Aetiology and clinical signs of bacterial meningitis in children admitted to Goroka Base Hospital, Papua New Guinea, 1989-1992

Children aged 1-59 months admitted to Goroka Base Hospital with signs suggestive of meningitis were recruited to determine what proportion of such children have clinical or bacterial meningitis and to investigate the bacterial aetiology. A laboratory classification of definite, probable, possible, indeterminate and no meningitis was established. Thirty per cent of 697 children had a final clinical diagnosis of meningitis, 12% had culture-proven bacterial meningitis (case fatality rate 34%) and 10% had probable or possible meningitis. Inability to feed, vomiting, drowsiness, "staring eyes" and haemoglobin < 9 g/dl in addition to the classical signs of meningitis were associated with increased mortality. Isolates from cerebrospinal fluid were 62 pneumococci, 22 Haemophilus influenzae type b (Hib) and one Neisseria meningitidis. Including blood culture-proven and antigen-proven Hib disease, Hib and pneumococci accounted for 44% and 46% of bacterial meningitis, respectively, and 23% of pneumococci were intermediately resistant to penicillin. Inability to feed, bulging fontanelle, convulsions in young children, neck stiffness, fever and "staring eyes" were all independently associated with bacterial meningitis. Conjugate Hib vaccine must be given to infants as early as possible. Conjugate pneumococcal vaccines, maternal immunization with 23-valent vaccine and pneumococcal protein vaccines are under investigation for prevention of pneumococcal disease.     

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.     

Impact of haemophilus influenzae type b conjugate vaccine in South Africa and Argentina

INTRODUCTION: Haemophilus influenzae type b (Hib) persists as a major cause of pediatric meningitis and pneumonia in developing countries in which Hib conjugate vaccines are not used. Demonstration of decreases in severe Hib disease after countries introduce Hib conjugate vaccine will help justify the resources necessary to purchase and provide the vaccine. Because surveillance for culture-confirmed Hib meningitis is not available in many countries, alternative means to measure the impact of Hib conjugate vaccine would be useful. METHODS: Laboratory records from the years before and after introduction of the Hib conjugate vaccine were reviewed at 4 hospitals, 2 in Argentina and 2 in South Africa. Potential indicators of bacterial meningitis including cerebrospinal fluid (CSF) culture, white blood cell count, appearance, protein and glucose were recorded. RESULTS: After introduction of Hib conjugate vaccine, culture-confirmed Hib meningitis declined significantly at 3 of 4 hospitals (2 in Argentina and 1 in South Africa). In the same 3 hospitals, there was a significant decline after vaccine introduction in some of the following CSF indicators of bacterial meningitis: proportion of CSF specimens with white blood cell count > or = 100 x 10(6)/L, 500 x 10(6)/L and 1,000 x 10(6)/L; glucose <40 mg/dL; protein >100 mg/dL; and turbid appearance. CONCLUSIONS: Culture-confirmed Hib meningitis declined at 3 of the 4 hospitals after Hib vaccine introduction. Surrogate indicators of bacterial meningitis also declined and might be useful measures of Hib conjugate vaccine impact at hospitals where capacity to culture Hib is not available.     

Evaluation of meningococcal meningitis vaccination strategies for the meningitis belt in Africa

BACKGROUND: Although the meningococcal polysaccharide vaccine has contributed to the control of Group A meningitis in the "meningitis belt" of Africa, recurrent large outbreaks have led to questions regarding vaccination strategy. We evaluated current and hypothetical vaccination strategies for the region. METHODS: A model was formulated to analyze the effectiveness and costs of vaccine campaigns in response to outbreaks based on 7 years of weekly incidence data from Burkina Faso. Additional models analyzed the potential impact and costs of either a 1- or 4-dose routine scheduled delivery of meningococcal polysaccharide vaccine based on data reported to the World Health Organization from 16 countries during 1948 through 1996. Vaccine efficacy, vaccination coverage and economic data from literature reviews provided model assumptions. RESULTS: For Burkina Faso neither 1- nor 4-dose vaccination schedules would prevent >30% of meningitis cases compared with the 42% prevented through an outbreak response program of vaccinating districts, which reach an incidence of 15 per 100000 persons for 2 weeks. For the entire meningitis belt, routine coverage with the 1- or 4-dose schedule meningococcal vaccine would require 4.9 and 19.6 million doses annually, respectively, for an annual net cost of $4.4 to $12.3 million and prevent an average 10300 to 12600 cases (23 to 28%), assuming a long term vaccine efficacy of 50%. In addition an initial "catch-up" campaign costing up to $72 million to vaccinate the population from 1 to 30 years of age would be required before achieving that level of effectiveness. CONCLUSION: Given the relatively poor routine vaccination coverage in this region, current strategies of vaccination campaigns that achieve higher coverage would generally be more effective and less costly than the modeled routine scheduled programs, assuming that campaigns can be rapidly implemented. Until a better vaccine is available, countries in this region would be more efficient in improving the response times to outbreaks, perhaps through improved surveillance, and in bolstering existing vaccination infrastructures rather than embarking on strategies of questionable effectiveness.     

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.     

Effectiveness of haemophilus influenzae type B conjugate vaccine for prevention of meningitis in Senegal

A total of 24 cases of hospitalized, laboratory-confirmed Haemophilus influenzae type b (Hib) meningitis were identified through a regional pediatric bacterial meningitis surveillance system. Each case was matched by age and residence to 4 neighborhood controls. The adjusted vaccine effectiveness for ≥ 2 doses was 95.8% (95% confidence interval, 67.9%-99.4%). Hib vaccine appears to be highly effective in preventing Hib meningitis in Senegal.     

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.     

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.     

H.<Emphasis Type="Italic">influenzae type b</Emphasis> (Hib) vaccine – controversies

Hib vaccine is the 8th vaccine knocking at the door to be included in the EPI the world over. However there are some controversies that need to be addressed, especially when it comes to use of this vaccine in India. It is difficult to culture Hib unless one uses sheep blood enriched media for culture. There is a lack of good community based data on Hib burden in India. This makes many feel that Hib is rare in India. However this is not true. There are many studies that have looked at this closely. Hib is a common cause of meningitis and pneumonitis in children less than 5 years old in India. There is wide spread problem of multi–drug resistance by Hib in India. Mortality of meningitis is as high as 100% if third generation cephalosporins are not used in time. Of the survivors of meningitis, 60% develop long-term sequelae. Hib vaccine is very effective and can lead to 99% reduction with mass vaccination in just 2–3 years. It is also a very safe vaccine. Of the conjugated vaccines available in India all are equally effective and safe and there is nothing to choose one over the other. There is a need to give a booster dose at 15–18 months of age. Even UK, which never gave the booster dose, is seriously thinking of changing their practice and give a booster dose. Lastly the combination vaccines of Hib with IPV, DPwT/DPaT, and Hepatitis B are safe and effective and should be encouraged to improve the compliance. The use of Hib vaccine is recommended in India, for those who can afford the vaccine.     

Experience with the prevention of invasive Haemophilus influenzae type b disease by vaccination in Alaska: the impact of persistent oropharyngeal carriage

OBJECTIVES: To report the epidemiology of invasive Haemophilus influenzae type b (Hib) disease in high-risk Alaska Native infants before and after universal infant Hib vaccination and evaluate an increase in invasive Hib disease in 1996 after changing Hib vaccine type. STUDY DESIGN: Statewide laboratory surveillance for invasive Hib disease has been conducted since 1980. Three cross-sectional Hib carriage studies were conducted in 1997 and 1998. RESULTS: The invasive Hib disease rate in Alaska Natives decreased from 332 cases per 100,000 children <5 years old in 1980-1991 to 17:100,000 in 1992-1995 but increased primarily in rural areas to 57.9:100,000 after a switch in Hib vaccine types. Carriage studies in 5 rural Alaska Native villages showed oropharyngeal Hib carriage as high as 9.3% in children aged 1 to 5 years; in contrast, carriage in urban Alaska Native children was <1%. CONCLUSIONS: Although Hib disease has decreased in Alaska, the rate of Hib disease and carriage in rural Alaska Natives did not decrease to the same extent as in non-Natives and urban Alaska Natives. Use of polyribosylribitol phosphate-outer-membrane protein conjugate vaccine for the first vaccine dose is critical to disease control in this population with continued transmission in infants <6 months of age. The ability to eliminate Hib carriage and disease may be affected by population characteristics, vaccination coverage, and Hib vaccine type used. This may pose a challenge to global elimination of Hib.     

Introduction of Haemophilus influenzae type B conjugate vaccine into routine immunization in Ghana and its impact on bacterial meningitis in children younger than five years

This report shows the impact of a pentavalent vaccine that includes Haemophilus influenzae type b (Hib) conjugate vaccine on bacterial meningitis in children younger than 5 years in Ghana. A review of the first 3 years of a pediatric bacterial meningitis surveillance program, started in August 2001 in Accra, Ghana, was undertaken. There was a significant reduction, P = 0.042 and 0.017, in percentage of purulent meningitis in children younger than 1 year, comparing the first year when the vaccine was introduced, to the second and third years, respectively.     

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.     

Invasive infections caused by haemophilus influenzae serotypes in twelve Canadian IMPACT centers, 1996-2001

BACKGROUND: Haemophilus influenzae type b (Hib) immunization has changed the epidemiology of pediatric bacterial invasive disease. We describe the epidemiology of H. influenzae invasive infections in 12 Canadian pediatric tertiary care [Immunization Monitoring Program, ACTive (IMPACT)] centers during the era of universal immunization against this pathogen. METHODS: Children with positive cultures for H. influenzae serotypes a to f (Hia to Hif) and nontypable H. influenzae from sterile sites were identified from the laboratory records at 12 IMPACT centers from January 1, 1996 to December 31, 2001. Hospital records were retrospectively reviewed for demographic and clinical information. RESULTS: Of 166 H. influenzae cases, 58 (35%) were caused by Hib, 89 (54%) by non-b serotypes, and 19 (11%) were not serotyped. The non-b serotypes included: 25 Hia (28%), 4 Hid (4%), 2 Hie (2%), 11 Hif (12%), and 47 were nontypable isolates (53%). For patients with Hib and Hia infection, meningitis was the most common presentation, accounting for 40% and 52% respectively, whereas the most common presentation for nontypable serotypes was pneumonia, seen in 43% of cases. Epiglottitis was associated mainly with Hib. Aboriginal ethnicity was an important risk factor for Hia cases, accounting for 76% of patients with infections caused by this serotype. Mean duration of hospitalization, need for admission to a pediatric intensive care unit, and case fatality rates were similar for the cases because of Hib, Hia, Hif, and nontypable serotypes. CONCLUSIONS: In 1996-2001, two-thirds of H. influenzae invasive disease in the 12 IMPACT centers was caused by non-b serotypes, which were associated with significant morbidity and mortality.     

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.     

A population-based retrospective assessment of the disease burden resulting from invasive Haemophilus influenzae in infants and young children in Santiago, Chile

Clinical discharge and laboratory records were reviewed in the seven government hospitals that provide care for 93% of the pediatric population of Santiago, Chile, to detect cases of meningitis and other invasive (bacteremia-associated) infections caused by Haemophilus influenzae. infections that occurred in children less than five years of age from January, 1985, through December, 1987, were recorded and matched with census data to calculate incidence rates. The incidence of meningitis and non-meningitis syndromes peaked in the 6- to 11-month age group and tapered sharply after 12 months of age. The city-wide incidence (ca. 21.6 cases/10(5) children less than 5 years of age) is one-third to one-half that reported for the general pediatric population in the United States. However, there is much evidence for under-reporting in Santiago. In Area Norte, served by Roberto del Rio Children's Hospital where H. influenzae has been a subject of research by pediatricians for years, the incidence of invasive H. influenzae infections (42.5/105) is approximately two-fold higher than the rest of Santiago. The cumulative proportions of episodes of H. influenzae disease occurring in successively older age groups closely parallel the pattern seen in the general United States pediatric population. Although only ca. 20% of all episodes occur during the first 6 months of life, nearly 80% of episodes are seen by 18 months of age. Based on the observed incidence rates, the apparent underreporting and the high city-wide case fatality of Hib meningitis (16%), invasive H. influenzae infections represent an important public health problem in Santiago, Chile.     

Characteristics of invasive pneumococcal disease in hospitalized children in Austria

In a prospective surveillance study covering all pediatric wards in Austria, 308 cases of invasive pneumococcal disease (IPD) were reported in hospitalized children <5 years of age between 2002 and 2012. Incidence was 7.1 per 100,000 per year for IPD with a case fatality rate of 3 %, and 1.9 per 100,000 per year for pneumococcal meningitis with a case fatality rate of 9 %. At hospital discharge, 17 % of the children were not fully recovered and suffered from problems such as hearing or motor deficits. Persistent sequelae 6 months after hospital discharge were present in 13 % of the children, a finding that emphasizes the seriousness of IPD. From 2007 onwards, we observed a shift of pneumococcal serotypes from those covered by the heptavalent vaccine to serotypes consequently added to 10- and 13-valent vaccines, particularly regarding serotype 19A. Among antimicrobial resistances detected, macrolide resistance was predominant; however, between 2002 and 2012, we saw an overall decrease of resistance rates. Conclusion: Considering this change of serotypes and the high rate of permanent sequelae after IPD, our data show the importance of pediatric pneumococcal vaccination and the relevance of continuous monitoring of circulating serotypes. By the end of 2012, which was the first year of universal mass vaccination against pneumococcal disease in Austria, no change in the incidence of invasive pneumococcal disease was observed yet.     

Epidemiology of invasive Haemophilus influenzae type b infections in Geneva, Switzerland, 1976 to 1989

We report a retrospective study of invasive Haemophilus influenzae type b (Hib) diseases in Geneva from 1976 to 1989. Among the 183 children who fulfilled the case definition, 6 (3.3%) presented with more than one site of infection. The overall incidence rate among children younger than 5 years of age was 60.2/100,000 but it was 92.1/100,000 in 1989. Forty-one percent of patients had meningitis, 37% had epiglottis and 22% had other forms of Hib infections. Fifty-four percent of cases occurred in children younger than 2 years of age. Invasive Hib infections were found more often in boys than in girls (1.6/1). From 1984, 21% of all Hib were beta-lactamase-producing strains. During the study period 2 children (1.1%) died from epiglottitis and 12 children with meningitis (15.8%) developed serious neurologic deficits. These data suggest that administration of a conjugate vaccine against Hib to all infants living in Geneva is justified.     

Sequelae of Haemophilus influenzae type b meningitis in Aboriginal and non-Aboriginal children under 5 years of age

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 100000 for non-Aboriginal and 152.2 per 100000 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.     

A high degree of natural immunologic priming to the capsular polysaccharide may not prevent Haemophilus influenzae type b meningitis

BACKGROUND: A current debate is whether the immunologic priming of infants with Haemophilus influenzae type b (Hib) conjugate vaccines would be protective in the absence of circulating antibody to the capsular polysaccharide (PS). Data from the prevaccine era on the PS antibody responses of older children to Hib meningitis may be informative on this issue. METHODS: PS antibody was assayed by radioantigen binding in sera taken in the first month postadmission in 47 children ages 2 to 136 months with culture-proved Hib meningitis. RESULTS: Sera obtained on admission had very low antibody concentrations, and the subsequent response during convalescence was age-dependent. The major finding is that some patients, including 10 of 11 children older than 2 years, had substantial antibody elevations within a few days of admission, increases resembling the response to PS vaccine in infants primed with PS-protein conjugate vaccines. CONCLUSIONS: In this group of patients with Hib meningitis, natural priming did not prevent infection. Hib may have the ability to invade despite the capacity for a vigorous antibody response.     

Detection of antigenuria for diagnosis of invasive Haemophilus influenzae type b disease

BACKGROUND: Haemophilus influenzae type b (Hib) diseases are responsible for an estimated 400,000 childhood deaths, mostly in developing countries. OBJECTIVES: To determine the value of the Wellcogen quantitative latex agglutination test (LA) in urine for the diagnosis of Hib pneumonia and meningitis. METHODS: Healthy and sick children aged <5 y were enrolled in Dhaka Shishu (Children's) Hospital. Boiled and non-concentrated urine specimens underwent LA testing. In vaccinated subjects, urine was tested by LA at 24 h, 4-6 and 7-10 d after vaccination. RESULTS: Of 1302 enrolled cases, 201 were healthy (90 Hib vaccine recipients and 111 provided NP) and 1101 were sick with either pneumonia (n=974) or meningitis (n=127). Among the healthy children enrolled, 41 (41/111, 37%) were colonised with Hib and two (2/41, 5%) were positive by LA test. Hib antigenuria among the children who had received Hib vaccination was mainly detected only on day 1 (7/90, 8%) of vaccination. Among the sick children, LA test for Hib antigen was positive for all confirmed cases of Hib pneumonia (10) and meningitis (35). In contrast, none of the urine specimens from the cases with a known aetiology other than Hib (n=104) was positive. Quantitative analysis of antigenuria of sick children showed that it is positive at least up to 1:8 and 1:16 dilutions for pneumonia and meningitis, respectively, in contrast with or=1:8 dilutions. CONCLUSIONS: The Wellcogen LA test for Hib using boiled and non-concentrated urine is more sensitive than blood culture alone and is highly specific.