Clin Infect Dis, 2004 Jan 15, 38(2), 234 - 42 Epub 2003 Dec 19. Association of clinical signs and symptoms with bacterial findings in acute otitis media; Palmu AA et al.; In acute otitis media (AOM), a means of prediction of the bacterial pathogen based on symptoms and signs would be valuable in selecting appropriate antimicrobial treatment . Children in the control arm (n=831) in the Finnish Otitis Media Vaccine Trial were prospectively observed in a study clinic setting from the age of 2 to 24 months . In patients with AOM, myringotomy with aspiration was performed, and middle ear fluid samples were cultured for bacterial pathogens . Symptoms and signs of respiratory infections were thoroughly recorded . Streptococcus pneumoniae, Moraxella catarrhalis, and Haemophilus influenzae were the most common bacterial pathogens . Pneumococcal AOM was associated with more-severe AOM characterized by fever and earache . AOM due to H . influenzae was associated with eye symptoms and findings . Accurate prediction of a bacterial cause of infection based on symptoms and signs of AOM was not possible, but a specific cause was predicted in some situations, with a high probability of applicability to clinical practice. Microbiol Immunol, 2003, 47(12), 937 - 43 Molecular cloning and characterization of the HmrM multidrug efflux pump from Haemophilus influenzae Rd; Xu XJ et al.; We cloned a gene responsible for norfloxacin resistance from the chromosomal DNA of Haemophilus influenzae Rd, and designated the gene as hmrM . HmrM showed sequence similarity with NorM of Vibrio parahaemolyticus and YdhE of Escherichia coli and others that belong to the MATE family multidrug efflux pumps . The recombinant plasmid carrying the hmrM gene conferred elevated resistance not only to norfloxacin but also to acriflavine, 4 ', 6-diamidino-2-phenylindole, doxorubicin, ethidium bromide, tetraphenylphosphonium chloride, Hoechst 33342, daunomycin, berberine, and sodium deoxycholate in Escherichia coli KAM32, a drug-hypersensitive strain . We observed an Na+-dependent efflux of ethidium and an ethidium-induced efflux of Na+ in E . coli KAM32 cells harboring the plasmid carrying the hmrM gene . These results indicate that HmrM is an Na+/drug antiporter-type multidrug efflux pump . A difference in substrate preference was observed between HmrM, NorM, and YdhE. Antimicrob Agents Chemother, 2004 Jan, 48(1), 203 - 8 In vitro pharmacodynamic activities of ABT-492, a novel quinolone, compared to those of levofloxacin against Streptococcus pneumoniae, Haemophilus influenzae, and Moraxella catarrhalis; Gunderson SM et al.; ABT-492 is a novel quinolone with potent activity against gram-positive, gram-negative, and atypical pathogens, making this compound an ideal candidate for the treatment of community-acquired pneumonia . We therefore compared the in vitro pharmacodynamic activity of ABT-492 to that of levofloxacin, an antibiotic commonly used for the treatment of pneumonia, through MIC determination and time-kill kinetic analysis . ABT-492 demonstrated potent activity against penicillin-sensitive, penicillin-resistant, and levofloxacin-resistant Streptococcus pneumoniae strains (MICs ranging from 0.0078 to 0.125 micro g/ml); beta-lactamase-positive and beta-lactamase-negative Haemophilus influenzae strains (MICs ranging from 0.000313 to 0.00125 micro g/ml); and beta-lactamase-positive and beta-lactamase-negative Moraxella catarrhalis strains (MICs ranging from 0.001 to 0.0025 micro g/ml), with MICs being much lower than those of levofloxacin . Both ABT-492 and levofloxacin demonstrated concentration-dependent bactericidal activities in time-kill kinetics studies at four and eight times the MIC with 10 of 12 bacterial isolates exposed to ABT-492 and with 12 of 12 bacterial isolates exposed to levofloxacin . Sigmoidal maximal-effect models support concentration-dependent bactericidal activity . The model predicts that 50% of maximal activity can be achieved with concentrations ranging from one to two times the MIC for both ABT-492 and levofloxacin and that near-maximal activity (90% effective concentration) can be achieved at concentrations ranging from two to five times the MIC for ABT-492 and one to six times the MIC for levofloxacin. Lancet Neurol, 2004 Jan, 3(1), 54 - 62 Adjunctive dexamethasone treatment in acute bacterial meningitis; Chaudhuri A; The initiation of antibiotic treatment on suspicion of bacterial meningitis is important, but it is not enough to improve the prognosis for patients, especially those with pneumococcal meningitis . The mortality and morbidity of pneumococcal meningitis are still devastating, and results of a recent randomised trial have shown evidence in favour of dexamethasone treatment given before or with the first antibiotic dose . Adjuvant dexamethasone is unequivocally recommended in children and adults with haemophilus meningitis or pneumococcal meningitis . The benefit of adjunctive dexamethasone is likely to be greatest in patients who are otherwise healthy and present early with acute bacterial meningitis . Dexamethasone is not currently recommended for the treatment of gram-negative bacillary meningitis and neonatal meningitis . Dexamethasone, before or with the first dose of antibiotic, is likely to be one of the most significant practice changes that will benefit many adults and children with common types of acute bacterial meningitis and has been of proven value in the developed world. Ann Allergy Asthma Immunol, 2003 Nov, 91(5), 501 - 5 Severe T- and B-cell immune deficiency associated with malignant thymoma; Yel L et al.; BACKGROUND: Immunodeficiency with thymoma syndrome is a rare disorder that generally occurs after the fourth decade of life . Typically, thymic tumors are benign, and gradually developing immunodeficiency consists of hypogammaglobulinemia with low B-cell counts and an inverted CD4+/CD8+ T-cell ratio due to excessive CD8+ T cells . OBJECTIVE: To report the case of a 32-year-old, white man with an invasive malignant thymoma and profound combined T- and B-cell immunodeficiency associated with a normal CD4+/CD8+ T-cell ratio, absence of circulating B cells, and infection with an unusual organism . METHODS: The patient presented with a superior vena cava syndrome caused by a malignant thymoma . During chemotherapy and radiotherapy, he experienced recurrent episodes of pulmonary infections due to Haemophilus influenza and Serratia marcescens and persistent oral thrush . He was diagnosed as having thymoma and underwent immunological evaluation . RESULTS: Sixteen months after the diagnosis of thymoma, the immunological evaluation revealed profound lymphopenia, eosinopenia, very low counts of both CD4+ T cells and CD8+ T cells, and a normal CD4+/CD8+ ratio with negative delayed-type hypersensitivity skin test results . Hypogammaglobulinemia and absent specific antibody responses were associated with a lack of peripheral blood CD19+ B cells . Despite treatment with intravenous immunoglobulin, the patient died of respiratory insufficiency and sepsis secondary to a chronic pulmonary infection . CONCLUSIONS: Malignant thymoma may be associated with severe combined immunodeficiency . A normal CD4+/CD8+ ratio and the absence of peripheral B cells suggest a bone marrow defect that affects both T and B cells in the pathogenesis of this syndrome . Comprehensive immunological evaluation should be performed when thymoma is diagnosed to initiate an early and effective treatment to prevent life-threatening complications. Ann Allergy Asthma Immunol, 2003 Nov, 91(5), 496 - 500 Coexistent yellow nail syndrome and selective antibody deficiency; Bokszczanin A et al.; BACKGROUND: Yellow nail syndrome (YNS) is a rare, often underdiagnosed condition of unknown origin . The clinical features of the syndrome include yellow nails, chronic sinusitis, bronchiectasis, pleural effusion, and lymphoedema . Despite the frequent occurrence of upper and lower respiratory tract infections in patients with YNS, comprehensive analysis of their humoral immunity has not been previously reported . OBJECTIVE: To present the case of a patient with YNS whose recurrent upper and lower respiratory tract infections may have been caused by an underlying selective antibody deficiency that manifests as impaired IgG antibody response to polysaccharide antigens . METHODS: The patient underwent cultures of purulent sputum for Streptococcus pneumoniae and Haemophilus influenzae, bronchial washings for H . influenzae, and nail scrapings for fungi . Her serum levels of IgG, IgA, IgM, IgG subclasses, and serum titers of IgG antitetanus toxoid, anti-H . influenzae, and anti-S . pneumoniae antibodies were measured . RESULTS: Cultures of purulent sputum were positive on multiple occasions for S . pneumoniae and H . influenzae and bronchial washings were positive for H . influenzae . Nail scrapings were consistently negative for fungi . She had no reductions in serum levels of IgG, IgA, IgM, or IgG subclasses and had normal serum titers of IgG antitetanus toxoid antibodies . However, she demonstrated impaired IgG antibody responses following immunization with Pneumovax and an H . influenza B vaccine . CONCLUSIONS: This case report describes the first comprehensive analysis of humoral immune function in a patient with YNS . The finding of a selective antibody deficiency in our patient provides a potential explanation for the occurrence of respiratory infections in YNS . Accordingly, we recommend that functional antibody determinations and quantitative serum immunoglobulins be evaluated in patients diagnosed as having this unusual, enigmatic syndrome. Jpn J Antibiot, 2003 Oct, 56(5), 365 - 95 {Susceptibilities of bacteria isolated from patients with lower respiratory infectious diseases to antibiotics (2001)}; Shimada K et al.; From October 2001 to September 2002, we collected the specimen from 370 patients with lower respiratory tract infections in 16 institutions in Japan, and investigated the susceptibilities of the isolated bacteria to various antibacterial agents and antibiotics and patients' characteristics . Of 458 strains that were isolated from specimen (mainly from sputum) and assumed to be bacteria causing in inflammation, 456 strains were investigated . The breakdown of the isolated bacteria were: Staphylococcus aureus 69, Streptococcus pneumoniae 72, Haemophilus influenzae 85, Pseudomonas aeruginosa (non-mucoid) 44, P . aeruginosa (mucoid) 13, Klebsiella pneumoniae 32, Moraxella subgenus Branhamella catarrhalis 32, and others . Of 69 S . aureus strains, those with 4 micrograms/mL or more of MIC of oxacillin (methicillin-resistant S . aureus: MRSA) occupied 43.5% . Vancomycin and arbekacin showed the most potent activities against MRSA as observed in 2000 . The frequency of S . pneumoniae exhibiting low sensitivity to penicillin (penicillin-intermediate S . pneumoniae: PISP + penicillin-resistant S . pneumoniae: PRSP) was 59.7% and both rates of PISP and PRSP were the highest after 1992 . Carbapenems had strong activities against S . pneumoniae . Especially, panipenem and imipenem inhibited the growth of all 72 strains at 0.125 and 0.5 microgram/mL, respectively . Generally, all drugs had strong activities against H . influenzae with MIC90s of 16 micrograms/mL or less . The drug that had the strongest activity against H . influenzae was levofloxacin, which inhibited the growth of 80 of the 85 strains at 0.063 microgram/mL . Against P . aeruginosa mucoid strain, meropenem had a strong activity with MIC90 of 0.5 microgram/mL while, against non-mucoid strain, tobramycin had a strong activity with MIC90 of 2 micrograms/mL . K . pneumoniae showed good susceptibilities to all drugs except ampicillin and minocycline, and the MIC90s were 4 micrograms/mL or less . Particularly, cefmenoxime, cefpirome, and imipenem had the strongest activity (MIC90: 0.125 microgram/mL), and cefozopran had a strong activity, inhibiting the growth of all strains at 0.25 microgram/mL . Also, all drugs generally had strong activities against M . (B.) catarrhalis . MIC90s of all drugs were 4 micrograms/mL or less . The drug that had the strongest activity was minocycline and levofloxacin inhibiting all 32 strains at 0.063 microgram/mL . Most of the patients with respiratory infection were aged 70 years or older, accounting for approximately a half of the total (40.5%) . As for the incidence by the diseases, bacterial pneumonia and chronic bronchitis were the highest, being noted in 39.2% and 37.3% of all the patients, respectively . The bacteria frequently isolated from the patients with bacterial pneumonia were S . aureus (19.3%) and S . pneumoniae (19.9%) . In contrast, H . influenzae (22.0%) were frequently isolated from the patients with chronic bronchitis . Before the drug administration, the bacteria frequently isolated from the patients were S . pneumoniae (20.8%) and H . influenzae (21.5%) . S . pneumoniae and H . influenzae decreased after the initiation of drug administration while S . aureus increased . The isolation frequency of P . aeruginosa was higher after than before the initiation of drug administration . The bacteria were frequently isolated from the patients who had already treated with cephems were S . aureus and P . aeruginosa . From the patients who had already treated with macrolides, S . pneumoniae was the most frequently isolated while S . aureus was the most frequently isolated from the patients pre-treated with quinolones. Clin Infect Dis, 2003 Dec 15, 37(12), 1593 - 9 Epub 2003 Nov 18. High incidence of Haemophilus influenzae type b infection in children in Pacific island countries; Russell FM et al.; The Haemophilus influenzae type b (Hib) disease burden among children <5 years old in 4 Pacific island countries (PICs) was estimated . The incidence of confirmed Hib meningitis was calculated using the numbers of culture-confirmed isolates . In addition, the World Health Organization (WHO) Hib Rapid Assessment Tool (RAT) was used to estimate the true Hib meningitis incidence and the number of Hib meningitis and pneumonia cases, as well as the number of deaths due to Hib meningitis and pneumonia . The Hib meningitis annual incidence in 3 PICs was 70-84 cases per 100,000 children <5 years old . For PICs, the RAT is likely to overestimate the Hib pneumonia burden, as it assumes a 5 : 1 ratio of Hib pneumonia to Hib meningitis . The true ratio is likely to be 1 : 1 . The high Hib disease burden and the relative cost-effectiveness of Hib vaccine make the introduction of Hib vaccine a good investment for PICs, costing US1000 dollars-US10,000 dollars for each death prevented--a number that ignores savings from reductions in the cost of treatment. Braz J Med Biol Res, 2004 Jan, 37(1), 151 - 8 Epub 2003 Dec 18. Reimmunization after bone marrow transplantation--current recommendations and perspectives; Machado CM; Autologous and allogeneic bone marrow transplantation (BMT) recipients lose immune memory of exposure to infectious agents and vaccines accumulated through a lifetime and therefore need to be revaccinated . Diphtheria toxoid, tetanus toxoid, pertussis vaccine (children <7 years old), Haemophilus influenzae type b conjugate, 23-valent pneumococcal polysaccharide, inactivated influenza vaccine, inactivated polio vaccine and live-attenuated measles-mumps-rubella vaccine are the currently recommended vaccines to be included in a vaccination program after BMT . For most of them, the best time to vaccinate, the number of vaccine doses and/or the duration of immunity after vaccination have not been established . Vaccination protocols vary greatly among BMT centers, suggesting that the lack of sufficient data has not permitted the formulation of reliable recommendations . The use of other vaccines and the perspectives for different vaccination protocols are analyzed in this review. J Pediatr (Rio J), 1995 Mar-Apr, 71(2), 62 - 6 {Vaccines against meningococcal disease}; Costa WA; The meningococcal disease has been a source of preoccupation all over the world . Epidemics have been registered periodically in developed or developing countries . The most frequent meningococci are those concerned with serogroups A, B and C.Researches to develop effective vaccines against the disease have been taking place since the 40's . Presently, only vaccines against the meningococci from the serogroups A, C, Y and W-135 are available . These vaccines have important limitations both due to the age range that they protect and the period of time that the protection lasts . They are not routinely used in vaccination programs and are indicated only in risky situations . This demands a strict epidemiological surveillance of the disease . There are no vaccines against the serogroup B meningococci with recognized effectiveness, although, in the last decades, many have been tested . There are perspectives of important advances in this area, mainly with the development of conjugated vaccines, like the Haemophilus influenzae type B vaccine . Until the present, the chemoprophylaxis of the intimate communicants of a case is the best way to avoid secondary cases. J Pediatr (Rio J), 1994 Jul-Aug, 70(4), 197 - 205 {Haemophilus influenzae type b infections and its prevention by vaccines}; Martins RM; Haemophilus influenzae type b (Hib) infections and its prevention by vaccines are reviewed . Its prevalence is underestimated, due to technical pitfalls in the laboratory and to the difficulties of diagnosing respiratory infections, chiefly pneumonia . Taking into account all infections (respiratory, meningitis and others), Hib is probably the most important pathogen, compared to S . pneumoniae and N . meningitidis . The incidence of Hib meningitis in Brazil is presented and risk factors are discussed, as well as the preventive alternatives . The different Hib vaccines are analyzed and schedules of immunization with two of them (PRP-T and HbOC) are presented . Possible eradication of Hib diseases is discussed. Pediatr Infect Dis J, 2003 Dec, 22(12), 1063 - 8 Microbiology of otitis media in Costa Rican children, 1999 through 2001; Arguedas A et al.; BACKGROUND: Because of the increasing number of resistant middle ear pathogens and the impact of the new conjugate Streptococcus pneumoniae vaccine, an active surveillance of the microbiology and susceptibility pattern of middle ear pathogens is required . OBJECTIVE: To study the microbiology and susceptibility pattern of middle ear pathogens obtained from Costa Rican children with acute otitis media (AOM), recurrent otitis media (ROM) and therapeutic failure otitis media (FOM) . METHODS: Between 1999 and 2001 middle ear fluid (MEF) was collected from 276 Costa Rican patients . S . pneumoniae serotyping and pulsed field gel electrophoresis analysis was done on available strains . RESULTS: Among the total study population, 102 were AOM patients, 98 were ROM patients and 76 were FOM patients . Overall S . pneumoniae (88 strains) was the most common pathogen isolated followed by Haemophilus influenzae (41 strains) and Streptococcus pyogenes (10 strains) . H . influenzae was the most common agent in FOM patients (P = 0.015) . Beta-lactamase production was observed in 3 of 41 (7%) H . influenzae strains and 3 of 3 (100%) Moraxella catarrhalis strains . Penicillin-nonsusceptible S . pneumoniae strains were more common in FOM (64%) and ROM (63%) patients than in AOM (42%) patients (P = 0.05) . S . pneumoniae serotype 19F was the most prevalent serotype, mainly within one distinct clone . CONCLUSIONS: Overall S . pneumoniae serotype 19F was the most common isolate from the middle ear fluid of Costa Rican children . Beta-lactamase-negative H . influenzae was the most prevalent in the subpopulation of patients with FOM . S . pyogenes was the third most common isolate and M . catarrhalis was uncommon. Int J Pediatr Otorhinolaryngol, 2004 Jan, 68(1), 101 - 10 Eustachian tube gland tissue changes are related to bacterial species in acute otitis media; Caye-Thomasen P et al.; BACKGROUND AND OBJECTIVE: Prior investigations have shown that the number of mucus producing goblet cells in the middle ear and Eustachian tube (ET) mucosa is highly increased during and up to at least six months after experimental acute otitis media (AOM) caused by Streptococcus pneumoniae (SP) . Further, the volume of the mucus producing paratubal gland components is increased up to 3 months after the acute infection . These changes may in conjunction with a deteriorated ET function predispose a subsequent development of secretory otitis media . The present investigation compares changes in goblet cell density and gland structures of the ET during and after AOM caused by various bacteria typically encountered in this disease, with emphasis on potential differences due to bacterial species . METHODS: Rat models of AOM caused by SP, non-typeable or type b Haemophilus influenzae (NTHI/HIB) or Moraxella catarrhalis (MC) were studied longitudinally up to 6 months after bacterial challenge . The ET was dissected and decalcified, paraffin embedded and serially sectioned, followed by PAS/alcian blue staining . The goblet cell density and the paratubal gland composition and volume were determined morphometrically in every 20th section, using a light microscope . RESULTS: Regardless of bacterial species, the ET goblet cell density was increased from day 8 and peaked day 16, followed by some degree of normalisation, although not reaching normal numbers within the 6 month period, except for MC . The highest increase was seen in AOM caused by the non-typeable Haemophilus strain, followed by HIB, SP and MC . Except with MC, pathological intra-epithelial glands formed and goblet cells were found in mucosal areas normally devoid of these . In all species but MC, the volume of the paratubal glands progressed to peak 16 days post-inoculation, followed by a gradual normalisation . The volume was still increased 3 months after the acute infection, but completely normalised after 6 months . The increase was primarily due to hypertrophy of the mucous gland components and highest in AOM caused by the Haemophilus species, followed by SP . CONCLUSION: The Eustachian tube goblet cell density is increased during and up to at least six months after AOM regardless of bacterial species, except when employing MC, by which the density was increased for a few weeks only . Except in AOM caused by MC, the volume of the ET glands increases during and up to at least 3 months after infection, primarily due to hypertrophy of the mucous gland components . The non-typeable Haemophilus strain induced the highest increase of both goblet cell density and mucous gland volume . The increased secretory capacity of the ET following AOM may by excessive mucus secretion contribute to the deteriorated ET function found after AOM and thus predispose, sustain or aggravate middle ear disease. Int J Pediatr Otorhinolaryngol, 2004 Jan, 68(1), 51 - 6 Alloiococcus otitidis in acute otitis media; Leskinen K et al.; OBJECTIVE: The bacterium Alloiococcus otitidis has been found to be associated with otitis media with effusion (OME) . When the culture method is used, its detection rate is low, whereas applying the polymerase chain reaction (PCR) yields significantly higher frequencies . This study was carried out to investigate the incidence of A . otitidis in children with acute otitis media (AOM) . METHODS: Multiplex PCR was used to detect A . otitidis together with Haemophilus influenzae, Moraxella catarrhalis, and Streptococcus pneumoniae in the middle ear effusions (MEEs) of 118 children with AOM . The clinical outcome of AOM and the bacterial findings of MEEs were compared . RESULTS: A . otitidis was detected in 25% (30 of 118) of the tested MEE samples . Children over 2 years of age had significantly more often A . otitidis-positive MEEs (37%; 22 of 59) than younger children (14%; 8 of 59) (chi-square test, P<0.01) . There were no significant differences in the duration, clinical failures (after antibiotic treatment), or number of recurrences of AOM between the A . otitidis-positive and A . otitidis-negative children . CONCLUSIONS: A . otitidis is found from the MEEs of AOM . The present data suggest that it has no clinical significance in AOM, and it does not increase the risk of developing OME after AOM. J Pediatr (Rio J), 1999 Jul, 75(Suppl 1), S149 - 54 {Immunization schedule: dynamics and updating}; Weckx LY et al.; OBJECTIVES: The objective of this article is to make an analysis of the dynamics of the imunization schedule and an updating of the practical aspects of the vaccination . METHODS: The authors, based on the official recommendations, in the imunization schedule of the Infectology Department of the Brazilian Society of Pediatrics and on their experience, present practical aspects to facilitate the understanding of the dynamics of application of the calendar . RESULTS: The current calendar of the Brazilian Society of Pediatrics (SBP) is presented with a practical analysis of the vaccines BCG, hepatitis B, poliomyelitis, Haemophilus influenzae type b (Hib), DPT and triple viral, which are also part of the Calendar of the National Program of Immunizations . Besides this, they analyze two other suitable vaccines for SBP, against varicella and hepatitis A . Finally they comment on the risk of urbanization of the yellow fever and the increasing indication of vaccination against this disease in Brazil . CONCLUSIONS: The imunization schedule should be dynamic, adapted to the epidemiologic characteristics of each country or place . The presented calendar is what is now recommended by the Infectology Department of the Brazilian Society of Pediatrics (SBP). J Pediatr (Rio J), 1999 Jul, 75(Suppl 1), S46 - 56 {Bacterial meningitis - diagnosis and treatment}; Faria SM et al.; OBJECTIVE: To present new concepts on diagnosis and treatment of bacterial meningitis regarding etiologic agents, pathophysiology and options about antimicrobial, antiinflammatory and supportive therapy . METHODS: Bibliographic review from MEDLINE data including articles published during the last ten years . One classic article published before this period and chapters of textbooks on infectious diseases were also included . RESULTS: Initial empirical antibiotic therapy is chosen according to probable etiologic agents for the age group . In the CSF microbiological analysis, the gram stains can reveal bacteria in 50% to 80% of the cases and the culture in nearly 85% . The tests for detection of bacterial antigens are useful for the diagnosis but they present low sensitivity . The most common agents during the neonatal period continue to be E . coli, Streptococcus B and L . monocytogenes . Beyond this period, the incidence of meningitis by Haemophilus influenzae b had a significant decrease after the introduction of conjugate vaccines . However, S . pneumoniae and N . meningitidis continue to be frequent agents . Currently, the thirdgeneration cephalosporins, ceftriaxone or cefotaxime, are the antibiotic therapy of choice . They are used with ampicillin up to two months of life and alone beyond this age . Dexamethasone has showed to be effective in reducing the inflammatory response and the sequelae, mainly the auditory sequelae . The fluid restriction doesn't offer advantages in the supportive care . CONCLUSIONS: Early diagnosis and prompt treatment are related to good outcome . The new insights on pathophysiology, the new antibiotics and the increasing bacterial resistance have determined changes in treatment. J Pediatr (Rio J), 1999 Nov, 75(Suppl 2), S177 - 84 {Clinical management of upper airway obstruction: epiglottitis and laryngotracheobronchitis}; Amantea SL et al.; OBJECTIVE: To present current concepts on diagnosis and treatment of upper airway obstruction, mainly related to differential diagnosis between acute viral laryngotracheobronchitis and epiglottitis.METHODS: Bibliographic review covering the last ten years, using both Medline system and direct research . The most relevant articles published about the subject were selected.RESULTS: Viral laryngotracheobronchitis is an acute self-limited disease of the upper airway in a child, clinically characterized by barking cough, stridor, hoarse voice, and upper respiratory symptoms . The disease is diagnosed by clinical signs and symptoms . Rarely, if no immediate airway management is needed, radiography of the neck may help to exclude other entities that cause laryngeal obstruction . In contrast to viral laryngotracheobronchitis, epiglottitis is characterized by inflammation of the supraglottic tissues and is caused mainly by Haemophilus influenzae type b . A previously healthy child suddenly develops a sore throat and fever . Within hours after the onset of symptoms the patient looks toxic, swallowing is painful and breathing is difficult . Drooling and cervical hyperextension are frequently present . Lateral neck radiograph is rarely required to the diagnosis and may delay appropriate management of the airway . Moderate viral laryngotracheobronchitis with stridor at rest and retractions should be treated with steroids (systemic or nebulized) and nebulized epinephrine . Severe viral laryngotracheobronchitis should be treated aggressively while arregements are made for endotracheal intubation . The diagnosis of epiglottitis requires immediate endotracheal intubation in the appropriate unit (emergency department, intensive care unit or surgical unit) and antimicrobial therapy . Alternatively at some medical centers children with severe upper airway obstruction have been treated with a mixture of helium and oxygen (70 to 80% concentration of helium) instead of room air or pure oxygen to avoid intubation.CONCLUSIONS: There are different levels of care for patients with upper airway obstruction, depending on their clinical presentation . The clinical manifestations of viral laryngotracheobronchitis may be confused with the presentation of epiglottitis . Despite this observation we believe that differential diagnosis between viral laryngotracheobronchitis and epiglottitis rests on clinical grounds. J Pediatr (Rio J), 1997 Jan-Feb, 73(1), 26 - 31 {Prevalence of Haemophilus influenzae resistant to ampicillin, cefaclor, cefotaxime, chloramphenicol and cotrimoxazol isolated from laboratories in the city of São Paulo, Brazil}; Rey LC et al.; OBJECTIVE: To determine Haemophilus influenzae resistant to ampicillin and other antibiotics isolated from different clinical specimens . METHODS: Isolates of H . influenzae were identified by culture with V and X factors and the aminolevulinic test . Nitrocefin was used to detect beta-lactamase (betaLac) production isolates were tested for antimicrobial susceptibility by disc diffusion and agar dilution methods . Serotype b was assessed by slide co-agglutination . RESULTS: From 245 H . influenzae identified, 155 were tested for serotype b, 28% (43/155) of which were positive . The global rate of beta-lactamase-positive isolates was 9% (22/245) . Resistance was similar among serotype b (11.6%) and non-type b H . influenzae (9.8%) (p>0.05) . No difference on betaLac production was found according to specimen's origin or the patients' age . Resistances to other antibiotics (by agar dilution and disc diffusion method, respectively) were: chloramphenicol 3.3 to 7.1%; cefaclor: 1.6 to 3.9% and cotrimoxazol: 9.1 to 10.5% . No resistance to cefotaxime has been detected; 63% (5/8) beta-Lac-positive isolates by agar dilution showed also resistance to chloramphenicol, compared to 3% (4/118) in the ss-Lac-negative group (p<0.001) . CONCLUSIONS: H . influenzae ampicillin-resistance has shown to be lower than other hospital-based-studies in Sao Paulo, and comparable to rates found in healthy carriers . The association between ampicillin and chloramphenicol resistance was significant: where this pattern is frequently found, the initial therapy for severe H . influenzae infections - like meningitis - should include a third generation cephalosporin. J Pediatr (Rio J), 1998 Jan-Feb, 74(1), 45 - 8 {Etiological profile of bacterial meningitis in a small hospital}; Elias ML et al.; OBJECTIVE: To determine the etiologic profile of cases of meningitis treated at a small hospital in Ribeirao Preto, State of Sao Paulo, and to compare it to those reported for other communities.METHODS: a retrospective study was conducted on 103 patients admitted from January 1992 to July 1996 with clinical and laboratory diagnosis of bacterial meningitis . The clinical criteria for diagnosis were based on patient history and physical signs and symptoms, and the laboratory criteria were based on cerebrospinal fluid examination (aspect, cytology, biochemistry, Gram staining, culture and countercurrent immunoelectrophoresis) and blood culture.RESULTS: The etiologic agent was identified in 81.5% of cases: Haemophilus influenzae type b in 32%, Neisseria meningitides in 25.2%, Streptococcus pneumoniae in 8.7%, Staphylococcus aureus and epidermidis in 8.7%, and others agents in 6.9% . CONCLUSIONS: The study showed that the cases of bacterial meningitis treated at the Santa Lydia Hospital of Ribeirao Preto are caused by the same agents detected in other places, with Haemophilus influenzae type b being the predominant one . The study also suggests that when many people are involved in the collection of material for laboratory tests, recovery of the agent may become difficult. J Pediatr (Rio J), 2002 Nov-Dec, 78 Suppl 2, S195 - 204 {Vaccination and the respiratory tract--what should we know?}; Farhat CK et al.; OBJECTIVE: This article aims at presenting a review of the main vaccines used in the pediatric population with direct impact on the prevention of infectious processes of the respiratory tract in children . SOURCES: Data from articles published in national and international scientific journals . The data were selected by means of direct search or search in the Lilacs and Medline databases . SUMMARY OF THE FINDINGS: This article was structured in topics, presenting issues related to immunization against frequent pathogens of the respiratory tract in human beings: Haemophilus influenza, influenza virus, respiratory syncytial virus and Streptococcus pneumoniae . CONCLUSIONS: The prevention of respiratory diseases through immunization is one of the main measures for the control of respiratory infection . These new vaccines, especially against Haemophilus influenza, have been available for some years with acknowledged efficacy . Now, the vaccine against Streptococcus pneumoniae (heptavalent vaccine) leads to a new perspective towards the management of respiratory diseases in children . In risk populations, the control of viral diseases through immunization, actively against the influenza virus and passively against the syncytial respiratory virus, is also an efficient measure to reduce respiratory disease. J Pediatr (Rio J), 2002 Nov-Dec, 78 Suppl 2, S129 - 40 {Etiological diagnosis of pneumonia--a critical view}; Rodrigues JC et al.; OBJECTIVES: To search literature related to the etiological diagnosis of acute pneumonia in children . SOURCES: Systematic review of Medline and Lilacs databases . SUMMARY OF THE FINDINGS: The use of new diagnostic methods such as immunological techniques and polymerase chain reaction has proven invaluable for specific diagnosis and epidemiological investigation, showing adequate sensitivity, specificity and promptness of results, with the aim of guiding therapy properly . Review of epidemiological studies of community acquired pneumonia showed that Streptococcus pneumoniae is still one of the most significant etiologic agents in all age groups, in developing and industrialized countries . Resistance of this agent to penicillin and cephalosporins is increasing in all continents and is worrisome . Atypical agents such as Mycoplasma pneumoniae and Chlamydia pneumoniae are common in community acquired pneumonia, mainly in children older than 4 years, representing one third of the cases in industrial countries . However, their prevalence in developing countries remain to be determined . Respiratory syncytial virus is also a very common etiology of community acquired pneumonia and may cause severe infections, mainly in infants and younger children . The introduction of new conjugated vaccines for Streptococcus pneumoniae and Haemophilus influenzae type b resulted in significant reduction of morbidity and mortality of pneumonia in children . CONCLUSIONS: A significant impact on morbidity and mortality of acute pneumonia in children is likely to occur if microbiological and antimicrobial control is continuously and dynamically performed, thus allowing for the development of new vaccines, particularly against the respiratory syncytial virus. Anal Chem, 2003 Sep 15, 75(18), 4918 - 24 Linking mass spectrometry and slab-polyacrylamide gel electrophoresis by passive elution of lipopolysaccharides from reverse-stained gels: analysis of gel-purified lipopolysaccharides from Haemophilus influenzae strain Rd; Gulin S et al.; Haemophilus influenzae is an important cause of human disease, and its lipopolysaccharide (LPS) is known to be a major virulence factor . H . influenzae produces short-chain LPS of which the heterogeneity is often visualized by sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) using silver staining for detection . Individual bands have not previously been recovered by this method in quantities sufficient for mass spectrometry . In an attempt toward the development of sensitive mass spectrometrical strategies to be used in structural studies of H . influenzae LPS and LPS from other bacteria, we have applied here our previously described slab-PAGE-based micropurification method to obtain unmodified LPS fractions of high purity (>95%) from a crude LPS preparation of H . influenzae strain Rd . Two LPS-fractions were obtained which, after a procedure including mild acid hydrolysis, dephosphorylation, and permethylation of the resulting oligosaccharides, were subjected to tandem electrospray ionization mass spectrometry (ESI-MS/MS) . The quantities of micropurified LPS fractions-the recovery of LPS in terms of total mass was 30%-were found sufficient to allow the characterization of LPS glycoforms . The ESI-MS spectra of the individual bands showed reduced heterogeneity . Furthermore, the integrity of the micropurified LPS was confirmed . The spectra-displayed molecular ions showed improved intensity, increased respective signal-to-noise ratios demonstrating the sensitivity of analysis . Consequently, both the direct determination of the molecular masses of the gel-separated LPS glycoforms and sequence analyses using ESI-MS/MS were possible. Nippon Rinsho, 2003 Dec, 61(12), 2170 - 4 {Administration of acute exacerbation of chronic obstructive pulmonary disease}; Ito T et al.; We have to consider the exacerbation of chronic obstructive pulmonary disease(COPD) may be caused not only by infection, but also by acute exacerbation of chronic heart failure, pulmonary embolism, pneumothorax, or other cardiopulmonary complications . Because it is characteristic that the exacerbation of COPD is often recurensive, the most important thing is the administration during stable status . Approximately 40% of pathogens of the acute infectious exacerbation of COPD are Haemophilus influenzae, Streptococcus pneumoniae, Moraxella catarrhalis, Pseudomonas aeruginosa, Staphylococcus aureus, and Echelisia coli . Also, approximately 15% is exacerbated by atypical pathogens such as Chlamydia pneumoniae and approximately 30% is by viral infection . We should contemplate the possibility of pathogens according to the statistics, when we choose antibiotics empirically. J Hepatol, 2004 Jan, 40(1), 31 - 9 Microbial mimics are major targets of crossreactivity with human pyruvate dehydrogenase in primary biliary cirrhosis; Bogdanos DP et al.; BACKGROUND/AIMS: Previous studies on patients with primary biliary cirrhosis (PBC) have shown extensive cross-reactivity between the dominant B- and T-cell epitopes of human pyruvate dehydrogenase complex-E2 (PDC-E2), and microbial mimics . Such observations have suggested microbial infection as having a role in the induction of anti-mitochondrial antibodies, through a mechanism of molecular mimicry . However the biological significance of these cross-reactivities is questionable, because PDC-E2 is so highly conserved among various species . METHODS: Interrogating protein databases, ten non-PDC-E2 microbial sequences with high degree of similarity to PDC-E2(212-226) were found in Escherichia coli (6), Helicobacter pylori, Pseudomonas aeruginosa, Cytomegalovirus, and Haemophilus influenzae . We report on a study testing reactivity and competitive cross-reactivity against these respective peptides, and in some cases the parent protein, using sera from 55 patients with PBC, compared to reactivity of 190 pathological and 28 healthy controls . RESULTS: Cross-reactivity to E . coli mimics was commonly seen in PBC, and in a subset of pathological controls except where there was no evidence of urinary tract infection and correlated with anti-mitochondrial reactivity . CONCLUSIONS: E . coli/PDC-E2 cross-reactive immunity characterizes primary biliary cirrhosis; the large number of E . coli immunogenic mimics may account for the dominance of the major PDC-E2 autoepitope. Kyobu Geka, 2003 Dec, 56(13), 1126 - 9 {Acute purulent pericarditis due to Haemophilus influenzae treated successfully with subxiphoid pericardial drainage; report of a case}; Takabayashi S et al.; A surgical case of acute purulent pericarditis in 1-year 2-month old boy who developed pericardial tamponade rapidly is reported . A subxiphoid pericardiectomy through a median incision was performed . Haemophilus influenzae was isolated from the effusion . He recovered successfully with an administration of antibiotics after the drainage procedures and did not develop constructive pericarditis . Our experience suggested that early subxiphoid pericardial drainage was effective in treatment of acute purulent pericarditis. Am J Med Sci, 2003 Dec, 326(6), 360 - 8 Current issues in the management of bacterial respiratory tract disease: the challenge of antibacterial resistance; Dunbar LM; The worldwide burden of respiratory tract disease is enormous . Resistance to penicillins, macrolides, and cephalosporins is now detected among the leading bacterial pathogens that cause respiratory tract infections (RTIs)-Streptococcus pneumoniae, Haemophilus influenzae, and Moraxella catarrhalis . The increasing role of atypical/intracellular pathogens (eg, Chlamydia pneumoniae, Mycoplasma pneumoniae, Legionella pneumophila) in RTIs, as well as their increase in antibiotic resistance prevalence, continues to be of great concern . More recently introduced treatment options for RTIs include the newer respiratory fluoroquinolones, along with the macrolides and azalides . Although these agents demonstrate good activity against common respiratory pathogens, reduced susceptibility to these agents has been reported . The ketolides are recently developed antibacterial agents with targeted-spectrum activity against common respiratory tract pathogens, including atypical/intracellular pathogens, and a low potential for inducing resistance . These promising new drugs have shown in vitro and in vivo efficacy in the treatment of community-acquired RTIs, such as community-acquired pneumonia, acute exacerbations of chronic bronchitis, and acute bacterial maxillary sinusitis. Carbohydr Res, 2003 Nov 14, 338(23), 2731 - 44 Structural profiling of lipopolysaccharide glycoforms expressed by non-typeable Haemophilus influenzae: phenotypic similarities between NTHi strain 162 and the genome strain Rd; Schweda EK et al.; Non-typeable Haemophilus influenzae (NTHi) is a significant cause of otitis media in children . We have employed single and multiple step electrospray ionization mass spectrometry (ESIMS) and NMR spectroscopy to profile and elucidate lipopolysaccharide (LPS) structural types expressed by NTHi strain 162, a strain obtained from an epidemiological study in Finland . ESIMS on O-deacylated LPS (LPS-OH) and core oligosaccharide (OS) samples of LPS provided information on the composition and relative abundance of glycoforms differing in the number of hexoses linked to the conserved inner-core element, L-alpha-D-Hepp-(1-->2)-{PEtn-->6}-L-alpha-D-Hepp-(1-->3)-L-alpha-D-Hepp-(1-->5)-{PPEtn-->4}-alpha-Kdop-(2-->6)-Lipid A of H . influenzae LPS . The strain examined was found to elaborate Hex2 to Hex5 LPS glycoform populations having structures identical to those observed for H . influenzae strain Rd {Risberg, A.; Masoud, H.; Martin, A.; Richards, J.C.; Moxon, E.R.; Schweda, E.K.H . Eur . J . Biochem . 1999, 261, 171-180}, the strain for which the complete genome has been sequenced . In addition, sialyllactose-containing glycoforms previously identified in strain Rd as well as several NTHi strains, were identified as minor components . Multiple step tandem ESIMS (MS(n)) on dephosphorylated and permethylated OS provided information on the arrangement of glycoses within the major population of glycoforms and on the existence of additional isomeric glycoforms . Minor Hex1 and Hex6 glycoforms were detected and characterized where the Hex6 glycoform was comprised of a dihexosamine-containing pentasaccharide chain attached at the proximal heptose residue of the inner-core unit . LPS structural motifs present in the NTHi strain 162 are expressed by a genetically diverse set of disease causing isolates, providing the basis for a vaccine strategy against NTHi otitis media. Vaccine, 2004 Jan 2, 22(3-4), 378 - 82 Impact of routine vaccination with a conjugate Haemophilus influenzae type b vaccine; Hviid A et al.; Based on a unique nationwide registration of vaccinated children, we studied the impact of routine Hib vaccination with special emphasis on vaccine uptake and adherence, vaccine effectiveness with respect to Hib meningitis, and indirect effects with respect to Hib meningitis among the unvaccinated children . Uptake and adherence was generally satisfactory . We estimated >97% effectiveness for all three doses of vaccine and observed herd-immunity in unvaccinated children comparable to a vaccine effectiveness of 94% 3.5 years into the programme . In conclusion, nationwide routine Hib vaccination is highly effective in protecting against Hib meningitis, and rapid achievement of herd immunity is possible with catch-up vaccination of older children. Eur J Clin Microbiol Infect Dis, 2004 Jan, 23(1), 46 - 8 Epub 2003 Dec 11. Haemophilus parainfluenzae: an underdiagnosed pathogen of biliary tract infections? Frankard J, Rodriguez-Villalobos H, Struelens MJ, Jacobs F. Presented here is a case of monobacterial peritonitis complicating cholecystitis and caused by an uncommon agent of gastrointestinal infections, Haemophilus parainfluenzae . The pathogenic role of this organism in digestive infections, particularly in those of the biliary tract, has been reported increasingly though sporadically . Indeed, it has been shown to be a coloniser of the gastrointestinal tract, and a recent hypothesis of an ascending route of infection to the biliary tract has been postulated to partly explain its pathogenicity . More frequent identification of Haemophilus parainfluenzae as a causal agent of biliary tract infection would probably be obtained through the use of specific culture media, since its potential implication has been demonstrated. J Pediatr Hematol Oncol, 2003 Dec, 25 Suppl 1, S28 - 33 Childhood chronic immune thrombocytopenic purpura: unresolved issues; Blanchette VS et al.; Chronic immune thrombocytopenic purpura (ITP), defined as a platelet count of below 150 x 109/L persisting for more than 6 months from onset of illness, occurs in approximately 20% to 25% of children with acute-onset ITP . A small subset of these patients (approximately 5%) will manifest symptomatic, severe thrombocytopenia (platelet counts <20 x 109/L) at 1 year or longer following diagnosis, and may require splenectomy . Complete/partial response rates following splenectomy in children with primary chronic ITP are of the order of 70% to 75%; response rates are lower in children with secondary ITP and those with complex autoimmune cytopenias (e.g., Evans syndrome) . Laparoscopic splenectomy is increasingly preferred over open splenectomy . Patients should be immunized with the pneumococcal, Haemophilus type b and meningococcal vaccines before splenectomy; the duration of postsplenectomy antibiotic prophylaxis using penicillin or an equivalent antibiotic is controversial but should be at least until 5 years of age and for a minimum of 1 year postsplenectomy . Some experts advocate life-long antibiotic prophylaxis . Treatment of postsplenectomy failures is a challenge; partial/complete remission rates are low, and multimodality therapy may be more efficacious than monotherapy . The presence of an accessory spleen should be sought and removal considered if present . The role of newer treatment modalities such as anti-CD 20 remains to be established. J Infect, 2004 Jan, 48(1), 56 - 65 Antimicrobial susceptibility among community-acquired respiratory tract pathogens in the USA: data from PROTEKT US 2000-01; Doern GV et al.; OBJECTIVES: The PROTEKT US surveillance program (Prospective Resistant Organism Tracking and Epidemiology for the Ketolide Telithromycin in the United States) commenced in 2000 to document the emergence and spread of antimicrobial resistance among respiratory tract pathogens in the United States . METHODS: During 2000-2001, 206 centers from 154 cities/metropolitan areas collected 16,727 clinical isolates (Streptococcus pneumoniae, n=10103, Streptococcus pyogenes, n=3918, Haemophilus influenzae, n=2706) . RESULTS: Among S . pneumoniae isolates, 38.9% showed decreased susceptibility to penicillin (12.5% intermediate, 26.4% resistant) with marked geographical variability . The erythromycin resistance rate was 31.0% and highly correlated with penicillin resistance . The rate of fluoroquinolone resistance was 0.8% . Telithromycin was nearly uniformly active against S . pneumoniae (MIC(90) 0.5 mg/l) . All isolates of S . pyogenes were penicillin-susceptible, 5.5% were resistant to erythromycin . Telithromycin minimum inhibitory concentrations (MICs) were lower than clindamycin and macrolide MICs against S . pyogenes (MIC(90) 0.03 mg/l versus 0.25 mg/l and 0.12 mg/l, respectively) . 28.3% of H . influenzae isolates produced beta-lactamase . Telithromycin activity versus H . influenzae was not affected by beta-lactamase production . CONCLUSIONS: The PROTEKT US study confirms the widespread prevalence of antimicrobial resistance among common bacterial respiratory pathogens in the US, and re-affirms the importance of continued surveillance to guide optimum empiric therapy for patients with Community-acquired respiratory tract infections (CARTIs) . The new ketolide, telithromycin, maintained potent activity against study isolates in vitro and offers promise for the effective treatment of CARTIs. J Infect, 2004 Jan, 48(1), 39 - 55 Antibacterial resistance among children with community-acquired respiratory tract infections (PROTEKT 1999-2000); Felmingham D et al.; OBJECTIVE: To determine the susceptibility of bacterial respiratory tract pathogens, isolated from children (0-12 years) as part of the global PROTEKT surveillance study (1999-2000), to a range of antibacterials, including the ketolide telithromycin . METHODS: Minimum inhibitory concentrations of the antibacterials studied were determined at a central laboratory using the NCCLS microdilution broth method . Macrolide resistance mechanisms were detected by PCR . RESULTS: Of 779 Streptococcus pneumoniae isolates worldwide, 43% were non-susceptible to penicillin (18% intermediate; 25% resistant) and 37% were resistant to erythromycin, with considerable intercountry variation . Eighteen per cent of 653 Haemophilus influenzae and >90% of 316 Moraxella catarrhalis isolates produced beta-lactamase . Of 640 Streptococcus pyogenes isolates, 10% were resistant to erythromycin, with considerable intercountry variation . All S . pneumoniae and 99.8% of H . influenzae isolates were susceptible to telithromycin using breakpoints proposed to the NCCLS (<or=1 and <or=4 mg/L, respectively) . All M . catarrhalis and 97% of S . pyogenes and isolates were susceptible to <or=1 mg/L telithromycin . CONCLUSIONS: Antibacterial resistance complicates the empirical treatment of respiratory tract infections in children and requires continued monitoring . Telithromycin may be a useful therapeutic alternative as it is highly active against strains exhibiting various resistance phenotypes. Eur J Haematol, 2003 Nov, 71(5), 319 - 26 Prevention of life-threatening infections due to encapsulated bacteria in children with hyposplenia or asplenia: a brief review of current recommendations for practical purposes; Castagnola E et al.; The aim of the present work was to summarise in a single paper all the options for prevention of life-threatening infections due to encapsulated bacteria in patients with hyposplenism or asplenia . Prevention of these infections should be obtained in all patients with 1) patient and family education, 2) prophylaxis by means of vaccination against Haemophilus influenzae and Streptococcus pneumoniae, 3) antibiotic prophylaxis, based primarily on penicillin, 4) delay of elective splenectomy or use methods of tissue salvage in splenic trauma . Vaccination is not effective against all serotypes of S . pneumoniae and Neisseria meningitidis causing life-threatening infections in hypo/asplenic patients . Moreover, antibacterial prophylaxis could select antibacterial-resistant pathogens and is highly conditioned by patient's compliance . Therefore, empirical antibacterial therapy of fever and/or suspected infection should be recommended to all splenectomised patients independently from time elapsing from splenectomy, vaccinal status and assumption of antibacterial prophylaxis. Cad Saude Publica, 2003 Sep-Oct, 19(5), 1267 - 75 Epub 2003 Dec 02. {Haemophilus influenzae type b: epidemiological situation in the State of Minas Gerais, Brazil, 1993-1997}; Miranzi Sde S et al.; Among Haemophilus influenzae type b (Hib) invasive diseases, pneumonia and meningitis are the most relevant in public health due to their frequency and severity . From 1993 to 1997, there were 720 cases of Hib meningitis in Minas Gerais State, Brazil, representing the most frequent cause of bacterial meningitis in infants (< 1 year) and the second most frequent among all causes of meningitis . The total estimated cases of invasive Hib diseases thus appear to justify the recent inclusion of the vaccine in the basic immunization protocol . The vaccine's high cost reinforces the need for more precise monitoring of the etiological diagnosis of meningitis cases, representing one of the weaknesses in the prevailing epidemiological surveillance system. Respiration, 2003 Sep-Oct, 70(5), 507 - 14 Organizing pneumonia presenting as a solitary nodular shadow on a chest radiograph; Watanabe K et al.; BACKGROUND: The role of infection as a cause of focal organizing pneumonia (OP) is not fully understood . OBJECTIVES: This study aimed to determine the clinical, radiological and pathological characteristics of patients with OP presenting a solitary nodular shadow on a chest radiograph . METHODS: Fourteen patients who presented with a solitary nodular shadow on a chest radiograph, pathologically diagnosed as OP after surgical resection, were allocated into two groups according to the histological findings . The first had OP with aggregates of neutrophils in airways and/or pulmonary parenchyma with or without necrosis or destruction of lung architecture (group 1: OP with neutrophilic infiltration; n = 10) . The second consisted of patients with OP presenting neither neutrophilic infiltration, necrosis nor destruction of lung architecture (group 2: OP without neutrophilic infiltration; n = 4) . RESULTS: Cough, sputum, and chest pain were the common symptoms in both groups of patients . Computed tomography (CT) revealed that all nodules in both groups were located in the peripheral lung parenchyma and had irregular margins, and their shapes varied from round to wedge-shaped . Haemophilus influenzae was isolated from sputum or transbronchial aspirates from 3 patients in group 1 . CONCLUSIONS: The specimens resected from patients with focal OP mostly show small aggregates of neutrophils . However, the dominant histological feature is OP and neutrophilic infiltration, suggesting infection was a minor histological component in all cases . Clinical symptoms and chest CT findings did not clearly distinguish these two groups of patients . It is thus reasonable to place these OPs in the same category and to treat them in the same way . Surgical excision appears to be the only method for a precise diagnosis . Ann Epidemiol, 2004 Jan, 14(1), 31 - 5 Invasive disease caused by Haemophilus influenzae: the sensitivity of statutory reporting; Dominguez A et al.; PURPOSE: The objective of the study was to investigate the sensitivity of the statutory reporting of Haemophilus influenzae invasive disease (HIID) during the period between 1996 and 1997 in Catalonia, Spain . METHODS: The incidence of HIID reported passively by clinicians was compared with the cases detected by a system of microbiological surveillance . In all cases isolated, the age of the patient, the clinical form and the serotype were investigated . RESULTS: Sixty-six cases were passively reported and 111 were detected by microbiological surveillance . Overall sensitivity of reporting was 59.5% (95% CI, 50.7-69.1), with differences being observed according to the variables studied . The highest values were obtained in children under 5 years (87.8%; 95% CI, 73.7-95.9), in cases with meningitis and/or sepsis (64.3%; 95% CI, 50.4-76.6) and in serotype b (73.0%; 95% CI, 60.3-83.4) . In the logistical regression analysis, only age under 5 years was associated with greater reporting (OR= 9.8; 95% CI, 2.5-37.8) . CONCLUSIONS: Reported morbidity in children under 5 years is a good estimate of the true incidence of HIID in Catalonia (underreporting was 12.2%), but not for those above this age in whom the underreporting was 57.2%. Presse Med, 2003 Nov 22, 32(37 Pt 1), 1752 - 9 {Bacteria and resistance to antibiotics in acute otitis media in paediatrics, depending on the geographical origin}; Bidet P et al.; EPIDEMIOLOGY OF THE BACTERIA RESPONSIBLE: Acute otitis media (AOM) is the most common bacterial infection in childhood below the age of 5 years . Bacteria may be isolated from middle ear fluid in about two-thirds of patients . The prevalence of bacteria varies from one country to the next . The most common pathogens recovered are Streptococcus pneumoniae, Haemophilus influenzae (20-50%) and less frequently Moraxella catarrhalis (10%) . However, several recent reports suggest an increasing rate of isolation of M . catarrhalis approaching 20% . Concomitant isolation of two or more organisms occurs in up to 10% of cases . The role of Group A Streptococci and Staphylococcus aureus in AOM has decreased since the use of antibiotics . EPIDEMIOLOGY OF ANTIMICROBIAL RESISTANCE: The recent spread of penicillin resistant S . pneumoniae and amoxycillin resistant H . influenzae varies considerably from one country to an other and appears related to the use of antibiotics and socio-economic conditions . A follow up of bacterial epidemiology and antibiotic resistance is necessary in each region of the world to define accurate strategies of acute otitis antibiotherapy. J Clin Microbiol, 2003 Dec, 41(12), 5546 - 50 Evaluation of methodology for serotyping invasive and nasopharyngeal isolates of Haemophilus influenzae in the ongoing surveillance in Brazil; Bokermann S et al.; To assess the magnitude of discrepant results obtained by routine Haemophilus influenzae serotyping, 258 isolates, collected by the epidemiological surveillance system in Brazil from individuals with invasive diseases or carriage, were evaluated by two slide agglutination (SlAg) methods: SlAg method 1, by which strains were initially screened with a serotype b-specific antiserum, and SlAg method 2, by which strains were tested against all serotype-specific antisera in parallel . Investigators comparing results of the two SlAg methods with those obtained by capsule type-specific PCR were blinded to the method used . The serotype prevalence rates found by the three methods were significantly different, involving discrepancies mainly between serotype b and noncapsulated (NC) isolates . For invasive isolates (n = 131), the overall agreement rate between SlAg method 1 or 2 and PCR was 68.0 or 88.3%, respectively, whereas for colonizing isolates (n = 127) the corresponding rate was 46.5 or 94.2%, respectively . SlAg method 2 improved the ascertainment of serotypes over that obtained with SlAg method 1, demonstrating good correlation with PCR . Use of the polyvalent antiserum as a screening reagent for SlAg for invasive and colonizing isolates showed poor discriminatory power, with a sensitivity of 65.8% and a specificity of 91.7% . We stress the importance of using a well-standardized SlAg methodology and suggest that reference laboratories should utilize PCR routinely to confirm SlAg results and to check all nonspecific SlAg reactions and apparent NC isolates by SlAg in order to provide reliable data on the prevalence of H . influenzae serotypes in the H . influenzae type b vaccine era. Int J Antimicrob Agents, 2003 Dec, 22(6), 557 - 61 In vitro activities of nine peptide deformylase inhibitors and five comparator agents against respiratory and skin pathogens; Bowker KE et al.; The activity of nine peptide deformylase (PDF) inhibitors undergoing clinical evaluation were compared with co-amoxiclav, levofloxacin, moxifloxacin, erythromycin and telithromycin against a range of respiratory and skin pathogens (n=166) . The PDF inhibitor showed good activity against Streptococcus pneumoniae, Moxarella catarrhalis, Group A streptococci and Staphylococcus aureus irrespective of beta-lactam or fluoroquinolone susceptibility . Against Haemophilus influenzae, MIC(90) values were generally higher . BB-88488 was the most active compound . Overall these data suggest that PDF inhibitors are an interesting new class of antimicrobial worthy of further investigation in the treatment of respiratory tract and skin infections. P N G Med J, 2002 Mar-Jun, 45(1-2), 44 - 50 Pneumonia vaccine trials at Tari; Riley ID; Pneumonia is the commonest cause of death of children in Papua New Guinea (PNG) . At Tari pneumonia is most commonly caused by Streptococcus pneumoniae and Haemophilus influenzae, which set up rapid severe infections in the lungs that require urgent treatment . In rural PNG, however, treatment is often delayed . Penicillin-resistant forms of these bacteria are on the increase . It is therefore important to have another means of protection against this serious disease . This paper describes three field trials of a vaccine against the commonest serotypes of S . pneumoniae found in PNG . The trials show that a pneumococcal vaccine can prevent deaths from uncomplicated acute lower respiratory tract infection in small children and adults . It is likely that the vaccine does this by limiting the replication of bacteria in the lungs and thus limiting their spread to other parts of the body. J Pediatr, 2003 Dec, 143(6 Suppl), S163 - 87 Global reduction of Hib disease: what are the next steps? Proceedings of the meeting Scottsdale, Arizona, September 22-25, 2002; Watt JP et al.; On September 22 to 25, 2002, a group of infectious disease specialists, public health officials, and vaccine experts from 33 countries gathered in Scottsdale, Arizona, to discuss the epidemiology and control of disease caused by Haemophilus influenzae type b (Hib) in the era of Hib conjugate vaccines . This supplement is a synthesis of the major themes and key lessons identified at the meeting . The objectives of the conference were to review the 10-year experience with Hib conjugate vaccines, discuss strategies to reduce Hib disease rates to lowest possible levels in industrialized countries, review impediments to the introduction of Hib vaccine in developing countries, and discuss strategies for disseminating lessons learned from countries using to those not using Hib conjugate vaccines . Over 10 years of international experience with Hib conjugate vaccines has demonstrated that they are safe and effective . Routine use of Hib conjugate vaccine has consistently led to decreases in the incidence of invasive Hib disease of 90% or more across a wide range of epidemiologic situations in industrialized countries . In some countries, the vaccine has caused a near-disappearance of invasive Hib disease through a combination of direct protection and herd immunity . Developing countries that have implemented routine vaccination (eg, The Gambia, Chile) have also had substantial disease reduction . In countries where Hib conjugate vaccine is being used, reducing Hib disease incidence to the lowest possible level will depend on maintaining high vaccine coverage levels, conducting surveillance for Hib disease, and investigating Hib disease cases . The optimal Hib vaccination strategy will depend on many factors, including local epidemiology and programmatic considerations . In countries that are not using Hib conjugate vaccine, information on the local burden of Hib disease will be essential for leaders considering vaccine introduction . Where disease burden is high, a multifaceted approach is urgently needed to evaluate and overcome barriers to vaccine introduction . In areas where Hib disease burden is not well characterized, additional work will be needed to understand the epidemiology of Hib disease and to communicate the value of Hib conjugate vaccine. Genome Res, 2003 Dec, 13(12), 2665 - 73 Hierarchy of sequence-dependent features associated with prokaryotic translation; Lithwick G et al.; Protein expression in the cell is affected by various sequence-dependent features . Several such sequence-dependent features have been individually studied,yet they have not been compared quantitatively in terms of their relative influence on protein expression,and a hierarchy of these elements has not been determined . Here we present a quantitative analysis examining sequence-dependent features involved in prokaryotic translation,namely,the base-pairing potential between the mRNA Shine-Dalgarno sequence and the ribosomal RNA,codon bias,and the identity of the stop codon . We analyzed these features both at intra- and intergenomic levels using the Escherichia coli and Haemophilus influenzae genomes . Within each genome,we examined the relationship between each feature and protein expression levels determined by 2D-gel analyses . At the intergenomic level,comparative genomic principles were applied to study the relative preservation of the different sequence-dependent properties between orthologs . From these analyses,we determined that biased codon usage is the property that is most highly associated with protein expression and that is most conserved . The identity of the stop codon and the base-pairing potential of the mRNA Shine-Dalgarno sequence and the rRNA seem to have less of an effect on protein expression. Eur J Pediatr, 2004 Feb, 163(2), 105 - 7 Epub 2003 Dec 04. The aetiology of paediatric inflammatory vulvovaginitis; Cuadros J et al.; Vulvovaginitis is the most common gynaecological problem in prepubertal girls and clear-cut data on the microbial aetiology of moderate to severe infections are lacking . Many microorganisms have been reported in several studies, but frequently the paediatrician does not know the pathogenic significance of an isolate reported in vaginal specimens of girls with vulvovaginitis . A multicentre study was performed, selecting 74 girls aged 2 to 12 years old with a clinical picture of vulvovaginitis and inflammatory cells on Gram stain . All the specimens were cultured following standard microbiological techniques and the paediatricians completed a questionnaire to highlight risk factors after interviewing the parents or tutors . The data were compared with those obtained in a control group of 11 girls without vulvovaginitis attending a clinic . Streptococcus pyogenesand Haemophilus spp.were isolated in 47 and 12 cases, respectively . Upper respiratory infection in the previous month ( P<0.001) and vulvovaginitis in the previous year ( P<0.05) were identified as significant risk factors . Foreign bodies, sexual abuse, poor hygiene and bad socioeconomic situation were not identified as risk factors for the infection . CONCLUSION: Paediatric inflammatory vulvovaginitis is mainly caused by pathogens of the upper respiratory tract and the most common risk factor for this infection is to have suffered an upper respiratory tract infection in the previous month. Pediatrics . 2003 Dec;112(6 Pt 1):e453. Injection-site reactions to booster doses of acellular pertussis vaccine: rate, severity, and anticipated impact; Skowronski DM et al.; BACKGROUND: Acellular pertussis (aP)-containing vaccines cause fewer adverse events than whole-cell versions for primary doses . Booster doses, however, may be followed by extensive injection-site reactions . This study compares the frequency, severity, and impact of local reactions among children receiving 5 consecutive doses of an aP combination vaccine (including inactivated polio virus, conjugated Haemophilus influenzae type b antigen, and diphtheria and tetanus toxoids) to children receiving a mixed series of whole-cell and aP combination vaccines . METHODS: Participants were parents or guardians of children 4 to 6 years old immunized at public health clinics across British Columbia, Canada . This included 398 children receiving the fifth consecutive dose of an aP combination vaccine and 402 receiving the fifth dose in a mixed series consisting of at least 1 prior dose of whole-cell pertussis combination vaccine with the remainder as aP combination vaccine . A cross-sectional telephone survey evaluated the extent of local reactions 48 to 96 hours after immunization by asking participants to compare the size of redness and swelling with familiar household items such as Oreo cookies or coins . Associated discomfort and impact on recreational activities, health care utilization, parental time off work, and attitudes toward immunization were also assessed . RESULTS: Children who received the fifth consecutive dose of an aP combination vaccine more often experienced redness (24%) or swelling (16%) the size of an Oreo cookie or larger (>or=46 mm) than children given a mixed series (10% and 9%, respectively) but less often experienced tenderness or limitation of movement at the injection site . Related health care utilization was low . There was no discernible effect on participation in recreational activities or parental attitudes toward vaccine; 90% would recommend the same vaccine to others with children of the same age . CONCLUSIONS: We conclude that injection-site reactions are more extensive after the fifth consecutive dose of an aP combination vaccine compared with the fifth dose in a mixed series of whole-cell and aP combination vaccines . These reactions are unlikely to affect parental acceptance of immunization recommendations or health care utilization. Hunan Yi Ke Da Xue Xue Bao, 2003 Jun, 28(3), 272 - 4 {Characteristics of bacteriology and drug sensitivity in patients with COPD combined with pneumonia}; Yi ZM et al.; OBJECTIVE: To investigate the characteristics of bacteriology and the drug resistance in the patients with chronic obstructive disease (COPD) combined with pneumonia at our respiratory intensive care unit(RICU) in 2001 . METHODS: The sputum of 543 patients with COPD combined with pneumonia was collected with a regular method, the bacteria were cultured, and then the drug sensitivity was analyzed with K-B method . RESULTS: There were 181 positive samples in the 543 patients with the positive rate 33.9% . The main bacteria in the G- bacillus were Pseudomonas (21.55%), Haemophilus influenza (14.36%), Enteric bacilli (13.26%), and Klebsiella (11.60%) which were sensitive to impipenem, amikacin, and ceftazidime . The main bacteria in G+ bacteria were Staphylococcus aureus (7.18%) and Staphylococcus epidermindis (4.42%) which were sensitive to vancomycin, imipenem, ceftazidime, and amikacin . CONCLUSION: The bacteria in the patients with COPD combined with pneumonia at RICU of the hospital in 2001 are mainly made up of G- bacillus and secondarily of G+ bacteria which are sensitive to imipenem, amikacin, and ceftazidime . The G+ bacteria are highly sensitive to vancomycin. J Pediatr (Rio J), 2001 Sep-Oct, 77(5), 387 - 92 {Haemophilus influenzae type b meningitis in the state of Paraná, Brazil}; Takemura NS et al.; OBJECTIVE: During the second half of 1996, the municipalities of Londrina and Curitiba (State of Parana, Brazil) included Haemophilus influenzae type b (Hib) vaccine into their routine vaccination regimen, approximately 30 months before its introduction into the National Immunization Program . The present study aimed at verifying the incidence of meningitis caused by Hib among children in Londrina, Curitiba, and in the remaining municipalities of the State, before and after the introduction of this vaccine into the immunization program . METHODS: An observational and retrospective study was carried out . The study included all cases of Haemophilus influenzae type b meningitis recorded by the epidemiological surveillance system in Londrina and by the State of Parana Health Secretariat between 1992 and 1999 among children aged less than 5 years . The incidence rates of Hib meningitis were calculated per 100,000 children aged less than five years . RESULTS: After the introduction of Hib vaccine, an important reduction in the incidence rate of Haemophilus influenzae type b meningitis was observed in Londrina (from 23.91 in 1996 to 2.79 in 1999) . A Similar decrease was observed in Curitiba . In the remaining localities of the state, which had not introduced the vaccine till mid-1999, the incidence rate remained almost unchanged . CONCLUSION: Regular vaccination against Hib was effective in reducing the incidence rate of meningitis amongst children younger than five years in Londrina and Curitiba . In order to maintain this low incidence rate, adequate vaccination coverage and strict epidemiological surveillance should be guaranteed. J Pediatr (Rio J), 2002 Jan-Feb, 78(1), 24 - 30 {Etiology and evolution of bacterial meningitis in a pediatric center}; Romanelli RM et al.; OBJECTIVE: To establish the prevalence of the etiological agents of bacterial meningitis in a reference center for the treatment of infectious diseases in the state of Minas Gerais . METHODS: Descriptive study including all children with probable diagnosis of meningitis between June/1999 and November/1999 . RESULTS: There were 210 cases of meningitis, and 111 (52.9%) were caused by bacteria . Actually, 52 were probable bacterial meningitis (with liquor alterations) and 59 were confirmed (with culture and/or antigen tests) . The main agents were: Haemophilus influenzae, Neisseria meningitidis and Streptococcus pneumoniae . The initial treatment for children aged between three months and five years consisted of ampicillin and chloramphenicol . Later, the antibiotic was changed to penicillin in cases of Neisseria meningitidis and Streptococcus pneumoniae . and to chloramphenicol in cases of Haemophilus influenzae . Extended spectrum antimicrobial agents were used on clinical or laboratory basis, but resistant microorganisms were not found in cultures . CONCLUSIONS: The epidemiology of meningitis should be continuous and should consider local data in order to guide antimicrobial therapy . The continuous monitoring of the prevalent agents in each institution and their resistance is fundamental to the selection of antimicrobial drugs, preserving the antimicrobial agents, and causing less interference with individual colonization, without contributing to the increasing resistance of the agents responsible for meningeal infections. J Pediatr (Rio J), 2002 Nov-Dec, 78(6), 467 - 74 {Etiological profile of bacterial meningitis in children}; Mantese OC et al.; OBJECTIVE: To determine the etiologic profile and analyze some epidemiological aspects of children with bacterial meningitis admitted to a public teaching hospital . METHODS: A prospective study was conducted on children with clinical and laboratory diagnosis of bacterial meningitis, admitted to Hospital das Clinicas da Universidade Federal de Uberlandia, from January 1987 to January 2001 . Patients with meningitis associated with trauma, intracranial devices or malformations of the neural tube, and tuberculosis, were not included in the study . RESULTS: From a total of 415 children with bacterial meningitis, the etiologic agent was detected in 315 (75.9%): Haemophilus influenzae b in 54.2%, meningococci in 20.6%, pneumococci in 18.1% and other agents, in 6.9% . Previous antibiotic treatment, observed in 47.2% of the cases, led to a significant decrease in positive blood cultures (from 50.8% to 38.7%) and in cerebrospinal fluid cultures (from 71.7% to 57.6%) . Among children younger than 48 months Haemophilus influenzae b was predominant, particularly when compared to meningococci . The overall mortality was 10.1%, with a significant difference between the rates of pneumococcal (17.5%) and meningococcal meningitis (4.6%) . CONCLUSIONS: Children affected by Haemophilus influenzae b and by pneumococci were younger than those with meningitis caused by meningococci . The blood and/or cerebrospinal fluid culture remains an important laboratory tool for etiologic diagnosis, despite the negative impact caused by antibiotic previous treatment . The agents most commonly detected were Haemophilus influenzae b, meningococci and pneumococci . Bacterial meningitis continues to present an important mortality among children, particularly when caused by pneumococci. J Bacteriol, 2003 Dec, 185(24), 7285 - 90 Differences in genetic and transcriptional organization of the glpTQ operons between Haemophilus influenzae type b and nontypeable strains; Song XM et al.; The glpTQ operon of Haemophilus influenzae type b (Hib) and nontypeable H . influenzae (NTHi) strains is highly conserved, except for a 1.4-kb glpTQ intergenic region that was found in most Hib strains . The presence of this intergenic region results in divergent glpTQ transcriptional profiles for Hib and NTHi where Hib strains appear to have evolved an alternative promoter for glpQ expression . Based on the intergenic region's low G+C content, we speculate that this DNA fragment was acquired by lateral transfer. Microb Pathog, 2004 Jan, 36(1), 25 - 33 Reduced severity of middle ear infection caused by nontypeable Haemophilus influenzae lacking the hemoglobin/hemoglobin-haptoglobin binding proteins (Hgp) in a chinchilla model of otitis media; Morton DJ et al.; Since Haemophilus influenzae lacks enzymes necessary for synthesis of the porphyrin ring, it has an absolute growth requirement for a porphyrin source . This requirement can be satisfied in vitro by hemoglobin and hemoglobin complexed to haptoglobin . The products of the hgp genes mediate the utilization of heme from hemoglobin-haptoglobin . These genes are also involved in the use of heme from hemoglobin, although additional gene products independently mediate the acquisition of heme from this substrate . Different strains of H . influenzae possess one to four hgp genes . A nontypeable H . influenzae mutant lacking all the hgp genes was constructed and compared to the wild-type strain in a chinchilla (Chinchilla lanigera) model of otitis media . Compared to the wild-type strain, the hgp-deficient mutant exhibited a significantly delayed onset of detectable middle ear infection and significantly reduced duration of infection as assessed by both video otoscopy and tympanometry and as evidenced by viable bacterial counts in middle ear effusions . In addition, the maximum bacterial load in the middle ears of chinchillas infected with the mutant strain was significantly reduced when compared to the parent . These data indicate that the hemoglobin/hemoglobin-haptoglobin binding proteins are required for bacterial proliferation during H . influenzae-induced otitis media in chinchillas. Arch Pediatr, 2003 Dec, 10(12), 1071 - 4 {Bilateral jugular thrombosis in Lemierre syndrome}; Benhayoun M et al.; An adolescent presented with a rhinosinusitis complicated with bilateral jugular veins and left superior ophthalmic vein thrombosis and respiratory distress with pulmonary hypertension . Blood culture was positive for Haemophilus influenzae and sinus puncture for Streptococcus constellatus . Evolution was under control after 1 week of appropriate antibiotherapy, antithrombotic and anti-inflammatory treatment . He had no neurologic, respiratory or ophthalmologic sequelae 6 months later . Despite lack of pharyngitis or isolation of anaerobic species on blood cultures, the picture was considered compatible with Lemierre syndrome . The risk for such a complication should be considered in cases of severe otorhinolaryngologic infection in young adults. Int J Pediatr Otorhinolaryngol, 2003 Dec, 67(12), 1317 - 23 Microbiology of otorrhea in children with tympanostomy tubes: implications for therapy; Dohar J; OBJECTIVE: Based on the prevalence of children with tympanostomy tubes who develop otorrhea, an analysis was performed to identify specific prognostic indicators in this population to enable clinicians to determine the likelihood of specific pathogens and select the best empiric therapy . METHODS: Data from two multicenter clinical trials of ofloxacin otic solution 0.3% (OFLX) trials in pediatric patients 1-12 years of age were used to develop a statistical model to predict the likelihood of external auditory canal (EAC) or nasopharyngeal (NPG) pathogens . Data were available for 283 microbiologically evaluable patients . Potential indicators included subject age, season of enrollment, ear aspiration, cleaning, otorrhea, and granulation tissue . The model used a stepwise logistic regression analysis relating the occurrence of NPG or EAC pathogens to the potential prognostic indicators . RESULTS: Among the total study population, 42.8 and 61.5% had NPG and EAC pathogens, respectively; 10.6% had both . The most frequently isolated valid pathogens were Streptococcus pneumoniae and Haemophilus influenzae . Significant prognostic indicators for NPG pathogens were subject age, season of enrollment, and presence of ear odor . Although these indicators were similar for EAC and NPG pathogens, the correlation was reversed, i.e . older subjects had EAC pathogens, and younger ones (< 2 years) had NPG pathogens; EAC pathogens were associated with presence of ear odor and NPG pathogens, with absence of ear odor . CONCLUSIONS: A statistically and clinically valid model has been developed that has prognostic value for the clinician treating children with otorrhea and tympanostomy tubes and serves as an aid in the appropriate choice of empiric therapy. Bone Marrow Transplant, 2004 Feb, 33(3), 337 - 46 Efficacy of donor vaccination before hematopoietic cell transplantation and recipient vaccination both before and early after transplantation; Storek J et al.; Allogeneic hematopoietic cell transplantation is followed by humoral immunodeficiency . We evaluated whether antibody levels can be improved by recipient vaccination on day -1 and 50 and whether the levels can be further improved by donor vaccination on day -20 . A total of 85 patients were randomized or assigned to one of the following strategies of immunization with Streptococcus pneumoniae polysaccharides, Haemophilus influenzae polysaccharide-protein conjugate, tetanus toxoid (protein recall antigen) and hepatitis B surface antigen (protein neo-antigen): (1) donor on day -20, recipient on days -1, +50 and +365 (D(-20)R(-1,50,365)); (2) donor nil, recipient on days -1, +50 and +365 (D(N)R(-1,50,365)); or (3) donor nil, recipient on day +365 (D(N)R(365)) . For H . influenzae and tetanus, IgG levels after grafting were the highest in the D(-20)R(-1,50,365) patients, intermediate in the D(N)R(-1,50,365) patients and the lowest in the D(N)R(365) patients . For S . pneumoniae and hepatitis B, antibody levels appeared to be similar in all three patient groups . The results suggest that for polysaccharide-protein conjugate antigens or protein recall antigens, recipient immunization on days -1 and 50 improves antibody levels and that donor vaccination on day -20 further improves the levels . In contrast, neither recipient immunization on days -1 and 50 nor donor immunization on day -20 appears to be efficacious for polysaccharide antigens and poorly immunogenic protein neo-antigens. Infect Immun, 2003 Dec, 71(12), 7202 - 7 Genetic analysis of the capsule locus of Haemophilus influenzae serotype f; Satola SW et al.; A 19-kb DNA region containing genes involved in the biosynthesis of the capsule of Haemophilus influenzae serotype f (Hif) has been cloned and characterized . The Hif cap locus organization is typical of group II capsule biosynthetic loci found in other H . influenzae serotype b bacteria and other gram-negative bacteria . However, the Hif cap locus was not associated with an IS1016 element . Three new open reading frames, Fcs1, Fcs2, and Fcs3, were identified in the Hif capsule-specific region II . The chromosomal location of the Hif cap locus and the organization of the flanking sequences differed significantly from previously described division I H . influenzae serotypes. Infect Immun, 2003 Dec, 71(12), 7178 - 82 Haemophilus ducreyi requires an intact flp gene cluster for virulence in humans; Spinola SM et al.; An intact Haemophilus ducreyi flp operon is essential for microcolony formation in vitro . tadA is the 9th of 15 genes in the operon and has homology to NTPases of type IV secretion systems . Fifteen human volunteers were experimentally infected with both H . ducreyi 35000HP and the tadA mutant, 35000HP.400 . Papules developed at similar rates at sites inoculated with the mutant and parent, while pustules formed at 36.4% of parent sites and at 0% of mutant sites (P = 0.001) . Compared to 35000HP, 35000HP.400 had only a modest but significant reduction in lesion scores in the temperature-dependent rabbit model of chancroid . These data suggest that proteins secreted by the flp locus are required for full expression of virulence by H . ducreyi in humans but have less of a role in virulence in an animal model of infection. Infect Immun, 2003 Dec, 71(12), 6971 - 7 A humoral immune response confers protection against Haemophilus ducreyi infection; Cole LE et al.; Haemophilus ducreyi is the etiologic agent of the sexually transmitted genital ulcer disease chancroid . Neither naturally occurring chancroid nor experimental infection with H . ducreyi results in protective immunity . Likewise, a single inoculation of H . ducreyi does not protect pigs against subsequent infection . Accordingly, we used the swine model of chancroid infection to examine the impact of multiple inoculations on a host's immune response . After three successive inoculations with H . ducreyi, pigs developed a modestly protective immune response evidenced by the decreased recovery of viable bacteria from lesions . All lesions biopsied 2 days after the first and second inoculations contained viable H . ducreyi cells, yet only 55% of the lesions biopsied 2 days after the third inoculation did . Nearly 90% of the lesions biopsied 7 days after the first inoculation contained viable H . ducreyi cells, but this percentage dropped to only 16% after the third inoculation . Between the first and third inoculations, the average recovery of CFU from lesions decreased approximately 100-fold . The reduced recovery of bacteria corresponded directly with a fivefold increase in H . ducreyi-specific antibody titers and the emergence of bactericidal activity . These immune sera were protective when administered to naive pigs prior to challenge with H . ducreyi . These data suggest that pigs mount an effective humoral immune response to H . ducreyi after multiple exposures to the organism. Infect Immun, 2003 Dec, 71(12), 6915 - 20 Th1-directing adjuvants increase the immunogenicity of oligosaccharide-protein conjugate vaccines related to Streptococcus pneumoniae type 3; Lefeber DJ et al.; Oligosaccharide (OS)-protein conjugates are promising candidate vaccines against encapsulated bacteria, such as Haemophilus influenzae, Neisseria meningitidis, and Streptococcus pneumoniae . Although the effects of several variables such as OS chain length and protein carrier have been studied, little is known about the influence of adjuvants on the immunogenicity of OS-protein conjugates . In this study, a minimal protective trisaccharide epitope of Streptococcus pneumoniae type 3 conjugated to the cross-reacting material of diphtheria toxin was used for immunization of BALB/c mice in the presence of different adjuvants . Subsequently, half of the mice received a booster immunization with conjugate alone . Independent of the use and type of adjuvant, all mice produced long-lasting anti-polysaccharide type 3 (PS3) antibody levels, which provided full protection against challenge with pneumococcal type 3 bacteria . All adjuvants tested increased the anti-PS3 antibody levels and opsonic capacities as measured by an enzyme-linked immunosorbent assay and an in vitro phagocytosis assay . The use of QuilA or a combination of the adjuvants CpG and dimethyl dioctadecyl ammonium bromide resulted in the highest phagocytic capacities and the highest levels of Th1-related immunoglobulin G (IgG) subclasses . Phagocytic capacity correlated strongly with Th1-associated IgG2a and IgG2b levels, to a lesser extent with Th2-associated IgG1 levels, and weakly with thiocyanate elution as a measure of avidity . Thus, the improved immunogenicity of OS-protein conjugates was most pronounced for Th1-directing adjuvants. Infect Immun, 2003 Dec, 71(12), 6884 - 91 Human antibodies specific for the high-molecular-weight adhesion proteins of nontypeable Haemophilus influenzae mediate opsonophagocytic activity; Winter LE et al.; The HMW1- and HMW2-like adhesion proteins of nontypeable Haemophilus influenzae are expressed by 75% of these strains, and antibodies directed against these proteins are protective in animal models of infection . The purpose of the present study was to define the functional activity of human antibodies specific for these proteins in an in vitro complement-dependent opsonophagocytic assay . Human promyelocytic cell line HL-60 served as the source of phagocytic cells, and a commercial preparation of intravenous immunoglobulin (IVIG) served as the source of human antibodies . High-molecular-weight (HMW) proteins were purified from four prototype nontypeable H . influenzae strains and used to prepare solid-phase affinity columns . IVIG was adsorbed on each column to remove strain-specific anti-HMW antibodies and to allow recovery of affinity-purified anti-HMW antibody fractions . Unadsorbed IVIG killed each of the prototype strains at titers of 1:80 to 1:320 . HMW-adsorbed sera demonstrated fourfold decreases in opsonophagocytic titer against the homologous strains compared to unadsorbed IVIG . Affinity-purified anti-HMW antibody preparations demonstrated opsonophagocytic titers of 1:20 to 1:80 against the respective homologous strains and opsonophagocytic titers as high as 1:80 against heterologous strains . None of the affinity-purified anti-HMW antibody preparations was opsonophagocytic for a representative nontypeable H . influenzae strain that did not express HMW1- or HMW2-like proteins . These data demonstrate that human antibodies specific for the HMW1/HMW2-like adhesion proteins of nontypeable H . influenzae are opsonophagocytic and that such antibodies recognize epitopes shared by the HMW proteins of unrelated nontypeable H . influenzae strains . These results argue for continued investigation of the HMW1/HMW2-like proteins as potential vaccine candidates for prevention of disease due to nontypeable H . influenzae. Infect Immun, 2003 Dec, 71(12), 6784 - 92 Identification of dimethyl sulfoxide reductase in Actinobacillus pleuropneumoniae and its role in infection; Baltes N et al.; Actinobacillus pleuropneumoniae, the causative agent of porcine pleuropneumonia, is capable of persisting in oxygen-deprived surroundings, namely, tonsils and sequestered necrotic lung tissue . Utilization of alternative terminal electron acceptors in the absence of oxygen is a common strategy in bacteria under anaerobic growth conditions . In an experiment aimed at identification of genes expressed in vivo, the putative catalytic subunit DmsA of anaerobic dimethyl sulfoxide reductase was identified in an A . pleuropneumoniae serotype 7 strain . The 90-kDa protein exhibits 85% identity to the putative DmsA protein of Haemophilus influenzae, and its expression was found to be upregulated under anaerobic conditions . Analysis of the unfinished A . pleuropneumoniae genome sequence revealed putative open reading frames (ORFs) encoding DmsB and DmsC proteins situated downstream of the dmsA ORF . In order to investigate the role of the A . pleuropneumoniae DmsA protein in virulence, an isogenic deletion mutant, A . pleuropneumoniae DeltadmsA, was constructed and examined in an aerosol infection model . A . pleuropneumoniae DeltadmsA was attenuated in acute disease, which suggests that genes involved in oxidative metabolism under anaerobic conditions might contribute significantly to A . pleuropneumoniae virulence. Antimicrob Agents Chemother, 2003 Dec, 47(12), 3831 - 9 Novel antibacterial class; Dandliker PJ et al.; We report the discovery and characterization of a novel ribosome inhibitor (NRI) class that exhibits selective and broad-spectrum antibacterial activity . Compounds in this class inhibit growth of many gram-positive and gram-negative bacteria, including the common respiratory pathogens Streptococcus pneumoniae, Haemophilus influenzae, Staphylococcus aureus, and Moraxella catarrhalis, and are nontoxic to human cell lines . The first NRI was discovered in a high-throughput screen designed to identify inhibitors of cell-free translation in extracts from S . pneumoniae . The chemical structure of the NRI class is related to antibacterial quinolones, but, interestingly, the differences in structure are sufficient to completely alter the biochemical and intracellular mechanisms of action . Expression array studies and analysis of NRI-resistant mutants confirm this difference in intracellular mechanism and provide evidence that the NRIs inhibit bacterial protein synthesis by inhibiting ribosomes . Furthermore, compounds in the NRI series appear to inhibit bacterial ribosomes by a new mechanism, because NRI-resistant strains are not cross-resistant to other ribosome inhibitors, such as macrolides, chloramphenicol, tetracycline, aminoglycosides, or oxazolidinones . The NRIs are a promising new antibacterial class with activity against all major drug-resistant respiratory pathogens. Acta Paediatr, 2003 Oct, 92(10), 1163 - 9 Hand, foot and mouth disease in Singapore: a comparison of fatal and non-fatal cases; Chong CY et al.; AIM: An epidemic of hand, foot and mouth disease (HFMD) occurred in Singapore between September and November 2000 . During the epidemic, there were four HFMD-related deaths and after the epidemic, another three HFMD-related deaths . This study sought to determine the risk factors predictive of death from HFMD disease . METHODS: The risk factors for fatal HFMD were determined by comparing clinical and laboratory findings between fatal cases (n = 7) and non-fatal controls (n = 131) admitted between September 2000 and April 2001 . Enterovirus 71 positive fatal cases (n = 4) and non-fatal controls (n = 63) were also compared . RESULTS: In total, 138 HFMD cases with a mean age of 32 mo were studied . The majority of fatal cases died from interstitial pneumonitis, of whom three also had brainstem encephalitis . Of the 131 non-fatal cases, 3 had concomitant infections (respiratory syncytial virus bronchiolitis, right-sided pneumonia, Haemophilus influenzae type b meningitis), 2 had aseptic meningitis, and 1 each had transient drowsiness, intravenous immunoglobulin-related complications and transverse myelitis . By multivariate logistic regression analysis, atypical physical findings (p = 0.0006), raised total white cell count (p = 0.0128), vomiting (p = 0.0116) and absence of mouth ulcers (p = 0.043) were predictive of a fatal course . Although previous epidemics have described neurogenic pulmonary oedema as the main cause of death, the fatal cases in this study died mainly from interstitial pneumonitis alone or with myocarditis or encephalitis . CONCLUSION: Although HFMD is generally a benign disease, risk factors such as vomiting, absence of mouth ulcers, atypical presentation and raised total white cell count should alert the physician of a fatal course of illness. Paediatr Drugs, 2003, 5 Suppl 1, 25 - 33 Acute bacterial rhinosinusitis in pediatric medicine: current issues in diagnosis and management; Anon JB; In children, acute bacterial rhinosinusitis is a common infection and although rare, carries a potential for serious, life threatening complications . Bacterial rhinosinusitis usually follows a viral infection or allergic rhinitis . Early, effective antibacterial therapy is essential to shorten the duration of infection and illness, to diminish mucosal damage, and to prevent contiguous infectious involvement of the orbit or central nervous system . Because the signs and symptoms of acute bacterial rhinosinusitis are similar to those of viral upper respiratory tract infection, establishing an accurate diagnosis in children poses a clinical challenge . Infection with Streptococcus pneumoniae accounts for 30-66% of episodes of acute bacterial rhinosinusitis in children . Other important pathogens include Haemophilus influenzae (20-30%) and Moraxella catarrhalis (12-28%) . In selecting initial antimicrobial therapy, priority should be given to drugs with activity against S . pneumoniae . The oral agents that currently offer the greatest activity against this pathogen include amoxicillin, amoxicillin-clavulanate, cefdinir, cefpodoxime proxetil, and cefuroxime axetil; all are considered appropriate for the initial treatment of acute bacterial rhinosinusitis in children . Amoxicillin is customarily used as first-line therapy for uncomplicated acute bacterial rhinosinusitis . For patients who are allergic to amoxicillin, second- or third-generation oral cephalosporins may be used as first-line therapy . Clarithromycin has been suggested as an alternative to amoxicillin or cephalosporins in beta-lactam allergic patients . Clindamycin may also be indicated as first-line treatment in patients who have culture-proven penicillin-resistant S . pneumoniae . If no clinical response occurs within 72 hours, the choice of a second-line antibiotic is governed by the drug's known antimicrobial efficacy, resistance patterns, dosing schedules, the potential for compliance, and knowledge of the patient's drug allergies . High-dose amoxicillin-clavulanate (90 mg/kg/d of the amoxicillin component) has been recommended for high-risk children (e.g . those in day care, and those who have recently received antibiotics) who show no improvement after treatment with the usual dose of amoxicillin (45 mg/kg/d) . Broad-spectrum, third-generation oral cephalosporins, such as cefdinir, should be considered as second-line agents when standard therapy has failed or when patients show hypersensitivity to penicillin . Intramuscular ceftriaxone may be appropriate for patients who fail on a second course of antibiotic treatment. Paediatr Drugs, 2003, 5 Suppl 1, 1 - 12 Acute otitis media in pediatric medicine: current issues in epidemiology, diagnosis, and management; Leibovitz E; Acute otitis media (AOM) is not only the most common bacterial infection in children in the United States, it is also the most common indication for the prescription of antibiotics . Unfortunately, antibiotic resistance to pathogens (Streptococcus pneumoniae, Haemophilus influenzae, and Moraxella catarrhalis) typically causative of AOM, continues to increase . More than 30% of the beta-lactamase producing H . influenzae are resistant to amoxicillin and virtually all strains of M . catarrhalis are beta-lactamase-positive . The emergence of multidrug-resistant strains, particularly S . pneumoniae, complicates the management of AOM and increases the risk for treatment failure . Because of growing resistance, the Centers for Disease Control and the American Academy of Pediatrics promote the judicious use of antibiotics in the treatment of AOM . Their recommendations emphasize the importance of distinguishing AOM from otitis media with effusion, minimizing the use of antibiotics, and discerning between first- and second-line antibiotics in the treatment of simple uncomplicated AOM versus non-responsive/recurrent AOM . Because spontaneous cure rates are lower in complicated AOM and AOM secondary to S . pneumoniae infection, antibiotic therapy remains an appropriate treatment option for most children with AOM . When amoxicillin, the treatment of choice in AOM, is not effective or not tolerated in children, the prescriber should consider an alternative that displays not only excellent antimicrobial activity against the suspected pathogens, but also characteristics, such as convenient dosing, tolerability, and palatability, that promote compliance and adherence in children . The cephalosporins offer an alternative to penicillins . Cephalosporins such as cefuroxime axetil (second-generation) and cefdinir and cefpodoxime proxetil (third-generation), offer a broad spectrum of activity and are approved for use in a convenient once- or twice-daily dosing schedule, thus increasing the likelihood of compliance with the full course of therapy . Cefdinir is a possible second-line alternative to amoxicillin for children with AOM, particularly among children who are likely to be noncompliant with a two- to three-times-daily dosing schedule, and those instances where there is a high likelihood for, or a known infection with an amoxicillin-resistant pathogen. Presse Med, 2003 Sep 6, 32(28 Suppl), S12 - 4 {Antipneumococcal vaccines in sickle-cell anemia and asplenia}; Cohen R; TWO MEANS OF PREVENTION: Asplenic and sickle-cell anemia patients are susceptible to infections caused by polysaccharide-encapsulated bacteria, particularly pneumococci, Haemophilus influenzae b, and meningococci . Prevention of these frequent and serious infections depends on antibiotic prophylaxis and vaccination . ANTI-POLYSACCHARIDE PNEUMOCOCCI: Vaccination Pneumo 23 is a 23-valent vaccine corresponding to more than 90% of the pneumococci strains implicated in systemic infections . The efficacy of conjugated polysaccharide vaccines for the prevention of systemic infections, particularly when caused by antibiotic-resistant strains, can optimize the efficacy potential of antibiotic prophylaxis, the immense majority of strains not covered by the conjugated vaccine being susceptible to penicillin . CONJUGATED PNEUMOCOCCAL VACCINE: Prevenar is a seven-valence vaccine which induces a thymodependent antibody response . The efficacy of the conjugated vaccine against systemic infections, particularly antibiotic resistant strains, can have a potentializing effect on antibiotic prophylaxis, the vast majority of the strains not present in the conjugated vaccine being sensitive to penicillin . OTHER VACCINES: Finally, it should be recalled that conjugated antigroup C meningococcal vaccines are recommended for asplenic and sickle-cell anemia patients . In France, the anti-Haemophilus b vaccine is included in the vaccination calendar for all infants. Presse Med, 2003 Sep 6, 32(28 Suppl), S5 - 9 {Asplenia and hyposplenism}; Beytout J et al.; FROM ASPLENIA TO SEVERE INFECTION: The most serious consequence of asplenia due to absence of the spleen, its resection or its functional failure is the risk of severe infection . RAPIDLY PROGRESSIVE SEPTICEMIA: It is estimated that the risk of death due to septicemia is 200 times higher in splectomized patients than in patients with a spleen . Death occurs within several days or even hours in most of the patients due to overwhelming post-splenectomy infection (OPSI) . The bacteria causing OPSI are predominantly pneumococci (50-80% of identified infections) as well as meningococci, Haemophilus sp, and other capsulated bacteria . IMPORTANCE OF AGE: The risk of infection is even greater if asplenia began early in life, either because of rapidly progressive congenital hemotological disease or splenectomy during infancy or early childhood . According to Holdsworth, infectious morbidity in subjects splenectomized before the age of 16 years is 4.4%, mortality reaches 2.2% . In adults, morbidity is 0.9% and mortality 0.8% . PREVENTION OF RECURRENCE: Furthermore, in an asplenic subject or in a patient with a chronic disease threatening the spleen, the development of infectious episodes is an expression of evolving immunodepression, calling for preventive measures against recurrence . Anti-pneumococcal vaccination and antibiotic prophylaxis using penicillin V considerably reduces the incidence of pneumococcal infection in splenectomized subjects. Pediatr Res, 2004 Feb, 55(2), 347 - 56 Epub 2003 Nov 19. Childhood vaccine development: an overview; Baker JP et al.; Vaccines against childhood diseases represent some of the most important applications of 20th-century pediatric research . This survey examines how the components of the current U.S . immunization schedule emerged in three phases during the course of the century . The first phase, after the development of bacterial culture techniques, witnessed numerous efforts in the early 1900s to develop bacterial vaccines . It proved most fruitful with respect to diphtheria, tetanus, and pertussis . The rise of viral tissue culture techniques in the 1950s brought about a second phase of innovation resulting in vaccines against polio, measles, mumps, rubella, and varicella . A third wave of innovation, still very much alive, has drawn on a variety of new technologies and led to vaccines against hepatitis B, Haemophilus influenzae type b, pneumococcus, and still other organisms . Although basic science research has thus been a primary factor shaping the history of vaccine development, the collaboration between the academic, private, and public sectors critical to its application has not always proceeded smoothly . The history of vaccine research and development has important implications for today, as a variety of factors threaten to fragment this network. Int J Clin Pract, 2003 Oct, 57(8), 686 - 8 Nasopharyngeal carriage rate of Haemophilus influenzae in children aged 7-12 years in Turkey; Ayyildiz A et al.; This study was undertaken to determine the nasopharyngeal carriage prevalence of Haemophilus spp . in children aged 7-12 years in Erzurum, Turkey . Three hundred randomly selected students from three regions with different socioeconomic properties were included in the study . Nasopharyngeal swabs taken from the students were streaked into selective media for Haemophilus spp . Isolated colonies were identified by macroscopic and microscopic examination and their X and V factor needs determined . Those identified as H . influenzae were serotyped by specific capsule antisera . Haemophilus spp . were recovered from 51 (17.0%), nine (3.0%) of which were H . influenzae type b (Hib), 30 (10.0%) H . influenzae non-type b, and 12 (4.0%) H . parainfluenzae . Results were evaluated by several risk factors such as age, gender, number of siblings, siblings attending a nursery, family smoking habits and family economic status. Bioorg Med Chem Lett, 2003 Dec 1, 13(23), 4209 - 12 New antibacterial tetrahydro-4(2H)-thiopyran and thiomorpholine S-oxide and S,S-dioxide phenyloxazolidinones; Singh U et al.; Combinatorial libraries of N-acylated 5-(S)-aminomethyloxazolidinone derivatives of S-oxide and S,S-dioxide tetrahydro-4(2H)-thiopyranyl and thiomorpholine phenyloxazolidinone series have been synthesized on a solid phase and evaluated for antimicrobial activity . Several novel potent leads have been identified, including orally active oxazolidinones with enhanced activity against respiratory tract infection pathogens Haemophilus influenzae and Moraxella catarrhalis. Pediatr Pulmonol, 2003 Dec, 36(6), 469 - 74 Global burden of acute respiratory infections in children: implications for interventions; Mulholland K; Despite dramatic advances in human health that have occurred during the 20th century, the end of the century still sees many places in the world with high child mortality rates . This is made worse by increasing inequity, such that there are still many communities in the world in which over 30% of children die before their fifth birthday . Estimates of the global burden of childhood pneumonia are based on the assumption that there is a predictable relationship between the childhood mortality rate and the proportion of that mortality that is attributable to pneumonia . As most child deaths occur at home and can only be investigated by verbal autopsy techniques, these estimates are very crude and provide only a guide to the overall burden of pneumonia . Recent estimates from the World Health Organization suggest that 1.9 million children die as a result of acute respiratory infection (ARI), mainly pneumonia, each year . For a number of reasons, this is likely to be an underestimate . Estimates of the morbidity burden attributable to pneumonia are also very approximate, as studies have used different and nonstandardized definitions of pneumonia . These estimates were originally used to assist with planning of ARI intervention activities and for advocacy to draw attention to the problem of ARI . Recently, the introduction of new vaccines against Haemophilus influenzae type b (Hib) and Streptococcus pneumoniae (pneumococcus) raised the prospect of prevention of pneumonia by vaccination . For reasons outlined in this paper, great caution must be exercised before using existing pneumonia burden estimates to predict mortality savings that may accompany the introduction of these vaccines into developing countries . J Bacteriol, 2003 Dec, 185(23), 6990 - 4 Slipped-strand mispairing can function as a phase variation mechanism in Escherichia coli; Torres-Cruz J et al.; Slipped-strand mispairing (SSM) has not been identified as a mechanism of phase variation in Escherichia coli . Using a reporter gene, we show that sequences that cause phase variation by SSM in Haemophilus influenzae also lead to phase variation when introduced onto the chromosome of E . coli, and the frequencies of switching are in the biologically relevant range . Thus, the absence of SSM-mediated phase variation in E . coli does not appear to be due to a mechanistic constraint. Mol Microbiol, 2003 Nov, 50(3), 1017 - 30 A Neisserial autotransporter NalP modulating the processing of other autotransporters; van Ulsen P et al.; Autotransporters constitute a relatively simple secretion system in Gram-negative bacteria, depending for their translocation across the outer membrane only on a C-terminal translocator domain . We have studied a novel autotransporter serine protease, designated NalP, from Neisseria meningitidis strain H44/76, featuring a lipoprotein motif at the signal sequence cleavage site . Indeed, lipidation of NalP could be demonstrated, but the secreted 70 kDa domain of NalP lacked the lipid-moiety as a result of additional N-terminal processing . A nalP mutant showed a drastically altered profile of secreted proteins . Mass-spectrometric analysis of tryptic fragments identified the autotransporters IgA protease and App, a homologue of the adhesin Hap of Haemophilus influenzae, as the major secreted proteins . Two forms of both of these proteins were found in the culture supernatant of the wild-type strain, whereas only the lower molecular-weight forms predominated in the culture supernatant of the nalP mutant . The serine-protease active site of NalP was required for the modulation of the processing of these autotransporters . We propose that, apart from the a