Commun Dis Intell, 1997 Feb 20, 21(4), 41 - 6 Epidemiology and prevention of pneumococcal disease; McIntyre P; There are comparatively little data on the incidence and morbidity from pneumococcal disease in Australia and elsewhere . Available data suggest that the overall incidence of invasive pneumococcal disease in Australia is comparable with similar populations . Very high rates are reported in Central Australian Aborigines, similar to invasive Haemophilus influenzae type b (Hib) disease . Disease incidence is probably greatly underestimated by case ascertainment from sterile site isolates alone . New diagnostic methods, such as serology to detect components of the pneumococcal cell wall, promise to significantly enhance detection of pneumococci as a cause of pneumonia, especially in childhood, but are epidemiologic rather than clinical tools . Resistance to penicillin and other antibiotics is an increasing problem worldwide, promoted by excessive antibiotic use, especially in children . This has focused attention on vaccine prevention . Fortunately, antibiotic-resistant pneumococci appear to belong to a limited range of serotypes, those commonly colonising children, in all areas so far studied . If conjugate pneumococcal vaccines prove to eradicate carriage, in a similar fashion to conjugate Hib vaccines, vaccination may be the major weapon against the spread of antibiotic-resistant pneumococcal infection . Conjugate pneumococcal vaccines are now in large scale efficacy trials, with outcomes of bacteraemia (California) and otitis media (Finland) . Results of these trials are eagerly awaited. FEMS Microbiol Lett, 1997 Feb 15, 147(2), 233 - 8 Characterization of a novel transporter family that includes multiple Escherichia coli gluconate transporters and their homologues; Peekhaus N et al.; The nucleotide sequences of seven Escherichia coli genes that encode members of the gluconate permease (GntP) family have recently become available . These genes include gntP, gntU, gntW, ORf449, dsdX, and ORFo454 . The deduced amino acid sequences of all seven E . coli genes are homologous to the gntP gene products from Bacillus subtilis and B . licheniformis as well as two additional gene products from Haemophilus influenzae . These 11 proteins are not demonstrably homologous to members of the major facilitator superfamily or other recognized permease families . Four of the E . coli gluconate transporter genes have been cloned and shown to encode gluconate transporters with apparent affinities ranging from 6 to 212 microM . These studies serve to characterize a novel family of bacterial permeases. MMWR Morb Mortal Wkly Rep, 1997 Feb 7, 46(5), 107 - 9 FDA approval for infants of a Haemophilus influenzae type b conjugate and hepatitis B (recombinant) combined vaccine. {Acute pericarditis in childhood . The 9-year experience of a tertiary referral center} Farinha NJ, Bartolo A, Trindade L, Vaz T, Monterroso J, Areias JC, Santos NT. Servico de Cardiologia Pediatrica, Departamento de Pediatria, Hospital S . Joao, PortoSixteen children, aged 7 months to 12 years, with acute pericarditis, admitted between 1985 and 1993 to a tertiary referral centre were analyzed retrospectively for their presentation, etiology, work-up, management and prognosis . It was found that most of the presenting signs were not specific and were often related to associated diseases such as respiratory tract infections . In 50% of the cases a cause was not found, the others had viral infections (12.5%), tuberculosis (12.5%), Haemophilus influenzae infection (6.25%), Toxocara canis infection (6.25%) and collagen diseases (12.5%) . In eight cases non-steroidal anti-inflammatory drugs associated with steroids were given, 7 patients received non-steroidal anti-inflammatory drugs and 1 steroids . The mean follow-up time was 3 years (1 to 5) . Six patients had one or more relapses . Five of the 6 patients with relapses were in the group which received steroids . The two patients with tuberculosis underwent pericardiectomy . One child died due to complex heart disease and the remaining 15 were cured . It was concluded that in pericarditis an extensive work-up may not reveal the major etiologies and that long term prognosis is good. Acta Med Port, 1997 Feb-Mar, 10(2-3), 129 - 38 {Anti-hepatitis B and anti-Haemophilus influenzae type b vaccines}; Dias PG; The epidemiologic aspects of hepatitis B are analysed . The author proposes the vaccination of all children, risk groups and teenagers . Also the high incidence of Haemophilus influenzae infections in Portugal justifies the use of an anti-Hib vaccine administered to all children under 5 years, preferentially in the first year of life. Pneumologie, 1997 Feb, 51(2), 99 - 103 {Differential cytology of bronchoalveolar lavage fluid in healthy children in comparison with children colonized by lung-specific pathogens}; Ahrens P et al.; BAL is increasingly used in the assessment of pulmonary diseases, however, the role in children remains to be defined . Therefore bronchoalveolar lavage (BAL) was performed on 21 healthy children in order to enable quantification and characterization of the alveolar cell populations . Reference values for cellular constituents of BAL fluid using rigid bronchoscopes are lacking-even though in children still 90% of bronchoscopies are done by rigid instruments and BAL is performed using a catheter leading into the lower lobe . The children, 12 months to 14 years of age, were lavaged adjusted to body weight with three 1 ml/kg aliquots of normal saline . Recovery was 31 +/- 12% . Each aliquot was analysed separately . The number of total cell count per milliliter was 29.8 x 10(4) (range 0.6-161 x 10(4) . Percentages of different cell types of the third simple were (mean): macrophages 88.5, lymphocytes 6.4, neutrophils 4.8, eosinophils 0.1, basophils 0% . Significantly more neutrophils and less lymphocytes were found in the first as compared to the second and third sample . No age dependency was observed for either cell type . The comparison to cellularity of BAL-fluid with proven evidence of Adenovirus, Streptococcus pneumoniae, Moraxella catarrhalis and Haemophilus influenzae type B showed a marked influence of viral and bacterial germs . The study provides the first reference data on BAL differential cytology in healthy children using rigid bronchoscopy. Oral Microbiol Immunol, 1997 Feb, 12(1), 27 - 32 Myeloperoxidase isoform activities released by human neutrophils in response to dental and periodontal bacteria; Miyasaki KT et al.; Myeloperoxidase is an enzyme released by polymorphonuclear leukocytes which has been used, experimentally, as an indicator of periodontal disease activity when measured in gingival crevicular fluid . There are three myeloperoxidase isoforms: MPO I, MPO II and MPO III . We examined the activities of myeloperoxidase isoforms released by neutrophils in response to serum-opsonized Actinobacillus actinomycetemcomitans, Haemophilus aphrophilus, Eikenella corrodens, Capnocytophaga sputigena and Streptococcus sanguis . Isoform activities were determined using intermediate-pressure liquid chromatography and microenzyme assay . A . actinomycetemcomitans stimulated higher levels of myeloperoxidase release than any other oral bacteria unless pre-opsonized with serum (or protein-A-purified immunoglobulin) from an individual with localized juvenile periodontitis . Most oral bacteria stimulated the release of all myeloperoxidase isoforms with a profile enriched in MPO I and diminished in MPO III . Exceptionally, serum-opsonized A . actinomycetemcomitans stimulated myeloperoxidase isoform release in proportion to the neutrophil granule constituency with or without localized juvenile periodontitis serum pre-opsonization . Because myeloperoxidase isoform profiles reflect how neutrophils were stimulated, isoform analysis may refine future diagnostic tests based upon myeloperoxidase. Vaccine, 1997 Feb, 15(3), 325 - 8 Factors associated with superior antibody responses to a single dose of Haemophilus influenzae type b-tetanus toxoid conjugate vaccine administered to Chilean infants at 2 months of age; Levine OS et al.; The anticapsular antibody response of Chilean infants to a single dose of Haemophilus influenzae type b capsular polysaccharide-tetanus toxoid conjugate, vaccine is substantially higher than that observed among infants of similar age from the USA . Comparison of selected demographic and environmental factors indicates that low maternal education and a greater number of persons in the home are significantly associated with the superior responder phenotype . High anticapsular antibody responses were associated with high antibody responses to tetanus toxoid, the carrier protein in this conjugate, but not to diphtheria toxoid . These data suggest that environmental factors may enhance the magnitude of the primary antibody response to PRP-T vaccine. Vaccine, 1997 Feb, 15(3), 295 - 300 Safety and immunogenicity of an acellular pertussis diphtheria tetanus vaccine given as a single injection with Haemophilus influenzae b conjugate vaccine; Halperin SA et al.; To determine if an acellular pertussis-diphtheria-tetanus vaccine could be combined with a Haemophilus influenzae b conjugate vaccine as a single injection, we randomized 468 children between 17 and 21 months of age previously immunized with three doses of each vaccine to receive a five-component acellular pertussis vaccine combined with diphtheria and tetanus toxoids, and Haemophilus influenzae b-tetanus toxoid conjugate vaccine either as separate injections on separate days, separate injections on the same day, or as a single combined injection . Rates of adverse reactions were similar amongst the groups except for increased injection site tenderness (29.2% vs 17%, RR 1.76, 95% CI 1.09-2.85) and fussiness (36.4% vs 23.3%, RR 1.59, 95% CI 1.05-2.41) in the group given the combined injection rather than separate injections on separate days . Antibody levels against the capsular polysaccharide of H . influenzae b after the single combined injection (47.1 micrograms ml-1) were lower than after separate injections on the same day (66.0 micrograms ml-1; P < 0.05) but higher than when the injections were administered on separate days (28.4 micrograms ml-1; P < 0.001) . We conclude that the five-component acellular pertussis vaccine is safe and immunogenic when combined with diphtheria and tetanus toxoids and H . influenzae b-tetanus toxoid conjugate vaccine in children receiving the fourth dose of the immunization series. Acta Paediatr Jpn, 1997 Feb, 39(1), 44 - 7 Rapid, sensitive and specific diagnosis of Bordetella pertussis using the polymerase chain reaction; Aoyama T et al.; Use of a repetitive DNA sequence of Bordetella pertussis allowed successful detection of the organism by the polymerase chain reaction (PCR) . The method was highly sensitive, being able to detect B . pertussis in specimens containing only a few cells . It was also highly specific, with no amplification of specimens containing other organisms, for example Haemophilus influenzae or Neisseria, being observed . A diagnosis could be made within 1 day . The PCR assay was also evaluated in clinical specimens . Among 47 nasopharyngeal specimens obtained from 24 patients with laboratory-confirmed pertussis, 27 were positive by PCR and 19 by culture . In particular, all three bronchial aspirates from one patient with pertussis were positive by PCR, but only one showed positive on culture . Eleven specimens from parapertussis patients and 65 specimens from patients without pertussis tested negative . It was concluded that this newly developed PCR method for the diagnosis of pertussis was more rapid and sensitive than the usual culture method . Polymerase chain reaction could have a major impact on the treatment and control of this infection and would be a useful tool for studying the pathogenesis of B . pertussis infection. Sex Transm Dis, 1997 Feb, 24(2), 64 - 8 Iron and virulence of Haemophilus ducreyi in a primate model; Sturm AW; BACKGROUND AND OBJECTIVES: The pathogenesis of chancroid is currently unclear . There are discrepancies between the virulence of Haemophilus ducreyi in the human and animal experiments . Iron availability influences the virulence of many pathogens . The objective of this study was to investigate the role of iron in virulence of H . ducreyi . STUDY DESIGN: Intradermal inoculation of the primate Macaca mulatta was studied as an animal model for pathogenesis of chancroid . This model then was used to study the influence of iron availability on virulence of H . ducreyi . Eleven strains of H . ducreyi with proven avirulence in the rabbit intradermal test and one virulent control strain were used . Two of the strains had been shown to cause ulcers in a human inoculation experiment . Strains were suspended in fluid with different iron compounds before intradermal injection . Other monkeys were treated with injectable iron before inoculation with bacteria suspended . RESULTS: All but one of the test strains produced a chancroid-like ulcer from which H . ducreyi could be isolated . The minimal ulcerative dose was 10(5) cfu . Iron in the injection fluid decreased this dose 10-fold . In animals pretreated with intramuscular iron, the minimal ulcerative dose decreased to 10(4) cfu and all eleven strains became ulcerative . CONCLUSIONS: The availability of iron increases virulence of H . ducreyi . The iron pretreated primate model is useful for the study of virulence factors of H . ducreyi because of its ability to produce lesions with strains that avirulent in other animal models but pathogenic to humans. J Chemother, 1997 Feb, 9(1), 44 - 50 Comparative trial of 3 days of azithromycin versus 10 days of clarithromycin in the treatment of children with acute otitis media with effusion; Arguedas A et al.; The authors compared the efficacy, safety and tolerance of azithromycin and clarithromycin in pediatric patients with acute otitis media . A randomized, open clinical trial was performed comparing azithromycin and clarithromycin in children aged 6 months to 12 years of age with acute otitis media with effusion . Patients were allocated to azithromycin at 10 mg/kg once daily for 3 days or to clarithromycin at 15 mg/kg day divided into two equal doses for 10 days . Clinical examinations and tympanometric evaluations were performed at baseline, day 3-5, day 10-14, day 28-30 and day 50-60 . Tympanocentesis fluid cultures were collected at enrollment and urine and blood samples were obtained at baseline and day 10-14 . Of 100 patients enrolled, 97 were considered evaluable . The most common middle ear pathogens were Streptococcus pneumoniae (60%), Haemophilus influenzae (15%) and Staphylococcus aureus (13%) . Fifty patients (100%) treated with azithromycin and 45 (95.7%) patients treated with clarithromycin had a satisfactory clinical response . Rates of persistence of middle ear effusion and possible drug related side effects were comparable . Based on the efficacy and safety results, azithromycin for 3 days and clarithromycin for 10 days are considered to represent an attractive alternative for the treatment of children with acute otitis media. J Antibiot (Tokyo), 1997 Feb, 50(2), 162 - 8 Structure-activity relationships of carbapenem compounds to anti-Haemophilus influenzae activity and affinity for penicillin-binding proteins . Effect of 1 beta-methyl group and C-2 side chain; Kanazawa K et al.; The anti-H . influenzae activity of meropenem (1a) was much higher than those of imipenem (4) . panipenem (2b) and biapenem (7) . To clarify the major structural features responsible for the anti-H . influenzae activity of carbapenem compounds, the structure-activity relationship to the anti-H . influenzae activity was investigated . The anti-H . influenzae activities of meropenem (1a) and 1 beta-methyl-panipenem (2a) were much higher than those of desmethyl-meropenem (1b) and panipenem (2b) . respectively . Two carbapenems (5, 6) and imipenem (4), that have a strong basic C-2 side chain, showed lower anti-H . influenzae activity than meropenem (1a) having a weakly basic C-2 side chain and N-acetyl thienamycin (3) having a neutral C-2 side chain, respectively . As a result, we found that the introduction of the 1 beta-methyl group or the reduction of the basicity (cationic character) of the C-2 side chain increased the antimicrobial activity and bactericidal activity of carbapenems against H . influenzae due to their increased affinity for PBP-4 and PBP-5. Pathology, 1997 Feb, 29(1), 72 - 5 In vitro susceptibility patterns of nonserotypable Haemophilus influenzae from patients with chronic bronchitis; Butt HL et al.; The antimicrobial susceptibility patterns of 76 nonserotypable Haemophilus influenzae (biotypes I-IV) from patients with chronic bronchitis were compared against ten orally administered antimicrobial agents . In addition the sputum ampicillin concentrations one hour after standard therapy were determined in five patients with chronic bronchitis . Ampicillin resistance was demonstrated in one strain (biotype IV) which produced beta-lactamase and two strains (biotype II) with innate resistance (MIC = 4 mg/l) . Resistance to trimethoprim, chloramphenicol, ciprofloxacin and cefaclor was not detected . The incidence of resistance to tetracycline was 0.5% and cephalexin 13.2% . A high incidence of resistance to erythromycin (95%) was noted . There was no association between resistance and biotype of nonserotypable H . influenzae . The sputum ampicillin concentrations from four out of five patients given standard antibiotic doses were shown to be sufficient to inhibit the growth of the majority of nonserotypable H . influenzae strains one hour after treatment . This study shows that the incidence of nonserotypable H . influenzae resistant to ampicillin is low in this community but that resistance levels to erythromycin, commonly prescribed for the management of acute bronchitis, are high . Regular sensitivity screens are important in monitoring the value of various antibiotic regimens in the management of acute bronchitis. Aust N Z J Med, 1997 Feb, 27(1), 59 - 61 Community acquired pneumonia in north eastern Australia--a hospital based study of aboriginal and non-aboriginal patients; Thompson JE; BACKGROUND: Although the most important organism causing community acquired pneumonia continues to be Streptococcus pneumoniae, the frequency of other pathogens varies considerably across the world . AIMS: To look for the causes of community acquired pneumonia (CAP) in north east Australia . To examine the differences between Aboriginal and non-Aboriginal subjects with emphasis on prevalence, risk factors, causative organisms and prognosis . METHODS: The records of 200 consecutive patients admitted to Cairns Hospital during 1992 with a diagnosis of pneumonia were studied . RESULTS: Aboriginal patients made up half the numbers admitted, but only 13% of the population . More Aboriginal adults died than non-Aboriginal adults, but no child died . Heavy alcohol use, chronic lung disease and diabetes mellitus were the commonest risk factors for Aborigines (alcohol, chronic lung disease and cancer for non-Aboriginal subjects) . S . pneumoniae, followed by Haemophilus influenzae were the most common pathogens found . Both were sensitive to amoxycillin . The yield of definite pathogens was low . Staphylococcal and melioidosis pneumonia were confined to Aboriginal patients . Chlamydia, legionella and Mycoplasma pneumoniae were not identified. J Trop Pediatr, 1997 Feb, 43(1), 10 - 2 Spectrum of Haemophilus influenzae type b disease in children at a university hospital in Riyadh, Saudi Arabia; Abdullah AM et al.; During a period of 5 years, 42 cases of invasive Haemophilus influenzae type b (Hib) disease were studied . An outstanding finding in our patients was occult bacteraemia, which was detected in 13 (31 per cent) patients . Other clinical conditions encountered were nine (21 per cent) patients with pneumonia, nine (21 per cent) with meningitis, six (14 per cent) with cellulitis, three (7 per cent) with arthritis, one (2 per cent) with epiglottitis, and one (2 per cent) with urinary tract infection . The mean age of children was 21 months (range 1-156 months); the majority (62 per cent) belonged to the age group 7-18 months . There were 24 females and 18 males . Eighty-one per cent of these patients were Saudi nationals . Five isolates (12 per cent) of Hib were resistant to ampicillin and similar numbers were resistant to chlorampenicol . Twenty-five children (60 per cent) were treated with ampicillin, nine (21 per cent) with chlorampenicol and eight (19 per cent) with ceftriaxone . All patients made complete recovery. J Formos Med Assoc, 1997 Feb, 96(2), 110 - 5 Safety and immunogenicity of a conjugated Haemophilus influenzae type B polysaccharide-Neisseria meningitidis outer membrane protein vaccine; Yeh SJ et al.; This study was performed to determine the immunogenicity and safety of a conjugate Haemophilus influenzae type b (Hib) vaccine (PedvaxHIB:Merck Sharp & Dohme Inc, West Point, PA, USA) in Taiwanese children . There were two groups in this study . Group A included 56 infants at 2 months of age, who received an initial dose of Hib conjugate vaccine at age 2 months and 4 months . Another booster dose was given between 12 and 15 months of age . Group B included 58 children, aged 11 to 14 months, who were vaccinated at the time of enrollment and 2 months after the first vaccination . The results showed that this Hib conjugate vaccine was highly immunogenic with 100% and 86% of vaccinees in group A developing anti-Hib polyribosylribitol phosphate (PRP) antibody titers above 0.15 microgram/mL and 1 microgram/mL, respectively, after two vaccinations . A slightly better response rate was observed in group B, with 100% and 97% of vaccinees developing antibody titers above 0.15 microgram/mL and 1 microgram/ml, respectively, after two vaccinations . A significant booster effect was seen in group A; the proportion of subjects with antibody titers above 1 microgram/mL increased from 38% to 95%, and the geometric mean titer increased from 0.68 microgram/mL to 11.92 micrograms/mL . Adverse reactions were uncommon . Mild reactions consisted of low-grade fever and local discomfort . We conclude that the Hib conjugate vaccine is highly immunogenic and safe when given to Taiwanese children as young as 2 months of age. Enferm Infecc Microbiol Clin, 1997 Feb, 15(2), 65 - 9 {Maternal-fetal vertical transmission of Haemophilus influenzae and Haemophilus parainfluenzae}; Garcia E et al.; BACKGROUND: Maternal-fetal transmission of Haemophilus influenzae (HI) and Haemophilus parainfluenzae (HPI) as well as characteristics of the infection in the neonate have been poorly described . METHODS AND RESULTS: From 1982 to 1994 18 HI and 12 HPI from vaginal secretion of 30 women obtained intrapartum or immediately post partum were isolated . The following was observed in the 18 patients in whom HI was isolated: 1 abortion, 2 antepartum death, 1 post partum death, and 14 live neonates from whom 10 were suspect a infection with 5 cases being confirmed with isolation of HI in blood culture . Mortality was 40% . The rate of vertical transmission of HI was 80% (8/10) and neonatal sepsis 50% (5/10) (71.4% of the infants whose mothers did not receive intrapartum antibiotics and 0% in those who did) . Twenty-seven point seven percent of the strains of HI were beta-lactamase producers with II and III being the most frequent biotypes observed . Of the 12 patients from whom HPI was isolated the following was reported: 1 antepartum death, and 12 live neonates of whom 10 were suspect a infection, but no case was confirmed because HPI was not isolated from blood culture . The vertical transmission of HPI was 20% (2/10) . CONCLUSIONS: The isolation of HI in the vagina of pregnant women should be considered as being potentially very virulent since despite a low prevalence, the rate of vertical transmission and, overall, neonatal sepsis, is high. J Antimicrob Chemother, 1997 Feb, 39(2), 209 - 16 Anti-CD11b monoclonal antibody in an infant rat model of Haemophilus influenzae type b sepsis and meningitis; Tan TQ et al.; Five-day-old infant rats were injected intraperitoneally (i.p.) with anti-CD11b monoclonal antibody (1 B6) at a dose of 2 mg/kg or phosphate-buffered saline (PBS) either 1 h before or 3 or 24 h after inoculation with 10(5) cfu Haemophilus influenzae type b (Hib) . When administered 1 h before infection, 23% of the 1B6- versus 17% of the PBS-treated rats and 87% of the 1B6- versus 83% of the PBS-treated animals died at 24 and 48 h, respectively . There was a similar mortality for 1B6 or PBS treatment at 3 h after infection . Thirteen of 15 (87%) 1B6 animals versus 16/17 (94%) PBS animals had positive CSF cultures at 48 h . No differences in mortality were observed in separate experiments where animals received 1B6 or PBS 3 or 24 h after infection with Hib and were treated with a single ampicillin dose (100 mg/kg) 24 h after infection . The median CSF white blood cell count/mm3 was 5627 and 4860 for the animals with meningitis receiving 1B6 and PBS, respectively, although the 1B6-treated animals had a lower percentage of polymorphonuclear cells in the CSF (P = 0.05) . Histologic examination of the meninges, choroid plexus and cochlea showed a slight decrease in the numbers of inflammatory cells in animals treated with 1B6 . 1B6 did not change the incidence of meningitis and only slightly decreased the degree of inflammation within the central nervous system, although animals treated with 1B6 have an altered CSF leucocyte response with the presence of more mononuclear cells as opposed to polymorphonuclear cells in their CSF . 1B6 may play a role in inhibiting neutrophil emigration to sites of inflammation within the central nervous system but is not beneficial in decreasing mortality in an infant rat model of H . influenzae type b sepsis and meningitis. Arch Dis Child, 1997 Feb, 76(2), 129 - 33 Evaluation of a protocol for selective empiric treatment of fever without localising signs; Browne GJ et al.; A protocol for management of young febrile children at risk for bacteraemia has been used at Westmead Hospital, a university based hospital in the western Sydney region, since early 1994 . Implementation of the protocol was retrospectively evaluated for the 12 month period 1 June 1994 to 31 May 1995, using the emergency department log book as the primary data source . Altogether 498 children, aged from 3 months to 3 years, with a fever > or = 39.5 degrees C were identified over this period, of whom 291 were admitted to hospital because of evidence of sepsis or identified focal infection and 207 children without focal infection were observed in the short stay annexe of the emergency department . Fifty children, considered at high risk of bacteraemia because of a total white cell count > or = 20 x 10(9)/1 received empiric antibiotic treatment with ceftriaxone, of whom 19 subsequently had proved bacteraemia and another 10 had focal infection identified during observation in the short stay annexe . Bacteraemia was due to Streptococcus pneumoniae in 16 cases and Haemophilus influenzae type b in three . No adverse events occurred at follow up . Use of a management protocol and selection on higher white cell count criterion than previously recommended by US centres resulted in restriction of empiric antibiotic treatment to a small proportion of young febrile children presenting to a busy emergency department of whom 38% were bacteraemic. Vaccine, 1997 Feb, 15(2), 209 - 19 Persistence of antibodies to meningococcal IgA1 protease versus decay of antibodies to group A polysaccharide and Opc protein; Thiesen B et al.; Sera were taken over a 5 year period from Gambian children vaccinated in 1983, when aged 1-4 years, with A + C meningococcal capsular polysaccharide, ELISA tests were devised to determine the concentrations of immunoglobulin A, G and M reacting with A polysaccharide and of IgG reacting with Opc protein, IgA1 protease and an internal 104 mer peptide derived from IgA1 protease . Vaccination resulted in a brief rise of antibodies to A polysaccharide followed by decline to pre-immunization levels . IgM levels were very high even before vaccination . Antibodies to Opc protein stimulated by natural exposure also declined over the 5 year period . In contrast, antibodies stimulated by natural exposure to IgA1 protease or to the internal peptide remained constant or increased (final geometric mean level of 47 micrograms IgG ml-1) . We speculate that healthy carriage of Neisseria meningitidis or Haemophilus influenzae is responsible for this increase in IgG concentration. Vaccine, 1997 Feb, 15(2), 149 - 54 Immunogenicity and safety of a liquid combination of DTP-PRP-T {corrected} vs lyophilized PRP-T reconstituted with DTP; Amir J et al.; The immunogenicity and safety of a combined diphtheria, tetanus, pertussis and Haemophilus influenzae type b-tetanus conjugate vaccine (DTP-PRP-T) was compared to the same combination obtained by the reconstitution of H . influenzae type b-tetanus conjugate vaccine lyophilized (PRP-T) with liquid diphtheria-tetanus-pertussis vaccine (DTP) . Two hundred and sixty-two healthy infants were randomized to receive a intramuscular injection of 0.5 ml of one of the above combination vaccines at 2, 4 and 6 months of age, and a subgroup of 134 infants received a booster dose at 12 months . Serum antibody levels to each vaccine component were measured at ages 2, 6, 7, 12 and 13 months . Systemic and local reactions were assessed during the first 3 days after each injection by diary cards distributed to the parents . After the third dose and booster administered at 12 months of age, significant equivalence between the groups was observed, and the geometric mean titer of anti H . influenzae type b capsular polysaccharide (Hib-CP) antibodies were 5.9 and 32.6 micrograms ml-1 for the liquid combination group and 5.8 and 19.4 for the lyophilized group, respectively . After the third dose, anti-Hib-PC antibody levels of > or = 1.0 microgram ml-1 and 0.15 microgram ml-1 were seen in 94% and 100%, respectively, of the liquid combination group and 90 and 99%, respectively of the lyophilized group . After the booster dose, levels of > or = 1.0 microgram ml-1 were observed in 100% and 93.5% of the liquid combination group and the lyophilized combination group, respectively . Systemic and local reactions to the vaccination were generally mild and did not differ significantly between the groups . We conclude that the liquid combination of DTP-PRP-T is safe and at least as immunogenic as the lyophilized preparation . This liquid preparation, like other combined vaccines may be helpful for planning vaccination programs with a reduced number of injections. Pediatr Emerg Care, 1997 Feb, 13(1), 16 - 8 Aerobic and anaerobic microbiology of bacterial tracheitis in children; Brook I; STUDY OBJECTIVES: Establish the aerobic and anaerobic microbiology of bacterial tracheitis in children . METHOD: Retrospective review of specimens obtained from 14 children with bacterial tracheitis that were cultured for aerobic and anaerobic bacteria . RESULTS: A total 30 bacterial isolates were recovered, 17 aerobic and facultative anaerobic and 13 anaerobic . Aerobic bacteria only were present in six (43%) specimens, anaerobes only in three (21%), and mixed aerobic and anaerobic flora in five (36%) . Polymicrobial flora was recovered in 10 of the 14 specimens . The predominant organisms were Staphylococcus aureus (5 isolates), Haemophilus influenzae type b (4), Peptostreptococcus sp . (4), pigmented Prevotella and Porphyromonas (4), Fusobacterium sp . (2), and Moraxella catarrhalis (2) . Two organisms that were also isolated from the tracheal aspirates were recovered from the blood of two patients (one each of H . influenzae and Prevotella intermedia) . Eleven beta-lactamase-producing organisms were isolated from nine patients . These included all isolates of S . aureus and M . catarrhalis, and two each of H . influenzae and Prevotella sp . CONCLUSIONS: These data confirm the predominance of S . aureus and H . influenzae in causing bacterial tracheitis in children and suggest a potential role for anaerobic bacteria. Acta Med Okayama, 1997 Feb, 51(1), 33 - 7 Clinical effect of low-dose, long-term roxithromycin chemotherapy in patients with chronic sinusitis; Kimura N et al.; We studied the clinical efficacy of roxithromycin (RXM) administered at the daily dosage of one tablet (150 mg) for 3 months in 30 patients with chronic sinusitis . The effectiveness of this drug was evaluated on a four-point scale . Subjective and objective symptoms disappeared or decreased markedly, especially postnasal drip and nature of discharge in 80 percent or more of the patients . All symptoms significantly decreased (P < 0.001; headache P < 0.05), except for the sensation of foul odor . Symptoms improved even in those cases in which Haemophilus influenzae was detected . It is suggested that RXM produce some clinically beneficial effect through an immunological and or anti-inflammatory mechanisms in addition to its antibiotic effect. Eur J Biochem, 1997 Feb 1, 243(3), 701 - 7 Structural studies of the cell-envelope oligosaccharide from the lipopolysaccharide of Haemophilus influenzae strain RM.118-28; Risberg A et al.; The structure of the oligosaccharide part of the Haemophilus influenzae RM.118-28 lipopolysaccharide (LPS) has been investigated . The oligosaccharide was obtained from the LPS by mild acid hydrolysis followed by gel-permeation chromatography, and was studied by methylation analysis, NMR spectroscopy and mass spectrometry . The structure of the major compound, which is a hexasaccharide, is proposed as follows . {formula: see text} In the structure, Kdo is 3-deoxy-D-manno-octulosonic acid, PEtn is phosphoethanolamine, PCho is phosphocholine and L,D-Hep is L-glycero-D-manno-heptose . Electrospray-ionization mass spectrometry on O-deacylated LPS obtained after treatment with anhydrous hydrazine gave evidence for the presence of two minor compounds, which show additional substitution of the main structure with phosphate and PEtn, respectively . These substitutions have not been localized. Otolaryngol Head Neck Surg, 1997 Feb, 116(2), 175 - 80 Middle ear mucin glycoprotein: purification and interaction with nontypable Haemophilus influenzae and Moraxella catarrhalis; Reddy MS et al.; Nontypable Haemophilus influenzae and Moraxella catarrhalis are important pathogens in children and adults . The mechanisms of their adherence to the epithelial cell surface and colonization are not clear . For the pathogen to adhere to the epithelial cell, it must first attach to and penetrate the mucus barrier . Mucin glycoproteins of the mucus layer generally are thought to be involved in bacterial attachment . To understand the precise mechanisms of middle ear mucin-bacterial interactions, we used an overlay binding assay with a highly purified middle ear mucin and outer membrane proteins of both nontypable H . influenzae and M . catarrhalis . Outer membrane proteins P2 and P5 were identified as the major components that medicate the binding between nontypable H . influenzae and human middle ear mucin . Moreover, the 57 kDa protein, CD, of the outer membrane protein of M . catarrhalis was found to be the only protein binding human middle ear mucin . Finally, it appears that a protein-oligosaccharide interaction is responsible for binding because asialo-mucin does not bind to either of the bacteria . Knowledge of the specific bacterial-mucin interaction may provide an understanding of the bacterial-epithelial cell colonization . Conversely, comprehension of this interaction between bacteria and purified mucin may be a strategy to prevent colonization of potential pathogens that cause otitis media and sinusitis in children. Postgrad Med, 1997 Feb, 101(2), 191 - 2, 195-6, 199-200 Haemophilus influenzae infections in adults: a pathogen in search of respect; Strausbaugh LJ; Despite the success of Haemophilus influenzae type b vaccines in preventing bacterial disease in children, H influenzae remains a common pathogen in adult patients in the United States and Europe . At least half of invasive H influenzae infections are caused by nontypable strains . The spectrum of diseases includes sinusitis, pneumonia, otitis media, epiglotitis, and meningitis . An etiologic diagnosis is most reliably established by positive cultures from a normally sterile site . Although resistance to ampicillin and amoxicillin has steadily increased in clinical H influenzae isolates during the past two decades, a variety of other antimicrobial agents are available for the treatment of infections caused by this bacterium. Mol Microbiol, 1997 Feb, 23(3), 569 - 77 Characterization of monoclonal antibodies recognizing three distinct, phosphorylated carbohydrate epitopes in the lipopolysaccharide of the deep rough mutant I-69 Rd-/b+ of Haemophilus influenzae; Rozalski A et al.; Monoclonal antibodies against the lipopolysaccharide (LPS) of the deep rough mutant I-69 Rd-/b+ of Haemophilus influenzae were obtained after immunization of mice with sheep erythrocytes which had been coated with de-O-acylated LPS . Characterization of antibodies was performed by enzyme immuno assay (EIA) using LPS or neoglycoconjugates containing partial structures of LPS as solid-phase antigens and by haemagglutination with sheep erythrocytes coated with de-O-acylated LPS . Binding data were confirmed by EIA inhibition experiments using deacylated LPS or synthetic partial structures thereof . Three antibodies were specific for 3-deoxy-D-manno-octulopyranosonic acid- (Kdo) 5-phosphate, one for Kdo-4-phosphate, and one required, in addition to a Kdo-phosphate, parts of the phosphorylated glucosamine backbone of lipid A . All antibodies also bound in (i) Western blots to bacterial whole-cell lysates or isolated LPS separated by SDS-PAGE, (ii) bacterial colony blots, and (iii) immunofluorescence with live bacteria . The latter result indicated that Kdo-4- and Kdo-5-phosphate are synthesized by the bacteria and are not the result of phosphate migration. Br J Oral Maxillofac Surg, 1997 Feb, 35(1), 43 - 5 Selective use of tracheostomy in surgery for head and neck cancer: an audit; Crosher R et al.; This retrospective study was designed to define the role of tracheostomy in the operative treatment of patients with cancers of the head and neck . The subjects were 51 patients who underwent neck dissection with resection of the tumour and repair during the period January 1992-December 1994, out of a total of 109 patients who were treated for cancers of the head and neck during that time . Three patients required tracheostomies, two of which were done preoperatively, and one immediately postoperatively for respiratory distress . There were no operative deaths . Morbidity included wound infection (n = 2), chest infection caused by Haemophilus influenzae (n = 1), transient fever associated with blood transfusion (n = 5), and transient fever of no obvious cause (n = 3) . Median hospital stay was 10 days (range 4-38) . Patients undergoing operations for cancers of the head and neck do not require routine tracheostomy . Further research on how to select patients who will need tracheostomy is necessary and is being done. Pediatr Infect Dis J, 1997 Feb, 16(2 Suppl), S21 - 4 Comparison of the efficacy, safety and acceptability of cefixime and amoxicillin/clavulanate in acute otitis media; Gooch WM 3rd et al.; BACKGROUND: Use of a beta-lactamase stable antibiotic is called for in cases of acute otitis media (AOM) likely to be caused by beta-lactamase-producing Haemophilus influenzae or Moraxella catarrhalis . Two beta-lactamase-stable agents commonly used for empirical treatment of AOM are amoxicillin/clavulanate and cefixime . METHODS: A multicenter, randomized clinical trial compared cefixime (CFX; 8 mg/kg once daily) with amoxicillin/clavulanate (A/C; 40 mg/kg/day in three divided doses) for the treatment of children with AOM . Three hundred thirteen children were randomly assigned to a 10-day course of either CFX (n = 158) or A/C (n = 155) . Based on history, physical examinations and otoscopic and tympanometric assessments, clinical responses were evaluated as cure, improvement, failure, relapse or nonevaluable . Compliance and patient/parent acceptability were also analyzed . RESULTS: Overall favorable clinical responses (cure plus improvement) were comparable post-therapy for the two treatments (CFX = 76%; A/C = 77%) . Significant differences in response rates for both treatments were noted among different geographic regions, with the highest response rates observed in the Northeast and South . Acceptability of CFX was significantly better than that of A/C (P = 0.0001), and the adverse experience rate was lower (P = 0.001) . The most frequently reported adverse experiences were diarrhea (CFX 15.2%, A/C 29.7%) and vomiting (CFX 3.2%, A/C 10.32%) . Relapse rates were 26% for CFX and 29% for A/C . CONCLUSION: This study demonstrated that CFX has comparable clinical efficacy and a better adverse events profile than A/C when used to treat AOM of childhood. Pediatr Infect Dis J, 1997 Feb, 16(2 Suppl), S17 - 20 Conjunctivitis in infants and children; Wald ER; BACKGROUND: Acute bacterial conjunctivitis, chiefly affecting young children, is generally caused by one of three common pathogens, Haemophilus influenzae, Streptococcus pneumoniae and adenovirus . H . influenzae is the most prevalent causative organism . Some patients presenting initially with conjunctivitis subsequently develop acute otitis media, with H . influenzae the most common etiologic agent of what has been termed the "conjunctivitis-otitis" syndrome . Optimal treatment of acute conjunctivitis would result in a clinical and bacteriologic cure of the conjunctivitis and the prevention of the development of otitis media . Application of topical antimicrobials at 4- to 6-h intervals a day for 1 week to 10 days results in the resolution of the conjunctivitis . However, topical treatment is difficult to administer to toddlers and does not effectively reduce the potential for the development of otitis media . Compared with topical and placebo treatment, oral antibiotics effective against H . influenzae have proved to be most effective in preventing the otitis media associated with conjunctivitis . CONCLUSION: Acute bacterial conjunctivitis is a common disorder in children < 6 years of age . H . influenzae is the most common etiology of the "conjunctivitis-otitis syndrome." The optimal treatment for this condition is still being studied. Pediatr Infect Dis J, 1997 Feb, 16(2 Suppl), S12 - 6 Using antibiotic concentrations in middle ear fluid to predict potential clinical efficacy; Harrison CJ; BACKGROUND: The effectiveness of an antibiotic in eradicating an infection within an anatomic compartment is related to both its availability (penetration) and the susceptibility of the causative pathogen . Antimicrobial penetration can be assessed by measuring concentrations in serum or tissue . However, to assess antibiotic effectiveness in the treatment of otitis media, both antibiotic concentrations and pathogen profiles in middle ear fluid (MEF) should be considered . Tympanocentesis is required to access fluid in the middle ear compartment . This paper considers data on (MEF) antibiotic concentrations obtained with this procedure . METHODS: Data on MEF antibiotic concentrations were considered in relation to the antibiotic susceptibility profiles of the more common otitis media pathogens . RESULTS: Amoxicillin reaches MEF concentrations that exceed MICs for penicillin-susceptible and penicillin relatively resistant Streptococcus pneumoniae, but not for beta-lactamase-producing Haemophilus influenzae . Several beta-lactamase-stable drugs, e.g . cefixime and amoxicillin/clavulanate, however, achieve MEF concentrations that easily exceed their respective MIC90s for both beta-lactamase-producing and nonproducing H . influenzae but at ordinary doses may not exceed MIC90s for penicillin relatively resistant S . pneumoniae . CONCLUSION: Ongoing observation of organisms and their antibiotic resistance patterns in patients failing initial therapy of acute otitis media indicate that stability to beta-lactamase remains an essential quality for effective second line therapies . However, when possible tympanocentesis with culture is the ideal method of targeting specific therapy for patients failing multiple consecutive antibiotic regimens. Pediatr Infect Dis J, 1997 Feb, 16(2 Suppl), S5 - 8 Role of nontypeable Haemophilus influenzae in pediatric respiratory tract infections; Klein JO; BACKGROUND: Nontypeable strains of Haemophilus influenzae may spread contiguously from the upper respiratory tract and cause sinusitis, otitis media and pneumonia . Unlike H . influenzae type b these strains rarely invade the bloodstream to cause widespread infections . These strains are primary pathogens of acute otitis media, sinusitis and the conjunctivitis-otitis syndrome . In developing countries these strains are also responsible for many cases of pediatric pneumonia . Currently approximately 30% of nontypeable H . influenzae strains are beta-lactamase-positive and can inactivate susceptible penicillins, including penicillins G and V, ampicillin and amoxicillin . Most second generation oral cephalosporins are active against beta-lactamase-producing H . influenzae . Some third generation oral cephalosporins, e.g . cefixime, however, have particularly good efficacy against H . influenzae . Sulfonamides and chloramphenicol are generally effective as well . CONCLUSION: Until a vaccine that provides adequate prophylaxis against nontypeable H . influenzae is developed, clinicians should be guided by knowledge of bacterial susceptibility and microbiologic efficacy in choosing appropriate agents for treating pediatric infections likely to involve this common pathogen. FEMS Microbiol Lett, 1997 Feb 1, 147(1), 11 - 6 Cloning and characterization of the groE locus from Actinobacillus pleuropneumoniae; Vezina G et al.; A 4.4-kb DNA fragment was cloned from Actinobacillus pleuropneumoniae (strain 4074, serotype 1) by genetic complementation with Escherichia coli groES-groEL mutant strains . Sequence analysis of this fragment revealed a purine nucleoside phosphorylase (DeoD)-encoding gene homolog (deoD), heat-shock response-encoding genes for the small (groES) and large subunits (groEL) and a partial open reading frame encoding an alcohol dehydrogenase homolog (adhE) . The predicted amino-acid sequence of groES and groEL genes showed extensive sequence identity (80-95%) with other Pasteurellaceae . The gene organization surrounding the groE locus was different from that of Haemophilus infuenzae . When expressed in E . coli, groES-groEL genes were capable of complementing the growth of a lambda lytic phage, indicating a structural as well as functional conservation. Am J Hematol, 1997 Feb, 54(2), 131 - 8 Infectious morbidity in long-term survivors of allogeneic marrow transplantation is associated with low CD4 T cell counts; Storek J et al.; Survivors of allogeneic marrow transplants are immunodeficient for at least 1 year after grafting . Multiple defects of immunity have been found; however, it is not known which defect primarily accounts for the high infectious morbidity of these patients . Twenty-nine allograft recipients who were in complete remission of the original disease were examined for the following parameters of immunity at 1 year after transplant: infection score (gauging the number and severity of infections within the 6 months prior to the annual exam), serum total IgM, IgG, and IgA, anti-Haemophilus influenzae IgG, anti-Streptococcus pneumoniae IgG, skin test reactivity, and the blood counts of B cells, CD4+ T cells, CD8+ T cells, and their subsets . THe only parameter inversely correlated with the infection score was CD4+ T cell count (P = 0.005 in univariable analysis, P = 0.06 in multivariable analysis) . We conclude that infectious morbidity of long-term transplant survivors is related to the reconstitution of CD4+ T cells. Antimicrob Agents Chemother, 1997 Feb, 41(2), 454 - 9 In vitro evaluation of a novel ketolide antimicrobial agent, RU-64004; Jamjian C et al.; Ketolides, a novel macrolide subclass, possess a mode of action that is similar to that of structurally related macrolide-lincosamide-streptogramin (MLS) compounds . By using reference in vitro tests, the in vitro activity of RU-64004 was compared to those of six other MLS compounds against more than 800 clinical pathogens, including 356 gram-positive organisms . The spectrum of activity of the ketolide was most similar to that of clindamycin versus staphylococci and streptococci and superior to those of all macrolides tested against oxacillin-resistant staphylococci and vancomycin-resistant (vanA, vanB, and vanC) enterococcal isolates . The activity of the ketolide was greater than those of the macrolides, azalides, or clindamycin tested against vancomycin-susceptible enterococci (MICs at which 90% of isolates are inhibited {MIC90S}, 0.25 to 4 micrograms/ml), penicillin-resistant pneumococci (MIC90, 0.25 micrograms/ml), and most beta-hemolytic streptococci . All Streptococcus pneumoniae and beta-hemolytic streptococcus strain were inhibited by ketolide concentrations of < or = 0.25 micrograms/ml . Against 165 erythromycin-resistant strains, RU-64004 inhibited (MICs, < or = 0.5 micrograms/ml) approximately one-third of staphylococci, all streptococci, and slightly more than one-half of the enterococci . Quinupristin-dalfopristin (a streptogramin combination) was active against all tested isolates with the exception of non-Enterococcus faecium enterococci, against which the ketolide exhibited greater potency (MIC50S, 0.03 to 2 micrograms/ml) . The ketolide was also active against Haemophilus influenzae (MIC90, 2 micrograms/ml), Moraxella catarrhalis (MIC90, 0.12 micrograms/ml), pathogenic Neisseria spp . (MIC90, 0.5 micrograms/ml), and many gram-positive anaerobes (MIC90, 0.5 micrograms/ml) . RU-64004 may enhance the role of macrolide drugs in the treatment of some serious infections caused by MLS-resistant gram-positive organisms. Antimicrob Agents Chemother, 1997 Feb, 41(2), 292 - 7 Antibiotic resistance among clinical isolates of Haemophilus influenzae in the United States in 1994 and 1995 and detection of beta-lactamase-positive strains resistant to amoxicillin-clavulanate: results of a national multicenter surveillance study; Doern GV et al.; A total of 1,537 clinical isolates of Haemophilus influenzae were recovered in 30 U.S . medical center laboratories between 1 November 1994 and 30 April 1995 and were characterized in a central laboratory with respect to serotype and beta-lactamase production and the in vitro activities of 15 oral antimicrobial agents . Overall, 36.4% of the isolates were found to produce beta-lactamase . The rank order of activity of six cephalosporins on the basis of MICs was cefixime > cefpodoxime > cefuroxime > loracarbef > or = cefaclor > cefprozil . On the basis of current National Committee for Clinical Laboratory Standards (NCCLS) breakpoints ages of isolates found to be resistant or intermediate to these agents were as follows: 0.1, 0.3, 6.4, 16.3, 18.3, and 29.8, respectively (National Committee for Clinical Laboratory Standards . Methods for dilution antimicrobial susceptibility tests for bacteria that grow aerobically, 4th ed . M7-A4, 1995) . Azithromycin was, on a weight basis, the most potent of the macrolides tested in this study, followed by erythromycin and then clarithromycin . Azithromycin was typically fourfold more active than erythromycin, which was, in turn, slightly more active than clarithromycin . However, when compared on the basis of the frequency of resistance determined by using current NCCLS breakpoints, there was essentially no difference between azithromycin and clarithromycin, i.e., 0.5 and 1.9%, respectively (P = 0.086) . Interpretive breakpoints for erythromycin MIC tests versus H . influenzae have not been developed . Resistance to other non- beta-lactam agents was variable, as follows: trimethoprim-sulfamethoxazole, 9.0%; chloramphenicol, 0.2%; tetracycline, 1.3%; and rifampin, 0.3% . Two conspicuous findings in this study were the identification of 39 strains H . influenzae that were beta-lactamase negative but ampicillin intermediate or resistant (BLNAR) and, even more surprisingly, 17 beta-lactamase-positive isolates that were resistant to amoxicillin-clavulanate (BLPACR) . Strains of H . influenzae in the first group have heretofore been very uncommon; organisms in the second group have not previously been described in the literature . The percentages of all study isolates comprised of BLNAR and BLPACR organisms were 2.5 and 1.1, respectively . Overall resistance to ampicillin was thus 38.9%, and that to amoxicillin-clavulanate was 4.5%. Soc Sci Med, 1997 Feb, 44(4), 441 - 54 STDS in women attending family planning clinics: a case study in Addis Ababa; Duncan ME et al.; For cultural reasons modern contraception has been slow to gain acceptance in Ethiopia . Knowledge about contraception and abortion is still limited in many family and community settings in which it is socially disapproved . By 1990 only 4% of Ethiopian females aged 15-49 used contraception . Little is known of sexually transmitted disease (STD) prevalence in family planning (FP) attenders in Africa in general and Ethiopia in particular, even though attenders of family planning clinics (FPCs) are appropriate target groups for epidemiological studies and control programmes . A study of 2111 women of whom 542 (25.7%) attended FPCs in Addis Ababa showed utilisation rates to be highest in women who were: Tigre (33%) or Amhara (31%), aged 20-34 years (30%), age 16 or older at first marriage/coitus (28%:38% in those first married after 25 years); who had a monthly family income of 10 Ethiopian Birr (EB) or more (33%:36% for those with income 100-500 EB), three or more children (37%), more than five lifetime husbands/sexual partners (39%); or were bargirls (73%) or prostitutes (43%) . The seroprevalence rates for all STDs, higher in FPC attenders compared with other women, were syphilis (TPHA) 39%, Neisseria gonorrhoeae 66%, genital chlamydia 64%, HSV-2 41%, HBV 40% and Haemophilus ducreyi 20% . Only 4% of FPC attenders had no serological evidence of STD: 64% were seropositive for 3 or more different STD . Clinical evidence of pelvic inflammatory disease (PID) was also more common in the FPC attenders (54%), 37% having evidence of salpingitis . The FPC provides a favourable setting for screening women likely to have high seroprevalence of STD, who for lack of symptoms will not attend either an STD clinic nor a hospital for routine check up . We recommend that measures be taken to adequately screen, treat and educate FPC attenders, their partners, and as appropriate and when possible their clients, in an attempt to control STDs and ultimately HIV in the community . Social, economic and cultural factors in the occurrence of STDs, prostitution, family planning and modern contraception coverage in Ethiopia are identified and deficiencies of current programmes briefly discussed with the objective of targeting services more effectively. Infect Immun, 1997 Feb, 65(2), 651 - 60 Identification of tandem genes involved in lipooligosaccharide expression by Haemophilus ducreyi; Stevens MK et al.; A transposon insertion mutant of Haemophilus ducreyi 35000 possessing a truncated lipooligosaccharide (LOS) failed to bind the LOS-specific monoclonal antibody 3E6 (M . K . Stevens, L . D . Cope, J . D . Radolf, and E . J . Hansen, Infect . Immun . 63:2976-2982, 1995) . This transposon was found to have inserted into the first of two tandem genes and also caused a deletion of chromosomal DNA upstream of this gene . These two genes, designated lbgA and lbgB, encoded predicted proteins with molecular masses of 25,788 and 40,236 Da which showed homology with proteins which function in lipopolysaccharide biosynthetic in other gram-negative bacteria . The tandem arrangement of the lbgA and lbgB genes was found to be conserved among H . ducreyi strains . Isogenic LOS mutants, constructed by the insertion of a cat cartridge into either the lbgA or the lbgB gene, expressed an LOS phenotype indistinguishable from that of the original transposon-derived LOS mutant . The wild-type LOS phenotype could be restored by complementation with the appropriate wild-type allele . These two LOS mutants proved to be as virulent as the wild-type parent strain in an animal model . A double mutant with a deletion of the lbgA and lbgB genes yielded equivocal results when its virulence was tested in an animal model. J Bacteriol, 1997 Feb, 179(3), 805 - 12 Neisseria meningitidis tonB, exbB, and exbD genes: Ton-dependent utilization of protein-bound iron in Neisseriae; Stojiljkovic I et al.; We have recently cloned and characterized the hemoglobin (Hb) receptor gene, hmbR, from Neisseria meningitidis . To identify additional proteins that are involved in Hb utilization, the N . meningitidis Hb utilization system was reconstituted in Escherichia coli . Five cosmids from N . meningitidis DNA library enabled a heme-requiring (hemA), HmbR-expressing mutant of E . coli to use Hb as both porphyrin and iron source . Nucleotide sequence analysis of DNA fragments subcloned from the Hb-complementing cosmids identified four open reading frames, three of them homologous to Pseudomonas putida, E . coli, and Haemophilus influenzae exbB, exbD, and tonB genes . The N . meningitidis TonB protein is 28.8 to 33.6% identical to other gram-negative TonB proteins, while the N . meningitidis ExbD protein shares between 23.3 and 34.3% identical amino acids with other ExbD and TolR proteins . The N . meningitidis ExbB protein was 24.7 to 36.1% homologous with other gram-negative ExbB and TolQ proteins . Complementation studies indicated that the neisserial Ton system cannot interact with the E . coli FhuA TonB-dependent outer membrane receptor . The N . meningitidis tonB mutant was unable to use Hb, Hb-haptoglobin complexes, transferrin, and lactoferrin as iron sources . Insertion of an antibiotic cassette in the 3' end of the exbD gene produced a leaky phenotype . Efficient usage of heme by N . meningitidis tonB and exbD mutants suggests the existence of a Ton-independent heme utilization mechanism . E . coli complementation studies and the analysis of N . meningitidis hmbR and hpu mutants suggested the existence of another Hb utilization mechanism in this organism. J Cell Biol, 1997 Jan 27, 136(2), 271 - 85 A novel membrane-associated metalloprotease, Ste24p, is required for the first step of NH2-terminal processing of the yeast a-factor precursor; Fujimura-Kamada K et al.; Many secreted bioactive signaling molecules, including the yeast mating pheromones a-factor and alpha-factor, are initially synthesized as precursors requiring multiple intracellular processing enzymes to generate their mature forms . To identify new gene products involved in the biogenesis of a-factor in Saccharomyces cerevisiae, we carried out a screen for MA Ta-specific, mating-defective mutants . We have identified a new mutant, ste24, in addition to previously known sterile mutants . During its biogenesis in a wild-type strain, the a-factor precursor undergoes a series of COOH-terminal CAAX modifications, two sequential NH2-terminal cleavage events, and export from the cell . Identification of the a-factor biosynthetic intermediate that accumulates in the ste24 mutant revealed that STE24 is required for the first NH2-terminal proteolytic processing event within the a-factor precursor, which takes place after COOH-terminal CAAX modification is complete . The STE24 gene product contains multiple predicted membrane spans, a zinc metalloprotease motif (HEXXH), and a COOH-terminal ER retrieval signal (KKXX) . The HEXXH protease motif is critical for STE24 activity, since STE24 fails to function when conserved residues within this motif are mutated . The identification of Ste24p homologues in a diverse group of organisms, including Escherichia coli, Schizosaccharomyces pombe, Haemophilus influenzae, and Homo sapiens, indicates that Ste24p has been highly conserved throughout evolution . Ste24p and the proteins related to it define a new subfamily of proteins that are likely to function as intracellular, membrane-associated zinc metalloproteases. MMWR Morb Mortal Wkly Rep, 1997 Jan 24, 46(3), 62 - 4 Antibiotic resistance among nasopharyngeal isolates of Streptococcus pneumoniae and Haemophilus influenzae--Bangui, Central African Republic, 1995; Synthesis of L-glycero-D-manno-heptopyranose-containing oligosaccharide structures found in lipopolysaccharides from Haemophilus influenzae; Department of Organic Chemistry, Arrhenius Laboratory, University of Stockholm, SwedenSyntheses are described of the tetrasaccharide 2-(4-trifluoroacetamidophenyl)ethyl O-(beta-D-galactopyranosyl)-(1-->2)-O- (L-glycero-alpha-D-manno-heptopyranosyl)-(1-->2)-O-(L-glycero-alpha-D- manno-heptopyranosyl)-(1-->3)-L-glycero-alpha-D-manno-heptopyranoside (20) and the three trisaccharides 2-(4-trifluoroacetamidophenyl)ethyl O-(L-glycero-alpha-D-manno-heptopyranosyl)-(1-->2)-O-(L-glycero-alpha-D- manno-heptopyranosyl)-(1-->3)-L-glycero-alpha-D-manno-heptopyranoside (17), 2-(4-trifluoroacetamidophenyl)ethyl O-(beta-D-glucopyranosyl)-(1-->4)- O-(beta-D-glucopyranosyl)-(1-->4)-L-glycero-alpha-D-manno-heptopyrano side (5), and 2-(4-trifluoro-acetamidophenyl)ethyl O-(beta-D-galactopyranosyl)-(1-->4)-O-(beta-D-glucopyranosyl)-(1-->4)- L-glycero-alpha-D-manno-heptopyranoside (8), corresponding to structures found in the lipooligosaccharides of Haemophilus influenzae. MMWR Morb Mortal Wkly Rep, 1997 Jan 17, 46(2), 35 - 40 Recommended childhood immunization schedule--United States, 1997; Bacterial findings in acute maxillary sinusitis--European study; Department of Otorhinolaryngology, Tampere University Hospital, FinlandBacteriology of acute maxillary sinusitis was studied in 569 patients in 16 centers of 6 countries located throughout Europe during 1992-1994 by ENT specialists . Patients with symptoms of acute sinusitis lasting less than 3 weeks with ongoing purulent nasal discharge were included . Diagnosis was verified by sinus x-ray or ultrasonography and a positive aspiration finding in maxillary sinus puncture . One or more pathogens were isolated from the maxillary sinus aspirates of 375 (66%) patients . Fifty-six percent of patients harboured 1 pathogen and 10% multiple pathogenic organisms, respectively . Haemophilus influenzae was the most common pathogen isolated (148 isolates), occurring as a single pathogen in 14% of the patients . The occurrence of H . influenzae was highest in Finnish military hospital patients (43-48%), as compared with the non-military Finnish patients (9-11%) or to patients from other European centers (mean 13%) . H . influenzae was more frequently beta-lactamase positive in other European centers (22%) than in Finnish centers (7%) . Streptococcus pneumoniae was the most common pathogen isolated in other European centers (20%) but second most common in Finnish centers (13%) . Moraxella catarrhalis occurred at quite similar frequency among Finnish centers (9-14%), but clearly less often in other centers (mean 4%) . S . aureus, which in acute maxillary sinusitis is regarded as a contaminant from the nasal cavity, was more prevalent in other European centers (12%) than in Finnish centers (4%) . In patients with acute maxillary sinusitis reliable bacteriological samples should be taken by antral aspiration directly from the diseased sinus. Acta Otolaryngol Suppl, 1997, 529, 162 - 4 Bacteriological evaluation of 194 adult patients with acute frontal sinusitis and findings of simultaneous maxillary sinusitis; Antila J et al.; In a prospective study bacteriological findings from frontal and maxillary sinus secretes were analyzed . Frontal sinus trephination was performed to 103 and maxillary irrigation to 192 patients . Main pathogens in the frontal as well as in the maxillary sinus secretes were Haemophilus influenzae and Streptococcus pneumoniae . beta-lactamase production of H . influenzae was found in 17% of frontal and in 16% of maxillary sinus samples . Bacteriological findings were supported by the staining results . The portion of anaerobic pathogens in cultures were poor, though Bacteroides fragilis antigen was detected in 8 frontal and 6 maxillary sinus samples . The acute frontal sinusitis should be treated with respective antibiotics . Complications seem not to develop in the acute phase and the disease can primarily be treated conservatively . It should however be controlled properly to avoid prolonged disease and late complications. Acta Otolaryngol Suppl, 1997, 529, 144 - 7 Do simple laboratory tests help in etiologic diagnosis in acute maxillary sinusitis? Savolainen S, Jousimies-Somer H, Karjalainen J, Ylikoski J. The aim of the present study was to evaluate whether the results of such simple hematologic tests as erythrocyte sedimentation rate (ESR), white blood cell count (WBC) and C-reactive protein (CRP) could give any useful information about the causative agents in 176 patients with acute maxillary sinusitis (AMS) . The great majority of tests (82%) showed values which were within normal limits . This may be due to the fact that 22% of AMS cases were culture negative for bacteria and about 60% of culture positive cases had Haemophilus influenzae as the etiologic agent . Significantly raised test values were seen in connection with Streptococcus pyogenes in the majority of cases, less frequently with Streptococcus pneumoniae and rarely with Haemophilus influenzae . We conclude that none of the evaluated routine blood tests are particularly sensitive indicators of the specific etiology of AMS in general . However, elevated CRP values (> 40 mg/l) associated with AMS should alert the physician to the suspicion of Streptococcus pyogenes or Streptococcus pneumoniae in etiology, since both, if left untreated, may lead to sinus empyema . With CRP or other evaluated tests Haemophilus influenzae- or Branhamella catarrhalis-positive AMS cannot be distinguished from a purely viral disease. Acta Otolaryngol Suppl, 1997, 529, 19 - 21 Are there microbiological markers to predict recurrent acute otitis media? Rynnel-Dagoo B. The nasopharynx is a natural reservoir for several bacterial species, including Streptococcus pneumoniae and Haemophilus influenzae . Carriership is a potential mechanism for pathogenicity, since bacteria might invade the Eustachian tube and cause middle ear disease . Whether the pattern of nasopharyngeal colonization is different in infection prone vs healthy children is still a matter of controversy . In several studies it has been shown that H . influenzae is carried significantly more often in otitis-prone children compared with healthy control children . Colonization with H . influenzae in young children may be regarded as a candidate for a microbiological marker for recurrent episodes of acute otitis media. SAAS Bull Biochem Biotechnol, 1997, 10, 49 - 58 Structure of the Haemophilus influenzae uvr-1+ gene: homology with other uvrC-like genes and characterization of the Haemophilus influenzae uvr-1 and uvr-2 mutations; Gottschalk VA et al.; A 3.9 kb Haemophilus influenzae genomic DNA fragment was cloned in plasmid pUC9 that partially complemented the ultraviolet light sensitivity (UVs) of Escherichia coli uvrC mutant hosts . This fragment also complemented the UVs of H . influenzae uvr-1 (DB112) and uvr-2 (DB116) mutants . It genetically transformed the latter mutants to wild type UV resistance . The nucleotide (nt) sequence of this fragment revealed 3 open reading frames (ORFs) . ORF2, now designated uvr-1+ (1746 nt), shows significant similarity in both the nt and amino acid (aa) composition to 7 complete proven or putative uvrC gene sequences . Computer analysis of the DNA sequence revealed several possible regulatory motifs 5' to uvr-1+, including a putative LexA-binding site as an inverted SOS box, located within the 3' region of ORF1, (extensive homology to the E . coli CMP-KDO synthetase gene), upstream of uvr-1+ . Further computer analysis has also predicted that the four putative active site amino acids, located in the C-terminal half of each protein, are each situated in an area of secondary structure that are highly conserved. Dev Biol Stand, 1997, 89, 379 - 89 Are serological responses to acellular pertussis antigens sufficient criteria to ensure that new combination vaccines are effective for prevention of disease? Granoff DM, Rappuoli R. Combining several vaccines in a single formulation can alleviate the increasing complexity of the paediatric vaccination schedule . However, vaccine antigens that are highly effective when administered singly may lose potency in combination; consequently, the efficacy of each component must be established for any new proposed combination vaccine . When the serological response to a vaccine correlates clearly with clinical efficacy, the efficacy of that component in a combination can be inferred from immunogenicity studies . Poliovirus, tetanus and diphtheria toxoids, Haemophilus influenzae type b and Neisseria meningitidis, and hepatitis B vaccines, can all be assessed in this manner . Unfortunately, the antibody titres induced by acellular pertussis vaccines do not correlate with vaccine efficacy . Thus, although diphtheria-tetanus-acellular pertussis (DTaP) vaccine has been considered a prime building block in the development of new combination vaccines, modifying DTaP by the addition of new vaccine components may decrease the ability of the vaccine to protect against pertussis without a change in serum antibody response . For this reason, immunogenicity is not an adequate or safe basis for licensing combination vaccines containing acellular pertussis . Development and licensing of new combination vaccines containing components with serological correlates of clinical efficacy can proceed more rapidly than DTaP-based combinations and should be pursued. Indian Pediatr, 1997 Jan, 34(1), 9 - 15 Haemophilus influenzae type b vaccine in India: need and timing, immunogenecity and tolerance; Acharya D et al.; OBJECTIVE: (i) To assess the natural immunity and susceptibility to Haemophilus influenzae type b (Hib) infections in children in India . (ii) To study the immunogenecity and tolerance of Hib vaccine (ACTHIB) in young infants . DESIGNS: (i) Cross sectional study . (ii) Prospective trial . SETTING: Well baby and immunization clinics . METHODS: (i) PRP antibody titers against Hib estimated in 172 healthy infants and children aged 1 month to 10 years . (ii) Antibody titres estimated before and after ACTHIB vaccine given with primary immunization (age group 6 to 8 weeks) in 50 babies . RESULTS: (i) Naturally protective levels of Hib antibodies found in less than 20% of infants under one year, but in over 80% above 4 years . (ii) Seroconversion after ACTHIB vaccination was 100% with very high protective levels . There were no significant adverse reactions . CONCLUSIONS: ACTHIB vaccine proved to be safe and highly immunogenic . As susceptibility to Hib is highest in the first year of life, the vaccine should be recommended in the primary immunization schedule (combined with DPT) . The very high titers achieved suggest the possibility of decreasing the number of doses or the amount of antigen to reduce the prevalent high cost. Ciba Found Symp, 1997, 207, 223 - 31; discussion 231-7 Epidemiological factors influencing the emergence of antimicrobial resistance; Cohen ML; Antimicrobial resistance is becoming an important public health problem for both hospital- and community-acquired infections . In the hospital, infections caused by drug-resistant Staphylococcus aureus, Mycobacterium tuberculosis, enterococci, and a variety of Gram-negative rods are resulting in increased morbidity, mortality and costs, in part because of prolonged hospitalization and the use of more expensive antimicrobial agents . Drug-resistant, community-acquired infections are also causing important problems in both the developed and the developing world . Although the relative importance of specific pathogens varies with the geographical area, community-acquired pathogens including Salmonella, Shigella, Neisseria gonorrhoeae, Haemophilus influenzae and Streptococcus pneumoniae are causing both sporadic cases and outbreaks of drug-resistant illness . The emergence of antimicrobial resistance is being attributed to a series of societal, technological, environmental and microbial changes . These include increasing populations of susceptible hosts, international travel and commerce, changes in technology and industry, microbial adaptation and change, and the breakdown of public health measures . Addressing emerging problems and antimicrobial resistance will require enhanced surveillance, prudent use of existing antimicrobial drugs, development of new antimicrobial agents, increased emphasis on infection control and hygienic practices, effective disease control programs, better use of existing vaccines, and development of more and better vaccines. Fundam Clin Pharmacol, 1997, 11(1), 90 - 5 Pharmacokinetics and pharmacodynamics of two oral forms of cefuroxime axetil; Garraffo R et al.; Cefuroxime axetil is a cefuroxime ester that can be administered by mouth . Two dosage forms (tablets and granules) have been developed for oral administration . We evaluated the pharmacokinetics and pharmacodynamics of these forms in an open cross-over study involving 12 healthy volunteers receiving single doses of 250 mg . The bioavailability of the two forms was different, the observed peak concentration and time-concentration curve values of the tablet form being, respectively, 39 and 27% higher than those of the granule form . However, ex vivo studies of serum bactericidal activity against Streptococcus pneumoniae showed no significant differences between the two formulations . This is in keeping with the fact that the bactericidal activity of samples from only six subjects gave evaluable data for Haemophilus influenzae; although small differences were found between the two formulations, further investigations are required . The pharmacodynamic approach is becoming an essential element in determining the equivalence of antibiotic dosage forms. Respiration, 1997, 64(3), 224 - 8 Hospitalized patients with community-acquired pneumonia in Hong Kong: a randomized study comparing imipenem/cilastatin and ceftazidime; Ho A et al.; The aetiology and outcome of hospitalized patients with moderate to severe community-acquired pneumonia (CAP) were evaluated in 60 adult patients (38 male 22 female, mean age 68.4 years) . They were randomized for treatment with either ceftazidime or imipenem/cilastatin intravenously for 7 days . Bacteriological diagnoses were made in 25 cases (41.6%): Streptococcus pneumoniae (5), Haemophilus influenzae (5), Pseudomonas spp . in particular Pseudomonas aeruginosa (8), Staphylococcus aureus (4), Chlamydia spp . (2), Mycobacterium tuberculosis (2) and Moraxella catarrhalis (3); mixed organisms were found in 4 patients . Forty-two patients (70%) responded satisfactorily to the regimens with improvement in sputum purulence cough and dyspnoea scores; there was no difference in response between the two groups . Sixteen patients (26.6%) underwent bronchoscopy on day 4 because of inadequate response to the antibiotics regimens, and 9 of them (15%) required a modification of the initial treatment with addition of erythromycin in 5 patients vancomycin in 1 cloxacillin in 1 and antituberculous drugs in 2 . Three out of the 60 patients (5%) died of pulmonary sepsis: the aetiological agents were M . tuberculosis in one, Pseudomonas spp./methicillin-resistant S . aureus in another, but were not identified in the third . We conclude that treatment with either ceftazidime or imipenem/cilastatin was efficacious for moderate to severe CAP in Hong Kong. Enferm Infecc Microbiol Clin, 1997 Jan, 15(1), 5 - 9 {Comparative study of the protective role of the vaccine against Haemophilus influenzae type b and partial splenectomy in an experimental model}; Perez Maestu R et al.; BACKGROUND: Although the vaccine against Haemophilus influenzae type b has demonstrated its efficacy in children, this bacteria continues to be a cause or overwhelming sepsis in splenetomized patients . METHODS: To compare the degree of protection provided by partial splenectomy and the conjugated diptheria toxoid vaccine against H . influenzae type b, the bacteremia generated 24, 48 and 96 hours after intravenous inoculation with this bacteria at concentrations of 5 x 10(14), 5 x 10(13) and 5 x 10(12) colony-forming units was assessed in rats subjected to total splenectomy, with and without previous vaccination, to partial splenectomy or to sham operation . RESULTS: With respect to both the proportion of positive blood cultures and the concentration of H . influenzae in the blood stream, the sham-operated control rats and those vaccinated prior to splenectomy presented similar behaviors; the widest differences with respect to the latter two groups were found in the nonvaccinated total splenectomy rats, and the results with the partial splenectomy group fell between these two extremes . CONCLUSIONS: The protection of H . influenzae type b vaccine against infection is equivalent to that provided by the intact spleen for inoculum concentrations of 5 x 10(13) colony-forming units and less . Thus, the possibility of its systematic use in asplenic patients should be considered . The protection provided by the remnant spleen following 50% splenectomy is intermediate between those observed with eusplenia and with asplenia . These results suggest that when partial splenectomy is to be performed in normal spleen, the attempt should be made to conserve as much of the organ as possible. Diagn Microbiol Infect Dis, 1997 Jan-Feb, 27(1-2), 35 - 9 The antibiotic treatment of acute otitis media and sinusitis in children; Cohen R; The development of resistance among the bacterial pathogens causing acute otitis media and sinusitis in children is causing considerable concern . Although normally a mild infection, acute otitis media can produce serious complications with sequelae that can have long-lasting effects . High levels of resistance are now being seen in the three principal pathogens . Streptococcus pneumoniae, Haemophilus influenzae, and Moraxella catarrhalis . Most clinical trials comparing the efficacy of different antibiotics have failed to show differences in clinical efficacy . To overcome this problem, alternative methods of assessing antibiotics have been developed including the "in-vivo sensitivity test" proposed by Howie and retrospective analyses of treatment failures . The treatment of sinusitis is complicated by the difficulty in establishing a clear differential diagnosis . To date, no definitive trials of bacteriologic efficacy in children have been published. Diagn Microbiol Infect Dis, 1997 Jan-Feb, 27(1-2), 21 - 8 Can antimicrobial activity be sustained? An appraisal of orally administered drugs used for respiratory tract infections; Jones RN; Respiratory tract infections (RTIs) represent a major cause of illness worldwide . Therefore, it is of great concern that common RTI pathogens have become increasingly resistant to many of the antimicrobial agents used for therapy . For example, Haemophilus influenzae and Moraxella catarrhalis have become resistant to beta-lactam drugs by producing efficient beta-lactamases (> 35 and 90% of strains, respectively) . More recently, pneumococci have become more resistant through the mechanism of altered penicillin-binding proteins (PBPs) . The rate of penicillin nonsusceptible isolates has risen to > 25% in the United States (1994-1995) . It is important to monitor the resistance characteristics of such pathogens and, if possible, to use regionally acquired data to guide empiric selection of therapeutic agents for RTIs . Currently, some antimicrobials remain effective against the majority of these three bacterial species, as exemplified by amoxicillin/clavulanic acid . Furthermore, amoxicillin alone seems to possess greater inhibition than other orally administered beta-lactams at clinically achievable concentrations against pneumococci with altered PBPs . It is critical that steps are taken to limit resistance problems, particularly through; 1) education of prescribers and the public; 2) initiation of the development of novel drugs with alternative modes of action or stability to existing resistance mechanisms; and 3) by continuing to generate quality susceptibility testing data to guide empiric chemotherapy against bacterial pathogens causing RTI. J Infect, 1997 Jan, 34(1), 69 - 74 HACEK group endocarditis at the Riyadh Armed Forces Hospital; el Khizzi N et al.; INTRODUCTION: Fastidious Gram-negative organisms classified as the HACEK group (Haemophilus spp., Actinobacillus actinomycetemcomitans, Cardiobacterium hominis, Eikenella corrodens and Kingella spp.) are rare causes of infective endocarditis . CASE REPORT: In this series, we report six cases of endocarditis in Saudi patients occurring between 1990 and 1994 in our hospital, caused by two of the organisms in the HACEK group, i.e . Cardiobacterium hominis and Actinobacillus actinomycetemcomitans . The clinical features, predisposing factors and treatment of the patients are briefly described . The microscopic and cultural characteristics of the organisms are described together with the laboratory methods of diagnosis . MAJOR FINDINGS: HACEK endocarditis was frequently associated with prosthetic heart valves or structural heart abnormalities . Dental caries or periodontal disease seems to be a predisposing factor . The prognosis of HACEK endocarditis is very good as clinical and bacteriological cure were achieved with antibiotic therapy in all our cases except one who required mitral valve replacement . Contrary to previous reports we did not find all the organisms sensitive to penicillin and aminoglycosides . However, all our isolates were sensitive to amoxycillin, cefuroxime, ceftriaxone and ciprofloxacin . CONCLUSIONS: Laboratory diagnosis of HACEK group of organisms requires a high index of suspicion and should be suspected in cases of endocarditis in which fastidious Gram-negative coccobacilli are isolated which fail to grow on MacConkey agar . Empiric therapy should be started in suspected cases with second generation cephalosporins or with ciprofloxacin, until antibiotic sensitivity results become available . Antibiotic therapy should be continued for 4-6 weeks . Progress and outcome was very good in the series. J Infect, 1997 Jan, 34(1), 41 - 8 The epidemiology of community-acquired pneumonia among hospitalized adults; Porath A et al.; OBJECTIVE: To identify and characterize the aetiological agents of community-acquired pneumonia (CAP) among hospitalized patients, as an aid in therapeutic decision-making . METHOD: A prospective 1 year study of all patients hospitalized with CAP in the Negev region of Israel . The aetiology was determined by blood and pleural fluid cultures, and specific serological testing for pathogenic agents . Eighty-nine percent of the patients underwent follow-up for a month after discharge . RESULTS: The study included 346 patients (53% males, mean age 49.3 +/- 19.5, range 17-94) . A single aetiologic agent was identified in 146 patients (42.2%), multiple agents were found in 133 (38.4%), and no agent was identified in 67 (19.4%) . Among the common pathogens were Pneumococcus sp . in 148 patients (42.8%) . Mycoplasma pneumoniae (101, 29.2%), Chlamydia pneumoniae (62, 17.9%), Legionella sp . (56, 16.2%), viruses (35, 10.1%), Coxiella burnetti (20, 5.8%) . Haemophilus influenzae (19, 5.5%), and other bacteria (21, 6.1%) . Approximately 70% of the patients infected with M . pneumoniae and C . burnetti were younger than 45 years (P < 0.05) . In contrast, about 50% of the patients with C . pneumoniae (TWAR) were over the age of 65 (P = 0.03) . The presence of comorbidity was associated with a greater frequency of bacterial aetiologies (57% vs . 44%, P = 0.02), and fewer infections with M . pneumoniae (15% vs . 36%, P = 0.0004), or C . burnetii (2% vs . 8%, P = 0.02) . Specific causative agents were associated with specific seasons: viruses between December and April (P = 0.03), and Legionella sp . from July to October (P = 0.003) . In contrast, no seasonal variation was associated with pneumococcus, M . pneumoniae, or C . pneumoniae (TWAR) . CONCLUSIONS: Patients are hospitalized with CAP throughout the year . Since the pathogen is usually unknown at hospitalization, epidemiological data is important for choosing medication . The findings of this study point to the importance of macrolides alone or in combination with cephalosporins, as the treatment of choice for patients in our region. Pediatrics . 1997 Jan;99(1):E4. Increasing immunization: a Medicaid managed care model; Browngoehl K et al.; OBJECTIVE:To evaluate the impact of an immunization outreach program on immunization rates . SETTING: A Pennsylvania independent practice association model managed care organization (100% Medicaid) . DESIGN: Retrospective cohort study (N = 2511) of children 30 to 35 months of age from two age cohorts that compared immunization rates for Advisory Committee on Immunization Practices schedules for diphtheria-tetanus-pertussis, oral polio vaccine, measles-mumps-rubella, and Haemophilus influenza type b . An evaluation of the outreach component of the program compared treatment and nontreatment subgroups of one age cohort (N = 1002) . INTERVENTION: The immunization program targeted approximately 19 000 members from birth to 6 years of age . The program components included computerized tracking and reminders, member and provider education, provider incentives, member incentives, and home visiting outreach . RESULTS: Data indicate that the treatment group has higher completed immunization rates at 35 months of age than does the control group . Furthermore, data show that members with home visits have significantly higher completed immunization rates than do other members . The corresponding comparisons for age-appropriate immunizations by 24 months indicate a nonsignificant trend of increased rates . CONCLUSION: The data provide evidence supporting a correlation between comprehensive strategies (computerized tracking, member and provider education and incentives, and home visiting) and increased immunization rates . Those individuals who received home visits were more likely to complete an immunization series by 35 months of age than those who did not . However, within the Mercy Health Plan program, age-appropriate immunizations are not significantly affected by home-visiting outreach. Arch Pediatr, 1997 Jan, 4(1), 52 - 60 {Role of corticoids in purulent meningitis in children: analysis of literature studies}; Jacqz-Aigrain E et al.; Steroid therapy, in combination with antibiotics for bacterial meningitis in paediatric patients remains controversial . Steroids, and primarily dexamethasone a very potent anti-inflammatory agent, regulate the liberation of various cytokines and inflammatory mediators such as prostaglandins, released during bacterial meningitis and leading to long term complications . Several clinical trials studying infants and children with bacterial meningitis due to Haemophilus influenzae have evaluated the beneficial effects of the administration of dexamethasone at the onset of antibiotherapy and demonstrated that dexamethasone reduced the risk of acquired sensorineural deafness (bilateral moderate or more severe hearing loss) and the incidence of neurological sequelae . Limited information is available for the other bacterial meningitis, although meningococcal meningitis will become more frequent with the use of effective anti-Haemophilus vaccines . In addition some Streptococcus pneumoniae are now resistant to third generation cephalosporins and the use of dexamethasone in that case may be at risk . Finally, no evidence is available for an effective role for dexamethasone in neonatal bacterial meningitis, although it is quite often administered in that age group. Glycoconj J, 1997 Jan, 14(1), 13 - 7 Chemical synthesis of Haemophilus influenzae glycopeptide conjugates; Kandil AA et al.; A simple procedure for conjugating synthetic fragments of the capsular polysaccharide of Haemophilus influenzae type b, poly-3-beta-D-ribose-(1,1)-D-ribitol-5-phosphate (sPRP) to linear peptides is described . The procedure consists of (i) reacting the amino group of amino-heptyl sPRP with m-maleimidobenzoyl-N-hydroxysuccinimide (MBS) in phosphate buffer, pH 7.5; (ii) selectively coupling the MBS-modified sPRP to the sulfhydryl group of the cysteine residue of peptides containing functional T-helper cell epitope(s) . The glycopeptide conjugates were purified by gel filtration chromatography, biochemically characterized, and elicited protective level of anti-PRP antibody responses in rabbits. S Afr Med J, 1997 Jan, 87(1), 51 - 6 Epidemiology of post-neonatal bacterial meningitis in Cape Town children; Hussey G et al.; Bacterial meningitis is a major cause of childhood morbidity and mortality in South Africa . However, comprehensive regional or national epidemiological data, essential for rational public health interventions, are lacking . The purpose of this 1-year prospective study, from 1 August 1991 to 31 July 1992, was to define the magnitude of the problem of childhood bacterial meningitis in Cape Town . The study group consisted of all children, aged > 1 month to < 14 years, who presented with proven bacterial meningitis at all the hospitals in the Cape Town metropolitan area . During the year 201 cases were identified: 101 (50.2%) were due to Neisseria meningitidis, 74 (36.8%) were due to Haemophilus influenzae and 26 (12.9%) were due to Streptococcus pneumoniae . The overall incidence rate (95% confidence interval) for children less than 14 years, 5 years and 1 year was 34 (30-40), 76 (65-88) and 257 (213-309) per 100,000 children, respectively . The rate was highest in black infants, 416 (316-545)/100,000 . This was 2 times greater than the rate in coloured infants and about 4.5 times greater than the rate in white infants . The median age of all the children was 10 months . The ages of children with haemophilus and pneumococcal meningitis were similar, 9 and 7.5 months respectively (P = 0.43), while children with meningococcal meningitis were significantly older (22 months) than the others (P < 0.01) . The overall case fatality rate was 5%, and 12.9% of survivors had significant neurological sequelae (disability) on discharge. Eur J Epidemiol, 1997 Jan, 13(1), 73 - 7 Incidence of invasive Haemophilus influenzae type b disease in Italian children; Tozzi AE et al.; To estimate the incidence of Haemophilus influenzae type b (Hib) invasive disease in Italian infants we performed a prospective study in a cohort of newborns enrolled for a randomized trial on safety and efficacy of three pertussis vaccines and followed for onset of serious disease or pertussis . The overall cumulative incidence observed in 15,601 children was 51.3/100,000 for all invasive Hib infections and 38.4/100,000 for Hib meningitis, over 27 months of observation . The incidence density of all invasive Hib disease was 28.7/100,000 person-years, while meningitis occurred with an incidence of 21.5/100,000 person-years . Among the eight cases detected, six were meningitis, one sepsis, and one cellulitis . The child with sepsis died . The incidence and epidemiology of invasive Hib disease in Italy are comparable to those reported from other European countries . Cost-benefit analyses are needed for planning Italian vaccination policy. J Clin Pathol, 1997 Jan, 50(1), 72 - 4 Endocarditis caused by Haemophilus parainfluenzae identified by 16S ribosomal RNA sequencing; Das I et al.; Haemophilus parainfluenzae, a human commensal, is an infrequent cause of serious disease . A case of endocarditis caused by this organism in a five year old boy with complex congenital heart disease is reported . The course of this disease was very aggressive, leading to heart failure, disseminated intravascular coagulation and multiorgan failure in spite of appropriate antibiotics and surgical intervention . The difficulties in the detection and identification of H parainfluenzae using conventional culture based technology, and the potential role of molecular techniques, are highlighted. Retina, 1997, 17(1), 28 - 32 Intravenous gentamicin and ceftazidime in penetrating ocular trauma: a swine model; Schech JM et al.; PURPOSE: A swine model of ocular trauma was used to determine the extent of penetration of systematically administered gentamicin and ceftazidime to the vitreous cavity of traumatized and normal eyes . METHODS: Forty-six pigs received a scleral laceration to the right eye and then underwent surgical repair . Thirty-six animals received intravenous gentamicin, and 10 pigs were given ceftazidime . RESULTS: The level of gentamicin in the vitreous of traumatized and nontraumatized eyes did not achieve the minimum inhibitory concentrations (MIC) for Pseudomonas and Haemophilus species despite multiple and large intravenous doses . Ceftazidime concentrations in traumatized eyes were above the minimum inhibitory concentration for these organisms . CONCLUSIONS: Ceftazidime achieves an intravitreal concentration 33 times the minimum inhibitory concentration of Haemophilus species and twice that of Pseudomonas species in traumatized eyes after systemic administration, a finding that lends support to its use as a prophylactic agent in the management of penetrating ocular trauma . Gentamicin does not appear to enter the traumatized eye at appreciable levels after systemic administration, and, therefore, it is not recommended for use as a prophylactic agent in the management of penetrating ocular trauma. Vaccine, 1997 Jan, 15(1), 20 - 4 Vaccination coverage of 2-year-old children and immunization practices--Canada, 1994; Duclos P; The purpose of the study was to assess vaccination coverage of 2-year-olds and estimate immunization practices in Canada using a postal survey with a panel of 862 households . RIM weighting was used to provide national estimates . 95% CIs were calculated using the binomial method . Completed questionnaires were received for 534 children born between February 1991 and January 1992 . Thirty nine percent of children had received all/most of their vaccinations at a public health clinic . Overall 5.6% parents indicated they had their child immunized because it was mandatory and 7.4% because of requirements for school, pre-school, nursery or day care attendance . A total of 78.7% of parents remembered receiving information on benefits of immunizations and 97% on the risks/side-effects . By their second birthday, 83.7% (95% CI 80.3-86.7) of 2-year-olds had received complete immunization against poliomyelitis; 97.2% (95% CI 95.4-98.4), at least one dose of a measles containing vaccine; 86.5% (95% CI 83.3-89.3), at least one dose of Haemophilus influenzae type b vaccine; and 81.6% (95% CI 78.1-84.8), at least, four doses of diphtheria, tetanus and pertussis vaccine. Acta Otolaryngol, 1997 Jan, 117(1), 109 - 12 The effect of antibiotic treatment on the release of endotoxin during nontypable Haemophilus influenzae-induced otitis media in the chinchilla; Jauris-Heipke S et al.; The gram negative bacteria, nontypable Haemophilus influenzae (NTHi) was used to induce otitis media in a total of 18 chinchillas . Three days post-inoculation, three cohorts of 6 chinchillas each were treated daily for four days with either ceftriaxone, chloramphenicol, or diluent without antibiotics . Middle ear fluid (MEF) was obtained daily, assayed for endotoxin content by means of the chromogenic limulus amebocyte lysate assay, and concentration of the NTHi/mL MEF determined by standard plate count . The endotoxin concentration per mL MEF from both the antibiotic treated cohorts decreased during the observation period, but increased in the MEF of the untreated control group . The data indicate that, unlike the dramatic increase in endotoxin concentration, after antibiotic treatment in the cerebrospinal fluid (CSF) during experimental Haemophilus influenzae-induced meningitis, there is no demonstrable sustained release of endotoxin in the middle ear subsequent to antibiotic treatment during experimental otitis media. Microb Pathog, 1997 Jan, 22(1), 39 - 46 Attachment of Haemophilus ducreyi to human foreskin fibroblasts involves LOS and fibronectin; Alfa MJ et al.; Haemophilus ducreyi is the causative agent of the genital ulcer disease Chancroid . Chancroid has been shown to increase the risk of heterosexual transmission of HIV . Little is known regarding the attachment or localization of this organism to human cells in either the dermal or epidermal layer . In this study the attachment of H . ducreyi to human foreskin fibroblast (HFF) cells was further characterized . Attachment was mediated by more than one mechanism . Proteinase K treatment but not trypsinization of H . ducreyi significantly reduced attachment suggesting protein involvement . In addition, purified lipooligosaccharide (LOS) was able to inhibit attachment in a dose dependent manner . It appeared that the organism binds to fibronectin in the extracellular matrix of HFF cells, since competition studies using fibronectin showed that it was able to significantly reduce attachment in a dose dependent manner whereas collagen did not . We hypothesize that the attachment of H . ducreyi involves both a protein mediator of attachment (likely pili) as well as LOS and that one or both of these bacterial components interacts with fibronectin in the extracellular matrix to mediate attachment to HFF cells. Microb Pathog, 1997 Jan, 22(1), 13 - 21 Modulation of phagocytic function of bovine mononuclear phagocytes by Haemophilus somnus; Gomis SM et al.; The interactions between bovine mononuclear cells and Haemophilus somnus are known to be complex . To study this interaction, a flow cytometric assay was developed to assess the effect of H . somnus on phagocytosis of killed opsonized Staphylococcus aureus by bovine alveolar macrophages and blood monocytes . Using this in vitro system, it was found that log phase H . somnus significantly inhibited the phagocytosis of killed opsonized S . aureus by bovine alveolar macrophages obtained both from healthy calves and from cattle experimentally infected with H . somnus . However, killed log-phase H . somnus, in vitro passaged and stationary phase H . somnus had no effect on the phagocytic activity of these cells . In contrast to bovine alveolar macrophages, blood monocytes showed a significant increase in their phagocytic activity following in vitro exposure to either log or stationary phase H . somnus . Using a lypophilic, non-toxic fluorophore PKH2 to label live H . somnus, it was possible to simultaneously measure the uptake of both S . aureus and H . somnus . Stationary and log phase H . somnus were taken up by macrophages equally well, even though phagocytosis of S . aureus was inhibited by only log phase H . somnus . These results demonstrate the ability of H . somnus to modulate bovine mononuclear phagocytic function which might contribute towards the pathogenesis of bovine hemophilosis. Microbiology, 1997 Jan, 143 ( Pt 1), 171 - 4 A Bacillus cereus member of the SNF2 family; Lindback T et al.; The complete sequence of a Bacillus cereus member of the SNF2 family of putative helicases showed conservation of all seven motifs typical of this family . Bcsnf predicted a protein of 1064 aa where the conserved SNF2 domain was located at the carboxy terminus, whereas the 633 amino-terminal aa showed no homology to any protein in the databases . A putative transcriptional start was identified by primer extension, indicating that Bcsnf is not a part of a larger operon . No phenotypical changes were observed after insertional inactivation of Bcsnf . The completely sequenced genomes of Mycoplasma genitalium and Haemophilus influenzae contain one ORF each with similarity to the SNF2 family: MG018 and HI0616, respectively . A phylogenetic tree of the SNF2 family showed that BcSNF and MG018 were most closely related, and appeared closer to the eukaryotic members of the SNF2 family than to the two other bacterial members of the family, HepA from Escherichia coli and HI0616. Nucleic Acids Res, 1997 Jan 1, 25(1), 246 - 7 The translational signal database, TransTerm: more organisms, complete genomes; Dalphin ME et al.; TransTerm is a database of initiation and termination sequence contexts from more than 250 organisms listed in GenBank, including the four complete genomes:Haemophilus influenzae, Methanococcus jannaschii, Mycoplasma genitalium,and Saccharomyces cerevisiae . For the current release, more than 60 000 coding sequences were analysed . The tabulated data include initiation and termination contexts organised by species along with quantitative parameters about individual coding sequences (length, %GC, GC3, Nc and CAI) . There are also tables of initiation- and termination-region nucleotide-frequencies, codon usage tables and summaries of stop signal usage . TransTerm is available on the World Wide Web at: tml Nucleic Acids Res, 1997 Jan 1, 25(1), 37 - 8 The metabolic pathway collection: an update; Selkov E et al.; The Metabolic Pathway Collection from EMP is an extraction of data from the larger Enzymes and Metabolic Pathways database (EMP) . This extraction has been made publicly available in the hope that others will find it useful for a variety of purposes . The original release in October 1995 contained 1814 distinct pathways . The current collection contains 2180 . Metabolic reconstructions for the first completely sequenced organisms-Haemophilus influenzae,Mycoplasma genitalium,Saccharomyces cerevisiaeandMethanococcus janaschii-are all included in the current release . All of the pathways in the collections are available as ASCII files in the form generated by the main curator, Evgeni Selkov . In addition, we are offering a more structured encoding of a subset of the collection; our initial release of this subcollection includes all of the pathways inMycoplasma genitalium, and we ultimately intend to offer the entire collection in this form as well. Heart Lung, 1997 Jan-Feb, 26(1), 80 - 2 Haemophilus influenzae sepsis resulting from pneumonia; Marinella MA; Haemophilus influenzae is a pleomorphic gram-negative bacterium that causes a myriad of infections in both adults and children . The organism frequently causes respiratory infections in patients with obstructive lung disease but may on occasion cause invasive infections including pneumonia with bacteremia . We report the case of a patient with underlying lung disease and metastatic malignancy in whom sepsis related to pneumonia caused by H . influenzae developed. J Mol Evol, 1997 Jan, 44(1), 66 - 73 Conserved clusters of functionally related genes in two bacterial genomes; Tamames J et al.; An approach for genome comparison, combining function classification of gene products and sequence comparison, is presented . The genomes of Haemophilus influenzae and Escherichia coli are analyzed, and all genes are classified into nine major functional classes, corresponding to important cellular processes . To study gene order relationships and genome organization in the two bacteria, we performed statistics on neighboring pairs of genes . To estimate the significance of the observations, a statistical model based on binomial distributions has been developed . Significant patterns of gene order are observed within, as well as between, the two bacterial genomes: Functionally related genes tend to be neighbors more often than do unrelated genes . Some of these groups represent well-known operons, but additional gene clusters are identified . These clusters correspond to genomic elements that have been conserved during bacterial evolution . In addition to nearest-neighbor relationships, the method is also useful to study the relative direction of transcription in genomes, which is also highly conserved between homologous gene pairs . This new approach combines the high-level description of molecular function with pair statistics that express genome organization . It is expected to complement traditional methods of sequence analysis in the study of genomic structure, function, and evolution. Eur J Pediatr, 1997 Jan, 156(1), 18 - 24 Evidence for induction of polysaccharide specific B-cell-memory in the 1st year of life: plain Haemophilus influenzae type b-PRP (Hib) boosters children primed with a tetanus-conjugate Hib-DTPa-HBV combined vaccine; Zepp F et al.; The lack of an adequate immune response to the major polysaccharide of the Haemophilus influenzae type b (Hib) capsule (polyribosyl ribitol phosphate) (PRP) in very young infants (< 18 months) can be overcome by conjugating PRP to a T-cell dependent carrier protein . We studied whether administration of a tetanus-PRP conjugate vaccine reconstituted with a diphtheria-tetanus-acellular pertussis-hepatitis B (DTPa-HBV) vaccine as a three dose primary course at 3, 4 and 5 months of age induced PRP-specific immunological memory, by examining the anti-PRP response to a dose of unconjugated PRP given with the DTPa-HBV booster approximately 1 year later . The unconjugated PRP elicited protective anti-PRP antibody levels (> or = 0.15 microgram/ml) in all but 3 of the 369 vaccinees, including 13 infants who failed to demonstrate a measurable immune response after the primary course . In a sub-cohort of 54 subjects all had anti-PRP levels > or = 0.5 microgram/ml within 7-14 days of the booster showing a rapid anamnestic type response . Both primary and booster responses were predominantly IgGl indicating a T-cell dependent response . The DTPa-HBV components elicited protective anti-diphtheria, anti-tetanus and anti-HBs antibody levels in > or = 98.5% of vaccinees, and immune responses to each of the acellular pertussis vaccine components in 92.3%-97.3% of subjects . CONCLUSION: The tetanus-PRP conjugate vaccine not only elicited a good primary humoral response, but also induced immunological memory so that the infants were able to mount a large and rapid immune response to subsequent exposure to plain PRP, indicating that protection against circulating wild-type Hib had been generated . Successful induction of immunological memory occurred even when there was no measurable humoral anti-PRP response to the primary course . Tetanus-PRP conjugate vaccine can be used in combination with DTPa-HBV vaccine, when administered separately or as a single injection in the same syringe, in primary immunisation schedules at 3, 4 and 5 months of age. Pediatr Infect Dis J, 1997 Jan, 16(1), 91 - 5; discussion 95-6, 123-6 Pathogenesis of bacterial bronchitis in cystic fibrosis; Smith A; OBJECTIVE: To describe the current understanding of the pathogenesis of infections in cystic fibrosis (CF) . SUMMARY: The key element in the pathogenesis of infections in CF is the abnormal mucin resulting from a defective chloride channel . Abnormal mucin and the lack of hydration of respiratory secretions entraps bacteria, permitting colonization and subsequent infection . "Normal" physiologic insults, such as microaspiration, and pollution evoke mucin secretion with bacteria-mucin aggregates causing infection of small airways . Microcolonies of pulmotropic bacteria (i.e . Haemophilus and Staphylococcus) in the trapped mucin cause mucosal injury which predisposes the patient to Pseudomonas aeruginosa infection . Eventually there is obstruction of medium-sized and small airways by inflammatory exudate and mucus . Ultimately these chronic endobronchial bacterial infections cause significant loss of pulmonary function with morbidity and a decrease in the life span of patients with CF . Although antibiotic therapy is beneficial for the management of bacterial respiratory tract infections in CF patients, gene therapy may provide the ultimate cure . CONCLUSION: New treatment strategies will emerge as the pathogenesis of cystic fibrosis is better elucidated. J Infect Dis, 1997 Jan, 175(1), 205 - 9 New murine model of bronchopneumonia due to cell-bound Haemophilus influenzae; Miyazaki S et al.; This murine model of nontypeable (unencapsulated) Haemophilus influenzae (NTHI) bronchopneumonia used organisms bound to mouse fetal lung (MFL) cells as an inoculum . Pretreatment of the mice with 40 microL of 1% formalin 3 days before intranasal instillation of the bacteria was necessary to allow infection . The number of NTHI recovered from the lungs plus trachea on day 7 after instillation was >100 times the number originally inoculated . Later, however, the number of recovered bacteria diminished gradually, and by day 14 it was almost identical to the original inoculum size . Serum IgM also peaked on day 7 after infection, after which IgG increased while IgM decreased . Histologically, bronchoalveolar infiltration of neutrophils was observed on day 3 after inoculation and continued at least for the following 4 days . The present experiment demonstrates that MFL cells can protect bacteria that have invaded the cells from the opsonizing and killing activities of host humoral defense mechanisms. J Infect Dis, 1997 Jan, 175(1), 77 - 83 Receptor affinity purification of a lipid-binding adhesin from Haemophilus influenzae; Busse J et al.; Thirteen clinical strains of Haemophilus influenzae, including types b, d, and untypeable, in vitro specifically recognize phosphatidylethanolamine (PE), gangliotetraosylceramide, gangliotriosylceramide (Gg3), sulfatoxygalactosylceramide, and to a lesser extent sulfatoxygalactosylglycerol . A PE affinity matrix was used to purify an adhesin of approximately 46 kDa from both type b and untypeable H . influenzae . This adhesin was a potent inhibitor of H . influenzae Gg3 and PE binding in vitro, and polyclonal antibodies specific for this protein prevented the attachment of H . influenzae Gg3 and PE and cultured HEp-2 epithelial cells in vitro. Infect Immun, 1997 Jan, 65(1), 261 - 6 Human Fab fragments specific for the Haemophilus influenzae b polysaccharide isolated from a bacteriophage combinatorial library use variable region gene combinations and express an idiotype that mirrors in vivo expression; Reason DC et al.; To determine whether the human antibody (Ab) repertoire to the Haemophilus influenzae type b capsular polysaccharide (Hib PS) could be studied at the molecular level with phage display technology, we constructed a phage Fab library by using peripheral blood from a vaccinated adult . Phage were selected based on Hib PS binding . Two distinct Hib PS-specific phage clones were identified whose Fab fragments used the same V(H) region paired with two different V(L) regions . The V(L) regions were derived from two independent rearrangements of the A2c gene with Jkappa1, and both contained a nontemplated arginine codon at the V-Jkappa junction . The two A2 V gene segments differed from the A2c germ line sequence in 0 and 5 bases . The V(H) region consisted of the V(H)26 gene segment having 98% identity to the germline nucleotide sequence, a D region of 9 bases, and J(H)4b1 . Usage of V(H)26 in combination with A2 V regions containing a junctional arginine is a predominant configuration of naturally occurring Hib PS-specific Abs . Liquid- and solid-phase assays showed that phage-derived Fab reacted with Hib PS and expressed HibId-1, an idiotype associated with the kappaII-A2 V region . These findings extend the database of V region polymorphisms that can contribute to the Hib PS repertoire and demonstrate that Hib PS-specific Fab fragments isolated from combinatorial phage libraries use V gene combinations which mirror the natural repertoire. Infect Immun, 1997 Jan, 65(1), 150 - 5 Importance of an immunodominant surface-exposed loop on outer membrane