Haemophilus

JAMA, 1994 Oct 12, 272(14), 1116 - 21
Effect of carrier protein priming on antibody responses to Haemophilus influenzae type b conjugate vaccines in infants; Granoff DM et al.; OBJECTIVE--To assess the effect of priming with diphtheria and tetanus toxoid vaccine (DT) at 1 month of age on the anticapsular polyribosylribitol phosphate (PRP) antibody responses of infants vaccinated with Haemophilus influenzae type b polysaccharide-tetanus toxoid conjugate (PRP-T) or PRP oligosaccharide-cross-reactive mutant diphtheria toxin conjugate (HbOC) . DESIGN--Randomized controlled trial with serum samples assayed blindly . PARTICIPANTS AND SETTING--Healthy infants enrolled in private pediatric practices; 94 (91%) of 103 infants had prevaccination and postvaccination serum samples available for analysis . INTERVENTIONS--Two groups received DT vaccination at 1 month of age and subsequent injections of PRP-T or HbOC conjugate vaccines at 2, 4, and 6 months of age . The control groups were not vaccinated with DT but received PRP-T or HbOC at the same ages as the carrier-primed groups . Infants in all groups were given a booster injection of unconjugated PRP at 12 months of age to assess induction of immunologic memory . MAIN OUTCOME MEASURE--Concentrations of serum antibody to PRP . MAIN RESULTS--The DT-primed infants given PRP-T had twofold to threefold higher geometric mean anti-PRP antibody responses after one (P < or = .01), two (P < or = .01), or three (P = .06) doses of conjugate vaccine than the infants of the unprimed group . The primed infants also had threefold higher memory antibody responses to the booster PRP injection given at 12 months of age (concentration of 24.4 vs 8.4 micrograms/mL in infants not primed with DT; P < .01) . The DT-primed infants given HbOC had twofold to threefold higher antibody responses after one (P = .07) or two (P < .01) doses of conjugate vaccine than the unprimed HbOC group, but there were no significant differences after the third dose of conjugate vaccine or after the PRP booster injection . CONCLUSIONS--Vaccination with DT at 1 month of age increases the magnitude of the anti-PRP antibody responses to conjugate vaccination . With HbOC, the effect of carrier priming was present for up to 6 months of age, whereas in infants vaccinated with PRP-T, enhanced immunity was present for at least 12 months.

Presse Med, 1994 Oct 8, 23(30), 1376 - 80
{Oropharyngeal flora . Epidemiologic survey of prevalence}; Bergogne-Berezin E et al.; OBJECTIVES: Epidemiological surveys which are not frequently carried out in medical practice should provide useful information for the choice of antibiotics to be prescribed in community-acquired infections particularly with the recent development of therapeutic difficulties due to resistant strains . We therefore analyzed the prevalent pharyngeal flora in a general patient population . METHODS: The study was conducted during a single 24-hour period in 1991 by 43 general practitioners and included 645 subjects consulting for benign affections . No patient selection was made . Two pharyngeal swabs were obtained from each subject and cultured in aerobic and anaerobic conditions . Internationally accepted methods for identifying bacteria in pharyngeal samples all performed by one well-equipped laboratory . Beta-lactamase activity was determined with the nitrocephine technique, both directly and after culture . RESULTS: Patient age varied from 16 to 45 years; most (68.5%) consulted for reasons other than ear-nose-throat affections . Only 41 patients (4.3%) consulted for sore throat and 65.4% had not received antibiotics for at least 6 months . Haemophilus influenzae was found in 59.6% of the patients, 20% of the strains were beta-lactamase producers as were 83.7% of the Moraxella catarrhalis strains identified . CONCLUSION: These factors are indicators of potential risk of therapeutic failure when using beta-lactams unstable to beta-lactamases for the treatment of pharyngeal infections.

MMWR Morb Mortal Wkly Rep, 1994 Oct 7, 43(39), 718 - 20
Update: childhood vaccine-preventable diseases--United States, 1994; Vaccination coverage of 2-year-old children--United States et al.; The primary goal of the Childhood Immunization Initiative (CII) is to increase, by 1996, vaccination levels for 2-year-old children to at least 90% for the most critical doses in the vaccination series (i.e., one dose of measles-mumps-rubella vaccine {MMR} and at least three doses each of diphtheria and tetanus toxoids and pertussis vaccine {DTP}, oral poliovirus vaccine, and Haemophilus influenzae type b vaccine {Hib}) and to at least 70% for three or more doses of hepatitis B (Hep B) vaccine (1) . This report presents estimates, based on the National Health Interview Survey (NHIS), of the annual national vaccination coverage levels for children aged 19-35 months (median: 27 months) for 1993, compares estimates for 1993 with those for 1992, and compares estimates for the first 6 months of 1993 with third and fourth quarter 1993 estimates.

Pharmacoeconomics, 1994 Nov, 6(5), 442 - 52
Cost of treatment and prevention of Haemophilus influenzae type b disease . An international perspective; Clements DA; On the basis of immunogenicity and protective efficacy studies, 4 Haemophilus influenzae type b (Hib) conjugate vaccines have been licensed for administration to infants and children . Population based studies of Hib disease from Australia, Chile, Finland, Gambia, Israel, Switzerland, UK and US show that the relative and absolute incidence of Hib disease varies significantly . These differences in Hib epidemiology, and associated sequelae and hospital costs affect the cost-benefit analysis of preventive vaccination, necessitating unique calculations for each country . Published papers on the cost of Hib disease and the cost-benefit relationship of Hib vaccination have been based primarily on reports from the US, but more recently also on studies from Australia, Finland, Israel, Switzerland, UK, Sweden and Chile . All studies to date have produced favourable cost-benefit ratios . The implementation of Hib vaccination has led to the virtual disappearance of Hib disease in some of these countries . The lessons gained from these analyses are instructive not only for better understanding of the epidemiology of Hib disease, but also as a template for assessing the cost-benefit ratio of the implementation of preventive vaccination for other diseases.

Control Clin Trials, 1994 Oct, 15(5), 360 - 78
Decision making during a phase III randomized controlled trial; Berry DA et al.; Experiments such as clinical trials should be carried out with specific objectives . For example, in a trial designed to prevent disease, specific considerations should be made concerning the impact of the trial on the health of the target population, including the participants in the trial . These objectives should be assessed continually in light of data accumulating from the trial . Accumulating evidence should be judged in the context of changing circumstances external to the trial, and the trial's design possibly modified . An important type of modification is stopping the trial . This is a sequential decision problem that can be addressed using a Bayesian approach and the methods of dynamic programming . As an example we consider a vaccine trial for the prevention of haemophilus influenzae type b . The objective we consider is minimizing the number of cases of this disease in a Native American population over a specified horizon . We assess the prior probability distribution of vaccine efficacy . We also assess the probability of regulatory approval for widespread use of the vaccine, depending on the data presented to the regulatory officials . In deciding whether to continue the trial we weigh the impact of the possible future results by their (predictive) probabilities . We address the sensitivity of the optimal stopping policy to the prior probability distribution, to the assessed probability of regulatory approval, and to the horizon.

Thorax, 1994 Oct, 49(10), 999 - 1001
Penetration of amoxycillin/clavulanic acid into bronchial mucosa with different dosing regimens; Gould IM et al.; BACKGROUND--The efficacy of an antibiotic is related to its concentration at the site of infection . Previous studies of the concentrations of amoxycillin and clavulanic acid (co-amoxiclav) in respiratory secretions or whole lung tissue have suffered from methodological problems . The concentration of amoxycillin and clavulanic acid was determined in bronchial mucosal biopsy samples obtained at bronchoscopy following five different dosing regimens . METHODS--Bronchial biopsy and serum samples were obtained from 50 patients undergoing diagnostic bronchoscopy . Ten patients each received 375 mg, 625 mg, 750 mg, and 3.25 g oral, and 1.2 g intravenous co-amoxiclav 1-3 hours before bronchoscopy . The concentrations of clavulanic acid and amoxycillin were determined by high performance liquid chromatography using a microbore column, solid phase extraction, and preconcentration to improve sensitivity tenfold over previous methods . RESULTS--Concentrations of both clavulanic acid and amoxycillin in bronchial mucosa were dose related and were well above the MIC90 of co-amoxiclav for the common bacterial respiratory pathogens including Haemophilus influenzae, Micrococcus catarrhalis and Streptococcus pneumoniae for all dosing regimens . Mean mucosal levels were 200% and 118% of the corresponding serum levels for amoxycillin and clavulanic acid respectively . CONCLUSIONS--Amoxycillin and clavulanic acid are concentrated in bronchial mucosa and, even at the lowest dose of 375 mg orally, are likely to produce tissue levels in the lung sufficient to inhibit all the common community acquired respiratory pathogens.

Pediatrics, 1994 Oct, 94(4 Pt 1), 517 - 23
Immunization practices of pediatricians and family physicians in the United States; Szilagyi PG et al.; OBJECTIVE . To assess current practices and attitudes among pediatricians and family physicians across the United States regarding immunizations . DESIGN . Survey of a random sample of pediatricians and family physicians . SUBJECTS . Fellows of the American Academy of Pediatrics (N = 746) and American Academy of Family Medicine (N = 429) . SURVEY TOPICS . General immunization practices (eg, types of visits during which vaccinations are provided, mechanisms to identify undervaccinated children); and opinions about perceived barriers to immunizations, acceptance of alternative sites for immunizations, and possible immunization requirements for Medicaid and The Special Supplemental Food Program for Women, Infants, and Children (WIC) . RESULTS . Pediatricians and family physicians (combined) reported the following: immunizing children during acute illness visits (28%), follow-up visits (90%), and chronic illness visits (77%); using computer or reminder files to identify undervaccinated children (13%); and simultaneously administering four vaccines (diphtheria-tetanus-pertussis, oral poliovaccine, measles, mumps, and rubella and Haemophilus influenzae type b) to an eligible 18-month-old child (66%) . Physicians perceived the following as barriers to immunizations: missed preventive visits (40%), vaccine costs (24%), lack of insurance coverage (24%), inability to track undervaccinated patients (22%), incomplete immunization records (12%), and missed vaccination opportunities (12%) . Physicians agreed with offering vaccinations during hospitalizations (51%) or emergency department visits (30%), and with immunization requirements for continued eligibility for Medicaid (66%) or WIC (64%) . Pediatricians were more likely to vaccinate during chronic illness and follow-up visits, and were more likely to use systems to track undervaccinated children (P < .05); however, most immunization practices and attitudes of pediatricians and family physicians were similar . Physicians who graduated from medical school more recently and those in high-risk urban practices were more likely to vaccinate during acute illness visits, provide simultaneous vaccinations, and favor vaccinations in hospital settings . CONCLUSIONS . Vaccination rates might be improved by closer adherence to current immunization guidelines regarding vaccinations during all encounters and simultaneous vaccinations, by developing systems to identify undervaccinated children, and by reducing patient costs for vaccinations . Current immunization practices fall short of the immunization guidelines; changes in individual practice styles will be required to conform with these standards.

Otolaryngol Head Neck Surg, 1994 Oct, 111(4), 513 - 8
Tobacco smoke and otitis media in the chinchilla model; Antonelli PJ et al.; To determine whether tobacco smoke contributes to the pathogenesis of acute otitis media, chinchillas were exposed to mainstream tobacco smoke or sham conditions (cigarettes not lit) in a Walton smoke exposure machine for 20-minute cycles two or three times daily . After 6 to 8 weeks of daily exposure, 12 chinchillas were nasally injected with Streptococcus pneumoniae, and 18 chinchillas were injected into both middle ears with nontypable Haemophilus influenzae . Smoke or sham exposures were continued for 2 to 4 weeks after injection . Otitis media developed in none of the 12 nasally injected chinchillas and in all 18 chinchillas whose middle ears were injected with nontypable Haemophilus influenzae . Persistence of middle ear effusion and persistence of nontypable Haemophilus influenzae in the middle ear effusion were not different between the smoke- and sham-exposed groups . This suggests that mainstream smoke exposure does not change the natural course of otitis media in the chinchilla model.

J Pediatr, 1994 Oct, 125(4), 581 - 4
Response of immunocompromised children with solid tumors to a conjugate vaccine for Haemophilus influenzae type b; Shenep JL et al.; Serum antibody response to a conjugated Haemophilus influenzae type b polyribosylribitol phosphate-diphtheria toxoid vaccine was assessed in nonvaccinated children aged 1 1/2 to 5 years receiving chemotherapy for solid tumors . Responses occurred in 21 (42%) of 50 children after first vaccination, and in 10 (45%) of 22 revaccinated children.

J Pediatr, 1994 Oct, 125(4), 571 - 6
Postlicensure effectiveness of the Haemophilus influenzae type b polysaccharide-Neisseria meningitidis outer-membrane protein complex conjugate vaccine among Navajo children; Harrison LH et al.; The incidence of invasive Haemophilus influenzae type b (Hib) infection was decreased significantly among Navajo children since the licensure of Hib conjugate vaccines, even though two lots of Hib (polyribosylribitol phosphate)-meningococcal B outer-membrane protein conjugate vaccine (PRP-OMP) widely used among the Navajo were later found to be of low immunogenicity . We measured the effectiveness of all Hib conjugate vaccines combined, PRP-OMP alone, and the PRP-OMP lots with lower-than-expected immunogenicity among Navajo infants and children . This was a matched case-control study using active, laboratory-based surveillance for the ascertainment of Navajo children 2 1/2 to 59 months of age with invasive Hib infection; 45 patients with infection and 180 control subjects were enrolled . The effectiveness of one, two, and three doses, respectively, of all Hib conjugate vaccines combined was 96% (95% confidence interval (CI) 65%, 99%), 99% (95% CI, 69%, 100%), and 99% (95% CI - 57%, 100%) . The effectiveness of one or more doses of PRP-OMP was 95% (95% CI, 66%, 99%) . The effectiveness of a single dose of the lots of lower-than-expected immunogenicity was 89% (95% CI, -8%, 99%) . The Hib conjugate vaccine coverage increased from 49% during 1991 to 94% during 1992; no control subjects younger than 18 months of age were enrolled during 1993 . The occurrence of invasive Hib infections in this population after licensure of Hib conjugate vaccines was the result of gradual vaccine uptake, not poor vaccine effectiveness . The use of PRP-OMP has been highly effective despite concerns about the immunogenicity of several lots.

J Infect Dis, 1994 Oct, 170(4), 862 - 6
Nasopharyngeal colonization with nontypeable Haemophilus influenzae and recurrent otitis media . Tonawanda/Williamsville Pediatrics; Harabuchi Y et al.; The relationship between nasopharyngeal colonization with nontypeable H . influenzae and recurrent otitis media was assessed in 157 children followed prospectively from birth through 12 months of age . Forty-nine (31%) became colonized . Nasopharyngeal secretory IgA (sIgA) reactive with the P6 outer membrane protein was detected in all colonized children . Reduction or elimination of the organism was associated with a better mucosal immune response (560 +/- 864 units/ng/mL of sIgA) than was persistence in the nasopharynx (121 +/- 81; P = .04) . Forty colonized children (82%) and 61 noncolonized children (56%) developed otitis media (P = .004); colonized children were four times more likely to be classified as otitis prone (P = .003) . The frequency of otitis media episodes was directly related to the frequency of colonization (r = .42, P < .01) . These results demonstrate a strong relationship between nasopharyngeal colonization patterns and otitis media . The mucosal immune response may be important in elimination of potential pathogens from the respiratory tract.

Infect Immun, 1994 Oct, 62(10), 4515 - 25
Identification of a locus involved in the utilization of iron by Haemophilus influenzae; Sanders JD et al.; Haemophilus influenzae has an absolute requirement for heme for aerobic growth . This organism can satisfy this requirement by synthesizing heme from iron and protoporphyrin IX (PPIX) . H . influenzae type b (Hib) strain DL42 was found to be unable to form single colonies when grown on a medium containing free iron and PPIX in place of heme . In contrast, the nontypeable H . influenzae (NTHI) strain TN106 grew readily on the same medium . A genomic library from NTHI strain TN106 was used to transform Hib strain DL42, and recombinants were selected on a medium containing iron and PPIX in place of heme . A recombinant plasmid with an 11.5-kb NTHI DNA insert was shown to confer on Hib strain DL42 the ability to grow on iron and PPIX . Nucleotide sequence analysis revealed that this NTHI DNA insert contained three genes, designated hitA, hitB, and hitC, which encoded products similar to the SfuABC proteins of Serratia marcescens, which have been shown to constitute a periplasmic binding protein-dependent iron transport system in this enteric organism . The NTHI HitA protein also was 69% identical to the ferric-binding protein of Neisseria gonorrhoeae . Inactivation of the cloned NTHI hitC gene by insertion of an antibiotic resistance cartridge eliminated the ability of the recombinant plasmid to complement the growth deficiency of Hib DL42 . Construction of an isogenic NTHI TN106 mutant lacking a functional hitC gene revealed that this mutation prevented this strain from growing on a medium containing iron and PPIX in place of heme . This NTHI hitC mutant was also unable to utilize either iron bound to transferrin or iron chelates . These results suggest that the products encoded by the hitABC genes are essential for the utilization of iron by NTHI.

Infect Immun, 1994 Oct, 62(10), 4460 - 8
Localization of high-molecular-weight adhesion proteins of nontypeable Haemophilus influenzae by immunoelectron microscopy; Bakaletz LO et al.; A family of high-molecular-weight (HMW) surface-exposed proteins important in the attachment of nontypeable Haemophilus influenzae (NTHi) to human epithelial cells was previously identified (J . W . St . Geme III, S . Falkow, and S . J . Barenkamp, Proc . Natl . Acad . Sci . USA 90:2875-2879, 1993) . In the present investigation, indirect immunogold labeling and electron microscopy were used to localize these proteins on three clinical isolates of NTHi, mutants deficient in expression of one or both HMW proteins, and embedded sections of human oropharyngeal cells after incubation with NTHi strain 12 . The filamentous material comprising the proteins was labeled with monoclonal antibodies directed against two prototype HMW proteins (HMW1 and HMW2) of prototype NTHi strain 12 . Gold labeling was observed as a cap or discrete aggregate off one pole or centrally along one long axis of the bacterial cell . Heavily labeled, non-bacterial-cell-associated, disk-like aggregates of the HMW proteins were frequently noted in both bacterial preparations as well as in association with the oropharyngeal cell surface and intracellularly . Mutants demonstrated diminished labeling or an absence thereof, respectively, which correlated well with their previously demonstrated reduced ability or inability to adhere to Chang conjunctival epithelial cells in vitro . The Haemophilus HMW proteins share antigenic determinants with and demonstrate amino acid sequence similarity to the filamentous hemagglutinin protein of Bordetella pertussis, a critical adhesin of that organism . The studies presented here demonstrate that the Haemophilus proteins and B . pertussis filamentous hemagglutinin show impressive morphologic and perhaps additional functional similarity.

Eur J Clin Microbiol Infect Dis, 1994 Oct, 13(10), 857 - 65
Multi-investigator evaluation of the efficacy and safety of cefprozil, amoxicillin-clavulanate, cefixime and cefaclor in the treatment of acute otitis media; Kafetzis DA; Cefprozil was evaluated in the treatment of acute otitis media with effusion in three open, randomized, multicenter comparative clinical trials . In two trials, 891 pediatric patients were enrolled to either cefprozil or amoxicillin-clavulanate dosage regimens . The treatment groups were comparable in demographic characteristics, and presented with otalgia, middle-ear effusion, or inflamed or bulging tympanic membrane on otoscopic examination . In all patients, tympanocentesis and a culture were required . Two cefprozil oral doses were evaluated, 30 mg/kg/day and 40 mg/kg/day divided into two equal doses (b.i.d.) . Amoxicillin-clavulanate was administered at 40 mg/kg/day in three divided doses (t.i.d.) . The recommended duration of therapy was ten days . The predominant bacteria isolated were Haemophilus influenzae and Moraxella catarrhalis . The overall satisfactory clinical response rates were similar for cefprozil (83%) and amoxicillin-clavulanate (81%) . The bacteriological response rates did not differ significantly, at 84% and 82% . Cefprozil eradicated the most common pathogen, Streptococcus pneumoniae, more often at 91%, vs . 84% for amoxicillin-clavulanate . The eradication rates were similar against Haemophilus influenzae and Moraxella catarrhalis . The patients treated with cefprozil had a lower rate of adverse clinical events (11%) compared to those with amoxicillin-clavulanate (20%) . More gastrointestinal adverse experiences, including diarrhea, were reported in the amoxicillin-clavulanate-treated patients . In Study 3, cefprozil 30 mg/kg/day (b.i.d.) was compared to cefaclor 40 mg/kg/day (t.i.d.) and cefixime 8 mg/kg/day (q.d) in the treatment of acute otitis media in 388 pediatric patients . The patients were treated for 10 days, with a follow-up of 18 days . The overall clinical cure rates were 85%, 89% and 85%, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

Mol Cell Probes, 1994 Oct, 8(5), 417 - 22
Single polymerase chain reaction for the detection of tetracycline-resistant determinants Tet K and Tet L; Pang Y et al.; Oligonucleotide primers were used in polymerase chain reaction assays to detect tetracycline-resistant determinants Tet K and Tet L . Forty-three isolates representing 11 genera carrying Tet K and/or Tet L determinants gave appropriate PCR products . The PCR products hybridized with labelled Tet K or Tet L probes, and differentiated the Tet K from the Tet L PCR products . We confirmed that two Haemophilus aphrophilus carried the Tet K determinant and two Veillonella parvula carried the Tet L determinant . This is the first time that either of these two genes have been found in Gram-negative species . Four vaginal samples, previously positive with the Tet M/O PCR assay, were also positive with the Tet K/L assay . This is the first report of a PCR assay for the detection of Tet K and Tet L determinants in bacteria or clinical specimens.

Mil Med, 1994 Oct, 159(10), 629 - 31
Pneumonia in military recruits; Amundson DE et al.; Lower respiratory disease is a major source of morbidity in military recruits, with hospitalization rates for pneumonia more than 30 times that of the non-recruit population . The etiologic agent remains unknown in over 75% of cases . This study prospectively examined the etiology of pneumonia among recruits at Naval Training Center, San Diego, California . Recruits presenting with cough, fever, or shortness of breath and pulmonary infiltrates on chest X-ray were eligible for enrollment . A standardized scoring form and focused physical exam were completed on each subject . Sputum specimens were obtained for Gram's stain and culture, DNA probing for Legionella and Mycoplasma species, and direct fluorescent antibody staining for Legionella . Acute and convalescent serologies were performed for adenovirus, influenza A and B, Mycoplasma pneumoniae, Chlamydia group, and respiratory syncytial virus . Of 110 eligible patients, 100 consented to enrollment and 75 patients completed the study . Etiologic diagnoses were obtained in 40 of the patients (53%) . M . pneumoniae, Haemophilus influenzae, and viruses accounted for the majority of infections . Mixed infections were seen in six patients . Forty-seven percent of patients had no diagnosis established . Pneumonia in this series of military recruits was frequently caused by M . pneumoniae and H . influenzae . Fifty percent of cases were undiagnosed with routinely available laboratory methods . Further studies are warranted to more clearly define the etiologic agents of recruit pneumonia and the utility of prophylactic measures.

J Vet Med Sci, 1994 Oct, 56(5), 1017 - 9
Characterization of Haemophilus paragallinarum isolated in the Philippines; Nagaoka K et al.; In 1989 and 1990, we isolated five strains of Haemophilus paragallinarum in the Philippines . Serological studies were done on three of these isolates . The results of haemagglutination, reactability to monoclonal antibodies and cross immunization with standard strains showed that they belonged to serotypes A, B and C respectively . This is the first report on the isolation of H . paragallinarum and on a related serological study in the Philippines.

J Chemother, 1994 Oct, 6(5), 319 - 21
Incidence of lower respiratory tract infections caused by Mycoplasma, Chlamydia and Legionella: an Italian Multicenter Survey; Schito GC et al.; A collaborative retrospective study based on serologic diagnosis was conducted to assess the etiological role sustained by privileged pathogens in Italy . The results obtained indicate the Mycoplasma, Chlamydia and Legionella are important etiologic agents of lower respiratory tract infections in Italy since they account for about 31% of the cases taken into consideration in this survey . We found a high incidence of M . pneumoniae (12.3%), C . pneumoniae (10.5%) and L . pneumophila (8.3%) . These results are in line with similar figures reported in the recent literature . While the data gathered in our survey do not allow us to clarify the nature of the agents involved in the etiology of the majority (70%) of the respiratory infections occurring in Italy, it seems safe to assume that after Streptococcus pneumoniae and Haemophilus influenzae, the privileged pathogens represent the most common cause of lower respiratory tract infections.

Pediatr Emerg Care, 1994 Oct, 10(5), 268 - 72
Delayed incubation of blood culture bottles: effect on recovery rate of Streptococcus pneumoniae and Haemophilus influenzae type B; Roback MG et al.; This study investigated the effects of incubation delay on the rate of recovery of common pediatric pathogens from blood culture bottles . Known concentrations of Streptococcus pneumoniae and Haemophilus influenzae type b (three isolates each) were inoculated into BACTEC NR-6A bottles with 1.0 mL of donor blood . Bottles were subjected to a time delay (zero to six hours) before incubation . The BACTEC NR-660 was used for incubation and measurement of positive conversion . Data were analyzed using chi 2 analysis, Fisher's exact test, logistic regression, and multiple logistic regression, with P < 0.05 considered significant . Immediate incubation yielded positive blood cultures in 88 of 100 and 65 of 70 bottles containing S . pneumoniae and H . influenzae type b, respectively, in the concentration range 1.0 to 9.99 colony-forming units per milliliter (CFU/ml) . For each organism, this was the minimal range required to produce a positive culture (P < 0.0001) . Bottles inoculated with 1 ml of blood containing organisms in the range of 1.0 to 9.99 CFU/ml were then subjected to incubation delay . The recovery rate of S . pneumoniae significantly (P = 0.0003) decreased from a two-hour delay (57 of 60; 95%) to a three-hour delay (42 of 60; 70%) . No significant change in recovery rate was seen in bottles inoculated with H . influenzae type b subjected to similar delays . Delayed incubation (two to six hours) of bottles inoculated with 1.0 ml of blood containing organisms in a concentration range of 1.0 to 9.99 CFU/ml of blood significantly decreases the recovery rate of S . pneumoniae but has no effect on H . influenzae type b.

Pediatr Emerg Care, 1994 Oct, 10(5), 264 - 7
Occult bacteremia: is there a standard of care?
Ros SP, Herman BE, Beissel TJ.
The evaluation and management of patients with occult bacteremia is controversial . The purpose of this study was to define the prevailing practices in the emergency management of occult bacteremia . Short, anonymous surveys were mailed to all 517 members of the Section on Emergency Medicine at the American Academy of Pediatrics . Three hundred six (59%) of those surveyed returned completed questionnaires . Eleven different temperature cutoff points are used, and 105 (34%) consider occult bacteremia in patients with temperature above 39 degrees C . Seventeen different age intervals are used to define the patients at risk for occult bacteremia, and the age range three to 24 months is used by 173 (57%) of those surveyed . Complete blood cell count is the most commonly used screening test; it is routinely ordered by 225 respondents (74%) . One hundred thirty-seven participants (45%) routinely obtain blood cultures in all patients at risk for occult bacteremia, whereas 111 (36%) use the clinical appearance (toxicity) of the patient to determine whether a blood culture should be drawn . One hundred sixty-one (53%) of those surveyed routinely administer antibiotics to toxic-appearing patients pending the results of the blood culture . Laboratory criteria are used by 135 (44%) in the decision whether to administer empiric antibiotics . Ceftriaxone is the most commonly used antibiotic; it is routinely administered by 230 respondents (75%) . Twenty participants (7%) routinely admit all patients with Streptococcus pneumoniae, whereas 217 (71%) admit all patients with Haemophilus influenzae bacteremia and 234 (76%) admit all patients with Neisseria meningitidis bacteremia . We conclude that diversity exists in the evaluation and management of occult bacteremia.

Antimicrob Agents Chemother, 1994 Oct, 38(10), 2419 - 25
In vitro activities of 12 orally administered antimicrobial agents against four species of bacterial respiratory pathogens from U.S . Medical Centers in 1992 and 1993; Barry AL et al.; Clinical isolates of Haemophilus influenzae, Streptococcus pneumoniae, Streptococcus pyogenes, and Moraxella catarrhalis were gathered from 19 different clinical laboratories throughout the continental United States . The in vitro activities of 12 orally administered antimicrobial agents were compared by broth microdilution tests with 3,151 bacterial isolates . Among 890 H . influenzae isolates, 30% were capable of producing beta-lactamase enzymes (12 to 41% in different medical centers) . Most of the 619 beta-lactamase-negative H . influenzae strains were susceptible to ampicillicin (MIC, < or = 1.0 micrograms/ml): 5 strains were intermediate in susceptibility (MIC, 2.0 micrograms/ml) and 1 strain was ampilicillin resistant (MIC, 4.0 micrograms/ml) . Ninety-two percent of 698 M . catarrhalis strains were beta-lactamase positive . Of 799 S . pneumoniae isolates, 15% were intermediate in susceptibility to penicillin and 7% were resistant to penicillin . The prevalence of penicillin-susceptible pneumococci in different institutions ranged from 63 to 95% . Only 1% of 764 S . pyogenes isolates were resistant to the macrolides, but 5% of S . pneumoniae isolates were macrolide resistant . Only 71% of 58 penicillin-resistant S . pneumoniae isolates were erythromycin susceptible, whereas 97% of the 622 penicillin-susceptible strains were erythromycin susceptible . Penicillin-resistant pneumococci were also relatively resistant to the cephalosporins and amoxicillin . Penicillin-susceptible pneumococci were susceptible to amoxicillin-clavulanic acid (MIC for 90% of isolates tested {MIC90}, < or = 0.12/0.06 microgram/ml), cefixime (MIC90, 0.25 microgram/ml), cefuroxime axetil (MIC90, < or = 0.5 microgram/ml), cefprozil (MIC90, < or = 0.5 micrograms/ml), cefaclor (MIC90, 0.5 microgram/ml), and loracarbef (MIC90, 1.0 microgram/ml) . Most strains of the other species remained susceptible to the study drugs other than amoxicillin.

Antimicrob Agents Chemother, 1994 Oct, 38(10), 2340 - 5
Evaluation of OPC-17116 against important pathogens that cause respiratory tract infections; Wakebe H et al.; The antibacterial activity of OPC-17116, a new fluoroquinolone antibacterial agent, against important pathogens that cause respiratory tract infections was evaluated in vitro and in vivo and compared with those of ciprofloxacin, ofloxacin, and norfloxacin . The pharmacokinetic profiles of OPC-17116 were studied in both mice and rats given the drug orally at doses of 50 and 40 mg/kg of body weight, respectively . OPC-17116 showed a high degree of distribution in the lung tissues of both species, with maximum concentrations of 29.6 and 32.0 micrograms/g, respectively . Furthermore, the drug concentrations in lung tissue were about 10 to 15 times greater than the concentrations in plasma . OPC-17116 showed potent antibacterial activity against such pathogens as Staphylococcus aureus, Streptococcus pneumoniae, Klebsiella pneumoniae, Pseudomonas aeruginosa, Haemophilus influenzae, and Moraxella catarrhalis . The MICs of this compound for 90% of these organisms except methicillin-resistant S . aureus and P . aeruginosa ranged from < or = 0.006 to 0.78 microgram/ml . The in vitro antibacterial activity of OPC-17116 was reflected by the efficacy of a single oral dose against systemic bacterial infections in mice . OPC-17116 showed a superior effect against gram-positive bacteria, H . influenzae, and M . catarrhalis . In comparison with the other reference compounds, the efficacy of OPC-17116 was less than that of ciprofloxacin against K . pneumoniae and P . aeruginosa . OPC-17116 showed a greater therapeutic effect than the other drugs against experimental acute pneumonia caused by these organisms in mice or rats . This excellent therapeutic effect against respiratory tract infections may be a result of its high level of distribution in lung tissue.

Clin Otolaryngol, 1994 Oct, 19(5), 441 - 5
Acute epiglottitis--aetiology, epidemiology and outcome in a population before large-scale Haemophilus influenzae type b vaccination; Hugosson S et al.; Over a period of 18 years 219 consecutive cases of acute epiglottitis were diagnosed and subsequently investigated in order to elucidate the aetiology, epidemiology and outcome of this disease in a well-defined population in Sweden before general vaccination against Haemophilus influenzae type b infection was introduced . Compared with the results from other parts of the industrialized world, high incidence rates were found in both children (14/100,000/year) and adults (2.3/100,000/year) . The annual trend showed a significant decline in incidence among children, whereas in adults it remained unchanged . In cases where the aetiological agent could be determined, infection with H . influenzae type b was the main cause of disease in all age groups . However, in adults 27% (6/22) had a disease caused by micro-organisms other than H . influenzae type b that were verified with a blood culture . Sixty-eight per cent had a negative blood culture . The mortality rate was 0.5% (1/219) and 6% (13/219) developed a significant complication of the disease.

J Paediatr Child Health, 1994 Oct, 30(5), 393 - 7
Sequelae of Haemophilus influenzae type b meningitis in aboriginal and non-aboriginal children under 5 years of age; Bower C et al.; Between 1984 and 1990, 257 cases of Haemophilus influenzae type b (Hib) meningitis occurred in children under five years of age in Western Australia . We obtained information on possible sequelae in 131 cases (all non-Aboriginal) by medical record review and parental interview, and in a further 116 cases (60 non-Aboriginal, 56 Aboriginal) by medical record review only; no follow-up information was available for ten children (nine non-Aboriginal, 1 Aboriginal) . The incidence of Hib meningitis in children under five years of age was 26.3 per 100,000 for non-Aboriginal and 152.2 per 100,000 for Aboriginal children . The case fatality rate was 3.5% for non-Aboriginal children and 14.0% for Aboriginal children . Sequelae were recorded for 17.1% of non-Aboriginal and 22.4% of Aboriginal children who survived Hib meningitis . Surviving Aboriginal children experienced severe sequelae following Hib meningitis almost three times more frequently than surviving non-Aboriginal children (10.5% vs 3.6%), although mild and moderate sequelae were not more common in Aboriginal children . The information on incidence and severity of sequelae in this study was obtained by chart review and parental interview, and hence may be subject to error or bias, particularly for mild and moderate disabilities . Outcomes like death and severe sequelae, such as cerebral palsy and profound intellectual and physical disability, are less subject to bias . Of Aboriginal children who contracted Hib meningitis in Western Australia over the study period, 22.8% either died or had severe sequelae, while only 7.0% of non-Aboriginal children experienced these severe outcomes.

Mol Microbiol, 1994 Oct, 14(2), 217 - 33
A Haemophilus influenzae IgA protease-like protein promotes intimate interaction with human epithelial cells; St Geme JW 3rd et al.; Haemophilus influenzae represents a common cause of human disease and an important source of morbidity and mortality . Disease caused by this organism begins with colonization of the upper respiratory tract . Several studies indicate that H . influenzae is capable of binding to and entering cultured human cells, properties which are potentially of relevance to the process of colonization . In the present study, we isolated an H . influenzae gene designated hap, which is associated with the capacity for in vitro attachment and entry . Analysis of the derived amino acid sequence of hap demonstrated significant homology with the serine-type IgA1 proteases expressed by H . influenzae and Neisseria gonorrhoeae . It is notable that the hap product shares the catalytic domain of the IgA1 proteases and appears to be processed and secreted in an analogous manner . We speculate that the hap gene product is an important determinant of colonization, perhaps enabling the organism to evade the local immune response and thereby persist within the respiratory tract.

J Clin Microbiol, 1994 Oct, 32(10), 2441 - 7
Determination of parallelism and nonparallelism in bioassay dilution curves; Plikaytis BD et al.; There is a lack of consensus among investigators who use a variety of immunoassay techniques (e.g., enzyme-linked immunosorbent assay {ELISA} and radioimmunoassay) regarding the protocols for describing and forming standard reference or calibration curves and interpolating serum antibody concentrations . This confounds the issue of detecting the presence or absence of parallelism between standard reference serum and serially diluted serum sample curves . These curves must be parallel to support the assumption that the antibody-binding characteristics are similar enough to allow the determination of antibody levels in the diluted serum sample . There is no universal and widely adopted strategy for assessing parallelism in bioassays, and without an assurance of parallelism, investigators are not able to calculate reliable estimates for antibody concentrations in serum samples . Furthermore, single-point (dilution) serum assays do not provide information related to parallelism and nonparallelism, and this, too, may lead to considerable error when calculating antibody concentrations . When assay methodology, technique, and precision improve to the extent that standard reference serum and serially diluted serum sample curves are fit with little error, standard analysis of variance techniques are overly sensitive to negligible departures from parallelism . We present a series of guidelines that compose a protocol for assessing parallelism between bioassay dilution curves that are applicable to data derived from ELISAs . These criteria should be applicable, with minor modifications, to most immunoassay experimental situations and, most importantly, are not dependent on the mathematical model used to form the standard reference curve . These guidelines have evolved in our laboratories over the past 4 years during the performance of thousands of ELISAs for antibodies to the capsular polysaccharides of Neisseria meningitidis groups A and C and Haemophilus influenzae type b.

J Clin Microbiol, 1994 Oct, 32(10), 2382 - 6
PCR for capsular typing of Haemophilus influenzae; Falla TJ et al.; A PCR method for the unequivocal assignment of Haemophilus influenzae capsular type (types a to f) was developed . PCR primers were designed from capsule type-specific DNA sequences cloned from the capsular gene cluster of each of the six capsular types . PCR product was amplified only from the capsular type for which the primers were designed . Product was confirmed by using either an internal oligonucleotide or restriction endonuclease digestion . A total of 172 H . influenzae strains of known capsular type (determined genetically) comprising all capsular types and noncapsulate strains were tested by PCR capsular typing . In all cases the PCR capsular type corresponded to the capsular genotype determined by restriction fragment length polymorphism analysis of the cap region . When used in conjunction with PCR primers derived from the capsular gene bexA, capsulate, noncapsulate, and capsule-deficient type b mutant strains could be differentiated . PCR capsular typing overcomes the problems of cross-reaction and autoagglutination associated with the serotyping of H . influenzae strains . The rapid and unequivocal capsular typing method that is described will be particularly important for typing invasive H . influenzae strains isolated from recipients of H . influenzae type b vaccine.

Jpn J Antibiot, 1994 Oct, 47(10), 1379 - 400
{Antibacterial activities of new quinolones against fresh clinical isolates}; Deguchi K et al.; In order to investigate antibacterial activities of new quinolones (NQs) against a number of clinical isolates obtained in our laboratory during a period from February, 1993 to January, 1994, minimum inhibitory concentrations (MICs) were determined using most of the NQs available in the market as of December, 1993 . The obtained results are summarized as follows: 1 . Noticeable differences were observed among the antibacterial activities of 8 different NQs tested against Gram-positive bacteria, i.e., there were large differences in their MIC distributions . Some differences were also observed among different NQs in ratios of NQ-resistant strains among Staphylococcus spp . From these results, it seems necessary to further study tolerance mechanisms of these Gram-positive bacteria toward different NQs and also to examine possible differences in antibacterial activities among different NQs against Gram-positive bacteria in clinical settings . 2 . MIC distributions against Gram-negative bacteria were also different among the 8 NQs tested . Though elevated MICs were observed against NQ-resistant Gram-negative bacteria in many cases, and somewhat higher, though not exceedingly high, MIC values than those against NQ-sensitive bacteria were found in other cases, patterns of MIC values against different NQ-resistant Gram-negative bacteria were similar for all of the 8 NQs tested . This may explain the fact that most of NQ-resistant Gram-negative bacteria showed similar resistant patterns to the 8 NQs tested . 3 . Among the NQ-resistant bacteria, were found Haemophilus influenzae and Neisseria gonorrhoeae strains . Ratios of resistant strains were approximately 10% or lower for the former and approximately 20% for the latter . 4 . With MICs of ampicillin and cefaclor used as control, it appears that benzylpenicillin (PCG)-insensitive or PCG-resistant Streptococcus pneumoniae (PISP or PRSP) and CEPs-resistant Escherichia coli are increasing.

Jpn J Antibiot, 1994 Oct, 47(10), 1369 - 78
{Antimicrobial activities of cefditoren against clinical isolates obtained from outpatients}; Deguchi K et al.; To examine the antimicrobial activity of cefditoren (CDTR) against strains clinically isolated from outpatients at this hospital from November, 1993 to February, 1994, the minimum inhibitory concentrations (MICs) were determined including those of the control drugs . The results were as follows: 1 . CDTR showed strong antimicrobial activities against Staphylococcus aureus subsp . aureus, Streptococcus pyogenes and Streptococcus pneumoniae . The MICs of CDTR against benzylpenicillin-insensitive or -resistant S . pneumoniae distributed in the lowest concentration range even compared to those of the control drugs . 2 . CDTR showed strong antimicrobial activities against Haemophilus influenzae, Moraxella subgenus Branhamella catarrhalis, Escherichia coli, and Klebsiella spp . The MIC of CDTR against CEPs-resistant E . coli was lower than those of most control drugs . 3 . Since the microbes described above the major pathogens for the community-acquired infections, CDTR will be effective against infectious diseases transmitted at outpatient visits.

Clin Infect Dis, 1994 Oct, 19(4), 768 - 9
Haemophilus influenzae epididymo-orchitis and bacteremia in a man infected with the human immunodeficiency virus; Cross JT Jr et al.; Haemophilus influenzae is a major bacterial pathogen in patients infected with the human immunodeficiency virus (HIV), although most infections with this organism occur in the respiratory tract . We describe an adult with HIV infection who presented with epididymo-orchitis due to H . influenzae . Eleven prior cases of H . influenzae epididymo-orchitis have been published, but all of these cases occurred in pediatric patients . Little is known about the prevalence of genitourinary tract infections caused by H . influenzae among adults . H . influenzae is a relatively rare cause of bacteremia in adults, but the frequency of H . influenzae bacteremia has been increasing among the HIV-positive population.

Microb Pathog, 1994 Oct, 17(4), 277 - 82
Mapping of a strain-specific bactericidal epitope to the surface-exposed loop 5 on the P2 porin protein of non-typeable Haemophilus influenzae; Yi K et al.; The P2 protein is the major outer-membrane protein of non-typeable Haemophilus influenzae (NTHI) and shows extreme heterogeneity among strains . Based on the analysis of antigenic structure, the P2 protein consists of eight potentially surface-exposed loops . Previous studies of monoclonal antibodies (mABs) to a single strain of NTHI showed that P2 contains potentially immunodominant epitopes in loop 5 of the molecule . The goal of the current work is to test the hypothesis that strain-specific and potentially immunodominant epitopes are located in loop 5 of P2 in other strains of NTHI as well . Gene fragments which encode peptides of loop 5 of strains 2019 and 5657 were cloned into an expression vector and subjected to immunoassays with mABs which recognize surface-exposed, bactericidal, strain-specific epitopes . Each mAB recognized loop 5 of the P2 protein of the homologous strain . Analysis of mutant clones with minor amino acid changes showed a loss of reactivity with the mABs . These observations indicate that loop 5 of the P2 molecule contains strain-specific, abundantly expressed surface-exposed epitopes . This further supports the hypothesis that loop 5 is an immunodominant region of the P2 molecule.

Clin Infect Dis, 1994 Oct, 19(4), 677 - 83
Haemophilus parainfluenzae endocarditis: application of a molecular approach for identification of pathogenic bacterial species; Hamed KA et al.; Haemophilus parainfluenzae is both a human oropharyngeal commensal bacterium and a cause of serious invasive disease . The fastidious growth characteristics of this organism and the poor specificity of traditional methods for species identification are likely to have led to inaccuracies in the diagnosis of infections caused by H . parainfluenzae and related organisms . We report a case of H . parainfluenzae endocarditis in which confusion related to microbial identification was resolved by the analysis of 16S ribosomal RNA sequences . Rapid identification was facilitated by amplification of 16S ribosomal DNA directly from cultured cells with use of the polymerase chain reaction and by direct DNA sequence determination of the amplified product . This procedure is potentially useful for the identification of fastidious bacterial pathogens by reference laboratories.

Endocrinology, 1994 Oct, 135(4), 1488 - 95
Role of the extracellular regions of the parathyroid hormone (PTH)/PTH-related peptide receptor in hormone binding; Lee C et al.; The PTH/PTH-related peptide receptor is a member of a newly discovered family of G-protein-coupled receptors . Strikingly conserved features among these receptors include the positioning of eight extracellular cysteines and several other residues that are located predominantly within the membrane-embedded region . Deletion mutants or receptors with point mutations of the highly conserved cysteine residues were transiently expressed in COS-7 cells to evaluate PTH binding and PTH-stimulated cAMP production . Deletion of residues 61-105, which are encoded by exon E2 in the PTH/PTH-related peptide receptor gene, did not affect receptor function . An epitope derived from Haemophilus influenza hemagglutinin was, therefore, introduced into this portion of most receptors to allow the independent assessment of cell surface expression . PTH binding capacity was not reduced by the deletion of residues 258-278 in the first extracellular loop . Receptors with deletion of either residues 31-47 in the amino-terminal extension or residues 431-440 in the third extracellular loop failed to bind PTH, although expression of the receptor on the cell surface was only marginally reduced . Most other receptor mutants, including those in which each of the six cysteines in the amino-terminus was replaced by serines, failed to be processed and/or expressed appropriately, whereas the substitution of cysteine-281 or -351 had a less severe effect . The combined replacement of both cysteines concomitantly increased PTH binding and cell surface expression, suggesting the formation of a disulfide bond between these two residues . Our data indicate that residues near the amino-terminus and within the third extracellular loop are necessary for ligand binding, whereas more than 25% of the receptor's extracellular region appears not to be involved.

Arch Intern Med, 1994 Sep 26, 154(18), 2086 - 91
Bacterial bronchitis and bronchiectasis in human immunodeficiency virus infection; Verghese A et al.; BACKGROUND: Bacterial pneumonia and sinusitis are important causes of morbidity in patients with human immunodeficiency virus (HIV) infection . We noted an increased incidence of bacterial bronchitis and bronchiectasis in our patients with HIV infection . METHODS: This study was conducted on persons with HIV infection at a county hospital and clinic . Bronchiectasis was diagnosed by bronchogram and computed tomography in one patient and by computed tomography alone in two others . Bacterial bronchitis was defined by a Gram's stain showing an abundance of neutrophils with a predominance of one or more bacteria and by a confirmatory sputum culture . Bronchoscopy with broncho-alveolar lavage was performed in patients with bronchitis to eliminate other causes of bronchial inflammation . RESULTS: Eighteen episodes of bacterial bronchitis in 10 patients are described . The mean CD4 lymphocyte counts for these patients was 0.061 x 10(9)/L (range, 0.001 to 0.203 x 10(9)/L) . The most common pathogens in 18 episodes of bacterial bronchitis were Haemophilus influenzae and Streptococcus pneumoniae (five episodes each) and Pseudomonas aeruginosa (four episodes) . Response to antibiotic therapy was usually rewarding though recurrences were frequent . Three patients with well-defined bronchiectasis who appeared to have developed, or who became symptomatic during the course of, HIV infection are described . Their mean CD4 cell count was 0.03 x 10(9)/L (range, 0.024 to 0.037 x 10(9)/L) . Haemophilus influenzae, Staphylococcus aureus, Pseudomonas cepacia, and P aeruginosa were recovered from these patients; the P aeruginosa was a mucoid strain . CONCLUSIONS: Recurrent bacterial bronchitis should be added to the list of bacterial infections that occur with increased frequency with HIV infection . Repeated bacterial bronchitis may lead to bronchiectasis, which may be more common in HIV infection than generally appreciated.

J Am Vet Med Assoc, 1994 Sep 15, 205(6), 874 - 7
Vesicular adenitis syndrome in beef bulls; Grotelueschen DM et al.; Vesicular adenitis syndrome was diagnosed in 69.3% (52/75) of a group of yearling bulls on breeding soundness examination . Association of Haemophilus somnus infection with vesicular adenitis syndrome was confirmed in these bulls by microbial culture of vesicular gland fluid or semen samples and serologic testing.

Clin Exp Immunol, 1994 Sep, 97(3), 411 - 6
Binding of mannan-binding protein to various bacterial pathogens of meningitis; van Emmerik LC et al.; Mannan-binding protein (MBP), a calcium-dependent plasma lectin, may play a role in the innate defence against microorganisms . After binding to carbohydrate structures at the bacterial surface, MBP activates the classical pathway of the complement system . To investigate the binding capacity of MBP to various bacteria associated with meningitis, an assay was developed to study the binding of MBP to bacteria grown in a semisynthetic fluid culture medium . Salmonella montevideo (containing a mannose-rich lipopolysaccharide (LPS)), used as a positive control strain, showed binding of radiolabelled MBP at a level of 80% compared with binding of MBP to zymosan . Binding of labelled MBP to Salm . montevideo was time-dependent, temperature-dependent and saturable . The binding was inhibited by unlabelled MBP, by mannose and by N-acetyl-D-glucosamine . Among bacterial pathogens often found to cause meningitis, a wide range of MBP binding capacities could be determined . The encapsulated Neisseria meningitidis (representatives from 11 serogroups other than group A were included: n = 22), N . mucosa (n = 1), Haemophilus influenzae type b (n = 10) and Streptococcus agalactiae (n = 5) had a low MBP binding capacity of 21.7% (95% confidence interval (CI) 3.3-40.1%) . Escherichia coli K1 (n = 11), Strep . suis (n = 5), Strep . pneumoniae (n = 10) and N . meningitidis serogroup A (n = 2) showed intermediate MBP binding capacity of 58.4% (95% CI 40.0-76.8%) . A third group consisting of non-encapsulated Listeria monocytogenes (n = 11), non-encapsulated H . influenzae (n = 2), non-encapsulated N . meningitidis (n = 2), N . cinera (n = 1) and N . subflava (n = 1) strains had a high MBP binding capacity of 87.5% (95% CI 62.5-112.5%) . The majority of encapsulated pathogens causing bacterial meningitis seem to have a rather low MBP binding capacity.

Clin Exp Immunol, 1994 Sep, 97(3), 396 - 402
Cytokines in nasopharyngeal secretions; evidence for defective IL-1 beta production in children with recurrent episodes of acute otitis media; Lindberg K et al.; The host-parasite relationship in the nasopharynx of young children with bacterial colonization and antigen uptake in the mucosa and lymphatic tissue provides an opportunity to investigate infectious/inflammatory processes and responses . IL-1 beta, IL-6 and tumour necrosis factor-alpha (TNF-alpha) were analysed in nasopharyngeal secretions and serum from children with or without recurrent episodes of acute otitis media, from healthy adults and adults with or without recurrent episodes of acute otitis media, from healthy adults and adults with hypogammaglobulinaemia or selective deficiency of IgG3 . Nasopharyngeal secretions generally contained substantial amounts of IL-1 beta, IL-6 and TNF-alpha . In contrast, IL-1 beta, IL-6 and TNF-alpha were not detectable in sera on the same occasion . Children were found to have higher levels of IL-1 beta, IL-6 and TNF-alpha than healthy adults and than adults with immunodeficiency . High levels of IL-1 beta were associated with low or undetectable levels of IL-6 and TNF-alpha, whereas the opposite pattern was seen in association with low levels of IL-1 beta . This was especially true for children with recurrent episodes of acute otitis media (RAOM) . In children with nasopharyngeal colonization with Haemophilus influenzae, significantly higher levels of IL-1 beta, IL-6 and TNF-alpha (P = 0.0001, respectively) were found compared with non-colonized children . Notably, the RAOM children exhibited significantly lower levels of IL-1 beta, IL-6, and TNF-alpha in nasopharyngeal secretions (P = 0.0001, 0.01 and 0.0001, respectively) than healthy children . These results demonstrate local production of inflammatory cytokines in nasopharynx, related to bacterial colonization, and suggest that children with RAOM are poor nasopharyngeal cytokine producers.

Infect Immun, 1994 Sep, 62(9), 4028 - 33
High-molecular-weight proteins of nontypeable Haemophilus influenzae mediate bacterial adhesion to cellular proteoglycans; Noel GJ et al.; A family of high-molecular-weight (HMW) surface-exposed proteins of nontypeable Haemophilus influenzae (NT H . influenzae) mediated adherence of these organisms to human epithelium . To better understand the molecular basis for this adherence, the role of glycosaminoglycans (GAGs), substances commonly expressed on cell surfaces, was examined . Bacterial adherence to cells with specific deficiencies in GAG biosynthesis was measured . HMW protein-dependent bacterial adherence to normal cells was significantly greater than adherence to cells deficient in sulfated GAGs or to cells deficient in heparan sulfate but overexpressing chondroitin sulfate . Cells expressing undersulfated heparan sulfate exhibited intermediate levels of bacterial adherence . The addition of exogenous dextran sulfate or heparin inhibited over 70% of the adherence of NT H . influenzae to normal cells, whereas hyaluronic acid and chondroitin sulfate tested at the same concentration (100 micrograms/ml) inhibited bacterial adherence by less than 11% . Treatment of cells with heparinase significantly reduced bacterial adherence . Following electrophoretic separation, HMW proteins were shown to bind directly to radiolabeled heparin . These results indicate that HMW protein-dependent adherence of NT H . influenzae is mediated by cellular sulfated GAGs and that heparan sulfate may be the predominant GAG involved in this process . However, the decreased adherence of bacteria to cells expressing undersulfated heparan sulfate and the inhibition of bacterial adherence by the addition of exogenous dextran sulfate suggest that bacterial adhesion to mammalian cells is likely to be influenced by a variety of factors, including the degree of sulfation and the specificity of the carbohydrate moieties contained in the cellular proteoglycans.

Infect Immun, 1994 Sep, 62(9), 3881 - 9
The HMW1 adhesin of nontypeable Haemophilus influenzae recognizes sialylated glycoprotein receptors on cultured human epithelial cells; St Geme JW 3rd; Disease due to nontypeable Haemophilus influenzae begins with colonization of the upper respiratory tract mucosa . We recently reported that two surface-exposed high-molecular-weight proteins (HMW1 and HMW2) expressed by a prototypic strain of nontypeable H . influenzae mediate attachment to cultured epithelial cells . In the present study, we examined the nature of the epithelial cell receptor with which HMW1 interacts . Both proteinase K pretreatment and periodate oxidation of epithelial monolayers resulted in a marked decrease in HMW1-mediated binding, suggesting interaction with a glycoprotein structure . Treatment with peptide-N-glycosidase F produced a similar decrease in attachment and thereby provided further evidence for this conclusion . Desialylation of the epithelial cell surface also reduced binding, implying the presence of sialic acid in the receptor structure . Furthermore, lectins specific for terminal alpha 2-3-linked sialic acid were capable of inhibiting HMW1-mediated attachment . In summary, our results indicate that the HMW1 adhesin interacts with a glycoprotein receptor containing N-linked oligosaccharide chains with sialic acid in an alpha 2-3 configuration.

Infect Immun, 1994 Sep, 62(9), 3873 - 80
Variable region sequences of a protective human monoclonal antibody specific for the Haemophilus influenzae type b capsular polysaccharide; Lucas AH et al.; A hybridoma secreting a human immunoglobulin G2 kappa monoclonal antibody (MAb) specific for the capsular polysaccharide of Haemophilus influenzae type b (Hib) was isolated . This MAb, designated CA4, was bactericidal to Hib in vitro and protected infant rats from Hib bacteremia . Nucleotide sequence analysis of CA4 variable (V) region cDNA showed that the heavy (H)-chain V region was of subgroup III and was 96% identical to the VH germ line gene segment DP77 (V3-21) . The light (L)-chain V region was of the kappa subgroup III and was 94% identical to the A27 (Humkv325) germ line gene, which is commonly used by rheumatoid factors and other autoantibodies . MAb CA4 did not have rheumatoid factor activity and did not react with histones, DNA, or chromatin . These findings identify an additional VHIII gene segment which can contribute to the anti-Hib capsular polysaccharide repertoire and demonstrate that a VL gene commonly encoding autoantibodies can be utilized for protective immunity.

Infect Immun, 1994 Sep, 62(9), 3739 - 44
Platelet-activating factor augments meningeal inflammation elicited by Haemophilus influenzae lipooligosaccharide in an animal model of meningitis; Townsend GC et al.; Research into the pathophysiology of bacterial meningitis has suggested a role for various endogenous inflammatory mediators, such as platelet-activating factor (PAF) . In the present study, rats were inoculated intracisternally with various doses of PAF, with Haemophilus influenzae lipooligosaccharide (LOS) in high doses (20 ng) alone, and with a low dose of LOS (200 pg) with or without low doses of PAF (25 ng to 2.5 micrograms) . Values for cerebrospinal fluid leukocytosis and percent blood-brain barrier permeability to systemically administered 125I-labeled albumin observed after inoculation of low-dose LOS with PAF were greater (P < 0.05) than those observed after inoculation of low-dose LOS alone and not statistically different from those observed after inoculation of high-dose LOS . PAF alone elicited an inflammatory response only at high doses (25 micrograms) . These results support the hypothesis that low cerebrospinal fluid PAF concentrations, such as those observed in children with bacterial meningitis, may augment the inflammatory response to the presence of bacteria in the subarachnoid space.

Can Vet J, 1994 Sep, 35(9), 573 - 80
The occurrence of Haemophilus somnus in feedlot calves and its control by postarrival prophylactic mass medication; Van Donkersgoed J et al.; Three field trials were conducted in a large commercial feedlot in Saskatchewan to determine the prevalence of Haemophilus somnus in calves and to evaluate the efficacy of prophylactic mass medication with long-acting oxytetracycline on day 17 (1990, n = 1336), day 11 (1991, n = 4372), or day 8 (1992, n = 5632) postarrival . Hemophilosis accounted for > 40% of the mortality in feedlot calves each year . Haemophilus somnus was cultured from the blood of one febrile calf on day 1 (0.1%, n = 895), but it was not cultured from nasal swabs on day 1 or day 11 (n = 881) or from blood samples on day 11 (n = 883) . Similarly, it was not cultured from nasal swabs or blood samples from sick calves first treated for bovine respiratory disease (BRD) (n = 219) . Serological titers to H . somnus increased (p < 0.05) in unvaccinated calves from day 1 (Geometric mean titer = 11,846) to day 96 (Geometric mean titer = 63,712), indicating natural infection following feedlot entry . Calves that relapsed twice with BRD or died from BRD +/- hemophilosis had significantly (p < 0.06) lower titers to H . somnus on days 1 and 96 than those that did not relapse twice or die . Postarrival mass medication with long-acting oxytetracycline did not reduce (p > 0.05) the risk of hemophilosis mortality . However, it reduced (p < 0.05) the risk of BRD treatment by 14% and the risk of BRD mortality by 71% . Additional epidemiological studies of H . somnus are needed so that we can develop strategic medication and vaccination programs to reduce losses from hemophilosis.

Jpn J Antibiot, 1994 Sep, 47(9), 1219 - 30
{A clinicobacteriologic study on sultamicillin fine granules in pediatric sinusitis}; Sugita R et al.; We carried out clinical and bacteriological studies on sultamicillin (SBTPC) in pediatric sinusitis at 10 general practice settings . The results are summarized as follows . 1 . The major isolated organisms from purulent nasal discharges were Streptococcus pneumoniae 27.5%, Haemophilus influenzae 32.4% and Moraxella catarrhalis 9.9% . Similar results were observed for the major isolates from nasopharynx . 2 . 33% of the isolated S . pneumoniae were penicillin-insensitive S . pneumoniae (PISP) against which the MICs were equal to or higher than 0.1 microgram/ml . 3 . PISP was isolated from 14% of all cases . 4 . The clinical efficacy rate was 77.5% and was deemed satisfactory . 5 . In the bacteriological study, persistence rate of PISP was 38.5% among the PISP from purulent nasal discharge and 60.0% among the PISP from nasopharynx which and these values were significantly higher than persistence rates of PSSP, H . influenzae and M . catarrhalis . 6 . Adverse reactions were observed in 21.5% of all cases, involving diarrhea and loose stool.

Jpn J Antibiot, 1994 Sep, 47(9), 1202 - 9
{The clinical study of cefpodoxime proxetil dry syrup preparation in the pediatric field}; Kasagi T et al.; The clinical efficacy was examined for the newly developed oral cephem antibiotic, cefpodoxime proxetil (CPDX-PR) dry syrup, in the treatment of various acute infections in the field of pediatrics . CPDX-PR dry syrup was administered at 10 mg/kg/day in 3-divided doses to 535 children at 21 institutions, including Tottori University Hospital and its related hospitals . The efficacy rate of this drug was determined to be 80.8% . Among isolates, Staphylococcus aureus and Streptococcus sp . were highly susceptible to the drug, whereas Haemophilus influenzae showed relatively poor susceptibility . Side effects were observed in 2.80% of all of the patients, and abnormal laboratory findings were detected in 1.87% . The low incident of side effects demonstrated its high safety, and this drug was considered to be very useful for such pediatric infections as acute tonsillitis, acute pharyngitis and acute bronchitis.

Jpn J Antibiot, 1994 Sep, 47(9), 1186 - 91
{Antimicrobial activities of fosfomycin against Streptococcus pneumoniae and Haemophilus influenzae recently observed in sinusitis patient}; Deguchi K et al.; In order to examine antimicrobial activities of fosfomycin (FOM), the minimum inhibitory concentrations (MICs) of FOM and those of control drugs were determined against Streptococcus pneumoniae and Haemophilus influenzae isolated from sinusitis patients from September to November, 1993, and the following results were obtained . 1 . Among 50 S . pneumoniae strains tested, there were 10 strains (20.0%) of benzylpenicillin (PCG)-insensitive S . pneumoniae (PISP) and 2 strains (4.0%) of PCG-resistant S . pneumoniae (PRSP); but the MIC distributions of FOM among the PISPs and the PRSPs were almost identical to those among the PCG-susceptible S . pneumoniae (PSSP) . 2 . There were 12 strains (24.0%) of beta-lactamase producing strains among 50 strains of H . influenzae tested, but the FOM's MIC distribution among these strains was almost identical to that among beta-lactamase non-producing strains . 3 . The results obtained on the MIC90s of FOM against S . pneumoniae and H . influenzae suggest that the nebulization treatment with FOM nasal preparation satisfies the condition "above the MIC".

J Clin Pathol, 1994 Sep, 47(9), 796 - 8
Rapid organism identification from Bactec NR blood culture media in a diagnostic microbiology laboratory; Claxton PM et al.; AIMS--To evaluate rapid organism identification on positive blood culture Bactec NR media (phial types 26, 27, 42 and 17), and to assess the usefulness of these procedures in a diagnostic microbiology laboratory . METHODS--Two hundred and sixty, first positive, blood culture bottles from individual patients were tested by rapid identification methods selected on the basis of Gram film organism morphology . Tube coagulase and latex agglutination were applied to presumptive staphylococci; latex agglutination antigen detection methods to suspected pneumococci, Neisseria and Haemophilus sp; and latex agglutination grouping tests for cultures thought to be non-pneumococcal streptococci . RESULTS--Media type did not influence test performance (p > 0.05 for all comparisons) . Misapplication of methods occurred on eight occasions and there were 14 false positive results, nine involving the latex reagents for group C streptococci and pneumococci . The positive predictive values for tube coagulase tests and latex reactions for H influenzae type b, and N meningitidis groups B and C were 100% . The pneumococcal and staphylococcal latex tests gave positive predictive values of 94.1% and 62.5%, respectively, and the corresponding figure for streptococcal grouping reactions was 75.9% . With the exception of staphylococcal latex testing (80%) all investigation negative predictive values were > 90% . CONCLUSIONS--The performance of the staphylococcal latex agglutination method was unsatisfactory and it is not appropriate for use with the media studied . In view of the cross-reactions observed with the tests used to identify group C streptococci and pneumococci, positive findings must be interpreted with caution . In all other regards the protocol evaluated produced rapid, reliable, clinically useful information and, subject to local experience, is recommended to users of Bactec NR media.

Chemotherapy, 1994 Sep-Oct, 40(5), 299 - 303
Antibiotic resistance patterns of Streptococcus pneumoniae, Haemophilus influenzae and Moraxella catarrhalis: a prospective study in Murcia, Spain, 1983-1992; Gomez J et al.; We prospectively determined the role of commonly used antibiotics in the emergence of antimicrobial resistance among the predominant pathogens associated with the respiratory tract . Clinical isolates of Streptococcus pneumoniae, Haemophilus influenzae and Moraxella catarrhalis from otic exudates, exudates obtained by puncture of the paranasal sinuses, sputum samples or blood cultures obtained from hospital inpatients with symptoms of significant upper or lower respiratory tract infection were analyzed . Between 1983 and 1992 a statistically significant increase in strains of S . pneumoniae and H . influenzae resistant to ampicillin, erythromycin and co-trimoxazole was detected . A significant increase in strains of M . catarrhalis resistant to ampicillin was also found . The increase in the consumption of aminopenicillins, co-trimoxazole and macrolides was associated with an increase in strains of S . pneumoniae, H . influenzae and M . catarrhalis resistant to these agents.

Plasmid, 1994 Sep, 32(2), 228 - 32
An analysis of the complete nucleotide sequence of the Haemophilus ducreyi broad-host-range plasmid pLS88; Dixon LG et al.; We present an analysis of the complete nucleotide sequence of pLS88, a naturally occurring, 4.8-kb broad-host-range plasmid isolated from Haemophilus ducreyi and encoding resistance to sulfonamides, streptomycin, and kanamycin . Sequence analysis of the genes encoding sulfonamide and streptomycin resistance revealed homology to the RSF1010 sulII and strA genes . The sulII-strA intergenic region of pLS88 has a 38-bp deletion identical to that of the RSF1010-like plasmid pHD8.1, isolated from Actinobacillus pleuropneumoniae . The kanamycin resistance gene shows strong homology to Tn903, but lacks the inverted repeats of the transposon . No other genes have been identified . The region downstream of the kanamycin resistance gene shows homology to the RSF1010 oriV region; however, this region is not essential to plasmid replication . The ori of pLS88 is contained within a 1060-bp region and does not appear to contain structures typical of plasmid origins . This region is flanked by DNA showing strong homology to regions both upstream and downstream of the Haemophilus influenzae ROB-1 beta-lactamase gene . Because of the small size of the origin, pLS88 appears to resemble the structure of narrow-host-range plasmids, but replicates, via an as yet unidentified mechanism, as a broad-host-range plasmid.

Cent Afr J Med, 1994 Sep, 40(9), 234 - 44
Teenage obstetric and gynaecological problems in an African city; Duncan ME et al.; OBJECTIVE: To measure the prevalence of sexually transmitted diseases (STD), pelvic inflammatory disease (PID), cervical cancer, pregnancy and use of contraception in teenagers, and to determine socioeconomic factors associated with these conditions to aid planners of medical services and promotion of sexual health . SUBJECTS: 181 Ethiopian teenagers and 1,845 women aged 20 to 45 years for comparison . SETTING: Gynaecological outpatient department, antenatal, postnatal and family planning clinics, in two teaching hospitals and a mother and child heath centre in Addis Ababa, Ethiopia . METHODS: Results of serologic tests for STD, clinical evidence of PID, and cervical cytology were analysed against socio-economic factors . RESULTS: In teenagers early age at first marriage/coitus, more common in those of rural origin, was associated with poverty, a greater number of lifetime sexual partners, and prostitution: 40 pc were first sexually active before the menarche . Prevalence of seropositivity to specific STD pathogens was; Treponema pallidum (TPHA) 21 pc, Neisseria gonorrhoeae (gonococcal antibody test: GAT) 40 pc, genital chlamydiae 51 pc, hepatitis B virus 36 pc, herpes simplex virus (HSV-2) 32 pc, and Haemophilus ducreyi 16 pc: 92 pc of teenagers were seropositive to one or more STD's . STD seroprevalence was higher in those with more than one sexual partner, those sexually active by age 15 (very high in those sexually active by age 12), those involved in prostitution and those attending the family planning clinic . Forty three pc had clinical evidence of PID; one married at age 10 had invasive cervical cancer by age 18; 40 pc of teenagers were pregnant compared with 25 pc of those aged 20 to 45; 21 pc attended for family planning; of regular FPC attenders 81 pc were GAT seropositive . CONCLUSION: Despite legislation early age of sexual debut is common, STD and PID are widely prevalent, the pregnancy rate in adolescents is high and contributes to the national population growth rate . Action is required at family, medical and governmental level to encourage cultural acceptance that marriage and sexual activity should not occur before the age of 16 years, with education appropriate to culture to prevent STD . Similar studies are recommended in other countries to establish a baseline for informed strategy regarding prevention of STD and health educationPIP: A survey of 181 Ethiopian females ages 14-19 years recruited from health facilities in Addis Ababa revealed a high incidence of obstetric and gynecologic problems . All subjects completed a questionnaire administered by a female health worker and underwent a gynecologic examination and serologic tests . 49% of subjects were married and 18% were divorced; 11% were prostitutes . Age at first intercourse was under 12 years in 18%, 13-15 years in 38%, and 16 years or above in 44%; 40% were sexually active before menarche . 92% of adolescents had at least one sexually transmitted disease (STD), predominantly gonorrhea (40%), genital chlamydia (51%), hepatitis B (36%), herpes simplex virus (32%), and syphilis (21%), and 43% had clinical signs of pelvic inflammatory disease (PID) . 53% had had at least one pregnancy . The earlier the age at first intercourse, the more likely it was that the adolescent would have multiple sexual partners and several STDs; adolescents in this category were also more likely to be from poor families from rural areas . Only 21% were attending a family planning clinic for annual check-ups; 14% of these females were using contraception . Although only 8% were infertile at the time of assessment, 23% had clinical evidence of salpingitis--a risk factor for future infertility . Given the long-term health risks (e.g., infertility, cervical cancer, and gonorrhea-related infant morbidity) associated with the patterns observed among these adolescents, it is recommended that STD education receive higher priority and that the Ethiopian Government consider greater enforcement of the law prohibiting sexual intercourse and marriage before the age of 16 years .

Semin Respir Infect, 1994 Sep, 9(3), 180 - 8
Community-acquired pneumonia: the future of the microbiology laboratory: focused diagnosis or syndromic management?
MacDonald KS, Scriver SR, Skulnick M, Low DE.
The traditional classification of community-acquired pneumonia into typical and atypical pneumonia to facilitate successful empirical treatment is no longer optimal . An accurate prediction of cause and adequate empirical therapy cannot be provided with this approach in severely ill patients . There is an increasing spectrum of recognized treatable pathogens presenting as community-acquired pneumonia including Legionella species, Chlamydia pneumoniae, and Pneumocystis carinii in addition to the traditional community pathogens . The variability of presentation in severely ill or compromised hosts makes clinical prediction of cause inadequate . A more rational approach may involve the classification of patients by the severity of illness and underlying disease with little or no microbiological workup in mild illness unless the results will contribute to the epidemiological surveillance of resistance because these investigations have not been shown to affect outcome in this setting . Etiologic diagnosis should be more aggressively sought and the microbiology laboratory can be best used by providing the efficient and rapid diagnosis of this expanded range of pathogens in more severely ill patients . The mounting antimicrobial resistance of common pathogens such as Streptococcus pneumoniae, Haemophilus influenzae, and Staphylococcus aureus will require not only a critical review of empirical therapy, but an increased emphasis on epidemiological monitoring of resistance by laboratories and effective communication with clinicians.

Semin Respir Infect, 1994 Sep, 9(3), 166 - 79
Initial investigation and treatment of the patient with severe community-acquired pneumonia; Ortqvist A; Approximately 5% to 10% of patients hospitalized with community-acquired pneumonia (CAP) require treatment in an intensive care unit (ICU) because of severe disease . The case fatality rates in these patients are high, between 20% and 50% in most series . Streptococcus pneumoniae, Legionella spp, Haemophilus influenzae, Staphylococcus aureus, and gram-negative enteric bacteria are the most common causes of severe CAP . However, because the spectrum of pathogens encountered in these patients is unlimited, including viruses, tuberculosis, and opportunistic pathogens, it is crucial to obtain an etiologic diagnosis . A complete diagnostic arsenal should be used, including, if possible, invasive diagnostic procedures before antibiotics are given . The initial empirical therapy must cover the most common pathogens, and in most patients this can be accomplished with a combination of a cephalosporin and a macrolide.

Blood Rev, 1994 Sep, 8(3), 179 - 91
Prophylaxis against late infection following splenectomy and bone marrow transplant; Fielding AK; There is a well documented risk of late infection following both splenectomy and bone marrow transplantation . In asplenic patients, the phagocytic and antibody producing roles of the spleen are lost and there is a lifelong susceptibility to infection which may be overwhelming and fatal . Patients most at risk are children, those with underlying lymphoproliferative disorders and those receiving immunosuppressive therapy . Although it is hard to prove benefit from preventative strategies, patients are likely to benefit from prophylactic antibiotic therapy and from immunisation with pneumococcal, Haemophilus influenzae-B and meningococcal vaccine given prior to splenectomy . Following an allogeneic bone marrow transplant (BMT), recovery of immune function takes up to a year . During this time, patients are at high risk from cytomegalovirus (CMV) and varicella zoster virus (VZV) infections and also from pneumocystis pneumonia . Prophylactic medications are used to good effect . The major threat of late infection occurs in patients with chronic graft versus host disease (cGVHD)--there is increased susceptibility to bacterial, fungal and viral infections . Many patients without cGVHD recover immune function fully and many develop antibodies to specific recall antigens . This does not occur in all patients and although there is a low risk of infection with organisms against which vaccines are available . If it is not possible to measure specific antibody titres and consequently offer selective re-immunisation, then a universal vaccination strategy should be in force . Response to vaccines is likely to be poor before one year post BMT . For autologous transplant recipients, immune recovery is probably complete and routine re-immunisation is not likely to offer much benefit . For both asplenic and bone marrow transplant patients, education of patient and physician is important.

Int J STD AIDS, 1994 Sep-Oct, 5(5), 332 - 7
Seroprevalence and incidence of sexually transmitted diseases in a rural Ugandan population; Wagner HU et al.; The aim of the study was to determine in a rural population the age- and sex-specific prevalence and incidence rates of serological reactivity of 5 common sexually transmitted diseases (STDs) and their association with HIV-1 antibody status . Of the adult population of two villages (529 adults aged 15 years or more) 294 provided an adequate blood specimen both on enrollment and at 12 months . The sera were tested at 3 collaborating laboratories for antibodies against HIV-1, Treponema pallidum, Haemophilus ducreyi, Chlamydia trachomatis and herpes simplex virus type 1 (HSV-1) and type 2 (HSV-2) . A sample of 45 children were tested for HSV-1 and HSV-2 . Seroprevalence rates in adults on enrollment were 7.8% for HIV-1, 10.8% for active syphilis, 10.4% for H . ducreyi, 66.0% for C . trachomatis, 91.2% for HSV-1 and 67.9% for HSV-2 . Males were significantly more likely than females to be seropositive for H . ducreyi (15.6% versus 6.6%), but less likely to be HSV-2 antibody positive (57.0% versus 74.4%) . Reactivity to H . ducreyi, C . trachomatis and HSV-2 rose with increasing age . In contrast, active syphilis showed no age trend . All STDs tended to be more common in those HIV-1 seropositive . Incidence rates over the 12 months were nil for HIV-1, 0.5% for syphilis, 1.2% for H . ducreyi, 11.3% for C . trachomatis, and 16.7% for HSV-2 . The results of this exploratory study indicate that all STDs included are common in this rural population . The high HSV-2 prevalence rate among adolescents suggests that HSV-2 may be an important risk factor for HIV-1 infection.(ABSTRACT TRUNCATED AT 250 WORDS)

PIP: A seroprevalence survey conducted in rural Uganda revealed a high potential for interaction between sexually transmitted diseases (STDs) such as herpes simplex virus type 2 (HSV-2) and human immunodeficiency virus (HIV) . Venous blood samples were collected at baseline and one year later from 294 randomly selected adults aged 15 years or over from two neighboring villages . At baseline, 23 (7.8%) adults were HIV-positive; no seroconversion occurred during the one-year study period . STD prevalence rates were 10.8% for syphilis, 10.4% for Hemophilus ducreyi, 66.0% for Chlamydia trachomatis, and 91.2% for HSV-1 and 67.9% for HSV-2 . More females (74.4%) than males (57.0%) were HSV-2 antibody-positive . Reactivity to H . ducreyi, C . trachomatis, and HSV-2 rose with increasing age, but there was no such trend for syphilis . HIV prevalence rates were 0.0% among those with no serologic evidence of previous STDs, 2.6% among those with one or two prior STDs, and 20.0% among those with three or four STD markers . Of particular concern was the high rate of HSV-2 prevalence among adolescents (85% among females aged 20-24 years and 82% in males aged 25-29 years) . It is suggested that age-specific HSV-2 seroprevalence can provide an accurate marker of premarital sexual activity among Ugandan adolescents since it lacks the potential for bias associated with self-reporting in this population .

Sex Transm Dis, 1994 Sep-Oct, 21(5), 280 - 8
Seroepidemiological studies of Haemophilus ducreyi infection in Ethiopian women; Duncan ME et al.; BACKGROUND AND OBJECTIVES: To measure prevalence of anti-Haemophilus ducreyi antibodies in sera from Ethiopian female attendees, and to determine significant socioeconomic associations . STUDY DESIGN: A modified ELISA immunoassay was used to test sera of 1,831 Ethiopian women attending gynecological, obstetric, and family planning clinics in Addis Ababa . RESULTS: Overall seropositivity was 19.4% . Prevalence rates for seropositivity for antibodies to H . ducreyi were significantly associated with ethnic group and religion, older age (> or = 50 years: 28%), early age at first coitus (< 13 years: 28%) and first coitus before the menarche (25%), being divorced (27%) or a prostitute (24%), longer duration of marriage (> 20 years: 27%) and sexual life (> 20 years: 24%), number of lifetime sexual partners (2 to 5 partners: 27%) and self-reported history of both syphilis and gonorrhea (31%) . Of these factors, the two most significant were first coitus before the menarche (P < 0.0001) and not being still married to the first husband/sexual partner (P < 0.001) . Differences in seropositivity according to ethnic group and religion may be explained by the number of women within each group who had only one lifetime sexual partner . Women with serological evidence of exposure to another sexually transmitted disease (STD) had a greater risk of exposure to H . ducreyi . The odds ratio for H . ducreyi seropositivity in women with syphilis or gonorrhea was 3.6, for women with genital chlamydial infection, 2.3, and for those with HBV or HSV-2, 1.4 and 1.3 respectively . CONCLUSIONS: This study illustrates the usefulness of the modified ELISA immunoassay for measuring exposure to H . ducreyi, and the usefulness of H . ducreyi as a marker for cumulative sexual exposure . Further studies on the association of HIV transmission and H . ducreyi in Ethiopia are now indicatedPIP: Genital ulcerated disease (GUD), which includes chancroid, has been identified as a risk factor for HIV transmission . This study reports the prevalence of anti-Hemophilus ducreyi (chancroid) antibodies in 1831 Ethiopian women and looks at the behavioral and social factors which might affect the incidence and potential spread of chancroid . Patient data regarding ethnic and socioeconomic aspects were collected from detailed questionnaires . Blood collection was performed under medical surveillance . Complete gynecological examinations were performed . Papanicolaou stained smears were used as the basis of the cytological data . Serological studies utilized an enzyme immunoassay (EIA) test for STD detection . Statistical tests used included the Chi-square test, the multivariate analysis technique, and the Cochran-Mantel-Haenszel General Association Statistic Test . Antibodies to H . ducreyi were found in 335 women (19.4%) . Prevalence of H . ducreyi was significantly associated with Amhara or Tigre ethnic heritage; older age; first coitus before beginning menstruation; history of STDs; divorced status; being a prostitute; longer duration of married and sexual life; and younger age at first coitus . Logistic regression demonstrated that 3 factors were significant when associated with H . ducreyi seropositivity . First coitus before beginning menstruation was highly significant (OR 1.95; 95% CI, 1.49-2.57; P 0.0001) . Not being still married to the first husband was also significant (OR 1.68; 95% CI, 1.23-2.30; P 0.001) . Being of the Ethiopian Orthodox religion was significant (OR 2.11; 95% CI, 1.21-3.68; P 0.005) . Prevalence in women with 2-5 lifetime husbands was higher than in women with only 1 husband .

Sex Transm Dis, 1994 Sep-Oct, 21(5), 247 - 57
Characterization of the cytopathic effect of Haemophilus ducreyi; Hollyer TT et al.; BACKGROUND AND OBJECTIVES: Haemophilus ducreyi is the etiologic agent of chancroid, which is a genital ulcer disease that increases the risk of acquiring and transmitting HIV . The pathogenesis of H . ducreyi is not well understood . GOAL OF THIS STUDY: The goal of this study was to use a quantitative tetrazolium-based XTT assay to characterize the cytopathic effect of H . ducreyi on human foreskin fibroblasts . STUDY DESIGN: Haemophilus ducreyi strains 35000, R018, A77 and CIP542 were evaluated using the XTT assay . The role of attachment on resultant CPE was assessed using a wash step 2 hours post-infection . Internalization was evaluated by the gentamicin kill assay . Secreted exotoxin was studied using permeable inserts to separate the bacteria from the HFF monolayer . RESULTS: HFF cell damage did not appear to be mediated by a secreted H . ducreyi cytotoxin . Direct contact of viable H . ducreyi with HFF cells was required for cell damage . H . ducreyi strains that attached poorly could be readily removed by a wash step . This reduced their capacity to damage HFF cells significantly . Although some H . ducreyi strains attach to high levels within 4 hours, no HFF cell damage was detected by the XTT assay . However, once HFF cell damage was detected by 24 hours, it was not easily reversible, despite antibiotic treatment that eradicated H . ducreyi . Internalization of H . ducreyi by HFF cells apparently did not occur to a significant degree . CONCLUSION: This study indicates that classic "soluble exotoxins" are not likely the key component in H . ducreyi pathogenesis . Attachment or direct contact with HFF cells are required for H . ducreyi to cause a CPE.

Mol Microbiol, 1994 Sep, 13(5), 863 - 73
The 100 kDa haem:haemopexin-binding protein of Haemophilus influenzae: structure and localization; Cope LD et al.; All Haemophilus influenzae strains have an absolute requirement for exogenously supplied haem for aerobic growth . A majority of strains of H . influenzae type b (Hib) produce a 100 kDa protein which binds haem: haemopexin complexes . This 100 kDa haem:haemopexin binding protein, designated HxuA, was originally detected on the Hib cell surface . Monoclonal antibody (mAb)-based analyses revealed that the HxuA protein was also present in soluble form in Hib culture supernatants . This soluble HxuA protein exhibited haem:haemopexin-binding activity in a direct binding assay . Nucleotide sequence analysis of the hxuA gene from Hib strain DL42, together with N-terminal amino acid analysis of HxuA protein purified from Hib culture supernatant, revealed that this protein was synthesized as a 101 kDa precursor with a leader peptide that was removed to yield a 99 kDa protein . Southern blot analysis of chromosomal DNA from four Hib and four non-typeable H . influenzae (NTHI) strains detected the presence of a single band in each strain that hybridized a Hib hxuA gene probe . Subsequent analysis of these NTHI strains showed that all four strains released into culture supernatant a haem:haemopexin-binding protein that migrated in SDS-PAGE at a rate similar or identical to that of the Hib HxuA protein . A Hib hxuA mutant was used to screen an NTHI genomic DNA library and an NTHI gene was cloned that complemented the mutation in this Hib strain . Nucleotide sequence analysis of this NTHI gene revealed that it encoded a protein with 87% identity to the Hib HxuA protein.(ABSTRACT TRUNCATED AT 250 WORDS)

Lung Cancer, 1994 Sep, 11(3-4), 243 - 9
Pulmonary infections in lung cancer patients at diagnosis; Putinati S et al.; We carried out a prospective study involving 96 consecutive lung cancer patients at diagnosis, in order to determine through quantitative cultures of the bronchoalveolar lavage (BAL) fluid, the prevalence of pulmonary infections; we also evaluated the relationship between a patient's performance status, immunocompetence, lung cancer stage, histotype and the occurrence of respiratory infections . The patients (81 males, 15 females) had a mean age of 64 +/- 9 years . Of these, 62 were smokers, 30 were ex-smokers and four had never smoked . Sixty-seven patients had a prior history of chronic bronchitis . A total of 42 micro-organisms were cultured from the BAL fluids of 33 patients (34.3%) . Fifty percent of these micro-organisms were gram-negative, 33.3% were gram-positive and the remaining 16.7% were other micro-organisms . The bacilli most often isolated were the Haemophilus species, accounting for 38.8% of all gram-negative bacilli . The most frequently isolated gram-positive pathogen was the Staphylococcus aureus . We have not found a significant relationship between the presence of a respiratory infection and the different cell types separately analyzed, nor with SCLC and NSCLC patient groups, nor with the stage of the disease . The performance status, the immunoregulatory ratio and the lymphocyte subsets were not significantly different in patients with or without a pulmonary infection . We think that the identification of a definite etiologic agent is of great importance for a rational anti-microbial treatment of pulmonary infections.

Antimicrob Agents Chemother, 1994 Sep, 38(9), 2003 - 7
Evaluation of antimicrobial activities of clarithromycin and 14-hydroxyclarithromycin against three strains of Haemophilus influenzae by using an in vitro pharmacodynamic model; Walker KJ et al.; An in vitro pharmacodynamic model was used to simulate the in vivo pharmacokinetics of clarithromycin and 14-hydroxyclarithromycin in order to generate time-kill curves for three clinical isolates of Haemophilus influenzae (isolates 2019, 91-183, and 1746) . Representative concentrations in serum or lung tissue and the pharmacokinetic parameters of clarithromycin and the 14-hydroxy metabolite, separately and in combination, were simulated for the time-kill studies . Amoxicillin-clavulanic acid was used as a control drug . The simulation of typical concentrations of the macrolides in serum in time-kill studies resulted in magnitudes of bacterial killing that were less than (for strains 2019 and 91-183, MICs = 4 mg/liter for clarithromycin and 14-hydroxy-clarithromycin) or equal to (for strain 1746, MIC = 1 mg/liter for clarithromycin and 14-hydroxyclarithromycin) those observed in amoxicillin-clavulanic acid studies . When typical concentrations in lung tissue were simulated, total log decreases in bacterial counts were greater than those achieved with typical concentrations in serum and, in the case of strain 1746, exceeded the magnitude observed with the control drug . In each case, the time to 3-log-unit killing was longer for the macrolides than for amoxicillin-clavulanic acid . Time-kill curve analyses demonstrated the presence of synergy (defined as a 2-log-unit decrease in the CFU per milliliter between the combination and the most active constituent at any time point) for the combination of clarithromycin and 14-hydroxyclarithromycin at simulated concentrations in serum for one strain of H . influenzae (isolate 91-183) . Synergism is likely bacterial strain specific, and the presence of synergy may be dependent on the antibiotic concentrations that are tested . Evaluation of the kill curve kinetics in terms of bactericidal rate for the various starting concentrations of clarithromycin did not result in a clear demonstration of either concentration-dependent or concentration-independent bactericidal activity.

Vet Immunol Immunopathol, 1994 Sep, 42(3-4), 349 - 56
Compartmentalization of specific B-cells in sheep mucosae associated lymphoid organs; Zanin C et al.; Numerous studies have shown that Peyer's patches (PP) contribute to the seeding of other lymphoid organs in sheep . This was demonstrated by perfusing labeled lymphocytes in PP, and later investigating their presence in drainage lymph nodes, spleen, peripheral blood or bone marrow . These data showed that PP export considerable numbers of cells every day, but provided no information as to their specificity . In this work, we used the enzyme-linked immunosorbent assay (ELISA) spot method to investigate, in the peripheral blood, mesenteric and cervical lymph nodes and tonsils from ten sheep, the numbers of specific B-cells, directed to four common bacteria of the oro-pharyngeal area of mammals: Streptococcus pneumoniae, Streptococcus pyogenes, Haemophilus influenzae or Klebsiella pneumoniae . The data were obtained from five sets of monozygous sheep, one animal of each pair being previously fed ribosomal preparations of these bacteria . Both prior to and after oral challenge, specific B-cells could be found in all the tissues tested . They were mostly IgG-producing cells and preferentially located in oro-pharyngeal drainage lymph nodes and tonsils . Their numbers increased in these lymph nodes after stimulation, while they decreased in mesenteric lymph nodes . These observations are consistent with the current hypothesis suggesting intestinal sensitization, proliferation and fast emigration of specific B-cells after oral challenge.

J Infect, 1994 Sep, 29(2), 203 - 5
Neonatal osteomyelitis in Down's syndrome due to non-encapsulated Haemophilus influenzae; Williams R et al.; A case of neonatal osteomyelitis in a baby with Down's syndrome is described . The causative organism was a non-encapsulated Haemophilus influenzae biotype I, which was isolated from pus at the site of infection . This organism has not previously been reported as a cause of neonatal osteomyelitis.

Microb Pathog, 1994 Sep, 17(3), 167 - 74
A quantitative chemiluminescent ribosomal probe method for monitoring adherence of Haemophilus ducreyi to eukaryotic cells; Alfa MJ et al.; This study evaluated a commercially available chemiluminescent-labelled, ribosomal RNA-directed DNA probe (CRP) as a method to quantitate attachment of H . ducreyi to human foreskin fibroblast (HFF) cells . Evaluation of four strains of H . ducreyi demonstrated that the CRP assay was unaffected by eukaryotic cells and its advantages were: (i) quantitation was done after attachment so it did not interfere with the attachment process, and (ii) it was a rapid, reliable method for quantitating bound bacteria, despite bacterial clumping . Gentamicin-killed H . ducreyi attached to both HFF cells and viable controls, suggesting that the adhesins are components constitutively present on the surface of H . ducreyi . This method may be widely applicable, since the probe recognizes most prokaryotic rRNA sequences.

J Bacteriol, 1994 Sep, 176(18), 5835 - 42
Sequencing analysis reveals a unique gene organization in the gyrB region of Mycoplasma hominis; Ladefoged SA et al.; The homolog of the gyrB gene, which has been reported to be present in the vicinity of the initiation site of replication in bacteria, was mapped on the Mycoplasma hominis genome, and the region was subsequently sequenced . Five open reading frames were identified flanking the gyrB gene, one of which showed similarity to that which encodes the LicA protein of Haemophilus influenzae . The organization of the genes in the region showed no resemblance to that in the corresponding regions of other bacteria sequenced so far . The gyrA gene was mapped 35 kb downstream from the gyrB gene.

Infect Immun, 1994 Sep, 62(9), 3712 - 22
Mapping of bactericidal epitopes on the P2 porin protein of nontypeable Haemophilus influenzae; Haase EM et al.; The P2 porin protein is the major outer membrane protein of nontypeable Haemophilus influenzae and is a potential target of a protective immune response . Nine monoclonal antibodies (MAbs) to P2 were developed by immunizing mice with nontypeable H . influenzae whole organisms . Each MAb reacted exclusively with the homologous strain in a whole-cell immunodot assay demonstrating exquisite strain specificity . All nine MAbs recognized abundantly expressed surface-exposed epitopes on the intact bacterium by immunofluorescence and immunoelectron microscopy . Each MAb was bactericidal to the homologous strain in an in vitro complement-mediated killing assay . Immunoblot assay of cyanogen bromide cleavage products of purified P2 indicated that MAb 5F2 recognized the 10-kDa fragment, and the other eight MAbs recognized the 32-kDa fragment . Competitive ELISAs confirmed that 5F2 recognized an epitope that is different from the other eight MAbs . To further localize epitopes, MAbs 5F2 and 6G3 were studied in protein footprinting by using reversed-phase high-performance liquid chromatography . Three potential epitope-containing peptides which were reactive in an enzyme-linked immunosorbent assay with both 5F2 and 6G3 were isolated . These peptides were identified by N-terminal amino acid sequence and localized to loops 5 and 8 of the proposed model for P2 . Fusion proteins consisting of glutathione S-transferase fused with variable-length peptides from loops 5 and 8 were expressed in the pGEX-2T vector . Immunoblot assay of fusion peptides of loops 5 and 8 confirmed that 5F2 recognized an epitope within residues 338 to 354 of loop 8; 6G3 and the remaining MAbs recognized an epitope within residues 213 to 229 of loop 5 . These studies indicate that nontypeable H . influenzae contains bactericidal epitopes which have been mapped to two different surface-exposed loops of the P2 molecule . These potentially protective epitopes are strain specific and abundantly expressed on the surface of the intact bacterium.

J Biol Chem, 1994 Aug 19, 269(33), 21340 - 5
Binding sites for bacteriophage HP1 integrase on its DNA substrates; Hakimi JM et al.; The temperate phage HP1 integrates its genome into the chromosome of Haemophilus influenzae by site-specific recombination between host and phage DNA segments, the attachment sites . This reaction is promoted by the HP1-encoded integrase . The interactions of HP1 integrase with its DNA substrates have been characterized by DNase I footprinting . Two classes of binding sites were identified . At sites of type I, integrase binding almost completely eliminated cleavage by DNase I; type I sites shared the consensus sequence 5'-AGGGATTTWW . At type II sites, integrase binding produced alternating regions of protection from and enhancement of cleavage, suggesting that binding at these sites distorted the DNA . The consensus sequence for type II sites was 5'-ACTGGCGRTW . Each binding site contained two copies of the relevant consensus . The host attachment site (attB) contains an inverted pair of type I consensus sequences surrounding the strand exchange points . The phage attachment site (attP) includes six binding sites, three of type I and three of type II, distributed along its 500 nucleotide pairs . All type I sites contain two consensus motifs arranged as inverted repeats . One of these surrounds the strand exchange points in this substrate, one is located internally, and the third coincides with the right boundary of the attP sequence . One type II site, consisting of an inverted repeat of two type II consensus motifs, coincides with the left boundary of the attP sequence . The other two type II sites contain directly repeated pairs of the consensus and are internally located.

Gene, 1994 Aug 19, 146(1), 95 - 100
Sequence of the rec-2 locus of Haemophilus influenzae: homologies to comE-ORF3 of Bacillus subtilis and msbA of Escherichia coli; Clifton SW et al.; The nucleotide sequence of a 4243-bp PstI fragment containing the rec-2 gene of Haemophilus influenzae was determined . The amino acid (aa) sequences of four putative proteins were deduced from the corresponding open reading frames (ORFs) . The 2400-bp ORF2 accounted for rec-2, based on the sequences of DNA fragments that contained rec-2::mini-Tn10 mutations . The rec-2 gene encoded a putative 800-aa protein with a M(r) of 90,561 . Sequence analysis suggested that the rec-2 product contained nine highly probable integral membrane-spanning segments . Database searches showed that rec-2 was homologous to the comE-ORF3 gene of Bacillus subtilis . This hypothesis is consistent with the known involvement of both of these genes in the passage of transforming DNA through the competent-cell envelope . Although the sequences of the other three ORFs were incomplete, sufficient data were available to allow inferences about their homologies to other genes . ORF4, which overlapped ORF1, was homologous to the Escherichia coli dnaK suppressor gene, dksA, and therefore was named dsh-1 (dnaK suppressor homolog) . Mutations in dsh-1 and its putative promoter region caused a mild sensitivity to UV light, but did not affect DNA recombination . ORF3, located downstream from rec-2, was homologous to msbA, an essential gene of E . coli with extensive similarity to the ATP-dependent translocators . ORF3 was named msh-1 (msbA homolog) . Mutations in msh-1 had no effects on genetic transformation . The close juxtaposition of rec-2 and msh-1 implied that the expression of msh-1 could be linked to the translation of the rec-2 ORF.

Gene, 1994 Aug 19, 146(1), 101 - 3
Cloning and sequencing of the Haemophilus influenzae ssb gene encoding single-strand DNA-binding protein; Jarosik GP et al.; The ssb gene of Haemophilus influenzae was cloned and sequenced . The deduced protein possessed 61 and 60% identity with the Serratia marcescens and Escherichia coli SSB proteins, respectively . H . influenzae ssb was also shown to complement an E . coli ssb-1 mutation.

Lancet, 1994 Aug 6, 344(8919), 362 - 6
Efficacy of Haemophilus influenzae type b conjugate vaccine PRP-T; Booy R et al.; Efficacy of the Haemophilus influenzae type b (Hib) conjugate vaccine PRP-T (Pasteur-Merieux) was evaluated in a controlled community intervention study in the Oxford region, UK . PRP-T was offered to infants from May 1, 1991 in three of the region's eight districts and from July 1, 1991, in a fourth district . It was given by separate injection in addition to the standard diphtheria, tetanus, and pertussis vaccine according to an accelerated 2, 3, and 4 month schedule without a booster dose in the second year of life . By October 1, 1992, more than 90% of infants in vaccine districts had received at least one dose of PRP-T . None of the infants given three doses had developed Hib infection, whereas 11 infections occurred in the control population (vaccine efficacy 100%, 95% CI 80-100%) . Intention-to-treat analysis also showed a high estimate of efficacy for the vaccine (90%, 50-99%) . Follow-up of study children until November 1, 1993, has shown only 1 vaccine failure in an infant, and no invasive infections in those older than 1 year (average age 22 months) . PRP-T vaccine had high protective efficacy with an accelerated immunisation schedule . Furthermore, the vaccine appears to remain protective through the second year of life without a booster dose . These findings provide encouragement for use of PRP-T in the Expanded Programme of Immunisation.

South Med J, 1994 Aug, 87(8), 811 - 3
Liver abscess following blunt trauma: a case report and review of the literature; Haight DO et al.; We report a case of Haemophilus paraphrophilus causing primary liver abscesses after blunt nonpenetrating trauma . A 32-year-old previously healthy white man sustained a back injury 2 months prior to admission with fever, chills, and night sweats . A computed tomography (CT) scan-directed needle aspirate of several hypoechoic hepatic lesions grew H paraphrophilus . Recent blunt trauma to the lower back may have contributed to the localization of this infection to an area of contusion or hematoma within the liver, followed by an episode of bacteremia that seeded the injury.

Am J Respir Crit Care Med, 1994 Aug, 150(2), 448 - 54
Bronchoalveolar lavage findings in cystic fibrosis patients with stable, clinically mild lung disease suggest ongoing infection and inflammation; Konstan MW et al.; To determine the extent of airway infection and inflammation in adolescents and adults with cystic fibrosis (CF) who have mild lung disease and are without symptoms of active infection, we performed bronchoalveolar lavage (BAL) on 18 CF patients > or = 12 yr of age who were stable, appeared clinically well, and had mean (+/- SEM) FEV1 of 79 +/- 4% of predicted . We quantitated the bacteria, inflammatory cells, immunoglobulins, and mediators of inflammatory tissue damage in the epithelial lining fluid (ELF) of these patients and in 23 healthy control subjects . All CF patients were found to be infected with Pseudomonas aeruginosa, Staphylococcus aureus, and/or Haemophilus influenzae; no organisms were isolated from the control subjects . The mean number of cells in the ELF was 14 times greater in the CF patients than in the control subjects . Neutrophils constituted 57% of the recovered cells in the CF patients versus 3% in the control subjects, and their concentration was 380 times greater in the CF patients versus the control subjects . IgG, IgA, and IgM were 2.5 to 6 times greater in CF ELF versus that of control subjects . Abundant active elastase was present in the ELF of the CF patients (2.3 +/- 0.9 microM) despite threefold elevated levels of alpha 1-protease inhibitor (alpha 1-PI) . No active elastase was detectable in the control subjects . alpha 1-PI was functional in CF as demonstrated by elevated elastase:alpha 1-PI complex (0.045 microM in CF versus 0.002 microM in control subjects) . This active elastase caused proteolytic destruction of surface complement receptors on airway neutrophils in situ.(ABSTRACT TRUNCATED AT 250 WORDS)

J Med Microbiol, 1994 Aug, 41(2), 120 - 6
Analysis by pulsed-field gel electrophoresis of insertion mutations in the transferrin-binding system of Haemophilus influenzae type b; Curran R et al.; A mutagenesis system involving the insertion of a non-transposable antibiotic resistance gene cassette was used to generate stable mutations in the chromosome of Haemophilus influenzae type b strain Eagan . The mutations generated were shown by pulsed-field gel electrophoresis (PFGE) to have unique SmaI fingerprint patterns and to be located randomly on the chromosome . Of 700 insertion mutants screened, 29 had stable insertions resulting in constitutive expression of transferrin-binding proteins (TBPs) . The high proportion of such mutants indicated that numerous regulatory loci could influence the expression of this phenotype . Five such regulatory mutations were analysed in detail by PFGE and DNA hybridisation and were shown to be located at five different chromosomal loci, although three of the five loci were located on the same 330-kb SmaI fragment of the wild-type strain Eagan chromosome . This fragment also contains several important virulence determinants, including the capb locus, and one of the five constitutive mutants had concomitantly lost the ability to synthesise a type-b capsule . No DNA homology was demonstrated between H . influenzae chromosomal fragments separated by PFGE and DNA probes for the TBPs from Neisseria meningitidis, but the possibility of shared regulatory mechanisms controlling the expression of TBPs in these two species remains to be investigated.

Infect Immun, 1994 Aug, 62(8), 3320 - 8
Genes encoding high-molecular-weight adhesion proteins of nontypeable Haemophilus influenzae are part of gene clusters; Barenkamp SJ et al.; We previously reported the cloning and sequencing of genes designated hmw1 and hmw2 from a prototype nontypeable Haemophilus influenzae strain . The genes encode proteins which are related to filamentous hemagglutinin of Bordetella pertussis and promote attachment of the nontypeable H . influenzae strain to human epithelial cells (J . W . St . Geme III, S . Falkow, and S . J . Barenkamp, Proc . Natl . Acad . Sci . USA 90:2875-2879, 1993) . Subcloning studies suggested that correct processing of these high-molecular-weight proteins required the products of additional downstream genes . In the present study we analyzed the 3'-flanking regions of the hmw1A and hmw2A structural genes and found that both genes are flanked by two additional downstream open reading frames (ORFs), designated B and C, respectively . The B ORFs are 1,635 bp long . Their derived amino acid sequences are 99% identical and demonstrate similarity to the derived amino acid sequences of two genes that encode proteins required for secretion and activation of hemolysins of Proteus mirabilis and Serratia marcescens . The C ORFs are 1,950 bp long, and their derived amino acid sequences are 96% identical . In Escherichia coli transformants, interruption of the hmw1C or both the hmw1B and hmw1C genes resulted in defective processing of the hmw1A structural gene product and loss of the ability of the transformants to adhere to human epithelial cells . The precise interactions of the proteins encoded by these gene clusters are yet to be defined, but their elucidation may further our understanding of the biology of nontypeable H . influenzae bacteria and the interaction of these organisms with the human host.

Infect Immun, 1994 Aug, 62(8), 3178 - 83
Antigenic relationships among immunoglobulin A1 proteases from Haemophilus, Neisseria, and Streptococcus species; Lomholt H et al.; To investigate the antigenic variation and relationships of immunoglobulin A1 (IgA1) proteases among different species and genera, we examined a comprehensive collection of serine type and metallo-type IgA1 proteases and corresponding antisera in enzyme neutralization assays . Sharing of neutralizing epitopes of metallo-type IgA1 proteases from Streptococcus pneumoniae, Streptococcus sanguis, Streptococcus mitis, and Streptococcus oralis and of serine type IgA1 proteases from Haemophilus and pathogenic Neisseria species was extremely limited . A number of limited to strong cross-reactions in such epitopes were found among serine type IgA1 proteases released by members of the genera Haemophilus and Neisseria, reflecting the common origin of their iga gene . However, the relatively limited prevalence of shared "neutralizing" epitopes of IgA1 proteases from the two genera indicates that they rarely induce immunity to each other . In contrast, extensive sharing of neutralizing epitopes was found between N . meningitidis and N . gonorrhoeae IgA1 proteases, making them potentially attractive vaccine components . Among metallo-type IgA1 proteases, several pneumococcal proteases were found to induce neutralizing antibodies to IgA1 proteases of oral streptococci whereas the opposite was not the case.

Infect Immun, 1994 Aug, 62(8), 3066 - 74
Heavy-chain isotype patterns of human antibody-secreting cells induced by Haemophilus influenzae type b conjugate vaccines in relation to age and preimmunity; Barington T et al.; The influence of preexisting immunity on the heavy-chain isotypes of circulating antibody-secreting cells (AbSC) induced by vaccination with Haemophilus influenzae type b (Hib) capsular polysaccharide (HibCP) coupled to tetanus toxoid (TT) or diphtheria toxoid (DT) and by vaccination with TT or DT alone in 51 healthy adults and 9 infants was studied . In adults, the isotypes of TT and DT AbSC were dominated by immunoglobulin G1 (IgG1) followed by IgG4 and IgA1 . HibCP AbSC were dominated by the isotype IgA1 followed by (in decreasing order) IgG2, IgA2, IgM, and IgG1 . The isotype distributions of TT and DT AbSC were independent of whether the toxoids were coupled to HibCP, and the isotypes of HibCP AbSC were not influenced by the nature of the carrier (TT or DT) . Furthermore, the isotype distributions were unaffected by recent immunization with components of the conjugates, although this reduced the numbers of AbSC . The heavy-chain gene usage of HibCP AbSC in adults differed clearly from that in infants, which was restricted largely to the genes mu, gamma 1, and alpha 1, all lying upstream in the heavy-chain constant-region gene locus, while the usage in adults also, to different extents, involved the downstream genes gamma 2 and alpha 2 . The ratio between the numbers of HibCP AbSC using heavy-chain genes from the downstream duplication unit (gamma 2, gamma 4, and alpha 2) and those using genes from the upstream duplication unit (gamma 3, gamma 1, and alpha 1) correlated with the preimmunization level of natural HibCP antibodies (r = 0.59; P = 0.00002) . A possible role of natural exposure for Hib or cross-reactive bacteria on the mucosal surfaces in the shaping of the isotype response to HibCP conjugate vaccines is discussed.

J Vet Med Sci, 1994 Aug, 56(4), 639 - 44
Pathologic observations of pigs intranasally inoculated with serovar 1, 4 and 5 of Haemophilus parasuis using immunoperoxidase method; Amano H et al.; Nineteen, 7- to 13-week-old pigs were inoculated intranasally with different strains of Haemophilus parasuis (serovar 1, 4 and 5), and the pathological lesions induced by each strain were compared . Eleven of thirteen pigs inoculated with either strain Nagasaki (serovar 5) or No . 4 (serovar 1) died between days 1 to 6 after inoculation, and had septicemic lesions, meningitis, or polyserositis . One of six pigs inoculated with strain SW124 (serovar 4) died with polyserositis, another one recovered after illness, and the remaining four pigs remained in good health . Five of the septicemic pigs had thrombi at many organs . Endotoxin was detected in the plasma of 10 pigs in the acute stage of infection . Using the immunoperoxidase technique, H . parasuis antigen was detected in lesions of infected pigs . In the serosal lesions the bacterial antigen was found mainly in the cytoplasm of infiltrating neutrophils and macrophages and appeared as degenerated bacteria and/or lytic bacterial material in dilated phagosomes . Many of the bacteria in the blood vessels of pigs with septicemic lesions were also degenerated . Although H . parasuis was reisolated from nasal secretions of infected pigs, the bacterial antigen could not be detected in the nasal cavities of these pigs . No lesions were observed in the parenchyma of the lung . However, H . parasuis antigen was detected in the tonsil of infected pigs.

Mol Microbiol, 1994 Aug, 13(4), 685 - 95
Identification of an HP1 phage protein required for site-specific excision; Esposito D et al.; Transposon insertion mutagenesis and transformation were used to locate genes responsible for excision in the temperature phage HP1 of Haemophilus influenzae . A 6.5 kb segment of DNA near the left end of the phage genome was sequenced, and 11 new open reading frames were identified . Two face-to-face overlapping promoter sequences organized these open reading frames into two operons transcribed in opposite directions . Interruption of the first open reading frame in the rightward operon created lysogens unable to produce phages . Provision of the uninterrupted open reading frame in trans restored phage production . The gene identified by this procedure, cox, was cloned and the protein product was expressed at high levels in Escherichia coli . The Cox protein is a 79-residue basic protein with a predicted strong helix-turn-helix DNA-binding motif . Extracts induced to express high levels of Cox contained a 9 kDa protein . These extracts inhibited integrative recombination and were required for excisive recombination mediated by HP1 integrase . The HP1 cox gene location is similar to that of the homologous excisive and regulatory genes from coliphages P2 and 186 . These phages appear to share a distinctive organization of recombination proteins and transcriptional domains differing markedly from phage lambda and its relatives.

Mol Microbiol, 1994 Aug, 13(4), 673 - 84
The fimbrial gene cluster of Haemophilus influenzae type b; van Ham SM et al.; Haemophilus influenzae infections are preceded by airway colonization, a process facilitated by fimbriae . Here, we identified the complete fimbrial gene cluster of H . influenzae type b . HifA forms the major subunit . HifB, a periplasmic chaperone, and HifC, an outer membrane usher, are typical assembly genes; their inactivation abolished fimbriae formation . HifD and HifE are putative minor subunits, both participating in fimbriae biogenesis . Inactivation of either one drastically reduced fimbriae expression . HifD represents a novel type of fimbrial subunit with lipoprotein characteristics, pointing to a membrane-associated function of HifD . Transcription of all fimbrial genes is coregulated through two clustered promoters . The flanking of the fimbrial gene cluster by repetitive extragenic palindromic sequences together with a partial duplication of an adjacent unrelated operon indicated that the cluster was once inserted in the H . influenzae genome as a mobile virulence unit.

J Otolaryngol, 1994 Aug, 23(4), 269 - 75
Otitis media: microbiology and management; Brook I; Otitis media (OM) is a common childhood disease and one that can cause significant morbidity . A knowledge of the pathogens responsible for OM can assist in the selection of the most appropriate treatment regimen and can minimize complications that may require surgery . The microbiology of acute, serous, and chronic OM is reviewed . The major organisms recovered from about three quarters of acute OM and half of serous OM cultures are Haemophilus influenzae, Streptococcus pneumoniae, and Moraxella catarrhalis . Streptococcus pyogenes, anaerobic cocci, and viruses can each be isolated in less than 5% of the patients with acute OM . The predominant organisms isolated from chronic OM are Staphylococcus aureus, Pseudomonas aeruginosa, and anaerobic bacteria . The predominant anaerobes are gram-positive cocci, pigmented Prevotella and Porphyromonas sp, Bacteroides sp, and Fusobacterium sp . Many of the aerobic and anaerobic organisms causing OM can produce beta-lactamase, rendering them resistant to many of the penicillins . The appropriate surgical and medical therapies for acute, serous, and chronic otitis media are discussed.

J Clin Microbiol, 1994 Aug, 32(8), 2019 - 23
Clear broth and plate media for culture of Haemophilus ducreyi; Totten PA et al.; Using catalase as a source of heme, we have developed both clear plate and broth media for the growth of Haemophilus ducreyi, the causative agent of chancroid . In the broth medium, the growth phase of the organism can be monitored and the organisms achieve a cell density of > 10(8) CFU/ml.

J Clin Microbiol, 1994 Aug, 32(8), 2013 - 5
Surveillance of susceptibility testing methodologies for Haemophilus influenzae in Canada, including evaluation of disk diffusion test; Scriver SR et al.; We surveyed 75 clinical laboratories to determine if National Committee for Clinical Laboratory Standards (NCCLS) were being used for the susceptibility testing of Haemophilus influenzae . Of the 66 laboratories that performed susceptibility testing, all claimed to follow current NCCLS guidelines . However, upon further questioning, only 23, all of which used disk diffusion testing, accurately interpreted and followed the guidelines . Proficiency testing of 22 of these laboratories found that an unacceptable number of interpretive errors (> 10%) occurred . These results query the merit of routine disk diffusion susceptibility testing of H . influenzae to beta-lactam agents.

Clin Infect Dis, 1994 Aug, 19(2), 323 - 4
Pediatric osteomyelitis in Panama; Saez-Llorens X et al.; Two hundred forty-one children who had osteomyelitis during a 19-year period, 1974 through 1992, were identified by chart review . Acute osteomyelitis or chronic osteomyelitis was the diagnosis for 221 (92%) and 20 (8%) of the children, respectively . Bacteriologic etiology was documented in 137 (57%) of the cases . Staphylococcus aureus, Pseudomonas aeruginosa, Salmonella species organisms, and Haemophilus influenzae type b were isolated from 97 (40%), 10 (4%), 8 (3%), and 7 (3%) of the children, respectively . S . aureus was the predominant microorganism in all age groups, whereas H . influenzae occurred only in children younger than 2 years of age . P . aeruginosa was recovered predominantly from children with a penetrating injury of the foot, while salmonella bone infections were diagnosed in patients with sickle cell disease . These data provide guidelines for the initial work-up for and management of osteomyelitis in children living in developing Latin American countries.

Clin Infect Dis, 1994 Aug, 19(2), 320 - 2
Haemophilus aphrophilus as a rare cause of arthritis; Merino D et al.; A case of septic arthritis due to Haemophilus aphrophilus is presented . This organism has rarely been reported as a cause of bone or joint infections . We believe this is the third reported case of septic arthritis caused by this microorganism . We review the clinical and bacteriologic findings and the previously reported cases of infection caused by H . aphrophilus . Treatment with ceftriaxone was followed by full recovery without sequelae.

Acta Paediatr, 1994 Aug, 83(8), 849 - 53
Diabetes mellitus in cystic fibrosis: effect of insulin therapy on lung function and infections; Lanng S et al.; The effect of insulin therapy on lung function and lung infections was studied in a retrospective case-control design in 18 diabetic cystic fibrosis (CF) patients; 18 non-diabetic CF patients, matched for sex, age and presence of chronic Pseudomonas aeruginosa lung infection, served as controls . Parameters of CF clinical status were collected for six years before and two years after the onset of insulin therapy in the diabetic patients . Before onset of insulin therapy, body mass index (BMI) and forced vital capacity (FVC) in (pre)diabetic patients deviated increasingly from those in control patients . Decreases in BMI and lung function during the past three months before onset of insulin therapy were reverted within three months of insulin therapy . From three months to two years after onset of insulin therapy, differences in BMI and lung function diminished between diabetic and control patients . After two years of insulin therapy, BMI was similar in diabetic and non-diabetic patients and the percentage differences in forced expiratory volume in 1s (FEV1) and FVC between the two groups were similar to those found six years before the onset of insulin therapy . The finding that insulin therapy improves lung function in diabetic CF patients suggests strongly that the insidious decline in lung function seen during the years before the diagnosis of diabetes mellitus results from the pre-diabetic condition . After onset of insulin therapy, the percentages of sputum examinations positive for Haemophilus influenzae and Streptococcus pneumoniae decreased in the diabetic patients, whereas parameters of lung infections with P . aeruginosa and Staphylococcus aureus remained unchanged.(ABSTRACT TRUNCATED AT 250 WORDS)

Pediatr Infect Dis J, 1994 Aug, 13(8), 724 - 8
Ceftriaxone therapy of bacterial meningitis: cerebrospinal fluid concentrations and bactericidal activity after intramuscular injection in children treated with dexamethasone; Bradley JS et al.; Antibiotic therapy is administered intravenously to children with bacterial meningitis to achieve the highest possible blood and cerebrospinal fluid (CSF) concentrations . However, intravenous access for the entire duration of therapy may be difficult in some children . Intramuscular therapy offers a more versatile option; however, CSF concentrations and bactericidal activity following im injection in children concurrently treated with dexamethasone have not been studied . We prospectively evaluated 37 children given an im dose of ceftriaxone on either the 3rd, 6th or 9th day of antibiotic therapy while receiving dexamethasone for the first 4 days of treatment . All children were required to have normal peripheral perfusion at the time of im injection . Four to 6 hours after im injection CSF was obtained . The average age of study patients was 28 months; Neisseria meningitidis, Streptococcus pneumoniae and Haemophilus influenzae type b were responsible for 95% of all infections . All children studied had detectable CSF ceftriaxone concentrations, with mean (+/- SD) concentrations (microgram/ml) on Days 3, 6 and 9 of therapy of 5.7 +/- 5.5 (n = 12), 5.2 +/- 5.0 (n = 14) and 2.0 +/- 2.6 (n = 10), respectively . All CSF bactericidal titers for N . meningitidis, S . pneumoniae and H . influenzae type b, regardless of day of im injection, were > or = 1:64 . Intramuscular ceftriaxone therapy of bacterial meningitis may be a reasonable therapeutic option for the convalescing child with good peripheral perfusion.

Pediatr Res, 1994 Aug, 36(2), 235 - 43
Inhibition of receptor-dependent and receptor-independent generation of the respiratory burst in human neutrophils and monocytes by human serum IgA; Wolf HM et al.; An important feature of the role of IgA in protection against infection and disease at the level of the mucosal surfaces might be the elimination of pathogens without induction of a strong inflammatory reaction . In the present study we addressed the question whether IgA has a regulatory effect on the generation of reactive oxygen intermediates in human neutrophils and monocytes (i.e . the respiratory burst) . Cells were stimulated with heat-inactivated Haemophilus influenzae type b or phorbol myristate acetate, stimuli known to use different recognition structures or signal transduction pathways . Concentrations of IgA as low as 10 mg/L significantly inhibited the receptor-dependent Haemophilus influenzae-induced respiratory burst in granulocytes, as assessed by measuring luminol-enhanced chemiluminescence . Furthermore, IgA had a dose-dependent inhibitory effect on the receptor-independent induction of the respiratory burst, as examined by flow cytometry in monocytes and granulocytes activated with phorbol myristate acetate . Our results therefore indicate that inhibition of receptor-ligand interaction is not a sufficient explanation for the IgA-mediated modulation of the respiratory burst in human phagocytic cells . In addition, IgA might directly regulate the activation of the respiratory burst at the level or downstream of protein kinase C activation . By modulating the release of mediators of inflammation such as reactive oxygen intermediates, the inflammatory response could be down-regulated at the level of the mucosal surfaces, thereby preventing the development of sequelae of an exaggerated inflammatory response potentially leading to local or systemic pathology.

Zh Mikrobiol Epidemiol Immunobiol, 1994 Aug-Sep, Suppl 1, 55 - 60
{The features of Haemophilus influenza and Streptococcus pneumoniae carriage and the comparative characteristics of strains isolated from healthy children and from patients with acute and chronic respiratory infections}; Katosova LK; The biological properties (serotypes, biotypes and adhesive activity) of 839 H.influenzae strains isolated from healthy children and from patients with acute and chronic respiratory infections, as well as the serotype composition of 739 S.pneumoniae isolated from the same groups of children, were studied . The occurrence of H.influenzae carriership among healthy children varied between 13% and 78%, decreasing among older children . In 98% of cases the respiratory tract of healthy children was colonized by noncapsular forms of H.influenzae . The isolation frequency of pneumococci in healthy children was 16%, but during the period of 2 years 45% of children were found to be the transitory carriers of this infective agent . The persistence of H.influenzae and S.pneumoniae with the same biological properties lasted for 1-4 months . Repeated infections were caused, as a rule, by bacteria with other properties . S.pneumoniae persisting in healthy children and causing a chronic bronchopulmonary process had no differences in their serological composition (19, 6, 3) . At the same time in acute pneumonia, complicated by pleuritis and pneumonia destruction, pneumococci of serotypes 1, 3, 5 and 14 were more frequently isolated . H.influenzae isolated from healthy children and from patients with chronic pneumonia had little difference in the occurrence of their capsular variants, but in the biotype composition of H.influenzae isolated from chronic pneumonia patients biotype 1 occurred more frequently.

Zhonghua Liu Xing Bing Xue Za Zhi, 1994 Aug, 15(4), 209 - 11
{Analysis on clinical epidemiology of acute bacterial pneumonia in children}; Wang H et al.; Results of quantitative culture of pathogenic bacteria in nasopharyngeal secretions of 154 cases of hospitalized children with bacterial pneumonia demonstrated that the highest culture rates were Haemophilus influenzae (39.0%) and streptococcus pneumoniae (20.8%) . Recovery rate of H . influenzae and Str . pneumoniae among children of various age groups demonstrated that the smaller the age, the higher the recovery rate . The recovery rates of these two bacteria were highest in December and in November, respectively.

Acta Paediatr Suppl, 1994 Aug, 400, 70 - 2
The use of antibiotics in the treatment and prevention of infection in HIV-infected children; Ruga E et al.; Children with HIV infection have an unusual susceptibility to bacterial infection, related to several immune abnormalities . Selection of initial antibiotic therapy must be individualized in these children . Patients with community-acquired disease are most likely to have infection by polysaccharide-encapsulated bacterial organism, most commonly Streptococcus pneumoniae and less frequently by Haemophilus influenzae type b . If it is possible to treat the patients at home, the use of amoxicillin-clavulanic acid might be appropriate . Other authors propose management with parenteral ceftriaxone because of the better compliance and the malabsorption . In hospitalized patients, concern for Gram-negative enteric pathogens other than polysaccharide-encapsulated organisms requires initial therapy with a third-generation cephalosporine in combination with an aminoglycoside . Trimethoprim-sulfamethizole is the most common drug used in HIV-infected children because it is recommended for the initial therapy and for prophylaxis of pneumocystis carinii pneumonia, which occurs in as many as 42% of these children.

Eur J Clin Microbiol Infect Dis, 1994 Aug, 13(8), 633 - 8
Prospective epidemiological study of invasive Haemophilus influenzae disease in adults; Deulofeu F et al.; The incidence and characteristics of invasive Haemophilus influenzae disease were studied in 43 adult patients admitted to the acute care hospitals in El Valles County (Barcelona, Spain) between January 1987 and June 1992 . The annual incidence of Haemophilus influenzae disease was 1.2 per 100,000 inhabitants . Pneumonia occurred in 24 patients, meningitis in five, intraabdominal infections in three, obstetric infections in two, epiglottitis in two and cellulitis in one . In six patients the source of infection was unknown . Ten (23%) of the infections were hospital acquired . Underlying conditions were diagnosed in 30 (70%) patients . Nontypeable Haemophilus influenzae strains predominated in all adult age groups . Sixty-one percent of type b and 34% of nontypeable strains were ampicillin resistant (p = 0.08) . Multiple antibiotic resistance was also high among type b (53%) and nontypeable (18%) strains . The mortality rate was significantly higher in patients with pneumonia, bacteremia from an unidentified focus or shock at presentation.

FEMS Immunol Med Microbiol, 1994 Aug, 9(2), 171 - 7
Binding of tissue-type plasminogen activator (t-PA) to Neisseria meningitidis and Haemophilus influenzae; Ullberg M et al.; Forty-nine bacterial strains representing five species known to interact with human plasminogen were tested for the ability to bind the two major human plasminogen activators, t-PA and urokinase . The bacterial species tested included Haemophilus influenzae, Neisseria meningitidis, Streptococcus pyogenes, Streptococcus equisimilis and human group G streptococci . All N . meningitidis and 11 of 14 H . influenzae strains displayed substantial binding of t-PA with values in the range of 20-46% . On the contrary, none of the streptococcal strains bound significant amounts of tPA . With urokinase no binding could be found for any of the bacterial species tested . Scatchard analysis with a selected H . influenzae strain (HI23354) demonstrated 10,000 receptors per bacterium for t-PA with a Kd value of about 20 nmol l-1 . The corresponding values with a selected N . meningitidis strain (Mo 52) was 8500 receptors per bacterium and 70 nmol l-1 . t-PA binding could be reduced about 40% by the addition of 10 mmol l-1 of the lysine analogue epsilon-aminocaproic acd (EACA) whereas no inhibitory effect could be demonstrated with arginine . Addition of 2 mumol l-1 of plasminogen which is enough to occupy all bacterial sites for plasminogen did not interfere with the t-PA binding, suggesting that the receptors for t-PA and plasminogen are distinct . Using very high plasminogen concentrations however, t-PA binding could be reduced by about 50% possibly due to an interaction between t-PA and plasminogen in the fluid phase . Our results demonstrate the occurrence of a previously unknown type of bacterial receptor that is capable of specifically binding t-PA.

Drugs, 1994 Aug, 48(2), 297 - 326
Roxithromycin . An update of its antimicrobial activity, pharmacokinetic properties and therapeutic use; Markham A et al.; Roxithromycin is a derivative of the macrolide antibacterial erythromycin with in vitro antibacterial activity resembling that of the parent compound . The drug has activity against some Staphylococcus spp., many Streptococcus spp., Moraxella (Branhamella) catarrhalis, Mycoplasma pneumoniae, Legionella pneumophila and Chlamydia trachomatis as well as many less common organisms . Measured using recently proposed guidelines, roxithromycin has in vitro activity against Haemophilus influenzae . In comparison with that of its parent compound, the pharmacokinetic profile of roxithromycin is characterised by high plasma, tissue and body fluid concentrations and a long half-life permitting an extended dosage interval . Roxithromycin has proven clinical efficacy in upper and lower respiratory infections, skin and soft tissue infections, urogenital infections and orodental infections, and appears to be as effective as more established treatments including erythromycin, amoxicillin/clavulanic acid and cefaclor . The drug has also shown promise in a variety of more specialised indications including opportunistic infections in human immunodeficiency virus (HIV)-positive patients and as part of a Helicobacter pylori eradication regimen . Roxithromycin is very well tolerated with an overall incidence of adverse events of approximately 4% . Thus, roxithromycin is an attractive therapeutic alternative in its established indications, especially when the option of once-daily administration is considered.

FEMS Microbiol Lett, 1994 Jul 15, 120(3), 279 - 83
Phase variation of Haemophilus influenzae lipopolysaccharide: characterization of lipopolysaccharide from individual colonies; Roche RJ et al.; The lipopolysaccharide (LPS) of Haemophilus influenzae expresses a number of core oligosaccharide epitopes on its outer surface . The expression of individual epitopes is subject to frequent (approximately 1% bacteria/generation) reversible phase variation, as determined by colony immunoblots . We have used a microtechnique for the extraction of LPS from individual colonies, whose LPS antigenic phenotype has been identified, so that the LPS can be studied by tricine sodium dodecylsulphate polyacrylamide gel electrophoresis (T-SDS-PAGE) . This avoids the introduction of heterogeneous phase-varying LPS which is inevitable if bacteria from colonies are grown in broth culture prior to LPS extraction and analysis . Using these techniques we have investigated the repertoire of LPS phase variation exhibited by H . influenzae strain RM7004 (a serotype b meningitis isolate) . This technique will facilitate the study of bacteria in which there is variable LPS expression.

Ugeskr Laeger, 1994 Jul 11, 156(28), 4141 - 4
{Ampicillin-resistant Haemophilus influenzae . Prevalence in isolates from Danish children}; Ejlertsen T et al.; The prevalence of ampicillin-resistance was assessed among a total of 2766 strains of H . influenzae isolated from lower respiratory tract secretions, middle ear secretions, spinal fluid specimens, and blood cultures from children 0-15 years of age tested in two separate counties in Denmark during the period from 1986 to May, 1993 . All strains were tested for susceptibility to ampicillin with disc or tablet diffusion technique and strains were examined for beta-lactamase production with a chromogenic cephalosporinase test . In the county of Northern Jutland the rate of beta-lactamase production in non-encapsulated H . influenzae was 2.5% in 1986 rising to 9.3% in 1993 . The rate of beta-lactamase production in H . influenzae type b was 4.1% without any rise . In the county of Copenhagen the rate of beta-lactamase production in non-encapsulated H . influenzae rose from 6.3% in 1986 to 10.6% in 1992 . In 1993 a further increase to 20.7% was noticed . This year the number of specimens sent to the laboratory and the number of H . influenzae isolated were lower compared to previous years . Thus a different selection of patients may explain the increase in the rate of beta-lactamase production in 1993 . The rate of beta-lactamase production in H . influenzae type b was 8.5% . No strains were resistant to ampicillin in diffusion test other than the beta-lactamase producers.

Clin Diagn Lab Immunol, 1994 Jul, 1(4), 464 - 8
Maternal antibodies and acquired serological response to Moraxella catarrhalis in children determined by an enzyme-linked immunosorbent assay; Ejlertsen T et al.; An enzyme-linked immunosorbent assay (ELISA) for determination of serum immunoglobulin G (IgG) antibodies to Moraxella catarrhalis was developed, with an ultrasonic extract of M . catarrhalis immobilized on polystyrene microtiter plates serving as the antigen . The specificity was determined by adsorption tests . All of the 541 women tested showed a high level of maternal IgG antibodies to M . catarrhalis in umbilical cord blood specimens . One hundred eighty-nine children aged 0 to 15 years were examined . A low level of IgG antibodies to M . catarrhalis in serum was found in children aged up to 1 year; in older children, the levels increased with age . Levels in the same range as maternal IgG antibody levels were reached at the age of 10 years . The level of antibodies in children did not correlate with the state of colonization with M . catarrhalis or with the state of acute lower respiratory tract infection . Pairs of acute-phase and convalescent-phase serum samples did not discriminate between the children with M . catarrhalis in pure culture and those with mixed cultures of M . catarrhalis, Haemophilus influenzae, and Streptococcus pneumoniae . In adult women, high IgG antibody levels and low colonization rates with M . catarrhalis were found, whereas in small children, low IgG antibody levels and high colonization rates were found.

Clin Diagn Lab Immunol, 1994 Jul, 1(4), 394 - 400
Quantitative flow cytometric analysis of opsonophagocytosis and killing of nonencapsulated Haemophilus influenzae by human polymorphonuclear leukocytes; Vogel L et al.; Since nonencapsulated Haemophilus influenzae persists in the lower respiratory tracts of patients with chronic bronchitis despite the presence of specific antibodies, complement, and polymorphonuclear leukocytes (PMNs), opsonophagocytosis of H . influenzae was analyzed . Nonencapsulated H . influenzae isolated from the sputa of chronic bronchitis patients was labeled with fluorescein isothiocyanate and incubated with human PMNs in the presence of complement and antibodies for 30 min at 37 degrees C . Candida albicans was added to each sample as an internal standard, and the reduction of the number of bacteria was determined by flow cytometry . Fluorescence quenching with ethidium bromide was used to discriminate between intracellular and extracellular bacteria . Opsonophagocytosis of viable H . influenzae d1 was 17% +/- 29% in the presence of complement and human pooled sera containing high titers of strain-specific antibodies . Opsonophagocytosis of six other H . influenzae strains was also poor . Under the same conditions, opsonophagocytosis of Staphylococcus aureus was 90% +/- 5%, and opsonophagocytosis of C . albicans was 55% +/- 23% . About half of the number of H . influenzae bacteria associated with PMNs was internalized . Opsonophagocytosis of heat-killed H . influenzae d1 (41% +/- 20%) was higher than that of viable bacteria of the same strain (P < 0.05) . This result suggests that the accessibility of epitopes on H . influenzae for opsonizing antibodies is better on killed than on viable bacteria . We conclude that viable nonencapsulated H . influenzae is poorly opsonophagocytized in the presence of strain-specific antibodies and complement.

Kansenshogaku Zasshi, 1994 Jul, 68(7), 842 - 7
{Antimicrobial susceptibilities of Haemophilus influenzae isolated from the nasopharynx of children}; Tomiyama M; Changes in susceptibilities to oral antimicrobials were investigated in 189 children, in whom Haemophilus influenzae was detected by nasopharyngeal culture, among the children who were diagnosed as having acute otitis media or chronic sinusitis with acute exacerbation in the Department of Otolaryngology in 1986, 1988 and 1991 . The minimum 50% inhibitory concentration (MIC50) and minimum 90% inhibitory concentration (MIC90) of ampicillin (ABPC), cefaclor (CCL) and erythromycin (EM) in the subjects examined in 1986 were almost the same as the levels in those examined in 1991 . The MIC50 level of minocycline (MINO) in the subjects examined in 1991 was lower by 2 test tubes than that determined in 1986, showing improvement in susceptibilities . The prevalence of resistance to antimicrobials was compared between 1986 and 1991 . The prevalence to ABPC tended to decrease very slightly, while the prevalence to CCL tended to increase very slightly . The prevalence of EM tended to increase slightly . Many CCL-resistant strains detected in 1991 showed resistance to ABPC and EM, but showed favorable susceptibilities to cefixime and norfloxacin . Future trends of CCL-resistant strains should be carefully observed . There was no marked change in the prevalence of resistance to ABPC or CCL . ABPC and CCL were considered to be the first choice drugs, even at present, for pediatric patients with acute otitis media due to infection with H . influenzae and in those with acute exacerbation of chronic sinusitis due to the infection.

Can J Microbiol, 1994 Jul, 40(7), 532 - 40
Transferrin receptors on ruminant pathogens vary in their interaction with the C-lobe and N-lobe of ruminant transferrins; Yu R et al.; The interaction between ruminant transferrins and receptor proteins on the surface of the ruminant pathogens Pasteurella haemolytica, Haemophilus somnus, Pasteurella multocida, Haemophilus agnii, and Moraxella bovis was evaluated by a combination of binding assays and affinity isolation procedures . Membranes isolated from P . haemolytica, P . multocida, and H . agnii were capable of binding sheep, goat, and cattle transferrins whereas binding by membranes from H . somnus and M . bovis was specific for bovine transferrin . Proteolytically derived bovine transferrin C-lobe was capable of inhibiting the interaction between bovine transferrin and both Tbp1 and Tbp2 from P . haemolytica and M . bovis but only Tbp1 from H . somnus and P . multocida . Proteolytically derived N-lobe inhibited the binding of P . multocida and H . somnus Tbp2 to bovine transferrin and the binding of bovine transferrin to the single receptor protein identified in H . agnii . The implications of these results regarding the nature of the ligand-receptor interaction and similarities of this interaction with ligand-receptor interactions in different species are discussed.

Int J Pediatr Otorhinolaryngol, 1994 Jul, 30(1), 41 - 9
Bacterial meningitis in the pediatric population: paradigm shifts and ramifications for otolaryngology-head and neck surgery; Bent JP 3rd et al.; Various population-based studies have suggested that the incidence and epidemiology of bacterial meningitis is changing . No studies have been published which examine a sample population of the United States at large . Records of pediatric patients age 5 and under who were treated for bacterial meningitis (n = 470) at all US Army medical facilities between 1986 and 1991 were reviewed . The incidence of bacterial meningitis declined by 75% in the study group during this period . The largest decrease occurred in infants less than 1 year of age . The bacterial organisms isolated most commonly, in decreasing frequency were: Haemophilus influenza type b (HIB), pneumococcal, streptococcal, and staphylococcal . The most dramatic abatement occurred in Haemophilus meningitis following the introduction of HIB vaccinations . Neurologic sequelae were identified in 10% of meningitis survivors . The 2 most common impairments were hearing loss and speech/language delay . Economic modeling demonstrates tremendous savings in health care dollars from the decrease in disease incidence . These changes will have substantial bearing on training programs and practitioners, since the management of neurologic sequelae requires the expertise of multiple subspecialists . In the face of a medical onslaught, once devastating diseases are in retreat.

J Pediatr, 1994 Jul, 125(1), 74 - 7
Immunity to Haemophilus influenzae type b polysaccharide capsule in children with human immunodeficiency virus infection immunized with a single dose of Haemophilus vaccine; Peters VB et al.; We studied immunity to Haemophilus influenzae type b (Hib) polysaccharide capsule in 19 children infected with human immunodeficiency virus (HIV) immunized with a single dose of a Hib vaccine at a mean age of 28 months (range, 15 to 56 months) . Four to eighty-five months after immunization, only 7 children (37%) were immune . There were no significant differences in the HIV classification of the Centers for Disease Control and Prevention, type of conjugate vaccine, age at vaccination or serologic testing, time from vaccination to antibody determination, and CD4 cell counts between children with and those without immunity.

Chest, 1994 Jul, 106(1), 15 - 22
A clinical profile of chronic bacterial pneumonia . Report of 115 cases; Kirtland SH et al.; OBJECTIVE: To review the clinical presentation, radiology, microbiology, and response to therapy of patients with chronic bacterial pneumonia . DESIGN: A retrospective analysis . SETTING: An urban tertiary care medical center . PARTICIPANTS: One hundred fifteen patients with pulmonary and/or constitutional symptoms of at least 1 month's duration with 4,000 or more colony-forming units (CFUs) of a single bacterial species identified by quantitative culture obtained via fiberoptic bronchoscopy . MEASUREMENTS: Charts were analyzed for presence or absence of any predisposing illness, symptoms at presentation, roentgenographic abnormalities, microbiologic results, findings at fiberoptic bronchoscopy, and results of therapeutic intervention . RESULTS: Sixty-five percent of patients with chronic bacterial pneumonia had a predisposing disease, 35 percent were "normal." Cough, fatigue, dyspnea, and weight loss were predominant symptoms in both groups . Bronchogenic carcinoma was newly diagnosed in 16 patients (14 percent) . Haemophilus influenzae or alpha-hemolytic streptococcus was isolated in 68 percent of patients . Risk of recurrence of infection was inversely associated with duration of therapy in both groups . CONCLUSIONS: Chronic bacterial pneumonia is more common than previously recognized . It occurs in patients with and without a predisposing illness . Clinical presentation, roentgenographic appearance, and bacteriology are similar between the two groups . Cure requires prolonged antibiotic therapy.

Am J Public Health, 1994 Jul, 84(7), 1154 - 7
An increase in Haemophilus influenzae type B vaccination among preschool-aged children in inner-city Los Angeles, 1990 through 1992; Ewert DP et al.; Haemophilus influenzae type b (Hib) vaccination coverage and disease incidence were measured among preschool-aged children residing in inner-city Los Angeles . Among children 1.5 to 14 months of age, vaccination coverage of at least one dose increased from 0% in 1990 to 82% (95% confidence interval {CI} = 73%, 91%) in 1992 . Among children 15 to 59 months old, vaccination coverage of at least one Hib dose administered at or after age 15 months increased from 35% (95% CI = 29%, 41%) in 1990 to 63% (95% CI = 56%, 70%) in 1992 . Although Hib vaccination has reduced disease incidence in this population, greater use of vaccine can result in further reductions.

J Infect Dis, 1994 Jul, 170(1), 76 - 81
Immunogenicity of Haemophilus influenzae type b tetanus toxoid conjugate vaccine in young infants . The Kaiser-UCLA Vaccine Study Group; Greenberg DP et al.; In a prospective, randomized, double-blind efficacy trial, the immunogenicity of 10 lots of Haemophilus influenzae type b capsular polysaccharide-tetanus toxoid conjugate vaccine (PRP-T) was evaluated . More than 10,000 infants received PRP-T or hepatitis B vaccine at about 2, 4, and 6 months of age along with other childhood vaccines . In a subset of infants, geometric mean concentrations of total anticapsular antibody were 0.08, 0.79, and 5.29 micrograms/mL after the first, second, and third doses, respectively . Four lots of reconstituted lyophilized PRP-T vaccine were significantly more immunogenic than 6 lots of aqueous vaccine (P = .03) . In a stepwise regression model, the most important additional factors affecting anticapsular antibody concentrations were the time between the third dose and the blood draw, race, and breast-feeding status at 6 months of age . Immune responses to diphtheria and tetanus toxoids were not significantly different for infants given PRP-T or hepatitis B vaccines along with diphtheria-tetanus toxoid-pertussis vaccine.

J Infect Dis, 1994 Jul, 170(1), 220 - 2
Use of serology to diagnose pneumonia caused by nonencapsulated Haemophilus influenzae and Moraxella catarrhalis; Burman LA et al.; Antibodies against nonencapsulated Haemophilus influenzae and Moraxella (Branhamella) catarrhalis were measured by ELISA in paired sera from 158 adult patients with pneumonia . A mixture of 10 clinical isolates of each species was used as antigen . Eleven patients (7%) showed significant increases in antibody to H . influenzae . In 3 of them, the organism was isolated from transtracheal aspirate and in another 7 from sputum, nasopharynx, or both . Six patients with nonencapsulated H . influenzae in transtracheal aspirate cultures did not show any antibody increase . Six patients had significant increases in antibody to M . catarrhalis . The organism was isolated in transtracheal aspirates from 1 of them and in sputum and nasopharynx (or both) from another 3 . Two patients with M . catarrhalis in transtracheal aspirate cultures showed no antibody response . In conclusion, the serologic methods increased the possibility to diagnose infections caused by the two agents but had low sensitivity.

Infect Immun, 1994 Jul, 62(7), 3041 - 3
Identification of a hemolytic activity elaborated by Haemophilus ducreyi; Palmer KL et al.; Haemophilus ducreyi is the causative agent of the sexually transmitted disease chancroid . We have identified a hemolytic activity expressed by H . ducreyi . This activity is most readily detected when horse erythrocytes are used as a target; however, low levels of activity can be detected with sheep, human, or rabbit erythrocyte targets . The activity is heat labile and protease sensitive.

Infect Immun, 1994 Jul, 62(7), 2707 - 14
Adenovirus infection enhances in vitro adherence of Streptococcus pneumoniae; Hakansson A et al.; Viruses are thought to facilitate bacterial infections of the respiratory tract, but the mechanisms are poorly understood . The present study analyzed the effect of adenovirus on bacterial adherence to human respiratory tract epithelial cells . The human lung carcinoma cell line A549 was infected with adenovirus of types 1, 2, 3, 4, 5, and 9 . At a multiplicity of infection of 75 particles per cell, cytopathic effects occurred in 75 to 100% of the cells within 48 h . The virus-infected cells were harvested at various times after infection and analyzed for the ability to bind strains of Haemophilus influenzae and Streptococcus pneumoniae . Adenovirus (types 1, 2, 3, and 5) commonly causing respiratory tract infections increased the binding of adherent S . pneumoniae strains to the cells . This effect was not seen for other adenovirus types . Adenovirus infection did not change the adherence of cells of poorly adhering strains of S . pneumoniae or H . influenzae . The increase in adherence of S . pneumoniae could be inhibited by the DNA synthesis inhibitor cytosine arabinofuranoside, which is known to block the late phase of the adenovirus infection . When electron microscopy was used, there was no evidence that virus particles bound directly to bacteria . Adherence was not affected by pretreatment of the cells with virus particles or viral proteins . This suggested that adenovirus infection upregulated receptors for S . pneumoniae . The increased attachment may be one mechanism by which viruses precondition the respiratory mucosa for bacterial infection.

Antimicrob Agents Chemother, 1994 Jul, 38(7), 1678 - 80
Determination of antimicrobial susceptibilities of Canadian isolates of Haemophilus influenzae and characterization of their beta-lactamases . Canadian Haemophilus Study Group; Scriver SR et al.; Susceptibility testing of 1,688 Haemophilus influenzae isolates found 484 ampicillin-resistant strains; 474 strains (28.4%) were beta-lactamase positive, and 5 strains (0.4%) were non-beta-lactamase producers . Restriction enzyme digestion of the beta-lactamase amplicon determined that, of 157 strains, 11 (7.0%) contained ROB-1 beta-lactamase and 146 (93.0%) contained a TEM-type beta-lactamase.

Antimicrob Agents Chemother, 1994 Jul, 38(7), 1647 - 8
Emergence of Haemophilus ducreyi resistance to trimethoprim-sulfamethoxazole in Rwanda; Van Dyck E et al.; The in vitro susceptibilities of 112 clinical isolates of Haemophilus ducreyi to six antimicrobial agents were determined . These isolates were obtained in Kigali, Rwanda, during three studies on genital ulcer disease performed in 1986 (18 isolates), 1988 (23 isolates), and 1991 (71 isolates) . All H . ducreyi isolates were susceptible to azithromycin, ceftriaxone, ciprofloxacin, and erythromycin; all isolates obtained in 1986 were also susceptible to trimethoprim and to the combination trimethoprim-sulfamethoxazole . In contrast, 39 and 9% of the isolates obtained in 1988 and 59 and 48% of the isolates obtained in 1991 were resistant to trimethoprim (MIC, > or = 4.0 mg/liter) and trimethoprim-sulfamethoxazole (MIC, < or = 4.0/76 mg/liter), respectively . These data indicate that trimethoprim-sulfamethoxazole can no longer be recommended for use in the treatment of chancroid in Rwanda, and possibly elsewhere in Africa.

Sex Transm Dis, 1994 Jul-Aug, 21(4), 231 - 4
Single dose azithromycin for the treatment of chancroid: a randomized comparison with erythromycin; Tyndall MW et al.; BACKGROUND AND OBJECTIVES: Chancroid is endemic in sub-Saharan Africa and enhances the sexual transmission of the human immunodeficiency virus Type 1 (HIV-1) . Azithromycin is an orally absorbed macrolide antibiotic that is active against Haemophilus ducreyi, the causative agent of chancroid, and has pharmacokinetic properties that are suitable for single dosing . STUDY DESIGN: In a randomized single-blinded study of 127 men presenting to a referral STD clinic with culture proven chancroid, we compared the efficacy of azithromycin, administered as a single 1 g dose, with erythromycin 500 mg given 4 times daily for 7 days . RESULTS: Cure rates were 89% (73 of 82) in the azithromycin group and 91% (41 of 45) in the erythromycin group . A failure to respond to treatment was associated with HIV-1 seropositivity and a lack of circumcision . Both regimens were well tolerated . CONCLUSIONS: Azithromycin, given as a single 1 g oral dose, is an effective treatment for chancroid in men, and offers major prescribing advantages over erythromycin.

Pediatr Infect Dis J, 1994 Jul, 13(7), 635 - 9
Enhanced antibody response in Venezuelan infants immunized with Haemophilus influenzae type b-tetanus toxoid conjugate vaccine; Castillo de Febres O et al.; The safety and immunogenicity of primary immunization at 2, 4 and 6 months of age with Haemophilus influenzae type b capsular polysaccharide conjugated to tetanus toxoid (PRP-T; Act-HIB) were evaluated in infants in Valencia, Venezuela . In order better to assess reactions to PRP-T, subjects received their initial PRP-T vaccine a mean of 6.5 days after their initial diphtheria-tetanus-pertussis (DTP) vaccine . The PRP-T vaccine was well tolerated . Serum was obtained at ages 2 and 7 months (before the first and 1 month after the third PRP-T dose) . Antibody responses were compared with those from Nashville infants who had received PRP-T and DTP simultaneously in a previous trial . The preimmunization titers in the Venezuelan and Nashville infants did not differ . The geometric mean postimmunization titer in the Venezuelan infants was 37.9 micrograms/ml, as compared with 3.63 micrograms/ml in the Nashville infants (P < 0.00001) . Possible explanations for the exceptional antibody response of these Venezuelan infants to PRP-T include carrier priming caused by prior DTP immunization, synergy associated with the specific DTP vaccine used, preimmunization immunologic experience that differed from their United States counterparts and genetic differences that altered response to the vaccines . Further studies are proposed to evaluate these possibilities.

Pediatr Infect Dis J, 1994 Jul, 13(7), 609 - 12
Antimicrobial susceptibility of nasopharyngeal isolates of potential pathogens recovered from infants before antibiotic therapy: implications for the management of otitis media; Faden H et al.; Antimicrobial susceptibility was determined for strains of Streptococcus pneumoniae, nontypable Haemophilus influenzae and Moraxella catarrhalis recovered from the nasopharynxes of children followed from birth . The bacteria tested were the first potential pathogens isolated from each child before any treatment with antibiotics . Minimal inhibitory concentrations of commonly used oral antibiotics demonstrated the following overall rates of resistance for (1) S . pneumoniae: penicillin 1.2% (intermediate susceptibility 4.8%), trimethoprim-sulfamethoxazole 20%; (2) nontypable H . influenzae: ampicillin 32%, cefaclor 17%; (3) M . catarrhalis: ampicillin 90%, trimethoprim-sulfamethoxazole 19% . Antibiotic regimens used for treatment of otitis media may have to be evaluated in light of changing antibiotic susceptibilities.

Can J Vet Res, 1994 Jul, 58(3), 211 - 9
Adherence of Haemophilus somnus to tumor necrosis factor-alpha-stimulated bovine endothelial cells in culture; Kwiecien JM et al.; Vascular thrombosis and tissue infarction is a principal lesion in Haemophilus somnus septicemia known also as thrombotic meningoencephalitis . This study was undertaken to examine whether tumor necrosis factor-alpha (TNF-alpha) can influence the adherence of H . somnus to cultured bovine aortic endothelial cells (BAEC) . Confluent BAEC were exposed to 0-100 nM of human recombinant TNF-alpha for 12-48 h . Suspensions of different strains of H . somnus (approximately 1.5-3 x 10(8) labelled with {methyl-3H}-thymidine, were added to BAEC and incubated for 1.5 h . Initial studies with one pathogenic (P) strain and one non-pathogenic (NP) strain revealed that both strains adhered to normal endothelial cells but minimally to subendothelial matrix remaining after removal of BAEC . Adherence to BAEC was reduced by an excess of unlabelled H . somnus of the same strain . Adherence was enhanced for both strains by exposure of BAEC to TNF-alpha in a manner that increased with TNF-alpha concentration and with duration of exposure to TNF-alpha prior to addition of bacteria . A survey of adherence of six live P strains and six NP strains demonstrated considerable variation but no difference in adherence between P and NP strains to normal or to TNF-alpha-stimulated BAEC . However, TNF-alpha consistently increased adhesion of each strain to BAEC . Both P and NP strains caused more severe cytotoxic changes in TNF-alpha-treated BAEC . Tumor necrosis factor-alpha also increased adhesion of formalin-killed bacteria of P and NP strains.(ABSTRACT TRUNCATED AT 250 WORDS)

Can J Vet Res, 1994 Jul, 58(3), 202 - 10
Ovine Haemophilus somnus: experimental intracisternal infection and antigenic comparison with bovine Haemophilus somnus; Lees VW et al.; Experimental infection was produced by two of four isolates of ovine Haemophilus somnus given by intracisternal inoculation into two to three-month-old lambs . Isolate 2041 (originally obtained from a septicemic lamb in Alberta) caused lethal infection in eight of nine lambs, isolate 67p from the prepuce of a normal lamb produced less acute disease in four of nine lambs, and the other two isolates (93p and 1190) caused no detectable disease . Significant lesions were limited to the brain and spinal cord . Purulent meningitis was characteristic but vasculitis or septicemia were not detected, perhaps due to the route of inoculation . Since a difference in virulence was noted among strains, we analyzed surface proteins thought to be virulence factors of bovine H . somnus . Protein profiles of bovine and ovine H . somnus done by sodium dodecyl sulphate-polyacrylamide gel electrophoresis showed similar patterns for virulent bovine isolates and ovine septicemic isolates . Preputial isolates showed a lower molecular mass major outer membrane protein than septicemic isolates . Antigenic analysis revealed that outer membrane proteins p270, p78, p76, p40, and p39 were detected in both ovine and bovine isolates except for 1190, which was probably not a true H . somnus isolate . Thus the preputial and septicemic isolates of ovine H . somnus were similar to bovine H . somnus in pathogenicity and in surface antigens.

J Am Board Fam Pract, 1994 Jul-Aug, 7(4), 335 - 41
Haemophilus influenzae intra-amniotic infection with intact membranes; Shute KM et al.; BACKGROUND: Amnionitis rarely occurs with intact membranes . Haemophilus influenzae is a rare pathogen in intra-amniotic infection, but its importance and prevalence could be increasing, as reflected by the growing number of reported cases in the last 20 years . METHODS: Using the key words "amnionitis," "intra-amniotic infection," "chorioamnionitis," and "Haemophilus influenzae," we searched MEDLINE files from 1980 to the present . Articles dating before 1980 were accessed from cross-reference of the more recent studies . RESULTS AND CONCLUSIONS: H . influenzae, a nonmotile, aerobic, gram-negative rod-shaped bacteria, is primarily responsible for respiratory tract infections in children and neonatal meningitis; it has a low prevalence rate in genital tract cultures but a high attack rate of infection in mothers and neonates . With intact membranes, intra-amniotic infection occurs rarely and is thought to be caused by hematogenous transplacental seeding, direct invasion of the fetal membranes, or inoculation of the amniotic fluid during an invasive procedure . It can also be idiopathic . It occurs most often in the second and early third trimesters and can be definitively diagnosed by a positive amniotic fluid culture or positive maternal or neonatal blood cultures and clinical evidence of intra-amniotic infection . We present a case of intra-amniotic infection with intact membranes at 15 to 16 weeks in a patient with clinical evidence of intra-amniotic infection and positive blood cultures whose infection was treated successfully with antibiotics, prolonging her pregnancy by 16 weeks . Physicians caring for obstetric patients must be vigilant in diagnosing intra-amniotic infection, even with intact membranes, and this infection should be considered in the differential diagnoses for acute abdomen in pregnancy.

Jpn J Antibiot, 1994 Jul, 47(7), 940 - 9
{Bacteriological and clinical studies of biapenem (L-627) in pediatric field}; Nishimura T et al.; We have carried out bacteriological and clinical studies on L-627 . The results are summarized as follows . Treatment with L-627 was made in 14 cases of pediatric bacterial infections including 5 cases of pneumonia and 2 cases each of tonsillitis, urinary tract infection and one case each of colitis, and phlegmon . Results obtained were excellent in 11 cases, good in 2 cases and poor in one case . The bacteriological effect of L-627 was excellent, all causative organisms (Staphylococcus aureus one strain, Streptococcus pyogenes 2 strains, Streptococcus pneumoniae 3 strains, Escherichia coli 3 strains, Haemophilus influenzae one strain, Haemophilus parainfluenzae one strain) were eradicated . No significant side effects due to the drug were observed in any cases, except 2 cases each of elevated eosinophil counts and elevated platelet counts.

Jpn J Antibiot, 1994 Jul, 47(7), 921 - 31
{Bacteriological and clinical studies of biapenem (L-627) in pediatrics}; Kusumoto Y et al.; Bacteriological and clinical studies in the pediatric field have been performed on biapenem (L-627), a newly-developed carbapenem antibiotic, and the following results were obtained . 1 . In the pharmacokinetic study, the plasma concentration of L-627 showed dose-dependant change: Cmax was 14.6 micrograms/ml and AUC was 15.4 micrograms.hr/ml with the administration of 6 mg/kg, while Cmax was 49.2 micrograms/ml and AUC was 60.1 micrograms.hr/ml with the administration of 12 mg/kg . After the administration of 6 mg/kg, the urinary concentration reached maximum within 2 hours and the cumulative urinary excretion rate in the first 6 hours was 49.4% . 2 . Antibacterial activities of L-627 against 27 strains of clinical isolates were determined . MICs of L-627 against such Gram-positive cocci as Staphylococcus aureus, Streptococcus pneumoniae and Streptococcus pyogenes were sufficiently low, and those against such Gram-negative rods as Haemophilus influenzae, Escherichia coli and Bordetella pertussis were satisfactory and as low as those of imipenem or ceftazidime . 3 . Clinical efficacies of L-627 were evaluated in 36 cases of bacterial infections . The overall efficacy rate was 100%, and excellent responses in 26 cases and good in 10 cases were obtained . As for bacteriological efficacies, all strains except 1 of B . pertussis were eradicated and a high eradication rate of 96.6% was obtained . 4 . No side effects were observed in 37 evaluated cases . As abnormal laboratory test results, eosinophilia was noted in 2 cases (5.4%), but they returned to normal values rapidly after the drug was discontinued . From these results, it has been concluded that L-627 is a safe and effective drug to be used in treatment of pediatric infectious diseases.

Jpn J Antibiot, 1994 Jul, 47(7), 896 - 902
{Pharmacokinetic, bacteriological and clinical studies on biapenem (L-627) in children}; Tajima T et al.; The results are summarized as follows: 1 . A total of 10 patients were treated with biapenem (L-627) . We received informed consent from all of their parents . Each dose was 6 mg/kg, and it was administered 3 times daily (40 mg/kg, 4 times daily in meningitis), in a 30-minute intravenous drip infusion for 5-17 days . The clinical efficacies of L-627 in 10 patients with bacterial infections (1 with purulent meningitis, 1 with sepsis, 5 with pneumonia, 2 with urinary tract infection and 1 with purulent tonsillitis) were evaluated as excellent in 8 patients, as good in 2 patients with an efficacy rate of 100% . Seven causative organisms found in 5 patients (Streptococcus pneumoniae in 2, Moraxella (Branhamella) catarrhalis in 2, Haemophilus influenzae in 2 and Pseudomonas aeruginosa in 1) were eradicated . No adverse reaction was observed in any of the 10 patients . 2 . Pharmacokinetic studies Peak plasma concentrations of L-627 were 12.5-13.7 micrograms/ml at the dose of 6 mg/kg administered by 30-minute drip infusion . Plasma half-lives of L-627 in the beta-phase averaged 0.72 hour (0.63-0.80 hour) . CSF concentration/plasma concentration ratios of L-627 were 1.12/8.16 micrograms/ml (Day 2, 1.17 hours after at dose of 20 mg/kg), 0.88/3.44 micrograms/ml (Day 3, 4.0 hours after at dose of 30 mg/kg) and 0.68/5.12 micrograms/ml (Day 13, 3.0 hours after at dose of 40 mg/kg) administered by 30-minute drip infusion in the child with purulent meningitis (case 1).(ABSTRACT TRUNCATED AT 250 WORDS)

Int J Immunopharmacol, 1994 Jul, 16(7), 497 - 505
Antibody-producing cells in peripheral blood and tonsils after oral treatment of children with bacterial ribosomes; Zanin C et al.; The efficacy of ribosomal preparations as mucosal immunostimulants was examined in the peripheral blood and tonsils of 14 children, before and after 28 days of oral treatment with D-53, a preparation of ribosomes from Klebsiella pneumoniae, Streptococcus pneumoniae, Haemophilus influenzae and Streptococcus pyogenes . Tonsils from 10 untreated children were used as controls . Immunofluorescence and ELISAspot were performed to analyse variations in the numbers of immunoglobulin-containing and immunoglobulin-secreting B-cells . Both isotypic and antigenic specificities of these two types of cells were investigated . Significant differences were observed after treatment in the peripheral blood as well as between tonsils from treated and untreated children . In the peripheral blood a significant increase in immunoglobulin-secreting cells directed against antigenic specificities of D-53 was the major change . In tonsils, higher numbers of specific immunoglobulin-containing and secreting cells, and higher numbers of IgA-secreting cells were induced in treated children . These data support the efficacy of D-53 as an oral immunostimulant.

Clin Microbiol Rev, 1994 Jul, 7(3), 346 - 56
Identification of veterinary pathogens by use of commercial identification systems and new trends in antimicrobial susceptibility testing of veterinary pathogens; Watts JL et al.; Veterinary diagnostic microbiology is a unique specialty within microbiology . Although isolation and identification techniques are similar to those used for human pathogens, many veterinary pathogens require unique cultivation or identification procedures . Commercial identification systems provide rapid, accurate identification of human pathogens . However, the accuracy of these systems with veterinary pathogens varies widely depending on the bacterial species and the host animal from which it was isolated . Increased numbers of veterinary strains or species in the data bases of the various systems would improve their accuracy . Current procedures and interpretive criteria used for antimicrobial susceptibility testing of veterinary pathogens are based on guidelines used for human pathogens . The validity of these guidelines for use with veterinary pathogens has not been established . As with fastidious human pathogens, standardized methodologies and quality control isolates are needed for tests of organisms such as Actinobacillus pleuropneumoniae and Haemophilus somnus . Furthermore, interpretive criteria for veterinary antimicrobial agents based on the MIC for veterinary pathogens, the pharmacokinetics of the antimicrobial agent in the host animal, and in vivo efficacy of the antimicrobial agent are needed . This article reviews both the commercial identification systems evaluated with veterinary pathogens and current methods for performing and interpreting antimicrobial susceptibility tests with veterinary pathogens . Recommendations for future improvements in both areas are discussed.

J Med Microbiol, 1994 Jul, 41(1), 63 - 8
Genomic DNA fingerprinting of clinical Haemophilus influenzae isolates by polymerase chain reaction amplification: comparison with major outer-membrane protein and restriction fragment length polymorphism analysis; van Belkum A et al.; Non-capsulate strains of Haemophilus influenzae were genotyped by analysis of variable DNA segments obtained by amplification of genomic DNA with the polymerase chain reaction (PCR fingerprinting) . Discrete fragments of 100-2000 bp were obtained . The reproducibility of the procedure was assessed by comparing: (i) the fingerprints of 16 colonies of a single H . influenzae strain; (ii) isolates obtained from individual sputum samples (a total of 57 H . influenzae isolates from three cystic fibrosis patients); and (iii) 17 isolates collected during an outbreak of H . influenzae infection in a local pulmonary rehabilitation centre . The discriminatory power of the method was demonstrated by showing that the PCR fingerprints of eight unrelated H . influenzae strains from sputum samples of patients with chronic obstructive pulmonary disease (COPD) and 32 strains from cystic fibrosis patients were all different . These 40 isolates also differed with respect to their restriction fragment length polymorphisms (RFLP) and major outer-membrane protein (MOMP) composition . Twelve MOMP antigenic strain variants from sputum samples of five COPD patients had identical PCR fingerprints and RFLPs . It was concluded that PCR fingerprinting is a reliable and reproducible method for genotyping non-capsulate strains of H . influenzae . The discriminatory power of PCR fingerprinting was similar to that of RFLP analysis, but the results of PCR fingerprinting were easier to interpret.

Braz J Med Biol Res, 1994 Jul, 27(7), 1627 - 34
Production and immunochemical characterization of Neisseria meningitidis group B antiserum for the diagnosis of purulent meningitis; Alkmin MG et al.; Unlike Neisseria meningitidis groups A, C, Y and W135, the group B capsular polysaccharide has been shown to be chemically and immunologically identical to the capsular polysaccharide of Escherichia coli K1 . Both components are sialic acid homopolymers and are poorly immunogenic . Nevertheless, due to the high incidence of Neisseria meningitidis group B meningitis in the population of the State of Sao Paulo, preparing antiserum to this serogroup for diagnostic purposes has become a matter of high priority . Of the many immunization schemes proposed, intravenous inoculation of whole bacteria previously inactivated with formaldehyde and simultaneous intradermal inoculation with a mixture of the bacterial polysaccharide fraction and whole bacteria in complete Freund;s adjuvant have produced the best results . The antiserum was treated with immunoadsorbents prepared with aluminum chloride and protein and/or polysaccharide antigens from each of the following heterologous bacteria: Haemophilus influenzae type b, Streptococcus pneumoniae, Escherichia coli other than K1, and Staphylococcus aureus, in order to eliminate cross-reactivity . For quality control analysis, the antiserum was assessed by the immunodiffusion, counterimmunoelectrophoresis, dot-ELISA, and immuno-blot techniques against homologous antigens . Specificity was obtained after treating the antiserum with Haemophilus influenzae type b polysaccharide immunosorbent.

Antibiot Khimioter, 1994 Jul, 39(7), 47 - 53
{Use of oral macrolide and azalide antibiotics in children with bronchopulmonary diseases}; Sereda EV et al.; The therapeutic efficacy of oral macrolides (erythromycin base and midekamycin, macropen) and azalides (azithromycin, sumamed) in the treatment of children with acute and chronic (during the aggravation) bronchopulmonary diseases was studied . The main etiological factors of acute and chronic pneumonia were Streptococcus pneumoniae and Haemophilus influenzae . The proportion of Staphylococcus aureus was high in infants with acute pleuropulmonary inflammations . The susceptibility of the isolates to the antibiotics was found to be high . The results of the trials showed that erythromycin, macropen and azithromycin were efficient in the treatment of acute and chronic pneumonia . The foci of acute pneumonia dissolved after oral administration of the drugs within the same periods as after the use of other parenteral antibiotics . The comparative estimation of the drug efficacy revealed that azithromycin was more active . The ease of the azithromycin administration (in the form of a suspension) in infants and children once a day for a shorter treatment course up to 5 days, high efficacy and no adverse reactions permitted to consider the antibiotic as the most promising antibacterial agent for the treatment of respiratory infections in children in hospitals and outpatient departments.

Avian Dis, 1994 Jul-Sep, 38(3), 672 - 8
Complicated infectious coryza outbreaks in Argentina; Sandoval VE et al.; Seventeen complicated outbreaks of infectious coryza in layer, broiler-breeder, and broiler flocks were studied . In the layer flock outbreaks, drops in egg production of up to 35% were seen . In the broiler flocks and several of the layer flocks, losses due to persistent mortality and/or culling varied between 2 and 5% . Signs of infectious coryza in both layers and broiler-breeders were typical; in broilers, however, swollen head-like syndrome was seen . Except in one flock, no viral diseases were clinically or serologically detected . Excluding broiler-breeders, birds from most other flocks were serologically positive for Mycoplasma gallisepticum, and some were also positive for M . synoviae . Haemophilus paragallinarum was isolated from all of the outbreaks, but only as a pure culture in three outbreaks . Isolation of H . paragallinarum from sites such as liver, kidney, and particularly tarsal arthritis and ocular globes appears to be reported for the first time . Serovar A was isolated in eight outbreaks, serovar B in six, serovar C in one, and untypable serovars in two . The severity of these infectious coryza outbreaks may have been increased by concurrent salmonellosis, pasteurellosis, and mycoplasmosis, although under certain conditions H . paragallinarum is able to cause septicemia . Ten of the outbreaks occurred in birds vaccinated against infectious coryza; this may be due to the use of vaccines that do not provide protection against the types of H . paragallinarum that affect poultry in the region.

Presse Med, 1994 Jun 4, 23(21), 972 - 5
{Streptococcus pneumoniae bacteremia and HIV infection . Retrospective study of 41 episodes in 30 patients}; Torri O et al.; OBJECTIVES: Pulmonary infections and bacteraemia, essentially due to Streptococcus pneumoniae and Haemophilus influenzae, are frequently reported in patients infected with the human immunodeficiency virus (HIV) . We retrospectively analyzed episodes of bacteraemia in HIV-infected patients to determine whether supplementary risk factors could be ascertained and whether it would be advisable to propose vaccination . METHODS: From June 1986 to February 1992, 41 episodes of bacteraemia in 30 HIV-infected patients were observed in 7 different wards . Data on age, sex, risk group, Centers for Disease Control classification, CD4 counts and clinical outcome were recorded . RESULTS: There were 18 males and 12 females, mean age 34 years (range 26-67 years) in CDC class II (n = 11), III (n = 5) and IV (n = 16) . There were 17 intravenous drug users (56.6%) . There were 8 heterosexuals (26%), 3 homosexuals or bisexuals (n = 3) and 2 patients infected after blood transfusions (6%) . All the heterosexual patients were of black-African or Carabean ethnic origin . Mean CD4 count was 239 mm3 (range 2-1148) during the episode of bacteraemia which occurred during an upper respiratory tract infection in 96% of the patients . Recurrent episodes were observed in 7 patients . Outcome of the infectious episode was favourable in 35/41 cases after antibiotic therapy . Six patients (all CDC class IV) died during the episode of bacteraemia . CONCLUSIONS: These observations showed that intravenous drug use and black-African ethnic origin are supplementary risk factors for S . pneumoniae infection in HIV-infected patients . The frequency of upper respiratory tract infections in these patients suggests that anti-S . pneumoniae vaccination should be evaluated further.

Am J Clin Pathol, 1994 Jun, 101(6), 729 - 32
The effects of nonclassic pediatric bacterial pathogens on the usefulness of the Directigen latex agglutination test; Hill RB et al.; Haemophilus influenzae type b, Escherichia coli, Neisseria meningitis, Streptococcus agalactiae, and Streptococcus pneumoniae are classically the predominant meningeal pathogens of children . The Directigen latex agglutination test identifies these pathogens by detecting specific antigens in cerebrospinal fluid (CSF) and urine . The authors tested 1151 specimens from 791 children with suspected meningeal infections . They found that the sensitivity of the Directigen test for detecting the five classic CSF pathogens of children was 83.3% with CSF and 60% with urine specimens . In detecting all pathogens, however, the sensitivity was only 50% with CSF and 37.5% with urine . Thus, an increased prevalence of nonclassic pathogens in a pediatric population adversely affects the efficacy of the Directigen test for confirming a diagnosis of meningitis and emphasizes the diagnostic importance of the clinical history and other routine CSF tests.

Am J Clin Pathol, 1994 Jun, 101(6), 726 - 8
Evaluation of the new DrySlide beta-lactamase test; Dyke JW et al.; Four hundred thirteen recent clinical isolates of Staphylococcus, Haemophilus, Moraxella, and Neisseria species were tested for beta-lactamase production using the Difco DrySlide beta-lactamase test . These results were compared with those of the BBL Cefinase reagent . Of the 413 isolates tested, 258 (62.5%) were beta-lactamase positive . There was 99.8% agreement between the two test methods; only one isolate of Staphylococcus aureus was DrySlide-negative and Cefinase-positive . The DrySlide beta-lactamase reagent is an accurate and convenient format for the evaluation of beta-lactamase activity in the clinical laboratory.

Laryngoscope, 1994 Jun, 104(6 Pt 1), 731 - 5
Disappearance of epiglottitis during large-scale vaccination with Haemophilus influenzae type B conjugate vaccine among children in Finland; Takala AK et al.; Surveillance of blood-culture-proven epiglottitis was conducted in Finland from 1985 through 1992 . Among children (< 16 years), all bacteria causing epiglottitis, and among adults, Haemophilus influenzae were included . H influenzae type b (Hib) caused 226 (97%) of cases among children . Among adults with H influenzae epiglottitis (total of 20), 19 were caused by Hib . In 1986, vaccine trials with Hib-conjugate vaccines started in Finland, with vaccination coverage of 94% to 98% of infants . Vaccinations did not yet have an effect on the occurrence of epiglottitis in 1985 or 1986 when the annual incidence among children was 5.3/100,000, among those less than 5 years of age was 13.2/100,000, and among adults was 0.08/100,000 . In 1987 through 1992 the proportion of vaccinated children increased steadily while the incidence of Hib epiglottitis decreased from 50 to 60 cases seen annually in 1985 and 1986 to 2 cases in 1992 . There was no increase in the occurrence of epiglottitis caused by other pathogens . In conclusion, there is now a safe and efficient way to prevent the majority of epiglottitis cases among children with the new Hib-conjugate vaccines.

J Infect Dis, 1994 Jun, 169(6), 1284 - 90
A primate model for chancroid; Totten PA et al.; Adult pigtailed macaques (Macaca nemestrina) were evaluated for their usefulness as a primate model for chancroid . To initiate infection, 10(7)-10(8) cfu of Haemophilus ducreyi were inoculated into the foreskins of 5 adult males and into the vaginal labia of 4 adult females . Lesions developed in the male macaques that were similar in appearance, histopathologic changes, and progression to those of human disease, including the development of ulcers 6-12 days after infection . In addition, H . ducreyi could be recovered from the lesions up to 20 days after inoculation, humoral antibodies were induced beginning 1 week after inoculation, and inguinal lymphadenopathy was noted in 4 of the 5 males . None of the 4 female macaques inoculated with the same preparation of live H . ducreyi developed comparable lesions . Thus, experimental chancroid in adult male macaques closely resembles human disease and should be useful for future studies of the pathogenesis of chancroid.

Arch Pediatr Adolesc Med, 1994 Jun, 148(6), 620 - 5
Clinical comparison of the Haemophilus influenzae type B polysaccharide-diphtheria toxoid and the oligosaccharide-CRM197 protein vaccines in infancy; Peltola H et al.; OBJECTIVE: To compare two Haemophilus influenzae type B (HiB) conjugate vaccines, a polysaccharide-diphtheria toxoid conjugate (PRP-D) vaccine and an oligosaccharide-CRM197 protein conjugate (HBOC {PRP-CRM}) vaccine, in the same population . DESIGN: One hundred twenty-five thousand infants were randomized to receive the PRP-D or HBOC vaccine . Primary immunization consisted of two doses of either vaccine administered at 4 and 6 months and a booster dose was given at 14 to 18 months . Protection was assessed by recording episodes of invasive disease with HiB isolated from the blood or another normally sterile body site . SETTING: One thousand thirty-six child health care centers in Finland . PARTICIPANTS: Infants born in Finland during the 24-month period from 1987 to 1989 . INTERVENTION: Each vaccine dose was injected intramuscularly in a volume of 0.5 mL . At the same time, a separate site was injected with the diphtheria and tetanus toxoids and pertussis vaccine at 4 months of age, with inactivated poliovirus vaccine at 6 months of age, and with measles-mumps-rubella vaccine at 14 to 18 months of age . MAIN RESULTS: The mean anticapsular antibody concentration 1 month after the second dose was 0.63 micrograms/mL and 4.32 micrograms/mL in the PRP-D and HBOC vaccine recipients, respectively . The booster dose resulted in a high antibody concentration: 33.3 micrograms/mL and 58.3 micrograms/mL for PRP-D and HBOC vaccine recipients, respectively . At 36 months of age, the antibody concentration declined to 2.5 micrograms/mL and 5.6 micrograms/mL for PRP-D and HBOC vaccine recipients, respectively . After two doses of the vaccine, there were five episodes (39 were expected based on historical controls) of invasive HiB disease in the PRP-D group and two episodes (35 were expected) in the HBOC group . Hence, an 87% (95% confidence limit {CL}, 69, 96) protection rate in the PRP-D group and a 95% (95% CL, 76, 99) protection rate in the HBOC group were achieved . No episodes occurred after the booster dose in either group . CONCLUSIONS: Both the PRP-D and HBOC vaccines are safe and effective . A two-dose primary vaccination schedule seems appropriate, at least in circumstances prevailing in Finland and probably in other areas with similar epidemiological effects of HiB disease.

Infect Immun, 1994 Jun, 62(6), 2639 - 43
Diversity of the P2 protein among nontypeable Haemophilus influenzae isolates; Bell J et al.; The genes for outer membrane protein P2 of four nontypeable Haemophilus influenzae strains were cloned and sequenced . The derived amino acid sequences were compared with the outer membrane protein P2 sequence from H . influenzae type b MinnA and the sequences of P2 from three additional nontypeable H . influenzae strains . The sequences were 76 to 94% identical . The sequences had regions with considerable variability separated by regions which were highly conserved . The variable regions mapped to putative surface-exposed loops of the protein.

Infect Immun, 1994 Jun, 62(6), 2628 - 32
Lactoferrin is a lipid A-binding protein; Appelmelk BJ et al.; Lactoferrin (LF), a cationic 80-kDa protein present in polymorphonuclear leukocytes and in mucosal secretions, is known to have antibacterial effects on gram-negative bacteria, with a concomitant release of lipopolysaccharides (LPS, endotoxin) . In addition, LF is known to decrease LPS-induced cytokine release by monocytes and LPS priming of polymorphonuclear leukocytes . Its mechanism of action is incompletely understood . We have now demonstrated by in vitro-binding studies that LF binds directly to isolated lipid A and intact LPS of clinically relevant serotypes of the species which most frequently cause bacteremia (Escherichia coli, Klebsiella pneumoniae, and Pseudomonas aeruginosa), as well as to lipid A and LPS of mucosal pathogens (among others, Neisseria meningitides and Haemophilus influenzae) . Binding to LPS was inhibitable by lipid A and polymyxin B but not by KDO (3-deoxy-D-manno-octulosonate), a glycoside residue present in the inner core of LPS . Binding of LF to lipid A was saturable, and an affinity constant of 2 x 10(9) M-1 was calculated for the LF-lipid A interaction . Our data may explain, in part, the mechanism whereby LF exerts its antibacterial and anti-endotoxic effects . Further studies on the ability of LF to block the detrimental effects of LPS, both in vitro and in vivo, are warranted.

Infect Immun, 1994 Jun, 62(6), 2470 - 7
A functional tonB gene is required for both utilization of heme and virulence expression by Haemophilus influenzae type b; Jarosik GP et al.; Haemophilus influenzae is nearly unique among facultatively anaerobic bacteria in its absolute requirement for exogenously supplied heme for aerobic growth . In this study, a mutant analysis strategy was used to facilitate identification of H . influenzae cell envelope components involved in the uptake of heme . Chemical mutagenesis was employed to produce a mutant of a nontypeable H . influenzae strain unable to utilize either protein-bound forms of heme or low levels of free heme . This mutant was transformed with a plasmid shuttle vector-based genomic library constructed from the same wild-type nontypeable H . influenzae strain, and a growth selection technique was used to obtain a recombinant clone that could utilize heme . Analysis of the DNA insert in the recombinant plasmid revealed the presence of several open reading frames, one of which encoded a 28-kDa protein with significant similarity to the TonB protein of Escherichia coli . This H . influenzae gene product was able to complement a tonB mutation in E . coli, allowing the E . coli tonB mutant to form single colonies on minimal medium containing vitamin B12 . When this H . influenzae gene was inactivated by insertional mutagenesis techniques and introduced into the chromosome of wild-type strains of H . influenzae type b, the resultant transformants lost their abilities to utilize heme and produce invasive disease in an animal model . Genetic restoration of the ability to express this TonB homolog resulted in the simultaneous acquisition of both heme utilization ability and virulence . These results indicate that the H . influenzae TonB protein is required not only for heme utilization by this pathogen in vitro, but also for virulence of H . influenzae type b in an animal model.

Infect Immun, 1994 Jun, 62(6), 2426 - 31
Comparison of nonhuman primate antibodies against Haemophilus influenzae type b polysaccharide with human antibodies in oligoclonality and in vivo protective potency; Kim KH et al.; Nonhuman primates are often used as a model for studying vaccines for humans . However, it is not always clear how closely the antibody responses in these species mimic human responses . Recent studies have characterized the human antibody response to Haemophilus influenzae type b (Hib) in great detail . In this study, we have compared the antibody response to Hib of humans with those of other primates . Studies of isoelectric points and V kappa subgroup usage show that, like humans, nonhuman primates produce oligoclonal antibodies . Also, monkey antibodies to the Hib polysaccharide are as protective as human antibodies in an in vivo model of Hib infection . Thus, we conclude that nonhuman primates produce antibodies to Hib polysaccharide that are structurally and functionally similar to human antibodies and are a good model for testing human vaccines.

Infect Immun, 1994 Jun, 62(6), 2379 - 86
Use of pyocin to select a Haemophilus ducreyi variant defective in lipooligosaccharide biosynthesis; Campagnari AA et al.; Haemophilus ducreyi, a cause of genital ulcer disease in developing countries, appears to facilitate the heterosexual transmission of the human immunodeficiency virus in Africa . Despite an increase in studies of this gram-negative human pathogen, little is known about the pathogenesis of chancroid . Our studies have shown that the lipooligosaccharides (LOS) of H . ducreyi may play an important role in ulcer formation . Monoclonal antibody and mass spectrometric analyses identified a terminal trisaccharide present on H . ducreyi LOS that is immunochemically similar to human paragloboside . This epitope is present on the LOS of Neisseria gonorrhoeae, and it may be the site of attachment for pyocin lysis . We have used pyocin, produced by Pseudomonas aeruginosa, to select LOS variants with sequential saccharide deletions from N . gonorrhoeae . On the basis of the similarities between N . gonorrhoeae and H . ducreyi LOS, we employed the same technique to determine if H . ducreyi strains were susceptible to pyocin lysis . In this study, we report the generation of a pyocin N-resistant H . ducreyi strain which synthesizes a truncated version of the parental LOS . Further studies have shown that this H . ducreyi variant has lost the terminal LOS epitope defined by monoclonal antibody 3F11 . This report demonstrates that H . ducreyi is sensitive to pyocins and that this technique can be used to generate H . ducreyi LOS variants . Such variants could be used in comparative studies to relate LOS structure to biologic function in the pathogenesis of chancroid.

Vaccine, 1994 Jun, 12(8), 700 - 6
Quantification of polysaccharide in Haemophilus influenzae type b conjugate and polysaccharide vaccines by high-performance anion-exchange chromatography with pulsed amperometric detection; Tsai CM et al.; A sensitive method for the quantification of polysaccharide (PS) in Haemophilus influenzae type b (Hib) conjugate and PS vaccines has been developed . It is based on measurement of the Hib PS subunit after depolymerization of the PS in sodium hydroxide to produce the subunit, which is characterized by chemical composition and 31P n.m.r . analyses as ribitol-ribose-phosphate . The Hib vaccines were first treated with 0.1 M sodium hydroxide . The Hib PS subunit in the treated vaccines was then analysed directly by high-performance anion-exchange chromatography using a CarboPak PA-1 column, and quantified by pulsed amperometric detection . The PS contents of three conjugate vaccines and three PS vaccines from different manufacturers were determined . Their values were in the expected ranges . This method is particularly useful for vaccines with a sugar stabilizer such as lactose which would interfere with the colorimetric orcinol assay currently used for determination of the PS . The method can measure 0.1 microgram of PS and its sensitivity is at least 30-fold higher than that of the orcinol assay . It may be used for stability studies of conjugate vaccines since a breakdown as low as 5% of the PS from the PS-protein conjugates would be detected.

Clin Infect Dis, 1994 Jun, 18(6), 951 - 7
Prevalence and resistance mechanisms of common bacterial respiratory pathogens; Jacoby GA; Organisms causing common infections of the respiratory tract are becoming increasingly resistant to antimicrobial agents . In 1990-1991 between 15% and 20% of isolates of Streptococcus pneumoniae from the United States had MICs of penicillin G of > or = 0.1 microgram/mL and 2%-3% had MICs of > or = 1.0 microgram/mL . The percentage of isolates that are resistant is even higher in other parts of the world . Although most penicillin-resistant strains of S . pneumoniae are susceptible to broad-spectrum cephalosporins, a few isolates resistant to cefuroxime, cefotaxime, and ceftriaxone have appeared . Unlike other respiratory pathogens in which the production of beta-lactamase is responsible for resistance, S . pneumoniae exhibits resistance that is caused by alterations in penicillin-binding proteins . Consequently, beta-lactam/beta-lactamase inhibitor combinations have no particular value against resistant pneumococci . Furthermore, penicillin-resistant pneumococci are often coresistant to macrolides, sulfa-based drugs, and tetracycline . Knowledge of how resistance is attained presumably will further the development of new strategies for treatment . The mechanisms of resistance of pneumococci and other common respiratory pathogens (particularly Haemophilus influenzae and Moraxella catarrhalis) to standard antimicrobial agents are examined in this report.

J Clin Microbiol, 1994 Jun, 32(6), 1594 - 6
Comparison of agar dilution, broth dilution, and disk diffusion testing of ampicillin against Haemophilus species by using in-house and commercially prepared media; Kohner PC et al.; An evaluation to determine the optimal method for the in vitro susceptibility testing of Haemophilus strains to ampicillin was undertaken . In our hands, in-house-prepared Haemophilus Test Medium used by either the broth macrodilution or agar dilution method produced the most consistent results, especially for beta-lactamase-negative, ampicillin-resistant H . influenzae strains.

Mol Cell Probes, 1994 Jun, 8(3), 205 - 8
Detection of the tetM determinant in Neisseria gonorrhoeae using a non-radioactively labelled oligonucleotide probe; Carballo M et al.; Three oligonucleotide probes, complementary to tetM sequences, were labelled non-radiometrically using the DIG-oligonucleotide tailing kit and evaluated for their specificity for the detection of plasmid mediated tetracycline resistance in Neisseria gonorrhoeae . Only Probe 3, 5'-GCT CAA CAA TTC TGT TCC AGC-3', was specific for tetM . It hybridized with the tetM-containing 25.2-MDa plasmids from all of the 232 TRNG and the 130 PP/TRNG isolates used in the study . Its sensitivity, determined by dot-blot hybridization, was 0.1 pg of pJ13 plasmid DNA or 10(4) cells . It did not hybridize with the DNA from non-PPNG, CMRNG and tetracycline susceptible isolates from seven other Neisseria species (N . meningitidis, N . subflava, N . cinerea, N . lactamica, N . sicca, N . mucosa, and N . flavescens), Moraxella spp . and Haemophilus influenzae . Probe 3 also hybridized to DNA of three tetracycline resistant P . magnus (MIC = 16 micrograms ml-1) isolates which presumptively carried the tetM determinant . Therefore, probe 3 can be used by reference laboratories as a confirmatory test for TRNG, as well as isolates from other genera containing the tetM determinant.

Eur J Clin Microbiol Infect Dis, 1994 Jun, 13(6), 481 - 9
Revised disk diffusion interpretive criteria for cefaclor, loracarbef, cefprozil and cefixime when testing Haemophilus influenzae on haemophilus test medium; Doern GV et al.; The aim of the current five-center collaborative study was to reassess the interpretive criteria for cefaclor, loracarbef, cefprozil and cefixime previously adopted or proposed by the National Committee for Clinical Laboratory Standards (NCCLS) for disk diffusion susceptibility tests with Haemophilus influenzae on Haemophilus Test Medium (HTM) agar . MICs and zones of inhibition were determined using NCCLS methods, HTM and two collections of strains of Haemophilus influenzae . One group of strains consisted of 118 stock organisms taken largely from various recent U.S . antibiotic resistance surveillance studies . The emphasis in this selected group of organisms was on strains that were beta-lactamase negative but ampicillin resistant (BLNAR) by some other mechanism . The second collection of test organisms consisted of 50 recent clinical isolates of Haemophilus influenzae obtained from each of the five participating study centers . This group was considered representative of the type of Haemophilus influenzae currently recovered from clinical sources in the USA . Frequency distribution assessment and error-rate bounded analysis of scattergram comparisons of MICs and zone sizes were used to develop the following zone diameters interpretive for disk diffusion susceptibility tests with Haemophilus influenzae on HTM agar: cefaclor, > or = 20 mm (susceptible, S) and < or = 16 mm (resistant, R); loracarbef, > or = 19 mm (S) and < or = 15 mm (R); and cefprozil, > 18 mm (S) and < 14 mm (R) . The respective MIC correlates for all three antimicrobial agents were < or = 8 micrograms/ml (S) and 32 micrograms/ml (R).(ABSTRACT TRUNCATED AT 250 WORDS)

Vet Microbiol, 1994 Jun, 40(3-4), 263 - 9
Rapid differentiation of avian Haemophilus-like strains by their whole-cell carbohydrate patterns; Mouahid M et al.; The whole-cell carbohydrate patterns of 14 Haemophilus-like strains isolated from diseased birds were examined by capillary gas chromatography/mass spectrometry . The analysis of the peracetylated aldononitrile and O-methyloxime derivatives allowed the differentiation between the phenotypically and genetically different isolates . Starting from a pure culture the procedure needs only 5 hours for the preparation of the samples and 30 minutes for subsequent analysis and is of special value for rapid diagnosis.

Pediatr Res, 1994 Jun, 35(6), 725 - 8
In vitro effect of dexamethasone, pentoxifylline, and anti-endotoxin monoclonal antibody on the release of proinflammatory mediators by human leukocytes stimulated with Haemophilus influenzae type B; van Furth AM et al.; The effects of dexamethasone, pentoxifylline, and MAb against endotoxin (HA-1A) on the release of various proinflammatory mediators, i.e . tumor necrosis factor-alpha (TNF), IL-1 beta, IL-8, and prostaglandin 2, by human leukocytes during stimulation with Haemophilus influenzae type B were studied . The results show that only monocytes, and thus neither lymphocytes nor granulocytes, release these mediators in response to H . influenzae . Dexamethasone inhibited the release of all of these mediators, whereas pentoxifylline only inhibited the release of TNF . HA-1A only reduced the release of IL-8 from adherent monocytes significantly and had no significant effect on the release of TNF, IL-1 beta, and prostaglandin E2 . In whole blood, no significant effect of HA-1A on the release of TNF, IL-1 beta, IL-8, and prostaglandin E2 was found . In summary, the results of this study demonstrate that dexamethasone is the most potent inhibitor of the release of proinflammatory mediators by monocytes induced by H . influenzae type B.

J Antimicrob Chemother, 1994 Jun, 33(6), 1209 - 18
Comparative efficacy and safety of cefprozil and amoxycillin/clavulanate in the treatment of acute otitis media in children; Gehanno P et al.; Cefprozil is a new oral cephalosporin with activity against the most common pathogens isolated in acute otitis media . This randomized study enrolled 361 patients (mean age 29 months) . Physical examination and culture via tympanocentesis were required less than 48 h before therapy . One hundred and ninety-one patients were evaluable for clinical efficacy; 99 received cefprozil (20 mg/kg/day bd) and 92 received amoxycillin/clavulanate (13.3 mg/kg/day tid) . Duration of treatment was 7-9 days for 81 patients, 10 days for 105 patients and 11-16 days for five patients . The treatment groups were comparable with respect to demographics, severity of infection and number of previous episodes . Clinical evaluations of efficacy were based on physical examination including otoscopy within a 14 day period after therapy . Satisfactory clinical responses were achieved in 84% of cefprozil-treated patients and 87% of amoxycillin/clavulanate-treated patients . Pathogens most commonly isolated included Haemophilus influenzae (33%) and Streptococcus pneumoniae (22%) . All 361 patients were evaluable for safety . Adverse clinical events were reported in 13% (24) of cefprozil-treated patients and 20% (36) of amoxycillin/clavulanate-treated patients . Cefprozil, administered twice a day, is comparable to a regimen of amoxycillin/clavulanate three times a day in the treatment of acute otitis media in children.

FEMS Immunol Med Microbiol, 1994 Jun, 9(1), 15 - 21
Detection of microbial surface antigens that bind Lewis(a) antigen; Essery SD et al.; There is evidence that the Lewis(a) blood group antigen is one of the receptors for a number of potentially pathogenic microorganisms . To determine how widely distributed the microbial adhesins are that bind this antigen, anti-idiotypic antibodies produced against monoclonal anti-Lewis(a) were used in coagglutination assays to screen a variety of species . The following were agglutinated: 7/7 strains of Staphylococcus aureus; 10/19 (53%) strains of Neisseria meningitidis; 8/13 (62%) strains of Haemophilus influenzae; 1/3 strains of Helicobacter pylori; 1/2 strains of Neisseria gonorrhoeae; 1/2 strains of Candida albicans . The application of the anti-idiotypic antibodies to studies of host cell receptors, isolation of adhesins and development of new epidemiological typing reagents is discussed.

Diagn Microbiol Infect Dis, 1994 Jun, 19(2), 93 - 9
Interpretive criteria for susceptibility tests with DU-6859a and FK-037 tested against Haemophilus influenzae and Neisseria gonorrhoeae; Jones RN et al.; Preliminary susceptibility testing interpretive criteria were determined for two investigational drugs, DU-6859a and FK-037, when tested against Haemophilus influenzae and Neisseria gonorrhoeae strains . National Committee for Clinical Laboratory Standards (NCCLS) methods with the Haemophilus Test Medium and GC agar base were utilized, and the study design conformed to the NCCLS M23-A guidelines . The proposed H . influenzae susceptibility testing criteria were for DU-6859a susceptible at < or = 1 microgram/ml (5-micrograms disk zone diameter correlate, > or = 19 mm) or < or = 2 micrograms/ml (disk zone diameter correlate, > or = 16 mm) and for FK-037 susceptible at < or = 2 micrograms/ml (30-micrograms disk zone diameter correlate, > or = 19 mm) . No other susceptibility categories were proposed . The gonococcal susceptibility testing criteria were for DU-6859a susceptible at < or = 0.12 microgram/ml (disk zone diameter correlate, > or = 34 mm) and for FK-037 susceptible at < or = 0.5 microgram/ml (disk zone diameter correlate, > or = 30 mm) and resistant at > 1 microgram/ml (disk zone diameter correlate, < or = 26 mm) . No resistant criterion was proposed for N . gonorrhoeae tests with DU-6859a . No interpretive discrepancies were observed between methods using these proposed testing criteria.

Scand J Dent Res, 1994 Jun, 102(3), 161 - 7
Use of a nonradioactive genetic probe identified, synthesized, and labeled in the polymerase chain reaction; Preus HR et al.; This study introduces a strategy to identify and produce sequences useful as genetic markers, or native genetic probes for DNA-DNA hybridization in bacterial strains where the genetics is not well described . Actinobacillus actinomy-cetemcomitans (A.a.) was used as an example . Fifty ng genomic DNA from A.a . ATCC 33384 and Haemophilus aphrophilus ATCC 33389 was amplified in a thermocycler using a single 10-mer primer . The PCR products were separated by electrophoresis on a 1% submarine agarose gel containing ethidium bromide and visualized by UV illumination, and the strain-specific amplitypes were compared . DNA from two bands, 0.9 and 4 kb, unique for the A.a . strain, was cut out, amplified under high stringency with the same primer and labeled by replacing 33.3 microM dTTP with digoxigenin-labeled dUTP in the reaction mixture . The labeled probe was then repeatedly used for hybridization to DNA from various A.a., H . aphrophilus, and other bacterial strains of the Pasteurellaceae family . The results showed that the 0.9-kb probe detected all A.a . tested, and distinguished it from other closely related bacterial species . We conclude that the described strategy is useful for identifying and selecting genetic sequences useful as genetic markers in A.a.

JAMA, 1994 May 25, 271(20), 1602 - 5
Adverse events associated with childhood vaccines other than pertussis and rubella . Summary of a report from the Institute of Medicine; Stratton KR et al.; In September 1993, the Institute of Medicine released a report entitled Adverse Events Associated With Childhood Vaccines: Evidence Bearing on Causality . The report examined putative serious adverse consequences associated with administration of diphtheria and tetanus toxoids; measles, mumps, and measles-mumps-rubella vaccines; oral polio vaccine and inactivated polio vaccine; hepatitis B vaccines; and Haemophilus influenzae type b (Hib) vaccines . The committee spent 18 months reviewing all available scientific and medical data, from individual case reports (published and unpublished) to controlled clinical trials . The committee found that the evidence favored the rejection of a causal relation between diphtheria and tetanus toxoids and encephalopathy, infantile spasms, and sudden infant death syndrome, and between conjugate Hib vaccines and susceptibility to Hib disease . The committee found that the evidence favored acceptance of a causal relation between diphtheria and tetanus toxoids and Guillain-Barre syndrome and brachial neuritis, between measles vaccine and anaphylaxis, between oral polio vaccine and Guillain-Barre syndrome, and between unconjugated Hib vaccine and susceptibility to Hib disease . The committee found that the evidence established causality between diphtheria and tetanus toxoids and anaphylaxis, between measles vaccine and death from measles vaccine-strain viral infection, between measles-mumps-rubella vaccine and thrombocytopenia and anaphylaxis, between oral polio vaccine and poliomyelitis and death from polio vaccine-strain viral infection, and between hepatitis B vaccine and anaphylaxis . For five vaccine-related adverse events, there was no evidence identified . For the remaining 33 vaccine-related adverse events, the evidence was inadequate to accept or reject a causal relation.

J Immunol, 1994 May 15, 152(10), 5009 - 13
Induction of a protective human polysaccharide-specific antibody response in hu-PBL SCID mice by idiotypic vaccination; Reason DC et al.; The human Ab repertoire to the Haemophilus influenzae type b (Hib) polysaccharide (PS) is dominated by Abs that use the kappa II-A2 VL region and that express an idiotype (Id) designated Hibld-1 . In this study we determined whether a human Hib PS-specific Ab response could be induced by idiotypic manipulation . We prepared a bispecific vaccine consisting of the F(ab')2 fragment of a mAb specific for Hibld-1, coupled to the F(ab')2 fragment of a mAb specific for CD3, a component of the TCR complex . This bispecific idiotypic vaccine stimulated production of human Abs to Hib PS in severe combined immunodeficient mice engrafted with normal human adult PBLs . The induced Abs uniformly expressed Hibld-1 and protected neonatal rats from Hib bacteremia . Experiments using additional conjugates demonstrated that covalent coupling of the CD3-specific moiety to the anti-Id was required for immunogenicity in this model, a result suggesting that engagement of B cell Id and proximate delivery of T cell signals are both necessary for B cell activation and differentiation . These findings demonstrate that human Ids can serve as targets for induction of a protective anti-PS Ab response.

FEMS Microbiol Lett, 1994 May 15, 118(3), 243 - 8
Binding of human hemoglobin by Haemophilus influenzae; Frangipane ME et al.; Binding of biotinylated human hemoglobin to Haemophilus influenzae was detected when organisms were grown in heme-deplete, but not heme-replete, conditions . Hemoglobin binding was completely inhibited by a 100-fold excess of unlabelled human hemoglobin or human hemoglobin complexed with human haptoglobin . Binding was only partially inhibited by rat hemoglobin, bovine hemoglobin, human globin, and bovine globin, and not at all by heme, human serum albumin, bovine serum albumin, human transferrin, or myoglobin . Hemoglobin binding was saturable at 16-20 ng of hemoglobin per 10(9) cfu . Binding of human hemoglobin was detected in serotypes a-f and serologically non-typable strains of H . influenzae, as well as Haemophilus haemolyticus but not Haemophilus parainfluenzae, Haemophilus aphrophilus, Haemophilus parahaemolyticus, or Escherichia coli.

J Mol Biol, 1994 May 13, 238(4), 626 - 9
Crystallization and preliminary crystallographic analysis of a DNA (cytosine-5)-methyltransferase from Haemophilus aegyptius bound covalently to DNA; Reinisch KM et al.; A DNA (cytosine)-5-methyltransferase from Haemophilus aegyptius (M.Hae III), which catalyzes methyl transfer from S-adenosyl-L-methionine to DNA, has been crystallized as a covalent complex with a suicide oligonucleotide substrate . Crystals of the co-complex were grown by vapor diffusion with hanging droplets, using polyethylene glycol 3500 as the precipitant . The crystals belong to the orthorhombic space group P2(1)2(1)2(1); the unit cell parameters are a = 57.6 A, b = 108.0 A, c = 155.8 A with two protein-DNA complexes in the asymmetric unit . Complete sets of native and derivative data have been collected to 2.7 A using a laboratory source.

Gene, 1994 May 3, 142(1), 9 - 15
Organization and sequence of the HpaII restriction-modification system and adjacent genes; Kulakauskas S et al.; We report the organization of the HpaII restriction and modification (R-M) system from Haemophilus parainfluenzae (recognition sequence: 5'...CCGG...3'), the sequence of the gene coding for the HpaII restriction endonuclease, and the sequence of the upstream flanking DNA . The HpaII system comprises two genes, hpaIIM, coding for the methyltransferase (MTase; 358 amino acids (aa), 40.4 kDa: product, Cm5CGG), and hpaIIR, coding for the restriction endonuclease (ENase; 358 aa, 40.9 kDa: product, C'CGG) . The genes are adjacent, they have the same orientation, and they occur in the order hpaIIM then hpaIIR . The ENase bears little as sequence similarity to the isoschizomeric R.BsuFI and R.MspI ENases . Upstream of, and partly overlapping hpaIIM is the coding sequence for a 141-aa protein that resembles the very-short-patch-repair endonuclease (Vsr) of Escherichia coli . Upstream of that is the coding sequence for a protein that resembles valyl-tRNA synthetase (ValS).

Am J Physiol, 1994 May, 266(5 Pt 2), H1755 - 61
Cerebrovascular responsiveness to CO2 in Haemophilus influenzae type b meningitis in rabbits; Slater AJ et al.; The effect of experimental meningitis on regional cerebral blood flow (rCBF), cerebral metabolic rate for oxygen (CMRO2), and cerebrovascular responsiveness to CO2 was determined in pentobarbital-anesthetized rabbits . The animals were inoculated intracisternally with saline (control) or log-phase Haemophilus influenzae type b (Hib) . Eighteen hours later rCBF was determined with radiolabeled microspheres at normocapnia, hypocapnia, and hypercapnia . Cerebrovascular responses to hypocapnia and hypercapnia were assessed by calculating the change in cerebrovascular resistance per millimeter mercury change in PaCO2 . At all CO2 levels, meningitis (M) was associated with elevated CBF compared with control (C: 47.5 +/- 3.0, M: 60.9 +/- 4.5 ml.100 g-1.min-1 at normocapnia, P < 0.01) . Regional differences were present . In forebrain, the hyperemia in meningitis was confined to the superficial cortical grey matter . When compared with control, meningitis was not associated with altered vasoreactivity during hypocapnia (C: -0.026 +/- 0.006, M: -0.026 +/- 0.008 mmHg.ml-1 x 100 g-1.min-1.mmHg PaCO2(-1)) or hypercapnia (C: -0.037 +/- 0.004, M: -0.026 +/- 0.008 mmHg.ml-1 x 100 g.min.mmHg PaCO2(-1)) . CMRO2 in meningitis was not significantly different from control (C: 3.53 +/- 0.29, M: 3.51 +/- 0.22 ml O2.100 g-1.min-1) . These findings indicate that cerebrovascular responsiveness to CO2 is preserved in experimental Hib meningitis . Furthermore, enhanced CBF together with unchanged CMRO2 indicates that "luxury" cerebral perfusion is present in this model of bacterial meningitis.

J Bacteriol, 1994 May, 176(10), 2914 - 21
A peroxide/ascorbate-inducible catalase from Haemophilus influenzae is homologous to the Escherichia coli katE gene product; Bishai WR et al.; Bacterial catalases are induced by exposure to peroxide (e.g., Escherichia coli katG) or entry into stationary phase (e.g., E . coli katE) . To study regulatory systems in Haemophilus influenzae, we complemented an E . coli rpoS mutant, which is unable to induce katE in stationary phase, with a plasmid library of H . influenzae Rd- chromosomal DNA . Nineteen complementing clones with a catalase-positive phenotype were obtained and characterized after screening about 10(5) transformants . All carried the same structural gene for an H . influenzae catalase . The DNA sequence of this gene, called hktE, encodes a 508-amino-acid polypeptide with strong homology to eukaryotic catalases and E . coli katE . However, hktE is regulated like E . coli katG, with catalase activity increasing 10-fold and hktE mRNA levels increasing 4-fold upon exposure to ascorbic acid, which serves to generate hydrogen peroxide . Mutations in the known global regulatory genes of H . influenzae--crp, cya, and sxy--do not affect the inducibility of hktE . The hktE gene maps to a 225-kb segment of the H . influenzae chromosome in a region encoding resistance to spectinomycin.

J Infect Dis, 1994 May, 169(5), 1146 - 50
Experimental human infection with Haemophilus ducreyi; Spinola SM et al.; Four subjects were experimentally infected with Haemophilus ducreyi . Lesions developed only at sites where live bacteria were inoculated on abraded skin . No subject developed fever, lymphadenopathy, or disseminated infection during a 3-day observation period . Two subjects who were rechallenged 2 months after initial infection also developed lesions . The amount of H . ducreyi recovered from 10 of 12 biopsies that were semiquantitatively cultured varied widely . Similar histologic features were present in initial and second infections . The epidermis contained pustules; the dermis contained an infiltrate of T cells and macrophages and reactive endothelial cells . Keratinocytes and T cells expressed HLA-DR, consistent with a delayed-type hypersensitivity response . The subjects did not mount humoral responses to bacterial proteins and to lipooligosaccharides after primary and secondary challenges . Thus, human experimental infection with H . ducreyi is well tolerated and safe . Recruitment of T cells and macrophages into chancroid lesions may partially explain the association between chancroid and human immunodeficiency virus transmission.

Infect Immun, 1994 May, 62(5), 1776 - 86
Variable region sequences and idiotypic expression of a protective human immunoglobulin M antibody to capsular polysaccharides of Neisseria meningitidis group B and Escherichia coli K1; Azmi FH et al.; We determined the heavy (H)- and light (L)-chain variable (V) region nucleotide and translated amino acid sequences of the human immunoglobulin M(kappa) monoclonal antibody (MAb) 5E1, which is specific for the polysaccharide capsule of Escherichia coli K1 and Neisseria meningitidis group B (poly{alpha(2-->8)-N-acetylneuraminic acid}) and which is protective in animal models of infection . The 5E1 VH gene is a member of the VHIIIb family and is 97% homologous to the 9.1 germ line gene . The 5E1 VL gene is a member of the kappa I subgroup and is 98% homologous to the germ line gene, 15A, also known as KLO12 . The VL and/or VH genes used by 5E1 are highly homologous to the V genes encoding antibodies to the Haemophilus influenzae type b polysaccharide and to antibodies reactive with self-antigens such as erythrocyte "i," DNA, and thyroid peroxidase . We also produced three murine anti-idiotype (Id) MAbs against 5E1 . All three anti-Ids recognize a minor subset of antimeningococcal B polysaccharide antibodies present in serum from normal adults . Two of the anti-Ids define distinct Ids associated with antibodies having kappa I-15A V regions . These 15A-associated Ids are expressed by some heterologous human antimeningococcal B polysaccharide MAbs, and they also are independently expressed by two human MAbs that are specific for either the H . influenzae b polysaccharide or the i erythrocyte antigen and that utilize the kappa I-15A V region . Taken together, these data indicate that the 5E1 antibody uses V regions that recur in the human antibody repertoires to this polysaccharide and to structurally dissimilar polysaccharides and autoantigens . Thus, the poor immunogenicity of poly{alpha(2-->8)-N-acetylneuraminic acid} cannot be explained by the unavailability of certain critical VH and VL genes required for generation of antibody response.

Infect Immun, 1994 May, 62(5), 1710 - 8
Synergistic effect of adenovirus type 1 and nontypeable Haemophilus influenzae in a chinchilla model of experimental otitis media; Suzuki K et al.; We recently reported the development of a chinchilla model of experimental otitis media (OM) that uses a pediatric clinical isolate of adenovirus type 1 (4) and in which an active infection with the wild-type strain was demonstrated . To expand upon these findings, this study was designed to determine whether we could demonstrate adenovirus infection-induced predisposition to bacterial OM in the chinchilla, as has been shown in human epidemiological studies (D . A . Clements, F . W . Henderson, and E . C . Neebe, p . 27-29, in D . J . Lim, C . D . Bluestone, J . O . Klein, D . J . Nelson, and P . L . Ogra, ed., Proceedings of the Fifth International Symposium on Recent Advances in Otitis Media, 1993; F . W . Henderson, A . M . Collier, M . A . Sanyai, et al., N . Engl . J . Med . 306:1377-1383, 1982) . In addition, we were interested in determining whether altering the order of pathogen acquisition would further affect the outcome of disease incidence and severity . Toward this end, cohorts of chinchillas were inoculated intranasally with a strain of nontypeable Haemophilus influenzae (NTHi) (86-028NP) which colonizes the chinchilla nasopharynx but does not consistently induce culture-positive OM when inoculated intranasally (L . O . Bakaletz, T . M . Hoepf, D . J . Lim, and B . Tallan, Abstr . 90th Annu . Meet . Am . Soc . Microbiol . 1990, abstr . B-66, p . 37, 1990), adenovirus type 1 and then inoculated 7 days later with NTHi, NTHi and then inoculated 7 days later with adenovirus type 1, or both pathogens concurrently . All cohorts were observed over a 35-day period and assessed for incidence and severity of OM by several methodologies . The data collectively indicated that all animals receiving both pathogens developed OM of greater severity than those receiving only a single agent . Adenovirus inoculation followed 7 days later by NTHi inoculation was the order of pathogen acquisition which induced the most prolonged presence of NTHi in both the nasopharynx and the middle ear, the most severe tympanic membrane inflammation overall, and the most significant damage to and altered function of both middle ear and eustachian tube mucosae.

Minerva Pediatr, 1994 May, 46(5), 193 - 200
{Bacterial meningitis . Review of literature and retrospective study of 208 cases observed}; Ceccarelli M et al.; Bacterial meningitis is a particularly dangerous infection of the central nervous system involving quite a number of mortal cases and frequent neurological sequelae . Etiology varies in relation to the patient's age . In the first 2 months of life Streptococcus B, Listeria monocytogenes, Escherichia coli and other Gram negative enteric bacilli are more frequently isolated while in older children Haemophilus influenzae, Neisseria meningitidis and Streptococcus pneumoniae are more common . Clinical symptoms take a different form according to the patient's age: symptoms of a general kind prevail in the first 2 months of life while in older children signs of meningeal irritation predominate . In a review of the survey of cases of bacterial meningitis observed at the Clinica Pediatrica in Pisa from 1970 to July 1993, with a retrospective research, 208 patients have been examined, considering age, etiology, clinical course especially observing the course of temperature, liquor characteristics, normalisation of the index of phlogosis, mortality and neurological sequelae . In the last ten years the availability of 3rd generation cephalosporin has provided the possibility of comparing two groups of patients of an age ranging between 1 month and 14 years . Twenty cases were treated with ampicillin and chloramphenicol and 30 cases with cephalosporins the evaluation made considering the course of temperature, the normalization of the liquor index has revealed a more favourable clinical course in the second group of patients.

Acta Otolaryngol, 1994 May, 114(3), 289 - 94
Nontypeable and encapsulated Haemophilus influenzae yield different clinical courses of experimental otitis media; Melhus A et al.; Middle ears of male Sprague-Dawley rats were injected with suspensions of thirteen Haemophilus influenzae strains of different sero- and biotypes and at various concentrations . Systemic and local changes were monitored by clinical observations, otomicroscopy, and analysis of bacterial samples from blood and middle ears . Two patterns of response were recognized, a nontypeable and an encapsulated pattern . The nontypeable H . influenzae middle ear infection required a high bacterial dose and was well past its peak 8 days after challenge, when the encapsulated H . influenzae otitis media was still purulent . The most severe infections were caused by H . influenzae type b strains . The overall mortality rate was zero and the animals recovered without permanent deterioration or otomicroscopically discernable changes . The results of this study show the rat to be a suitable animal model for the study of H . influenzae otitis media.

Pediatr Infect Dis J, 1994 May, 13(5), 362 - 7
Decline of Haemophilus influenzae type b disease in a region of high risk: impact of passive and active immunization; Singleton RJ et al.; Haemophilus influenzae type b (Hib) is a major cause of serious childhood bacterial infections . Before 1989 Alaska Native infants in the Yukon Kuskokwim Delta (YKD) had the highest recorded Hib disease rate, 2960:100,000 in children less than 1 year of age with 6 to 35 (mean, 13) cases/year between 1980 and 1988 . In July, 1989, Alaska Area Native Health Service initiated a passive immunization project in the YKD using bacterial polysaccharide immunoglobulin (BPIG) administered at 3-month intervals to prevent Hib infections in infants less than 13 months of age . On January 1, 1991, after licensure of Hib conjugate vaccines for infants, the program was modified to a passive-active strategy using BPIG at birth and PedvaxHIB at 2, 4 and 12 months of age . Between July 1, 1989, and December 31, 1990, 80% of YKD children less than 1 year of age received at least 1 dose of BPIG . During this period there were 7 Hib cases in this age group, but only 1 of the cases had received any BPIG . Between January 1, 1991, and December 31, 1992, 4 Hib cases occurred in 2 YKD children . During the combined period, July 1, 1989, to December 31, 1992, the incidence of Hib disease for infants less than 1 year of age was 302:100,000 . A dramatic decrease in Hib disease was observed in this high incidence region concurrent with implementation of passive and passive-active immunization strategies.

Pediatr Infect Dis J, 1994 May, 13(5), 356 - 62
Safety and immunogenicity in young infants of Haemophilus b-tetanus protein conjugate vaccine, mixed in the same syringe with diphtheria-tetanus-pertussis-enhanced inactivated poliovirus vaccine; Dagan R et al.; Because inactivated poliovirus vaccine (IPV) and Haemophilus influenzae b vaccine are advised in many programs and may be incorporated further in other programs, we undertook a study to determine whether the administration of a tetravalent preparation of diphtheria-tetanus-pertussis-IPV mixed in one syringe with tetanus-conjugate H . influenzae b vaccine (DTP-IPV-PRPT) is associated with increased reactogenicity or interference with immunogenicity of individual vaccine components . In a placebo-controlled, double blind study, a total of 161 infants were enrolled (80 DTP-IPV-PRPT and 81 DTP-IPV-placebo) . Vaccine was administered at 2, 4 and 6 months of age . Oral poliovirus vaccine was added at 7 months of age and a booster of oral poliovirus vaccine and DTP-IPV was also administered at 12 months of age, according to the policy in Israel . Local and systemic side effects were similar in both groups except for irritability after the second dose and use of acetaminophen which we observed slightly but significantly more often in the DTP-IPV-PRPT recipients . After the third dose the geometric mean titers of anti-polyribosyl-ribitol phosphate antibodies were 3.7 and 0.05 micrograms/ml in the PRPT and placebo groups, respectively (P < 0.001) . Higher tetanus antitoxin titers were observed among recipients of DPT-IPV-placebo (1.1 IU/ml vs . 0.7 IU/ml, P = 0.003) . A similar trend was found for pertussis agglutinin titers (93.4 vs . 65.4, P = 0.054) . No difference was observed for anti-diphtheria toxoid and poliovirus 1, 2, and 3.(ABSTRACT TRUNCATED AT 250 WORDS)

Pediatr Infect Dis J, 1994 May, 13(5), 348 - 55
Safety and immunogenicity of Haemophilus influenzae vaccine (tetanus toxoid conjugate) administered concurrently or combined with diphtheria and tetanus toxoids, pertussis vaccine and inactivated poliomyelitis vaccine to healthy infants at two, four and six months of age; Gold R et al.; The safety and immunogenicity of Haemophilus influenzae vaccine (tetanus toxoid conjugate (PRP-T) administered concurrently in separate sites or mixed in the same syringe with diphtheria and tetanus toxoids, pertussis vaccine and inactivated poliomyelitis vaccine were assessed in 439 infants at 2, 4 and 6 months of age . The proportions with local redness, tenderness and swelling in the separate and combined groups were 18% vs . 11% (P < 0.001), 27% vs . 24% and 15% vs . 13%, respectively . Systemic reactions occurred at similar rates in both groups . The combined vaccine induced tetanus and diphtheria antitoxin titers > or = 0.01 IU/ml in 99.5 and 99.1% of infants, pertussis agglutinin titers > or = 64 in 92.4%, anti-polyribosylribitol phosphate titers > or = 0.15 microgram/ml in 93.8% and > or = 1.0 microgram/ml in 75% and polio-neutralizing titers > or = 8 in > 98% of infants . However, antibody concentrations to PRP-T, some pertussis antigens and tetanus toxoid were significantly lower after combined than after separate injections of DPT/diphtheria and tetanus toxoids, pertussis vaccine and inactivated poliomyelitis vaccine and PRP-T . The clinical significance of these differences is not known, but the interactions observed among the components of the pentavalent vaccine may be of concern because they might influence antibody persistence until the fourth dose is administered.

Ann Pharmacother, 1994 May, 28(5), 633 - 42
Update on childhood immunizations; de Clavijo IV et al.; OBJECTIVE: To provide an overview of childhood immunizations with emphasis in new recommendations, as well as recent vaccine developments and special populations . DATA SOURCES: English language literature identified via a MEDLINE search . Additional references were obtained from cited references . STUDY SELECTION AND DATA EXTRACTION: Original articles, reviews, and official publications were used to obtain the most accurate data on safety and efficacy of available pediatric vaccines, as well as current recommendations for their use . DATA SYNTHESIS: Immunizations have been an area of vigorous research for several years . New vaccines have been developed by improving older products to maximize immunogenicity and minimize adverse effects . Some of these novel vaccines, like the Haemophilus influenzae type b conjugate vaccines (HibCV), have already contributed significantly to the prevention of diseases in childhood . New recommendations have been issued to help speed this process . Adverse effects of routine immunizations are generally mild and transient . CONCLUSIONS: The development of new effective and safe vaccines for children is an important step in the global eradication of contagious diseases . A new generation of combination vaccines has started with the combination of the diphtheria-tetanus-pertussis vaccine and HibCV . Some other combined products are yet to come that would eventually make immunization schedules more cost-effective and improve compliance rates . Our colleagues in the community and in the ambulatory care setting must actively participate in the implementation of vaccination programs and provide education to parents regarding all aspects of the immunization process.

Antimicrob Agents Chemother, 1994 May, 38(5), 973 - 80
Use of biotinylated beta-lactams and chemiluminescence for study and purification of penicillin-binding proteins in bacteria; Dargis M et al.; A new reagent for the detection of penicillin-binding proteins (PBPs) was developed . An N-hydroxysuccinimide ester of biotin was used to tag beta-lactam antibiotics with free side chain amino groups such as ampicillin (BIO-AMP), 6-aminopenicillanic acid (BIO-APA), and 7-aminocephalosporanic acid (BIO-ACA) . Bacterial PBPs from cells or isolated cytoplasmic membranes of Escherichia coli, Haemophilus influenzae, Staphylococcus aureus, and Streptococcus pneumoniae were labeled with BIO-AMP, subjected to electrophoresis on sodium dodecyl sulfate (SDS)-polyacrylamide gels, and transferred onto nitrocellulose membranes . Electrophoretic PBP profiles were detected on blots, using colorimetric or chemiluminescence systems, on the basis of the interaction of BIO-AMP-PBP complexes and a streptavidin-peroxidase conjugate . The chemiluminescent reaction permitted a high sensitivity of detection, and PBP profiles could be determined within seconds . All PBP profiles were similar to those obtained with a traditional PBP labeling technique with 125I-labeled penicillin V, except that an additional unidentified PBP (approximately 55,000 Da) was labeled with BIO-AMP in E . coli and H . influenzae . Differences in the intensities of labeling for specific PBPs were observed between the chemiluminescent and radioactive labeling agents and were attributed to the differences in their affinities for PBPs . Similarly, BIO-AMP, BIO-APA, and BIO-ACA produced different PBP profiles . We also investigated the use of BIO-AMP in PBP purification . BIO-AMP-PBP complexes from a mixture of H . influenzae proteins were allowed to bind to avidin immobilized on an agarose support in a microcentrifuge tube . After several washes in the presence of salts, PBPs were eluted by boiling and treatment with SDS . The eluted proteins were separated by electrophoresis on SDS-polyacrylamide gels, and biotinylated proteins were identified on blots by a chemiluminescence reaction . Biotinylation of beta-lactams is rapid, safe, and inexpensive . Our results demonstrate the feasibility of using biotinylated beta-lactams as nonradioactive reagents for the study of PBPs and for the purification of these proteins.

Antimicrob Agents Chemother, 1994 May, 38(5), 1118 - 22
In vitro and in vivo antibacterial activities of KRM-1648 and KRM-1657, new rifamycin derivatives; Fujii K et al.; The in vitro and in vivo antibacterial activities of the new rifamycin derivatives KRM-1648 and KRM-1657 were compared with those of rifampin . Rifabutin, ciprofloxacin, and clarithromycin were also tested for reference . The respective MICs of KRM-1648 and KRM-1657 for 90% of the strains tested (MIC90S) were 0.016 and 0.0078 microgram/ml, respectively, for methicillin-susceptible Staphylococcus aureus, 0.016 and 0.0039 microgram/ml, respectively, for methicillin-resistant S . aureus, and 0.0625 and 0.016 microgram/ml, respectively, for methicillin- and quinolone-resistant S . aureus . These MIC90S of KRM-1657 were equal to or 2- to 64-fold lower than those of rifampin . KRM-1648 and KRM-1657 with MIC90S of between 0.002 and 0.078 microgram/ml were 2- to 128-fold more active than rifampin against Staphylococcus epidermidis and Streptococcus species, including Streptococcus pneumoniae and Streptococcus pyogenes . The MIC90S of KRM-1657 for Haemophilus influenzae and Neisseria gonorrhoeae were 0.25 and 0.1 microgram/ml, respectively; KRM-1657 was almost as active as rifampin and was 8- to 16-fold more active than KRM-1648 against these strains . The frequency of occurrence of spontaneous mutations to resistance to KRM-1648 and KRM-1657 was equal to that to rifampin . Against systemic infection with S . aureus in mice, the efficacies of KRM-1648 and KRM-1657 were comparable to that of rifampin.

J Comp Pathol, 1994 May, 110(4), 329 - 39
Pneumonia in pigs infected with pseudorabies virus and Haemophilus parasuis serovar 4; Narita M et al.; Six HPCD (hysterectomy-produced, colostrum-deprived) pigs were inoculated endobronchially with pseudorabies virus (PRV) in the right caudal lobe by means of a bronchoscope . Two pigs, killed on days 5 and 7, had severe purulent pneumonia in the right caudal lobe, associated with an accidental Haemophilus parasuis serovar 4 infection . The three surviving animals were treated with antibiotics . The pigs infected with PRV had necrotizing bronchiolitis and alveolitis . PRV antigen was closely associated with necrotic foci, and was sometimes surrounded by profuse H . parasuis antigen . PRV antigen and IgG- and IgA-containing cells were also detected in bronchioalveolar lavage fluid . These results suggested that the PRV infection destroyed respiratory epithelial cells and allowed H . parasuis to proliferate in the lungs.

Urologe A, 1994 May, 33(3), 188 - 95
{Urethro-adnexitis in the man and acute urethral syndrome in the woman . Microbiological and immunologic studies of etiologic classification}; Schiefer HG et al.; Both common pathogens and unconventional, fastidious bacteria, viruses, parasites, and fungi are causative agents in male urethro-adnexitis and in female acute urethral syndrome . Uropathogens, Neisseria gonorrhoeae, Treponema pallidum, Mycobacterium tuberculosis, Chlamydia trachomatis, Mycoplasma spp., Haemophilus ducreyi, Calymmatobacterium granulomatis, Gardnerella vaginalis, anaerobic bacteria, Herpes simplex virus type II (HSV II), papillomaviruses (HPV), Trichomonas vaginalis and Candida spp . must be considered . The various diagnostic procedures and criteria applied for aetiological classification in cases of balanitis, urethritis, prostatitis, epididymitis, orchitis, and acute urethral syndrome are reviewed and evaluated.

Enferm Infecc Microbiol Clin, 1994 May, 12(5), 235 - 40
{Isolation of Haemophilus spp . from samples of pleural fluid: 11 years' review}; Olsina M et al.; BACKGROUND: The incidence and significance of Haemophilus spp . in plural fluid were retrospectively studied over a period of 11 years . METHODS: Gram staining and culture in aerobic and anaerobic media was performed in 7517 pleural fluids . Haemophilus spp . was identified with the AMS-Vitek and/or conventional systems . The presence of beta-lactamase was assessed by this method or by the acidometric method . RESULTS: Haemophilus spp . was identified in 72 samples (0.9%) corresponding to 37 patients . The medical records of 22 were reviewed . The most common species isolated was H . influenzae . Gram stain exam was positive on 28 occasions (38.8%), with gram-negative bacilli being observed in 78.5% . A pure culture was obtained in 43 samples with anaerobic bacteria associated in 18% of the cases . Only 10 strains (16.4%) produced beta-lactamase . No predominance of any determined biotype was observed . Most of the patients were male with a mean age of 59.2 years (range: 2-82) . Seventeen patients presented with community-acquired pneumonia, as well as tuberculous sequelae, pneumonectomy and pulmonary and/or upper GI truct neoplasms . All were treated with antibiotics, beta-lactam drugs alone or with aminoglycosides . Half of them also required surgical drainage . Four patients died in relation with the underlying disease . CONCLUSIONS: Haemophilus spp . was isolated in 7.7% of 7517 samples of pleural fluid . This finding may indicate the coexistence of an underlying thoracic disease of neoplastic origin.

J Pediatr Surg, 1994 May, 29(5), 667 - 70
A bacteriologic basis for the evolution and severity of empyema; Bhattacharyya N et al.; The management of pediatric empyema remains controversial . An experimental study was undertaken to evaluate the role of bacteria in the evolution and severity of empyema, using specific bacteria that are pathogens of empyema in children . A rabbit model was used . The groups were Haemophilus influenzae (n = 9), Bacteroides fragilis (n = 8), the combination (n = 12), Staphylococcus aureus (n = 6), and control (n = 6) . The total bacterial inoculum (10(8)) was constant . Diagnostic thoracentesis was performed at regular intervals . Characteristics of the empyema were evaluated when the rabbits were killed (at 4, 7, and 10 days) . Most rabbits other than those of the mixed-bacteria group cleared the bacteria from their pleural cavities . Eleven of 12 mixed-bacteria animals had multiloculated empyemas; only one resolved spontaneously . In the other groups, the tendency was toward unilocular empyemas, which resolved by the 10th day in one third of the H influenzae animals, two thirds of the Bacteroides fragilis animals, and half the S aureus animals . The empyemas that persisted until the 10th day were in the exudative or fibrinopurulent stage, except for those of the mixed-bacteria group, all of which were in the advanced organizing stage . The amount of pleural debris and the degree of organization were significantly greater for the mixed bacteria group (P > .01) . These findings support the clinical management of monobacterial empyema by simple drainage, whereas mixed aerobic-anaerobic empyemas may require more aggressive drainage procedures.

Isr J Med Sci, 1994 May-Jun, 30(5-6), 408 - 11
Rebound fever in bacterial meningitis: role of dexamethasone dosage; Pichard E et al.; Since introducing dexamethasone as adjuvant therapy to antibiotics for bacterial meningitis, we have noticed an increase in the number of cases with secondary fever . Therefore, we performed a retrospective analysis of the 19 consecutive cases occurring during the last 5 years . Six patients received dexamethasone for 4 days, 5 received a 2-day course of dexamethasone and 8 received antibiotics only . The etiologic agents included: Haemophilus influenzae (in 11 patients), Streptococcus pneumoniae (in 6) and Neisseria meningitidis (in 2) . Among the 11 patients receiving dexamethasone, the fever remitted within 1-5 days (average 1.7 +/- 1.2) while among the 8 patients not receiving dexamethasone the initial fever lasted 1-17 days (average 5.3 +/- 1.7) (P = 0.009) . There was secondary fever without a definable clinical or bacteriological source in 9 of 11 patients receiving dexamethasone and in none of those who were treated without steroids (P < 0.001) . The secondary fever among those who received dexamethasone for 2 days was low grade (37.5 degrees-38 degrees C) and lasted for 1 day only, while among those who received dexamethasone for 4 days it was > 38 degrees C and more prolonged (7 +/- 2.3 days) (P < 0.03) . Total days of fever were 2.2 +/- 0.2 days when dexamethasone was administered for 2 days only vs . 7.8 +/- 1.7 for the patients in each of the two other groups (P < 0.03) . The relatively benign course with the 2-day regimen of dexamethasone makes us consider whether a 2-day course of dexamethasone might save costly evaluations of secondary fever and much concern . Further studies are needed in order to document the efficacy of this regimen in reducing neurological sequelae.

Isr J Med Sci, 1994 May-Jun, 30(5-6), 351 - 5
Epidemiology of pediatric meningitis caused by Haemophilus influenzae B, Streptococcus pneumoniae and Neisseria meningitidis in Israel; Dagan R; Bacterial meningitis remains a serious cause of morbidity and mortality in childhood . We report 3 year data on meningitis caused by Haemophilus influenzae b, Streptococcus pneumoniae and Neisseria meningitidis in Israeli children younger than 13 years of age . The data were obtained prospectively through an active surveillance system involving all 25 centers in which children are hospitalized . A case was defined by: a) culture positive cerebrospinal fluid; or b) positive blood culture with > 10 cells . During the study period, 482 cases of meningitis due to the three organisms were identified . Of these, 58%, 20% and 22% were caused by H . influenzae b, S . pneumoniae and N . meningitidis, respectively . The male/female ratio was 1.5:1 . An over-representation of the non-Jewish population was seen only in cases caused by S . pneumoniae . The median age was 11 months and 59% of all cases occurred by the age of 12 months . The median age was 10, 12 and 36 months and the age-specific incidence for children aged 0-4 years was 18.5, 5.3 and 5.2 per 100,000, respectively, for H . influenzae b, S . pneumoniae and N . meningitidis . The chance of being hospitalized with meningitis during the first 5 years of life was estimated at 146.2 per 100,000 . Meningitis was seasonal: 59% al all cases occurred during fall and winter and only 18% during summer . A total of 2,097 hospitalization days were required when extrapolated to a population in which 100,000 live births occur yearly . The case fatality rate was 2.2%, 5.9% and 6.3% for H . influenzae b, S . pneumoniae and N . meningitidis, respectively, with a higher fatality in females and non-Jews.

Arzneimittelforschung, 1994 May, 44(5), 668 - 70
{Comparative antibacterial activity of cefpodoxime against Haemophilus influenzae, Streptococcus pyogenes, Streptococcus pneumoniae and Moraxella catarrhalis}; Wallrauch-Schwarz C et al.; The antimicrobial activity of cefpodoxime (Podomexef, CAS 80210-62-4) against 236 clinical isolates of H . influenzae, Moraxella catarrhalis, Streptococcus pyogenes and Streptococcus pneumoniae was investigated and compared with that of another 8 commonly used oral antibiotics . beta-Lactamase negative, beta-lactamase positive and multiresistant strains of H . influenzae were inhibited by cefpodoxime at a concentration of 0.13 mg/l . 10% of Moraxella catarrhalis isolates were moderately susceptible to cefpodoxime, with minimum inhibitory concentration (MIC) of cefpodoxime ranging between 0.13 and 2.0 mg/l . All isolates of Streptococcus pyogenes and Streptococcus pneumoniae were susceptible to < or = 0.25 mg/l cefpodoxime . Cefpodoxime was clearly more active than the older oral cephalosporins against all species tested . The activity was comparable to that of cefixime against all species except Streptococcus pneumoniae, against which cefpodoxime was more active than cefixime.

Intensive Care Med, 1994 May, 20(5), 371 - 4
Relation between cytokines and routine laboratory data in children with septic shock and purpura; Hazelzet JA et al.; OBJECTIVE: To establish the relation between routine laboratory data (lactate, fibrinogen, CRP) and cytokines (TNF,IL-1 and -6) and to estimate their prognostic value in pediatric patients with severe infectious purpura on admission . DESIGN: Prospective study . SETTING: Pediatric intensive care unit (PICU) . PATIENTS: 17 children aged 5-172 months (median 46) were hospitalized in our PICU in 1989-90 with severe infectious purpura . Neisseria meningitidis was isolated in 15 children and Haemophilus influenzae in two . The patients were divided into 3 groups: non-shock, shock and severe shock leading to death . Shock was defined by standard criteria . MEASUREMENTS: Arterial blood was sampled for lactate, CRP, fibrinogen, TNF, and IL-1 and -6 on admission . The PRISM (pediatric risk of morality)-score was recorded . METHODS: Statistical analysis was performed with the Student's t-test using the logarithmic values of the cytokine concentration, and Spearman correlation analysis . RESULTS: According to the shock criteria, 9 patients were in shock of whom 4 did not survive . Significant differences existed between the 3 groups concerning lactate, TNF, and IL-6 . Fibrinogen, CRP, IL-1, and PRISM-score discriminated only between survivors and non-survivors . A highly significant correlation existed between cytokines, the PRISM-score and lactate (TNF: r = 0.69, IL-1: r = 0.56, IL-6: r = 0.65, PRISM: r = 0.65) . A significant inverse correlation existed between cytokines and CRP (TNF: r = -0.55, IL-1: r = -0.64, and IL-6: r = -0.56), and IL-6 and fibrinogen (r = -0.65) . CONCLUSION: These results show a significant correlation between cytokines and lactate, and lactate, TNF and IL-6 are closely associated with the severity of septic shock with purpura in children.

Sante, 1994 May-Jun, 4(3), 227 - 30
{Control of Haemophilus influenzae infections}; Guerin N; The results of all clinical trials and mass immunization programmes carried out over the past few years are extremely encouraging and should be the prelude to systematic immunization . Three vaccines that are immunogenic in infants over 6 weeks old, are now available: HbOC linked to diphtheria toxin, PRP-OMP linked to a meningococcus protein, and PRP-T linked to tetanus toxoid . Their safety has been demonstrated particularly when administration at a very early age before the period of risk . Efficacy has been demonstrated, even in population groups who do not respond well to non-conjugate vaccines . Immunogenicity persists even in unfavourable contexts such as individuals with sickle-cell anaemia or leukosis or a previous history of vaccine failure . The duration of immunity amply covers the period of risk and probably a longer because of the booster effect of natural infections . The possibility of combining Hib vaccine with other routine immunizations in infancy will reduce the cost of this additional immunization . Thus it is possible to envisage its integration into immunization programmes in developing countries . Cost/benefit studies show advantages . What is needed now is to achieve high immunization coverage, guaranteeing efficacy of immunization at national level, by ensuring that health personnel as well as families are fully informed about the seriousness of Hib infections and the good tolerance and efficacy of the conjugate vaccines.

Sante, 1994 May-Jun, 4(3), 183 - 7
{Towards a new vaccine economy?}; Poirot P et al.; When Jonas Salk announced in the mid-50s the availability of a new vaccine against poliomyelitis, the world had the impression that it was now controlling infectious diseases . In fact, the success of this vaccine has been considerable and although some innovations lead to the launch of vaccines against flu, measles, rubella or mumps, the world vaccine market remained remarkably stable till the mid-80s . However, since 1984 (launch of the hepatitis B vaccine) there have been very substantial changes and further change is expected in the next ten years in the world market . Today, big companies are making a concentrated supply: Pasteur Merieux with its subsidiary Connaught, SmithKline Beecham who acquired the Belgian company RIT, and Merck & Co . who is joining its forces with Pasteur Merieux . Medium sized and small companies remain and reflect the situation of the past, but must work hard to secure their long term existence eventhough the world demand is going to double before the year 2000 . Very substantial technological innovations explain to a large extent the development of the supply: progress in molecular biology, and particularly genetic engineering, lead to recombinant vaccines of which hepatitis B is the best example with worldwide sales in the range of $600 million a year . Similarly, conjugation technologies have allowed the development of new vaccines against meningitis, particularly Haemophilus influenzae type b . More recently, an efficacious vaccine against hepatitis A has been launched and many new products will be marketed in the next years against herpes, Lyme disease, and agents of other meningitis, etc.(ABSTRACT TRUNCATED AT 250 WORDS)

J Hosp Infect, 1994 May, 27(1), 17 - 27
A nosocomial outbreak due to non-encapsulated Haemophilus influenzae: analysis of plasmids coding for antibiotic resistance; Anderson JR et al.; An outbreak of infections with non-encapsulated Haemophilus influenzae, resistant to ampicillin, chloramphenicol, sulphonamide and tetracycline involved 13 elderly patients and three nurses on acute admission and care of the elderly wards . Thirty-two isolates were found to be indistinguishable on analysis of biotype, antibiogram, serotype and major outer membrane proteins (MOMP) . Plasmids could not be identified in the original isolates but after mating with a Rec A H . influenzae recipient, the resultant transconjugates were found to harbour either a 72 kilobase pair (kB) plasmid coding for resistance to chloramphenicol, ampicillin, sulphonamide and tetracycline or a 65 kB plasmid coding for resistance to chloramphenicol, ampicillin and sulphonamide . Both plasmids yielded virtually indistinguishable restriction digest patterns . This suggests that the tetracycline resistance gene (Tc gene) is a non-essential component of one basic plasmid responsible for the multiple antibiotic resistances seen in the strains recovered during the outbreak . This illustrates the value of plasmid profiles to compare strains of non-encapsulated H . influenzae, and suggests that plasmid restriction enzyme analysis is critical.

J Clin Microbiol, 1994 May, 32(5), 1308 - 11
Detection of Streptococcus pneumoniae in sputum samples by PCR; Gillespie SH et al.; A method for the detection of Streptococcus pneumoniae in sputum samples by PCR has been developed . The assay employs oligonucleotide primers specific for a portion of the autolysin gene lytA of S . pneumoniae . Other closely related streptococci, Haemophilus influenzae, and Moraxella catarrhalis do not give a positive result in the assay . The assay was capable of detecting between 10 and 100 CFU of S . pneumoniae in distilled water and 1.4 x 10(4) CFU/ml in simulated sputum samples . Sputum samples from 33 patients with acute pneumonia were collected and subjected to culture, PCR, and C-polysaccharide antigen detection by enzyme-linked immunosorbent assay (ELISA) . A significant isolate of S . pneumoniae was isolated from 14 patients, of which 13 were positive by PCR and C-polysaccharide antigen ELISA . No positive results were obtained for the 19 patients in whom other pathogens or upper respiratory tract floras only were isolated . The sensitivity of the autolysin PCR is 92.8%, the specificity is 100%, the predictive value of a positive result is 100%, and the predictive value of a negative result is 95% . This suggests that autolysin PCR is suitable for the detection of S . pneumoniae in clinical samples.

Infect Immun, 1994 May, 62(5), 2002 - 20
Role of fimbriae expressed by nontypeable Haemophilus influenzae in pathogenesis of and protection against otitis media and relatedness of the fimbrin subunit to outer membrane protein A; Sirakova T et al.; Nontypeable Haemophilus influenzae is a primary pathogen in both acute otitis media (OM) and chronic OM, yet the pathogenesis of this disease is not fully understood . Although fimbriae have been observed on all clinical OM isolates examined to date, their role in pathogenesis remains unclear . Therefore, the gene which codes for the fimbrial subunit protein (fimbrin) in nontypeable H . influenzae 1128 was isolated, cloned, and sequenced . The nucleotide sequence of the fimbrin gene was found to contain an open reading frame of 1,077 bp which would encode a mature fimbrin protein consisting of 338 amino acid with a calculated molecular mass of 36.4 kDa . The translated amino acid sequence was found to be homologous with various OmpA proteins of other gram-negative bacteria, and algorithmic analysis predicted that this protein is organized as a coiled coil . To directly test whether fimbriae are involved in pathogenesis, the fimbrin gene was disrupted, and the biological consequences of disruption were absence of both expression of the fimbrial appendage and the specific immunogold labeling thereof with antisera directed against isolated fimbrial protein, reduced adherence to human oropharyngeal cells in vitro, augmented clearance from the tympanum post-transbullar inoculation, and significantly reduced induction of OM post-intranasal inoculation in a chinchilla model compared with the fimbriated parent strain . We additionally find that either passive immunization or active immunization against isolated fimbrial protein confers partial protection against transbullar challenge . A Western blot (immunoblot) indicated a degree of serological relatedness among fimbrin proteins of 15 nontypeable and type b isolates . These data suggest that fimbrin could be useful as a component of a vaccine to protect against OM.

Pathol Biol (Paris), 1994 May, 42(5), 481 - 6
{Beta-lactamase-producing Haemophilus influenzae isolated in Portugal, 1989-1992}; Bajanca Lavado MP et al.; Within the framework of a national multicentric study between 1989 and 1992, 118 strains of betalactamase producing Haemophilus influenzae were isolated . Biotyping demonstrated the predominance of biotypes I, II and III, with 22, 36 and 24% of the strains, respectively . Encapsulated strains accounted for 13% of the total; all, but one, were serotype b . The antimicrobial susceptibility test (dilution method) of the 118 ampicillin--resistant strains showed: 33.9% resistance to tetracycline, 29.7% to chloramphenicol, 10.2% to erythromycin, 9.3% to trimethoprim, 0.8% to rifampicin, and 29.7% of multiresistance . All strains were susceptible to augmentin, cefotaxime, ceftriaxone and ceprofloxacin . Ninety strains were screened for resistant plasmids . A large plasmid (30-50 Mdal) was isolated in 38.9% of the strains and a small plasmid (3-4.4 Mdal) in 10% . No plasmid was found in 51% of the strains . Isoelectric focusing of 54 beta-lactamases showed that all were type TEM-1 (pI = 5.4), with the exception of one, which was type TEM-2 (pI = 5.6).

Pathol Biol (Paris), 1994 May, 42(5), 375 - 7
{Comparative activity of oral beta-lactam antibiotics against fifty strains of Haemophilus influenzae producing a beta-lactamase according to bacterial inoculum}; Gaillot O et al.; Minimal inhibitory concentrations (MICs) of amoxycillin alone and in combination with 2 mg/l or 4 mg/l clavulanic acid, ampicillin alone and in combination with 4 mg/l or 8 mg/l sulbactam, cefuroxime and cefaclor, were determined by the agar dilution method, with bacterial inoculum size ranging from 3 x 10(7) to 3 x 10(9) colony-forming units per ml . As expected, an inoculum effect was observed with cefaclor . In contrast, MICs of amoxycillin in combination with clavulanic acid did not significantly increase with the inoculum size . Ampicillin combined with sulbactam, and cefuroxime were less efficient at the highest bacterial concentration tested.

MMWR Morb Mortal Wkly Rep, 1994 Apr 22, 43(15), 282 - 3
Vaccination coverage of 2-year-old children--United States, 1992-1993; Structural studies of the cell envelope lipopolysaccharides from Haemophilus ducreyi strains ITM 2665 and ITM 4747; Clinical Research Center, Karolinska Institute, NOVUM, Huddinge Hospital, SwedenThe structures of the lipopolysaccharides from Haemophilus ducreyi strains ITM 2665 and ITM 4747 have been investigated . Oligosaccharides were obtained from phenol/water-extracted lipopolysaccharide by mild acid hydrolysis and were studied with methylation analysis, fast atom bombardment-mass spectrometry, and NMR spectroscopy . The major oligosaccharide obtained from strain 2665 is a nonasaccharide with the following structure: beta-D-Galp-1-->4-beta-D-GlcNAcp-1-->3-beta-D-Galp-1-->4-D-alpha-D -Hepp- 1-->6-beta-D-Glcp-1-->(L-alpha-D-Hepp-1-->2-L-alpha-D-Hepp-1 -->3)-4-L-alpha- D-Hepp-Kdo, where the reducing terminal 3-deoxy-D-manno-octulosonic acid (or Kdo) exists in reduced anhydro forms . The proposed structure complements the preliminary structure described for Haemophilus ducreyi strain 35000 (Melaugh, W., Phillips, N . J., Campagnari, A . A., Karalus, R., and Gibson, B . W . (1992) J . Biol . Chem . 267, 13434-13439) with the missing anomeric configurations . The saccharide isolated from strain 4747 is a markedly simpler hexasaccharide with the following structure: beta-D-Galp-1-->4-beta-D-Glcp-1-->(L-alpha-D-Hepp-1-->2-L-alpha-D- Hepp- 1-->3)4-L-alpha-D-Hepp-Kdo . Apart from a different phosphorylation of the inner core region the proposed structure is identical to the structure of lipopolysaccharide from an only distantly related bacterium, viz . Haemophilus influenzae nontypable strain 2019 (Phillips, N . J., Apicella, M . A., Griffiss, J . M., and Gibson, B.W . (1992) Biochemistry 31, 4515-4526) . The implications of these findings as regards the role of lipopolysaccharide as a virulence factor are discussed.

Med J Aust, 1994 Apr 18, 160(8), 512 - 4
Haemophilus paraphrophilus vertebral osteomyelitis; Wilson CM et al.; OBJECTIVE: To report the first case of Haemophilus paraphrophilus vertebral osteomyelitis--the second reported case of osteomyelitis of any site caused by this organism . CLINICAL FEATURES: A 41-year-old male bus driver with no significant previous medical history presented with severe abdominal and back pain, which was eventually localised to the eleventh thoracic vertebra (T11) . H . paraphrophilus was isolated from pus aspirated from the vertebral body . INTERVENTIONS AND OUTCOME: The patient was treated with penicillin given intravenously for four weeks, then with antibiotics given orally for a further three weeks, with good clinical response . CONCLUSION: H . paraphrophilus is an infrequent pathogen which may be difficult to identify and test for antibiotic susceptibility, but can cause serious infection, including primary haematogenous osteomyelitis.

Med J Aust, 1994 Apr 18, 160(8), 483 - 8
The burden of Haemophilus influenzae type b disease in Australia and an economic appraisal of the vaccine PRP-OMP; Harris A et al.; OBJECTIVES: To estimate the incidence and sequelae of Haemophilus influenzae type b disease (Hib) in the Australian population, and to evaluate the costs and outcomes of a vaccination program using the vaccine PRP-OMP at two, four and 12 months . DESIGN: The evaluation was based on a decision analytic model developed by Merck Sharp and Dohme (Australia) Pty Ltd, to predict the number of children who would contract Hib, and suffer mild or severe sequelae or die as a result . The state of health of a cohort of children was modelled each month over a five-year period . A survey of medical records and interviews with parents of children who contracted meningitis in Western Australia from 1984-1990 was undertaken to provide data on the extent and costs of sequelae . RESULTS: The incidence of Hib among non-Aboriginal Australians under five years of age was estimated as 53 per 100,000, and 460 per 100,000 among Aborigines . In a single year at least 630 children may contract Hib, up to 19 may die, and a further 46 may have neurological damage, this being severe in up to 18 children . The number of deaths could be reduced by 17 per year and a further 25 cases of severe and 16 cases of mild disability could be averted . At a price of $20 per dose, and a 5% discount rate, the expected cost per year of life extended by a vaccination program is $3148 . When adjusted for the increased number of years without neurological impairment, the incremental cost per quality adjusted life year (QALY) is $1965 . Compared with a single vaccine at 18 months, the incremental cost per additional QALY gained is $5047 . A separate analysis of the Aboriginal population showed that the proposed vaccination program would be of significant benefit, leading to a saving of resources.

Ugeskr Laeger, 1994 Apr 18, 156(16), 2420 - 3
{Acute epiglottitis . 27 years of experience with and future development of nasotracheal intubation}; Nielsen TG et al.; During a 27-year period 295 patients in Copenhagen County were treated for acute epiglottitis . One hundred and eight-two were adults and 113 were children . Most children were treated by nasotracheal intubation while only a few adults required nasotracheal intubation in order to secure the airway . The incidence of acute epiglottitis in children less than five years old was calculated to be 8.7/100,000 with minor annual variation . Since vaccination against Haemophilus influenzae type b has been implemented in Denmark from May 1993, this figure will probably be markedly reduced, and the disease even may be even eradicated in children, but in adults the same reduction cannot be expected as the causative agent in this group is less frequently Haemophilus influenzae type b . It is emphasized that this reduced incidence will make it even more important that each department engaged in the treatment of suspected acute epiglottitis have a departmental protocol for management of the condition, so that the future rarity of acute epiglottitis does not cause the mortality rate to rise.

Am J Epidemiol, 1994 Apr 15, 139(8), 793 - 802
Pneumonia hospitalizations in the US Navy and Marine Corps: rates and risk factors for 6,522 admissions, 1981-1991; Gray GC et al.; The authors identified hospitalizations for pneumonia (n = 6,522) in active-duty Navy and Marine Corps personnel during 1981-1991 from computerized inpatient records . The crude mean annual rate of pneumonia hospitalization was 77.6 per 100,000 active-duty personnel; 65% of pneumonia hospitalizations had no etiologic agent identified . The most commonly reported agents to cause pneumonia hospitalization were Streptococcus pneumoniae (12.3%), Mycoplasma pneumoniae (10.8%), other streptococcal species (2.1%), and Haemophilus influenzae (1.9%) . The median age at hospitalization was 22 years . The median duration of hospital stay was 4 days and the case fatality rate was 0.4% . The authors used a 2% sample of the entire population and by means of stepwise unconditional multivariate logistic regression modeling for pneumonia found that, independent of age, the most junior Navy and Marine Corps personnel were at highest risk . Whites were at higher risk than blacks, Hispanics, or Filipinos . These results indicate that among this generally healthy US young adult military population, pneumonia hospitalization is common, often brief, and frequently without specifically identified pathogens.

Schweiz Med Wochenschr, 1994 Apr 9, 124(14), 575 - 82
{Effect of conjugated PRP vaccines on the incidence of invasive diseases caused by Haemophilus influenzae Type B in childhood}; Desgrandchamps D et al.; Prior to the introduction of conjugate vaccines, Haemophilus influenzae type b (Hib) was the leading cause of severe invasive infections in young children, in Switzerland as in other countries . From 1976 to 1990, 150 children were treated for Hib meningitis at the Children's Hospital of Lucerne, corresponding to an annual incidence of 9.2 cases per 100,000 children aged under 15 years . In the same time period, the case fatality rate for meningitis was 4% . 87.3% of the meningitis cases occurred among children aged under 5 years . For this age group an annual incidence of 26.4 cases per 100,000 children was calculated . From 1979 to 1990, 141 children were hospitalized for epiglottitis, corresponding to an annual incidence of 10.9 cases per 100,000 children aged under 15 . The introduction of conjugated vaccines resulted in a significant reduction in the frequency of invasive Hib disease . From 1991 to 1992, 9 cases each of meningitis and epiglottitis were observed . In 1993, only one case of meningitis and 2 cases of epiglottitis were seen . For children under 15 years these 21 cases represent annual incidences of 3.2 cases of meningitis and 3.6 cases of epiglottitis per 100,000 children . 2 of 10 meningitis cases occurred in twice vaccinated children under 2 years of age with no signs of immunodeficiency, and another case was seen in a 5-month-old infant vaccinated with only one dose . Assuming a vaccination coverage of 70% among children under 5 during the years 1991 and 1992, the calculated efficacy is 80 to 85% for the vaccine PRP-D in this predominantly affected age group during the period when only this vaccine was available.(ABSTRACT TRUNCATED AT 250 WORDS)

J Biol Chem, 1994 Apr 8, 269(14), 10566 - 73
Divergence of genetic sequences for the vacuolating cytotoxin among Helicobacter pylori strains; Cover TL et al.; Approximately 50% of Helicobacter pylori isolates produce a cytotoxin in vitro that induces vacuolation of eukaryotic cells . Screening a lambda ZapII library of H . pylori 60190 chromosomal fragments permitted the identification of a 3864-base pair (bp) open reading frame (vacA) that encoded the vacuolating cytotoxin, and a > or = 567-bp upstream gene that was homologous to Escherichia coli cysteinyl-tRNA synthetase . The sequence data suggest that a 33-amino-acid leader sequence and a C-terminal peptide are cleaved from a 139-kDa protoxin to yield the mature 87-kDa cytotoxin . The vacA gene product contains a C-terminal motif that is present in several other bacterial proteins that undergo C-terminal cleavage, including IgA proteases of Haemophilus influenzae and Neisseria gonorrhoeae . Isogenic H . pylori mutants with insertional mutation of the vacA gene lacked vacuolating cytotoxin activity and failed to produce the 87-kDa protein . Southern analysis of naturally occurring tox-H . pylori strains with vacA probes indicated the presence of hybridizing bands, but both Southern analysis and polymerase chain reaction studies suggested that the vacA sequences of tox- strains differed from those of tox+ strains . Sequence analysis of a 1541-bp region of polymerase chain reaction-amplified vacA from tox- strain 87-203 indicated 64.8% amino acid identity with the corresponding region from tox+ strain 60190 . Thus, sequence divergence in vacA genes may explain the lack of functionally active cytotoxin production by some H . pylori isolates.

Acta Paediatr Jpn, 1994 Apr, 36(2), 220 - 2
Haemophilus influenzae type D infection and IgG2 deficiency in a patient with chronic mucocutaneous candidiasis; Sakano T et al.; A 14 year old boy with chronic mucocutaneous candidiasis and persistent pulmonary infection caused by Haemophilus influenzae and Streptococcus pneumoniae is reported . Initial bacterial culture studies showed H . influenzae type B and S . pneumoniae as causative agents . H . influenzae type D was constantly isolated from the patient's sputum . Abnormally low levels of serum immunoglobulin G2 (IgG2) found in the patient may have contributed to the pulmonary infection and H . influenzae type D may be an important causative agent in immunodeficient patients.

Thorax, 1994 Apr, 49(4), 367 - 8
Community acquired lobar pneumonia in patients with HIV infection and AIDS; Miller RF et al.; BACKGROUND--Community acquired bacterial pneumonia is increasingly encountered in HIV infected individuals and some patients have a radiographic lobar pneumonia . METHODS--A retrospective review of clinical features, microbiological diagnosis, and outcome of community acquired lobar pneumonia was carried out in HIV positive patients admitted to a specialist unit from 1987 to 1993 . RESULTS--Forty nine episodes occurred in 45 patients, all of whom were men . CD4 counts ranged widely . A bacteriological diagnosis was made in 25 episodes (51%), seven patients had more than one infective cause . The commonest pathogens were Streptococcus pneumoniae (11 episodes), Staphylococcus aureus (six), Pneumocystis carinii (three), Haemophilus influenzae (three), and Pseudomonas aeruginosa (two) . Four patients died . Other complications included intrapulmonary cavitation or abscess formation (11 episodes), empyema (three), and pleural effusion (10 episodes) . CONCLUSIONS--Many different infections cause community acquired lobar pneumonia in HIV positive men . Some patients have co-infections and there is a high complication rate.

Jpn J Antibiot, 1994 Apr, 47(4), 409 - 27
{Basic and clinical studies on cefditoren pivoxil in pediatric field}; Motohiro T et al.; Cefditoren pivoxil (CDTR-PI, ME1207) granules, a new oral cephem, was given to pediatric patients with infectious diseases to evaluate antibacterial activities against clinical isolates, pharmacokinetics, clinical efficacy and safety, and the following results were obtained . 1 . In sensitivity test, 30 strains were used comprised of 5 species, isolated from the patients before administered with CDTR-PI . Against Staphylococcus aureus, MICs of 7 agents, cefditoren (CDTR), cefaclor, cefixime, cefteram, cefotiam, cefpodoxime and methicillin, were determined . Against other 4 species, MICs of the above 6 agents excluding methicillin were determined . Among Gram-positive cocci tested, the MICs of CDTR were 0.78 to 100 micrograms/ml or higher against S . aureus (16 strains), < or = 0.025 microgram/ml against Streptococcus pyogenes (5 strains), and 0.10 or 0.39 microgram/ml against Streptococcus pneumoniae (2 strains) . These values were equal to or lower than those of conventional cephems and of methicillin . Among Gram-negative rods tested, the MICs of CDTR were < or = 0.025 microgram/ml against Haemophilus influenzae (3 strains), and 0.10 or 0.20 microgram/ml against Escherichia coli (4 strains) . Also, these values were equal to or lower than those of conventional cephems . 2 . When CDTR-PI granules was orally administered in a single dose of 3.0 mg/kg to 1 patient and that of 6.0 mg/kg to 2 patients 30 minutes after meal, plasma CDTR concentrations reached their maxima 4 hours after administration in the former patient and 1 or 2 hours after administration in the latter 2 patients, and the peak plasma concentrations were 1.91, 3.46 and 4.82 micrograms/ml with half-lives of 1.01, 0.81 and 0.88 hours and AUCs of 8.62, 9.89 and 13.52 micrograms.hr/ml, respectively . Dose-dependency was observed for the peak plasma concentrations and AUCs also tended to depend on dose excepting for the AUC in one 6.0 mg/kg patient . 3 . The urinary concentrations in the above patients reached their peaks at 4 to 6 hours after administration in one 3.0 mg/kg patient and at 4 to 6 hours and 2 to 4 hours after administration in two 6.0 mg/kg patients, and the corresponding values were 126.0, 195.0 and 234.0 micrograms/ml, respectively . Recovery rates in the first 8 hours after administration were 18.2, 24.6 and 21.3%, respectively . 4 . Of 53 patients with 13 diseases, CDTR-PI was clinically judged "excellent" in 32 (60.4%) and "good" in 21 (39.6%), showing excellent efficacy . 5 . Bacteriologically, excellent results were obtained, i.e., 29 (96.7%) of 30 strains from 5 species were eradicated . 6 . Side effects were observed in none of the 54 patients treated.(ABSTRACT TRUNCATED AT 400 WORDS)

Jpn J Antibiot, 1994 Apr, 47(4), 365 - 82
{Antimicrobial activities of cefuroxime against recent clinical isolates}; Deguchi K et al.; Antimicrobial activity of cefuroxime axetil (CXM-AX) was compared with those of other cephem antibiotics against clinically isolated strains obtained mainly from outpatients of our center in a period from January to September of 1990 and 1993 . Minimum inhibitory concentrations were determined and the following results were obtained . 1 . The results suggested that, compared with reports of studies conducted with clinical isolates in early 1980's, MIC80 of CXM were equal to or lower against Staphylococcus spp., Streptococcus pyogenes, Escherichia coli, Klebsiella spp., Proteus mirabilis, Haemophilus influenzae, Moraxella subgenus Branhamella catarrhalis, Neisseria gonorrhoeae, Peptostreptococcus spp., and Propionibacterium acnes, except for Streptococcus pneumoniae, MIC80 which was slightly higher . 2 . MIC90 of comparator drugs reflected those of new resistant organisms recently appeared, such as benzylpenicillin (PCG)-insensitive S . pneumoniae (PISP), cephem-resistant E . coli and Klebsiella spp., new quinolone-resistant H . influenzae and N . gonorrhoeae . Methicillin-resistant Staphylococcus aureus (MRSA) was detected also from specimens of community acquired infections . From the nature of MRSA detected in those situations MRSA appeared to present a continuing problem . 3 . MIC90 against strains obtained from patients with community acquired infections was a good index of increases of multidrug-resistant organisms in the past . Therefore, the determination of MIC90 is important in examining changes with time of sensitivities or resistances of clinically isolated strains to antimicrobial drugs . 4 . Antimicrobial activities of CXM against recent clinical isolates showed the existence of problems as mentioned above . However, MIC of CXM as well as those of comparator drugs indicated that antimicrobial activities of CXM against Staphylococcus spp., Streptococcus spp., H . influenzae appeared to be relatively strong, and it is concluded that cefuroxime axetil still is one of the clinically useful oral antimicrobial drugs in the 1990's.

Immunol Cell Biol, 1994 Apr, 72(2), 143 - 51
An alteration in the host-parasite relationship in subjects with chronic bronchitis prone to recurrent episodes of acute bronchitis; Taylor DC et al.; Acute episodes of bronchitis have been shown to be unequally distributed within a population of subjects with chronic bronchitis . Two groups were identified based on incidence of acute bronchitis--subjects who were 'infection-prone' (2-5 infections per year) and those who were 'non-infection-prone' (0-1 infections per year) . Minor differences in clinical parameters existed, except for smoking experience . The non-infection-prone group included more current smokers, and the total smoking experience (in 'pack years') was significantly greater in this group . Between-year analysis demonstrated a stability of classification, established after a minimum of two years' prospective observation . Parameters of the host-parasite relationship were assessed in both groups . A significantly greater polybacterial colonization of the oropharynx was observed for chronic bronchitics, both infection-prone (P < 0.0001) and non-infection-prone (P < 0.001), compared with control subjects . Infection-prone chronic bronchitics had significantly greater total bacteria cultured from the oropharynx compared to the non-infection-prone group (P < 0.05); adherence of indigenous microflora to buccal epithelial cells, in particular Gram-positive cocci (P < 0.01) and in vitro adherence of non-serotypable Haemophilus influenzae to buccal cells (P < 0.05) compared with the control and non-infection-prone groups . These studies suggest that an important variation in subjects with chronic bronchitis is the binding capacity of epithelial cells for bacteria, which when increased enhances susceptibility to colonization and clinical infection.

Am J Obstet Gynecol, 1994 Apr, 170(4), 1008 - 14; discussion 1014-7
Observations concerning the microbial etiology of acute salpingitis; Soper DE et al.; OBJECTIVES: The specific aims of this study were (1) to describe the microbiologic characteristics of patients with acute salpingitis and (2) to determine the incidence of bacterial vaginosis in patients with acute salpingitis and whether bacterial vaginosis microorganisms were common upper-genital-tract isolates in these patients . STUDY DESIGN: Women with pelvic inflammatory disease underwent laparoscopy to confirm the diagnosis of acute salpingitis and for culture of the fallopian tubes and cul-de-sac . Endometrial and minute fimbrial biopsies were performed, and specimens were evaluated for evidence of inflammation . Bacterial vaginosis was diagnosed by vaginal Gram stain . RESULTS: Eighty-four patients had visually confirmed acute salpingitis . Neisseria gonorrhoeae or Chlamydia trachomatis was isolated from 65 (77.4%) patients . Vaginal microorganisms were isolated from the endometrium in 16 (31.4%) of 51 cases and from the cul-de-sac in 12 (14.3%) of 84 cases . Bacterial vaginosis was present in 61.8% of patients with acute salpingitis, and 100% of anaerobes isolated from the upper genital tract of patients with acute salpingitis were bacterial vaginosis microorganisms . These anaerobes were isolated from the upper genital tract in the absence of a concurrent gonococcal, chlamydial, or Haemophilus influenzae infection in only two cases . CONCLUSIONS: The initiation of acute salpingitis is predominantly due to the ascending spread of sexually transmitted microorganisms . Bacterial vaginosis is a common concurrent disorder of women with acute salpingitis, and bacterial vaginosis microorganisms are commonly isolated from the upper genital tracts of patients with pelvic inflammatory disease.

Am J Med, 1994 Apr, 96(4), 342 - 7
Nosocomial transmission of disease caused by nontypeable strains of Haemophilus influenzae; Goetz MB et al.; PURPOSE: The authors evaluated a geographic and temporal cluster of lower respiratory tract infections due to unencapsulated (serologically nontypeable) Haemophilus influenzae to determine whether this event represented the transmission of a single clone . METHODS AND MATERIALS: H influenzae was recovered from eight patients at a nursing home and from three patients in an adjacent acute care hospital . Serotypes, biotypes, outer membrane protein profiles, and multilocus enzyme genotypes were determined to characterize bacterial isolates . Patient records were retrospectively examined to determine clinical and epidemiologic characteristics . RESULTS: During a 10-day period in September 1991, lower respiratory tract infections caused by H influenzae were diagnosed in four patients residing in a single nursing home unit . Oropharyngeal cultures from four of seven asymptomatic roommates of these patients also grew H influenzae . During the month before and after the nursing home cluster of cases, four other individuals in acute care areas of the hospital had positive sputum cultures for H influenzae . Three of these latter specimens were also available for analysis . All H influenzae isolates were unencapsulated and beta-lactamase-negative . Eight of the nine isolates from the nursing home patients (two morphologically distinct colony types of H influenzae were isolated from one case) had a single outer membrane protein profile arbitrarily designated as X and a single multilocus enzyme genotype arbitrarily designated as A . In contrast, none of the isolates from the acute care cases had this profile (P < or = 0.02; two-tailed Fisher's exact test) . The isolates obtained from two of the patients in acute care areas had an outer membrane protein profile arbitrarily designated as Y and a single multilocus enzyme genotype designated as B . These two patients were contemporaneously hospitalized in adjacent intensive care unit cubicles . The remaining isolates displayed an outer membrane protein profile arbitrarily designated as W . All roommates of the four patients in the nursing home were administered oral rifampin 600 mg daily for 4 days . H influenzae was not recovered from follow-up oropharyngeal cultures obtained 1 week after the completion of therapy . No beta-lactamase-negative H influenzae were identified in this unit during the subsequent 9 months . CONCLUSION: This study furnishes strong evidence for the nosocomial transmission of a clone of unencapsulated H influenzae in a nursing home unit . Epidemiologic data showed temporal and geographic clustering of respiratory tract infections and colonization by H influenzae . Outer membrane protein profiles and multilocus enzyme genotype analysis indicated that seven of eight patients at the nursing home carried a single clone of unencapsulated H influenzae . Laboratory and epidemiologic data also demonstrated the presence, and possible nosocomial transmission, of a second clone of unencapsulated H influenzae in a physically separate area of the hospital . Finally, although a causal relationship is not proven, the outbreak ended following the administration of rifampin prophylaxis of asymptomatic carriers.

J Allergy Clin Immunol, 1994 Apr, 93(4), 793 - 8
Gamma delta T lymphocytes and proinflammatory cytokines in bacterial meningitis; Raziuddin S et al.; BACKGROUND: Patients with bacterial meningitis have a T-cell defect and impaired cytokine production . METHODS: The phenotype and percentage of circulating alpha beta and gamma delta T-cell receptor-bearing lymphocytes were determined from patients with bacterial meningitis (Haemophilus influenzae, Streptococcus pneumoniae, and Neisseria meningitidis), patients with bacterial infection but without meningitis, and healthy control subjects by a monoclonal antibody staining method . The in vitro production of cytokines, interleukins (IL-2, IL-6), interferon-gamma and tumor necrosis factor-alpha was measured by the bioassay or ELISAs . RESULTS: The percentage of circulating gamma delta T cells with a CD3+CD4+CD8- phenotype was significantly (p < 0.001) increased in all patients with bacterial meningitis compared with patients with bacterial infection and healthy control subjects . The CD3+ gamma delta T cells from patients with meningitis produced highly elevated levels of two proinflammatory cytokines, tumor necrosis factor-alpha and IL-6 . However, interferon-gamma production was enhanced by CD3+ alpha beta T cells . CONCLUSION: The increased percentage of circulating T-cell receptor gamma delta T cells and their in vitro production of tumor necrosis factor-alpha and IL-6 cytokines may play an important role in the pathogenesis and inflammatory response in bacterial meningitis.

Ann Emerg Med, 1994 Apr, 23(4), 888 - 90
Varicella-associated acute supraglottitis; Nozicka CA et al.; Acute bacterial supraglottitis is a well-recognized pediatric entity . There are reports in the literature of numerous supraglottic infections not limited to the usual organism, Haemophilus influenzae type b . We present a case of acute supraglottitis that is associated with varicella infection.

J Pediatr, 1994 Apr, 124(4), 504 - 12
Intramuscular versus oral antibiotic therapy for the prevention of meningitis and other bacterial sequelae in young, febrile children at risk for occult bacteremia; Fleisher GR et al.; Because studies of the treatment of children with occult bacteremia have yielded conflicting results, we compared ceftriaxone with amoxicillin for therapy . Inclusion criteria were age 3 to 36 months, temperature > or = 39 degrees C, an acute febrile illness with no focal findings or with otitis media (6/10 centers), and culture of blood . Subjects were randomly assigned to receive either ceftriaxone, 50 mg/kg intramuscularly, or amoxicillin, 20 mg/kg/dose orally for six doses . Of 6733 patients enrolled, 195 had bacteremia and 192 were evaluable: 164 Streptococcus pneumoniae, 9 Haemophilus influenzae type b, 7 Salmonella, 2 Neisseria meningitidis, and 10 other . After treatment, three patients receiving amoxicillin had the same organism isolated from their blood (two H . influenzae type b, one Salmonella) and two from the spinal fluid (two H . influenzae type b), compared with none given ceftriaxone . Probable or definite infections occurred in three children treated with ceftriaxone and six given amoxicillin (adjusted odds ratio 0.43, 95% confidence interval 0.08 to 1.82, p = 0.31) . The five children with definite bacterial infections (three meningitis, one pneumonia, one sepsis) received amoxicillin (adjusted odds ratio 0.00, 95% confidence interval 0.00 to 0.52, p = 0.02) . Fever persisted less often with ceftriaxone (adjusted odds ratio 0.52, 95% confidence interval 0.28 to 0.94, p = 0.04) . Although the difference in total infections was not significant, ceftriaxone eradicated bacteremia, prevented significantly more definite focal bacterial complications, and was associated with less persistent fever.

Clin Exp Immunol, 1994 Apr, 96(1), 54 - 8
Qualitative and quantitative analyses of the antibody response elicited by Haemophilus influenzae type b capsular polysaccharide-tetanus toxoid conjugates in adults with IgG subclass deficiencies and frequent infections; Avanzini MA et al.; Twenty-one IgG subclass-deficient adult patients with repeated infections of the respiratory tract, were immunized with Haemophilus influenzae type b capsular polysaccharide (HibCP) covalently bound to tetanus toxoid (TT) . Specific immunoglobulin and IgG subclasses to HibCP and TT were quantified; the biological activities of HibCP antibodies were also investigated . Most patients showed an antibody response similar to that observed in healthy adults, and the bactericidal activity related to the post-immunization levels of HibCP antibodies . No relation was found between immunoglobulin isotype deficiency, the clinical symptoms and the IgG subclass responsiveness, and no relation was observed between HibCP and TT antibody responses . Our data indicate that some, but not all, patients with recurrent infections and IgG subclass deficiency have an abnormal serum antibody response to polysaccharide and protein epitopes of Hib-TT conjugate vaccine . Analysis of the antibody response after vaccination with HibCP-TT conjugate vaccine did not seem to predict the clinical course of such patients.

Pediatrics, 1994 Apr, 93(4), 663 - 8
National trends in Haemophilus influenzae meningitis mortality and hospitalization among children, 1980 through 1991; Schoendorf KC et al.; OBJECTIVE . Haemophilus influenzae type b (Hib) conjugate vaccines were licensed for routine use in the United States in December 1987 . We compared national trends in deaths and hospitalization from H influenzae meningitis among children < 5 years old before and after Hib conjugate vaccine licensure . METHODS . H influenzae meningitis mortality rates were calculated using data from the 1980 through 1991 computerized national mortality files . Hospitalization rates from H influenzae meningitis were calculated using data from the 1980 through 1991 National Hospital Discharge Surveys . Trends in H influenzae mortality and hospitalization from 1980 through 1887 were compared with trends from 1988 through 1991 . Trends for Streptococcus pneumoniae and Neisseria meningitidis meningitis were also examined . RESULTS . From 1980 through 1987, mortality from H influenzae meningitis decreased an average of 8.5% each year, compared with a 48% annual decrease from 1988 through 1991 (P < .001 for difference in trends) . H influenzae meningitis hospitalization rates increased 1% each year from 1980 through 1987, and decreased an average of 34% each year from 1988 through 1991 . There was no significant difference in mortality or hospitalization trends for S pneumoniae or N meningitidis meningitis during the two periods . Among infants, H influenzae meningitis mortality decreased an average of 8% per year from 1980 through 1987 and 43% per year from 1988 through 1991 . One- to four-year-old children had similar average annual declines, 8% and 58% for the two periods . Although there were regional differences in the absolute mortality rates, all regions of the country had similar trends in meningitis mortality . CONCLUSIONS . Among US children < 5 years old, we found substantial decreases in deaths and hospitalization from H influenzae meningitis, but not S pneumoniae or N meningitidis meningitis, in the years after Hib conjugate vaccine licensure . These results suggest that the declines in H influenzae meningitis were due primarily to the use of Hib conjugate vaccines.

J Infect Dis, 1994 Apr, 169(4), 912 - 6
Epidemiology of pediatric meningitis caused by Haemophilus influenzae type b, Streptococcus pneumoniae, and Neisseria meningitidis in Israel: a 3-year nationwide prospective study . Israeli Pediatric Bacteremia and Meningitis Group; Dagan R et al.; In a 3-year nationwide prospective study on pediatric meningitis caused by Haemophilus influenzae type b, Streptococcus pneumoniae, and Neisseria meningitidis in Israel, 1258 invasive infections with a known focus were observed . Meningitis was found in 482 (38%): 56%, 16%, and 76% of all infections by H . influenzae type b, S . pneumoniae, and N . meningitidis, respectively . The incidence of meningitis during the first year of life was 67.1, 17.5, and 9.5/100,000 for H . influenzae type b, S . pneumoniae, and N . meningitidis, respectively, and in children < 5 years old it was 18.5, 5.3, and 5.2 . Extrapolated for a population in which 100,000 live births occur yearly, 2097 hospital days were required . The case fatality rate was 2.2%, 5.9%, and 6.3% for H . influenzae type b, S . pneumoniae, and N . meningitidis, respectively . Boys were affected significantly more often than girls, but mortality was higher among girls . On the basis of the observed serotypes and age distribution, even with optimal vaccine development in the next 5 years, it is not likely that > 50% of all cases will be prevented.

J Infect Dis, 1994 Apr, 169(4), 853 - 8
Dexamethasone therapy for bacterial meningitis in children: 2- versus 4-day regimen; Syrogiannopoulos GA et al.; Four-day dexamethasone therapy has been used to treat bacterial meningitis . This prospective, randomized study compared the effect of a 2-day versus a 4-day regimen . Children (n = 118, ages 2.5 months to 15 years) were evaluated; 50% of the cases were due to Neisseria meningitidis and 40% to Haemophilus influenzae type b . Patients were treated intravenously (iv) mainly with conventional antimicrobial therapy and were randomly assigned to receive dexamethasone, 0.15 mg/kg iv every 6 h for 2 or 4 days . The clinical response was similar for both dexamethasone regimens . The meningococcal meningitis patients survived without neurologic or audiologic sequelae . On long-term follow-up, neurologic sequelae or moderate or more severe unilateral or bilateral hearing impairment (or both) were found in 1.8% and 3.8% of patients treated with dexamethasone for 2 and 4 days, respectively . The 2-day regimen appears appropriate for the treatment of H . influenzae and meningococcal meningitis.

J Infect Dis, 1994 Apr, 169(4), 754 - 9
Human T cell lymphotropic virus type I infection among female sex workers in Peru; Gotuzzo E et al.; Four hundred female sex workers attending a sexually transmitted disease clinic in Lima, Peru, were interviewed for demographic information and medical, contraceptive, and sexual practice histories . Cervical cultures were done for Neisseria gonorrhoeae and Chlamydia trachomatis, and serum was tested for antibodies to human immunodeficiency virus, human T cell lymphotropic virus type I (HTLV-I), Treponema pallidum, C . trachomatis, herpes simplex virus type 2 (HSV-2), and Haemophilus ducreyi . The prevalence of HTLV-I increased with duration of prostitution from 3.6% (< 3 years) to 9.3% (3-6 years) to 15.9% (> 6 years; P < .01) . After adjustment for duration of prostitution, reduced risk of HTLV-I was significantly correlated with condom use for more than half of all sexual exposures for > 3 years (odds ratio {OR}, 0.34; 95% confidence interval {CI}, 0.13-0.89) . Further adjusting for condom use, HTLV-I seropositivity was associated with C . trachomatis (OR, 3.7; 95% CI, 1.4-13.2) and with antibody to HSV-2 (OR, 3.7; 95% CI, 0.5-29.6) . Thus, duration of prostitution, lack of consistent condom use, and past infection with C . trachomatis were significantly associated with HTLV-I seropositivity.

Infect Immun, 1994 Apr, 62(4), 1427 - 36
Mucosal and systemic immunizations with killed Pseudomonas aeruginosa protect against acute respiratory infection in rats; Cripps AW et al.; The aim of this study was to determine the efficacies of prior mucosal (oral, intra-Peyer's patch, or intratracheal) and systemic (subcutaneous) immunizations with killed Pseudomonas aeruginosa in clearance of an acute P . aeruginosa respiratory infection in rats . Rats were immunized with paraformaldehyde-killed P . aeruginosa at various doses, and 2 weeks later, the rats were challenged with a log10 dose of 8.7 live bacteria . This dose was fatal for unimmunized rats, with death occurring approximately 12 h after challenge . The numbers of surviving bacteria in the airways and lung tissue were determined by analyses of bronchoalveolar lavage fluid (BAL) and lung homogenate samples, respectively . Enhanced bacterial clearance was associated with survival of intra-Peyer's patch-immunized rats . Determination of bacterial clearance in BAL 4 h after challenge demonstrated that the use of all immunization routes led to significant clearance compared with the bacterial levels in unimmunized controls (the order of effectiveness was intra-Peyer's patch > oral-intratracheal > intratracheal > subcutaneous > oral) . Bacterial clearance in the lung homogenate was also significantly greater for all immunization routes than in the unimmunized controls (the order of effectiveness was intra-Peyer's patch > subcutaneous > oral-intratracheal > oral = intratracheal) . Prior oral immunization with killed P . aeruginosa also induced enhanced bacterial clearance of heterologous strains of P . aeruginosa, Haemophilus influenzae, and to a lesser extent, Klebsiella pneumoniae . Because of the ease of antigen delivery, oral immunization with killed P . aeruginosa may be an important route of immunization for induction of enhanced bacterial clearance of subsequent acute respiratory infection with P . aeruginosa and other gram-negative bacteria.

Infect Immun, 1994 Apr, 62(4), 1369 - 80
Isolation and characterization of a gene involved in hemagglutination by an avian pathogenic Escherichia coli strain; Provence DL et al.; In this article, we report the isolation and characterization of a gene that may be important in the adherence of avian pathogenic Escherichia coli to the avian respiratory tract . The E . coli strain HB101, which is unable to agglutinate chicken erythrocytes, was transduced with cosmid libraries from the avian pathogenic E . coli strain chi 7122 . Enrichment of transductants that could agglutinate chicken erythrocytes yielded 19 colonies . These isolates contained cosmids that encompassed four nonoverlapping regions of the E . coli chromosome . Only one group of cosmids, represented by pYA3104, would cause E . coli CC118 to agglutinate chicken erythrocytes . A 10-kb fragment of this cosmid was subcloned in pACYC184 . Transposon mutagenesis of this fragment with Tn5seq1 indicated that a contiguous 4.4-kb region of cloned DNA was required for hemagglutination . In vitro transcription/translation assays indicated that this 4.4-kb region of DNA encoded one protein of approximately 140 kDa . The nucleotide sequence of this region was determined and found to encode one open reading frame of 4,134 nucleotides that would encode a protein of 1,377 amino acids with a deduced molecular weight of 148,226 . This gene confers on E . coli K-12 a temperature-sensitive hemagglutination phenotype that is best expressed when cells are grown at 26 degrees C, and we have designated this gene tsh and the deduced gene product Tsh . Insertional mutagenesis of the chromosomal tsh gene in chi 7122 had no effect on hemagglutination titers . The deduced protein was found to contain significant homology to the Haemophilus influenzae and Neisseria gonorrhoeae immunoglobulin A1 proteases . These data indicate that (i) a single gene isolated from the avian pathogenic E . coli strain chi 7122 will confer on E . coli K-12 a hemagglutination-positive phenotype, (ii) chi 7122 contains at least two distinct mechanisms to allow hemagglutination to occur, and (iii) the hemagglutinin Tsh has homology with a class of proteins previously not known to exist in E . coli.

Rev Soc Bras Med Trop, 1994 Apr-Jun, 27(2), 87 - 91
{The cerebrospinal fluid in bacterial meningitis}; de Campos CE et al.; Samples of 1815 cerebrospinal fluid (CSF) were studied in a meningitis outbreak during 1989 in Sao Paulo, Brazil . Neisseria meningitis 56% with 44% type B, Haemophilus influenzae 17%, from which 72% in children (days to 3-year-old) and Streptococcus pneumoniae 14% from which 60% in children (day to 1-year-old) of 443 (24%) of all strains . Cytochemistry study showed: purulent or turbidity aspects in 70 to 79% positive bacterioscopy or culture of CSF; white cells count > 500/mm3; glucose < 45 mg/dl; protein > 90 mg/dl in 90% of all patients . We concluded that: CSF prognostic factors: (aspect and cytochemistry) were correlated with bacterial meningitis . Bacterioscopy and positive cultures were correlated to NM, SP and HI isolation from these patients (Goodman Test).

Mol Microbiol, 1994 Apr, 12(2), 307 - 19
Genetic analysis of the Helicobacter pylori vacuolating cytotoxin: structural similarities with the IgA protease type of exported protein; Schmitt W et al.; The human gastric bacterial pathogen Helicobacter pylori has been implicated in type B gastritis, peptic ulceration and gastric adenocarcinoma . Here we report on the cloning and genetic characterization of an H . pylori gene named vacA, which encodes the vacuolating cytotoxin VacA, a novel type of antigenic bacterial toxin that induces the formation of intracellular vacuoles in epithelial cells . The vacuolating cytotoxin activity is expressed by a subset of clinical isolates (Vac+), all of which produce the 87 kDa cytotoxin antigen, but strains which produce neither the activity nor the cytotoxin protein (Vac-) also carry the gene . Isogenic H . pylori mutants in vacA generated by transposon shuttle mutagenesis produce neither the VacA antigen nor a vacuolating activity in a cell culture model . The vacA gene itself encodes a precursor protein of 139.6 kDa consisting of a 33-amino acid signal sequence, the 87 kDa cytotoxin and a 50 kDa C-terminal domain with features typical of a bacterial outer membrane protein . The VacA precursor shows no significant primary sequence homology with any previously reported protein, but its structural organization closely resembles the IgA protease-type of exoprotein produced by pathogenic Neisseriae and Haemophilus species . Our current data support a model for secretion of the cytotoxin through the two bacterial membranes which involves the 50 kDa domain for outer membrane translocation with subsequent proteolytic cleavage and release of the mature 87 kDa cytotoxin into the extracellular environment.

Acta Odontol Scand, 1994 Apr, 52(2), 93 - 8
Microorganisms on toothbrushes at day-care centers; Malmberg E et al.; The microflora on 44 toothbrushes at 4 day-care centers in the city of Goteborg have been investigated as a presumptive risk factor for transmission of microorganisms by children . Non-supervised toothbrushing without the use of toothpaste was performed at the day-care centers twice a day . Streptococci, predominantly S . salivarius, S . sanguis, and S . mitis, were the most frequently recorded group of microorganisms and generally constituted the greatest part of the flora (on average, 50%) . Beta-hemolytic streptococci were not found in any sample . Haemophilus species were noted in 82% of the samples . H . parainfluenzae being the most frequent, and H . influenzae being identified in only one sample . Anaerobes constituted on average a third of the microflora . Staphylococci were identified in 86% of the samples, S . epidermidis dominating . Fungi including molds were found in 50% of the samples, and from one day-care center large numbers of enteric organisms were identified . Thus this study shows that unsupervised toothbrushing at day-care centers can be questioned, more from a general hygienic point of view than from the risk of transmitting serious pathogens.

Pediatr Infect Dis J, 1994 Apr, 13(4), 274 - 80
Protection provided by Haemophilus influenzae type b conjugate vaccines in Los Angeles County: a case-control study; Vadheim CM et al.; The objective was to assess the degree of disease control and to evaluate the protective efficacy of licensed Haemophilus influenzae type b (Hib) conjugate vaccines (HbOC, PRP-OMP, PRP-D) used routinely in children 2 to 35 months of age . We conducted a case-control study in Los Angeles County between January 1, 1991, and December 31, 1992, and a cohort analysis of Hib cases between 1983 and 1992 . For the case-control study 105 cases of invasive Hib disease were identified and 767 geographically and age-matched controls were selected by random digit telephone dialing . Sixteen HbOC vaccine failures occurred > 14 days after a single dose of vaccine, 6 vaccine failures after 2 doses and 3 failures after 3 doses; 2 cases occurred 6 and 12 days, respectively, after an initial dose of HbOC . The protective efficacy of a single HbOC vaccine dose was 71.1% (95% confidence interval (CI), 37.5 to 87.2%) . After 2 doses the efficacy was 88.8% (95% CI, 59.5 to 96.9%) and after 3 doses it was 94.4% (95% CI, 68.0% to 99.0%) . Similar 95% CIs were seen for 1 and 2 doses of PRP-OMP vaccine . Adjustment of efficacy estimates for potential confounding variables did not significantly alter the results . Despite relatively low rates of immunization (20 to 60%) the rates of Hib disease decreased strikingly between 1990 and 1992 (from 24.2 to 4.4/100,000 children < 5 years of age) . The HbOC conjugate vaccine, used predominantly but incompletely during this period, provided substantial protection against invasive Hib disease in children immunized between 2 and 35 months of age.(ABSTRACT TRUNCATED AT 250 WORDS)

Antimicrob Agents Chemother, 1994 Apr, 38(4), 872 - 5
Clinical and bacteriological efficacy and tolerability of FCE 22891 in patients with exacerbations of chronic obstructive pulmonary disease; Boersma WG et al.; A beta-lactamase-stable antibiotic, the oral penem FCE 22891 (ritipenem acoxil), was investigated for use in exacerbations of chronic obstructive pulmonary disease (COPD) . Thirteen of the 15 COPD patients had a proven lower respiratory tract infection . Symptom scores and forced expiratory volumes in 1 s significantly improved during therapy with FCE 22891 in combination with bronchodilators and intravenous corticosteroids . Conversion of representative sputum to nonrepresentative sputum or eradication of the original pathogen in representative sputum was effected in 12 patients . Resistance to FCE 22891 was observed in three cases with Haemophilus influenzae . Gastrointestinal disturbances, of which one was severe, were experienced by eight patients . Although FCE 22891 has some beneficial effect in exacerbations of COPD, there are reservations about its use because of adverse effects and potential inefficacy in the treatment of infection with H . influenzae.

Vaccine, 1994 Apr, 12(5), 403 - 5
Haemophilus type B conjugate vaccine: postimmunization kinetics of IgM and IgG antibody responses in ten vaccinated children; Vincent-Ballereau F et al.; A new Haemophilus type b conjugate vaccine coupling capsular polysaccharide of Haemophilus influenzae b to tetanus toxoid is available in France and other countries . We have studied the kinetics of the immune response in ten children aged 17 to 50 months during the 4 weeks after immunization with one dose of Haemophilus type b conjugate vaccine . Eight serum samples were collected from each child at day 0 (D0), D2, D4, D7, D10, D14, D21 and D28 . An ELISA method has been used to discriminate between IgM and IgG classes of anti-polyribosylribitol phosphate antibodies . A high level of IgM appeared at D7 and persisted until D28 . The increase in IgG was regular and progressive from D7.

Ear Hear, 1994 Apr, 15(2), 116 - 25
Progress in the prevention of hearing loss in infants; Stein LK et al.; Two leading causes of hearing loss in infants and young children have been bacterial meningitis due to Haemophilus influenzae Type b (Hib) and congenital toxoplasmosis . In this two-part review, we describe the essential nature and incidence of these two diseases and how the availability of a Hib vaccine effective and safe with infants as young as 2 mo of age; the prospect of universal immunization against Hib disease; the introduction of cephalosporin antibiotic and corticosteroid treatment; and the use of early and prolonged antimicrobial therapy with children with congenital toxoplasmosis promises significant reduction, if not complete eradication, of hearing loss in infants and toddlers attributable to Hib bacterial meningitis and congenital toxoplasmosis . As a result, there may be up to a third fewer children under the age of five with severe hearing impairment annually in the United States.

Avian Dis, 1994 Apr-Jun, 38(2), 361 - 5
Characterization of two monoclonal antibodies directed against serovar A Haemophilus paragallinarum; Blackall PJ et al.; Two monoclonal antibodies (MAbs) raised against a serovar A Haemophilus paragallinarum were evaluated for their ability to react with 11 reference strains that represented all the recognized serovars and with 27 field isolates of Page serovar A collected from around the world . The MAbs were used in a hemagglutination-inhibition assay . Both MAbs recognized type strains of Page serovar A and Kume serovars A-1 and A-2 but not the type strains of Kume serovars A-3 and A-4 . Neither MAb recognized the type strains of Page serovars B and C or Kume serovars B-1, C-1, C-2, C-3, or C-4 . When evaluated with the 27 Page serovar A field isolates, both MAbs recognized only 10 isolates . All of the recognized isolates belonged to Kume serovars A-1 (nine isolates) or A-2 (one isolate) . All of the field isolates that were not recognized by one or the other of the MAbs either were Kume serovar A-4 (seven isolates) or could not be placed in an existing Kume A serovar (10 isolates) . The results indicate that the epitope recognized by these MAbs is present only in strains of H . paragallinarum that belong to Kume serovars A-1 and A-2.

Avian Dis, 1994 Apr-Jun, 38(2), 289 - 92
Protective effect of oral administration of killed Haemophilus paragallinarum serotype A on chickens; Nakamura T et al.; Orally administered bacterin of killed Haemophilus paragallinarum effectively induced production of serum hemagglutination-inhibition antibodies in chickens, and all immunized chickens were protected from subsequent infection . Although one intramuscular dose of 10(8) cells adjuvanted with aluminium phosphate gel (equivalent to commercial vaccine) induced protective immunity, two oral doses of 10(10) cells each with no adjuvants were required to induce effective immunity.

Avian Dis, 1994 Apr-Jun, 38(2), 269 - 74
Characterization of isolates of avian haemophili from Brazil; Blackall PJ et al.; The biochemical and serological properties of 29 isolates of avian haemophili obtained from chickens in Brazil are described . Twenty-seven of the isolates had the typical biochemical properties of Haemophilus paragallinarum . The two remaining isolates had the typical properties of Pasteurella avium, formerly known as Haemophilus avium . All of the H . paragallinarum isolates were serotyped according to the Page scheme using a hemagglutination-inhibition test . Fourteen of the isolates were serovar A, one was serovar B, 11 were serovar C, and one isolate could not be serotyped . The isolates were also examined using a panel of monoclonal antibodies for Page serovars A (one monoclonal antibody available) and C (three monoclonal antibodies available) . As expected, the serovar B isolate failed to react with any monoclonal antibody, whereas the 11 serovar C isolates reacted with all three serovar C monoclonal antibodies but not with the serovar A monoclonal antibody . Only eight of the 14 serovar A isolates reacted with the serovar A monoclonal antibody.

Diagn Microbiol Infect Dis, 1994 Apr, 18(4), 243 - 9
Validation of NCCLS macrolide (azithromycin, clarithromycin, and erythromycin) interpretive criteria for Haemophilus influenzae tested with the Haemophilus test medium . National Committee for Clinical Laboratory Standards; Jones RN et al.; Some recently marketed macrolide antimicrobial agents possess physiochemical, antimicrobial, and pharmacokinetic advantages that enable their wider clinical use against Haemophilus influenzae infections . A five-laboratory study assessed the validity of existing or proposed azithromycin, clarithromycin, and erythromycin interpretive criteria for tests with H . influenzae isolates . National Committee for Clinical Laboratory Standards (NCCLS) methods, criteria, and quality-control guidelines were used . A total of 350 H . influenzae strains were processed, including fresh clinical isolates (250 strains) and replicate tests of 100 stock cultures sampling strains isolated from 1984 to 91 . Azithromycin interpretive criteria (susceptible at < or = 4 micrograms/ml, > or = 12 mm) produced a 99.8% absolute agreement between the minimum inhibitory concentrations and disk diffusion results (0.2% false-susceptible error) . Clarithromycin breakpoint criteria (susceptible at < or = 8 micrograms/ml, > or = 13 mm; and resistant at > or = 32 micrograms/ml, < or = 10 mm) produced high minor interpretive error, but < or = 1% combined false-susceptible and false-resistant discrepancies . Erythromycin interpretive guidelines were initially proposed for susceptible at < or = 0.5 microgram/ml, > or = 26 mm . This categorizes nearly all H . influenzae strains as resistant to this older macrolide . The NCCLS should consider the proposed erythromycin criteria for publication in appropriate tables, and a class drug should also be selected (azithromycin) that would best predict macrolide-class susceptibility for those agents indicated by the US Food and Drug Administration for H . influenzae infection chemotherapy (azithromycin and clarithromycin) . No serious interpretive problems were observed with the current NCCLS criteria using Haemophilus test medium.

Transplantation, 1994 Mar 15, 57(5), 677 - 84
Polysaccharide conjugate vaccine responses in bone marrow transplant patients; Guinan EC et al.; Bone marrow transplant patients have impaired responses to pure polysaccharide (PS) vaccines and are at an increased risk for disease caused by PS encapsulated pathogens such as Haemophilus influenzae type B (HIB) and Streptococcus pneumoniae . We immunized 35 BMT patients (21 allogeneic and 14 autologous) ages 2-45 years with pure PS pneumococcal (Pnu-imune 23) HIB-conjugate (HibTITER), and tetanus toxoid vaccines . Patients were assigned to receive vaccines at either 12 and 24 months after transplantation or at 24 months only . Only 19% of all enrolled patients developed protective antibody concentrations (> or = 0.300 microgram antibody nitrogen/ml) to the 6 pneumococcal serotypes measured after the 24-month immunization . Poor response to pneumococcal vaccine was not different for the 2 study groups and was similar to previous studies . In contrast, HIB-conjugate vaccine elicited protective concentrations of antibody (> or = 1.0 microgram/ml) in 56% of patients after 1 dose and in 80% after 2 doses . The group that received 2 doses of HIB-conjugate vaccine had a significantly higher geometric mean antibody concentration of 14.5 micrograms/ml as compared with 1.43 micrograms/ml for those receiving only 1 dose (P = 0.012) . Responses to tetanus toxoid vaccine were similar to HIB-conjugate vaccine, with a booster response documented after the second dose . In summary, 2 doses of HIB-conjugate vaccine given at 12 and 24 months after transplantation produced protective antibody concentrations in 80% of patients . While the response to pure PS pneumococcal vaccine was poor, the results with HIB-conjugate vaccine suggest that future pneumococcal conjugate vaccines may also benefit BMT patients.

MMWR Morb Mortal Wkly Rep, 1994 Mar 4, 43(8), 144 - 8
Progress toward elimination of Haemophilus influenzae type b disease among infants and children--United States, 1987-1993; Development of experimental respiratory infections in neutropenic rats with either penicillin-resistant Streptococcus pneumoniae or beta-lactamase-producing Haemophilus influenzae; SmithKline Beecham Pharmaceuticals, Betchworth, Surrey, United KingdomAcute respiratory infections with penicillin-resistant strains of Streptococcus pneumoniae and a beta-lactamase-producing strain of Haemophilus influenzae were established in neutropenic weanling rats . By use of nonsurgical intrabronchial instillation of the bacteria suspended in molten agar, reproducible, acute respiratory infections suitable for experimental antibiotic efficacy studies were established.

Klin Padiatr, 1994 Mar-Apr, 206(2), 108 - 11
Epidemiology of invasive Haemophilus influenzae disease in a German city; Severien C et al.; This study was done to analyze the epidemiology of invasive Haemophilus influenzae disease in Bochum city area . Forty-eight children with invasive Haemophilus influenzae infections were treated at the University Children's Hospital in Bochum during the study period from January 1971 to June 1992 . Clinical manifestations included meningitis (n = 34), epiglottitis (n = 8), pneumonia (n = 2), bacteremia (n = 2), cellulitis (n = 1) and osteomyelitis (n = 1) . The overall yearly incidence rate for all invasive Haemophilus influenzae infections was 13 per 100,000 children younger than five years of age, with a marked increase in the last six years . Haemophilus influenzae meningitis showed no significant change during the study period with an overall yearly incidence of 9 per 100,000 children younger than five years . Twenty-eight cases (58%) of all invasive Haemophilus influenzae infections occurred in patients under two years of age and five cases (10%) were younger than six months . Invasive Haemophilus influenzae disease showed no seasonal prevalence . All isolates were susceptible to ampicillin . No deaths occurred, but severe bilateral deafness resulted in one patient with meningitis . Prospective epidemiologic studies are needed to estimate clinical efficacy of the Haemophilus influenzae type b immunization program in Germany.

J Clin Microbiol, 1994 Mar, 32(3), 725 - 31
A 4-year survey of antimicrobial susceptibility trends for isolates from cattle with bovine respiratory disease in North America; Watts JL et al.; The antimicrobial susceptibility trends of bovine respiratory disease (BRD) pathogens isolated from 1988 to 1992 were determined . A total of 880 isolates representing Pasteurella haemolytica, Pasteurella multocida, and Haemophilus somnus were used in the study . Overall, resistance to ampicillin, tetracycline, erythromycin, and sulfamethazine was frequently encountered among strains of P . haemolytica and P . multocida . Ceftiofur, an extended-spectrum cephalosporin originally marketed in 1988 for the treatment of BRD, was very active against the BRD pathogens tested; the MIC of ceftiofur for 90% of isolates tested was < or = 0.06 microgram/ml . Resistance to spectinomycin varied on the basis of the breakpoint used . Substantial variation in the year-to-year susceptibility of BRD pathogens to tilmicosin, a new macrolide antimicrobial agent, was observed . The proportion of susceptible P . haemolytica isolates ranged from 84.7% in the second year to 7.1% in the third year and 78.2% in the fourth year . Similar fluctuations were observed with strains of P . multocida.

Pediatr Infect Dis J, 1994 Mar, 13(3), 183 - 8
A prospective cohort study on breast-feeding and otitis media in Swedish infants; Aniansson G et al.; This study analyzed the effect of breast-feeding on the frequency of acute otitis media . The protocol was designed to examine each child at 2, 6 and 10 months of age . At each visit nasopharyngeal cultures were obtained, the feeding pattern was recorded and the acute otitis media (AOM) episodes were documented . The analysis was based on 400 children from whom complete information was obtained . They represented 83% of the newborns in the study areas . By 1 year of age 85 (21%) children had experienced 111 AOM episodes; 63 (16%) had 1 and 22 (6%) had 2 or more episodes . The AOM frequency was significantly lower in the breast-fed than in the non-breast-fed children in each age group (P < 0.05) . The first AOM episode occurred significantly earlier in children who were weaned before 6 months of age than in the remaining groups . The frequency of nasopharyngeal cultures positive for Haemophilus influenzae, Moraxella catarrhalis and Streptococcus pneumoniae was significantly higher in children with AOM . At 4 to 7 and 8 to 12 months of age, the AOM frequency was significantly higher in children with day-care contact and siblings (P < 0.05 and < 0.01, respectively) . The frequency of upper respiratory tract infections was increased in children with AOM but significantly reduced in the breast-fed group.

J Infect Dis, 1994 Mar, 169(3), 676 - 9
Natural genetic transfer of a putative virulence-enhancing mutation to Haemophilus influenzae type a; Kroll JS et al.; Haemophilus influenzae strains of serotype a very rarely cause life-threatening infections . Examination of strains from the Gambia, West Africa, that caused septicemia, meningitis, or both revealed that a clone has emerged that carries a DNA deletion previously identified only in type b strains that is hypothesized to contribute to the special virulence of that serotype . This clone appears to have arisen by transfer of DNA between type a and type b strains, a transformation event that has happened more than once, as shown by the discovery Kenya, East Africa, of a clonally distinct type a strain bearing the identical deletion . The implications for the emergence of clinically important non-type b strains of H . influenzae are obvious.

J Bacteriol, 1994 Mar, 176(6), 1630 - 8
A gene at 59 minutes on the Escherichia coli chromosome encodes a lipoprotein with unusual amino acid repeat sequences; Ichikawa JK et al.; We report a 1.432-kb DNA sequence at 59 min on the Escherichia coli chromosome that connects the published sequences of the pcm gene for the isoaspartyl protein methyltransferase and that of the katF or rpoS (katF/rpoS) gene for a sigma factor involved in stationary-phase gene expression . Analysis of the DNA sequence reveals an open reading frame potentially encoding a polypeptide of 379 amino acids . The polypeptide sequence includes a consensus bacterial lipidation sequence present at residues 23 to 26 (Leu-Ala-Gly-Cys), four octapeptide proline- and glutamine-rich repeats of consensus sequence QQPQIQPV, and four heptapeptide threonine- and serine-rich repeats of consensus sequence PTA(S,T)TTE . The deduced amino acid sequence, especially in the C-terminal region, is similar to that of the Haemophilus somnus LppB lipoprotein outer membrane antigen (40% overall sequence identity; 77% identity in last 95 residues) . The LppB lipoprotein binds Congo red dye and has been proposed to be a virulence determinant in H . somnus . Utilizing a plasmid construct with the E . coli gene under the control of a phage T7 promoter, we demonstrate the lipidation of this gene product by the incorporation of {3H}palmitic acid into a 42-kDa polypeptide . We also show that treatment of E . coli cells with globomycin, an inhibitor of the lipoprotein signal peptidase, results in the accumulation of a 46-kDa precursor . We thus designate the protein NlpD (new lipoprotein D) . E . coli cells overexpressing NlpD bind Congo red dye, suggesting a common function with the H . somnus LppB protein . Disruption of the chromosomal E . coli nlpD gene by insertional mutagenesis results in decreased stationary-phase survival after 7 days.

Blood, 1994 Mar 1, 83(5), 1278 - 88
Human serum IgA downregulates the release of inflammatory cytokines (tumor necrosis factor-alpha, interleukin-6) in human monocytes; Wolf HM et al.; While the protective effect of IgA antibodies against infection of the mucosal surfaces is well documented, the mechanisms involved are not entirely clear . The aim of the current study is to investigate the effect of human serum IgA on the release of inflammatory cytokines in human monocytes activated with a particulate stimulus, Haemophilus influenzae type b (Hib), or soluble lipopolysaccharide (LPS) purified from Escherichia coli . Our results show that IgA downregulates tumor necrosis factor-alpha (TNF-alpha) and interleukin-6 (IL-6) production, whereas IgG examined in parallel had no effect . IgA had no inhibitory effect on Hib-induced granulocyte-macrophage colony-stimulating factor release . TNF-alpha and IL-6 release were downmodulated if IgA was present during cytokine induction, and IgA was also inhibitory if added to Hib-pretreated monocytes during the phase of cytokine release . These findings indicate that there are at least two mechanisms whereby IgA antibodies can downregulate TNF-alpha and IL-6 release in human monocytes: by a mechanism acting during the time of monocyte activation, and a mechanism that downregulates the production and/or the release of these cytokines in activated monocytes . Regulation of TNF-alpha and IL-6 release by IgA may be among the antiinflammatory mechanisms preventing an uncontrolled release of potentially noxious levels of inflammatory cytokines during acute and/or chronic inflammation.

Infect Immun, 1994 Mar, 62(3), 868 - 73
Proteins found within porcine respiratory tract secretions bind lipopolysaccharides of Actinobacillus pleuropneumoniae; Belanger M et al.; Affinity for porcine respiratory tract secretions was found in some isolates of Actinobacillus pleuropneumoniae and involved lipopolysaccharides (LPS) (M . Belanger, S . Rioux, B . Foiry, and M . Jacques, FEMS Microbiol . Lett . 97:119-126, 1992) . In the present study, the affinity for a crude preparation of porcine respiratory tract mucus of isolates of the Pasteurellaceae family, i.e., Actinobacillus, Haemophilus, and Pasteurella spp., and of some unrelated gram-negative bacteria was examined . Affinity for crude porcine respiratory tract mucus was not a property shared by all Pasteurellaceae isolates tested . Furthermore, affinity for the porcine crude mucus preparation was not unique to the Pasteurellaceae group and did not seem to be restricted to bacteria originating from pigs . Different surface properties of A . pleuropneumoniae isolates in relation to their adherence to crude mucus were examined . The capsular layer seemed to mask the adhesin and interfered with adherence to crude mucus . Two poorly capsulated isolates, which had a more hydrophobic surface and bound Congo red, were also heavily labeled by gold particles coated with polymyxin, which is known to interact with the lipid A-core region of LPS, and adhered strongly to respiratory tract secretions . Tetramethylurea, charged polymers, divalent cations, chelators, monosaccharides and amino sugars, or lectins were unable to inhibit adherence of A . pleuropneumoniae to the crude mucus preparation . To identify the receptor(s) recognized by the lipopolysaccharidic adhesin of A . pleuropneumoniae, affinity chromatography was used . Two bands, which were proteinaceous in nature, of 10 and 11 kDa were recovered . Our results suggest that two low-molecular-mass proteins present in porcine respiratory tract secretions bind A . pleuropneumoniae LPS.

Infect Immun, 1994 Mar, 62(3), 779 - 84
Opsonic antibodies to outer membrane protein P2 of nonencapsulated Haemophilus influenza are strain specific; Troelstra A et al.; The ability of monoclonal antibodies (MAbs) specific for variable and conserved epitopes of outer membrane protein (OMP) P2 (b,c) of nonencapsulated Haemophilus influenza to promote opsonophagocytosis of this bacterium by human polymorphonuclear leucocytes (PMNs) was determined by flow cytometry . MAbs rendering PMNs fluorescent because of association with fluorescein isothiocyanate-labelled bacteria were defined as stimulating opsonophagocytosis . Opsonophagocytosis was dependent on the presence of both antibodies and complement . Of the 14 MAbs directed to the variable parts of OMP P2 (L . van Alphen, P . Eijk, L . Geelen-van den Broek, and J . Dankert, Infect . Immun . 59:247-252, 1991), 9 stimulated opsonophagocytosis . Four of the five nonopsonophagocytic MAbs that were immunoglobulin G1 were unable to cause complement activation . The MAbs promoting opsonophagocytosis included MAbs specific for one or more OMP P2 antigenic variants of H . influenzae strains isolated from patients with chronic bronchitis during persistent infection . MAbs cross-reacting in enzyme-linked immunosorbent assays with nonrelated H . influenzae did not promote opsonophagocytosis of strains from other patients . Opsonophagocytosis was not observed in the presence of three MAbs reacting with OMP P2 epitopes common in H . influenzae . These results indicate that OMP P2-dependent opsonophagocytosis of nonencapsulated H . influenzae is strictly strain specific.

Infect Immun, 1994 Mar, 62(3), 1015 - 25
Identification and characterization of the Treponema pallidum tpn50 gene, an ompA homolog; Hardham JM et al.; Treponema pallidum is a pathogenic spirochete that has no known genetic exchange mechanisms . In order to identify treponemal genes encoding surface and secreted proteins, we carried out TnphoA mutagenesis of a T . pallidum genomic DNA library in Escherichia coli . Several of the resulting clones expressed enzymatically active T . pallidum-alkaline phosphatase fusion proteins . The DNA sequence of the 5' portion of a number of the treponemal genes was obtained and analyzed . A recombinant clone harboring plasmid p4A2 that encoded a treponemal protein with an approximate molecular mass of 50,000 Da was identified . Plasmid p4A2 contained an open reading frame of 1,251 nucleotides that resulted in a predicted protein of 417 amino acids with a calculated molecular mass of 47,582 Da . We have named this gene tpn50 in accordance with the current nomenclature for T . pallidum genes . A 1.9-kb HincII-ClaI fragment from p4A2 that contained the tpn50 gene was subcloned to produce p4A2HC2 . Comparison of the predicted amino acid sequence of TpN50 with protein sequences in the National Center for Biotechnology Information data base indicated statistically significant homology to the Pseudomonas sp . OprF, E . coli OmpA, Bordetella avium OmpA, Neisseria meningitidis RmpM, Neisseria gonorrhoeae PIII, Haemophilus influenzae P6, E . coli PAL, and Legionella pneumophila PAL proteins . These proteins are all members of a family of outer membrane proteins that are present in gram-negative bacteria . The tpn50 gene complemented E . coli ompA mutations on the basis of two separate criteria . First, morphometry and electron microscopy data showed that E . coli C386 (ompA lpp) cells harboring plasmid vector pEBH21 were rounded while cells of the same strain harboring p4A2HC2 (TpN50+), pWW2200 (OprF+), or pRD87 (OmpA+) were rod shaped . Second, E . coli BRE51 (MC4100 delta sulA-ompA) cells harboring pEBH21 grew poorly at 42 degrees C in minimal medium, while the growth of BRE51 cells harboring p4A2HC2 was similar to that of the parental MC4100 cells . These results demonstrate that the TpN50 protein is functionally equivalent to the E . coli OmpA protein . If TpN50 functions in a similar fashion in T . pallidum, then it may be localized to the treponemal outer membrane.

Microb Pathog, 1994 Mar, 16(3), 243 - 7
Haemophilus ducreyi adheres to human keratinocytes; Brentjens RJ et al.; Haemophilus ducreyi, Moraxella catarrhalis and a non-piliated Escherichia coli K-12 strain were studied for their ability to bind to human keratinocytes in vitro . Epidermal cells isolated from neonatal foreskins were grown to confluence in serum-free keratinocyte media . Probing of the monolayers with anti-cytokeratin antibody showed that 97% of cells were keratinocytes . Bacteria were grown to mid-log phase and seeded onto the monolayers . At various time-points monolayers were washed with PBS to remove non-adherent bacteria, and the monolayers were quantitatively cultured . After 120 min, 15 to 23% of the H . ducreyi inocula bound to the monolayer, while less than 1% of the M . catarrhalis or E . coli controls bound . Wet mounts of fixed monolayers observed with differential interference contrast microscopy confirmed the quantitative data . We conclude that H . ducreyi binds to keratinocytes and that this process may play a role in the initiation of chancroid.

Pediatr Med Chir, 1994 Mar-Apr, 16(2), 129 - 33
{Haemophilus influenzae type b meningitis . The therapeutic considerations and the authors' personal experience}; Bolesani C et al.; The authors describe five clinical cases concerning meningitis due to Haemophilus influenzae type b recorded in our hospital from June 1991 to April 1993 . We studied the therapeutical association between ceftriaxone and dexamethasone, and we analysed, according to the newest data in the literature, its physiopathological and clinical assumptions which would advice its usual use against the meningitis caused by Haemophilus influenzae type b.

Sex Transm Dis, 1994 Mar-Apr, 21(2 Suppl), S76 - 80
Recent changes in the epidemiology of genital ulcer disease in the United States . The crack cocaine connection; Martin DH et al.; The incidence of syphilis and chancroid began to increase in the United States among heterosexuals in the mid-1980s, with most cases reported among minorities living in Eastern cities and in the South . A number of studies have established a link between increasing syphilis incidence rates and cocaine use, specifically the smoked form of the drug, which is known as "crack." A similar link was hypothesized for chancroid, but supporting data became available only recently . In New Orleans, we showed that Haemophilus ducreyi infection in male patients was strongly associated with crack cocaine use . However, our studies also demonstrated that drug use by the patient actually was a marker for a more important risk factor: sexual exposure to a cocaine-using woman . Thus, although the details of the relationships among crack, sexual behavior, and the size and nature of core transmitter groups are not known, it is clear that crack cocaine abuse is the driving force behind the recent syphilis and chancroid epidemics in the United States . Although it is not possible to predict the effects of these events on human immunodeficiency virus (HIV) transmission, the potential for significant synergism between them exists . New approaches to HIV surveillance should be developed taking this possibility into account . During the last 3 to 4 years, incidence rates of syphilis and chancroid have fallen in the United States, despite continued problems throughout the country with crack cocaine abuse . However, our studies and those of others have shown how difficult it is to recognize chancroid clinically, suggesting that the disease may be grossly underreported.(ABSTRACT TRUNCATED AT 250 WORDS)

Mil Med, 1994 Mar, 159(3), 220 - 3
Evaluation of health, sanitation, and nutrition in Forces Command Child Development Centers; Arday DR et al.; In 1992, Forces Command had 42 Child Development Centers on 22 installations . We evaluated program compliance in the areas of health, sanitation, and nutrition using inspection findings from April 1991 through June 1992 . Each program was rated on 20 items, using inspection checklists developed for this evaluation . We also surveyed Haemophilus influenza type b (Hib) vaccination records among enrolled children . Most programs and facilities were fully or partially compliant in most areas . By quantifying the inspection findings, we were able to identify compliance items that needed further attention . The most frequent problem area across all programs was documentation of child immunization and health records . For children between 13 and 60 months of age, 77.7% had records indicating appropriate vaccination against Hib . Comparisons with the prior year's findings indicated a trend toward improvement.

Mol Microbiol, 1994 Mar, 11(6), 1181 - 9
Antigenic drift of non-encapsulated Haemophilus influenzae major outer membrane protein P2 in patients with chronic bronchitis is caused by point mutations; Duim B et al.; The sequence of the gene encoding major outer membrane protein (MOMP) P2 of antigenic variants of non-encapsulated Haemophilus influenzae isolated from persistently infected chronic bronchitis patients was analysed . Antigenic drift was shown to result from single base changes in the P2 gene, all generating amino acid changes in the surface-exposed loops of MOMP P2, predominantly in loop 6 . Similar single base changes were observed in H . influenzae persistently present in a subcutaneous cage implanted in rabbits, as well as in a spontaneous H . influenzae mutant that had survived MOMP P2 specific monoclonal-antibody-dependent bactericidal killing in vitro . We hypothesize that accumulation of point mutations under the selection pressure of immunity is a mechanism of antigenic drift of a surface-exposed protein during persistent H . influenzae infection.

Rev Inst Med Trop Sao Paulo, 1994 Mar-Apr, 36(2), 105 - 9
{Isolation of Haemophilus aegyptius associated with Brazilian purpuric fever, of Chloropidae (Diptera) of the genera Hippelates and Liohippelates}; Tondella ML et al.; The recognition of the Brazilian purpuric fever (BPF) in 1984 led to a number of studies which showed a relation between this disease and conjunctivitis caused by Haemophilus aegyptius . The increase in cases of conjunctivitis in children associated with higher population density of eye gnats (Chloropidae: Hippelates) has been reported since last century . This phenomenon is related to the attraction that those flies show for the eyes, secretions and wounds, from where they feed on . Although there are evidences on the role of these flies in the mechanical transmission of seasonal bacterial conjunctivitis, the isolation of Haemophilus aegyptius from them in their natural habitat had not been demonstrated yet . In this study Haemophilus aegyptius associated to BPF was isolated from two pools of chloropids collected around the eyes of children with conjunctivitis which were identified as Liohippelates peruanus (Becker) and a new species Hippelates neoproboscideus.

Berl Munch Tierarztl Wochenschr, 1994 Mar, 107(3), 78 - 81
{The lipopolysaccharide structure of Haemophilus parasuis strains in SDS-PAGE}; Zucker B et al.; The LPS patterns of 231 H.p . strains were studied by using SDS-PAGE . The strains were isolated from the nasal mucous membrane of clinical healthy animals, from animals with GK and from animals with pneumonia without any symptoms of GK . The LPS patterns of H.p . strains consists of 2 to 4 bands of high electrophoretical mobility . In all it was possible to distinguish seven different LPS electrophoretic profiles . The distribution of the H.p . isolates from clinically healthy animals and animals with GK or pneumonia to the 7 LPS electrophoretic profiles shows a similar picture . Variation in the growth conditions showed a process of a standardization of the LPS structure as a result of an increased CO2 atmosphere or lack of O2 respectively.

Wiad Lek, 1994 Mar, 47(5-6), 231 - 3
{Diagnostic and therapeutic difficulties in a case of infection with Haemophilus influenzae}; Dzianott A et al.; A case is presented of generalized Haemophilus infection followed by its concentration in the central nervous system, joints and middle ear.

Southeast Asian J Trop Med Public Health, 1994 Mar, 25(1), 123 - 31
Upper airway carriage by Haemophilus influenzae and Streptococcus pneumoniae in Australian aboriginal children hospitalised with acute lower respiratory infection; Gratten M et al.; When nasopharyngeal secretions from 171 Australian Aboriginal children hospitalized with acute lower respiratory tract infections (ALRI) were cultured selectively for Streptococcus pneumoniae and Haemophilus influenzae, 136 (79.5%) and 151 (88.3%) children yielded 166 and 254 isolates of S . pneumoniae and H . influenzae, respectively . In colonized subjects multiple populations of S . pneumoniae (20% of carriage-positive patients) and H . influenzae (55%) were common . Pneumococci belonging to 27 types or groups were identified . H . influenzae serotype b colonized 16.4% of all children studied . More than one half of 152 children tested were excreting antibiotics at the time of admission to hospital . Significantly fewer children with serum antibiotic residues were colonized with S . pneumoniae than were antibiotic free children . Antibiotic usage had no measurable impact on the isolation rate of H . influenzae.

S Afr Med J, 1994 Mar, 84(3), 135 - 7
Carriage of Haemophilus influenzae in Cape Town children; Hussey GD et al.; Little is known about the epidemiology of Haemophilus influenzae infections in South Africa . This study was designed to determine the prevalence, serotype distribution, antimicrobial susceptibility pattern and effect of age and hospitalisation on the carriage of H . influenzae in 322 Cape Town children . The overall and type b specific carriage rates in normal children (N = 107) were 45.8% and 4.7% respectively . The yield following nasopharyngeal culture was twice that following throat culture (P < 0.001) . Children hospitalised with tuberculosis (N = 62) had significantly greater carriage rates, 66.1% and 37.1% respectively (P = 0.02) . Institutionalised mentally handicapped children (N = 77) and children with tuberculosis attending an outpatient clinic (N = 76) had lower carriage rates (P < 0.02) . Antimicrobial resistance was a major problem only in children hospitalised with tuberculosis (rifampicin 100%, penicillin 43.9%, erythromycin 85.4%, co-trimoxazole 82.9%) . This universal resistance to rifampicin has not been reported previously . There was no difference in the mean age of children with positive or negative cultures, with the exception of those hospitalised with tuberculosis . In this group children infected with type b were much younger (mean 19.7 months) than those with other and non-typeable infections (32.1 months) and the non-infected (50.1 months) (P = 0.04) . Duration of hospitalisation or outpatient therapy in the patients with tuberculosis did not influence carriage rates.(ABSTRACT TRUNCATED AT 250 WORDS)

Biol Chem Hoppe Seyler, 1994 Mar, 375(3), 173 - 82
Mapping of antigenic and immunogenic sites of Haemophilus influenzae outer membrane protein P6 using synthetic lipopeptides; Beck-Sickinger AG et al.; The immune response to the P6 protein of Haemophilus influenzae was characterized with 24 synthetic icosapeptides and 45 dodecapeptides conjugated to the immune stimulator N-palmitoyl-S-{2,3-(bispalmitoyloxy)-(2RS)-propyl}-(R)-cysteinyl-( S)-serine . The antigenicity of these lipopeptides was investigated by enzyme-linked immunosorbent assays with rabbit anti-P6 serum . The epitopes of P6 protein were identified and localized within residues 31-46 and 59-70 and in the C-terminal part of the P6 protein . Mice were immunized with lipoicosapeptides without using additional adjuvants or carriers and the antibody titers were measured with isolated P6 protein and lipopeptides in a dot blot assay . Lipopeptides containing the sequence pattern QILDAHAA (P6 47-54) and the mouse B cell epitope GEYV (P6 43-46) induced high titers of anti P6 antibodies . These murine antibodies were able to neutralize the intact bacterium Haemophilus influenzae.

JAMA, 1994 Feb 16, 271(7), 525 - 30
Immunization status of children of employees in a large corporation; Fielding JE et al.; OBJECTIVE--To assess immunization levels for children of employees of a large corporation . DESIGN--A mail survey of a random sample of employees on the immunization history of one child per family . SETTING--US employees of Johnson & Johnson . PARTICIPANTS--1500 employees with children born between 1984 and 1991 . MAIN OUTCOME MEASURES--Coverage rates for recommended vaccines at different ages up to 6 years . MAIN RESULTS--Only 45.2% and 55.3% of the study children at ages 2 and 6 years were current for all recommended immunizations (65.1% and 70.3%, respectively, excluding the Haemophilus influenzae type b vaccine) . Using the minimum standard required by many states for school entry, the coverage level at age 6 years was 90.4% . Factors associated with higher immunization rates at age 2 years were the corporate health plan (choices), higher pay level, greater parental formal education, white race, and knowing when to initiate immunization . Lower immunization rates at age 2 years were associated with delayed receipt of the first dose of diphtheria, tetanus, and pertussis vaccine, use of city or county clinics, employee-reported barriers of difficulty leaving work, and provider access problems, but not cost of services . After adjusting for the effects of other variables through logistic regression, race, pay level, and plan choice were no longer significant . Modeling with the remaining variables predicted rates of adequate immunization at age 2 years from 15% to 81% . CONCLUSION--Even in this relatively affluent group with good insurance (including immunizations), preschool immunization rates did not reach public health goals . Changing modifiable factors, such as knowing when to initiate immunization, enabling parents to leave work more easily, and improving provider access, might improve preschool immunization rates.

MMWR Morb Mortal Wkly Rep, 1994 Feb 4, 43(4), 57 - 60
Reported vaccine-preventable diseases--United States, 1993, and the childhood immunization initiative; Haemophilus influenzae: the efficiency of reporting invasive disease in England and Wales; Department of Public Health Medicine, Trent Regional Health AuthorityThis study compares the efficiency of a special regional survey with routine laboratory reporting to measure the incidence of invasive disease caused by Haemophilus influenzae before routine immunisation against type b strains was introduced . Incomplete reporting does not prevent the monitoring of trends, but it becomes important if the level of underreporting changes with time . This study illustrates the importance of assessing the quality of surveillance data before using them to inform policy or evaluate intervention . Underreporting to the regional survey was found to be 17% and underreporting to the Public Health Laboratory Service (PHLS) Communicable Disease Surveillance Centre (CDSC) was 24% . In response to this study a system has been set up to send reference laboratories a weekly list of reports to CDSC . Manual cross checking helps to complete the ascertainment of cases . All isolates of H . influenzae from cases of invasive disease should be sent to the reference laboratories for serotyping as well as being reported to CDSC.

J Fam Pract, 1994 Feb, 38(2), 175 - 9
Penicillin failure and copathogenicity in streptococcal pharyngotonsillitis; Brook I; Recurrent group A beta-hemolytic streptococcus (GABHS) pharyngotonsillitis related to penicillin failure presents a serious clinical problem . Failure to eradicate streptococci from patients can occasionally lead to rheumatic fever and rarely to glomerulonephritis . beta-lactamase-producing strains of aerobic and anaerobic bacteria in inflamed tonsils have been associated with increased failure rates of penicillins in the eradication of these infections . These organisms include Staphylococcus aureus, Haemophilus influenzae and H parainfluenzae, Moraxella catarrhalis, Fusobacterium sp, and pigmented Prevotella and Porphyromonas spp . The indirect pathogenicity of these organisms is apparent in their ability not only to survive penicillin therapy but also to protect penicillin-susceptible pathogens from that drug . These organisms have demonstrated the ability to protect GABHS in vitro and in vivo from penicillin . Numerous reports have described the successful therapy of recurrent GABHS tonsillitis with antimicrobials directed at both GABHS and the beta-lactamase-producing organisms.

J Pediatr, 1994 Feb, 124(2), 323 - 7
Immunogenicity and safety of Haemophilus influenzae type b-tetanus protein conjugate vaccine alone or mixed with diphtheria-tetanus-pertussis vaccine in infants; Kaplan SL et al.; Haemophilus capsular polysaccharide-tetanus toxoid conjugate (PRP-T) and diphtheria-tetanus-pertussis (DTP) vaccines were administered in a single syringe (group 1) or separate syringes (group 2) to 284 infants at 2, 4, and 6 months of age . Group 1 infants had a slightly greater incidence of local reactions . Systemic reactions were similar . The geometric mean titers of polyribosylribitol phosphate (PRP) serum antibody concentrations after the third dose of PRP-T vaccine were 4.8 and 4.3 micrograms/ml for groups 1 and 2, respectively . Antibody responses to DTP antigens were also similar . The immunogenicity and safety of the PRP-T and DTP vaccines are equivalent when the vaccines are administered in separate syringes or the same syringe to infants.

J Pediatr, 1994 Feb, 124(2), 193 - 8
Human milk secretory IgA antibody to nontypeable Haemophilus influenzae: possible protective effects against nasopharyngeal colonization; Harabuchi Y et al.; Sixty-eight children fed human milk were followed prospectively from birth to 12 months of age to assess the effect of milk antibody on nasopharyngeal colonization . Human milk secretory IgA antibody to P6, a highly conserved outer membrane protein of nontypeable Haemophilus influenzae, was measured with the use of an enzyme-linked immunosorbent assay . Nasopharyngeal colonization with nontypeable H . influenzae and the occurrence of otitis media were determined . Nasopharyngeal colonization was found in 22 children (32%), and 39 children (57%) had otitis media . Frequency of isolation of nontypeable H . influenzae was directly related to episodes of otitis media (r = 0.35; p = 0.001) . The level of human milk anti-P6 secretory IgA antibody was inversely related to frequency of isolation of the organism (r = -0.27; p = 0.026) . The average antibody level, expressed as nanograms per 0.1 mg total secretory IgA, in human milk fed to children with no colonization of nontypeable H . influenzae was significantly higher than in milk fed to children in whom colonization occurred on multiple occasions (156 +/- 120 vs 69 +/- 50; p = 0.013) . Prevention of colonization was most evident during breast-feeding . These data suggest that the protective effects of human milk against otitis media may be due in part to inhibition of nasopharyngeal colonization with nontypeable H . influenzae by specific secretory IgA antibody.

J Bacteriol, 1994 Feb, 176(3), 691 - 5
Involvement of phospholipid end groups of group C Neisseria meningitidis and Haemophilus influenzae type b polysaccharides in association with isolated outer membranes and in immunoassays; Arakere G et al.; There are several bacterial polysaccharides (PSs) which contain a terminal lipid moiety . It has been postulated that these terminal lipid moieties anchor the PSs to the outer membrane of the bacteria . Our studies have shown that incubation of native PS from group C Neisseria meningitidis or Haemophilus influenzae type b with isolated outer membrane vesicles results in association of a portion of the PS with the vesicles . Removal of the terminal lipid from the PS by treatment with phospholipase A2 or phospholipase D eliminates this association . In other studies, it was shown that delipidated PSs are not suitable as solid-phase antigens in a currently used enzyme-linked immunosorbent assay (ELISA) . Measurement of antibody units in the reference sera by using delipidated PSs as antigens in an ELISA yielded negligible absorbance compared with native PSs when methylated human serum albumin was used to coat the PSs to the plate . Nevertheless, phospholipase A2 and phospholipase D treatment did not noticeably affect antigenic epitopes, since soluble group C PS without the terminal lipid bound antibody as effectively as the native PS did, as measured by a competitive inhibition assay . Both hydrophobic and electrostatic interactions are important for the binding of group C N . meningitidis PS to the ELISA plate, while charge interactions seem to be sufficient for binding the more negatively charged H . influenzae type b PS.

Curr Opin Pediatr, 1994 Feb, 6(1), 29 - 35
Bacterial meningitis in children; Booy R et al.; Bacterial meningitis is an important problem in childhood . Vaccines can prevent Haemophilus influenzae type b disease and are being developed for infections caused by meningococci and pneumococci . Lumbar puncture is an important part of the diagnostic workup although care is required with its use . Once meningitis is diagnosed, antibiotic treatment should be started forthwith, even before hospital admission . Third-generation cephalosporins are the treatment of choice in children over 3 months of age . Increases in antibiotic resistance, especially among pneumococci, are of concern . The next few years should see major advances in the immunoprophylaxis of these serious infections.

Monaldi Arch Chest Dis, 1994 Feb, 49(1), 57 - 60
Current role of vaccination in preventing acute respiratory infections in children in developing countries; Cattaneo A; Acute respiratory infections (ARI) cause more than four million childhood deaths each year in developing countries . In addition to standard case management, vaccines have a great potential for reducing these deaths . Immunization against measles and pertussis, already reaching more than 70% of infants in developing countries, contributes to the prevention of more than one million childhood deaths . New conjugate vaccines against Haemophilus influenzae type b, if shown to be effective against pneumonia in developing countries, could reduce acute lower respiratory infection (ALRI) deaths by 4% . A further 10% reduction could be obtained by the availability of an effective conjugate vaccine against Streptococcus pneumoniae . A safe vaccine against respiratory syncytial virus could also prevent 10% of ALRI deaths . The potential role of other bacterial and viral vaccines needs to be clarified.

Antimicrob Agents Chemother, 1994 Feb, 38(2), 315 - 8
Comparison of cefuroxime axetil and amoxicillin-clavulanate suspensions in treatment of acute otitis media with effusion in children; McLinn SE et al.; Two hundred sixty-three pediatric patients from the ages of 3 months to 11 years were enrolled in a randomized, investigator-blinded, multicenter study comparing the clinical and bacteriological efficacies and safety of cefuroxime axetil suspension (CAE) with those of amoxicillin-clavulanate suspension (AMX-CL) in the treatment of acute otitis media with effusion . Patients received CAE at 30 mg/kg of body weight per day (n = 165) in two divided doses or AMX-CL at 40 mg/kg/day (n = 98) in three divided doses for 10 days . The primary pathogens among 200 isolates from pretreatment cultures of middle ear fluid were identified as follows: Haemophilus influenzae (39%), over a third of which were beta-lactamase positive; Streptococcus pneumoniae (34%); and Moraxella catarrhalis (16%) . Pathogens were eradicated or presumed to be eradicated from 81% (95 of 118) and 76% (50 of 66) of bacteriologically evaluable patients in the CAE and AMX-CL groups, respectively . A satisfactory clinical response (cure or improvement with or without resolution of effusion) occurred in 113 (77%) of 146 clinically evaluable patients in the CAE group and in 66 (74%) of 89 evaluable patients in the AMX-CL group . Clinical failure or recurrence (within 2 weeks following the completion of treatment) occurred in 22 and 26% of CAE- and AMX-CL-treated patients, respectively . Drug-related adverse events occurred in 18% of CAE-treated patients, whereas they occurred in 39% of AMX-CL-treated patients (P < 0.001); diarrhea or loose stools was the most commonly reported adverse event (CAE, 12%; AMX-CL, 31%; P < 0.001) . These results indicate that CAE given twice daily is as effective as AMX-CL given three times daily in the treatment of acute otitis media with effusion in pediatric patients, but CAE was associated with significantly fewer drug-related adverse events.

Pediatr Infect Dis J, 1994 Feb, 13(2), 122 - 8
Importance of enteric bacteria as a cause of pneumonia, meningitis and septicemia among children in a rural community in The Gambia, West Africa; O'Dempsey TJ et al.; Two thousand eight hundred ninety-eight children younger than 5 years old were investigated during a 2-year period in a rural area of The Gambia for possible pneumonia, meningitis or septicemia . After clinical examination and appropriate investigations, 1014 children were diagnosed as having pneumonia, 31 as having meningitis and 100 as having septicemia . Nine hundred seven children had a final diagnosis of malaria including 702 who satisfied the World Health Organization criteria for a diagnosis of pneumonia . A bacterial etiology was established in 115 (11%) patients with a final diagnosis of pneumonia, in 25 (81%) with meningitis and in 29 (29%) with suspected septicemia . Overall the pneumococcus was the leading pathogen identified among children with pneumonia and meningitis and ranked third among those with septicemia . However, during the wet season, when malaria transmission was highest, 50% of blood culture isolates obtained from children satisfying the World Health Organization criteria for a diagnosis of pneumonia were Salmonella or coliform species, and the pneumococcus and Haemophilus influenzae type b accounted for only 43% of isolates . Thus enteric bacteria may be as important as those bacteria more usually associated with respiratory disease among children presenting with a clinical picture of pneumonia during the wet season . This finding has important implications for case management and surveillance for antibiotic resistance.

J Antimicrob Chemother, 1994 Feb, 33(2), 299 - 307
Penetration of clarithromycin and its 14-hydroxy metabolite into middle ear effusion in children with secretory otitis media; Sundberg L et al.; Clarithromycin suspension was given at a dosage of 7.5 mg/kg bd for 7 days to 31 children with secretory otitis media, scheduled for insertion of grommets . The fifth dose was given approximately 2.5 h before myringotomy and aspiration of the middle ear effusion at which time a blood sample also was taken . In addition, in 16 children blood samples were taken at 1, 1.5 and 4 h after the fifth dose . The concentrations of clarithromycin and its active 14-hydroxylated metabolite, in middle ear effusion and serum, were determined by HPLC . Before therapy, at surgery on day 3 and after completion of treatment, nasopharyngeal samples were taken for culture and susceptibility testing . In the middle ear effusions mean concentrations of clarithromycin (2.5 mg/L) and metabolite (1.3 mg/L) were considerably higher than the serum concentrations (1.7 and 0.8 mg/L, respectively) . The mean concentrations in middle ear effusion exceeded the MICs for most respiratory pathogens . Complete eradication of Streptococcus pneumoniae, Moraxella catarrhalis and Streptococcus pyogenes from the nasopharynx was achieved after three days of therapy . Approximately 50% of the isolates of Haemophilus influenzae were eradicated from approximately 50% of the patients and the growth of the persisting strains was decreased from abundant or moderate to sparse . Adverse events were mild and transient and were experienced by only two of the 31 children.

Jpn J Antibiot, 1994 Feb, 47(2), 181 - 94
{Pharmacokinetic, bacteriological and clinical evaluation of cefditoren pivoxil in pediatrics}; Iwai N et al.; Pharmacokinetic, bacteriological, and clinical studies were performed in pediatrics on cefditoren pivoxil (CDTR-PI, ME1207) in granules . 1 . Serum concentrations and urinary excretions of CDTR after administration of CDTR-PI to children (ages between 1 and 10) were investigated . Five cases were administrated with CDTR-PI at a dose level of 3 mg/kg 30 minutes after meal . Serum concentrations in these cases reached their peaks at 2 hours after administration with an average level of 1.23 +/- 0.34 micrograms/ml and diminished to 0.04 +/- 0.04 micrograms/ml at 8 hours after administration with a half-life of 1.60 +/- 0.38 hours . Urinary recovery rates of CDTR in the first 8 hours after administration of CDTR-PI averaged 14.9 +/- 0.9% . Five cases were administered with CDTR-PI at a dose level of 6 mg/kg 30 minutes after meal . Serum concentrations with the drug after meal reached their peaks at 1 hour after administration with an average level of 2.62 +/- 0.42 micrograms/ml and diminished to 0.21 +/- 0.11 micrograms/ml at 8 hours after administration with a half-life of 1.58 +/- 0.31 hours . Urinary recovery rates of CDTR in the first 8 hours after administration of CDTR-PI averaged 17.0 +/- 0.7% . These data also showed that serum and urinary concentrations of the drug depended on dose levels . 2 . CDTR-PI was administered to 31 pediatric patients (their ages ranged between 1 year and 10 years) with various infections, and clinical and bacteriological effects and adverse reactions were investigated . Clinical effects were evaluable in 24 cases including 2 cases of scarlet fever, 1 case of acute pharyngitis, 12 cases of acute purulent tonsillitis, 4 cases of acute bronchitis, 5 cases of acute pneumonia . Clinical responses were excellent in 16 cases, effective in 8 cases, with an efficacy rate of 100% . Antimicrobial effects against a total of 16 strains identified or assumed to be pathogenic bacteria were evaluated . The 16 strains of bacteria included 4 strains of Staphylococcus aureus, 6 strains of Streptococcus pyogenes, 2 strains of beta-Streptococcus, 4 strains of Haemophilus influenzae . All the bacteria listed here were judged to have been eradicated except 2 strains of H . influenzae (1 was decreased and 1 was unchanged) thus, the eradication rate was 87.5% . Two strains of bacteria replaced infection causing bacteria . Streptococcus pneumoniae replaced S . pyogenes and S . aureus replaced H . influenzae . No adverse side reactions were observed.(ABSTRACT TRUNCATED AT 400 WORDS)

J Clin Microbiol, 1994 Feb, 32(2), 563 - 4
Case report of spinal epidural abscess caused by Haemophilus paraphrophilus; Scerpella EG et al.; Haemophilus paraphrophilus was recovered in pure culture from purulent material collected at surgery from a patient presenting with a spinal epidural abscess and a severe neurological deficit . This is the first report of such an occurrence.

J Clin Microbiol, 1994 Feb, 32(2), 551 - 3
Early recognition of atypical Francisella tularensis strains lacking a cysteine requirement; Bernard K et al.; Seven cultures referred to in our laboratories as unidentified gram-negative bacilli or Haemophilus species were identified as atypical strains of Francisella tularensis lacking a requirement for cysteine or enriched medium for growth . The use of cellular fatty acid composition analysis facilitated early recognition of this pathogen and prompt implementation of appropriate biosafety measures.

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