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