Invasive Haemophilus influenzae type B diseases in Bangladesh, with increased resistance to antibiotics

OBJECTIVE: To determine the prevalence, age-group distribution, serotype, and antibiotic susceptibility patterns of invasive Haemophilus influenzae type b (Hib) isolates in Bangladeshi children because data regarding Hib diseases in developing countries are scarce, which has led to delay of the introduction of Hib vaccine in these countries. METHODS: Children diagnosed with meningitis (n = 1412) and pneumonia (n = 2434) were enrolled in this surveillance study for Hib invasive diseases. Cerebrospinal fluid (CSF) and blood specimens, and the subsequent isolates, were processed using standard procedures. RESULTS: During 1993 to 2003, 455 H influenzae strains were isolated from patients with meningitis (n = 425) and pneumonia (n = 30), and an additional 68 Hib meningitis cases were detected by latex agglutination (LA) testing. Overall, 35% of pyogenic meningitis cases were a result of H influenzae, 97.1% of which were Hib. Most (91.4%) cases occurred during the first year of life. Resistance to ampicillin, chloramphenicol, and cotrimoxazole was 32.5%, 21.5%, and 49.2%, respectively. There was a trend toward increasing resistance for all three drugs. Resistance to ampicillin and chloramphenicol was almost universally coexistent and was associated with increased sequelae compared with the patients infected with susceptible strains (31% [23/75] vs 11% [21/183]; P <.001). CONCLUSION: Hib is the most predominant cause of meningitis in young Bangladeshi children. Resistance to ampicillin and chloramphenicol and the high cost of third-generation cephalosporin highlight the importance of disease prevention through vaccination against Hib.     

Excretion of Haemophilus influenzae type b polysaccharide antigen in urine of healthy nasopharyngeal carriers

We measured concentrations of Haemophilus influenzae type b (Hib) polysaccharide antigen by ELISA in urine samples from 81 healthy North American children with positive or negative throat cultures for Hib, to investigate the possibility that asymptomatic carriers may have antigenuria. For comparison, we determined the concentrations of Hib polysaccharide antigen in urine samples from 56 patients with proven Haemophilus disease, including 13 children with lower respiratory infections who resided in developing countries. Among the healthy children, antigen was detected in the urine of seven of 19 (37%) carriers of Hib compared with one of 62 (2%) children with negative throat cultures (p less than 0.001). Among the patients with invasive Haemophilus infections, 93% had antigen detected. Although there was overlap in the concentrations of antigen in the positive urines from the asymptomatic carriers and those of the ill patients, the concentrations of the ill patients were higher than those of the carriers. The respective geometric means of the positive patients were: American patients with meningitis, 42.5 ng/mL (range 1.7-9800 ng/mL); American patients with infections not involving the CNS, 5.8 ng/mL (range: 1.0-96 ng/mL); patients from developing countries with lower respiratory infections, 29.6 ng/mL (range: 0.9-5290), and American asymptomatic carriers, 1.9 ng/mL (range: 0.6-16.7 ng/mL). Thus, antigenuria is present in a high proportion of healthy children with positive throat cultures for Hib, and the antigen concentrations of the carriers overlap those of ill patients. These results suggest that either mucosal colonization itself is sufficient to produce antigen-uria, or asymptomatic carriers may be experiencing asymptomatic invasive Hib infection.     

Defining the burden of pneumonia in children preventable by vaccination against Haemophilus influenzae type b

OBJECTIVES: To determine the burden of pneumonia requiring hospitalization in infants and young children preventable by vaccination against Haemophilus influenzae type b (Hib). DESIGN: Vaccination centers in Santiago, Chile, were randomly selected to administer PRP-T, an Hib conjugate vaccine, combined with diphtheria-tetanus toxoids-pertussis (DTP) vaccine or DTP alone. SUBJECTS: Infants who received > or =2 doses of DTP or DTP and Hib conjugate vaccine combined. MAIN OUTCOME MEASURES: Pneumonia episodes leading to hospitalization accompanied by indicators of likely bacterial infection including radiologic evidence of alveolar consolidation or pleural effusion, an elevated erythrocyte sedimentation rate (> or =40 mm/h) or bronchial breath sounds on auscultation. RESULTS: In participants age 4 to 23 months, PRP-T reduced the incidence of pneumonia associated with alveolar consolidation or pleural effusion by 22% (95% confidence interval, -7 to 43) from 5.0 to 3.9 episodes per 1000 children per year. When the pneumonia case definition included any of the following, alveolar consolidation, pleural effusion, erythrocyte sedimentation rate > or =40 mm/h or bronchial breath sounds, PRP-T provided 26% protection (95% confidence interval, 7 to 44) and prevented 2.5 episodes per 1000 children per year. CONCLUSIONS: Hib vaccine provides substantial protection against nonbacteremic pneumonia, particularly those cases with alveolar consolidation, pleural effusion or other signs of likely bacterial infection. Hib vaccination prevented approximately 5 times as many nonbacteremic pneumonia cases in infants as meningitis cases, thus indicating that the largest part of the effect of Hib vaccination might be undetectable by routine culture methods.     

Evaluation of polymerase chain reaction (PCR) for diagnosing Haemophilus influenzae b meningitis

A polymerase chain reaction (PCR) for detecting Hib in cerebrospinal fluid (CSF) was evaluated and compared with culture and a latex agglutination test (LAT) in a hospital-based prospective surveillance. We studied 107 children aged from 1 month to 12 years with a clinical and CSF profile suggestive of acute bacterial meningitis. CSF culture was performed on blood-chocolate agar by standard technique, LAT by a commercially available kit (Wellcogen) and PCR using total DNA extracted from CSF samples. Of 107 children, 79% had received one or more doses of injectable antibiotics. Hib was detected by culture in 14 cases, by LAT in 23 and by PCR in 37. All CSF samples that reveal Hib by culture or LAT had a PCR positive for Hib (sensitivity 100%). PCR also detected 14 additional cases of Hib meningitis which were not detected by culture or LAT. We conclude that PCR is a sensitive and specific diagnostic tool that may be valuable in a population with high pre-hospital antibiotic usage.     

Problems in determining the etiology of community-acquired childhood pneumonia

Fifty-seven children ages 1 month to 12 years hospitalized because of community-acquired pneumonia were compared with age-matched controls who had acute asthma without pneumonia to test the value of rapid bacterial antigen detection and clinical and radiographic criteria for diagnosis of bacterial pneumonia. Bacterial pneumonia, defined on the basis of positive cultures of blood or pleural fluid, was diagnosed in 4 children (7%), 1 of whom also had viral pneumonia. Viral pneumonia, defined as a positive nasopharyngeal sample or positive serology, was diagnosed in 20 children (35%). Serum and concentrated urine were tested by latex agglutination (Wellcogen) for Haemophilus influenzae type b and pneumococcal antigens and by countercurrent immunoelectrophoresis for pneumococcal antigens. Pneumococcal antigen could not be detected in serum or urine from 3 children with culture-proved pneumococcal pneumonia, indicating poor sensitivity of the tests. In contrast apparent H. influenzae type b antigenuria was detected by latex agglutination in 4 of 40 children with pneumonia but also in 5 of 57 controls, and a sensitive enzyme-linked immunosorbent assay for polyribosyl ribitol (PRP) phosphate antigen showed that all 9 cases were false positives. The specificity of H. influenzae type b antigen detection was thus poor. Children with viral and bacterial pneumonia could not be distinguished by radiographic or clinical criteria (symptoms, fever) or by total or differential white blood cell counts, serum C-reactive protein or nasal or serum interferon levels. It is not possible to distinguish reliably childhood viral from bacterial pneumonia clinically or by rapid diagnostic tests.     

Invasive Haemophilus influenzae type b infections in Singapore children: a hospital-based study

OBJECTIVE: A 6-year (1990-95) hospital-based retrospective study was carried out to investigate the pattern of invasive Haemophilus influenzae type b (Hib) disease. METHODOLOGY: Cases with Hib isolated from sterile sites (blood, cerebrospinal fluid, or joint aspirate) were identified from the hospital's microbiological records, and their reviewed case records. Patients with pyogenic meningitis in the same study period were also identified to estimate the incidence of Hib meningitis. RESULTS: Twelve patients had positive cultures from sterile sites, of whom nine children were less than 5 years of age. These included seven cases of meningitis, one patient with acute epiglottitis, and one case of pneumonia. Three of the seven patients with meningitis had significant long-term sequelae. Our data also suggests a relatively low proportion of ethnic Chinese children with invasive disease. It was estimated that 18.4% to 41.1% of pyogenic meningitis in children admitted to the National University Hospital were due to Hib. The estimated annual attack rate of invasive Hib disease was at most 3.3 per 100 000 children aged less than 5 years (95% confidence interval: 2.6-3.5/100 000). CONCLUSION:: Invasive Hib infections are relatively uncommon in our community. This justifies the need for a cost effectiveness study before a universal Hib vaccination program is implemented.     

Counterimmunoelectrophoresis and latex particle agglutination in the etiologic diagnosis of presumed bacterial pneumonia in pediatric patients

A commercial latex agglutination (LA) kit (Wellcogen, Wellcome Diagnostics) used to detect bacterial polysaccharide antigens (Haemophilus influenzae type b and Streptococcus pneumoniae) was compared with a modified counterimmunoelectrophoresis technique and blood culture for etiologic diagnosis of presumptive bacterial pneumonia requiring hospitalization in 60 infants and children. Serum, urine and either sputum or nasopharyngeal secretions were collected during the first 5 days of therapy for antigen detection. Blood culture was positive in 6 of 52 (11.5%) of cases. Antigens were detected by counterimmunoelectrophoresis and/or LA in 13 of 60 (21.7%) serum samples, 2 of 16 (12.5%) unconcentrated urine samples, 19 of 42 (45.2%) urine samples concentrated 25-fold and 21 of 45 (46.7%) sputum or nasopharyngeal secretions. Antibiotic treatment for 5 days did not affect the antigen detection rate. Counter-immunoelectrophoresis was more sensitive than LA in serum and urine but not in sputum. However, because false positive reactions were frequently obtained with LA on nasopharyngeal secretions of an age-matched control group, this test appears unreliable.     

Antigenuria after immunization with Haemophilus influenzae oligosaccharide CRM197 conjugate (HbOC) vaccine

We tested the urine of 30 infants 6 weeks to 7 months of age after they received standard 10-micrograms (0.5-ml) doses of HbOC (HibTITER) Haemophilus influenzae b (Hib) conjugate vaccine for the presence of Hib antigenuria using a commercially available latex particle agglutination assay (Directigen). Urines were collected within 1 hour, from 1 to 3 hours, at 24 hours and at 3, 6 and 9 days after vaccine administration and reactions were quantitated from 0 to 3+. In contrast to previous studies in older children which showed little or no antigenuria following HbOC vaccination, our study shows that in infants intense Hib antigenuria is evident within 2 to 3 hours and persists 3 days after vaccine administration and that less intense antigenuria may be detected in some infants for several days. With efficacious vaccines now being used in 2- to 6-month-old infants, invasive Hib disease may soon be limited to infants of this age just before their seroconversion. It should be recognized that antigenuria occurs for several days after vaccination with Hib conjugate vaccines and that it could be erroneously interpreted as evidence of invasive Hib infection.     

Haemophilus influenzae type b still remains a leading cause of meningitis among unvaccinated children--a prospective CSF analysis study

A prospective, hospital-based cerebrospinal fluid (CSF) analysis study was undertaken in 65 children who had diagnostic lumbar puncture on admission for suspected central nervous system infections. Twenty-three children were clinically diagnosed to have had sepsis and/or meningitis. CSF bacterial culture grew Haemophilus influenzae type b (Hib) in four cases and Streptococcus pneumonia (SP) was cultured in another child. Bacterial antigen was detected in 13 other CSF specimens and the pathogens were Hib (n = 9), SP (n = 3) and Group B Streptococcus (n = 1). No etiologic cause was identified to explain the abnormal CSF pleocytosis and biochemistry in the remaining five cases. In contrast, the CSF analysis was normal in 42 other children with probable viral and non-infectious neurological condition, mostly febrile convulsions. The overall frequency rate for all types of meningitis and especially for Hib meningitis were 43 and 31 cases per 100,000 children < 5 years of age, respectively. These findings support our earlier observations that Hib meningitis still remains the leading cause of childhood meningitis in our region. Also it reaffirms the observation that bacterial meningitis may often be under-reported if CSF positive culture alone is considered for the diagnosis.     

Haemophilus influenzae type b meningitis in the state of Paraná, Brazil

OBJECTIVE: During the second half of 1996, the municipalities of Londrina and Curitiba (State of Paraná, Brazil) included Haemophilus influenzae type b (Hib) vaccine into their routine vaccination regimen, approximately 30 months before its introduction into the National Immunization Program. The present study aimed at verifying the incidence of meningitis caused by Hib among children in Londrina, Curitiba, and in the remaining municipalities of the State, before and after the introduction of this vaccine into the immunization program. METHODS: An observational and retrospective study was carried out. The study included all cases of Haemophilus influenzae type b meningitis recorded by the epidemiological surveillance system in Londrina and by the State of Paraná Health Secretariat between 1992 and 1999 among children aged less than 5 years. The incidence rates of Hib meningitis were calculated per 100,000 children aged less than five years. RESULTS: After the introduction of Hib vaccine, an important reduction in the incidence rate of Haemophilus influenzae type b meningitis was observed in Londrina (from 23.91 in 1996 to 2.79 in 1999). A Similar decrease was observed in Curitiba. In the remaining localities of the state, which had not introduced the vaccine till mid-1999, the incidence rate remained almost unchanged. CONCLUSION: Regular vaccination against Hib was effective in reducing the incidence rate of meningitis amongst children younger than five years in Londrina and Curitiba. In order to maintain this low incidence rate, adequate vaccination coverage and strict epidemiological surveillance should be guaranteed.     

Effectiveness of Haemophilus influenzae type B conjugate vaccine on prevention of pneumonia and meningitis in Bangladeshi children: a case-control study

BACKGROUND: Few Asian countries have introduced Haemophilus influenzae type b (Hib) conjugate vaccine because of its cost and uncertainty regarding disease burden. METHODS: To estimate the effectiveness of Hib conjugate vaccine in preventing pneumonia and meningitis in children age <2 years, an incident case-control study was conducted in a birth cohort of about 68,000 infants in Dhaka city, Bangladesh. DPT vaccine was systematically replaced by a combined Hib-DPT vaccine in selected immunization centers of the study area. Four matched community- and 2 hospital-controls were randomly selected for each confirmed case of pneumonia and meningitis from the study area. RESULTS: About 35% of the infants received each of the 3 doses of Hib-DPT vaccine. There were 2679 children who had a chest roentgenogram. For 475 children, a radiologist and a pediatrician independently identified substantial alveolar consolidation. Following at least 2 doses of Hib vaccine, the preventable fractions [95% confidence intervals (CI)] using community and hospital controls were 17% (-10% to 38%) and 35% (13% to 52%) respectively. Of these 475 cases, 2 radiologists with the World Health Organization concurred with the findings for 343 patients, yielding preventable fractions of 34% (6% to 53%) and 44% (20% to 61%). Fifteen confirmed Hib meningitis cases were identified; the preventable fractions (95% CI) using community and hospital controls, respectively, were 89% (28% to 100%) and 93% (53% to 100%). CONCLUSIONS: The study documented that significant fractions of pneumonia and meningitis in Bangladeshi children age <2 years can be prevented by the Hib conjugate vaccine.     

Vaccine-preventable haemophilus influenza type B disease burden and cost-effectiveness of infant vaccination in Indonesia

BACKGROUND: Most of Asia, including Indonesia, does not use Haemophilus influenzae type b (Hib) conjugate vaccines. We estimated total vaccine-preventable disease burden and the cost-effectiveness of Hib conjugate vaccine in Indonesia. METHODS: Hib pneumonia and meningitis incidences for children with access to health care were derived from a randomized vaccine probe study on Lombok Island, Indonesia during 1998-2002. Incidences were adjusted for limited access to care. Health system and patient out-of-pocket treatment cost data were collected concurrent with the probe study. For Hib vaccine in monovalent and combined (with DTP-HepB) presentations, we used 2007 UNICEF vaccine prices of US$3.30 and $3.75 per dose. RESULTS: For the 2007 Indonesian birth cohort, Hib vaccine would prevent meningitis in 1 of every 179 children, pneumonia in 1 of every 18 children, and 4.9% of mortality among those younger than 5 years. The total incremental societal costs of introducing Hib vaccine in monovalent and pentavalent presentations were, respectively, US$11.74 and $8.93 per child vaccinated. Annual discounted treatment costs averted amounted to 20% of pentavalent vaccine costs. For the pentavalent vaccine, the incremental costs per discounted death and disability adjusted life-year averted amounted to US$3102 and $74, respectively, versus $4438 and $102 for monovalent vaccine. CONCLUSIONS: Routine infant Hib vaccination would prevent a large burden of pediatric illness and death in Indonesia. Even without external funding support, Hib vaccine will be a highly cost-effective intervention in either a monovalent or pentavalent presentation based on commonly used benchmarks.     

Non-type b Haemophilus influenzae disease: clinical and epidemiologic characteristics in the Haemophilus influenzae type b vaccine era

BACKGROUND: As a result of the decline in Haemophilus influenzae type b (Hib) disease caused by the widespread use of conjugate vaccines, non-type b H. influenzae will become a more important cause of H. influenzae (Hi) disease. Characterization of the clinical and epidemiologic features of non-b Hi disease is needed in the Hib vaccine era. METHODS: A prospective active surveillance study of invasive Hi disease involving pediatricians in the United Kingdom and Republic of Ireland. For the first phase of the study (October 1, 1992, to October 31, 1995) pediatricians were asked to report any child who had invasive Hi disease and who had received Hib conjugate vaccine. For the second phase of the study (November 1, 1995. To December 31, 1998) pediatricians were asked to report any child with invasive Hi disease regardless of vaccination status. RESULTS: During the study period 102 cases of invasive non-type b Hi disease and 106 cases of invasive Hib disease were reported in children who had been fully vaccinated against Hib. Children with non-type b disease were younger (16 vs. 22 months of age, P = 0.08), less likely to have meningitis and epiglottitis (P < or = 0.001) and more likely to have pneumonia and bacteremia (P < or = 0.001) than children with type b disease. For the last 2 years of the study invasive Hi disease occurring in a fully vaccinated child was more likely to be caused by a non-b strain than by a type b strain (58 vs. 38). In 1998 the incidence of non type-b Hi disease in all children <5 years of age in the UK was 1.3/100,000 as compared with an incidence of Hib disease of 0.6/100,000. The majority (88%) of non-b strains isolated in children were nontypable strains. CONCLUSIONS: Non-b Hi is a rare cause of disease in children, but in the Hib vaccine era it has become more common than type b as a cause of Hi disease in fully vaccinated children.     

Systemic infections due to type b Haemophilus influenzae. A retrospective study of 114 cases

The choice of treatment, the importance of chemoprophylaxis in household contacts and the potential impact of immunization with vaccines against Haemophilus influenzae type b (Hib) currently under investigation are discussed on the basis of the patients hospitalized for invasive Hib infections at the University Children's Hospital Geneva from 1976 to 1985. Among 122 culture-proven infections due to Hib, there were 41% of cases of meningitis, 37.7% of epiglottitis, 9.8% of pneumonia, 5.7% of septicemia, 3.3% of cellulitis and 2.4% of septic arthritis. From 1981 to 1983, one strain of Hib produced beta-lactamase, but between 1984 and 1985, 5 strains (19.2%) produced beta-lactamase. Only one case of possible horizontal transmission of the infection was found in this 10-year period. We conclude that 1. the appearance of beta-lactamase producing strains of Hib requires that treatment be initiated with an antimicrobial agent resistant to beta-lactamase when a Hib infection is suspected; 2. in our region, only one case of an invasive Hib infection could theoretically have been prevented by chemoprophylaxis; and 3. the calculated theoretical impact of vaccination with the new types of vaccines against Hib could have prevented 106 of 122 cases of invasive Hib infections.     

Passive exposure to tobacco smoke and bacterial meningitis in children

OBJECTIVE: To determine whether an association exists between passive exposure to tobacco smoke and bacterial meningitis in childhood, in an Australian population. METHODOLOGY: A retrospective, case-controlled telephone survey of the parents of 71 children admitted to the Women's and Children's Hospital, North Adelaide, with bacterial meningitis between 1990 and 1999. RESULTS: The annual incidence of Haemophilus influenzae type b (Hib) meningitis decreased significantly during the study period (11.0 cases per year 1991-93 and 1.5 cases per year 1994-99, Fisher's exact test; P < 0.001) whilst pneumococcal cases significantly increased (2.3 cases per year 1991-93 and 4.9 cases per year 1994-99, Fisher's exact test; P < 0.001). Although comparable numbers of cases and controls came from smoking families (41% vs 45%), more cases came from bi-parental smoking households (17% vs 8%; odds ratio (OR) = 2.20, 95% confidence interval (CI) 0.77-6.24) and cases were more likely to live in households where parents smoked inside (27% vs 13%; OR 2.51, 95% CI 1.05-6.03). In households where parents smoked, children who had had meningitis were significantly more likely to have parents who smoked inside the house, than children who had not had meningitis (66% vs 28%, Fisher's exact test; P = 0.005). CONCLUSION: This study suggests there may be an association between high levels of passive exposure to tobacco smoke and bacterial meningitis in Australian children. A study with larger numbers of affected children which quantifies passive exposure to tobacco smoke is needed to determine the strength of this association.     

Value of antigen quantitation in Haemophilus influenzae type b meningitis

We studied Haemophilus influenzae type b meningitis in 68 patients to evaluate whether quantitative determination of PRP in body fluids obtained at admission or measurement of the duration of its presence helped identify patients at risk for complications. Geometric mean admission PRP concentrations in CSF, blood, and urine increased with severity of disease, but individual values varied greatly. Measurements of the duration of antigenemia and antigenuria also varied widely and were best predicted by the admission or peak PRP concentration. The mean duration of both antigenemia and antigenuria increased with severity of disease. In contrast, the elimination half-life of PRP did not differ significantly with severity of hospital course, peak PRP concentration in blood or urine, or patient age. Clearance from CSF could not be accurately assessed, but PRP was detectable in only six of 41 patients in whom spinal fluid was obtained after the eighth day of hospitalization; all had complicated courses. Although latex particle agglutination assay is a valuable aid in rapid diagnosis of invasive Hib infections, the predictive value of antigen quantitation at admission and the determination of its duration in body fluids is limited by the wide range of observed values.     

Bacterial meningitis following introduction of Hib conjugate vaccine in northern Uganda

BACKGROUND: St Mary's Hospital, Lacor is in Gulu district in northern Uganda. Owing to conflict and insurgency, the majority of the hospital population live in internally displaced people's camps. There is ongoing public health surveillance of paediatric bacterial meningitis by the hospital. Before the introduction of Haemophilus influenza type b (Hib) conjugate vaccine in June 2002, Hib was the leading cause of bacterial meningitis in the area. METHODS: All patients with suspected bacterial meningitis between April 2003 and August 2006 were recruited. Meningitis was confirmed by isolation of bacteria. RESULTS: During the study period, 4986 cases of suspected bacterial meningitis were identified, 395 of whom had purulent cerebrospinal fluid (CSF). A culture was obtained from 259 (65%): Streptococcus pneumoniae 132 (51%), H. influenzae 22 (8.5%), salmonella spp 85 (32.8%), Neisseria meningitidis 9 (3.5%) and others 11 (4.2%). Over the surveillance period, there was a remarkable decline in the prevalence of H. influenza meningitis to only three cases or fewer per year compared with 42 in 2001. The minimum incidence of Streptococcus pneumoniae meningitis among children under 5 years of age was 33.7/100,000 of population and it was more prevalent during the dry season. The minimum incidence of non-typhoidal salmonella spp meningitis was 22.7/100,000, making it the second most common cause of paediatric bacterial meningitis with a case fatality rate of 18.2%. CONCLUSION: Hib conjugate vaccine delivered through the national immunisation programme is very effective in reducing Hib meningitis in children under 5 years of age. Continued laboratory-based surveillance of bacterial meningitis in Africa is needed to assess the effectiveness of vaccination programmes and detect other vaccine-preventable pathogens.     

Evaluation of a commercially available latex agglutination test for rapid diagnosis of group B streptococcal infection

We studied the clinical value of Wellcogen, a latex particle agglutination test designed to diagnose rapidly Group B streptococcal infections in 620 infants. The sensitivity and specificity were 18 of 20 (90%) and 18 of 22 (81%), respectively. False negatives were documented in 2 patients and false positive tests occurred in 4. Also 10 of 620 (1.6%) infants had detectable antigen in the absence of proved infection. In addition, in 4 other infants with Group B streptococcal bacteremia, antigenemia was absent in serum obtained on the day of hospitalization but antigen was detected in specimens obtained subsequently. We also assayed the sera of 102 randomly chosen hospitalized adults; 4 (4%) contained "antigen" but none had Group B streptococcal infection. None of 50 urines obtained from other randomly chosen hospitalized adults contained "antigen." In patients with Group B streptococcal meningitis cerebrospinal fluid and unconcentrated urine uniformly contained antigen but in bacteremia without focality, assay of blood and urine were both necessary to diagnose correctly all 7 patients with the Wellcogen test. We conclude that despite acceptable sensitivity and specificity, the interpretation of the Wellcogen test must be performed with caution and knowledge of its limitations.     

The epidemiology of Haemophilus influenzae type b meningitis in Burkina Faso

BACKGROUND: Haemophilus influenzae type b (Hib) disease burden studies are important to conduct in African countries that plan to introduce vaccine so that vaccine impact can be documented. METHODS: We implemented population-based meningitis surveillance in 3 districts of Burkina Faso for 12 months each during 2002-2003 and 2004-2005 using polymerase chain reaction, culture and antigen detection. RESULTS: Lumbar puncture was performed on 1686 patients and 112 had Hib identified. Persons <1, <5, 5-14 and 15+ years of age had annual Hib meningitis incidences of 97, 34, 2.1 and 0.55 per 100,000, respectively; overall case fatality proportion was 25%. During the historic meningitis epidemic season months of December through April, the proportion of purulent cerebrospinal fluid among children aged <5 years that yielded Hib was 27% compared with 30% during other months. Twenty-five of 98 persons with information available were treated with only one or 2 doses of oily chloramphenicol. Among children age <5 years with Hib meningitis, 28% were pretreated with antimalarials and antimalarial pretreatment was associated with delay in hospitalization. CONCLUSIONS: In Burkina Faso, Hib meningitis incidence and case fatality proportion are high and thus vaccine could have a substantial impact. While awaiting well-implemented routine infant Hib vaccination, empiric case management for pediatric meningitis in sub-Saharan Africa must recognize that Hib is likely even during the epidemic season. In malaria-endemic areas, pediatric Hib meningitis case management may be adversely affected by the similar presentation of these 2 diseases.     

Haemophilus influenzae type b unsuspected bacteremia

To further define the clinical features and natural history of unsuspected Haemophilus influenzae type b (Hib) bacteremia, we retrospectively reviewed the records of 322 Hib infections observed during a 45-month period at Children's Hospital, Boston. We identified 31 patients with unsuspected Hib bacteremia and 19 with unsuspected Hib antigenemia and sterile blood cultures. Bacteremic patients were typically under two years of age (81%), had high fevers (mean = 39.5 degrees C), and frequently had otitis media (65%) diagnosed as their only focus of infection at presentation. Nineteen of 31 were empirically treated with oral antibiotics. Ten of 31 (32%) developed focal infectious complications consisting of meningitis (n = 7), cellulitis (n = 2), and pneumonia (n = 1). Children with focal infectious complications differed from those without infectious complications in having a significantly higher mean fever of 40.3 degrees C compared to 39.7 degrees C (P less than 0.05). Five of 19 (26%) empirically treated patients developed focal complications (all meningitis) compared to five of 12 (42%) untreated patients. Blood cultures at follow-up visit were positive in three of 19 (9%) treated patients and seven of 12 (42%) untreated patients (P less than 0.05). Of the 19 children with antigenemia and sterile blood cultures, 16 (84%) were empirically treated with antibiotics, and none had positive blood cultures or focal infections on follow-up evaluation. Children with occult Hib bacteremia are at high risk for developing serious focal infections, particularly meningitis, despite empiric antibiotic therapy. Once Hib bacteremia is suspected, strong consideration should be given to parenteral in hospital antibiotic therapy. The utility of rapid antigen detection for identifying high-risk patients requires further evaluation.