with doxycycline, a newer macrolide, or an extended-spectrum oral cephalosporin; and patients with complicated COPD are treated with amoxicillin/clavulanate or a fluoroquinolone . The major goals of antibacterial therapy for exacerbations of COPD are acceleration of symptom resolution and prevention of the complications of exacerbation.

Pharmacotherapy, 2002 Oct, 22(10), 1278 - 93
Cefditoren, a new aminothiazolyl cephalosporin; Balbisi EA; Cefditoren pivoxil, an oral third-generation cephalosporin, was approved by the Food and Drug Administration in September 2001 . It has been used in Japan for several years . The greatest therapeutic potential of cefditoren appears to be its activity against gram-positive and gram-negative organisms causing respiratory tract infections and skin and skin-structure infections, such as Haemophilus influenzae, Streptococcus pneumoniae, and Moraxella catarrhalis . Cefditoren is also effective against methicillin-susceptible strains of Staphylococcus aureus . Nevertheless, cefditoren has no activity against atypical pathogens, including Chlamydia pneumoniae, Mycoplasma pneumoniae, and Legionella sp . Moreover, cefditoren does not inhibit Pseudomonas aeruginosa or Bacteroides fragilis . In virtually all studies, cefditoren has compared favorably against other orally administered antibiotics used against the most commonly isolated respiratory tract pathogens . Its side effect profile includes diarrhea, nausea, vomiting, headache, and dyspepsia . Cefditoren is indicated for treatment of mild-to-moderate acute exacerbations of chronic bronchitis, pharyngitis-tonsillitis, and uncomplicated skin and skin-structure infections caused by susceptible strains of organisms in adults and adolescents (> or = 12 yrs of age) . Based on its reported antimicrobial activity, cefditoren has potential for empiric management of most commonly encountered respiratory tract infections . Additional studies will further define its role in clinical practice.

Arch Pediatr, 2002 Sep, 9(9), 892 - 7
{Non-tubercular bacterial meningitis in children in Antananarivo, Madagascar}; Migliani R et al.; OBJECTIVE: To determine the bacterial causal agents of meningitis and their pattern of resistance, in children more than one month to 14 years of age . METHODS: A 2 years, prospective study (June 1998 to June 2000) on bacterial meningitis in children was carried out in the main hospitals in Antananarivo . The enrollment criteria upon admission were fever with symptoms of meningitis and/or convulsions and/or coma . A lumbar puncture was systematically performed in each child . The aspect of the cerebrospinal fluid was described, the level of protein and glucose estimated, soluble antigens measured . Following the examination of a Gram straining, an aliquot of the fluid was cultured on specific medium . Antimicrobial sensitivity testing of isolated pathogens was performed . RESULTS: Bacterial meningitis was confirmed in 119 children: 95 (80%) and 111 (93%) were less than 12 and 24 months of age, respectively . The sex distribution was 1:1 . Three predominant microorganisms were identified: Streptococcus pneumoniae (45%), Haemophilus influenzae b (43%) and Neisseria meningitidis (10%) of which ten of 12 cases were belonging to serogroup B . The other microorganisms isolated were E . coli (2%) . S . pneumoniae were found to be sensitive to penicillin G and H . influenzae were found to be sensitive to the third generation cephalosporins . Seven percent of the S . pneumoniae strains were mildly resistant (R + I) to chloramphenicol and between 29 and 50% to aminoglucosides . A moderate resistance against gentamicin and amoxicillin was found in 22-29% of the H . influenzae strains . The mortality rate was high (31%) and among the surviving children 30% presented with neurosensitive disorders . CONCLUSION: According to these data we may recommend the inclusion of vaccination against H . influenzae in the children immunization program in Madagascar . The early diagnosis and treatment with appropriate antibiotics, such as third generation of cephalosporins, are other critical measures to be taken in order to reduce the risk of developing severe complications associated to bacterial meningitis.

Glycoconj J, 2001 Sep, 18(9), 649 - 59
Terminal glycosylation in cystic fibrosis (CF): a review emphasizing the airway epithelial cell; Rhim AD et al.; Altered terminal glycosylation, with increased fucosylation and decreased sialylation is a hallmark of the cystic fibrosis (CF) glycosylation phenotype . Oligosaccharides purified from the surface membrane glycoconjugates of CF airway epithelial cells have the Lewis x, selectin ligand in terminal positions . This review is focused on the investigations of the glycoconjugates of the CF airway epithelial cell surface . Two of the major bacterial pathogens in CF, Pseudomonas aeruginosa and Haemophilus influenzae, have binding proteins which recognize fucose in alpha-1,3 linkage and asialoglycoconjugates . Therefore, consideration has been given to the possibility that the altered terminal glycosylation of airway epithelial glycoproteins in CF contributes to both the chronic infection and the robust, but ineffective, inflammatory response in the CF lung . Since the glycosylation phenotype of CF airway epithelial cells have been modulated by the expression of wtCFTR, the hypotheses which have been proposed to relate altered function of CFTR to the regulation of the glycosyltransferases are discussed . Understanding the effects of mutant CFTR on glycosylation may provide further insight into the regulation of glycoconjugate processing as well as new approaches to the therapy of CF.

Int J Antimicrob Agents, 2002 Sep, 20(3), 201 - 5
Species-independent pharmacodynamics of gemifloxacin and ciprofloxacin with Haemophilus influenzae and Moraxella catarrhalis in an in vitro dynamic model; Portnoy YA et al.; To demonstrate the antimicrobial effects of the different pharmacokinetics of gemifloxacin and ciprofloxacin, the pharmacodynamics of gemifloxacin and ciprofloxacin were studied using two clinical isolates each of Haemophilus influenzae and Moraxella catarrhalis . Monoexponentially decreasing concentrations of gemifloxacin (single dose, half-life 7.4 h) and ciprofloxacin (two 12-h doses, half-life 4 h) were simulated in an in vitro dynamic model over 8-fold ranges of the area under the curve (AUC)-to-MIC ratio: from 56 to 466 and 112-932 h, respectively . With each quinolone, log-linear relationships were established between the intensity of the antimicrobial effect (I(E)) and AUC/MIC . The I(E)-log AUC/MIC plots were bacterial strain- and species-independent and the gemifloxacin and ciprofloxacin plots were not superimposable . To generalize the findings obtained with the studied organisms, the effects of gemifloxacin and ciprofloxacin on hypothetical strains of H . influenzae and M . catarrhalis with MICs equal to the respective MIC(90)s were predicted . Based on these predictions, the AUC/MIC(90)s of 320 mg gemifloxacin (800 h with H . influenzae and 400 h with M . catarrhalis) may be 31-34% more efficient than those of 2 x 500 mg ciprofloxacin (730 and 365 h, respectively) . These data suggest greater efficacy of gemifloxacin against H . influenzae and M . catarrhalis relative to ciprofloxacin at clinically achievable AUC/MIC ratios .

Int J Antimicrob Agents, 2002 Sep, 20(3), 186 - 95
In vitro activity of moxifloxacin against recent community-acquired respiratory tract pathogens isolated in France: a national survey; Decousser JW et al.; Between February and June 2000, 2345 consecutive strains of Streptococcus pneumoniae, Haemophilus influenzae, Moraxella catarrhalis, Staphylococcus aureus and Klebsiella pneumoniae were isolated from 2088 adult patients suffering from community-acquired respiratory tract infections, in 97 hospital laboratories . Of the 1037 S . pneumoniae isolates, 48.3% were intermediately or highly penicillin resistant . For invasive isolates, the MIC90s of penicillin G, amoxycillin, cefuroxime, ceftriaxone, erythromycin, ofloxacin, ciprofloxacin and moxifloxacin were 2, 2, 4, 0.5, 1024, 2, 2 and 0.25 mg/l, respectively . All but one invasive strain were susceptible to moxifloxacin whereas 97.5% were susceptible to levofloxacin . The MIC90s of clinical isolates with intermediate susceptibility or high resistance to penicillin G, were 2, 2, 4, 1, 1024, 2, 2 and 0.25 mg/l . About 98.1, 97.0, and 83.1% of strains were inhibited by concentrations < or = 1 mg/l of moxifloxacin, levofloxacin and ciprofloxacin, respectively (E-test) . Eight of the 1037 S . pneumoniae strains were not susceptible to moxifloxacin and had mutations in gyrA (eight strains), parC (four strains) or parE (three strains) . Against H . influenzae (32.7% were beta-lactamase producers) and M . catarrhalis (96.3% were beta-lactamase producers), the MIC90s of moxifloxacin, amoxycillin and co-amoxiclav were 0.094 and 0.125 mg/l, 64 and 8 mg/l, and 1.5 and 0.25 mg/l, respectively . Against oxacillin-susceptible S . aureus and K . pneumoniae, the MIC90s of moxifloxacin were 0.125 and 0.84 mg/l respectively . Moxifloxacin had the highest in vitro activity of all antibiotics tested .

Int J Antimicrob Agents, 2002 Sep, 20(3), 180 - 5
Comparison of telithromycin, a new ketolide, with erythromycin and clarithromycin for the treatment of Haemophilus influenzae pneumonia in suckling, middle aged and senescent mice; Thadepalli H et al.; We studied the efficacy of telithromycin in Haemophilus influenzae pneumoniae in three different age groups of mice . Pneumonia was produced by endotracheal instillation of 1 x 10(4) CFU/ml of bacteria and treatment was initiated with saline for control and compared with two different doses, 50 and 100 mg/kg per BID telithromycin twice a day for 1 week . For comparison, we used erythromycin (ERY) and clarithromycin (CLA), both given twice a day at 50 mg/kg per BID . Some animals were euthanized on the third or 7th day of therapy and their lung tissue was cultured for bacteria . Presence of bacteria was considered a failure and a sterile lung was considered cured . As expected, about one half of middle-aged animals (8-10 months) were cured on saline . In contrast, almost none of the young (2-3 weeks) and old animals (18-20 months) were cured without antibiotic therapy . Among the young, the cure rates with telithromycin, ERY and CLA were 81, 50 and 33%, respectively . Of the senescent mice, the cure rate with ERY was 50% whereas the rates with CLA and telithromycin (50 mg/kg) were 62 and 75%, respectively . In conclusion, telithromycin is effective against H . influenzae at both extremes of life .

Int J Antimicrob Agents, 2002 Oct, 20(4), 263 - 9
The Italian Epidemiological Survey 1997-1999 . Antimicrobial susceptibility data of Haemophilus influenzae, Haemophilus parainfluenzae and Moraxella catarrhalis in Italy; Nicoletti G et al.; The Italian Epidemiological Survey began a surveillance study with the aim of monitoring the antimicrobial resistance of respiratory pathogens . From 1997 to 1999, 2028 strains of Haemophilus influenzae and 523 strains of Haemophilus parainfluenzae were collected from 59 Clinical Microbiology Laboratories distributed throughout Italy . In 1998, the study was extended to include Moraxella catarrhalis and a total of 360 isolates were collected . There was a significant increase in the beta-lactamase production both for H . influenzae (from 5% in 1997 to 16% in 1999) and for H . parainfluenzae (from 5% in 1997 to 22% in 1999) . Beta-lactamase production in M . catarrhalis was 84% in 1998 and 87% in 1999 . Beta-lactamase production affected the susceptibility to unprotected penicillins (87% in H . influenzae, 85% in H . parainfluenzae and 34% in M . catarrhalis), and in part the susceptibility to cefaclor (about 98%) . Amoxycillin/clavulanate, cefixime, ceftriaxone and ciprofloxacin were active against all strains of H . influenzae, H . parainfluenzae and M . catarrhalis.

Antimicrob Agents Chemother, 2002 Nov, 46(11), 3641 - 3
Antimicrobial resistance in Haemophilus influenzae isolated during population-based surveillance for meningitis in Salvador, Brazil; Reis JN et al.; Antimicrobial susceptibility was determined for 150 Haemophilus influenzae isolates obtained during population-based surveillance for meningitis in Salvador, Brazil . Ten (6.7%) isolates were resistant to ampicillin and chloramphenicol . Of these, two isolates, a beta-lactamase and non-beta-lactamase producer, were resistant to amoxacillin-clavulinic acid . These findings indicate that present antibiotic regimens in Brazil may not be appropriate for the treatment of H . influenzae meningitis.

Protein Sci, 2002 Nov, 11(11), 2551 - 60
Structural and nucleotide-binding properties of YajQ and YnaF, two Escherichia coli proteins of unknown function; Saveanu C et al.; Structural genomics is a new approach in functional assignment of proteins identified via whole-genome sequencing programs . Its rationale is that nonhomologous proteins performing similar or related biological functions might have similar tertiary structure . We used dye pseudoaffinity chromatography, two-dimensional gel electrophoresis, and mass spectrometry to identify two novel Escherichia coli nucleotide-binding proteins, YnaF and YajQ . YnaF exhibited significant sequence identity with MJ0577, an ATP-binding protein from a hyperthermophile (Methanococcus jannaschii), and with UspA, a protein from Haemophilus influenzae that belongs to the Universal Stress Protein family . YnaF conserves the ATP-binding site and the dimeric structure observed in the crystal of MJ0577 . The protein YajQ, present in many bacterial genomes, is missing in eukaryotes . In the absence of significant similarities of YajQ to any solved structure, we determined its structural and ligand-binding properties by NMR and isothermal titration calorimetry . We demonstrate that YajQ is composed of two domains, each centered on a beta-sheet, that are connected by two helical segments . NMR studies, corroborated with local sequence conservation among YajQ homologs in various bacteria, indicate that one of the beta-sheets is mostly involved in biological activity.

J Microbiol Immunol Infect, 2002 Sep, 35(3), 184 - 6
Haemophilus aphrophilus brain abscess: a case report; Kao PT et al.; Haemophilus aphrophilus infection is rare, and the organism is infrequently implicated in serious infection . We report a case of a 61-year-old patient who experienced left hemiparesis with dizziness . Computed tomography of the brain demonstrated a lesion with ring enhancement in the right frontotemporal region . Craniotomy was performed, abscess was drained, and H . aphrophilus was isolated . Following the surgical procedure and further antibiotic treatment, the patient recovered completely.

Eur J Epidemiol, 2001, 17(11), 1015 - 8
Asymtomatic carriage of Neisseria meningitidis and Neisseria lactamica in relation to Streptococcus pneumoniae and Haemophilus influenzae colonization in healthy children: apropos of 1400 children sampled; Bakir M et al.; Meningococcal disease is one of the most important causes of morbidity and mortality among children in many parts of the world . Main reservoir of carriage and site of meningococcal dissemination appears to be the upper respiratory tract . Colonization of Neisseria meningitidis and lactamica and factors affecting this carriage were determined in a group of healthy children aged 0-10 years . Meningococcus and N . lactamica carriage were detected in 17 (1.23%) and 245 (17.7%) of 1382 subjects, respectively . Number (%) of serogroups for meningococci was 1 (6), 5 (29), 0 (0), 1 (6), 1 (6), and 9 (53) for A, B, C, D, W135, and Y, respectively . Having more than three household members, elementary school attendance, pharyngeal carriage of Streptococcus pneumoniae and Haemophilus influenzae were associated with carriage of meningococci, whereas age less than 24-month was associated with carriage of N . lactamica . There was a reverse carriage rate between N . meningitidis and N . lactamica by age which may suggest a possible protective role of N . lactamica against meningococcal colonization among pre-school children.

Infect Immun, 2002 Nov, 70(11), 6158 - 65
The Haemophilus ducreyi serum resistance antigen DsrA confers attachment to human keratinocytes; Cole LE et al.; Haemophilus ducreyi is the etiologic agent of the sexually transmitted genital ulcer disease chancroid . H . ducreyi serum resistance protein A (DsrA) is a member of a family of multifunctional outer membrane proteins that are involved in resistance to killing by human serum complement . The members of this family include YadA of Yersinia species, the UspA proteins of Moraxella catarrhalis, and the Eib proteins of Escherichia coli . The role of YadA, UspA1, and UspA2H as eukaryotic cell adhesins and the function of UspA2 as a vitronectin binder led to our investigation of the cell adhesion and vitronectin binding properties of DsrA . We found that DsrA was a keratinocyte-specific adhesin as it was necessary and sufficient for attachment to HaCaT cells, a keratinocyte cell line, but was not required for attachment to HS27 cells, a fibroblast cell line . We also found that DsrA was specifically responsible for the ability of H . ducreyi to bind vitronectin . We then theorized that DsrA might use vitronectin as a bridge to bind to human cells, but this hypothesis proved to be untrue as eliminating HaCaT cell binding of vitronectin with a monoclonal antibody specific to integrin alpha(v)beta(5) did not affect the attachment of H . ducreyi to HaCaT cells . Finally, we wanted to examine the importance of keratinocyte adhesion in chancroid pathogenesis so we tested the wild-type and dsrA mutant strains of H . ducreyi in our swine models of chancroid pathogenesis . The dsrA mutant was less virulent than the wild type in both the normal and immune cell-depleted swine models of chancroid infection.

Jpn J Antibiot, 2002 Aug, 55(4), 412 - 39
{In vitro and in vivo antibacterial activities of pazufloxacin mesilate, a new injectable quinolone}; Nomura N et al.; We investigated the in vitro and in vivo antibacterial activities of pazufloxacin mesilate (PZFX mesilate), a new injectable quinolone, and obtained the following results . 1) The MIC50 and MIC90 values of PZFX against clinically isolated Gram-positive and -negative bacteria, ranged from 0.0125 to 12.5 micrograms/ml and 0.025 to 100 micrograms/ml, respectively . PZFX showed broad spectrum activity . The antibacterial activities of PZFX against quinolone-susceptible, methicillin-resistant Staphylococcus aureus, beta-lactamase-negative, ampicillin-resistant Haemophilus influenzae, extended spectrum beta-lactamase possessing Klebsiella pneumoniae and imipenem/cilastatine (IPM/CS)-resistant Pseudomonas aeruginosa were superior to those of ceftazidime (CAZ), ceftriaxone, IPM/CS, meropenem and panipenem/betamipron . 2) PZFX showed superior bactericidal activity against S . aureus, Escherichia coli, Proteus mirabilis, Serratia marcescens and P . aeruginosa to those of CAZ and IPM/CS after treatment for 15 minutes at the drug concentration equivalent to that in human serum at clinical dose to be continued for 15 minutes . 3) CAZ and IPM/CS had no bactericidal activity at the 16 times of MIC against P . aeruginosa in human polymorphonuclear leucocytes, while PZFX exhibited potent bactericidal activity in a dose-dependent manner against such bacteria . 4) PZFX inhibited both DNA gyrase and topoisomerase IV from S . aureus at nearly the same level . PZFX showed poor inhibitory activity against topoisomerase II from human placenta and showed high selectivity to bacterial topoisomerase . 5) PZFX mesilate showed superior therapeutic activity to that of CAZ with following infection model caused by S . aureus and P . aeruginosa or each; systemic infection with cyclophosphamide-treated mice, systemic infection in mice with high challenge doses, CMC pouch infection in rat, and calculus infection in rat bladder . 6) Intravenous administration of PZFX with high plasma concentration just after administration, showed more excellent therapeutic effect against the rat intraperitoneal infection, than p.o . and s.c . administration.

Bull World Health Organ, 2002, 80(9), 690 - 5
Epidemiology of meningitis due to Haemophilus influenzae type b in children in Bulgaria: a prospective, population-based surveillance study; Kojouharova M et al.; OBJECTIVE: To assess the incidence of meningitis caused by Haemophilus influenzae type b (Hib) among children in Bulgaria and to provide evidence for an informed decision on the use of Hib vaccines in Bulgaria . METHODS: From 1 July 1997 to 31 December 1999, active surveillance for meningitis was conducted in six regions . For children with suspected meningitis, a cerebrospinal fluid (CSF) specimen was sent for cytology, chemistry, latex agglutination testing, culture and sensitivity . FINDINGS: During the 2.5-year study period, surveillance was conducted among 138 249 children aged <5 years - a sample representing 40% of all Bulgarian children in this age group . Overall, 285 children with suspected meningitis were identified . In eight children, clinical symptoms of meningitis resolved rapidly before a CSF specimen could be obtained . Of the remaining 277 children, 121 (44%) were classified as having probable bacterial meningitis on the basis of a CSF examination . An organism was identified for 88 (73%) of the 121 cases with probable bacterial meningitis . There were 21 cases of Hib, giving a mean annual incidence of 6.1 Hib meningitis cases per 100 000 children <5 years; the case-fatality rate was 10% . Nearly 60% of Hib isolates were resistant to one or more antibiotics, but they were not resistant to third-generation cephalosporins . CONCLUSION: On the basis of these findings, Hib conjugate vaccines have been included in the list of vaccines recommended for children by the Bulgarian Ministry of Health . The recommended initial treatment for paediatric bacterial meningitis has been changed to third-generation cephalosporins.

Diagn Microbiol Infect Dis, 2002 Sep, 44(1), 101 - 7
Haemophilus influenzae in respiratory tract infections in community-based clinical practice: therapy with gatifloxacin; Nicholson SC et al.; In this community-based safety surveillance study, the advanced-generation fluoroquinolone gatifloxacin was administered empirically to 15625 adults with community-acquired respiratory tract infections (RTIs), including 1562 clinically evaluable patients with community-acquired pneumonia (CAP) and 2391 with acute exacerbations of chronic bronchitis (AECB) . Haemophilus influenzae was the most common pathogen isolated in AECB (40.1%) and the second most common in CAP (36.8%) . In vitro susceptibility to gatifloxacin and other fluoroquinolones, amoxicillin/clavulanate, ceftriaxone, cefuroxime axetil, tetracycline, and azithromycin ranged from 95.8% to 100% . In comparison, a significant percentage of the isolates were not susceptible to clarithromycin ( approximately 41%), ampicillin (22% to 28%), and trimethoprim/sulfamethoxazole (14% to 18%) . The susceptibility pattern was generally independent of exposure to another antimicrobial in the previous 30 days . CAP and AECB patients infected with H . influenzae had signs and symptoms similar to those infected with Streptococcus pneumoniae . Among clinically evaluable patients with H . influenzae, gatifloxacin cured 159 of 166 (95.8%) with AECB and 112 of 118 (94.9%) with CAP . The cure rate was independent of the beta-lactamase status or serotype of the H . influenzae strain . H . influenzae is not a more benign pathogen in community-acquired RTIs but causes signs and symptoms that are indistinguishable from those caused by other pathogens, notably S . pneumoniae.

Diagn Microbiol Infect Dis, 2002 Sep, 44(1), 85 - 91
Oral gatifloxacin in outpatient community-acquired pneumonia: results from TeqCES, a community-based, open-label, multicenter study; Gotfried M et al.; Gatifloxacin is an 8-methoxy fluoroquinolone with broad activity against respiratory tract pathogens, including those commonly associated with community-acquired pneumonia (CAP) . To evaluate the efficacy and safety of oral gatifloxacin 400 mg once daily for seven to 14 days, community-based physicians enrolled adult outpatients with confirmed or suspected CAP in a prospective, single-arm, open-label, noncomparative study . Of 1488 clinically evaluable patients with radiographically confirmed or clinically suspected CAP, 1417 (95.2%) were cured . All strains of Streptococcus pneumoniae, Haemophilus influenzae, and Moraxella catarrhalis, the most commonly isolated pathogens, were susceptible to gatifloxacin . Penicillin nonsusceptibility was seen in 32.6% of S . pneumoniae isolates, and beta-lactamase production was detected in H . influenzae (26.9%) and M . catarrhalis (88%) isolates . Clinical cure rates of 91%, 94%, and 92% were achieved in patients with S . pneumoniae, H . influenzae, and M . catarrhalis, respectively . All seven patients with fully penicillin-resistant S . pneumoniae (MIC > or =2 micro g/ml) were cured . Gatifloxacin was well tolerated, with the most common drug-related adverse events being nausea (2.8%) and diarrhea (1.7%) . Gatifloxacin is effective and well tolerated as empiric therapy for CAP in the outpatient community setting.

Methods Mol Med, 2003, 71, 1 - 28
The pathogenesis of disease due to nontypeable Haemophilus influenzae; Hardy GG et al.; To summarize, the pathogenesis of disease due to nontypeable H . influenzae involves multiple steps and the interplay of a number of bacterial and host factors, as shown in Fig . 1 . Following entry into the upper respiratory tract, bacteria encounter the mucociliary escalator . The P2 and P5 outer-membrane proteins and probably other factors promote bacterial binding to mucus, and elaboration of LOS causes damage to ciliated cells and impairs mucociliary function . Subsequently, several adhesins, including HMW1 and HMW2, pili, Hia, Hap, and others, mediate direct adherence to nonciliated epithelial cells . Cleavage of IgA1, invasion into cells and the subepithelial space, and phase and antigenic variation facilitate evasion of local immune mechanisms . Binding and uptake of iron and heme allow organisms to persist on the respiratory mucosa despite the relative scarcity of these nutrients . In the setting of a viral infection, allergic disease, or exposure to cigarette smoke, bacteria spread from the nasopharynx to other sites within the respiratory tract and produce symptomatic disease.

Przegl Epidemiol, 2002, 56(2), 265 - 73
{Meningitis and encephalitis in Poland in 2000}; Stefanoff P et al.; A total of 2,033 cases of meningitis and 570 of encephalitis were reported in Poland in 2000 . Among cases of meningitis 1,051 (51.7%) were classified as viral and 982 (48.3%) as bacterial . Etiological factors were determined in 36.7% (360/982) cases of bacterial meningitis . Neisseria meningitidis, Haemophilus influenzae, and Streptococcus pneumoniae were found in 10.3% (101/982), 8.7% (85/982), and 7.5% (74/982) cases, respectively . As in previous years, N . meningitidis typed B was strongly predominating . Out of 570 cases of encephalitis, 170 (29.8%) were tick borne, of which most were reported from endemic areas of north-eastern part of the country.

Przegl Epidemiol, 2002, 56(2), 217 - 25
{Infectious diseases in Poland in 2000}; Mazurek J et al.; The decreasing tendency in incidence of infectious diseases observed in Poland in previous years as compared with 2000 has weakened or stopped . Increase in the incidence of selected infectious diseases can be linked with the improvement of surveillance resulting from the better diagnostics and greater attention paid to these diseases (including borreliosis, salmonella, and Haemophilus influenzae meningitis) . Between 1999 and 2000, the most intense decrease in the number of mumps, measles, and scarlet fever cases as an effect of the end of epidemics was observed . At the same time increase in the number of pertussis, rubella, chickenpox, and meningitis cases was noticed . In 2000, the first case of human rabies since 1986 has been reported . In 2000, compared with 1999, among all notified deaths percentage of deaths attributed to infectious diseases (0.83%) and infectious diseases death rate (0.79 per 10,000) were slightly higher and were the highest in the last decade . As in 1999 the observed increase was effect of the influenza deaths increase (358 deaths, mortality 0.022%) . The main disease causing the largest number of deaths, as in previous years, was tuberculosis (36.5% of total infectious diseases deaths).

Neuropediatrics, 2002 Aug, 33(4), 169 - 73
Late shunt infection: incidence, pathogenesis, and therapeutic implications; Vinchon M et al.; Shunt infections (SI) are a major concern in pediatric neurosurgery . Although SI occurs generally shortly after surgery, it can be very delayed in a number of cases . The incidence of late shunt infection (LSI) is not established, and the sources of contamination are poorly understood . We reviewed 1,793 pediatric cases from our database, with a mean follow-up of 9.12 years . We selected 40 cases of SI occurring more than one year after the previous shunt operation . These represented 12.7 % of SI, and the annual incidence of LSI was 0.28 % in our series . Peritonitis, generally due to appendicitis, was the cause of LSI in 11 cases . Hematogenous contamination was diagnosed in eight cases, because the germ was Haemophilus,Pneumococcus, or Listeria, or an ENT infection had preceded SI; the incidence of purulent meningitis was significantly higher in shunted patients than in the general population . LSI was due in seven cases to bowel perforation, and in four to direct inoculation, after abdominal surgery or traumatic exposure of the shunt . In the remaining 10 cases, no potential cause of infection was identified, and persistence of a germ since the previous shunt operation was suspected . SI represents a life-long threat after shunting, and may be unrelated to shunt surgery.

Int J Pediatr Otorhinolaryngol, 2002 Oct 21, 66(1), 41 - 8
The clinical role of Alloiococcus otitidis in otitis media with effusion; Leskinen K et al.; OBJECTIVE: To investigate the presence of Alloiococcus otitidis (A . otitidis) in MEEs from patients with otitis media with effusion (OME) using PCR and to correlate the findings with the clinical picture of children with OME for assessing the clinical role of A . otitidis in OME . METHODS: Bacterial culture and PCR were used to detect A . otitidis, Streptococcus pneumoniae, Haemophilus influenzae and Moraxella catarrhalis in MEE samples from 123 patients with OME . The culture and PCR results and the clinical picture of the patients were compared . RESULTS: Bacteria were cultured in 55 (45%) of the 123 MEEs, and major pathogens (S . pneumoniae, H . influenzae and M . catarrhalis) were found in 40 (33%); A . otitidis was not found in culture . PCR of the MEEs yielded positive results for one or more of the four tested pathogens in 108 (88%) of the samples and 25 (20%) were positive for A . otitidis . The effusions that persisted 3 months or longer had a higher prevalence of A . otitidis than those with shorter durations (P=0.03) . A . otitidis was found to be more often positive in PCR in mucoid MEEs than in mucoserous MEEs (30 vs . 9%; P=0.015) . CONCLUSIONS: While A . otitidis is extremely difficult to detect with bacterial culture, PCR provides a sensitive and specific means for detecting it . A . otitidis is associated with a more prolonged course and mucoid MEEs in OME . Thus, its existence seems to be related to a more chronic stage of OME, but its pathogenic potential should be the subject of further investigation.

N Z Med J . 2002 Aug 09;115(1159):U122.
The beneficial impact of Hib vaccine on disease rates in New Zealand children; Wilson N et al.; AIM: To examine the impact of Haemophilus influenzae type b (Hib) vaccine on the burden of Haemophilus influenzae (Hi) disease in New Zealand children aged under five years (under-5s) . METHODS: Analysis of national mortality, hospitalisation, laboratory, and notification data . RESULTS: The introduction of Hib vaccine in 1994 led to a 92% decline (95%CI = 89 94%) in the hospitalisation rate of Hi meningitis for under-5s (1995 2000 compared to 1988 1993) . Pre-vaccine, the Hi meningitis hospitalisation rate was 27 per 100 000 in the under-5s and this declined to 2 per 100 000 . Even though Hi meningitis declined in all ethnic groups (eg down to 3 per 100 000 among Maori), there was a worsening of equity with the proportion of children hospitalised with Hi meningitis who were Maori increasing from 23% to 40% of all cases . The rate of epiglottitis hospitalisations also declined substantially (by 94%, 95%CI = 89 - 96%) . CONCLUSIONS: Hib vaccination appears to be preventing at least 80 cases of meningitis and 30 cases of epiglottitis every year in under-5s in New Zealand . But the beneficial impact of Hib vaccination has been less for Maori and so there is a need for further improvements in immunisation coverage in those populations with the highest disease burdens.

Microbes Infect, 2002 Sep, 4(11), 1141 - 8
Haemophilus ducreyi: clinical features, epidemiology, and prospects for disease control; Bong CT et al.; Haemophilus ducreyi is the causative agent of the genital ulcer disease chancroid . Chancroid is common in developing countries and facilitates human immunodeficiency virus transmission . In this review, the clinical features, epidemiology, and prospects for disease control are discussed in the context of experimental and natural infection of humans.

Pediatrics, 2002 Oct, 110(4), 712 - 9
Development and validation of a multivariable predictive model to distinguish bacterial from aseptic meningitis in children in the post-Haemophilus influenzae era; Nigrovic LE et al.; CONTEXT: Children with meningitis are routinely admitted to the hospital and administered broad-spectrum antibiotics pending culture results because distinguishing bacterial meningitis from aseptic meningitis is often difficult . OBJECTIVE: To develop and validate a simple multivariable model to distinguish bacterial meningitis from aseptic meningitis in children using objective parameters available at the time of patient presentation . DESIGN: Retrospective cohort study of all children with meningitis admitted to 1 urban children's hospital from July 1992 through June 2000, randomly divided into derivation (66%) and validation sets (34%) . PATIENTS: Six hundred ninety-six previously healthy children aged 29 days to 19 years, of whom 125 (18%) had bacterial meningitis and 571 (82%) had aseptic meningitis . INTERVENTION: Multivariable logistic regression and recursive partitioning analyses identified the following predictors of bacterial meningitis from the derivation set: Gram stain of cerebrospinal fluid (CSF) showing bacteria, CSF protein > or =80 mg/dL, peripheral absolute neutrophil count > or =10 000 cells/mm3, seizure before or at time of presentation, and CSF absolute neutrophil count > or =1000 cells/mm3 . A Bacterial Meningitis Score (BMS) was developed on the derivation set by attributing 2 points for a positive Gram stain and 1 point for each of the other variables . MAIN OUTCOME MEASURE: The accuracy of the BMS when applied to the validation set . RESULTS: A BMS of 0 accurately identified patients with aseptic meningitis without misclassifying any child with bacterial meningitis in the validation set . The negative predictive value of a score of 0 for bacterial meningitis was 100% (95% confidence interval: 97%-100%) . A BMS > or =2 predicted bacterial meningitis with a sensitivity of 87% (95% confidence interval: 72%-96%) . CONCLUSIONS: The BMS accurately identifies children at low (BMS = 0) or high (BMS > or =2) risk of bacterial meningitis . Outpatient management may be considered for children in the low-risk group.

Pediatrics, 2002 Oct, 110(4), 653 - 61
Impact of universal Haemophilus influenzae type b vaccination starting at 2 months of age in the United States: an economic analysis; Zhou F et al.; OBJECTIVE: To evaluate the economic impact of universal Haemophilus influenzae type b (Hib) vaccination starting at 2 months of age . METHODS: Decision-tree-based analysis was conducted of a hypothetical US birth cohort of 3 815 469 infants using population-based vaccination coverage and disease incidence data . All costs were estimated from both the direct cost (medical and nonmedical) and societal perspectives . Net present value, cost-effectiveness ratios, and benefit-cost ratios of the US Hib vaccination program were evaluated . RESULTS: The results of these analyses showed that the universal vaccination program using the Hib conjugate vaccines in the United States in 2000 was cost-saving from both the direct and societal perspectives, with the benefit of the Hib vaccination program (net present value) from the direct cost and societal perspectives of $0.95 billion and $2.09 billion, respectively . Without a Hib vaccination program, the direct and societal costs of Hib invasive cases would be $1.35 billion and $2.58 billion, respectively . The direct and societal costs of the Hib vaccination program were estimated at $0.39 billion and $0.48 billion, respectively . The direct and societal benefit-cost ratios for the Hib vaccination program were 3.4 and 5.4, respectively . Varying the proportion of vaccines purchased and administered in the public versus the private sector and the proportion of combination vaccine versus monovalent vaccine administered did not have much effect on the results . CONCLUSIONS: Regardless of the perspective (direct cost or societal) and the assumptions used, the benefit-cost ratios of the US vaccination program are >1.0 . Potential changes in the program, including use of more or less Hib combination vaccines, would not significantly alter the benefit-cost ratio . The national Hib vaccination program is highly cost beneficial and results in substantial cost savings.

J Pharm Belg, 2002 Jul-Aug, 57(4), 73 - 81
{Conjugate vaccines}; Swennen B et al.; Conjugate vaccines extend the vaccinal prevention for children to more diseases . Conjugating the capsular polysaccharide to a carrier protein transforms a T-independent antigen in a T-dependent, allowing protection of the children (before 2 years of age) against Haemophilus influenzae type b, meningococcal C and pneumococcal infections . This article reviews the 3 conjugate vaccines and their results with focus on some questions: antigens interference in the immunological response, serological subrogate for protection, herd immunity and replacement of circulating serotypes.

J Antimicrob Chemother, 2002 Oct, 50(4), 525 - 32
Effect of protein binding on the in vitro activity and pharmacodynamics of faropenem; Boswell FJ et al.; The influence of protein binding upon different aspects of the in vitro activity of faropenem on recently isolated Staphylococcus aureus and respiratory pathogens was determined . The protein binding of faropenem was investigated in inactivated human serum and albumin by ultrafiltration . The effect of the presence of inactivated human serum and albumin on the in vitro activity of faropenem and amoxicillin was established and the influence of protein binding on the pharmacodynamic properties of faropenem and amoxicillin was compared . The protein binding of faropenem was 96% and 95% in pooled inactivated human serum and 99% and 98% in 45 mg/L human albumin, at 8 and 25 mg/L, respectively . The presence of inactivated human serum (20% and 70%) increased the mean faropenem MICs by two dilution steps and albumin increased the mean faropenem MICs by three dilution steps . The mean amoxicillin MICs were less affected than faropenem by the presence of either inactivated human serum or albumin . Faropenem and amoxicillin exhibited similar time-dependent kinetics . Faropenem was bacteriostatic on Moraxella catarrhalis, Haemophilus influenzae and group A streptococci, and bactericidal for Streptococcus pneumoniae (after 4 h with concentrations equivalent to 5 x and 10 x MIC) in Iso-Sensitest broth . In 70% inactivated human serum faropenem was slowly bactericidal against M . catarrhalis, H . influenzae (one strain) and S . pneumoniae (one strain) but not group A streptococci and the other S . pneumoniae strain . A significant inoculum effect was observed with all strains except S . pneumoniae . Both faropenem and amoxicillin appeared more active in 70% inactivated human serum than in Iso-Sensitest broth.

J Antimicrob Chemother, 2002 Oct, 50(4), 495 - 502
Comparison of the in vitro activities of several new fluoroquinolones against respiratory pathogens and their abilities to select fluoroquinolone resistance; Boswell FJ et al.; In this study the in vitro activities and pharmacodynamic properties of moxifloxacin, levofloxacin, gatifloxacin and gemifloxacin were compared on recently isolated respiratory pathogens and strains of Streptococcus pneumoniae with known mechanisms of fluoroquinolone resistance . In addition, the resistance selection frequencies of moxifloxacin and levofloxacin on three recently isolated respiratory pathogens and four strains of S . pneumoniae with known mechanisms of fluoroquinolone resistance were investigated . The four fluoroquinolones had similar activities against both Moraxella catarrhalis (MIC(90)s 0.015-0.06 mg/L) and Haemophilus influenzae (MIC(90)s 0.008-0.03 mg/L) . More marked differences in activity were noted with S . pneumoniae, with MIC(90)s of 0.25, 1, 0.5 and 0.03 mg/L for moxifloxacin, levofloxacin, gatifloxacin and gemifloxacin, respectively . With the S . pneumoniae strains, the four fluoroquinolones exhibited similar concentration-dependent time-kill kinetics . The resistance selection frequencies of levofloxacin were higher than those of moxifloxacin at concentrations equivalent to those at the end of the dosing interval . Therefore moxifloxacin may have less of an impact on the development of resistance than levofloxacin.

J Biol Chem, 2002 Dec 6, 277(49), 47444 - 50 Epub 2002 Sep 27.
Inhibition of p38 MAPK by glucocorticoids via induction of MAPK phosphatase-1 enhances nontypeable Haemophilus influenzae-induced expression of toll-like receptor 2; Imasato A et al.; Despite the importance of glucocorticoids in suppressing immune and inflammatory responses, their role in enhancing host immune and defense response against invading bacteria is poorly understood . We have demonstrated recently that glucocorticoids synergistically enhance nontypeable Haemophilus influenzae (NTHi)-induced expression of Toll-like receptor 2 (TLR2), an important TLR family member that has been shown to play a critical role in host immune and defense response . However, the molecular mechanisms underlying the glucocorticoid-mediated enhancement of TLR2 induction still remain unknown . Here we show that glucocorticoids synergistically enhance NTHi-induced TLR2 expression via specific up-regulation of the MAPK phosphatase-1 (MKP-1) that, in turn, leads to dephosphorylation and inactivation of p38 MAPK, the negative regulator for TLR2 expression . Moreover, increased expression of TLR2 in epithelial cells greatly enhances the NTHi-induced expression of several key cytokines, including tumor necrosis factor-alpha and interleukins 1beta and 8, thereby contributing significantly to host immune and defense response . These studies may bring new insights into the novel role of glucocorticoids in orchestrating and optimizing host immune and defense responses during bacterial infections and enhance our understanding of the signaling mechanisms underlying the glucocorticoid-mediated attenuation of MAPKs.

Onderstepoort J Vet Res, 2002 Sep, 69(3), 189 - 96
Virulence of South African isolates of Haemophilus paragallinarum . Part 3: experimentally produced NAD-independent isolate; Taole M et al.; A NAD-dependent isolate 46 (C-3) of Haemophilus paragallinarum, which was previously demonstrated to be of high virulence, was transformed to NAD independence using a plasmid isolated from a naturally occurring NAD-independent isolate of H . paragallinarum . The transformation was performed by two different methods and the identity of all of the isolates, before and after transformation was confirmed using a H . paragallinarum-specific PCR test . The transformed NAD-independent serovar C-3 isolate and the wild-type serovar C-3 isolate were used to experimentally infect vaccinated layer chickens . It was shown that the transformation to NAD independence significantly altered the virulence of the serovar C-3 isolate that was used in the transformation experiment . The mechanisms responsible for a decrease in virulence are not clear, but may be related to the pathology of the transformed isolate in the sinus of the chickens.

J Infect Dis, 2002 Oct 15, 186(8), 1115 - 21 Epub 2002 Sep 16.
Immunization with Haemophilus influenzae Hap adhesin protects against nasopharyngeal colonization in experimental mice; Cutter D et al.; Nontypeable Haemophilus influenzae is a common cause of respiratory tract disease and initiates infection by colonizing the nasopharynx . The H . influenzae Hap adhesin is an autotransporter protein that was discovered because it promotes intimate interaction with human epithelial cells . Hap contains an extracellular domain called Hap(s) that has adhesive and protease activity and an outer membrane domain called Hap(beta) that serves to present Hap(s) on the surface of the cell . Hap(s) purified from nontypeable H . influenzae strain P860295 was used to immunize BALB/c mice intranasally . Immunization stimulated significant mucosal and serum anti-Hap(s) antibody titers, which were augmented by the addition of mutant cholera toxin (CT-E29H) as an adjuvant . Immunization was associated with a marked reduction in the density of nasopharyngeal colonization when mice were challenged with a heterologous strain of nontypeable H . influenzae . These results suggest that intranasal immunization with Hap formulated with CT-E29H may be a valuable vaccine strategy for the prevention of nontypeable H . influenzae disease.

J Clin Microbiol, 2002 Oct, 40(10), 3694 - 702
Development of a rapid immunodiagnostic test for Haemophilus ducreyi; Patterson K et al.; Haemophilus ducreyi is the etiologic agent of chancroid, a sexually transmitted disease that increases the rate of transmission of human immunodeficiency virus . Chancroid ulcerations are difficult to distinguish from those produced by syphilis and herpes . Diagnosis based solely on clinical grounds is inaccurate, and culture is insensitive . Highly sensitive PCR has largely superseded culture as the preferred method of laboratory diagnosis; however, neither culture nor PCR is feasible where chancroid is endemic . We developed a rapid (15-min) diagnostic test based on monoclonal antibodies (MAbs) to the hemoglobin receptor of H . ducreyi, HgbA . This outer membrane protein is conserved in all strains of H . ducreyi tested and is required for the establishment of experimental human infection . MAbs to HgbA were generated and tested for cross-reactivity against a panel of geographically diverse strains . Three MAbs were found to be unique and noncompetitive and bound to all strains of H . ducreyi tested . Using an immunochromatography format, we evaluated the sensitivity and specificity of the test using geographically diverse strains of H . ducreyi, other Haemophilus strains, and other bacteria known to superinfect genital ulcers . All H . ducreyi strains were positive, and all other bacteria were negative, resulting in a specificity of 100% . The minimum number of CFU of H . ducreyi detected was 2 x 10(6) CFU, and the minimum amount of purified HgbA protein detected was 8.5 ng . Although this level of sensitivity may not be sufficient to detect H . ducreyi in all clinical specimens, further work to increase the sensitivity could potentially make this a valuable bedside tool in areas where chancroid is endemic.

Pediatr Infect Dis J, 2002 Sep, 21(9), 854 - 9
Impact of a birth dose of hepatitis B vaccine on the reactogenicity and immunogenicity of diphtheria-tetanus-acellular pertussis-hepatitis B-inactivated poliovirus-Haemophilus influenzae type b combination vaccination; Pichichero ME et al.; OBJECTIVES: To assess the impact of a birth dose of hepatitis B vaccine (HepB) on the reactogenicity and immunogenicity of a novel diphtheria-tetanus-acellular pertussis (DTaP)- HepB-inactivated poliovirus (IPV)/ type b (Hib) combination vaccine administered subsequently at 2, 4 and 6 months of age . METHODS: Neonates ( = 550) were randomized into two groups with regard to receipt of HepB at birth . All subjects in both groups received DTaP-HepB-IPV/Hib at 2, 4 and 6 months of age . Solicited local and general adverse events were recorded for 8 days after each dose . Antibodies to hepatitis B surface antigen were measured 1 month after the third dose of DTaP-HepB-IPV/Hib in a subset of 170 infants; titers of at least 10 mIU/ml were considered protective . RESULTS: The DTaP-HepB-IPV/Hib combination vaccine was well-tolerated in both groups . Of the infants who received a birth dose of HepB, 22.6% had severe (Grade 3) reactions after any of the three doses of DTaP-HepB-IPV/Hib combination vaccine compared with 23.2% of subjects who did not receive a birth dose of HepB (difference, -0.5%; 90% confidence interval, -7.4 to 6.1) . Antibody to hepatitis B surface antigen titers were > or =10 mIU/ml for all tested infants . Geometric mean titers were 2996.2 and 1240.1 mIU/ml with and without a birth dose of HepB, respectively . CONCLUSIONS: A HepB birth dose does not increase the reactogenicity of a combination DTaP-HepB-IPV/Hib vaccine administered at 2, 4 and 6 months of age, and all tested subjects achieved protective anti-HBs titers (> or =10 mIU/ml), although geometric mean titers were higher when a birth dose of HepB was given.

Pediatr Infect Dis J, 2002 Sep, 21(9), 822 - 6
Standard and alternative regimens of Haemophilus influenzae type b conjugate vaccine (polyribosylribitol phosphate-tetanus toxoid conjugate vaccine) elicit comparable antibody avidities in infants; Campbell JD et al.; BACKGROUND: Haemophilus influenzae type b conjugate vaccines are relatively expensive in the developing world . Previous study of the type b conjugate vaccine polyribosylribitol phosphate-tetanus toxoid conjugate vaccine showed that two dose and fractional three dose schedules elicit protective antibody concentrations equivalent to three full doses . METHODS: Antibody avidity was measured in 73 of these vaccinees with a modified enzyme-linked immunosorbent assay using NH(4) SCN as the chaotrope . Avidity index (AI) is the molarity causing a 50% reduction in OD(405) . RESULTS: The postprimary series AI was similar for all dosing regimens . Preboost AI was highest in those receiving three half-doses, although there was no statistical difference among groups . Rises in avidity from age 8 to 12 months were also similar among regimens . Our data support the equivalence of anti-polyribosylribitol phosphate IgG avidity in infants primed with these alternative regimens . CONCLUSIONS: Given the known correlation of avidity with assays of bacterial killing and memory priming, these potentially more economical alternative schedules should be studied in the developing world.

Pediatr Infect Dis J, 2002 Sep, 21(9), 816 - 21
Long term enhancement of the IgG2 antibody response to Haemophilus influenzae type b by breast-feeding; Silfverdal SA et al.; SUBJECTS: Sets of sera were obtained from 30 children <6 years of age with invasive type b (Hib) infection and their mothers . Duration and mode of breast-feeding were monitored . Titers of IgG1, IgG2, IgA and IgM antibodies against Hib capsular polysaccharide were determined in sera taken during the acute illness and during early and late convalescence . RESULTS: Children 18 months or older with longer durations of exclusive breast-feeding (13 weeks or more; mean, 19.3 weeks) had higher Hib antibody concentrations of the IgG1, IgG2, IgA and IgM isotypes than those with a shorter duration of exclusive breast-feeding (<13 weeks; mean, 5.4 weeks) . The difference was greatest for the IgG2 isotype . In regression analyses the association between the duration of exclusive breast-feeding and the anti-Hib IgG2 concentration was significant when breast-feeding, type of Hib infection, maternal Hib antibody titer and age were used as explanatory factors . In the group of 14 children <18 months of age no significant differences were noted . DISCUSSION: This study indicates the presence of a long lasting enhancing effect of breast-feeding on the antibody response to Hib in children, in particular on IgG2 Hib antibody production . This may result from the content in the milk of IFN-gamma and IFN-gamma-producing cells and possibly other factors, which can support IgG2 antibody production.

EPI Newsl . 1999 Aug;21(4):8.
Mexico introduces pentavalent vaccine; Introduction of Hib vaccine in the Americas: lessons learned; PIP: By December 1999, 81% of all newborn infants in the Americas (75% in Latin America and the Caribbean) will receive Haemophilus influenzae type b vaccine (Hib) as part of their regular immunization schedule . The introduction of this vaccine in the region has been remarkably successful and fast . Hib vaccine was included in Uruguay's routine immunization schedule in 1994, and in Chile's in 1996 . 2 different strategies were followed in both countries mainly because of the increased cost of Hib vaccine to the national immunization programs . By the end of 1996, the Pan American Health Organization (PAHO) took a leading role in promoting the establishment of Hib surveillance in the region, as well as evaluating its possible introduction to routine immunization programs . By 1998, many of the region's countries had integrated Hib vaccine into their immunization programs . Since 1997, PAHO has taken measures to strengthen the surveillance system in place to monitor S . pneumoniae . The role of PAHO's Revolving Fund for Vaccine Procurement is described .

Afr Health . 1997 Nov;20(1):13, 15.
Hib vaccine introduced in The Gambia; Wenger J; PIP: Acute respiratory infection (ARI) is the most common infectious cause of childhood death in Africa . Most deaths from ARI are caused by bacteria, including Haemophilus influenzae type b (Hib) . Hib is also the most common bacterial cause of meningitis, except in those areas with outbreaks of meningococcal disease . Up to 40% of infants with meningitis die, and many of the survivors have permanent deafness and brain damage . Until recently, however, early diagnosis and treatment was the only defence against these infections . The newly developed Hib conjugate vaccines have been shown to be effective against Hib meningitis and pneumonia, and are now routinely used in infants in more than 25 countries around the world . A study of the efficacy of the vaccine in The Gambia's Western Region in 1993-95 showed that it was 95% effective in preventing meningitis and bloodstream infection, and 100% effective in preventing pneumonia . Hib vaccine was introduced this year in The Gambia as a routine immunization for children, to be given in the same injection as DTP at 2, 3, and 4 months of age . A 1-year study is underway to evaluate the impact of the vaccine upon disease . Trials are now underway for new pneumococcal and meningococcal vaccines which may be ready for wider use within 5-10 years .

EPI Newsl, 1997 Oct, 19(5), 1 - 4
SVI technical advisory group meets; Technical Advisory Group Meeting on Vaccine-Preventable Diseases (12th: 1997: Guatemala City); PIP: The 12th Technical Advisory Group Meeting on Vaccine-Preventable Diseases (TAG) was held in Guatemala during September 8-12, 1997 . Created in 1985 during the polio eradication campaign, TAG meets every 2 years and is the leading forum to promote regional initiatives to control and eliminate vaccine-preventable diseases . One of the group's main objectives has been to strengthen the policy dialogue upon immunization among governments in the region and participating agencies . Some of TAG's major conclusions and recommendations are presented with regard to immunization in a changing policy environment, measles eradication, poliomyelitis, neonatal tetanus, rubella and congenital rubella, hepatitis B, yellow fever, Haemophilus influenzae type B (Hib), vaccines of quality, and research and development in the regional vaccine initiative .

EPI Newsl . 1996 Dec;18(6):6.
Impact of Uruguay's introduction of the Haemophilus influenzae type b (Hib) vaccine.
Andean region: measles on the way out}
PIP: In August 1996, health officials, program managers, epidemiologists, laboratory representatives, UNICEF, Rotary International, and Pan American Health Organization staff attended the VII Andean EPI Meeting in Quito, Ecuador, to review the progress of the Expanded Program on Immunization (EPI) . All Andean countries have conducted catch-up measles vaccination campaigns targeting children 9 months to 15 years old . These campaigns achieved 90% vaccine coverage and a strong reduction in measles incidence (only 7 confirmed cases in 1996) . Follow-up campaigns were conducted during 1995-1996 in Colombia, Peru, and Chile . They were expected in Bolivia, Ecuador, Peru, and Venezuela during 1997-1999 . The Andean countries implemented a national surveillance system for measles in 1995 . Meeting representatives made eight recommendations regarding measles . For example, health officials should reach and maintain routine vaccination coverage greater than 95% for children 12-23 months old in each municipality . Laboratory representatives proposed recommendations on uniform criteria for measles diagnosis . The last indigenous wild poliovirus in the Americas was isolated in 1991 . Imported wild poliovirus remains a concern . The Andean countries are expanding surveillance of neonatal tetanus activities . Since 1989 the frequency of neonatal tetanus has been falling in the Andean region, especially in Bolivia and Peru . The impact of migration on the control of neonatal tetanus should be a higher priority . Participants repeated the need for systematic use and continuous monitoring of EPI indicators (e.g., vaccination coverage) . Three countries plan on analyzing surveys on missed opportunities for vaccination in 1996 . Three countries presented progress reports on hepatitis B vaccination and surveillance . Participants issued recommendations on quality control of vaccines . The responsibility for quality control lies with the manufacturers and the government . Vaccines for invasive diseases (e.g., Haemophilus influenzae type b) may be included in national EPI programs .

Otolaryngol Head Neck Surg, 2002 Sep, 127(3), 182 - 9
Community-based treatment of acute uncomplicated bacterial rhinosinusitis with gatifloxacin; Sher LD et al.; OBJECTIVE: We sought to evaluate gatifloxacin in adults with acute uncomplicated bacterial rhinosinusitis . STUDY DESIGN: TeqCES was an open-label, multicenter, noncomparative study of the safety and efficacy of gatifloxacin . More than 11,000 adult patients with acute uncomplicated rhinosinusitis received gatifloxacin 400 mg once daily for 10 days . RESULTS: Moraxella catarrhalis (91% beta-lactamase producers), Haemophilus influenzae (28% beta-lactamase producers), Streptococcus pneumoniae (18% intermediately resistant and 14% fully resistant to penicillin), and Staphylococcus aureus were the predominant pathogens isolated from purulent nasal discharge . More than 99% of rhinosinusitis pathogens isolated from the nasopharynx of patients meeting the clinical criteria for rhinosinusitis were susceptible to gatifloxacin . Among 10,353 patients whose clinical response could be determined, 91.6% were cured . Clinical cure rates exceeded 90% for the major pathogens . Gatifloxacin was well tolerated; drug-related adverse events that occurred in 1% or more of patients were nausea (4.4%), dizziness (1.8%), diarrhea (1.4%), and headache (1.0%) . CONCLUSION: Gatifloxacin is effective for patients with acute bacterial rhinosinusitis in the community.

Vaccine, 2002 Oct 4, 20(29-30), 3590 - 7
Detection and characterization of pediatric serum antibody to the OMP P5-homologous adhesin of nontypeable Haemophilus influenzae during acute otitis media; Novotny LA et al.; We reported earlier that antibody in sera collected from seven children with acute otitis media (AOM) due to nontypeable Haemophilus influenzae (NTHI) recognized immunodominant regions of P5-fimbrin just as we had observed in a chinchilla model of experimental NTHI-induced AOM . To expand upon those preliminary findings, we further characterized pediatric serum antibodies directed against this adhesin during AOM . Collectively, the data show that children respond immunologically to P5-fimbrin and they do so in a manner that allows for the distinction of sequence diversity within short linear peptides representing a focused region of this surface-exposed protein . The immune recognition we observed encourages us to further develop a P5-fimbrin based vaccine component.

Vaccine, 2002 Oct 4, 20(29-30), 3509 - 22
Physico-chemical and immunological examination of the thermal stability of tetanus toxoid conjugate vaccines; Ho MM et al.; The thermal stability of meningococcal C (MenC)- and Haemophilus influenzae b (Hib)-tetanus toxoid (TT) conjugate vaccines was investigated using spectroscopic and chromatographic techniques and immunogenicity assays in animal models . In this stability study, both the bulk concentrate and final fills were incubated at -20, 4, 23, 37 or 55 degrees C for 5 weeks or subjected to cycles of freeze-thawing . The structural stability, hydrodynamic size and molecular integrity of the treated vaccines were monitored by circular dichroism (CD), fluorescence and nuclear magnetic resonance (NMR) spectroscopic techniques, size exclusion chromatography (FPLC-SEC), and high performance anion exchange chromatography coupled with pulsed amperometric detection (HPAEC-PAD) . Only storage at 55 degrees C for 5 weeks caused some slight unfolding and modification in the tertiary structure of the carrier protein in the MenC-TT conjugate . Substantial loss of saccharide content from the MenC conjugates was observed at 37 and 55 degrees C . Unexpectedly, the experimental immunogenicity of MenC-TT vaccine adsorbed to Alhydrogel was significantly reduced only by repeated freeze-thawing, but not significantly decreased by thermal denaturation . Neither the molecular integrity nor the immunogenicity of the lyophilised Hib-TT vaccines was significantly affected by freeze-thawing or by storage at high temperature . In conclusion, the MenC- and Hib-TT conjugate vaccines were relatively stable when stored at higher temperatures, though when MenC-TT vaccine was adsorbed to Alhydrogel, it was more vulnerable to repeated freeze-thawing . When compared with CRM(197) conjugate vaccines studied previously using similar techniques, the tetanus toxoid conjugates were found to have higher relative thermal stability in that they retained immunogenicity following storage at elevated temperatures.

Int J Antimicrob Agents, 2002 Aug, 20(2), 130 - 5
Oral antimicrobial susceptibilities of Streptococcus pneumoniae, Haemophilus influenzae, and Moraxella catarrhalis isolates from Japanese children; Nishi J et al.; The minimum inhibitory concentrations (MICs) of 11 oral antibiotics were measured for 140 Streptococcus pneumoniae, 115 Haemophilus influenzae, and 46 Moraxella catarrhalis strains isolated from Japanese children . The antibiotics selected included a range of commonly prescribed agents together with a selection of new cefems and a penem . Cefditoren was most active against the highly penicillin resistant S . pneumoniae, beta-lactamase-producing H . influenzae and beta-lactamase-negative ampicillin-resistant H . influenzae . However, amoxycillin retained good activity against the penicillin-susceptible or -intermediately resistant S . pneumoniae (88.6%) and most of ampicillin-susceptible or -intermediately resistant H . influenzae (87.9%) . We thus consider that amoxycillin remains a useful initial choice for the treatment of paediatric respiratory infections in Japan.

Int J Antimicrob Agents, 2002 Aug, 20(2), 76 - 85
Antimicrobial susceptibilities of Streptococcus pneumoniae, Haemophilus influenzae and Moraxella catarrhalis isolated in two successive respiratory seasons in the US; Karlowsky JA et al.; Antimicrobial susceptibilities of clinical isolates of Streptococcus pneumoniae, Haemophilus influenzae, and Moraxella catarrhalis were determined in two consecutive respiratory seasons in the US and suggested that national susceptibilities to commonly tested antimicrobials changed only slightly from the 1999-2000 to the 2000-2001 respiratory season . However, a significant regional variation in S . pneumoniae susceptibilities was observed, as was a decrease in beta-lactamase rates among H . influenzae from the 1999-2000 to 2000-2001 respiratory seasons.

EPI Newsl . 1998 Jun;20(3):6.
Update: Hib vaccination in the Americas; A plan for immediate action et al.; PIP: The Children's Vaccine Initiative's (CVI) strategic plan for making high-quality vaccines available to all of the world's children was first drafted in 1992-93 as a blueprint for the activities of the international vaccine community broadly working together as the CVI coalition . The goal was to protect all children against the major infectious diseases . The CVI task force on strategic planning met in April to update the plan relative to the current stage of immunization affairs and accomplishments with an eye to moving ahead during the next 10-15 years . While the vision of protecting children against infectious diseases remains, it will be quite a while before it is realized; modern vaccines are much more complex and expensive than the earlier vaccines used against polio, tetanus, measles, tuberculosis, pertussis, and diphtheria . The task force set 2005 as the deadline for expanding the scope of use of licensed vaccines for Haemophilus influenzae type b, hepatitis B, rubella, and measles . The task force chairman comments upon the feasibility of the new targets, the CVI's interest in the developing world, CVI's weaknesses, and the current state of affairs .

Glimpse . 1997 Sep;19(3):6.
The laboratory of reproductive tract infections; Bogaerts J; PIP: The laboratory of reproductive tract infections (RTIs) is a new entity within the Laboratory Sciences Division of the ICDDR,B . The objectives of the laboratory are to conduct epidemiologic research in RTIs, including sexually transmitted diseases (STDs), to provide technical support to protocols developed in other scientific divisions of the center, to provide training in diagnostic procedures, and to give diagnostic support to patient care . The RTI laboratory has an extremely important role in the national STD control program . Research priorities are to monitor the susceptibility patterns of Neisseria gonorrhoeae and Haemophilus ducreyi, to study the prevalence and etiology of RTIs/STDs among people with high-risk behaviors, and to study the etiology of syndromes such as pelvic inflammatory disease, urethral discharge, and genital ulceration . The laboratory also plans to develop new diagnostic methods and conduct research upon the resistance and virulence mechanisms of STD pathogens .

EPI Newsl, 1997 Dec, 19(6), 4 - 5
Caribbean meeting stresses surveillance.
{Prevention of infectious diseases in the drepanocytic child}
Koumakpai S, Hazoume FA, Dan V, Ayivi B.

PIP: Children with sickle cell anemia are more exposed to infection than healthy children . Indeed, infections are the major cause of morbidity and mortality in children with sickle cell anemia, especially those aged 6 months to 5 years . Phagocytosis is reduced in these children . Polynuclear neutrophils reveal various poorly understood irregularities and are associated with a reduction of phagocytic power: zinc deficiency, reduced post-phagocytic oxidative metabolism, and a prevalence of neutrophils not forming red sheep-like globule carriers of immunoglobulin H . The power of the antibody which renders germs susceptible to phagocytosis in the serum is reduced in sickle cell patients . This may be tied to a disorder in the alternate complementary route with reduction of C3 and properdin . Sequestration of sickle cell-shaped red blood cells, splenic congestion, and short circuits of important functional territories contribute to spleen dysfunction, which occurs early . Common pathogens attacking sickle cell patients are pneumococci, salmonella species, and Haemophilus influenzae . They cause very grave infections (e.g., septicemia and purulent meningitis) . Prevention of infections dwells on three perspectives: early screening for sickle cell anemia and for spleen dysfunction, preventive penicillin therapy, and vaccination . In Benin, vaccination is the only means to prevent infections . Essential vaccinations for children with sickle cell anemia include BCG, diphtheria-pertussis-tetanus, polio, and Rouvax . Strongly recommended vaccinations are Pneumovax 23, HEVAC B, TAB, vaccine against H . influenzae, and vaccine against mumps . A vaccine calendar for children with sickle cell anemia guides health workers when they must administer the vaccines and their boosters over a six year period . It is not yet universal in health facilities in Benin . A short- and long-term evaluation of the calendar's efficacy would allow one to appreciate its real impact on reducing morbidity and mortality in children with sickle cell anemia .

Arch Domin Pediatr, 1994 Jan-Apr, 30(1), 21 - 4
{Meningitis caused by Haemophilus influenzae type b: its immunological prevention . A necessity?}; Fernandez J; PIP: This work argues that the vaccine used to control Haemophilus influenza type b (Hib) in the US should become a routine vaccination for infants in the Dominican Republic as well . Hib was the most common cause of meningitis in children under five years old in the US before the vaccine became available . Mortality from meningitis caused by Hib has declined from 90% before antibiotics became available to between 3 and 5%, but there has been no significant further decline in three decades despite development of powerful new antibiotics . Haemophilus influenza is the principal cause of meningitis at the Robert Reid Cabral Children's Hospital in Santo Domingo, accounting for 50-52% of cases . The great majority of patients are under 15 months old . The case fatality rate is 7% and serious sequelae are not uncommon . The impact of the conjugated vaccine against Hib was demonstrated in the US by an 85-90% decline in secondary infections due to Hib . The vaccine has also been highly effective in Finland, reducing the incidence of meningitis in infants aged 0-4 from a peak of 43/100,000 in the 1970s to 0 in 1991 . In the US, the greatest decline in children under age 5 began in 1989, one year before the vaccine was approved for use in this age group . The reason for the timing of the decline is not clear, but transmission from immunized older children may have been reduced . The vaccine, in addition to its efficacy, appears to be associated with few secondary effects . The use of this vaccine despite its high cost in comparison to other routine vaccines is justified in the Dominican Republic .

J Bacteriol, 2002 Oct, 184(20), 5762 - 71
Escherichia coli DegP protease cleaves between paired hydrophobic residues in a natural substrate: the PapA pilin; Jones CH et al.; The DegP protein, a multifunctional chaperone and protease, is essential for clearance of denatured or aggregated proteins from the inner-membrane and periplasmic space in Escherichia coli . To date, four natural targets for DegP have been described: colicin A lysis protein, pilin subunits and MalS from E . coli, and high-molecular-weight adherence proteins from Haemophilus influenzae . In vitro, DegP has shown weak protease activity with casein and several other nonnative substrates . We report here the identification of the major pilin subunit of the Pap pilus, PapA, as a natural DegP substrate and demonstrate binding and proteolysis of this substrate in vitro . Using overlapping peptide arrays, we identified three regions in PapA that are preferentially cleaved by DegP . A 7-mer peptide was found to be a suitable substrate for cleavage by DegP in vitro . In vitro proteolysis of model peptide substrates revealed that cleavage is dependent upon the presence of paired hydrophobic amino acids; moreover, cleavage was found to occur between the hydrophobic residues . Finally, we demonstrate that the conserved carboxyl-terminal sequence in pilin subunits, although not a cleavage substrate for DegP, activates the protease and we propose that the activating peptide is recognized by DegP's PDZ domains.

Ann Pharmacother, 2002 Oct, 36(10), 1550 - 3
Fatal aspiration pneumonia during transition from donepezil to rivastigmine; Taylor AM et al.; OBJECTIVE: To report a case of fatal aspiration pneumonia in a patient shortly after initiation of rivastigmine and discontinuation of donepezil, with no washout period between therapies . CASE SUMMARY: An 83-year-old white man presented to the emergency department in respiratory distress (O2 saturation 70%; RR 44 breaths/min) secondary to aspiration . He had started rivastigmine 1.5 mg twice daily that same day . The patient had been previously treated with donepezil 10 mg/d, and there was no washout period . He was intubated due to worsening respiratory status and was transferred to the cardiac care unit . He then became hypotensive and required dopamine and fluid support . Brief bronchoscopy revealed food particles in the lower airways and bile-stained secretions . Intubation was notable for the large amount of secretions . The patient died approximately 27 hours after presentation to the emergency department . Blood and sputum cultures were subsequently positive for Haemophilus influenzae . DISCUSSION: Cholinesterase (ChE) inhibitors approved for treatment of Alzheimer disease are associated with nausea and vomiting in a sizable percentage of patients, ranging from 5% to 31% in clinical trials . Most of these adverse events occur during the initiation/titration phase of therapy . An additive risk of adverse events may be expected with coadministration of ChE inhibitors or cholinergic agents or, potentially, with an inadequate washout period between such agents . Review of MEDLINE (1966-July 2002) and International Pharmaceutical Abstracts (1970-July 2002) failed to identify any previous reports of aspiration with rivastigmine or donepezil . CONCLUSIONS: A washout period should be considered when switching between ChE inhibitors to minimize the risk of vomiting and aspiration.

Avian Dis, 2002 Jul-Sep, 46(3), 686 - 90
Identification and characterization of Ornithobacterium rhinotracheale isolates from Mexico; Soriano VE et al.; Ten gram-negative, pleomorphic, rod-shaped isolates from coryza-like, respiratory diseased laying and broiler chickens were identified as Ornithobacterium rhinotracheale . All O . rhinotracheale isolates showed typical biochemical and enzymatic characteristics . Also, all isolates showed hemagglutinating activity with glutaraldehyde-fixed erythrocytes . On the basis of this property, a rabbit-raised antiserum was produced for an isolate . All isolates were identified by antiserum by hemagglutination-inhibition tests . No cross-reactions were observed when O . rhinotracheale isolates were tested with Haemophilus paragallinarum antisera, and vice versa . Mild respiratory signs, including mild nasal discharge, slight rales, and sneezing, were observed in challenged chickens . At postmortem examination, multifocal pneumonia, airsacculitis, and foamy exudate in abdominal cavity were observed . Furthermore, because bacterial adherence is regarded as an essential step in the infection process, in vitro adherence of O . rhinotracheale isolates to chicken tracheal epithelial cells was tested . All isolates showed positive adherence . Obtained results indicate that O . rhinotracheale is a pathogenic agent present in the Mexican poultry.

AIDS Patient Care STDS, 2000 Jan, 14(1), 19 - 36
Chancroid: from clinical practice to basic science; Lewis DA; Chancroid is a sexually transmitted disease caused by the bacterium Haemophilus ducreyi . It usually presents as a genital ulcer and may be associated with regional lymphadenopathy and bubo formation . H . ducreyi infection is predominantly seen in tropical resource-poor regions of the world where it is frequently the most common etiological cause of genital ulceration . Genital ulcer disease has been shown to be an extremely important co-factor in HIV transmission . With the advent of the AIDS epidemic, there has been increased research effort to elucidate those factors involved in the pathogenesis of chancroid . Several putative virulence factors have now been identified and isogenic H . ducreyi mutants constructed by mutagenesis of their encoding genes . This approach has facilitated investigations into the role each of these putative virulence factors may play in H . ducreyi pathogenesis through the use of in vitro and in vivo model systems . One major goal of current chancroid research is to identify antigens which are immunogenic and could form the basis of a vaccine against H . ducreyi infection . Such a vaccine, if shown to be effective in decreasing the prevalence of chancroid, could have the added benefit of slowing down the HIV incidence rates in those populations where chancroid is a major co-factor for HIV transmission.

J Antimicrob Chemother, 2002 Sep, 50 Suppl S1, 61 - 70
Clinical and economic implications of antimicrobial resistance for the management of community-acquired respiratory tract infections; Nicolau D; Lower respiratory tract infections (RTIs), particularly community-acquired pneumonia (CAP), account for over 50 million deaths annually worldwide . They place an extensive clinical and financial burden on healthcare authorities . Upper RTIs, usually mild and non-life threatening, also incur significant healthcare costs . The rising prevalence of resistance of the major causative agents of CAP (Streptococcus pneumoniae, Haemophilus influenzae and Moraxella catarrhalis) to beta-lactam antimicrobials and newer macrolides has necessitated new strategies for appropriate antimicrobial usage . A successful clinical outcome will depend on the patient, choice of drug, and the epidemiology and resistance of the pathogen . Treatment failure will result in increased costs, particularly if hospitalization is required . Pharmacokinetic and pharmacodynamic parameters are being used increasingly to predict maximally effective therapy and optimal bacterial eradication, thus limiting the development of resistance . Antimicrobial susceptibility criteria by MIC should be dictated by the type and location of the infection . Modifying the current MIC breakpoints for penicillin so that more pneumococcal pneumonia isolates are reported appropriately as being susceptible may lead to a decrease in the use of broad-spectrum antimicrobial therapy and its associated increased costs, in favour of more narrow-spectrum therapy . Targeting the pathogen with the most effective antimicrobial in an appropriately selected patient should optimize clinical and microbiological success and, consequently, maximize response rates and economic outcomes . In addition, research efforts need to concentrate on developing new agents with low propensity to select for or induce resistance.

J Antimicrob Chemother, 2002 Sep, 50 Suppl S1, 49 - 59
The PROTEKT surveillance study: antimicrobial susceptibility of Haemophilus influenzae and Moraxella catarrhalis from community-acquired respiratory tract infections; Hoban D et al.; This paper presents data relating to Haemophilus influenzae and Moraxella catarrhalis from PROTEKT (1999-2000), a surveillance study that examined the susceptibility of respiratory pathogens to current and new antibacterials . Beta-lactamase production is the principal mechanism of resistance to ampicillin and other beta-lactam antibacterials in H . influenzae and M . catarrhalis . The PROTEKT study showed that globally, the prevalence of beta-lactamase production in H . influenzae varied considerably: of 2948 isolates, 489 (16.6%) were beta-lactamase-positive {range: 1.8% (Italy) to 65% (South Korea)} . Beta-lactamase-negative, ampicillin-resistant (BLNAR) strains of H . influenzae were uncommon (<0.1%) but their very detection highlights the need for continued vigilance . Overall, few isolates of H . influenzae showed resistance to either macrolides or telithromycin . The emergence of clarithromycin-resistant strains is worrying, however, as such isolates may also show resistance to other macrolides . There was a geographical correlation between beta-lactamase production and the prevalence of resistance to chloramphenicol and tetracycline among the H . influenzae isolates . Of 1131 M . catarrhalis isolates, 92% were beta-lactamase-positive . Most isolates, however, were fully susceptible to nearly all the antibacterials tested, except ampicillin . The most active were ciprofloxacin and levofloxacin (both having MIC(90) values of 0.03 mg/L), moxifloxacin (MIC(90) 0.06 mg/L), azithromycin (MIC(90) < or = 0.06 mg/L) and telithromycin (MIC(90) 0.12 mg/L) . Overall, there were no concerns in terms of resistance to fluoroquinolones for both H . influenzae and M . catarrhalis . In summary, the PROTEKT surveillance study confirmed the problem of widespread prevalence of beta-lactamase-producing strains of H . influenzae and M . catarrhalis, although these pathogens generally remain susceptible to macrolides, fluoroquinolones and the new ketolide telithromycin.

J Wildl Dis, 2002 Jul, 38(3), 649 - 52
Antibodies to selected viral and bacterial pathogens in European wild boars from southcentral Spain; Vicente J et al.; Serum samples from 78 European wild boars (Sus scrofa) harvested during the 1999-2000 hunting season were tested for antibodies to Brucella spp., classical swine fever virus, Erysipelothrix rhusiopathiae, Haemophilus parasuis, Leptospira interrogans serovar pomona, Mycoplasma hyopneumoniae, pseudorabies virus (PRV), porcine parvovirus (PPV), porcine reproductive and respiratory syndrome virus, Salmonella serogroups B, C, and D, Streptococcus suis, and swine influenza virus (SIV) serotypes H1N1 and H3N2 . Samples were collected from Sierra Morena and Montes de Toledo in southcentral Spain . Antibodies were detected to PRV (36%), L . interrogans serovar pomona (12%), PPV (10%), E . rhusiopathiae (5%), SIV serotype H1N1 (4%), Salmonella serogroup B (4%), and Salmonella serogroup C (3%) . Our results suggest that more research is needed to describe the epidemiology of infectious diseases of Spanish wild boars.

J Biol Chem, 2002 Nov 22, 277(47), 45547 - 57 Epub 2002 Sep 16.
Transforming growth factor-beta -Smad signaling pathway cooperates with NF-kappa B to mediate nontypeable Haemophilus influenzae-induced MUC2 mucin transcription; Jono H et al.; Transforming growth factor-beta (TGF-beta) and related factors are multifunctional cytokines that regulate diverse cellular processes, including proliferation, differentiation, apoptosis, and immune response . The involvement of TGF-beta receptor-mediated signaling in bacteria-induced up-regulation of mucin, a primary innate defensive response for mammalian airways, however, still remains unknown . Here, we report that the bacterium nontypeable Haemophilus influenzae (NTHi), an important human respiratory pathogen, utilizes the TGF-beta-Smad signaling pathway together with the TLR2-MyD88-TAK1-NIK-IKKbeta/gamma-IkappaBalpha pathway to mediate NF-kappaB-dependent MUC2 mucin transcription . The NTHi-induced TGF-beta receptor Type II phosphorylation occurred at as early as 5 min . Pretreatment of NTHi with TGF-beta neutralization antibody reduced up-regulation of MUC2 transcription . Moreover, functional cooperation of NF-kappaB p65/p50 with Smad3/4 appears to positively mediate NF-kappaB-dependent MUC2 transcription . These data are the first to demonstrate the involvement of TGF-beta receptor-mediated signaling in bacteria-induced up-regulation of mucin transcription, bring insights into the novel role of TGF-beta signaling in bacterial pathogenesis, and may lead to new therapeutic intervention of NTHi infections.

Infection, 2002 Aug, 30(4), 208 - 11
Influence of moxifloxacin, comparator drugs and some fractions of pulmonary surfactant on adherence of some respiratory pathogens; Ferrara A et al.; BACKGROUND: This study evaluated the effect of moxifloxacin and comparator drugs with or without some fractions of pulmonary surfactant, as surfactant protein-A (SP-A) and phospholipids, on the adherence of the most common respiratory pathogens . MATERIALS AND METHODS: The adherence of respiratory pathogens to a bronchial epithelial cell line was tested . Antimicrobials were used at 1/2, 1/4 and 1/8 minimum inhibitory concentration (MIC), SP-A at 1 and 5 microg/ml and phospholipids at 50 microg/ml . RESULTS: At 1/2 MIC moxifloxacin, ciprofloxacin, amoxicillin-clavulanate and ceftriaxone reduced the adherence of Staphylococcus aureus and Streptococcus pneumoniae to values of 40-50% . At the same concentration, cotrimoxazole reduced the adherence values of Moraxella catarrhalis and Haemophilus influenzae to about 50%, while beta-lactams showed high efficacy only on H . influenzae, with adherence values of about 40% . The addition of SP-A and/or phospholipids to the tested antibiotics had no effect on bacterial adherence . CONCLUSION: The non-interference of SP-A and/or phospholipids with the suppressive effect that some antibiotics exert on bacterial adherence could represent a favorable event during antibiotic therapy.

J Membr Biol, 2002 Sep 15, 189(2), 131 - 41
Altered channel properties of porins from Haemophilus influenzae: isolates from cystic fibrosis patients; Arbing MA et al.; Changes in amino-acid sequence of the unique pore-forming protein of H . influenzae (OmpP2; porin) have been associated with increased antimicrobial resistance in H . influenzae strains isolated from cystic fibrosis patients . From patients who were subjected to long-term antimicrobial therapy, H . influenzae strains 67d and 69a (patient 27) and strains 77a and 77f (patient 30) were isolated . Strains 67d and 77a were previously shown to have elevated values for minimal inhibitory concentrations of antibiotics compared to strains 69a and 77f . Porins were extracted from all four H . influenzae strains by detergent treatment and purified to homogeneity by ion exchange chromatography . By reconstitution of the clinical Hi porins into planar lipid bilayers, single-channel conductance, ionic selectivity, and voltage-gating characteristics were assessed . Porins 77a and 77f displayed similar single-channel conductance and ionic selectivity . Current-voltage relationships were determined for the different porins: porin 77f displayed substantial voltage gating at both positive and negative polarity; porin 77a gated at negative polarity only . Porins 67d and 69a showed substantial differences in their pore-forming properties: the single-channel conductance of porin 69a was significantly increased (1.05 nS) relative to porin 67d (0.73 nS) . Porin 67d was twice as permeable to cations as porin 69a, and at both positive and negative polarities the extent of voltage gating was greater for porin 67d relative to porin 69a . Expression of the porins in an isogenic, porin-deleted H . influenzae background allowed for assessment of the contribution of each porin to the minimum inhibitory concentrations of various antimicrobial compounds . Porin 67d was found to have a decreased susceptibility to the antimicrobials novobiocin and streptomycin . This decreased susceptibility of porin 67d to novobiocin and streptomycin correlates with its decrease in single-channel conductance.

Onderstepoort J Vet Res, 2002 Jun, 69(2), 171 - 5
Virulence of South African isolates of Haemophilus paragallinarum . Part 2: naturally occurring NAD-independent field isolates; Bragg RR; Naturally occurring NAD-independent variants of Haemophilus paragallinarum, which have been isolates from poultry showing clinical signs of infectious coryza, were used to determine their virulence using a newly developed challenge model for infectious coryza . It was established that the NAD-independent isolates belonging to a particular serogroup, were less virulent when compared to the virulence of the NAD-dependent isolates from the same serogroup . It was shown that the virulence of the NAD-independent isolates belonging to serogroup C and serogroup A were very similar to each other . This differs to the results obtained with NAD-dependent isolates reported on previously, in which the serogroup C isolates were found to be more virulent then the serogroup A isolates.

Onderstepoort J Vet Res, 2002 Jun, 69(2), 163 - 9
Virulence of South African isolates of Haemophilus paragallinarum . Part 1: NAD-dependent field isolates; Bragg RR; The virulence of four South African field isolates of NAD-dependent Haemophilus paragallinarum, representing the four serovars known to occur in that country, was investigated . During this study an alternative challenge model for infectious coryza was used, in which the infectivity as well the virulence of different isolates could be evaluated . The challenge model consisted of the direct challenge, via intrasinus injection of one chicken in a row of interconnected layer cages, containing 10 chickens, which are subsequently infected by natural routes . A scoring system of the clinical signs was established in which a score is given to the ability of the isolate to produce clinical signs in the challenge birds . The mean daily disease score for the flock can be calculated and plotted on a graph to give a graphic representation of the disease profile . A mean disease score, calculated over a 20-day examination period can be calculated . Isolates can then be compared to each other, either graphically or by a comparison of the mean disease scores . It has been demonstrated using this scoring system that the South African serogroup C isolates appear to be more virulent than the South African serogroup A or B isolates . It was further established that the serovar C-3 isolate appeared to be the most virulent.

Onderstepoort J Vet Res, 2002 Jun, 69(2), 129 - 32
Isolation of serovar C-3 Haemophilus paragallinarum from Zimbabwe: A further indication of the need for the production of vaccines against infectious coryza containing local isolates of H . paragallinarum; Bragg RR; Various isolates of Haemophilus paragallinarum, collected from a severe outbreak of infectious coryza in poultry from Zimbabwe, were serotyped and were found to belong to serovar C-3 . Previously, isolates were serotyped using polyclonal antiserum produced against serogroup reference strains (0083 for serogroup A, 0222 for serogroup B and Modesto, or H-18 for serogroup C) of H . paragallinarum . In this case, polyclonal antiserum produced against these reference isolates were used, as well as polyclonal antiserum that has been raised specifically against the serovar C-3 isolate 46 C-3 . When using the latter serum at a 1 in 50 dilution, no cross-reaction with other members of serogroup C were found . The severity of the disease outbreak in Zimbabwe, the vaccination history of the infected flocks on the sites and the isolation of the uniquely southern African serovar C-3, further highlights the need for vaccines composed of local isolates to control infectious coryza in regions where vaccination failures occur.

Ned Tijdschr Geneeskd, 2002 Aug 31, 146(35), 1651 - 3
{Haemophilus influenzae type a as the causative agent of meningitis in an infant}; Mulder DC et al.; A 6-month-old girl had been ill with a cold for several days and was increasingly drowsy . She had been fully vaccinated against Haemophilus influenzae type b and had meningitis due to H . influenzae type a . She made a complete recovery after treatment with ceftriaxone and amoxicillin . In the Netherlands, vaccination with the conjugated H . influenzae type b vaccine was started in 1993 and since then invasive infections caused by H . influenzae type b have almost disappeared . Vaccination may suppress carriership of H . influenzae type b . However, vaccination does not elicit cross-protective antibodies against other serotypes of H . influenzae . H . influenzae non-type b may profit from the vaccination state, resulting in a higher carrier rate and an increased incidence of invasive infections . In the Netherlands, H . influenzae type a as the causative agent of an invasive infection has been recorded for the first time since registration started in 1975 and since then five such cases have been reported . In the literature, 45 cases of infection with H . influenzae type a have been described up until now.

J Infect Dis, 2002 Oct 1, 186(7), 958 - 65 Epub 2002 Sep 13.
Reemergence, in southwestern Alaska, of invasive Haemophilus influenzae type b disease due to strains indistinguishable from those isolated from vaccinated children; Lucher LA et al.; Haemophilus influenzae type b (Hib) invasive disease and oropharyngeal carriage continue in rural Alaska despite widespread vaccination . This study investigated whether invasive-disease reemergence during 1996-1997 could be attributed to strains distinguishable from strains carried by vaccinated children . Twenty-four invasive and 42 carriage Hib isolates, collected during 1992-1997, were characterized by pulsed-field gel electrophoresis (PFGE), multilocus enzyme electrophoresis, and biotyping . This Hib population was highly clonal, since only 2 strains, electrophoretic type (ET) 55/PFGE 1 and ET 56/PFGE 3, accounted for 62% of all isolates . The ET 55/PFGE 1 and ET 56/PFGE 3 strains were found in 74% of the carriers and caused 80% of the invasive Hib disease that occurred during April 1996-March 1997 . Strains causing invasive disease could not be distinguished from strains carried by vaccinated children . Continued monitoring of Hib carriage may provide insights into the epidemiology of continued transmission in an era of widespread vaccination.

Infect Immun, 2002 Oct, 70(10), 5887 - 92
Identification and characterization of the N-acetylglucosamine glycosyltransferase gene of Haemophilus ducreyi; Sun S et al.; Haemophilus ducreyi is the causative agent of chancroid, a sexually transmitted ulcerative disease . In the present study, the Neisseria gonorrhoeae lgtA lipooligosaccharide glycosyltransferase gene was used to identify a homologue in the genome of H . ducreyi . The putative H . ducreyi glycosyltransferase gene (designated lgtA) was cloned and insertionally inactivated, and an isogenic mutant was constructed . Structural studies demonstrated that the lipooligosaccharide isolated from the mutant strain lacked N-acetylglucosamine and distal sugars found in the lipooligosaccharide produced by the parental strain . The isogenic mutant was transformed with a recombinant plasmid containing the putative glycosyltransferase gene . This strain produced the lipooligosaccharide glycoforms produced by the parental strain, confirming that the lgtA gene encodes the N-acetylglucosamine glycosyltransferase.

Infect Immun, 2002 Oct, 70(10), 5438 - 45
Fimbrial ghf gene cluster of genital strains of Haemophilus spp; Bruant G et al.; We analyzed the LKP fimbrial gene clusters of six piliated strains of a cryptic genospecies of Haemophilus isolated from the genital tracts of adult patients (five strains) and from an infected neonate . In a group of 19 genital strains, LKP-like genes have been found in only these 6 strains . In addition to the ghfA, ghfD, and ghfE genes previously described, we characterized two genes, designated ghfB and ghfC, encoding the putative chaperone and assembly platform proteins . All six strains had a complete and unique LKP-like gene cluster consisting of the five genes ghfA to ghfE, homologous to genes hifA to hifE of Haemophilus influenzae . The sequences of the coding and intergenic regions of the ghf clusters of the six strains were remarkably homologous . Unlike hif clusters, which are inserted between purE and pepN, the ghf cluster was inserted between purK and pepN on the chromosome . Analysis of the flanking regions of the ghf cluster identified a large deletion, identical in the 5' end regions of all strains, including the whole purE gene and much of the purK gene . Ultrastructural observations, an attempt at enriching LKP fimbriae, and hemagglutination experiments demonstrated that none of the strains had LKP-type fimbriae . Nevertheless, reverse transcription (RT)-PCR showed that ghf genes were transcribed in four of the six strains . Sequencing of the intergenic ghfA-ghfB regions, including the ghf gene promoters, showed that the absence of transcripts in the remaining two strains was due to a decrease in the number of TA repeats (4 or 9 repeats rather than 10) between the -10 and -35 boxes of the two overlapping and divergent promoters . The other four strains, which had ghf transcripts, had the optimal 10 TA repeats (one strain) or 5 repeats associated with putative alternative -35 boxes (three strains) . The absence of 10 repeated palindromic sequences of 44 or 45 nucleotides upstream of ghfB induces an increased instability of mRNA, as quantified by real-time RT-PCR, and may explain why the LKP fimbrial gene cluster is not expressed in these strains.

Acta Paediatr, 2002, 91(8), 885 - 91
Anogenital bacteriology in non-abused preschool children: a descriptive study of the aerobic genital flora and the isolation of anogenital Gardnerella vaginalis; Myhre AK et al.; The purpose of the study is to describe the genital aerobic bacterial flora including Gardnerella vaginalis in girls and the occurrence of anal G . vaginalis in both genders . From a group of 3773 children, 278 (99 boys and 179 girls) with a mean age of 5.63 y (range: 5.13-6.73) were recruited . Inclusion in the study was based on self-selection, whereby parents who did not suspect any occurrence of sexual abuse of their child gave informed consent to participate . Several mechanisms were undertaken to exclude abused children . At least one bacterial species was isolated from the genitals of 59 (33.9%) girls . Most isolates (39 out of 99) were bacteria representing skin flora (staphylococci and coryneform organisms), with viridans streptococci and related organisms as the second most common group of isolates (31 out of 99) . S . anginosus was the single most frequent bacterial species identified (17 isolates) . Streptococcus pyogenes was isolated from the genitals of two girls, Streptococcus pneumoniae from one girl and Haemophilus influenzae from eight girls . G . vaginalis was not isolated from the genitals in any girl, but the organism was isolated from the anal canal in three children.

J Mol Biol, 2002 Aug 23, 321(4), 591 - 9
Zebularine: a novel DNA methylation inhibitor that forms a covalent complex with DNA methyltransferases; Zhou L et al.; Mechanism-based inhibitors of enzymes, which mimic reactive intermediates in the reaction pathway, have been deployed extensively in the analysis of metabolic pathways and as candidate drugs . The inhibition of cytosine-{C5}-specific DNA methyltransferases (C5 MTases) by oligodeoxynucleotides containing 5-azadeoxycytidine (AzadC) and 5-fluorodeoxycytidine (FdC) provides a well-documented example of mechanism-based inhibition of enzymes central to nucleic acid metabolism . Here, we describe the interaction between the C5 MTase from Haemophilus haemolyticus (M.HhaI) and an oligodeoxynucleotide duplex containing 2-H pyrimidinone, an analogue often referred to as zebularine and known to give rise to high-affinity complexes with MTases . X-ray crystallography has demonstrated the formation of a covalent bond between M.HhaI and the 2-H pyrimidinone-containing oligodeoxynucleotide . This observation enables a comparison between the mechanisms of action of 2-H pyrimidinone with other mechanism-based inhibitors such as FdC . This novel complex provides a molecular explanation for the mechanism of action of the anti-cancer drug zebularine.

Plasmid, 2002 Jul, 48(1), 38 - 48
Characterisation and genetic organisation of a 24-MDa plasmid from the Brazilian Purpuric Fever clone of Haemophilus influenzae biogroup aegyptius; Kroll JS et al.; Strains of Haemophilus influenzae biogroup aegyptius causing septicaemia were identified in Brazil in the 1980s, causing the life-threatening illness of Brazilian Purpuric Fever (BPF) . The strains were found to fall into a single clonal group, the BPF clone, characterised by their possession of the approximately 24MDa "3031" plasmid . In this work we report the characterisation and genetic organisation of this plasmid . Analysis of the gene content of what appears to be a typical broad host range conjugative plasmid, its presence in non-BPF strains as revealed by Southern hybridisation, and the recent discovery of plasmid-lacking BPF strains, has led us to conclude that it is unlikely to play a critical role in bacterial virulence . Establishing its entire sequence has nonetheless been an important step on the road to delineating, by comparison of BPF and non-BPF strains, chromosomal genetic loci that are involved in the special virulence of the BPF clone.

Commun Dis Intell, 2002, 26(2), 118 - 203
Australia's notifiable diseases status, 2000 . Annual report of the National Notifiable Diseases Surveillance System; Lin M et al.; In 2000, there were 89,740 notifications of communicable diseases in Australia collected by the National Notifiable Diseases Surveillance System (NNDSS) . The number of notifications in 2000 was an increase of 5.9 per cent over those reported in 1999 (84,743) and the largest reporting year since the NNDSS commenced in 1991 . Notifications in 2000 consisted of 28,341 bloodborne infections (32% of total), 24,319 sexually transmitted infections (27%), 21,303 gastrointestinal infections (24%), 6,617 vaccine preventable infections (7%), 6,069 vectorborne infections (7%), 2,121 other bacterial infections (legionellosis, meningococcal infection, leprosy and tuberculosis) (2%), 969 zoonotic infections (1%) and only one case of a quarantinable infection . Steep declines in some childhood vaccine preventable diseases such as Haemophilus influenzae type b, measles, mumps and rubella, continued in 2000 . In contrast, notifications of pertussis and legionellosis increased sharply in the year . Notifications of bloodborne viral diseases (particularly hepatitis B and hepatitis C) and some sexually transmitted infections such as chlamydia, continue to increase in Australia . This report also summarises data on communicable diseases from other surveillance systems including the Laboratory Virology and Serology Surveillance Scheme (LabVISE) and sentinel general practitioner schemes . In addition this report comments on other important developments in communicable disease control in Australia in 2000.

Clin Orthop, 2002 Sep, (402), 202 - 5
Haemophilus influenza infection complicating a total knee arthroplasty; Bezwada HP et al.; Haemophilus influenza is rarely a cause of septic arthritis in adults . It has not been reported as a cause of infection in total knee arthroplasties . Haemophilus influenza septic arthritis is a late stage, hematogenous infection . A 43-year-old woman with a history of rheumatoid arthritis was found to have Haemophilus influenza infection 3 years after the index total knee arthroplasty . The patient was treated with debridement and systemic antibiotics . At the 5-year followup, the patient was comfortable and free of clinical signs of infection . This approach was successful at eradicating infection and salvaging the total knee arthroplasty.

Chemotherapy, 2002 Sep, 48(4), 168 - 73
Antimicrobial action of Nitens mouthwash (cetyltrimethylammonium naproxenate) on multiple isolates of pharyngeal microbes: a controlled study against chlorhexidine, benzydamine, hexetidine, amoxicillin, amoxicillin-clavulanate, clarithromycin, and cefaclor; Pilloni AP et al.; BACKGROUND: Acute oropharyngeal and respiratory tract infections are due to a wide spectrum of microorganisms . The aim of this study was to compare and evaluate the in vitro activity of four antiseptics (cetyltrimethylammonium naproxenate, chlorhexidine, benzydamine, hexetidine) to four antibiotics (amoxicillin, amoxicillin-clavulanate, clarithromycin, cefaclor) on strains of Haemophilus influenzae, Moraxella catarrhalis, Streptococcus pyogenes and Streptococcus pneumoniae . METHODS: Susceptibility tests were performed on 90, aerobic and anaerobic, bacterial strains, isolated from nasopharyngeal swabs and sputum . Minimum inhibitory concentrations (by microdilution) and minimum bactericidal concentrations were determined and compared . RESULTS: Our selected panel of bacteria was highly susceptible to the antiseptics, particularly to chlorhexidine and naproxenate, even more so than two of the most frequently used antibiotics . Data were statistically significant (p < 0.005) . CONCLUSIONS: In view of their bactericidal and anti-inflammatory properties, these antiseptics may be effective in controlling the transitory colonization of the oral cavity by microbes that cause or worsen disease in patients with mild infections .

Vestn Ross Akad Med Nauk, 2001, (10), 18 - 25
{Genomics of pathogenic bacteria}; Shestakov SV; The general principles of structural and functional organization of genomes in pathogenic bacteria are considered . Main data on the specific features of genomes of Chlamydia trachomatis, Rickettsia prowazekii, Treponema pallidum, Helicobacter pylori, Haemophilus influenzae, Neisseria meningitidis, Vibro cholerae and pathogenic strains of Escherichia coli are summarized . Particular attention is paid to the problems of genetic control of pathogenicity, intraspecies variations in bacterial genomes, to the environmental and evolutionary meaning of horizontal gene transfer . Whether methods for genotyping bacterial strains can be used is discussed.

MMWR Morb Mortal Wkly Rep, 2002 Aug 16, 51(32), 706 - 7
Serotyping discrepancies in Haemophilus influenzae type b disease--United States, 1998-1999; Haemophilus influenzae type b and cross-reactive antigens in natural Hib infection dynamics; modelling in two populations; National Public Health Institute, Helsinki, FinlandNatural immunity to Haemophilus influenzae type b (Hib) invasive disease is based on antibodies arising in response to encounters with Hib or cross-reactive (CR) bacteria . The relative importance of Hib and CR contacts is unknown . We applied a statistical model to estimate the total rate of immunizing infections of Hib and CR prior to wide-scale vaccinations in Finland and the UK . The average rates of these contacts were 0.7 and 1.2 per year per child in Finland and the UK, respectively . Using a rough estimate of 0.1 Hib acquisitions per year per child in the UK based on carriage rates, the proportion of Hib among all immunizing contacts was in the order of 10%, suggesting that CR bacteria have a major role . In general, varying frequency of CR contacts may explain some differences in the pre-vaccination incidence and age-distribution of invasive disease in different countries.

J Clin Microbiol, 2002 Sep, 40(9), 3442 - 8
Genotypic diversity of clinical Actinomyces species: phenotype, source, and disease correlation among genospecies; Clarridge JE 3rd et al.; We determined the frequency distribution of Actinomyces spp . recovered in a routine clinical laboratory and investigated the clinical significance of accurate identification to the species level . We identified 92 clinical strains of Actinomyces, including 13 strains in the related Arcanobacterium-Actinobaculum taxon, by 16S rRNA gene sequence analysis and recorded their biotypes, sources, and disease associations . The clinical isolates clustered into 21 genogroups . Twelve genogroups (74 strains) correlated with a known species, and nine genogroups (17 strains) did not . The individual species had source and disease correlates . Actinomyces turicensis was the most frequently isolated species and was associated with genitourinary tract specimens, often with other organisms and rarely with inflammatory cells . Actinomyces radingae was most often associated with serious, chronic soft tissue abscesses of the breast, chest, and back . Actinomyces europaeus was associated with skin abscesses of the neck and genital areas . Actinomyces lingnae, Actinomyces gravenitzii, Actinomyces odontolyticus, and Actinomyces meyeri were isolated from respiratory specimens, while A . odontolyticus-like strains were isolated from diverse sources . Several of the species were commonly coisolated with a particular bacterium: Actinomyces israelii was the only Actinomyces spp . coisolated with Actinobacillus (Haemophilus) actinomycetemcomitans; Actinomyces meyeri was coisolated with Peptostreptococcus micros and was the only species other than A . israelii associated with sulfur granules in histological specimens . Most genogroups had consistent biotypes (as determined with the RapID ANA II system); however, strains were misidentified, and many codes were not in the database . One biotype was common to several genogroups, with all of these isolates being identified as A . meyeri . Despite the recent description of new Actinomyces spp., 19% of the isolates recovered in our routine laboratory belonged to novel genospecies . One novel group with three strains, Actinomyces houstonensis sp . nov., was phenotypically similar to A . meyeri and A . turicensis but was genotypically closest to Actinomyces neuii . A . houstonensis sp . nov . was associated with abscesses . Our data documented consistent site and disease associations for 21 genogroups of Actinomyces spp . that provide greater insights into appropriate treatments . However, we also demonstrated a complexity within the Actinomyces genus that compromises the biochemical identification of Actinomyces that can be performed in most clinical laboratories . It is our hope that this large group of well-defined strains will be used to find a simple and accurate biochemical test for differentiation of the species in routine laboratories.

J Clin Microbiol, 2002 Sep, 40(9), 3269 - 76
Effects of various test media on the activities of 21 antimicrobial agents against Haemophilus influenzae; Jacobs MR et al.; As considerable variation in the antimicrobial susceptibility of Haemophilus influenzae has been reported, the effects of various test media on the susceptibility of H . influenzae were studied . MICs were determined by three laboratories for 21 antimicrobial agents against a panel of 100 selected isolates . Testing was performed using a reference NCCLS frozen broth microdilution method with Haemophilus test medium (HTM) broth and dried commercial MIC trays rehydrated with the following media: in-house and commercially prepared HTM broth, Mueller-Hinton broth with 2% lysed horse blood and NAD, IsoSensitest broth with 2% lysed horse blood and NAD, and IsoSensitest broth-based HTM . Overall, all results were very reproducible, with the MIC at which 50% of the isolates tested are inhibited (MIC(50)), MIC(90), and geometric mean MIC being within one doubling dilution by all six methods and at all three testing centers for 15 of the 21 agents tested . Interlaboratory differences were more marked than intralaboratory differences or differences among media . Cefprozil, cefaclor, and trimethoprim-sulfamethoxazole results differed the most, while results for ampicillin, amoxicillin-clavulanic acid, cefdinir, cefixime, ceftriaxone, and clarithromycin were the most reproducible . However, these variations in results caused considerable differences in susceptibility rates for agents for which NCCLS susceptible breakpoints were close to the geometric mean MIC, particularly for cefaclor and cefprozil . This was much less of a problem when pharmacokinetic-pharmacodynamic breakpoints were used . Reproducible susceptibility results were obtained for a wide range of agents against H . influenzae in three laboratories using a variety of media that support the growth of this fastidious species.

Microb Pathog, 2002 Aug, 33(2), 49 - 62
Toxicity and immunogenicity of purified Haemophilus ducreyi cytolethal distending toxin in a rabbit model; Wising C et al.; The cytolethal distending toxin of Haemophilus ducreyi (HdCDT) is a three-component toxin that induces the arrest of the mammalian cell cycle in the G2 phase . All of the individual gene products, CdtA, CdtB and CdtC, are required for toxic activity on cultured mammalian cells . The CdtB component alone exerts nuclease activity . The individual HdCDT components were purified by affinity chromatography or ion-exchange chromatography followed by gel-filtration . HdCDT was reconstituted and purified by the immobilization of a GST-CdtB fusion on a GSTrap column and the subsequent addition of cell sonicates from Escherichia coli recombinants that produced CdtA and CdtC . The purified HdCDT preparation contained all three CDT proteins, as detected by immuno-blotting, and had high cytotoxic activity (10(6)CPU/ml) . Immunization of rabbits with the HdCDT complex and with the individual CdtA, CdtB and CdtC proteins elicited high titres of antibodies, as detected by ELISA . All of the immune sera had toxin-neutralizing activities . The pathological effects of the HdCDT complex were investigated in rabbits, since the proliferation of two rabbit cell lines, SIRC and RK-13, was inhibited by HdCDT . Intradermal injection of HdCDT (1, 10, 50 and 100microg protein) into naive rabbits resulted in dose-dependent skin reactions (erythema) about 24h after injection . Similar effects were not observed when the individual HdCDT proteins were injected . HdCDT injection into immune rabbits resulted in dose-dependent skin responses that were characterized by both erythema and oedema . Histological evaluation of the 24-h lesions in naive rabbits that were injected with HdCDT, revealed moderate levels of inflammatory cells, which were mainly granulocytes and macrophages, and dilatation of blood vessels . The skin reactions in HdCDT-injected immunized rabbits showed pronounced vascular changes and extensive infiltration of inflammatory cells, including eosinophils . All of the pathological changes healed after 3 days . In conclusion, purified HdCDT holotoxin is a complex of all three CDT proteins and all three components induce neutralizing antibodies when injected in rabbits . HdCDT causes dose-dependent pathologic skin reactions in both naive and immune rabbits, which is characterized by increased inflammatory responsiveness after each immunization.

Thorax, 2002 Sep, 57(9), 759 - 64
Relationship between bacterial colonisation and the frequency, character, and severity of COPD exacerbations; Patel IS et al.; BACKGROUND: Patients with chronic obstructive pulmonary disease (COPD) are prone to frequent exacerbations which are a significant cause of morbidity and mortality . Stable COPD patients often have lower airway bacterial colonisation which may be an important stimulus to airway inflammation and thereby modulate exacerbation frequency . METHODS: Twenty nine patients with COPD (21 men, 16 current smokers) of mean (SD) age 65.9 (7.84) years, forced expiratory volume in 1 second (FEV(1)) 1.06 (0.41) l, FEV(1) % predicted 38.7 (15.2)%, FEV(1)/FVC 43.7 (14.1)%, inhaled steroid dosage 1.20 (0.66) mg/day completed daily diary cards for symptoms and peak flow over 18 months . Exacerbation frequency rates were determined from diary card data . Induced sputum was obtained from patients in the stable state, quantitative bacterial culture was performed, and cytokine levels were measured . RESULTS: Fifteen of the 29 patients (51.7%) were colonised by a possible pathogen: Haemophilus influenzae (53.3%), Streptococcus pneumoniae (33.3%), Haemophilus parainfluenzae (20%), Branhamella catarrhalis (20%), Pseudomonas aeruginosa (20%) . The presence of lower airway bacterial colonisation in the stable state was related to exacerbation frequency (p=0.023) . Patients colonised by H influenzae in the stable state reported more symptoms and increased sputum purulence at exacerbation than those not colonised . The median (IQR) symptom count at exacerbation in those colonised by H influenzae was 2.00 (2.00-2.65) compared with 2.00 (1.00-2.00) in those not colonised (p=0.03) . The occurrence of increased sputum purulence at exacerbation per patient was 0.92 (0.56-1.00) in those colonised with H influenzae and 0.33 (0.00-0.60) in those not colonised (p=0.02) . Sputum interleukin (IL)-8 levels correlated with the total bacterial count (rho=0.459, p=0.02) . CONCLUSION: Lower airway bacterial colonisation in the stable state modulates the character and frequency of COPD exacerbations.

Semin Pediatr Infect Dis, 2002 Jul, 13(3), 182 - 9
Vaccines for the prevention of meningococcal disease in children; Soriano-Gabarro M et al.; Neisseria meningitidis is one of the most feared infections in pediatrics as the result of its rapid progression, high fatality rate, and frequent occurrence of sequelae . The 5 major meningococcal serogroups associated with disease are A, B, C, Y, and W-135 . Currently available polysaccharide vaccines are effective in preventing disease caused by serogroups A, C, Y, and W-135 in older children and adults but do not elicit good long-term protection in young children . Vaccines that protect against serogroup B disease are still in development . As with the Haemophilus influenzae type b and pneumococcal polysaccharide vaccines, conjugation of the polysaccharide vaccine to a protein carrier dramatically changes vaccine characteristics, with resulting efficacy in infants . New meningococcal conjugate vaccines against serogroups A, C, Y, and W-135 are being developed . A serogroup C conjugate vaccine has been introduced successfully into the routine childhood schedule in the United Kingdom . New meningococcal conjugate vaccines are likely to have a dramatic effect on the burden of meningococcal disease within the next decade.

Jpn J Antibiot, 2002 Jun, 55(3), 302 - 10
{Microbiological and clinical studies of Haemophilus influenzae isolated at Kitakyushu Municipal Medical Center from 1996 through 1999}; Furugo I et al.; Epidemiological and microbiological studies were carried out using 575 strains of Haemophilus influenzae isolated from clinical specimens at Kitakyushu municipal medical center from January 1996 through December 1999 . The strains isolated multiply were excluded . The strains of H . influenzae did not increase for 4 years, and were detected more in summer season, peaked in July, and less in winter season . Like the cases of Streptococcus pneumoniae, most (91.8%) of the strains was detected in the specimens from the respiratory tract, and also they were isolated mainly from infants under 4-years old (25.6%) and adults over 65-years old (24.2%) MICs of 7 antimicrobial agents, such as ampicillin (ABPC), sulbactam/ABPC, cefaclor, imipenem, panipenem, meropenem (MEPM), and levofloxacin (LVFX) were determined using broth microdilution methods . Among 575 strains of H . influenzae isolated from clinical specimens, 51 ABPC-resistant strains (8.9%) produced beta-lactamase, and 67 strains (11.6%) were beta-lactamase negative ampicillin resistant H . influenzae . The ABPC-resistant strains existed in 20.5% . Both of MEPM and LVFX showed excellent antimicrobial activity against H . influenzae including ABPC-resistant strains . Four cases of meningitis were reviewed . All of H . influenzae isolated possessed type b capsular antigen . All patients recovered by appropriate antimicrobial treatment . But one adult patient developed serious sequela.

Br J Cancer, 2002 Aug 27, 87(5), 511 - 2
Haemophilus influenzae type b vaccine formulation and risk of childhood leukaemia; Groves F et al.; Incidence of childhood leukaemia was studied among subjects of a vaccine trial in Finland comparing the polysaccharide-diptheria toxoid conjugate and oligosaccharide-CRM197 conjugate Haemophilus influenzae type b conjugate vaccine formulations . Eighty cases of childhood leukaemia were detected: 35 among children on the polysaccharide-diptheria toxoid conjugate arm, and 45 among children on the oligosaccharide-CRM197 conjugate arm, which was not statistically significant.

Rinsho Byori, 2002 Jul, 50(7), 664 - 71
{Medical supports for the diagnosis of infectious diseases; the role and responsibilities of clinical pathologist and microbiology technologist . Acute purulent meningitis; the position of the technologists in microbiology laboratory}; Misawa S; The features and limitations of microbiology processes for the diagnosis of bacterial meningitis were summarized . Requests for physicians were also emphasized . The microbiology laboratory should be responsible for providing highly reliable and concordant data with a variety of clinical settings . Technologists in a microbiology laboratory should perform following subjects: i) Direct smear examination: Presumptive identification by the observers with abundant experience and sufficient training . ii) Rapid bacterial antigen detection tests: Active utilize alone in combination with the direct microscopy . iii) Culture: Cost effective utilize for appropriate media and culture condition based on the bacteriological statistics . Report with bacteriological interpretations and with additional proper comments, if necessary . iv) Antimicrobial susceptibility tests: Determination of penicillin resistance among the strains of penicillin-resistant or-intermediate Streptococcus pneumoniae (PI or PRSP) should be confirmed by MIC procedures; Detection of beta-lactamase producing Haemophilus influenzae (BLP) could detect by beta-lactamase tests, but not clearly identify for beta-lactamase-negative ampicillin-resistant isolates (BLNAR) . In addition, a laboratory should provide appropriate information by using the accumulated routine clinical microbiology data, which may help to physicians in selecting an empiric therapy and to the microbiology technologists in processing the routine microbiology . In recent status, the most common organisms isolated from patients with bacterial meningitis continue to be S . pneumoniae and H . influenzae . Among S . pneumoniae strains, penicillin-intermediate(PISP) and--resistant(PRSP) strains had exceeded 50%, and the strains of beta-lactamase producing H . influenzae (BLP) had decreased with less than 10% and beta-lactamase negative ampicillin-resistant strains (BLNAR) have increasing . To providing rapid and accurate results, a laboratory should require the clinical information, including patient's age, major presenting symptoms, and receive antimicrobials prior to specimen collection.

Hosp Med, 2002 Jul, 63(7), 401 - 7
Management of acute and chronic osteomyelitis; Ray PS et al.; The incidence of acute and subacute osteomyelitis is declining . Vaccination has almost eradicated Haemophilus bone infection in infants . However, chronic traumatic osteomyelitis is becoming more frequent following an increase in motorcycle accidents and infected internal fixation of fractures . There are now effective means of treating this using the Ilizarov external circular frame.

Natl Med J India, 2002 May-Jun, 15(3), 135 - 40
Community prevalence of sexually transmitted diseases and human immunodeficiency virus infection in Tamil Nadu, India: a probability proportional to size cluster survey; Thomas K et al.; BACKGROUND: Human immunodeficiency virus (HIV) infection and AIDS is threatening the survival of many nations . To evaluate ongoing interventional strategies and burden of illness estimates, valid data on the prevalence of HIV are required . Often, in the absence of community prevalence data, estimates are based on surrogate markers such as prevalence of HIV in antenatal clinics . Even though the antenatal prevalence of HIV is easier to measure and can be repeated for evaluation, it is important to establish the association between antenatal and community prevalence of sexually transmitted diseases (STDs) and HIV, so that the validity of the estimates can be verified . METHODS: A 'probability proportional to size' cluster survey was conducted in three randomly selected districts of Tamil Nadu in India . The basic unit of the survey was households from rural and urban clusters . Adults 15-45 years of age from the selected households were eligible for recruitment . Demographic, behavioural and laboratory data were collected . Clinical examination was done to identify STD syndromes and blood, urine, vaginal/urethral and endocervical swabs were taken for laboratory diagnosis of STDs from the subjects . Direct smear examination for Trichomonas vaginalis; serological tests for syphilis, hepatitis B, HIV, herpes simplex virus 2, Chlamydia trachomatis; and culture of Neisseria gonorrhoeae and Haemophilus ducreyi were performed on the collected specimens . The data were analysed adjusting for cluster effect . RESULT: We selected and screened 1981 individuals (1157 women and 824 men) for STDs and HIV from 1114 households representing the 25 million projected adult population of Tamil Nadu . The overall community prevalence of STDs including HIV and hepatitis B in Tamil Nadu was 14.6% (CI: 14.1-15.1), and 8.3% (CI: 7.9-8.6) when HIV and hepatitis B were excluded . Community prevalence of HIV and hepatitis B infection was 1.8% (CI:1.7-1.9) and 5.3% (CI: 5.1-5.5), respectively . The distribution of HIV involved both rural and urban regions of Tamil Nadu . On clinical examination, at least one STD syndrome was noted in 486 (24.5%) of the women subjects; vaginal discharge was the most common and found in 421 women (38.4%) . CONCLUSION: The prevalence of STD and HIV in Tamil Nadu is higher than expected and has extended into the non-high risk population (generalized epidemic).

J Fam Pract, 2002 Aug, 51(8), 709 - 16
Evidence-based guidelines for management of nursing home-acquired pneumonia; Hutt E et al.; We convened a multidisciplinary, multispecialty panel to develop comprehensive evidence and consensus-based guidelines for managing nursing home-acquired pneumonia . The panel began with explicit criteria for process of care quality measures, performed a comprehensive review of the English-language literature, evaluated the quality of the evidence, and drafted a set of proposed guidelines . The panel reviewed the draft, an annotated bibliography, and data from a study of 30-day survival from nursing home-acquired pneumonia, and then participated in an all-day meeting in January 2001 . Using a modified Delphi process, the panel refined the guidelines and developed a care pathway . The guidelines recommend a comprehensive approach, including immunization of staff and residents, and communication between nursing staff and the attending physician within 2 hours of symptom onset . Probable pneumonia was defined . An algorithm was delineated for assessing the patientamprsquos wishes for hospitalization and aggressive care, and deciding on hospitalization based on the severity of the illness as well as the capacity of the nursing home to provide acute care . The timing and extent of evaluation in a nursing home relative to the rapid initiation of antibiotics should depend on whether the patient has any unstable vital signs . An antibiotic covering Streptococcus pneumoniae, Haemophilus influenzae, common gram-negative rods, and Staphylococcus aureus should be given for 10 to 14 days, orally if the patient is able to take medications by mouth.

Ann Otol Rhinol Laryngol, 2002 Aug, 111(8), 696 - 700
Interference of nontypeable Haemophilus influenzae and Moraxella catarrhalis by Streptococcus oralis in adenoid organ culture: a possible strategy for the treatment of the otitis-prone child; Bernstein JM et al.; The role of viridans group streptococci (Streptococcus oralis) in the prevention of colonization with nontypeable Haemophilus influenzae and Moraxella catarrhalis was investigated in an adenoid organ culture system . The adenoids from 100 patients who were undergoing adenoidectomy for either hypertrophy or recurrent otitis media were used . Streptococcus oralis Parker uniformly inhibited colonization with nontypeable H . influenzae or M . catarrhalis over a 24-hour period of incubation in adenoid organ culture . Streptococcus oralis Booth, a noninhibitory strain, did not significantly reduce colonization with nontypeable H . influenzae and M . catarrhalis . The results indicate that some strains of S . oralis may inhibit colonization with potential pathogens in the nasopharynx . It is therefore possible that colonization with inhibitory strains of viridans streptococci may be used in the nasopharynx as a relatively safe and inexpensive approach to prevention of recurrent otitis media in some children.

Infect Immun, 2002 Sep, 70(9), 5287 - 9
Susceptibility of nontypeable Haemophilus influenzae to human beta-defensins is influenced by lipooligosaccharide acylation; Starner TD et al.; Nontypeable Haemophilus influenzae (NTHI) lipooligosaccharide htrB mutants exhibited greater than 45-fold-increased sensitivity to human beta-defensin 2 (HBD-2) compared to the wild type . Complementation by htrB in trans to acylation competence reversed this increased sensitivity . In contrast, NTHI was more susceptible to HBD-3 and showed no changes in sensitivity as a result of lipooligosaccharide mutations in oligosaccharide and lipid A biosynthesis genes.

Infect Immun, 2002 Sep, 70(9), 4902 - 7
The Haemophilus influenzae Hap autotransporter binds to fibronectin, laminin, and collagen IV; Fink DL et al.; Nontypeable Haemophilus influenzae (NTHI) initiates infection by colonizing the upper respiratory tract mucosa . NTHI disease frequently occurs in the context of respiratory tract inflammation, where organisms encounter damaged epithelium and exposed basement membrane . In this study, we examined interactions between the H . influenzae Hap adhesin and selected extracellular matrix proteins . Hap is an autotransporter protein that undergoes autoproteolytic cleavage, with release of the adhesive passenger domain, Hap(s), from the bacterial cell surface . We found that Hap promotes bacterial adherence to purified fibronectin, laminin, and collagen IV and that Hap-mediated adherence is enhanced by inhibition of autoproteolysis . Adherence is inhibited by pretreatment of bacteria with a polyclonal antiserum recognizing Hap(s) . Purified Hap(s) binds with high affinity to fibronectin, laminin, and collagen IV but not to collagen II . Binding of Hap(s) to fibronectin involves interaction with the 45-kDa gelatin-binding domain but not the 30-kDa heparin-binding domain of fibronectin . Taken together, these observations suggest that interactions between Hap and extracellular matrix proteins may play an important role in NTHI colonization of the respiratory tract.

Infect Immun, 2002 Sep, 70(9), 4870 - 9
Incorporation of N-acetylneuraminic acid into Haemophilus somnus lipooligosaccharide (LOS): enhancement of resistance to serum and reduction of LOS antibody binding; Inzana TJ et al.; Haemophilus somnus isolates from cases of thrombotic meningoencephalitis, pneumonia, and other disease sites are capable of undergoing a high rate of phase variation in the oligosaccharide component of their lipooligosaccharides (LOS) . In contrast, the LOS of commensal strains isolated from the normal reproductive tract phase vary little or not at all . In addition, the LOS of H . somnus shares conserved epitopes with LOS from Neisseria gonorrhoeae, Haemophilus influenzae, and other species that can incorporate sialic acid into their LOS . We now report that growth of disease isolates of H . somnus with CMP-N-acetylneuraminic acid (CMP-NeuAc) or NeuAc added to the medium resulted in incorporation of NeuAc into the LOS . However, NeuAc was not incorporated into the LOS of commensal isolates and one disease isolate following growth in medium containing CMP-NeuAc or NeuAc . Sialylated LOS was detected by an increase in the molecular size or an increase in the amount of the largest-molecular-size LOS electrophoretic bands, which disappeared following treatment with neuraminidase . Sialylated LOS could also be detected by reactivity with Limax flavus agglutinin lectin, which is specific for sialylated species, by dot blot assay; this reactivity was also reversed by neuraminidase treatment . H . somnus strain 2336 LOS was found to contain some sialic acid when grown in medium lacking CMP-NeuAc or NeuAc, although supplementation enhanced NeuAc incorporation . In contrast strain 738, an LOS phase variant of strain 2336, was less extensively sialylated when the growth medium was supplemented with CMP-NeuAc or NeuAc, as determined by electrophoretic profiles and electrospray mass spectrometry . The sialyltransferase of H . somnus strain 738 was confirmed to preferentially sialylate the Gal(beta)-(1-3)-GlcNAc component of the lacto-N-tetraose structure by capillary electrophoresis assay . Enhanced sialylation of the strain 2336 LOS inhibited the binding of monoclonal antibodies to LOS by enzyme immunoassay and Western blotting . Furthermore, sialylation of the LOS enhanced the resistance of H . somnus to the bactericidal action of antiserum to LOS . Sialylation and increased resistance to killing by normal serum also occurred in a deletion mutant that was deficient in the terminal Gal-GlcNAc disaccharide . LOS sialylation may therefore be an important virulence mechanism to protect H . somnus against the host immune system.

Antimicrob Agents Chemother, 2002 Sep, 46(9), 2956 - 62
In vitro selection of resistance in Haemophilus influenzae by amoxicillin-clavulanate, cefpodoxime, cefprozil, azithromycin, and clarithromycin; Clark C et al.; Abilities of amoxicillin-clavulanate, cefpodoxime, cefprozil, azithromycin, and clarithromycin to select resistant mutants of Haemophilus influenzae were tested by multistep and single-step methodologies . For multistep studies, 10 random strains were tested: 5 of these were beta-lactamase positive . After 50 daily subcultures in amoxicillin-clavulanate, MICs did not increase more than fourfold . However, cefprozil MICs increased eightfold for one strain . Clarithromycin and azithromycin gave a >4-fold increase in 8 and 10 strains after 14 to 46 and 20 to 50 days, respectively . Mutants selected by clarithromycin and azithromycin were associated with mutations in 23S rRNA and ribosomal proteins L4 and L22 . Three mutants selected by clarithromycin or azithromycin had alterations in ribosomal protein L4, while five had alterations in ribosomal protein L22 . Two mutants selected by azithromycin had mutations in the gene encoding 23S rRNA: one at position 2058 and the other at position 2059 (Escherichia coli numbering), with replacement of A by G . One clone selected by clarithromycin became hypersusceptible to macrolides . In single-step studies azithromycin and clarithromycin had the highest mutation rates, while amoxicillin-clavulanate had the lowest . All resistant clones were identical to parents as observed by pulsed-field gel electrophoresis . The MICs of azithromycin for azithromycin-resistant clones were 16 to >128 micro g/ml, and those of clarithromycin for clarithromycin-resistant clones were 32 to >128 micro g/ml in multistep studies . For strains selected by azithromycin, the MICs of clarithromycin were high and vice versa . After 50 daily subcultures in the presence of drugs, MICs of amoxicillin-clavulanate and cefpodoxime against H . influenzae did not rise more than fourfold, in contrast to cefprozil, azithromycin, and clarithromycin, whose MICs rose to variable degrees.

Antimicrob Agents Chemother, 2002 Sep, 46(9), 2752 - 64
N-alkyl urea hydroxamic acids as a new class of peptide deformylase inhibitors with antibacterial activity; Hackbarth CJ et al.; Peptide deformylase (PDF) is a prokaryotic metalloenzyme that is essential for bacterial growth and is a new target for the development of antibacterial agents . All previously reported PDF inhibitors with sufficient antibacterial activity share the structural feature of a 2-substituted alkanoyl at the P(1)' site . Using a combination of iterative parallel synthesis and traditional medicinal chemistry, we have identified a new class of PDF inhibitors with N-alkyl urea at the P(1)' site . Compounds with MICs of <or=4 micro g/ml against gram-positive and gram-negative pathogens, including Staphylococcus aureus, Streptococcus pneumoniae, and Haemophilus influenzae, have been identified . The concentrations needed to inhibit 50% of enzyme activity (IC(50)s) for Escherichia coli Ni-PDF were <or=0.1 micro M, demonstrating the specificity of the inhibitors . In addition, these compounds were very selective for PDF, with IC(50)s of consistently >200 micro M for matrilysin and other mammalian metalloproteases . Structure-activity relationship analysis identified preferred substitutions resulting in improved potency and decreased cytotoxity . One of the compounds (VRC4307) was cocrystallized with PDF, and the enzyme-inhibitor structure was determined at a resolution of 1.7 A . This structural information indicated that the urea compounds adopt a binding position similar to that previously determined for succinate hydroxamates . Two compounds, VRC4232 and VRC4307, displayed in vivo efficacy in a mouse protection assay, with 50% protective doses of 30.8 and 17.9 mg/kg of body weight, respectively . These N-alkyl urea hydroxamic acids provide a starting point for identifying new PDF inhibitors that can serve as antimicrobial agents.

Curr Opin Immunol, 2002 Oct, 14(5), 553 - 7
Challenges for the development of vaccines against Haemophilus influenzae and Neisseria meningitidis; Cripps AW et al.; The development of protein-polysaccharide conjugate vaccines has had a major impact on Haemophilus influenzae type b disease . The application of this technology to Neisseria meningitidis is also striking, particularly for serogroup C . However, significant challenges exist for the development of vaccines against non-typeable H . influenzae and against N . meningitidis serogroup B . Issues such as non-vaccine-strain replacement and correlates of protection need to be addressed as well as the longer-term implications of vaccination against what are essentially 'normal' microflora.

Pediatr Infect Dis J, 2002 Jun, 21(6), 599 - 604; discussion 613-4
Acute otitis media in an era of increasing antimicrobial resistance and universal administration of pneumococcal conjugate vaccine; Pelton SI; The last decade has witnessed a shift in the epidemiology of acute otitis media (AOM) with an earlier onset of disease and a greater proportion of children with recurrent episodes before 1 year of age . In addition antimicrobial resistance to beta-lactams, macrolides and trimethoprim-sulfamethoxazole among otopathogens has increased significantly . Most recently universal administration of a seven valent pneumococcal conjugate vaccine has been endorsed by the American Academy of Pediatrics and the Advisory Committee on Immunization Practices . Earlier onset of disease and the decrease in antimicrobial susceptibility among pediatric respiratory bacterial pathogens is likely to increase the risk of failure among young children with AOM . A seven valent pneumococcal conjugate vaccine (PCV7) has demonstrated efficacy for prevention of serotype-specific pneumococcal otitis; however, increase in disease caused by nonvaccine serotypes and Haemophilus influenzae has been reported . With these events as the background, I have reviewed the strategies most likely to be successful for the treatment of AOM in 2002.

Pediatr Infect Dis J, 2002 Jun, 21(6), 592 - 8; discussion 613-4
Management of community-acquired pediatric pneumonia in an era of increasing antibiotic resistance and conjugate vaccines; Bradley JS; The antibiotic management of infants and children with pneumonia is based on the clinician's assessment of the most likely infecting pathogens, the susceptibilities of the infecting pathogens and the seriousness of the illness . The bacterial etiology of pneumonia changed significantly following the universal use of protein-conjugated vaccines for Haemophilus influenzae type b . Similar significant changes are likely to occur with universal use of protein-conjugated vaccines for Streptococcus pneumoniae, requiring the clinician to alter assumptions of the risk of invasive bacterial infection in the child who presents with pneumonia . New strategies are likely to require fewer ancillary tests (e.g . white blood cell count, C-reactive protein and blood culture) and suggest a decreased need for empiric antibiotic therapy . Although the majority of lower respiratory tract infections in children have a viral etiology and are not amenable to antibiotic therapy, for the seriously ill child who is thought to be likely to have pneumonia caused by a bacterial pathogen, recent changes in the susceptibility patterns of both common organisms such as S . pneumoniae and more unusual pulmonary pathogens such as Staphylococcus aureus have forced changes in the selection of both empiric and definitive antibiotic therapy . Third generation cephalosporins ceftriaxone and cefotaxime appear to be effective therapy for pneumonia caused by virtually all current isolates of S . pneumoniae . In contrast antibiotic regimens for life-threatening pulmonary infections in which Staphylococcus aureus is a suspected pathogen should include vancomycin.

Pediatr Infect Dis J, 2002 Jun, 21(6), 584 - 8; discussion 613-4
Management of the febrile child without a focus of infection in the era of universal pneumococcal immunization; Klein JO; Should strategies of management of invasive disease in the febrile child without focus of infection (occult bacteremia) be reconsidered in communities with universal immunization of infants with the conjugate vaccines for Haemophilus influenzae type b and Streptococcus pneumoniae (PCV7)? The incidence of occult bacteremia is likely to decrease with the virtual elimination of H . influenzae type b and vaccine serotype pneumococcal invasive diseases . The number of children with fever coming to physicians' offices, however, is unlikely to change . The challenge of distinguishing the febrile child with invasive bacterial disease who requires aggressive therapy from the febrile child who has a viral infection and requires only symptomatic therapy will persist . The bacteriology of invasive disease in infants and young children in 2002 will include pneumococcal serotypes not in PCV7; serotypes in PCV7 that occur in the unimmunized, partially immunized or fully immunized child (vaccine failures); Neisseria meningitidis; Salmonella spp., group A Streptococcus, Staphylococcus aureus and gram-negative enteric bacilli . Management plans published in the 1990s suggested an aggressive diagnostic approach to the febrile child 3 to 36 months old who was toxic or had a temperature of >39 degrees C . Diagnostic tests included white blood cell counts, cultures of blood and urine and chest radiograph and lumbar puncture as indicated by clinical signs and administration of parenteral ceftriaxone . Although PCV7 was extraordinarily effective in prevention of serotype-specific invasive pneumococcal disease in clinical trials, pediatricians need to know whether the results based on 38,000 enrollees will be maintained as millions of children are immunized . In addition questions about change in serotype of pneumococci causing invasive disease (serotype switching), herd immunity and durability of protection after immunization need to be answered . Until more experience is available to answer these questions, the febrile child without focus of infection should be managed without consideration of immunization with PCV7 . Evaluation of the organism (serotype) and the host (acute and convalescent sera) should be undertaken for each case of invasive pneumococcal disease in this era of universal pneumococcal immunization.

Pediatr Infect Dis J, 2002 Jun, 21(6), 568 - 9
Lack of association between receipt of conjugate haemophilus influenzae type B vaccine (HbOC) in infancy and risk of type 1 (juvenile onset) diabetes: long term follow-up of the HbOC efficacy trial cohort; Black SB et al.; We evaluated the effect of infant vaccination with HbOC Haemophilus influenzae type b (Hib) conjugate vaccine on the risk of onset of type 1 juvenile diabetes later in life by examining data from a large controlled prospective Phase III clinical efficacy trial conducted within Northern California Kaiser Permanente between 1988 and 1990 . The overall study population included children who were offered the Hib conjugate vaccine (acceptors and refusers) as well as a cohort of children who were systemically excluded from the trial on the basis of their birth date . These children are now 10 to 12 years of age . We found no evidence that vaccination with Hib conjugate vaccine in infancy is associated with risk of diabetes later in life.

Pediatr Infect Dis J, 2002 Jun, 21(6), 535 - 41
Antibody persistence in five-year-old children who received a pentavalent combination vaccine in infancy; Carlsson RM et al.; BACKGROUND: Antibody persistence was studied in 5.5-year-old Swedish children who in infancy completed a vaccine trial of a combined diphtheria toxoid, tetanus toxoid, acellular pertussis, inactivated polio and Haemophilus influenzae type b conjugate vaccine . Three priming doses at ages 2-4-6 months induced higher geometric mean concentrations of antibodies for all antigens than did two doses at 3-5 months, but there were no differences in proportions with protective antibody concentrations . After the booster dose administered at 13 or 12 months of age, respectively, there were no differences in concentrations or proportions between the groups . METHODS: In the present follow-up serum samples from 180 of the 228 vaccinees, 88 from the 4-dose and 92 from the 3-dose group, were 4.5 years later again tested for antibodies . RESULTS: The two groups did not differ significantly in antibody concentrations or proportions with antibodies above protective or other defined levels, with the exception of poliovirus type 3 (P < or = 0.01) . In all 89% had > or = 0.01 IU/ml antibodies against diphtheria by enzyme-linked immunosorbent assay and 76% by the Vero cell neutralization test, 93% had > or = 0.01 IU/ml antibodies against tetanus, 96 to 99% had detectable antibodies against the polioviruses and 97% had > or = 0.15 microg/ml H . influenzae type b antibodies . As for pertussis only 44% had detectable antibodies against pertussis toxoid by enzyme-linked immunosorbent assay but 99% by Chinese hamster ovary cell neutralization test, and 94% had detectable antibodies against filamentous hemagglutinin . CONCLUSION: We found the persistence of antibodies satisfactory, with no clinically relevant differences in antibody concentrations demonstrated between children vaccinated according to a three dose or a four dose schedule in infancy.

Pediatr Infect Dis J, 2002 Jun, 21(6), 498 - 504
Childhood vaccinations and risk of asthma; DeStefano F et al.; BACKGROUND: A few previous studies have suggested that childhood vaccines, particularly whole cell pertussis vaccine, may increase the risk of asthma . We evaluated the suggested association between childhood vaccinations and risk of asthma . METHODS: Cohort study involving 167,240 children who were enrolled in 4 large health maintenance organizations during 1991 to 1997, with follow-up from birth until at least 18 months to a maximum of 6 years of age . Vaccinations were ascertained through computerized immunization tracking systems, and onset of asthma was identified through computerized data on medical care encounters and medication dispensings . RESULTS: In the study 18,407 children (11.0%) developed asthma, with a median age at onset of 11 months . The relative risks (95% confidence intervals) of asthma were: 0.92 (0.83 to 1.02) for diphtheria, tetanus and whole cell pertussis vaccine; 1.09 (0.9 to 1.23) for oral polio vaccine; 0.97 (0.91 to 1.04) for measles, mumps and rubella (MMR) vaccine; 1.18 (1.02 to 1.36) for Haemophilus influenzae type b (Hib); and 1.20 (1.13 to 1.27) for hepatitis B vaccine . The Hib result was not consistent across health maintenance organizations . In a subanalysis restricted to children who had at least 2 medical care encounters during their first year, the relative risks decreased to 1.07 (0.71 to 1.60) for Hib and 1.09 (0.88 to 1.34) for hepatitis B vaccine . CONCLUSION: There is no association between diphtheria, tetanus and whole cell pertussis vaccine, oral polio vaccine or measles, mumps and rubella vaccine and the risk of asthma . The weak associations for Hib and hepatitis B vaccines seem to be at least partially accounted for by health care utilization or information bias.

Wiad Lek, 2002, 55(3-4), 150 - 7
{Profile of microorganisms isolated in nasopharyngeal swabs from the patients with acute infectious mononucleosis}; Fota-Markowska H et al.; Infectious mononucleosis is a self-limiting lymphoproliferative disorder, which contribute to the development of the various clinical symptoms . Exudative tonsillitis was found to be caused by Epstein-Barr virus in 19% of all viral infections and may imitate a bacterial etiology . The aim of this study was to identify the microbes from the nasopharyngeal swabs obtained from the patients with exudative tonsillitis and to assess their susceptibility to antibiotics . The patients were hospitalized as an infectious mononucleosis after unsuccessful antibiotic therapy . 84 patients were investigated: group I--patients with serological positive infectious mononucleosis tests and group II--patients with acute exudative tonsillitis and with serologically excluded infectious mononucleosis . The diagnosis was confirmed clinically, haematologically, biochemically and serologically . Nasopharyngeal specimens were taken, once, at the first day of hospitalization . Then, routine microbiological assays were performed . Isolated strains were identified biochemically: API Strep, API Staph, API E, API Ne, APINH (bioMerieux) . The susceptibility to antibiotics with an agar diffusion assay was performed according to Kirby-Bauer . We concluded that various, potentially pathogenic bacterial flora was found in throat during infectious mononucleosis . Haemophilus spp . and Staphylococcus aureus MSSA were isolated more frequently . Haemophilus influence was susceptible to cefotaxime and azytromycine . Candida albicans was isolated in every fourth patient . Streptococcus pyogenes as an etiological agent of exudative tonsillitis was confirmed in the group II . The pharyngeal candidiosis was also observed more frequently in the group II.

N Engl J Med, 2002 Aug 15, 347(7), 465 - 71
New strains of bacteria and exacerbations of chronic obstructive pulmonary disease; Sethi S et al.; BACKGROUND: The role of bacterial pathogens in acute exacerbations of chronic obstructive pulmonary disease is controversial . In older studies, the rates of isolation of bacterial pathogens from sputum were the same during acute exacerbations and during stable disease . However, these studies did not differentiate among strains within a bacterial species and therefore could not detect changes in strains over time . We hypothesized that the acquisition of a new strain of a pathogenic bacterial species is associated with exacerbation of chronic obstructive pulmonary disease . METHODS: We conducted a prospective study in which clinical information and sputum samples for culture were collected monthly and during exacerbations from 81 outpatients with chronic obstructive pulmonary disease . Molecular typing of sputum isolates of nonencapsulated Haemophilus influenzae, Moraxella catarrhalis, Streptococcus pneumoniae, and Pseudomonas aeruginosa was performed . RESULTS: Over a period of 56 months, the 81 patients made a total of 1975 clinic visits, 374 of which were made during exacerbations (mean, 2.1 per patient per year) . On the basis of molecular typing, an exacerbation was diagnosed at 33.0 percent of the clinic visits that involved isolation of a new strain of a bacterial pathogen, as compared with 15.4 percent of visits at which no new strain was isolated (P<0.001; relative risk of an exacerbation, 2.15; 95 percent confidence interval, 1.83 to 2.53) . Isolation of a new strain of H . influenzae, M . catarrhalis, or S . pneumoniae was associated with a significantly increased risk of an exacerbation . CONCLUSIONS: The association between an exacerbation and the isolation of a new strain of a bacterial pathogen supports the causative role of bacteria in exacerbations of chronic obstructive pulmonary disease .

Eur J Biochem, 2002 Aug, 269(16), 4009 - 19
Identification and structural characterization of a sialylated lacto-N-neotetraose structure in the lipopolysaccharide of Haemophilus influenzae; Cox AD et al.; A sialylated lacto-N-neotetraose (Sial-lNnT) structural unit was identified and structurally characterized in the lipopolysaccharide (LPS) from the genome-sequenced strain Rd {corrected} (RM118) of the human pathogen Haemophilus influenzae grown in the presence of sialic acid . A combination of molecular genetics, MS and NMR spectroscopy techniques showed that this structural unit extended from the proximal heptose residue of the inner core region of the LPS molecule . The structure of the Sial-lNnT unit was identical to that found in meningococcal LPS, but glycoforms containing truncations of the Sial-lNnT unit, comprising fewer residues than the complete oligosaccharide component, were not detected . The finding of sialylated glycoforms that were either fully extended or absent suggests a novel biosynthetic feature for adding the terminal tetrasaccharide unit of the Sial-lNnT to the glycose acceptor at the proximal inner core heptose.

Int J Pediatr Otorhinolaryngol, 2002 Sep 2, 65(2), 109 - 16
Intranasal immunization with recombinant outer membrane protein P6 induces specific immune responses against nontypeable Haemophilus influenzae; Hotomi M et al.; OBJECTIVE: Nontypeable Haemophilus influenzae (NTHi) is one of the leading causative pathogens for otitis media . The outer membrane protein P6 of NTHi is highly conserved among the strains and is an attractive candidate for a preventive vaccine . However, for the production of a relatively small amount P6 containing lipopolysaccharides, the development of a recombinant version of this protein is required . This study was designed to investigate the specific mucosal immunity induced by intranasal immunization of recombinant P6 (rP6) with cholera toxin (CT) . METHODS: BALB/c mice were immunized with of rP6 (30 microg) and CT (2 microg) intranasally every 2 days for 2 weeks . Anti-rP6 specific IgG, IgA and IgM antibodies and the subclass of anti-rP6 specific IgG antibody were determined by enzyme linked immunosorbent assay (ELISA) . Anti-rP6 specific IgA in nasopharyngeal washings were also determined by ELISA . Nasopharyngeal clearance of inoculated NTHi after the intranasal immunization were assessed . All statistical differences between the two groups were assessed by ANOVA parametric test . RESULTS: Intranasal immunization with rP6 and CT evoked rP6-specific mucosal IgA immune response as well as the systemic IgG immune response against rP6 and enhanced nasopharyngeal clearance of inoculated live NTHi . CONCLUSION: These results indicate the good immunogenicities of rP6 to induce specific immune responses against NTHi . Intranasal immunization with rP6 will be an effective approach to protect infections of NTHi .

Paediatr Drugs, 2002, 4(9), 609 - 30
Pneumococcal conjugate vaccine (Prevnar; PNCRM7): a review of its use in the prevention of Streptococcus pneumoniae infection; Darkes MJ et al.; PNCRM7 (Prevnar) is a pneumococcal vaccine containing seven capsular polysaccharide antigens from the bacterium Streptococcus pneumoniae, each of which is conjugated to diphtheria protein {cross-reactive material (CRM(197))} . CRM(197) is an inert but immunogenic variant of diphtheria toxoid that is also used as a carrier molecule in one Haemophilus influenzae type b conjugate vaccine . Unlike the 23-valent unconjugated pneumococcal vaccines, PNCRM7 elicits a T cell-dependent response and thus protects young children against pneumococcal disease . The immunogenicity of PNCRM7 has been demonstrated in both healthy children aged <2 years and older children in high-risk groups . Two randomized, double-blind trials conducted in the US demonstrated that all PNCRM7 serotypes were immunogenic in healthy infants and young children when compared with a control vaccine . A booster dose of PNCRM7 elicited an anamnestic response to all seven serotypes . Data from a large, randomized, double-blind study conducted in California (US) have confirmed the protective efficacy of PNCRM7 against invasive pneumococcal disease (e.g . bacteremia, meningitis) caused by serotypes included in the vaccine . The vaccine efficacy in the per-protocol analysis was 97.4% and its efficacy against invasive disease caused by any pneumococcal serotype in the intent-to-treat (ITT) analysis was 89.1% . Indeed, a postlicense surveillance study (n = 211,565) showed that the introduction and routine use of PNCRM7 was associated with a marked reduction in invasive pneumococcal disease in children <5 years of age . In addition, the US trial and another randomized, double-blind trial conducted in Finland, showed that PNCRM7 vaccine efficacy against all otitis media episodes was between 6 and 7% . PNCRM7 vaccine was generally well tolerated and had a similar local and systemic adverse events profile to other pediatric vaccines . The most common local adverse event associated with PNCRM7 administration was inflammation at the injection site, and the most common systemic adverse effect was febrile illness (> or =38 degrees C) that usually resolved without treatment . The limited available pharmacoeconomic data suggest that PNCRM7 could be cost effective depending, in part, on the manufacturer's list price of the vaccine . Results of the base case analysis in a US study showed a cost-effectiveness ratio for PNCRM7 of US dollars 80,000 per life-year saved from a societal perspective compared with US dollars 176,000 from a healthcare payer perspective, assuming a nondiscounted list price of US dollars 58 per dose (1997 costs) . Concomitant administration of PNCRM7 vaccine with hepatitis B, oral polio, meningococcal oligosaccharide protein conjugate or H . influenzae type b vaccines did not affect the immunogenicity of these pediatric vaccines to a clinically relevant extent . CONCLUSION: PNCRM7 vaccine will be of great benefit to those societies that have active immunization programs implemented . In infants and vulnerable children throughout the world, PNCRM7 vaccine has the potential to reduce the mortality and morbidity rates associated with S . pneumoniae infections . In developed countries, the vaccine will be of particular benefit in preventing disabling infections but its impact in developing countries will be more pronounced with the potential to greatly reduce mortality.

J Appl Microbiol, 2002, 93(3), 487 - 91
Oral bacteria influenced by the functional status of the elderly people and the type and quality of facilities for the bedridden; Tada A et al.; AIMS: To analyse the relationship between oral bacteria and the health and functional status of the elderly . METHODS AND RESULTS: The bacteria species in the oral cavity of the elderly were examined . It was found that the bedridden subjects staying at two hospitals for long-term (HOBR) showed significantly lower detection rates of commensal bacteria species and significantly higher detection rates of Pseudomonas aeruginosa, of methicillin-resistant Staphylococcus aureus (MRSA) and of coagulase(-) Staph . aureus than those living independently (the independent) . In addition, the detection rate of Haemophilus parainfluenzae in NUBR was discovered to be higher than that found in the independent . In HOBR, the detection rate of Ps . aeruginosa was significantly higher among in-patients who required continual care than those in need of partial care, while the detection rate of MRSA was significantly higher among in-patients with low serum albumin than those with normal serum albumin . CONCLUSIONS: Oral bacteria examination analysis proved that the risks of infection of some pathogenic bacteria species were correlated with functional status, physical function and nutritional state . SIGNIFICANCE AND IMPACT OF THE STUDY: Our study suggests that the oral bacteria, especially pathogenic bacteria were influenced by the functional status of the elderly and the type and quality of the facilities for the bedridden, physical function and nutritional state.

Indian J Pediatr, 2002 Jul, 69(7), 625 - 6
Recurrent pneumococcal meningitis in homozygous C3 deficiency; Totan M; Congenital deficiencies of complement system proteins are rare . A 4-year-old girl was admitted for meningitis . She had had repeated attacks of pneumococcal meningitis and otitis media at the age of 3 years . Analysis of cerebrospinal fluid showed that this meningitis was due to pneumococcal infection . Complement 3 and CH50 values of the proband and her brother were low, while her parents were normal . The patient was given polyvalent pneumococcal and anti-haemophilus vaccines plus ceftriaxone . Recovery was complete after 15 days of antibiotic therapy . This is the first description of a case of recurrent meningitis with C3 and CH50 deficiency in a Turkish family.

Int J STD AIDS, 2002 Jul, 13(7), 469 - 74
Validation of syndromic algorithm for the management of genital ulcer diseases in China; Wang QQ et al.; OBJECTIVES: 1 . To determine the aetiologies of genital ulcers in China . 2 . To evaluate a modified WHO syndromic management algorithm for genital ulcer disease (GUD) . METHODS: Patients with genital ulcers were enrolled at their first visit to STD clinics in the cities of Shanghai and Chengdu . They were managed according to a modified WHO algorithm for GUD, in which no treatment was given for chancroid . A multiplex polymerase chain reaction was used to detect Treponema pallidum, Herpes simplex and Haemophilus ducreyi . Dark field examination and serology (rapid plasma reagin and Treponema pallidum particle agglutination assay (TPPA) were also used to diagnose syphilis . RESULTS: A total of 227 male and female patients were enrolled . Syphilis alone was diagnosed in 78 (35%), genital herpes alone in 43 (19%), and both infections were present in 28 (12%) . No diagnosis was made in 76 (34%) . No case of chancroid was identified . The sensitivity of the algorithm for syphilis and herpes was 88.7% and 69.0% respectively, the specificity 95.0% and 50.0% . 12/106 cases of syphilis were incorrectly classified as herpes (11%), and did not receive treatment . More than 97% of patients followed up responded clinically to treatment . CONCLUSION: Further validation and revision of the WHO flowchart for GUD are needed.

Ann Trop Med Parasitol, 2002 Jun, 96(4), 397 - 403
Single-tube, nested PCR for the diagnosis of human brucellosis in Kuwait; Al Nakkas AF et al.; The polymerase chain reaction (PCR) offers a sensitive and specific way of detecting microbial DNA in clinical samples . The aims of the present study were to develop an assay, based on a single-tube, nested PCR, for identifying Brucella in samples of human blood and then to explore the use of this test in diagnosis . The primers chosen were derived from IS711, the insertion sequence gene found in all species of Brucella . The assay amplified a 52-bp final product which was detected colorimetrically . The PCR was sensitive and specific, giving positive reactions with 14 strains of Brucella from five species . The lower limit of detection in vitro was 30 organisms . There were no false-positive reactions either with a range of bacteria known to evoke serological cross-reactions with Brucella (Vibrio cholerae, Yersinia enterocolitica, Serratia marcescens, Haemophilus influenzae, Pseudomonas aeruginosa and Escherichia coli K12) or with organisms producing similar clinical syndromes (Mycobacterium tuberculosis and Salmonella typhi) . The results of a preliminary field trial of the assay in Kuwait indicate that the assay may be a valuable technique in the diagnosis of human brucellosis, meriting further study with larger numbers of cases . All 28 subjects with brucellosis (diagnosed on the basis of typical clinical features and confirmed by positive serology and, in three cases, by positive blood cultures) were PCR-positive whereas 28 healthy controls and 28 patients with febrile illness attributable to infections other than brucellosis were PCR-negative.

J Bacteriol, 2002 Sep, 184(17), 4868 - 74
Structure and function of Hib pili from Haemophilus influenzae type b; Mu XQ et al.; Pathogenic bacteria are specifically adapted to bind to their customary host . Disease is then caused by subsequent colonization and/or invasion of the local environmental niche . Initial binding of Haemophilus influenzae type b to the human nasopharynx is facilitated by Hib pili, filaments expressed on the bacterial surface . With three-dimensional reconstruction of electron micrograph images, we show that Hib pili comprise a helix 70 A in diameter with threefold symmetry . The Hib pilus filament has 3.0 subunits per turn, with each set of three subunits translated 26.9 A along and rotated 53 degrees about the helical axis . Amino acid sequence analysis of pilins from Hib pili and from P-pili expressed on uropathogenic Escherichia coli were used to predict the physical location of the highly variable and immunogenic region of the HifA pilin in the Hib pilus structure . Structural differences between Hib pili and P-pili suggest a difference in the strategies by which bacteria remain bound to their host cells: P-pili were shown to be capable of unwinding to five times their original length (E . Bullitt and L . Makowski, Nature 373:164-167, 1995), while damage to Hib pili occurs by slight shearing of subunits with respect to those further along the helical axis . This capacity to resist unwinding may be important for continued adherence of H . influenzae type b to the nasopharynx, where the three-stranded Hib pilus filaments provide a robust tether to withstand coughs and sneezes.

Clin Pediatr (Phila), 2002 Jul-Aug, 41(6), 373 - 90
Treatment of acute otitis media consensus recommendations; Hoberman A et al.; The objective of this paper is to provide consensus recommendations for the management of acute otitis media (AOM) that pediatricians can incorporate into their daily practices . These recommendations were developed during a roundtable meeting that convened clinicians versed in the management of AOM . This meeting was sponsored by an educational grant from SmithKline Beecham Pharmaceuticals . In addition, clinical studies on AOM identified via MEDLINE search were considered in the development of these recommendations . The Drug-Resistant Streptococcus pneumoniae Therapeutic Working Group guidelines for the management of AOM are reviewed in detail . All of the articles identified from the data sources were evaluated and all information deemed relevant was included in this review . AOM is one of the most common infectious diseases affecting infants and children and one of the leading causes of office visits and antibiotic prescriptions for this population . The incidence of AOM has increased during the past 25 years, probably the result of an increased utilization of day care facilities in the United States . The predominant pathogens in AOM include S . pneumoniae, Haemophilus influenzae, and Moraxella catarrhalis . The high prevalence of drug-resistant S . pneumoniae and beta-lactamase-producing organisms presents a clinical challenge for practitioners in the selection of empiric antimicrobial therapy . Pharmacokinetic/pharmacodynamic principles should be considered in addition to minimum inhibitory concentrations in selecting antibiotics for AOM . Amoxicillin at conventional or high doses (80-90 mg/kg/day) remains an appropriate choice for first-line therapy for AOM . For patients in whom amoxicillin is unsuccessful, second-line therapy should have demonstrated activity against penicillin-resistant S . pneumoniae as well as beta-lactamase-producing pathogens . Appropriate options for second-line therapy include high-dose amoxicillin/clavulanate (90 mg/kg/day based on the amoxicillin component) and ceftriaxone . Cefuroxime has been suggested as a second-line agent in the past, but recent surveillance data suggest it may no longer be active against penicillin-resistant strains of S . pneumoniae . Tympanocentesis is useful for identifying the causative pathogen, and it may be beneficial for patients who have failed multiple courses of antibiotics . The pneumococcal conjugate vaccine recently was approved for use in children and should be administered to all children less than 2 years old and those at risk for recurrent AOM (e.g., day care attendance, siblings with a history of recurrent AOM) . Consensus recommendations are provided for the management of AOM, with a focus on antimicrobial therapy . The current challenges in the management of AOM include the need for an increased understanding of epidemiology, increasing resistance among common middle ear pathogens, use of pharmacokinetic/pharmacodynamic principles in designing treatment strategies, and understanding the potential impact of the pneumococcal conjugate vaccine.

Pediatrics . 2002 Aug;110(2 Pt 1):e15.
Vaccination coverage of foreign-born children 19 to 35 months of age: findings from the National Immunization Survey, 1999-2000; Strine TW et al.; OBJECTIVE: To compare coverage estimates of foreign-born children 19 to 35 months old with those of US-born children of the same age group . METHODS: The National Immunization Survey is a multistage, random-digit dialing survey designed to measure vaccination coverage estimates of US children 19 to 35 months old . Data from 1999-2000 were combined to permit comparison of vaccination coverage among foreign- and US-born children . RESULTS: Foreign-born and US-born children 19 to 35 months of age had comparable 3:3:1 series coverage (3 or more doses of diphtheria and tetanus toxoids and pertussis vaccine {DTP/DTaP/DT}, 3 or more doses of poliovirus vaccine, and 1 or more doses of measles-containing vaccine), the standard in most countries . However, coverage for a US standard, 4:3:1:3 series (4 or more doses of DTP/DTaP/DT, 3 or more doses of poliovirus vaccine, 1 or more doses of measles-containing vaccine, and an adequate number of Haemophilus influenzae type b {Hib} doses based on age at first dose) was lower among foreign-born children because of markedly lower Hib cover and marginally lower DTP/DTaP/DT coverage . In addition, hepatitis B coverage was markedly lower in foreign-born children . CONCLUSION: Lower vaccination coverage among foreign-born children, especially against Hib and hepatitis B, is of concern because foreign-born children often live in households and communities characterized by more intense exposure to these diseases, and many originate from countries with much higher prevalence rates of these diseases than the United States . The differences in Hib and hepatitis B coverage suggest a need for increased culturally competent public health immunization interventions to increase coverage among foreign-born children.

Prev Vet Med, 2002 Aug 30, 54(4), 337 - 49
Infectious and rearing-system related risk factors for chronic pleuritis in slaughter pigs; Enoe C et al.; Chronic pleuritis (CP) in Danish pigs for slaughter is by far the most frequent finding at the routine post-mortem meat inspection . An initial investigation published in 1990 demonstrated infectious and management-related risk factors . Serological testing for additional infectious agents, as well as the need to consider the effect of disease clustering at the herd level, required a re-analysis of the data . Our re-analysis used a representative sample of 4,800 pigs originating from 623 Danish herds . Each pig was examined for the presence of CP and progressive atrophic rhinitis (PAR) . The gender of the pig, the weight of the carcass, and the herd of origin were also recorded . Individual blood samples were examined for seropositivity for Actinobacillus pleuropneumoniae (AP) serotypes 2, 6, 7, 12, Haemophilus parasuis, Mycoplasma hyopneumoniae (MYC) and swine influenza (SI) . Herd-level information retrieved through a questionnaire included health status, production type, herd size (i.e . pigs per year) and vaccination procedures . Associations between CP and infectious, individual and herd-related factors were investigated by logistic regression with random effects . Among pigs from herds with conventional health status, seropositivity for AP serotypes 2 and 6, and MYC had odds ratios (ORs) of CP of 9.0, 1.6 and 1.8, respectively . Neither seropositivity for AP serotype 7 nor SI were associated with CP by themselves, but interacted: OR of CP of 5.3 (1.8) when present at the same time among pigs exhibiting (not exhibiting) PAR . An association of PAR with CP was found, and PAR interacted with AP serotype 7: OR=10.0 (4.3) when both factors were present among pigs exposed (non-exposed) to SI . The OR (0.97) for an increase of carcass weight by 1 kg was negligible.In pigs from specific pathogen-free (SPF) herds, seropositivity for MYC and herd size were associated with CP . Moreover, for a herd size of 1,000 pigs, CP was associated with exposure to MYC by an OR of 3.3 (decreasing to 1.9 when the herd size was increased by 1,000) . Farrow-to-finish as opposed to finishing herd had an OR of CP of 3.2 . In conventional herds, seropositivity for AP serotype 2 and MYC were associated with 51% and 29% of the occurrence of CP . In SPF herds, farrow-to-finish as opposed to finishing herds was associated with 47% of the occurrence of CP . Seropositivity for MYC was associated with 33% (39%) of the occurrence of CP in herds with a size > (< or =) 1,500 pigs.

Proc Natl Acad Sci U S A, 2002 Aug 20, 99(17), 11115 - 20 Epub 2002 Aug 02.
Transplanting allosteric control of enzyme activity by protein-protein interactions: coupling a regulatory site to the conserved catalytic core; Pawlyk AC et al.; Glycerol kinase from Escherichia coli, but not Haemophilus influenzae, is inhibited allosterically by phosphotransferase system protein IIA(Glc) . The primary structures of these related kinases contain 501 amino acids, differing at 117 . IIA(Glc) inhibition is transplanted from E . coli glycerol kinase into H . influenzae glycerol kinase by interconverting only 11 of the differences: 8 residues that interact with IIA(Glc) at the allosteric binding site and 3 residues in the conserved ATPase catalytic core that do not interact with IIA(Glc) but the solvent accessible surface of which decreases when it binds . The three core residues are crucial for coupling the allosteric site to the conserved catalytic core of the enzyme . The site of the coupling residues identifies a regulatory locus in the sugar kinase/heat shock protein 70/actin superfamily and suggests relations between allosteric regulation and the active site closure that characterizes the family . The location of the coupling residues provides empirical validation of a computational model that predicts a coupling pathway between the IIA(Glc)-binding site and the active site {Luque, I . & Freire, E . (2000) Proteins Struct . Funct . Genet . Suppl . 4, 63-71} . The requirement for changes in core residues to couple the allosteric and active sites and switching from inhibition to activation by a single amino acid change are consistent with a postulated mechanism for molecular evolution of allosteric regulation.

Laryngoscope, 2002 Jun, 112(6), 975 - 9
Identification of upper respiratory bacterial pathogens with the electronic nose; Lai SY et al.; OBJECTIVE: To use an electronic nose to identify common upper respiratory bacterial pathogens . STUDY DESIGN: Controlled in vitro analysis . METHODS: Swabs of bacteria were obtained from in vitro samples . The specimens were vaporized and analyzed over the organic semiconductor-based electronic nose (Cyranose 320) . Data from the 32-element sensor array were subjected to principal component analysis for depiction in two-dimensional space and differences in odorant patterns were assessed by calculating Mahalanobis distances . RESULTS: The electronic nose was able to distinguish between control swabs and bacterial samples . Furthermore, calculation of the Mahalanobis distances among the various bacteria demonstrated distinct odorant classes (Mahalanobis distance > or = 3) . This demonstrates that the electronic nose could differentiate among various common bacterial pathogens of the upper respiratory tract, including Staphylococcus aureus, Streptococcus pneumoniae, Haemophilus influenza, and Pseudomonas aeruginosa . CONCLUSIONS: The electronic nose represents a novel method to identify potential upper respiratory infections and to discriminate among common upper respiratory bacterial pathogens . This technology could provide a rapid means to identify organisms causing upper respiratory infections.

Diagn Microbiol Infect Dis, 2002 Aug, 43(4), 323 - 6
Evaluation of in vitro susceptibility testing criteria for gemifloxacin when tested against Haemophilus influenzae strains with reduced susceptibility to ciprofloxacin and ofloxacin; Biedenbach DJ et al.; Although Hemophilus influenzae resistance to fluoroquinolones is low, it is important to monitor the development of populations with decreased susceptibility to this class of antimicrobials . The activity of gemifloxacin, a new fluoroquinolone, was measured against a collection of susceptible wild-type strains (MIC(90,) 0.008 microg/ml for both beta-lactamase-negative and -positive strains) and strains less susceptible to quinolones (MIC(90,) 1 microg/ml) . Using a 5microg disk, the gemifloxacin-susceptible strains had MIC results ranging from </= 0.004 to 0.25 microg/ml (the proposed breakpoint), corresponding to zone diameters of 20 to 39 mm . However, some H . influenzae strains having multiple QRDR mutations were less susceptible to gemifloxacin (MIC range, 0.016-2 microg/ml), although gemifloxacin remained active against 57.1% of strains . In vitro testing, using these selected resistant strains, defined the categorical interpretive criteria for routine clinical laboratory use.

Diagn Microbiol Infect Dis, 2002 Aug, 43(4), 315 - 8
In vitro assessment of gatifloxacin spectrum and potency tested against Haemophilus influenzae, Moraxella catarrhalis, and Streptococcus pneumoniae isolates from the Asia-Western Pacific component of the SENTRY antimicrobial surveillance program (1998-1999); Bell JM et al.; Fluoroquinolones, especially the newer agents, have an increased role in the management of respiratory tract infections worldwide . In the SENTRY Antimicrobial Surveillance Program for the Asia-Pacific Region for 1998 and 1999, 630 Streptococcus pneumoniae, 583 Hemophilus influenzae and 274 Moraxella catarrhalis isolates were examined to determine the comparative activity of the new fluoroquinolone, gatifloxacin, compared with those of ciprofloxacin, levofloxacin and trovafloxacin . Gatifloxacin was highly active against all three species . Decreased susceptibility (MIC >/=2 microg/mL) to gatifloxacin was noted in only seven strains of S . pneumoniae (3 of which were resistant); in three strains of H . influenzae (MIC >/= 0.12 microg/mL), and 2 M . catarrhalis (MIC > 2 microg/mL).

Expert Opin Investig Drugs, 2002 Aug, 11(8), 1051 - 60
New therapies and vaccines for bacterial meningitis; Foster C et al.; Acute bacterial meningitis remains an important cause of morbidity and mortality worldwide . There have recently been major advances in the prevention of the major causes of bacterial meningitis following improvements in vaccinology . The success of immunisation against Haemophilus influenzae type b infection is being mirrored with serogroup C conjugated meningococcal vaccine and pneumococcal conjugate vaccine . However, there remain major challenges, notably, serogroup B meningococcal infection and shifts in epidemiology caused by vaccine introduction . In addition, much of the world's population is unvaccinated . Therefore, improvements in management of acute bacterial meningitis are vital . In this review we attempt to summarise important advances in both prevention and treatment of acute bacterial meningitis.

Expert Opin Pharmacother, 2002 Aug, 3(8), 1073 - 90
Otitis media; Pichichero ME et al.; Bacterial pathogens are isolated from middle ear fluid in up to 90% of children with acute otitis media (OM) . Streptococcus pneumoniae, Haemophilus influenzae and Moraxella catarrhalis predominate . Acute OM can be classified as uncomplicated, persistent, recurrent or chronic . Patient age, symptom severity, prior treatment history and exposure through day-care attendance in children influences pathogen distribution, antimicrobial susceptibility and anticipated clinical and microbiological responses to empirical and pathogen-directed therapies . The natural history of acute OM without intervention is favourable . However, meta-analysis of clinical trials shows an improvement in symptom and middle ear effusion resolution with antimicrobials . Aminopenicillins, cephalosporins and macrolides are often selected as therapy for acute OM . The various agents have differing activity against acute OM pathogens, particularly organisms with resistance mechanisms and they differ in dosing schedule, side effects and compliance enhancing factors . Consideration should be given to pharmacokinetic and pharmacodynamic principles in antibiotic selection . Selection criteria include antibiotic activity against drug-resistant S . pneumoniae and efficacy against beta-lactamase-producing Gram-negative organisms . The necessary duration of treatment for acute OM varies according to multiple factors, including local preferences, but there is growing, compelling data to support short-course therapy . Tympanocentesis has been endorsed in various guidelines as a diagnostic and therapeutic procedure . Best-practice for management of acute OM continues to advocate antibiotic therapy with careful, accurate diagnosis and consideration of the major pathogens and their mechanisms of resistance.

Laryngoscope, 2002 Apr, 112(4), 676 - 80
Effect of bacterial endotoxin and middle ear effusion on ciliary activity: implications for otitis media; Mason PS et al.; OBJECTIVES/HYPOTHESIS: Otitis media with effusion (OME) is the most common cause of childhood deafness . The pathogenesis is not fully understood, especially the reasons for failure of mucociliary clearance of the middle ear . It is not clear whether the cilia function normally in the middle ear and eustachian tube in the chronic phase of otitis media with effusion . However, impaired ciliary function in primary ciliary dyskinesia is known to be frequently associated with the development of otitis media with effusion . We hypothesized that endotoxin or the bacterial products in middle ear fluid in otitis media with effusion would adversely affect ciliary activity, thereby contributing to the pathogenesis of the disease . STUDY DESIGN: Laboratory-based study of human ciliary activity with reference to otitis media with effusion . METHODS: We have studied the activity of human adenoidal cilia under various conditions . Ciliary activity in the presence of Haemophilus influenzae endotoxin additions (at varying concentrations) to cultured adenoidal explants has been measured . In addition, ciliary activity of these explants was also observed after addition of middle ear effusion aspirated from patients . RESULTS: We have shown that endotoxin in concentrations far in excess of those found in the middle ear with chronic otitis media with effusion had no effect on ciliary activity . Furthermore, ciliary activity was completely unaffected by the presence of middle ear effusion . CONCLUSION: There is no evidence that ciliary activity is reduced by the constituents of middle ear fluid in chronic otitis media with effusion.

J Infect, 2002 Feb, 44 Suppl A, 3 - 10
Evolving resistance patterns in community-acquired respiratory tract pathogens: first results from the PROTEKT global surveillance study . Prospective Resistant Organism Tracking and Epidemiology for the Ketolide Telithromycin; Felmingham D; In recent years, antibacterial resistance among respiratory pathogens implicated in community-acquired respiratory tract infections (RTIs) has spread worldwide at an alarming rate . Thus, there is a pressing need for new antibacterials that retain activity against resistant organisms, have a low potential to select for resistance and do not induce cross-resistance . Telithromycin is the first of a new class of antibacterials - the ketolides - that have been designed specifically to overcome resistance among respiratory tract pathogens . This paper presents the first results of the PROTEKT study (Prospective Resistant Organism Tracking and Epidemiology for the Ketolide Telithromycin), a worldwide surveillance study initiated to chart the prevalence of important resistance phenotypes and genotypes and the comparative activity of telithromycin against such strains . Analysis of over 7,000 bacterial isolates by April 2001 has confirmed the notable prevalence of strains resistant to commonly prescribed RTI antibacterials for all the pathogens studied . Telithromycin demonstrates high activity against isolates of Streptococcus pneumoniae, irrespective of penicillin G, macrolide or fluoroquinolone resistance . Telithromycin is also highly active against other respiratory tract pathogens, including Streptococcus pyogenes and beta-lactamase-producing strains of Haemophilus influenzae and Moraxella catarrhalis . These data justify the assertion that telithromycin is a promising new candidate for the empirical treatment of community-acquired RTIs, particularly in the face of increasing antibacterial resistance.

J Infect, 2002 Feb, 44 Suppl A, 25 - 30
Clinical efficacy of new antibacterial therapies in at-risk populations; Lorenz J; Infections of the lower respiratory tract, such as community-acquired pneumonia (CAP) and acute bacterial exacerbations of chronic bronchitis (AECB), comprise the more serious respiratory tract infections (RTIs), and are associated with considerable morbidity and mortality, particularly in groups such as the very young, the elderly and those with co-morbid illness . Up to 80% of community-acquired RTIs are caused by Streptococcus pneumoniae, Haemophilus influenzae or Moraxella catarrhalis and are usually treated empirically . However, antibacterial resistance among common respiratory tract pathogens currently threatens the usefulness of existing therapies . The new ketolide antibacterial, telithromycin, has been developed specifically to provide optimal empirical treatment of community-acquired RTIs in the face of widespread antibacterial resistance . Telithromycin 800 mg once-daily offers efficacy equivalent to currently available antibacterials in the treatment of lower RTIs . Moreover, telithromycin demonstrates excellent activity in the treatment of CAP and AECB patients at risk for increased morbidity and mortality, including elderly patients, those with severe infections, and those with CAP complicated by pneumococcal bacteraemia . Telithromycin is also extremely effective in the treatment of patients with lower RTIs caused by atypical and intracellular pathogens (such as Mycoplasma pneumoniae, Legionella pneumophila and Chlamydophila {Chlamydia} pneumoniae--increasingly recognized as important aetiological agents of RTIs, particularly CAP), or by pathogens resistant to beta-lactams and macrolides . Telithromycin therefore represents a promising new agent for the empirical treatment of community-acquired RTIs.

Pediatr Infect Dis J, 2002 May, 21(5), 399 - 405
Use of lidocaine-prilocaine patch to decrease intramuscular injection pain does not adversely affect the antibody response to diphtheria-tetanus-acellular pertussis-inactivated poliovirus-Haemophilus influenzae type b conjugate and hepatitis B vaccines in infants from birth to six months of age; Halperin BA et al.; BACKGROUND: Topical lidocaine-prilocaine (EMLA) effectively decreases the pain associated with minor procedures including immunization, although the effect on the antibody response to diphtheria-tetanus-acellular pertussis-inactivated poliovirus-Haemophilus influenzae type b conjugate (DTaP-IPV-Hib) and hepatitis B vaccines has not been assessed . OBJECTIVE: To measure the antibody response to DTaP-IPV-Hib and hepatitis B vaccines; to measure pain reduction associated with the use of the lidocaine-prilocaine (EMLA) patch; and to assess safety by comparing adverse reactions . PARTICIPANTS AND SETTING: One hundred nine healthy 6-month-old infants (Part A of study) and 56 healthy infants birth to 2 months of age (Part B of study) undergoing primary immunization with DTaP-IPV-Hib and hepatitis B vaccines in an ambulatory setting . DESIGN AND INTERVENTIONS: Two center, randomized, double blind, controlled trial of EMLA patch or placebo before DTaP-IPV-Hib and hepatitis B immunization . Antibody titers measured at 0 to 2, 6 and 7 months . OUTCOME MEASURES: The primary outcome measure was the antibody response to diphtheria, tetanus, pertussis antigens, Haemophilus influenzae type b and hepatitis B by enzyme immunoassay; and poliovirus 1, 2 and 3 by neutralization . The secondary outcomes were pain scores by the Modified Behavioral Pain Scale and drug- and vaccine-associated adverse events collected with a parent diary and structured questionnaire . RESULTS: There was no difference in the antibody response between the EMLA- and placebo-treated groups as assessed by geometric mean antibody titers, rates of seroconversion or the proportion of participants achieving protective or positive antibody titers postimmunization . At the 6-month visit, EMLA recipients had less pain after immunization (total pain score, 6.75 vs . 7.35; P = 0.005; pain score increase, 3.99 vs . 4.74; P = 0.004) than did placebo recipients . Skin pallor and erythema at the patch application site were more frequently reported after EMLA use . Rates of vaccine-associated adverse events were similar in the two groups . CONCLUSIONS: The EMLA patch has no adverse effect on the antibody response to the vaccine antigens, is effective in reducing pain associated with DTaP-IPV-Hib and hepatitis B immunizations and does not result in any significant or unexpected adverse reactions.

J Clin Microbiol, 2002 Aug, 40(8), 2832 - 6
Nasopharyngeal carriage of potential bacterial pathogens related to day care attendance, with special reference to the molecular epidemiology of Haemophilus influenzae; Peerbooms PG et al.; Nasopharyngeal carriage of Haemophilus influenzae, Streptococcus pneumoniae, and Moraxella catarrhalis was studied in 259 children attending day care centers (DCC) in Amsterdam, The Netherlands, and in 276 control children . The DCC children were sampled a second time after 4 weeks . Carriage rates for DCC children and controls were 58 and 37% for S . pneumoniae, 37 and 11% for H . influenzae, and 80 and 48% for M . catarrhalis, respectively . No increased antibiotic resistance rates were found in strains isolated from DCC children . All H . influenzae isolates were typed by random amplified polymorphic DNA (RAPD) analysis . Evidence for frequent transmission of H . influenzae strains within DCC was found . In the control group only two isolates (4%) displayed identical RAPD types versus 38% of strains from DCC children . Colonization with H . influenzae appeared to be short-lived in these children; more than half of the children harboring H . influenzae in the first sample were negative in the second sample, whereas most children still positive in the second sample had a different genotype than in the first sample . Of the newly acquired strains in the second sample, 40% were identical to a strain that had been found in a child in the same DCC in the first sample . DCC are to be considered epidemiological niches with a high potential for the spread of pathogenic microorganisms.

Laryngoscope, 2002 Mar, 112(3), 420 - 3
Growth factors and their receptors in the middle ear mucosa during otitis media; Palacios SD et al.; OBJECTIVE: The hyperplastic response of the middle ear mucosa during bacterial otitis media is thought to be mediated by the actions of growth factors and their respective receptors . The purpose of the study was to explore the expression of growth factors known to stimulate epithelial cells in other systems, as well as their receptors, in the middle ear mucosa during otitis media . STUDY DESIGN: Expression of mRNA growth factors and receptors was measured over time after inoculation of the rat middle ear with bacteria . METHODS: The middle ears of 12 male Sprague-Dawley rats were injected with 10(5)/mL Haemophilus influenzae strain 3655 (nontypeable, biotype II) . Three rats were killed at 6, 24, 48, and 72 hours . Three untreated rats were also killed to serve as negative controls . The middle ear mucosa samples were surgically removed and homogenized . Reverse transcription-polymerase chain reaction was performed on each sample with primers for rat epidermal growth factor, epidermal growth factor receptor (ErbB), heparin binding epidermal-like growth factor, hepatocyte growth factor, hepatocyte growth factor receptor, keratinocyte growth factor, betacellulin, amphiregulin, and neuregulin-alpha . RESULTS: Hepatocyte growth factor and epidermal growth factor receptor primers demonstrated polymerase chain reaction products of the expected size that were not displayed in the normal middle ear mucosa . Keratinocyte growth factor and hepatocyte growth factor receptor demonstrated polymerase chain reaction products at all time points tested . Betacellulin and neuregulin-alpha products were present at all time points except 72 hours after infection . CONCLUSIONS: The results of the study support a role for growth factors in the middle ear mucosa during otitis media . These bioactive ingredients contribute to mucosal hyperplasia.

Presse Med, 2002 Jun 15, 31(21 Pt 2), S11 - 4
{Update on levofloxacin in the management of acute sinusitis with risk of complications}; Pessey JJ; THE DIAGNOSIS OF ACUTE BACTERIAL MAXILLARY SINUSITIS: Is based on at least two of three major criteria: sinus pain, unilateral signs, increasingly voluminous and purulent rhinorrhea . Minor criteria can also be retained for diagnosis if they persist for three days . THE NEED FOR ANTIBIOTIC THERAPY: In this diagnostic context is undeniable, similar to the situation after failure of symptomatic treatment or complication . Likewise for unilateral maxillary sinusitis due to homolateral infection of the superior dental archade or for frontal, ethmoidal, or sphemoidal sinusities . THE MOST FREQUENTLY CAUSAL BACTERIA: Are Streptococcus pneumoniae and Haemophilus influenzae . For first intention treatment generally relies on beta-lactams (amoxicilin/clavulanic acid, second or third generation cephalosporins); pristinamycin may also be useful . Fluoroquinolones active against pneumococci, e.g . levofloxacin, are reserved for cases of sinusitis with risk of complications and for second line treatment after failure in patients with acute maxillary sinusitis . COMPLICATIONS OF SINUSITIS: Can result from anatomic anomalies or from infectious mechanisms such as metastasis of a locoregional infection: peri-orbital cellulitis, orbital cellulitis, thrombophlebitis of the cavernous sinus, extradural, subdural or intracerebral abscess . Three clinical trials are under way to assess efficacy in the treatment of complicated or high risk sinusitis.

Clin Infect Dis, 2002 Aug 15, 35(4), 428 - 33 Epub 2002 Jul 24.
Bacteriologic findings associated with chronic bacterial maxillary sinusitis in adults; Finegold SM et al.; An open-label, multicenter study was performed to assess bacteriologic findings associated with chronic bacterial maxillary sinusitis in adults . Seventy aerobic (52.2%) and 64 anaerobic (47.8%) pathogens were recovered from clinically evaluable patients at baseline (before therapy) . The most commonly isolated anaerobes were Prevotella species (31.1%), anaerobic streptococci (21.9%), and Fusobacterium species (15.6%) . The aerobes most frequently recovered included Streptococcus species (21.4%), Haemophilus influenzae (15.7%), Pseudomonas aeruginosa (15.7%), and Staphylococcus aureus and Moraxella catarrhalis (10.0% each) . Recurrences of signs or symptoms of bacterial maxillary sinusitis associated with anaerobes were twice as frequent as were those associated with aerobes when counts of anaerobes were > or =10(3) cfu/mL . A pathogenic role for Granulicatella species in cases of chronic sinusitis was documented for the first time.

South Med J, 2002 Jul, 95(7), 672 - 4
Facial cellulitis in childhood: a changing spectrum; Fisher RG et al.; BACKGROUND: Before conjugated Haemophilus influenzae type b (Hib) vaccination, a syndrome known as buccal cellulitis, usually caused by Hib and often accompanied by bacteremia, was seen . We investigated the incidence and cause of facial cellulitis at our hospital during the 10 years before and the 10 years after introduction of the vaccine . METHODS: Records of patients discharged with a diagnosis of facial cellulitis or infections of the oral cavity were reviewed . Fisher's exact test was used to compare rates of cellulitis during the two decades . RESULTS: Trauma was the most common antecedent to facial cellulitis in both eras . Buccal cellulitis accounted for 7/25 (28%) of cases before Hib vaccination and 0/19 cases since . Pneumococcal buccal cellulitis was not seen in either decade . CONCLUSIONS: Buccal cellulitis due to Hib is a disappearing disease . Eighty-nine percent of recent inpatient cases of childhood facial cellulitis were related to trauma, tooth problems, or severe sinusitis . Facial cellulitis due to S pneumoniae is rare.

Rev Med Brux, 2002 Jun, 23(3), 165 - 74
{Conjugated vaccines}; Swennen B et al.; Conjugate vaccines extend the vaccinal prevention for children to more diseases . Conjugating the capsular polysaccharide to a carrier protein transforms a T-independent antigen in a T-dependent, allowing protection of the children (before 2 years of age) against Haemophilus influenzae type b, meningococcal C and pneumococcal infections . This article reviews the 3 conjugate vaccines and their results with focus on some questions: antigens interference in the immunological response, serological subrogate for protection, herd immunity and replacement of circulating serotypes.

J Bacteriol, 2002 Aug, 184(16), 4582 - 93
Genome-scale metabolic model of Helicobacter pylori 26695; Schilling CH et al.; A genome-scale metabolic model of Helicobacter pylori 26695 was constructed from genome sequence annotation, biochemical, and physiological data . This represents an in silico model largely derived from genomic information for an organism for which there is substantially less biochemical information available relative to previously modeled organisms such as Escherichia coli . The reconstructed metabolic network contains 388 enzymatic and transport reactions and accounts for 291 open reading frames . Within the paradigm of constraint-based modeling, extreme-pathway analysis and flux balance analysis were used to explore the metabolic capabilities of the in silico model . General network properties were analyzed and compared to similar results previously generated for Haemophilus influenzae . A minimal medium required by the model to generate required biomass constituents was calculated, indicating the requirement of eight amino acids, six of which correspond to essential human amino acids . In addition a list of potential substrates capable of fulfilling the bulk carbon requirements of H . pylori were identified . A deletion study was performed wherein reactions and associated genes in central metabolism were deleted and their effects were simulated under a variety of substrate availability conditions, yielding a number of reactions that are deemed essential . Deletion results were compared to recently published in vitro essentiality determinations for 17 genes . The in silico model accurately predicted 10 of 17 deletion cases, with partial support for additional cases . Collectively, the results presented herein suggest an effective strategy of combining in silico modeling with experimental technologies to enhance biological discovery for less characterized organisms and their genomes.

Emerg Infect Dis, 2002 Aug, 8(8), 850 - 1
Haemophilus aphrophilus endocarditis after tongue piercing; Akhondi H et al.; Piercing invades subcutaneous areas and has a high potential for infectious complications . The number of case reports of endocarditis associated with piercing is increasing . We studied a 25-year-old man with a pierced tongue, who arrived at Memorial Health University Medical Center with fever, chills, rigors, and shortness of breath of 6 days' duration and had an aortic valvuloplasty for correction of congenital aortic stenosis.

Zh Mikrobiol Epidemiol Immunobiol, 2002 May-Jun, (3), 56 - 8
{Cultivation of Haemophilus influenzae, serotype B, in amino peptide-based semisynthetic nutrient medium}; Orlova OE et al.; The work shows the possibility of the cultivation of H . influenzae, serotype b, in semisynthetic nutrient medium with amino peptide as the only source of amino acids, glucose--as the main source of carbon and energy and containing, in addition, the necessary growth factors and vitamins.

Pediatr Int, 2002 Aug, 44(4), 381 - 6
Pharyngeal colonization with Haemophilus influenzae type b among healthy Turkish infants and children; Bakir M et al.; BACKGROUND: An absence of Haemophilus influenzae type b (Hib) disease surveillance and epidemiological data on the pharyngeal carriage of Turkish children causes delay in the introduction of conjugated Hib vaccination into proposed national vaccination programs . METHODS: Oropharyngeal cultures were obtained from 1404 healthy infants and children . Six healthy child clinic (HCC), 11 day-care centers (DCC) and seven elementary schools (ES) were randomly selected in seven different counties at the Anatolian side of Istanbul between January and April 2000 . RESULTS: Haemophilus influenzae was isolated from 315 (22.8%) of all participants and 98 (31%) isolates were serotype b . The carriage rate for Hib was higher in children at DCC (43 out of 448, 9.6%) and ES (46 out of 504, 9.1%) compared to infants 0-24 months of age (nine out of 430, 2.1%) presented to HCC . All Hib isolates were susceptible to azithromycin, chloramphenicol and cefotaxime . Beta-lactamase production was detected in only one isolate . Trimethoprim-sulfamethoxazole resistance was found in 8.5% of Hib isolates . Multivariate analysis showed that DCC and ES attendance were independent predictors of Hib carriage . CONCLUSION: A significant proportion of healthy Turkish children was shown to be colonized with Hib . The burden of invasive Hib infections should be determined in order to evaluate the Hib conjugated vaccine as a part of a routine immunization program in Turkey.

Pediatr Int, 2002 Aug, 44(4), 376 - 80
Incidences of nasopharyngeal colonization of respiratory bacterial pathogens in Japanese children attending day-care centers; Masuda K et al.; BACKGROUND: In Japan, many younger children attending day-care centers tend to frequently experience acute respiratory infections and prolonged otitis media . OBJECTIVES: To evaluate the carriage rate of respiratory bacterial pathogens in children attending day-care centers in our district . METHODS: Nasopharyngeal cultures of 156 healthy children between the ages of 1 month and 5 years were conducted at two day-care centers in Japan, in April 1999 . The carriage rates of four major pathogens (Streptococcus pneumoniae, Haemophilus influenzae, Moraxella catarrhalis and Staphylococcus aureus) and the antibiotic susceptibilities of the isolates were examined . RESULTS: Streptococcus pneumoniae, H . influenzae, M . catarrhalis and S . aureus were detected in 94 (60.3%), 83 (53.2%), 54 (34.6%) and 28 (17.9%) children, respectively . A total of 141 (90.4%) children carried at least one pathogen among these four pathogens and 87 (55.8%) children carried more than one pathogen . Fifty-seven of the 94 (60.6%) S . pneumoniae isolates were penicillin-intermediately or highly resistant strains of S . pneumoniae (PISP/PRSP) . Beta-lactamase producing H . influenzae was not detected . Twelve of the 28 (42.9%) S . aureus isolates were methicillin-resistant . The incidence of colonization by PISP/PRSP in children younger than 3 years (43/69, 62.3%) was significantly higher than that in children aged 3-5 years (14/87, 16.1%) (P < 0.0001) . CONCLUSIONS: We conclude that the rates of colonization by respiratory bacterial pathogens, especially by antibiotic-resistant strains, were high in children attending day-care centers in our district, suggesting their horizontal spread among children in day-care centers . Considering that the majority of children attending day- care centers carried one or more of the bacterial pathogens, the judicious use of antimicrobials will be required to prevent the increase of antibiotic-resistant rates among the colonizing pathogens.

Vet Rec, 2002 Jul 6, 151(1), 18 - 21
Effect of vaccinating sows and their piglets on the development of Glässer's disease induced by a virulent strain of Haemophilus parasuis serovar 5; Baumann G et al.; Ten pregnant gilts were divided into two groups of five and one group was vaccinated at 80 and 95 days of pregnancy with a commercial bacterin containing Haemophilus parasuis serovars 2, 3 and 5 . Half the piglets born to each group of gilts were vaccinated at seven and 21 days of age with the same bacterin, and one week after they were weaned at five weeks, all the piglets were inoculated intratracheally with 10(6) colony-forming units of Hparasuis serovar 5 . At slaughter, a significantly smaller percentage of the lungs of the pigs born to the vaccinated gilts was affected by pneumonic lesions, and significantly fewer of them had arthritic joint changes . The average daily liveweight gain of the pigs born to the vaccinated gilts was significantly greater than that of those born to the unvaccinated gilts, but the vaccination of the piglets had no effect . There was no significant difference between the feed conversion ratios of the four groups of piglets, and none between the average times they took to reach slaughter weight . The pigs born to the vaccinated gilts had higher ELISA titres to Hparasuis than those born to the unvaccinated gilts.

J Infect Dis, 2002 Aug 1, 186(3), 361 - 71 Epub 2002 Jul 10.
The inhibitory effect of C-reactive protein on bacterial phosphorylcholine platelet-activating factor receptor-mediated adherence is blocked by surfactant; Gould JM et al.; Numerous major bacterial pathogens in the human respiratory tract, including Streptococcus pneumoniae and Haemophilus influenzae, express cell-surface phosphorylcholine (ChoP), a ligand for the receptor for platelet-activating factor (rPAF) . ChoP is also bound by C-reactive protein (CRP), which, in the presence of complement, may be bactericidal . This study found that CRP can block the attachment of bacteria expressing cell-surface ChoP to host cells . Concentrations of CRP equivalent to those on the mucosal surface of the human airway blocked most adherence of both S . pneumoniae and H . influenzae to human pharyngeal epithelial cells . ChoP-mediated adherence was also reduced in the presence of an rPAF antagonist . The antiadhesive effects of the rPAF antagonist and CRP were not additive, suggesting that CRP activity is specific to the area of adherence mediated by the receptor . The binding of CRP to ChoP and the effect of CRP on adherence were inhibited by human surfactant (primarily ChoP) . The antiadhesive effect of CRP may be diminished in the terminal airway, where surfactant is abundant.

Lancet, 2002 Jul 20, 360(9328), 211 - 8
Dexamethasone treatment in childhood bacterial meningitis in Malawi: a randomised controlled trial; Molyneux EM et al.; BACKGROUND: Steroids are used as adjuvant treatment in childhood pyogenic meningitis to attenuate host inflammatory responses to bacterial invasion . We aimed to assess the effectiveness of dexamethasone in management of acute bacterial meningitis in a developing country . METHODS: In a double-blind, placebo controlled trial, we included 598 children with pyogenic meningitis who had been admitted to the children's wards of the Queen Elizabeth Central Hospital, Blantyre, Malawi . We did physical, neurological, developmental, and hearing assessments at 1 and 6 months after discharge . The primary outcome was overall death . Secondary outcomes included sequelae, in-hospital deaths, and death after discharge . Analysis was done by intention to treat . FINDINGS: Of the 598 included children, 307 (51%) were assigned to dexamethasone and 295 (49%) to placebo . 338 (40%) of 598 patients had Streptococcus pneumoniae, 170 (28%) Haemophilus influenzae type b, 66 (11%) Neisseria meningitidis, and 29 (5%) Salmonella spp . 78 (13%) patients had no growth on culture . The number of overall deaths was the same in the two treatment groups (relative risk 1.00 {95% CI 0.8-1.25}, p=0.93) . At final outcome, sequelae were identified in 84 (28%) of children on steroids and in 81 (28%) on placebo (relative risk 0.99 {95% CI 0.78-1.27}, p=0.97) . The number of children dying in hospital did not differ between groups . INTERPRETATION: Steroids are not an effective adjuvant treatment in children with acute bacterial meningitis in developing countries.

Vaccine, 2002 Jul 26, 20(23-24), 2989 - 94
The epidemiology of invasive Streptococcus pneumoniae disease in Catalonia (Spain) . A hospital-based study; Dominguez A et al.; The aim of this study was to investigate the incidence of invasive pneumococcal disease (IPD) in Catalonia . A hospital-based incidence study of the period 1997-1999 was carried out by reviewing the isolations of Streptococcus pneumoniae obtained from normally sterile sites reported by the hospitals that voluntarily participate in the Microbiological Reporting System of Catalonia (MRSC), and those obtained by active retrospective surveillance of cases recorded by microbiology laboratories of the remaining hospitals . Cases of pneumonia were included only if the blood culture was positive . The age, sex and clinical presentation of each patient were recorded . The global incidence of hospital-based IPD was 10.5 per 100,000 persons-year, and was much higher in subjects <2 years of age (59.6) and in those aged > or = 65 years (27.9) . In subjects > or = 65 years, bacteremic pneumococcal pneumonias were more frequent in the months from December to March than they were in children <2 years of age (P<0.0001) . The global incidence of IPD (10.5 per 100,000 persons-year) is high in Catalonia, greater than that of meningococcal or Haemophilus influenzae invasive disease . In children <2 years, the incidence is nearly six times higher (59.6 per 100,000 persons-year) with pneumonias (rate of 26.2 per 100,000 persons-year) and non-focal bacteremias (rate of 22.1 per 100,000 persons-year) being especially frequent.

Curr Infect Dis Rep, 2002 Aug, 4(4), 317 - 323
Prevention of Pneumococcal Meningitis; Tan TQ; With the success of the conjugated Haemophilus influenzae type b vaccines, Streptococcus pneumoniae has become one of the most important causes of bacterial meningitis worldwide, causing significant morbidity and mortality . Additionally, the increasing amount of resistance that this organism is developing to multiple classes of antimicrobial agents has made the treatment of pneumococcal infections, especially meningitis, much more difficult . Immunization has been shown to be one of most effective methods for preventing pneumococcal meningitis, resulting not only in a decrease in disease burden, but also a decrease in antimicrobial resistance . Currently, a 23-valent pneumococcal polysaccharide vaccine and a heptavalent protein conjugate vaccine are licensed for use . However, the 23-valent polysaccharide vaccine is poorly immunogenic in infants and young children . The continued development, licensing, and use of pneumococcal conjugate vaccines have the best potential to both prevent disease and decrease the prevalence of pneumococcal meningitis.

Dtsch Tierarztl Wochenschr, 2002 Jun, 109(6), 271 - 6
The effect of a homologous bacterin given to sows prefarrowing on the development of Glässer's disease in postweaning pigs after i.v . challenge with Haemophilus parasuis serotype 5; Hoffmann CR et al.; The trial was carried out to evaluate the impact of maternal antibodies on the development of Glasser's disease after i.v . exposure of weaned pigs with a homologous serovar of Haemophilus parasuis (HPS) . Two groups of weaned pigs were formed . Group one VI (n = 10): born to vaccinated sows, weaners i.v . challenged one week postweaning and euthanatized 14 days postweaning . Group two NVI (n = 10 wearners): born to non vaccinated sows, i.v . challenged one week postweaning euthanatized 14 days postweaning . One week postweaning all weaners were i.v . inoculated with HPS serovar 5 . The following parameters were evaluated: clinical signs (depression, centralnervous signs, fever, lameness), macroscopic lung, pleura, peritoneum, liver and joint changes, and mortality . All trial sows were HPS seronegative prior to vaccination . The HPS vaccinated sows were proven seropositive on day 3 p.p . (values > 0.24), the non vaccinated ones were tested seronegative (values < 0.23) . The progeny of sows vaccinated prefarrowing with two doses of HPS serovar 5 bacterin were partially protected against HPS caused clinical and pathological signs . The majority of clinical signs as fever, depression, recumbency, lack of response to verbal stimuli and lameness showed significant (P < 0.05) milder clinical symptoms in VI than in NVI animals . Respiratory signs (P = .169) and involvement of the central nervous system as ataxia, muscular tremor, incoordination of hind legs and convulsions (P = 1) showed no significant differences between the groups . Except lesions of pericard (VI vs . NVI, P = .14) and pleura (VI vs . NVI, P = .14) there were significant (P < 0.05) macroscopic differences at necropsy in lung, liver, joints and cerebrospinal fluid between the offspring of vaccinated sows and the ones of non vaccinated dams . No HPS were isolated from the nasal mucosa of the pigs prior to inoculation . HPS serovar 5 was recovered at necropsy from the nasal mucosa of all pigs in both groups . One pig from group VI presented in all examined organs the presence of HPS serovar 5 . The remaining animals in group VI revealed in lung, pericard, pleura, liver, joints and cerebrospinal fluid no presence of HPS . The rate of isolation between VI and NVI groups revealed a significant (P < 0.05) difference . All the survived piglets of group NVI showed positive ELISA titres against HPS serovar 5 (values > .24) . The piglets that died or were euthanatized before the end of the study have not been subjected to ELISA serological testing . One piglet died in group VI before the end of the study . Non of the remaining animals in group VI showed seroconversion to HPS serovar 5 . Implications: Vaccination of sows did not influence the colonisation of nasal mucosa, but progeny of sows vaccinated prefarrowing with two doses of HPS serovar 5 bacterin were partially protected against HPS caused diseases.

Mol Microbiol, 2002 Jul, 45(2), 485 - 500
Genes of non-typeable Haemophilus influenzae expressed during interaction with human epithelial cell lines; van Ulsen P et al.; Non-typeable Haemophilus influenzae may infect the lower respiratory airways of chronic obstructive pulmonary disease patients . We characterized genes of non-typeable H . influenzae expressed during interaction with two human respiratory tract-derived epithelial cell lines . A library of 8000 clones was constructed in H . influenzae Rd (rec1) by cloning chromosomal fragments upstream of a promoterless cat gene . Exposure of this library to NCI-H292 epithelial cell layers in the presence of chloramphenicol (Cam) resulted in survival of bacteria expressing cat . A total of 52 clones were selected that were resistant to Cam in the presence of epithelial cells of cell line NCI-H292 . These did not (n = 42) or hardly grow (n = 10) on sBHI plates containing Cam and were sensitive to Cam in cell culture medium alone . All clones, moreover, survived Cam in the presence of Hep2 epithelial cell layers . Sequence analysis showed that four clones contained sequences without homology to Rd or any other sequence, and therefore contained promoters and parts of open reading frames (ORFs) of novel genes . The other 48 clones were homologous to Rd, and characterization was based upon this genome . Six different functional classes were distinguished: (i) metabolic processes; (ii) stress response; (iii) gene expression; (iv) cell envelope biosynthesis; (v) DNA-related processes and cell division; and (vi) ORFs encoding proteins of unknown function . The contribution of identified genes to non-typeable H . influenzae adaptation to the epithelial cell environment is discussed.

Int J Infect Dis, 2002 Jun, 6(2), 113 - 7
Antibody response to Haemophilus influenzae type b tetanus conjugate vaccine with two doses given at 3 and 5 months of age; Guimaraes T et al.; BACKGROUND: In developed countries, the use of Hib conjugate vaccines has led to the near disappearance of invasive Hib disease, but costs have limited its use in developing countries . In order to identify more economical vaccination schedules, we carried out a trial to evaluate the immunogenicity of an alternative two-dose PRP-T regimen, based on a previous report in which carrier priming could be obtained with prior diphtheria-tetanus-pertussis (DTP) vaccination . METHODS: Healthy infants were enrolled to receive the PRP-T given at 3 and 5 months of age, with DTP vaccination given at 2, 4 and 6 months of age . Serum specimens were obtained at 3, 6 and 15 months of age . IgG anti-Hib titer determination was performed using enzyme-linked immunosorbent assay to evaluate serologic response and its duration . RESULTS: One-hundred and seventeen infants were enrolled . The geometric mean titer (GMT) of antibody to PRP was low in the pre-immunization samples (0.13 mg/mL), achieving high values after two doses of PRP-T (27.42 mg/mL), with all titers over 1 mg/mL; the GMT at 15 months was 5.45 mg/mL; 94.6% of infants had serologic responses after the two doses of vaccination, with average intervals of 27 and 22 days between DTP and PRP-T first-to-first and second-to-second administrations, respectively . However, these intervals were 11 and 3 days for infants who did not have serologic responses (P50.0013 and 0.0030, respectively) . CONCLUSIONS: These results indicate that two doses of PRP-T can induce high antibody titers using the proposed schedule; moreover, the GMT assessed at 15 months of age was also protective . The enhanced immune response observed in the study could be explained by the previous administration of the DTP vaccine, since the longer the interval between DTP and PRP-T, the better the response to Hib vaccine . The PRP-T vaccine given at 3 and 5 months of age may be an economical alternative to the current proposed schedule, which could make the introduction of Hib vaccination in developing countries more feasible, considering the relatively high cost of this vaccine.

Southeast Asian J Trop Med Public Health, 2002 Mar, 33(1), 49 - 55
Dengue hemorrhagic fever in infants; Hongsiriwon S; A report of 19 cases of serologically-proven dengue hemorrhagic fever (DHF) in infants aged 3-12 months who were admitted to the Department of Pediatrics, Chon Buri Regional Hospital, Thailand, during 1995 to 1998 . Subjects were 8 males and 11 females, with the peak age of 8 months . Four cases (21%) had DHF and other common co-infections ie pneumonia (2 cases), Staphylococcus aureus sepsis (1 case) and Haemophilus influenzae meningitis (1 case) . The clinical manifestations of the 15 DHF cases were high fever (100%), coryza (93.3%), hepatomegaly (80%), drowsiness (53.3 %), and vomiting (46.7%); rash was observed in only 27%; one-fifth developed febrile convulsions . Sites of bleeding were the skin (petechiae) 58%, gastrointestinal system (melena) 16%, and mucous membrane (epistaxis) 5%; thrombocytopenia and increased hematocrit (> or =20%) were noted in 95% and 84% respectively . The majority of the patients (18 cases, 95%) had primary infection; only one (5%) had secondary infection . The clinical severity of the DHF was Grade I, II, and III (dengue shock syndrome) in 21%, 47% and 32% of cases respectively . After appropriate and effective management, all the infants recovered fully.

Infect Immun, 2002 Aug, 70(8), 4729 - 34
Identification of Klebsiella pneumoniae genes involved in intestinal colonization and adhesion using signature-tagged mutagenesis; Maroncle N et al.; Klebsiella pneumoniae is an opportunistic pathogen responsible for nosocomial infections that initially colonize the intestinal tract of patients . Signature-tagged mutagenesis was used to identify genes required for this function . A library of 2,200 mutants was analyzed for the inability of the mutants to survive in a murine model of intestinal colonization and to adhere to human intestinal cells (Int-407) in vitro . Twenty-nine attenuated mutants were selected for further analyses after competition assays against the wild-type strain . Whatever the screening model, most of the transposon insertions occurred in genes involved in metabolic pathways, membrane transport, DNA metabolism, transcriptional regulation, and unknown functions . Only one mutant was attenuated in both the murine colonization and the in vitro adhesion models, and the sequence disrupted by the transposon had homology to adhesin-encoding genes of Haemophilus sp.

Infect Immun, 2002 Aug, 70(8), 4661 - 8
Acylation of the lipooligosaccharide of Haemophilus influenzae and colonization: an htrB mutation diminishes the colonization of human airway epithelial cells; Swords WE et al.; Haemophilus influenzae is a commensal and opportunistic pathogen of the human airways . A number of surface molecules contribute to colonization of the airways by H . influenzae, such as adhesins, including structures found in the lipooligosaccharide (LOS) . A human bronchiolar xenograft model was employed to investigate the host-bacterial interactions involved in the colonization of the airway by H . influenzae . Differential display was used to identify H . influenzae mRNA that reflect genes which were preferentially expressed in the xenograft compared to growth . Eleven mRNA fragments had consistent increased expression when the bacteria grew in xenografts . On sequencing these fragments, eight open reading frames were identified . Three of these had no match in the NCBI or the TIGR database, while an additional three were homologous to genes involved in heme or iron acquisition and utilization: two of the mRNAs encoded proteins homologous to enzymes involved in LOS biosynthesis: a heptosyl transferase (rfaF) involved in the synthesis of the LOS core and a ketodeoxyoctonate phosphate-dependent acyltransferase (htrB) that performs one of the late acylation reactions in lipid A synthesis . Inoculation of human bronchiolar xenografts revealed a significant reduction in colonization capacity by htrB mutants . In vitro, htrB mutants elicited lesser degrees of cytoskeletal rearrangement and less stimulation of host cell signaling with 16HBE14o(-) cells and decreased intracellular survival . These results implicate acylation of H . influenzae lipid A as playing a key role in the organisms' colonization of the normal airway.

Ann Clin Biochem, 2002 Jul, 39(Pt 4), 374 - 7
Are there any clinical indications for measuring IgG subclasses?
Maguire GA, Kumararatne DS, Joyce HJ.
It is questionable as to whether a low serum concentration of one of the IgG subclasses identifies a disease state . A low IgG(1) concentration is found in primary or secondary immunodeficiency states but does not occur in isolation . Low IgG(2) concentration is associated with an increased risk of bacterial infections but only in some individuals and not in others . Isolated IgG(3) and IgG(4) deficiency have not been convincingly demonstrated . Therefore, the isolated finding of low concentrations of one or more IgG subclass does not identify individuals at risk . In contrast, the finding of low serum concentrations of antibodies to specific bacterial antigens (Haemophilus influenzae type B, pneumococcus, tetanus and diphtheria) does identify individuals at risk and these measurements should be used in preference to IgG subclass measurement.

Clin Ther, 2002 Jun, 24(6), 906 - 17
Efficacy and tolerability of gatifloxacin in community treatment of acute exacerbations of chronic bronchitis; Anzueto A et al.; BACKGROUND: Recognizing acute exacerbations of chronic bronchitis (AECB) and selecting appropriate antibiotic treatment for patients who would benefit most is a challenge for community-based physicians . OBJECTIVE: The Tequin Clinical Experience Study, an open-label, noncomparative, postmarketing trial, assessed the efficacy and tolerability of gatifloxacin, an 8-methoxy fluoroquinolone, in the treatment of AECB in the community-practice setting . METHODS: Consecutive patients with respiratory tract infections in community-based settings were eligible for participation . Treated patients (N = 2512) included 1107 men (44.1%) and 1405 women (55.9%) aged > or =18 years with a clinical diagnosis of chronic bronchitis . All participants received oral gatifloxacin 400 mg once daily for 7 to 10 days . Clinical response was determined via telephone contact conducted by the investigator or study coordinator using case-report forms or during an office visit after the last dose . The investigator or coordinator collected expectorated or induced sputum specimens that were then smeared on a microscope slide, stored in a tube, and transported to a central reference laboratory for Gram-staining and culture . Of 1388 pretreatment sputum specimens submitted, pathogens were isolated from 424 . RESULTS: The most frequently detected pathogens were Haemophilus influenzae, Moraxella catarrhalis, and Streptococcus pneumoniae . All H . influenzae and 99% of S . pneumoniae isolates tested were susceptible to gatifloxacin . Of the 2267 patients with a determinable clinical response, 2084 (91.9% {95% CI, 90.8%-93.0%}) were cured (all acute symptoms improved or returned to baseline level, no new symptoms present, no additional antibiotic required) . The 95.8% cure rate in 166 patients with H . influenzae included 100% of those with beta-lactamase-positive strains . Overall, 89.2% of 111 patients with M . catarrhalis were cured; rates were similar regardless of beta-lactamase production . The clinical cure rate in 74 patients with S . pneumoniae was 98.6% and was independent of the degree of penicillin resistance (minimum inhibitory concentration > or =2.0 microg/ mL) . All 6 patients infected with S . pneumoniae fully resistant to penicillin were cured . Gatifloxacin was generally well tolerated, and the majority of adverse events were mild to moderate; only 11 drug-related adverse events in 10 patients (0.4%) were serious . Drug-related nausea (3.0%), dizziness (1.5%), diarrhea (1.2%), and vomiting (0.9%) were the most common adverse events . CONCLUSIONS: The high clinical cure rate and favorable tolerability support gatifloxacin as a rational choice for the treatment of AECB in patients such as those in this community-based study.

Acta Paediatr, 2002, 91(5), 599 - 603
Vaccination coverage estimates by EPI cluster sampling survey of children (18-24 months) in Flanders, Belgium; Vellinga A et al.; A random cluster sample according to the EPI cluster sampling technique was conducted in 1999 in Flanders (North Belgium) to ascertain the vaccination coverage of 18 to 24-mo-old children . Polio is the only mandatory vaccine . Diphtheria-tetanus-pertussis (DTP), Haemophilus influenzae type b (Hib), hepatitis B (HB) and measles-mumps-rubella (MMR) are included in the recommended schedule of vaccinations . For Hib and HB, a minimal cost was charged . Professional interviewers conducted interviews with the parents of 1110 children randomly selected in 89 municipalities . Analysis was conducted on the results of 1005 children . The coverage level (95% confidence interval) for the full schedule was 96% (95-97) for polio, 89% (87-91) for DTP, 78% (74-82) for Hib, 68% (64-72) for HB and 83% (81-87) for MMR . The vaccinations were administered by the regional children's health organization (70%), paediatricians (17%) and GPs (11%) . No sociodemographic factors could be associated with vaccination coverage . One province showed significantly (p < 0.01) lower vaccination coverage levels compared with those of the other four provinces for DTP (91% vs 82%), Hib (78% vs 53%), HB (73% vs 46%) and MMR (87% vs 66%) . Conclusion: There is a need for more and better information about vaccination for parents as well as for the healthcare providers.

Proteins, 2002 Aug 1, 48(2), 220 - 6
Crystal structure of the YjeE protein from Haemophilus influenzae: a putative Atpase involved in cell wall synthesis; Teplyakov A et al.; A hypothetical protein encoded by the gene YjeE of Haemophilus influenzae was selected as part of a structural genomics project for X-ray analysis to assist with the functional assignment . The protein is considered essential to bacteria because the gene is present in virtually all bacterial genomes but not in those of archaea or eukaryotes . The amino acid sequence shows no homology to other proteins except for the presence of the Walker A motif G-X-X-X-X-G-K-T that indicates the possibility of a nucleotide-binding protein . The YjeE protein was cloned, expressed, and the crystal structure determined by the MAD method at 1.7-A resolution . The protein has a nucleotide-binding fold with a four-stranded parallel beta-sheet flanked by antiparallel beta-strands on each side . The topology of the beta-sheet is unique among P-loop proteins and has features of different families of enzymes . Crystallization of YjeE in the presence of ATP and Mg2+ resulted in the structure with ADP bound in the P-loop . The ATPase activity of YjeE was confirmed by kinetic measurements . The distribution of conserved residues suggests that the protein may work as a "molecular switch" triggered by ATP hydrolysis . The phylogenetic pattern of YjeE suggests its involvement in cell wall biosynthesis .

Pharmacoeconomics, 2002, 20(8), 513 - 28
Cost-effective approaches to the treatment of community-acquired pneumonia in the era of resistance; Kuti JL et al.; Community-acquired pneumonia (CAP) infects upwards of four million people in the US each year, of which 20% require subsequent hospitalisation . Consequently, it is a large contributor to excessive healthcare resource consumption and cost . Since the aetiology of CAP is not identified in a majority of patients, treatment is often empiric, aimed at the most common causes, Streptococcus pneumoniae, Haemophilus influenzae, Moraxella catarrhalis, and the atypical pathogens (Mycoplasma pneumoniae, Chlamydia pneumoniae and Legionella pneumophila) . A variety of pharmaceutical agents exist for the treatment of CAP, most notably the cephalosporin and penicillin derivatives, the macrolide/azalide antibacterials, the newer tetracyclines, and most recently the respiratory fluoroquinolones . Choosing an agent is usually related to issues such as patient compliance, adverse event profiles, and the presence of resistance . Of these, resistance seems to be the main factor today . S . pneumoniae, the most common cause of CAP, is steadily acquiring resistance to a majority of the currently available antibacterials, thus further increasing costs due to prolonged hospitalisation, treatment of relapses and the use of more expensive antibacterials . Understanding and maximising the pharmacodynamic properties of the available antibacterials will not only prevent the emergence of resistance, thus prolonging their clinical utility, but also reduce the costs associated with treating the infection through rapid symptom improvement and earlier patient discharge . Numerous methods for reducing costs in patients with bacterial infections are documented in the literature and can be applied to CAP . Choosing monotherapy instead of combination therapy can reduce costs associated with the administration of the antibacterial . Agents with longer half-lives allow for once-daily administration, which in turn, leads to improved compliance, successful outcomes, and decreased costs . Administering antibacterials to maximise their pharmacodynamics, such as with continuous infusion of beta-lactams, reduces the amount of drug needed in addition to savings associated with administration and supplies . Finally, transitioning patients to oral therapy as soon as they are clinically stable can significantly reduce the length of hospital stay, which is the major contributing factor of healthcare costs . The use of a clinical pathway in an institution is the most effective way to apply these cost-saving approaches in the treatment of CAP . These pathways should be specific to each institution, thus considering the resistance rates in the area and encouraging the use of the most active, cost-effective agents to produce rapid, positive clinical outcomes.

J Med Chem, 2002 Jul 18, 45(15), 3246 - 56
Discovery of aminopyridine-based inhibitors of bacterial enoyl-ACP reductase (FabI); Miller WH et al.; Bacterial enoyl-ACP reductase (FabI) catalyzes the final step in each cycle of bacterial fatty acid biosynthesis and is an attractive target for the development of new antibacterial agents . Our efforts to identify potent, selective FabI inhibitors began with screening of the GlaxoSmithKline proprietary compound collection, which identified several small-molecule inhibitors of Staphylococcus aureus FabI . Through a combination of iterative medicinal chemistry and X-ray crystal structure based design, one of these leads was developed into the novel aminopyridine derivative 9, a low micromolar inhibitor of FabI from S . aureus (IC(50) = 2.4 microM) and Haemophilus influenzae (IC(50) = 4.2 microM) . Compound 9 has good in vitro antibacterial activity against several organisms, including S . aureus (MIC = 0.5 microg/mL), and is effective in vivo in a S . aureus groin abscess infection model in rats . Through FabI overexpressor and macromolecular synthesis studies, the mode of action of 9 has been confirmed to be inhibition of fatty acid biosynthesis via inhibition of FabI . Taken together, these results support FabI as a valid antibacterial target and demonstrate the potential of small-molecule FabI inhibitors for the treatment of bacterial infections.

Acta Microbiol Immunol Hung, 2002, 49(2-3), 337 - 46
Identification and incidence of fungal strains in chronic rhinosinusitis patients; Dosa E et al.; The fungal revolution taking place in otorhinology inspired us to study the frequency of occurrence of fungi in the nasal mucus of chronic rhinosinusitis (CRS) patients (with or without polyposis) in order to evaluate the incidence of eosinophilic fungal sinusitis in CRS patients . Ninety-six samples were examined from patients with CRS . In 74 cases mucus was collected non-invasively, and in 22 cases during operation . The Gram-stained direct smears of all samples were also evaluated . Bacteria and fungi colonizing in the mucus were detected by culturing method . The control group consisted of 50 healthy volunteers . Typical aerobic pathogenic bacteria could be isolated from 34 patients . Fifty-seven aerobic bacteria were isolated, i.e . 1.6 bacteria/positive patient with a maximum of 3 different bacteria/sample . The most frequently isolated bacteria were Staphylococcus aureus, Escherichia coli, Klebsiella pneumoniae, Streptococcus pneumoniae, and Haemophilus influenzae . Yeasts and moulds could be detected from 79 patients (83%): Candida albicans, Candida spp., Aspergillus spp., Cladosporium spp, and Penicillium spp . were isolated most frequently . Altogether 237 yeasts and moulds were isolated, i.e . 3.0 different fungi/positive patient, with a maximum of 5 different fungi/sample . In the control group aerobic pathogens were not isolated, only apathogenic species . Fungi were isolated from 22 healthy patients (44%) . These data indicate that fungi are frequently involved in the aetiology of CRS . IgE-medicated hypersensitivity to fungal allergens could not be proven in our patients.

Arch Pediatr, 2002 Jun, 9(6), 629 - 37
{Efficacy and tolerance of vaccinations in premature infants}; Saliou P et al.; Immunization may prevent an enhanced risk of infectious diseases, providing that it is completed on time . A review of the literature summarizes several studies on effectiveness, safety and duration of protection in preterm infants . Immune maturation depends on chronological age rather than gestational age . Then immunization against diphteria-tetanus-pertussis-poliomyelitis-Haemophilus influenzae b should be initiated at 2 months of age and completed prior than 6 months . The youngest preterm infants, still hospitalized at 8 weeks of age should be monitored following the first immunization as they may develop apnea episodes, probably linked with the pertussis component of the vaccine . In premature, BCG vaccination induces a delayed hypersensitivity to tuberculin less important than in full-term neonates, and should not be given right after birth in newborns less than 33 weeks of gestational age . Hepatitis B vaccination should be offered as soon as two months of age and even at birth to children born from HBs Ag carriers . Neither duration of immunity, nor safety are modified by prematurity.

Am J Pathol, 2002 Jul, 161(1), 19 - 26
Sampling tumor-draining lymph nodes for phenotypic and functional analysis of dendritic cells and T cells; Vuylsteke RJ et al.; Immune responses against tumor antigens will initially occur in the first tumor-draining lymph node, the sentinel node (SN) . Because of extensive diagnostic procedures, obtaining a piece of SN to isolate viable immune cells for functional analyses is often impossible . For this reason an alternative method to obtain viable cells from a lymph node (LN) was investigated, ie, scraping LNs with a surgical blade, and compared with dissociation of total LNs . Tumor-draining lymph nodes were retrieved from five oncological patients . The collected dendritic cells and T cells were phenotypically and functionally characterized by flow cytometry and antigen-specific interferon (IFN)-gamma release in an ELISPOT assay . Results were compared between the two isolation methods . Viabilities and phenotypic characteristics of the collected cells were entirely comparable for both methods . T-cell functionality was also comparable between both methods, with equal T-cell expansion factors and similar frequencies of cytotoxic T cells specifically recognizing the M1 matrix protein of Influenza haemophilus or the tumor antigen Her-2/neu . In conclusion, scraping LNs to obtain cells for analysis of immune functions in LNs is feasible and presents a good alternative to dissociation of LNs . Scraping may even be applied to small LNs that a pathologist will submit entirely for histological examination and may thus prove useful in the monitoring of immune responses in SNs.

Microbiology, 2002 Jul, 148(Pt 7), 2171 - 9
Molecular analysis of a haemagglutinin of Haemophilus paragallinarum; Hobb RI et al.; The gene encoding a haemagglutinin of H . paragallinarum, hagA, has been identified and the full-length nucleotide sequence determined . A approximately 39 kDa protein, recognized by an anti-haemagglutinin monoclonal antibody, mAb4D, was purified from H . paragallinarum strain 0083 and the N-terminal sequence obtained . The full-length nucleotide sequence was obtained by inverse PCR and the deduced amino acid sequence of the protein encoded was shown to be similar to other outer-membrane proteins of closely related organisms in the HAP group (Haemophilus, Actinobacillus, Pasteurella), especially the P5 protein of Haemophilus influenzae . The hagA gene was cloned into a His-tag expression vector and overexpressed in Escherichia coli strain M15(pREP4) . The identity of the purified recombinant protein as a H . paragallinarum haemagglutinin was confirmed by haemagglutination of chicken red blood cells and reactivity, in a Western blot, with the monoclonal antibody specific for the serovar A haemagglutinin.

Mol Microbiol, 2002 Jul, 45(1), 109 - 22
CpsK of Streptococcus agalactiae exhibits alpha2,3-sialyltransferase activity in Haemophilus ducreyi; Chaffin DO et al.; Streptococcus agalactiae (GBS) is a major cause of serious newborn bacterial infections . Crucial to GBS evasion of host immunity is the production of a capsular polysaccharide (CPS) decorated with sialic acid, which inactivates the alternative complement pathway . The CPS operons of serotypes Ia and III GBS have been described, but the CPS sialyltransferase gene was not identified . We identified cpsK, an open reading frame in the CPS operon of most serotypes, which was homologous to the lipooligosaccharide (LOS) sialyltransferase gene, lst, of Haemophilus ducreyi . To determine if cpsK might encode a sialyltransferase, we complemented a H . ducreyi lst mutant with cpsK . CpsK was expressed in H . ducreyi and LOS was isolated and analysed for sialic acid content by SDS-PAGE and high-performance liquid chromatography (HPLC) . Sialo-LOS was seen in the wild-type, cpsK- or lst-complemented mutant strains, but not in the mutant without cpsK . Addition of Neu5Ac to the LOS was confirmed by mass spectroscopy . Lectin binding studies detected terminal Neu5Ac(alpha 2-->3)Gal(beta 1- on LOS produced by the wild-type, cpsK or lst-complemented mutant strain LOS, compared with the mutant alone . Our data characterize the first sialyltransferase gene from a Gram- positive bacterium and provide compelling evidence that its product catalyses the alpha2,3 addition of Neu5Ac to H . ducreyi LOS and therefore the terminal side-chain of GBS CPS . Phylogenetic studies further indicated that lst and cpsK are related but distinct from sialyltransferases of most other bacteria and, along with their similar codon usage bias and G + C content, suggests acquisition by lateral transfer from an ancestral low G + C organism.

J Microbiol Immunol Infect, 2002 Jun, 35(2), 115 - 20
Clinical experience of managing empyema thoracic in children; Huang FL et al.; Data of 54 children with a diagnosis of thoracic empyema at a medical center in central Taiwan from January 1991 through April 2001 were analyzed . Their mean age was 4.4 years and the mean hospital stay was 13 days . Streptococcus pneumoniae was the most common pathogen, followed by Staphylococcus aureus and Haemophilus influenzae . These patients were divided into 2 groups according to the treatment method . Twenty-two patients were treated successfully with antibiotics and tube thoracostomy, whereas the other 32 children required further pleural decortication with antibiotic treatment . In patients with empyema, decortication allowed for more rapid defervescence than did closed tube thoracostomy (1.94 vs 5.04 days; p<0.001) and there were no complications in the group that underwent decortication treatment (p<0.03) . In conclusion, the decortication of loculated empyema thoracis in children is a safe and effective management procedure.

Respiration, 2002, 69(3), 217 - 22
Randomized, double-blind study of prulifloxacin versus ciprofloxacin in patients with acute exacerbations of chronic bronchitis; Grassi C et al.; BACKGROUND: Recently the role of bacteria in acute exacerbations of chronic bronchitis (AECB) as well as antibiotic treatment with selected drugs, especially fluoroquinolones, have been better defined . OBJECTIVE: To assess the efficacy and safety in patients with AECB of prulifloxacin in comparison with ciprofloxacin . METHODS: AECB was defined according to the guidelines for the evaluation of new anti-infective drugs for the treatment of respiratory tract infections (1992) . 235 patients took part in the trial; 117 (88 males and 29 females, mean age 64.8 years) received 600 mg prulifloxacin once daily and 118 (91 males and 27 females, mean age 64.5 years) 500 mg ciprofloxacin twice a day, for a duration of 10 days . The study design was randomized, multicenter, double-blind, double-dummy . Efficacy evaluations were performed by comparing pretreatment and posttreatment assessments . The clinical response was determined by 4-point rating scores on cough, dyspnea, and expectoration (volume and appearance) . The microbiological response was assessed on sputum specimen . RESULTS: Clinical success was observed in 84.7 and 85% of patients in the prulifloxacin and ciprofloxacin groups, respectively . The 95% confidence interval proved the equivalence of treatments . Both drugs successfully eradicated the most commonly isolated strains, including Haemophilus influenzae, Streptococcus pneumoniae, Klebsiella pneumoniae and Pseudomonas aeruginosa . Both treatments were well tolerated . Adverse drug reactions were always of mild or moderate intensity . CONCLUSION: The study showed that a 10-day course of prulifloxacin is as effective and safe as ciprofloxacin in the treatment of patients with AECB .

J Antimicrob Chemother, 2002 Jul, 50(1), 33 - 41
Activity of cefditoren against respiratory pathogens; Clark CL et al.; The activity of cefditoren and six other cephalosporins was tested against 250 pneumococci, including strains resistant to macrolides and quinolones . Cefditoren gave the lowest MICs, with MIC(50) and MIC(90) values of < or =0.016/0.03, 0.125/0.5 and 0.5/2.0 mg/L for penicillin-susceptible, -intermediate and -resistant pneumococci, respectively . A time-kill study of 12 pneumococcal strains with varying drug susceptibilities showed that cefditoren, at 2 x MIC, gave 99% killing of all strains after 12 h, with 99.9% killing after 24 h . Other cephalosporins gave similar kill kinetics but at higher concentrations . Against 160 Haemophilus influenzae, cefditoren had the lowest MICs (MIC(50) and MIC(90) both < or =0.016 mg/L), irrespective of beta-lactamase production . Time-kill studies of cefditoren compared with five other oral cephalosporins showed that cefditoren, at 8 x MIC, was bactericidal against 8/9 strains and gave 90% killing of all strains at the MIC after 12 h . Activity was bactericidal (99.9% killing) after 24 h with all drugs tested . Multistep studies of four penicillin-susceptible, four penicillin-intermediate and four penicillin-resistant strains showed that cefditoren, co-amoxiclav and cefprozil did not select for resistant mutants after 50 subcultures, compared with cefuroxime and azithromycin, where resistant mutants were selected in two and nine strains, respectively . Single-step mutation studies showed that cefditoren, at the MIC, had the lowest frequency of spontaneous mutants compared with other drugs.

Drugs, 2002, 62(10), 1441 - 5
Prevention of otitis media by vaccination; Russell F et al.; Otitis media (OM) is one of the commonest infections in childhood and a frequent reason for prescribing antibacterials in infancy . However, the increase in prevalence of antibacterial-resistant respiratory bacterial pathogens has not been matched by the development of new antibacterial agents . Bacterial vaccine strategies aim to prevent OM directly and to reduce nasopharyngeal carriage of pneumococci, thereby reducing the likelihood of developing acute OM . Complete protection against OM would require an approach targeting both bacterial and viral agents . Immunisation with a pneumococcal conjugate vaccine provides protection against acute OM caused by pneumococcal serotypes included in the vaccine, reduces serotype-specific pneumococcal carriage, and reduces carriage of penicillin-resistant pneumococci . However, an increase in non-vaccine serotype OM has been observed in vaccinated children, which may limit the overall effectiveness of this vaccine . New vaccines targeting non-typable Haemophilus influenzae and Mycoplasma catarrhalis are in the early stages of development . Efficacy studies with influenza vaccine have shown the most promising results to date in terms of overall reduction in OM episodes . A more substantial reduction in the burden of OM in childhood would require a combination of vaccines that are effective against the bacterial and viral pathogens involved and that can be administered early in infancy.

Rev Esp Salud Publica, 2002 May-Jun, 76(3), 197 - 206
{Haemophilus Influenzae infection before and after the immunization campaign among children in the Valencia community (1996-2000)}; Goicoechea Saez M et al.; BACKGROUND: The introduction of a conjugate type b Haemophilus influenzae (Hib) vaccine for children has led to a sharp drop in the incidence of H . influenzae disease . The purpose of this study is that of analyzing the major characteristics of invasive disease due to H . influenzae as regards epidemiology, clinical aspects, evolution and immunization status among the infantile population of the Autonomous Community of Valencia for the 1996-2000 period . METHOD: The data was taken from the clinical records of those children under age 15, who have shown clinical signs and symptoms indicative of invasive disease entailing isolation of Haemophilus influenzae and/or meeting the established case definition requirements, who were treated at all of the public hospitals in the Autonomous Community of Valencia throughout the 1996-2000 period . The trend of incidence was assessed by mean of incidence rates . The clinical pattern and the evolution there of (sequelae and life-threatening aspects) by frequency and age range . RESULTS: A total of 36 cases of invasive disease due to Haemophilus influenzae were recorded . The incidence rate among children under age 15 dropped from 3.56/10(5) in 1996 to 1.07/10(5) in 1997 (coinciding with the immunization campaign and the subsequent including of the conjugate Hib vaccine in the Routine Vaccination Schedule of the Autonomous Community of Valencia) and 0.30/10(5) in 1998, this being a situation which has continued over the following years . Fifty-three percent (53%) of the cases occur in children under age 18 months . Both the sequelae as well as the deaths occurred throughout the period prior to the routine use of the conjugate vaccine . No child properly immunized died . Two cases of non-b type H . influenzae occurred in immunized children . CONCLUSIONS: The incidence of infection due to type b Haemophilus influenzae dropped drastically as of the start of the routine immunization of the infantile population.

Eur J Epidemiol, 2001, 17(8), 779 - 82
Epidemiology of childhood bacterial meningitis in Poland . Incidence of bacterial meningitis with special reference to Haemophilus influenzae type b among children 0-59 months old in the former Kielce and Bydgoszcz districts in Poland in 1998-1999; Zielinski A et al.; Population based surveillance was undertaken to assess the incidence of meningitis caused by Haemophilus influenzae type b in children 0-59 months old in Kielce and Bydgoszcz districts in Poland in 1998 and 1999 . The cases were prospectively identified in pediatric and neuroinfection wards of local hospitals where all cases of children with suspected meningitis are referred in both districts . The mean annual incidence of meningitis caused by Haemophilus influenzae type b in children 0-59 months old in Kielce district during the study period was estimated at 3.1 per 100,000 per year (10.3% of cases of bacterial meningitis with confirmed etiology) . In Bydgoszcz district, the annual incidence was 9.7 per 100,000 (50% of confirmed cases) . These estimations are lower than reported in most Western European countries before the immunization against Hib was introduced . Small numbers of Hib vaccinations reported from both districts do not seem likely to have influenced the data significantly.

Expert Opin Investig Drugs, 2002 Jul, 11(7), 911 - 25
Antibiotics in the treatment of acute exacerbations of chronic bronchitis; Dever LL et al.; The benefit of antimicrobial therapy for patients with an acute exacerbation of chronic bronchitis (AECB) remains controversial for two main reasons . First, the distal airways of patients with chronic bronchitis are persistently colonised, even during clinically stable periods, with the same bacteria that have been associated with AECB . Second, bacterial infection is only one of several causes of AECB . These factors have led to conflicting analyses on the role of bacterial agents and the response to antimicrobial therapy of patients with AECB . An episode of AECB is said to be present when a patient with chronic obstructive pulmonary disease (COPD) experiences some combination of increased dyspnoea, increased sputum volume, increased sputum purulence and worsening lung function . While the average COPD patient experiences 2 - 4 episodes of AECB per year, some patients, particularly those with more severe airway obstruction, are more susceptible to these attacks than others . Bacterial agents appear to be particularly associated with AECB in patients with low lung function and those with frequent episodes accompanied by purulent sputum . Non-typeable Haemophilus influenzae, Streptococcus pneumoniae and Moraxella catarrhalis account for up to 50% of episodes of AECB . Gram-negative bacilli are more likely to occur in patients with more severe lung disease . Antibiotics have been used to ameliorate AECB, to prevent AECB and to prevent the long-term loss of lung function that characterises COPD . Numerous prevention trials have been conducted with fairly consistent results; antibiotics do not lessen the number of episodes of AECB but do reduce the number of days lost from work . Most antibiotic trials have studied the impact of treatment on episodes of AECB and results have been inconsistent, largely due to patient selection and end point definition . In patients with severe airway obstruction, especially in the presence of purulent sputum, antibiotic therapy significantly shortens the duration of symptoms and can be cost-effective . Over the past 50 years, virtually all classes of antimicrobial agents have been studied in AECB . Important considerations include penetration into respiratory secretions, spectrum of activity and antimicrobial resistance . These factors limit the usefulness of drugs such as amoxicillin, erythromycin and trimethoprim-sulfamethoxazole . Extended-spectrum oral cephalosporins, newer macrolides and doxycycline have demonstrated efficacy in clinical trials . Amoxicillin-clavulanate and flouoroquinolones should generally be reserved for patients with more severe disease . A number of investigational agents, including ketolides and newer quinolones, hold promise for treatment of AECB.

Biochem Biophys Res Commun, 2002 Jul 5, 295(1), 1 - 8
Overexpression and biochemical characterization of beta-1,3-N-acetylgalactosaminyltransferase LgtD from Haemophilus influenzae strain Rd; Shao J et al.; The lipopolysaccharide of capsule deficient Haemophilus influenzae strain Rd contains an N-acetylgalactosamine residue attached to the terminal globotriose moiety in the Hex5 glycoform . Genome analysis identified an open reading frame HI1578, referred to as lgtD, whose amino acid sequence shows significant level of similarity to a number of bacterial glycosyltransferases involved in lipopolysaccharide biosynthesis . To investigate its function, overexpression and biochemical characterization were performed . Most of the protein was obtained in a highly soluble and active form . By using standard glycosyltransferase assay and HPLC, we show that LgtD is an N-acetylgalactosaminyltransferase with high donor substrate specificity and globotriose is a highly preferred acceptor substrate for the enzyme . The K(m) for UDP-GalNAc and globotriose are 58 microM and 8.6 mM, respectively . The amino acid sequence of the enzyme shows the conserved features of family II glycosyltransferases . This is the first N-acetylgalactosaminyltransferase identified from H . influenzae, which shows potential application in large-scale synthesis of globo-series oligosaccharides . (c) 2002 Elsevier Science (USA).

J Antimicrob Chemother, 2002 Jul, 50 Suppl, 23 - 7
Clinical efficacy of cefpodoxime in respiratory tract infection; Cohen R; Acute otitis media (AOM), sinusitis and tonsillopharyngitis are respiratory tract infections frequently encountered by primary-care physicians . Increasing bacterial resistance, particularly in Streptococcus pneumoniae, which is one of the most important respiratory tract bacteria implicated in community-acquired respiratory tract infections, has led to concern about the current options for empirical antibiotic treatment and has prompted a search for effective alternative treatments . Data from in vitro studies show that cefpodoxime has good activity against the main respiratory tract pathogens, S . pneumoniae, Haemophilus influenzae, Moraxella catarrhalis and Streptococcus pyogenes . Clinical studies confirm the efficacy of cefpodoxime in AOM, sinusitis and tonsillopharyngitis . As with all broad-spectrum antibiotics, there is the risk of promotion of bacterial resistance associated with overuse . However, if used with care, cefpodoxime can be considered as an alternative for empirical treatment of bacterial respiratory tract infections encountered in general practice, particularly where penicillins and macrolides have reduced efficacy against the main bacterial pathogens.

J Antimicrob Chemother, 2002 Jul, 50 Suppl, 13 - 7
Pharmacokinetics and pharmacodynamics of oral beta-lactam antibiotics as a two-dimensional approach to their efficacy; Auckenthaler R; Pharmacokinetic and pharmacodynamic parameters are increasingly recognized as important determinants of the therapeutic efficacy of an antibiotic . For beta-lactam antibiotics, the most important determinant of the antimicrobial efficacy, and hence predictor of therapeutic efficacy, is the length of time that serum concentrations exceed the MIC . Dosing schedules for beta-lactam antibiotics should maintain serum concentrations above the MIC for the bacterial pathogen for at least 50% of the dosing interval to achieve therapeutic efficacy and prevent the development of resistance . This is a basic criterion for the clinical efficacy of beta-lactams . A combination of microbiological activity and pharmacokinetic characteristics was applied to calculate the time that serum antibiotic concentrations exceed the MIC for the major respiratory tract pathogens such as Streptococcus pneumoniae, Haemophilus influenzae, Moraxella catarrhalis, Streptococcus pyogenes and Klebsiella pneumoniae . In contrast with some other oral beta-lactam antibiotics, cefpodoxime 200 mg bd maintains serum concentrations above the MIC for each organism for at least 50% of the dosing interval and may therefore be an attractive choice for empirical therapy of community-acquired lower respiratory tract infections.

J Antimicrob Chemother, 2002 Jul, 50 Suppl, 7 - 11
Antibacterial activity of oral antibiotics against community-acquired respiratory pathogens from three European countries; Schito GC et al.; Antimicrobial resistance is universally recognized as a major problem . A European resistance survey was established to monitor the activity of widely used oral antibiotics against common respiratory tract pathogens . Studies were conducted in Italy, Spain and Austria to monitor resistance patterns among respiratory Streptococcus pneumoniae, Haemophilus influenzae, Moraxella catarrhalis, Streptococcus pyogenes, Staphylococcus aureus and Klebsiella pneumoniae to amoxicillin, co-amoxiclav, penicillin, cefaclor, cefadroxil, cefalexin, cefprozil, cefuroxime, cefixime, ceftibuten, cefpodoxime, clarithromycin and azithromycin (the antibiotics tested varying slightly from country to country) . Minimum inhibitory concentrations were determined using the NCCLS-recommended broth microdilution method . Among the antibiotics tested, cefpodoxime, an oral cephalosporin, was remarkably active against the major respiratory pathogens in all three countries . Cefpodoxime was more potent than cefaclor, cefixime and ceftibuten against pneumococci, especially against strains with decreased sensitivity to penicillin, and more active than cefaclor and cefuroxime against Gram-negative respiratory pathogens . Pneumococci and staphylococci displayed a very high level of in vitro macrolide resistance . These data indicate that cefpodoxime represents an appropriate choice in the treatment of community-acquired respiratory tract infection in the three countries surveyed.

Pediatr Infect Dis J, 2002 Apr, 21(4), 315 - 21
Reduced effectiveness of Haemophilus influenzae type b conjugate vaccine in children with a high prevalence of human immunodeficiency virus type 1 infection; Madhi SA et al.; BACKGROUND: Haemophilus influenzae type b (Hib) conjugate vaccines have successfully reduced the burden of invasive Hib disease in developed countries; however, their effectiveness in countries with a high incidence of pediatric HIV-1 is unknown . METHODS: The effectiveness of Hib conjugate vaccine was prospectively evaluated in South African children . The burden of invasive Hib disease in children < 1 year old was compared in 2 cohorts . The first cohort included 22,000 African children born in 1997 {969 (4.45%) of whom were estimated to be HIV-1-infected} who were not vaccinated with Hib conjugate vaccine . This group was compared with 19,267 children {1162 (6.03%) of whom were estimated to be HIV-1 infected} vaccinated at 6, 10 and 14 weeks of age with an Hib conjugate vaccine {TETRAMUNE (polyribosylribitol phosphate-CRM(197)-diphtheria-tetanus toxoids-whole cell pertussis)} between March, 1998, and June, 1999 . RESULTS: The estimated burden of invasive Hib disease in nonimmunized HIV-1-infected children < 1 year of age was 5.9-fold {95% confidence interval (95% CI), 2.7 to 12.6} higher than in HIV-1-uninfected children . The overall estimated effectiveness of Hib conjugate vaccine in fully vaccinated children <1 year of age was 83.2% (95% CI 60.3 to 92.9) . Vaccine effectiveness was significantly reduced in HIV-1-infected {43.9% (95% CI -76.1 to 82.1)} compared with uninfected children {96.5% (95% CI 74.4 to 99.5); P < 10(-5)} . Among three of the fully vaccinated HIV-1-infected children who developed invasive Hib disease, the anti-Hib polyribosylribitol phosphate serum antibody concentrations were 0.23, 0.25 and 0.68 microg/ml . CONCLUSION: Although the Hib conjugate vaccine was less effective among HIV-1-infected than among uninfected children, it was 83% effective in preventing overall invasive Hib disease and therefore should be considered for inclusion in the routine vaccination schedule by other African countries.

Pediatr Infect Dis J, 2002 Apr, 21(4), 271 - 7
Relative frequency of Haemophilus influenzae type b pneumonia in Chinese children as evidenced by serology; Wang YJ et al.; OBJECTIVES: It is commonly held that Haemophilus influenzae pneumonia among children in Asia is mostly caused by serotypes other than b (Hib) . If so, Hib conjugate vaccines would play little role in the prevention of pneumonia . In two prospective series of children hospitalized for pneumonia in China, the causative agents were searched for with a wide panel of microbiologic assays . METHODS: In the university hospitals of Beijing and Hefei, 156 consecutive children 3 months of age and older with symptoms and signs of pneumonia were studied . Blood culture, chest radiograph, nasopharyngeal aspirate for viral antigen detection and paired sera for 20 microbiologic assays were taken . Severity was graded, and the course of illness was monitored uniformly . RESULTS: In Beijing only likely contaminants grew from blood cultures, and in Hefei pathogens were identified in two cases . In combined series evidence for bacterial, mixed and viral etiology was obtained in 30, 7 and 21% of cases, respectively . The dominant bacteria were pneumococcus, Hib, Mycoplasma pneumoniae and Chlamydia pneumoniae, responsible for 13, 10, 8 and 8% of cases, respectively . Most patients were treated with extended spectrum antimicrobials such as piperacillin, cefotaxime or ceftriaxone, alone or in combination . One child died . CONCLUSIONS: As in most other series from other countries, the leading agent causing childhood pneumonia was pneumococcus but, in line with our previous experience from Beijing, the second most common agent detected was Hib . This observation suggests great potential for pneumococcal and Hib vaccinations in China . Because no evidence supported the need for routine use of extended spectrum antimicrobials, narrower spectrum agents would be safer for patients, would be cheaper for the community and would offer a way to address increasing resistance problems.

Bull World Health Organ, 2002, 80(4), 264 - 70
Economic analyses of rubella and rubella vaccines: a global review; Hinman AR et al.; OBJECTIVE: To investigate whether the incorporation of rubella vaccine into immunization programmes in developing countries is economically justified . METHODS: A MEDLINE search was conducted for articles published between 1970 and 2000 that dealt with economic analyses of rubella and rubella-containing vaccines . The Eastern Mediterranean, South-East Asia, and Africa regional Index Medicus databases and the LILACS database for Latin America and the Caribbean were also searched . FINDINGS: For developed countries, five cost- benefit analyses of rubella vaccine and five of measles-mumps-rubella vaccine as well as two cost-effectiveness analyses were found . For developing countries, five cost analyses and five cost-benefit analyses were found . All the cost-benefit analyses had a benefit:cost ratio greater than 1 and the cost-effectiveness studies indicated that rubella immunization was a cost-effective means of reducing the impact of congenital rubella syndrome . However, the methodologies were not standardized . CONCLUSION: The data support the inclusion of rubella vaccine in the immunization programmes of both developing and developed countries and indicate economic benefits comparable to those associated with hepatitis B vaccine and Haemophilus influenzae type b vaccine . More studies should be carried out on costs for care and immunization using standardized methodologies and locally obtained information.

J Pak Med Assoc, 2002 Feb, 52(2), 87 - 90
Determination of anti-microbial susceptibilities of Haemophilus influenzae, Streptococcus pneumoniae and Moraxella catarrhalis; Tabassum N et al.; OBJECTIVE: A retrospective study to determine the antibiotic resistance pattern seen in respiratory tract pathogens . MATERIALS AND METHODS: All sputum samples received during one year period (2000) were cultured by standard laboratory technique and antibiotic sensitivity was performed by Kirby Bauer disc method . RESULT: A total of 238 respiratory pathogens were isolated . All three isolates (Haemophilus influenzae, Streptococcus pnuemoniae and Moraxella catarrhalis) were highly resistant against Trimethoprim Sulfamethoxazole . Strep . pnuemoniae was not resistant to Penicillin . Rest of the antibiotics showed good response . CONCLUSION: Strep . pnuemoniae is still very sensitive to Penicillin and all three pathogens were resistant to Timethoprim Sulfamethoxazale.

Protein Expr Purif, 2002 Jun, 25(1), 189 - 94
Expression and purification of aspartate beta-semialdehyde dehydrogenase from infectious microorganisms; Moore RA et al.; l-Aspartate-beta-semialdehyde dehydrogenase (ASA DH) lies at the first branch point in the aspartate metabolic pathway that leads to the formation of the amino acids lysine, isoleucine, methionine, and threonine in most plants, bacteria, and fungi . Since the aspartate pathway is not found in humans, but is necessary for bacterial cell wall biosynthesis, the enzymes in this pathway are potential targets for the development of new antibiotics . The asd gene that encodes for ASA DH has been obtained from several infectious organisms and ligated into a pET expression vector . ASA DHs from Haemophilus influenza, Pseudomonas aeruginosa, and Vibrio cholerae were expressed as soluble proteins in Escherichia coli, while ASA DH from Helicobacter pylori was obtained primarily as inclusion bodies . The V . cholerae genome contains two asd genes . Both enzymes have been expressed and purified, and each displays significant ASA DH activity . The purification of highly active ASA DH from each of these organisms has been achieved for the first time, in greater than 95% purity and high overall yield . Kinetic parameters have been determined for each purified enzyme, and the values have been compared to those of E . coli ASA DH .

Antimicrob Agents Chemother, 2002 Jul, 46(7), 2208 - 18
Diversity of beta-lactam resistance-conferring amino acid substitutions in penicillin-binding protein 3 of Haemophilus influenzae; Dabernat H et al.; The sequences of the ftsI gene, encoding the transpeptidase domain of penicillin binding protein (PBP) 3A and/or PBP 3B, which are involved in septal peptidoglycan synthesis, were determined for 108 clinical strains of Haemophilus influenzae with reduced susceptibility to beta-lactam antibiotics with or without beta-lactamase production and were compared to those of the ampicillin-susceptible Rd strain and ampicillin-susceptible clinical isolates . The sequences have 18 different mutation patterns and were classified into two groups on the basis of amino acid substitutions deduced from the nucleotide sequences located between bp 960 and 1618 of the ftsI gene . In group I strains (n = 7), His-517 was substituted for Arg-517 . In group II strains (n = 101), Lys-526 was substituted for Asn-526 . In subgroup IIa (n = 5; H . influenzae ATCC 49247), the only observed substitution was Lys-526 for Asn-526; in subgroup IIb (n = 56), Val-502 was substituted for Ala-502 (n = 13), along with several other substitutions: Asn-350 for Asp-350 (n = 15), Asn-350 for Asp-350 and Glu-490 for Gly-490 (n = 14), and Asn-350 for Asp-350 and Ser-437 for Ala-437 (n = 5) . In subgroup IIc (n = 25), Thr-502 was substituted for Ala-502 . In subgroup IId, Val-449 was substituted for Ile-449 (n = 15) . The MICs of beta-lactam antibiotics for the 108 strains were to 8 to 16 times the MICs for susceptible strains . The strains, isolated from both adults and children, were analyzed for genetic relationship by pulsed-field gel electrophoresis and by determination of ftsI sequence phylogeny . Both analyses revealed the lack of clonality and the heterogeneity of the strains, but some clusters suggest the spread and/or persistence of a limited number of strains of the same pulsotype and pattern of amino acid substitutions . Reduced susceptibility to beta-lactam, brought about by mutations of the ftsI gene, is becoming a frequent phenomenon, affecting both strains that produce beta-lactamase and those that do not . The level of resistance remains low but opens the way to greater resistance in the future.

Antimicrob Agents Chemother, 2002 Jul, 46(7), 2194 - 9
Experimental acute otitis media due to nontypeable Haemophilus influenzae: comparison of high and low azithromycin doses with placebo; Babl FE et al.; Treatment of acute otitis media (AOM) with azithromycin results in apparent clinical success, but tympanocentesis performed 4 to 6 days after initiation of therapy in children with nontypeable Haemophilus influenzae (NTHI) recovered from initial middle ear cultures demonstrates persistence of infection in more than 50% of episodes . We sought to determine the effect of azithromycin at different doses on the density of middle ear infection due to NTHI to provide additional understanding of this dichotomy between clinical and microbiologic outcome measures in AOM . In a chinchilla model of experimental otitis media (EOM), animals treated with placebo were compared to animals receiving a single daily dose 30 or 120 mg of azithromycin per kg of body weight per day for 5 days . Microbiologic outcome was assessed by obtaining quantitative cultures from the middle ear during a 5-day course and for 1 week following therapy . Azithromycin concentrations were measured to ascertain whether a concentration-dependent effect was present . Azithromycin at 30 and 120 mg/kg/day demonstrated a dose-dependent effect on the quantitative assessment of middle ear infection due to NTHI . A 30-mg/kg dose of azithromycin daily resulted in levels in serum and areas under the serum concentration-time curve at 24 h comparable to published data obtained with children given azithromycin at 5 to 10 mg/kg in multiday regimens . Increased doses of azithromycin (120 mg/kg) achieved 2.5- to 4-fold-higher levels in serum and 3- to 6-fold-higher total levels and levels in extracellular middle ear fluid as well as more rapid reduction in bacterial density and a greater proportion of middle ears with complete sterilization than either placebo or the 30-mg/kg/day regimen.

Arq Neuropsiquiatr, 2002 Jun, 60(2-A), 281 - 4
{Clinical and laboratory aspects of acute bacterial meningitis in infants}; Lucena R et al.; OBJECTIVE: to describe clinical and laboratorial characteristics of acute bacterial meningitis in infants . METHOD: data from the prospective follow-up of infants with acute bacterial meningitis, admitted at the Hospital Couto Maia between March and December 1997, were analyzed with specific statistical software . RESULTS: acute bacterial meningitis was more prevalent in infants with ages varying from 6 months to 1 year . The most frequent etiologic agent was Haemophilus influenzae . The global lethality was 25.9% and among the survivors 39.3% left the hospital with some abnormality in the neurological exam compatible with the brain involvement . CONCLUSION: acute bacterial meningitis in infants is a high lethality disease that in the majority of cases can be prevented . We consider of great relevance the adoption of health prevention strategies in order to reduce the incidence of this disease.

J Biol Chem, 2002 Sep 6, 277(36), 33291 - 9 Epub 2002 Jun 14.
Crystal structure of Haemophilus influenzae NadR protein . A bifunctional enzyme endowed with NMN adenyltransferase and ribosylnicotinimide kinase activities; Singh SK et al.; Haemophilus influenzae NadR protein (hiNadR) has been shown to be a bifunctional enzyme possessing both NMN adenylytransferase (NMNAT; EC ) and ribosylnicotinamide kinase (RNK; EC ) activities . Its function is essential for the growth and survival of H . influenzae and thus may present a new highly specific anti-infectious drug target . We have solved the crystal structure of hiNadR complexed with NAD using the selenomethionine MAD phasing method . The structure reveals the presence of two distinct domains . The N-terminal domain that hosts the NMNAT activity is closely related to archaeal NMNAT, whereas the C-terminal domain, which has been experimentally demonstrated to possess ribosylnicotinamide kinase activity, is structurally similar to yeast thymidylate kinase and several other P-loop-containing kinases . There appears to be no cross-talk between the two active sites . The bound NAD at the active site of the NMNAT domain reveals several critical interactions between NAD and the protein . There is also a second non-active-site NAD molecule associated with the C-terminal RNK domain that adopts a highly folded conformation with the nicotinamide ring stacking over the adenine base . Whereas the RNK domain of the hiNadR structure presented here is the first structural characterization of a ribosylnicotinamide kinase from any organism, the NMNAT domain of hiNadR defines yet another member of the pyridine nucleotide adenylyltransferase family.

Infect Immun, 2002 Jul, 70(7), 3551 - 6
Identification of the lipooligosaccharide biosynthesis gene lic2B as a putative virulence factor in strains of nontypeable Haemophilus influenzae that cause otitis media; Pettigrew MM et al.; Nontypeable (NT) strains of Haemophilus influenzae are an important cause of acute otitis media (OM) . The pathogenic process by which NT H . influenzae strains cause OM is poorly understood . In order to identify specific virulence factors important for OM pathogenesis, genomic subtraction of the NT H . influenzae middle ear isolate G622 against H . influenzae strain Rd was conducted and the resulting subtraction products were used to screen a panel of H . influenzae isolates . Subtraction identified 36 PCR fragments unique to strain G622, which were used in a preliminary screen of 48 middle ear isolates and 46 nasopharyngeal and throat isolates to identify genes found more frequently among middle ear isolates . These experiments identified a PCR fragment with high homology to the lipooligosaccharide biosynthesis gene lic2B (originally identified in an H . influenzae type b strain) among 52% of the middle ear isolates and 9% of nasopharyngeal and throat isolates . The lic2B gene cloned from NT H . influenzae strain G622 was 99% identical at the amino acid level to that of the H . influenzae type b strain RM7004 . The lic2B gene was used to screen a larger panel of H . influenzae isolates including the original 48 middle ear isolates, 40 invasive type b isolates, 90 NT H . influenzae throat isolates from children attending day care, and 32 NT H . influenzae nasopharyngeal clinical isolates . The lic2B gene was found 3.7 times more frequently among middle ear isolates than in throat isolates from children attending day care . These data suggest that a specific NT H . influenzae gene is associated with OM.

Scand J Infect Dis, 2002, 34(4), 289 - 98
The changing epidemiology of bacterial meningitis and invasive non-meningitic bacterial disease in scotland during the period 1983-99; Kyaw MH et al.; We reviewed population-based laboratory reports of invasive meningococcal, pneumococcal, Haemophilus influenzae, Group B Streptococcus (GBS) and Listeria monocytogenes isolates in order to examine the changing epidemiology of meningitis and invasive non-meningitic disease (INMD) caused by these 5 pathogens in the 2 periods before (1983-91) and after (1992-99) routine use of H . influenzae type B conjugate vaccine (Hib) in Scotland . Neissieria meningitidis was the most common cause of meningitis, accounting for 39.2% of cases of meningitis in 1983-91 and 47% of cases in 1992-99, followed by H . influenzae (31%), Streptococcus pneumoniae (22.4%), GBS (3.9%) and L . monocytogenes (3.5%) in 1983-91 and S . pneumoniae (36.3%), H . influenzae (7.8%), GBS (6.1%) and L . monocytogenes (2.8%) in 1992-99 . The important epidemiological features of meningitis and INMD caused by these 5 pathogens between 1983-91 and 1992-99 include: 1 . The incidence of bacterial meningitis due to S . pneumoniae and GBS was stable; 2 . S . pneumoniae was the predominant cause of INMD in both periods; 3 . The incidences of INMD caused by N . meningitidis, GBS and S . pneumoniae increased, by 27%, 55% and 56%, respectively; 4 . Decreases in the incidences of bacterial meningitis (by 50%) and INMD (by 50%) due to L . monocytogenes were detected; and 5 . There were dramatic reductions in the proportions of bacterial meningitis (by 92%) and INMD (by 56%) due to H . influenzae in vaccinated and non-vaccinated individuals . Continued surveillance is necessary to monitor the disease trend, population at risk, serotype distribution and antimicrobial susceptibility in order to implement appropriate public health interventions against invasive bacterial disease.

No To Shinkei, 2002 May, 54(5), 431 - 3
{A case of Fisher's syndrome after Haemophilus influenzae infection}; Ogawa M et al.; We report a case of Fisher's syndrome with serological evidence of antecedent Haemophilus influenzae infection . A 66-year-old woman developed unsteady gait and multiple cranial nerve palsies after upper respiratory infection . Serum anti-GQ 1 b and anti-GT 1 a IgG antibodies were positive . In the acute phase of the illness, her serum had high titers of IgM, IgG and IgA anti-H . influenzae antibodies, which significantly decreased during the clinical course . Further study is needed to clarify the clinical and immunological features of Fisher's syndrome after H . influenzae infection.

J Bacteriol, 2002 Jul, 184(13), 3442 - 9
Natural transformation and DNA uptake signal sequences in Actinobacillus actinomycetemcomitans; Wang Y et al.; Actinobacillus actinomycetemcomitans is a member of the family Pasteurellaceae and a major causative agent of periodontitis . While several genera from this family are known to be competent for transformation, A . actinomycetemcomitans has yet to be fully characterized . Here we show that the competence of A . actinomycetemcomitans is remarkably similar to that of Haemophilus influenzae . In addition to having a similar frequency of transformation as H . influenzae, A . actinomycetemcomitans competence could also be induced at least 100-fold by cyclic AMP, suggesting that, as in H . influenzae, at least some competence genes are regulated by catabolite repression . Even more intriguing was the discovery of a putative A . actinomycetemcomitans DNA uptake signal sequence (USS) virtually identical to the USS of H . influenzae . Moreover, we provide evidence that this sequence functions in the same capacity as that from H . influenzae; the sequence appears to be required and sufficient for DNA uptake in a variety of assays . Finally, we have taken advantage of this system to develop a simple, highly efficient competence-based method for generating site-directed mutations in the wild-type fimbriated A . actinomycetemcomitans.

J Am Soc Mass Spectrom, 2002 Jun, 13(6), 724 - 34
Characterization of lipooligosaccharides from Haemophilus ducreyi containing polylactosamine repeats; Schilling B et al.; Haemophilus ducreyi, a gram-negative human mucosal pathogen, is one of the principal causes of genital ulcer disease . The lipooligosaccharides (LOS) of these bacteria are considered to be a major virulence factor and have been implicated in the adherence and invasion of H . ducreyi to several human cell types . An isogenic heptosyltransferase-III knockout strain (waaQ) was recently constructed from H . ducreyi 35000 wild-type strain and immunochemical and molecular weight data of the isolated LOS suggested the presence of poly-N-acetyllactosamine (LacNAc) (Filiatrault et al., Infect . Immun . 2000, 68, 3352-3361) . In this present study, the structures of these novel LOS-glycoforms were characterized by matrix-assisted laser desorption/ionization (MALDI) and electrospray ionization (ESI) mass spectrometry in combination with exoglycosidase digestion . Detailed structural information was obtained for the oligosaccharide (OS) portions of these LOS showing between one to five linear LacNAc repeats on the non-reducing terminus of the main oligosaccharide branch . When grown on solid media, the organism produced LacNAc repeats that were further modified by the addition of sialic acid . Enzymatic digestion with beta-galactosidase, beta-N-acetylhexosaminidase, and neuraminidase type VI-A yielded truncated glycoforms consistent with a polyLacNAc structure capped at various end points with sialic acid . ESI-MS/MS mass spectrometry on a quadrupole time-of-flight instrument was particularly effective in obtaining detailed structural information on the least abundant, high-mass glycoforms . Although LOS containing terminal di-LacNAc have been reported, this is the first time to our knowledge that a linear polyLacNAc structure has been characterized in bacteria.

J Mol Biol, 2002 May 3, 318(3), 779 - 85
Crystal structure of HslUV complexed with a vinyl sulfone inhibitor: corroboration of a proposed mechanism of allosteric activation of HslV by HslU; Sousa MC et al.; On the basis of the structure of a HslUV complex, a mechanism of allosteric activation of the HslV protease, wherein binding of the HslU chaperone propagates a conformational change to the active site cleft of the protease, has been proposed . Here, the 3.1 A X-ray crystallographic structure of Haemophilus influenzae HslUV complexed with a vinyl sulfone inhibitor is described . The inhibitor, which reacts to form a covalent linkage to Thr1 of HslV, binds in an "antiparallel beta" manner, with hydrogen-bond interactions between the peptide backbone of the protease and that of the inhibitor, and with two leucinyl side chains of the inhibitor binding in the S1 and S3 specificity pockets of the protease . Comparison of the structure of the HslUV-inhibitor complex with that of HslV without inhibitor and in the absence of HslU reveals that backbone interactions would correctly position a substrate for cleavage in the HslUV complex, but not in the HslV protease alone, corroborating the proposed mechanism of allosteric activation . This activation mechanism differs from that of the eukaryotic proteasome, for which binding of activators opens a gated channel that controls access of substrates to the protease, but does not perturb the active site environment . (c) 2002 Elsevier Science Ltd.

J Theor Biol, 2002 Mar 7, 215(1), 67 - 82
The genome-scale metabolic extreme pathway structure in Haemophilus influenzae shows significant network redundancy; Papin JA et al.; Genome-scale metabolic networks can be characterized by a set of systemically independent and unique extreme pathways . These extreme pathways span a convex, high-dimensional space that circumscribes all potential steady-state flux distributions achievable by the defined metabolic network . Genome-scale extreme pathways associated with the production of non-essential amino acids in Haemophilus influenzae were computed . They offer valuable insight into the functioning of its metabolic network . Three key results were obtained . First, there were multiple internal flux maps corresponding to externally indistinguishable states . It was shown that there was an average of 37 internal states per unique exchange flux vector in H . influenzae when the network was used to produce a single amino acid while allowing carbon dioxide and acetate as carbon sinks . With the inclusion of succinate as an additional output, this ratio increased to 52, a 40% increase . Second, an analysis of the carbon fates illustrated that the extreme pathways were non-uniformly distributed across the carbon fate spectrum . In the detailed case study, 45% of the distinct carbon fate values associated with lysine production represented 85% of the extreme pathways . Third, this distribution fell between distinct systemic constraints . For lysine production, the carbon fate values that represented 85% of the pathways described above corresponded to only 2 distinct ratios of 1:1 and 4:1 between carbon dioxide and acetate . The present study analysed single outputs from one organism, and provides a start to genome-scale extreme pathways studies . These emergent system-level characterizations show the significance of metabolic extreme pathway analysis at the genome-scale .

J Mol Biol, 2002 Apr 26, 318(2), 373 - 86
Functional studies of potential intrastrand triplex elements in the Escherichia coli genome; Hoyne PR et al.; We previously used a pattern recognition program for nucleic acids to detect sequences with the potential to form intrastrand triplexes . Potential intrastrand triplex (PIT) element families were found in Escherichia coli, Synechocystis sp . and Haemophilus influenza . We were particularly intrigued with the family found in E . coli, which contained 25 dispersed copies of a particular PIT sequence corresponding to the purine triplex motif . E . coli PIT elements appear to occur exclusively in non-coding regions . We now report biochemical experiments testing the interaction of E . coli PIT elements with polymerases and single-stranded DNA-binding protein (SSB) . The elements were also tested in genetic experiments as promoters, transcription terminators, or replication pause sites in E . coli . We show that PIT elements display provocative characteristics in certain biochemical assays . When appropriately oriented, the elements block elongation by Taq DNA polymerase at 72 degrees C, but not elongation by T7 DNA polymerase at 37 degrees C . The G-rich strand of the E . coli PIT sequence folds into a form with reduced affinity for SSB . On the other hand, in vivo studies did not detect replication delays for conjugal transfer of episomes containing PIT elements . These sequences were shown not to act as promoters, but the presence of PIT elements in RNA leaders upstream of a coding region could strongly influence expression of the downstream gene . These effects were shown to be post-transcriptional and were solely dependent on the Watson-Crick stem-loop structure within the PIT element . Thus, although PIT element DNA displays unusual biochemical properties, it remains unknown how these elements arose, and why they persist in the E . coli genome . (c) 2002 Elsevier Science Ltd.

Ned Tijdschr Geneeskd, 2002 May 18, 146(20), 938 - 40
{Universal vaccination against group-C meningococci and pneumococci; summary of the advice from the Health Counsil of the Netherlands}; Ruitenberg EJ et al.; The Health Council of the Netherlands (Gezondheidsraad) assessed the vaccination of infants against both group-C meningococci and pneumococci in terms of general criteria and basic principles for inclusion in the national vaccination programme . Vaccination against meningococci C in the Netherlands is expected to prevent about 300 cases of meningococcal disease (meningitis or sepsis), 22 deaths and 12 cases of severe lasting problems (neurological problems or amputations) per year . Vaccination against pneumococci may prevent about 100 cases of meningitis or sepsis, 3200 cases of pneumonia, 36,000 cases of acute otitis media, 11 deaths, 11 cases of severe permanent damage (neurological problems, deafness) per year . The Health Council advised implementing vaccination against group-C meningococci as soon as possible, through 2 injections at the ages of 5 and 6 months or through 1 injection shortly after the child's first birthday, and to carry out a catch-up programme for all children and adolescents up to and including 18 years of age . The council also advised starting a vaccination programme against pneumococci, at ages 2, 3 and 4 months, as soon as the current vaccinations against diphtheria, tetanus, pertussis and polio and against Haemophilus influenzae type b are combined into 1 injection (in 2002 or 2003) . In view of the concentration of pneumococci disease in the first years of life, a catch-up programme is not indicated in this case . The Health Council emphasised the importance of microbiological and clinical monitoring of potential adverse effects and of public education programmes . The cost of vaccination against group-C meningococci is comparable to that of other accepted programmes for primary prevention . Compared to other programmes and at the current vaccine price, the cost of vaccination against pneumococci is high.

Bioinformatics, 2002 May, 18(5), 679 - 88
Sequence complexity profiles of prokaryotic genomic sequences: a fast algorithm for calculating linguistic complexity; Troyanskaya OG et al.; MOTIVATION: One of the major features of genomic DNA sequences, distinguishing them from texts in most spoken or artificial languages, is their high repetitiveness . Variation in the repetitiveness of genomic texts reflects the presence and density of different biologically important messages . Thus, deviation from an expected number of repeats in both directions indicates a possible presence of a biological signal . Linguistic complexity corresponds to repetitiveness of a genomic text, and potential regulatory sites may be discovered through construction of typical patterns of complexity distribution . RESULTS: We developed software for fast calculation of linguistic sequence complexity of DNA sequences . Our program utilizes suffix trees to compute the number of subwords present in genomic sequences, thereby allowing calculation of linguistic complexity in time linear in genome size . The measure of linguistic complexity was applied to the complete genome of Haemophilus influenzae . Maps of complexity along the entire genome were obtained using sliding windows of 40, 100, and 2000 nucleotides . This approach provided an efficient way to detect simple sequence repeats in this genome . In addition, local profiles of complexity distribution around the starts of translation were constructed for 21 complete prokaryotic genomes . We hypothesize that complexity profiles correspond to evolutionary relationships between organisms . We found principal differences in profiles of the GC-rich and other (non-GC-rich) genomes . We also found characteristic differences in profiles of AT genomes, which probably reflect individual species variations in translational regulation . AVAILABILITY: The program is available upon request from Alexander Bolshoy or at http://csweb.haifa.ac.il/library/#complex.

J Nutr Biochem, 1995 Jul, 6(7), 362 - 366
Antimicrobial activity of lipids added to human milk, infant formula, and bovine milk; Isaacs CE et al.; Lipids previously shown to have antiviral and antibacterial activity in buffers were added to human milk, bovine milk, and infant formulas to determine whether increased protection from infection could be provided to infants as part of their diet . Fatty acids and monoglycerides with chain lengths varying from 8 to 12 carbons were found to be more strongly antiviral and antibacterial when added to milk and formula than long chain monoglycerides . Lipids added to milk and formula inactivated a number of pathogens including respiratory syncytial virus (RSV), herpes simplex virus type 1 (HSV-1), Haemophilus influenzae, and Group B streptococcus . The results presented in this study suggest that increased protection from infection may be provided to infants at mucosal surfaces, prior to the digestion of milk and formula triglycerides, by the addition of antimicrobial medium chain monoglycerides to an infant's diet.

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