Hib Meningitis Research Articles

Bacterial meningitis following introduction of Hib conjugate vaccine in northern Uganda

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. All patients with suspected bacterial meningitis between April 2003 and August 2006 were recruited. Meningitis was confirmed by isolation of bacteria. 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%. 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.

Bacterial Meningitis Clinical Findings at Admission Predict Outcome

Source: Roine I, Peltola H, Fernández J, et al. Influence of admission findings on death and neurological outcome from childhood bacterial meningitis. Clin Infect Dis. 2008;46(8):1248–1252; doi:10.1086/533448Investigators from South America and Finland previously reported on admission and outcome data from 654 cases of childhood bacterial meningitis in a prospective, randomized, double-blind study.1In the current report they present the results of a post hoc analysis to determine independent predictors of outcome. Of the 654 patients in the study, 86 (13%) died and 556 (98%) of the 568 surviving patients were available for analysis. Degree of neurological deficit was predefined. Severe neurological deficits were identified in 44 (8%) and mild neurological deficits in 102 (18%) patients.Admission data were analyzed for three categories: death, death and severe neurological sequelae, and death and any neurological sequelae. By univariate analysis, young age, convulsions, delay in presentation, Glasgow Coma Score (GCS) below 13, slow capillary-filling time, low CSF glucose and high protein concentrations, low blood leukocyte count, low blood hemoglobin, and pneumococcal etiology were each associated with an increased risk of all three outcome categories. In multiple logistic regression analysis only GCS was an independent predictor for all three outcomes.There was a nine-fold increased risk of death with a GCS of ≤6 compared with a GCS of 13–15 (P=.002). The relationship of lower GCS with death or severe neurological sequelae was even stronger. As compared with a GCS of 13–15, the risk of death or severe neurological sequelae increased 3.51 times with a GCS of 10–12 (95% CI, 1.49–8.25), increased 10.64 times when GCS was 7–9, and increased 28.83 times with a GCS ≤6.For children with GCS of 13–15, risk of death was almost five times higher among those with Streptococcus pneumoniae than those with Haemophilus influenzae type b (Hib) meningitis. However, for those with GCS ≤12 the risk of death was predicted by GCS and not the etiologic agent. The authors conclude that the child’s level of consciousness at the time of hospitalization was the most important predictor of outcome in bacterial meningitis.Dr. Rathore has disclosed no financial relationship relevant to this commentary. This commentary does not contain a discussion of an unapproved/investigative use of a commercial product/device.With the introduction of Hib and S. pneumoniae conjugate vaccines for infants, the prevalence of childhood bacterial meningitis has decreased significantly in the US. However, bacterial meningitis still occurs and is one of the most common reasons for litigation when the outcome is poor.2Previous studies have primarily focused on etiology of meningitis and CSF glucose concentration as predictors of outcome. The results of this study indicate that these are important predictors but that etiology was important only when the level of consciousness was close to normal (risk of death was higher in patients with pneumococcus when GCS was 13–15), and low CSF glucose was significant only when milder neurological sequelae were included in the analysis. This finding is of obvious benefit in under-resourced areas of the world where childhood meningitis is common, sophisticated evaluation techniques are lacking, and treatment and intervention decisions have to be made based on rationed availability of resources.In addition, as the authors suggest, one must be careful in reaching conclusions about treatment interventions in childhood bacterial meningitis by combining studies from populations that differ considerably in clinical conditions and available resources. The inherent weaknesses of any post hoc analysis limit the interpretation of the results of this study. Until prospective studies validate its findings, the present study should assist physicians in the US and other developed nations in discussing meningitis outcomes with families.

Corticosteroids Don't Reduce Mortality in Children with Bacterial Meningitis

Administration of adjuvant corticosteroids mitigates hearing loss in children with Haemophilus influenzae type B (Hib) meningitis. However, the

Action for child survival: elimination of Haemophilus influenzae type b meningitis in Uganda

To guide immunization policy, we determined the public health benefit of introducing Haemophilus influenzae type b (Hib) vaccine in Uganda and estimated the vaccine effectiveness. Surveillance data for acute bacterial meningitis among children aged 0-59 months were reviewed from three hospital sentinel sites, for July 2001 to June 2007, to determine the incidence of Hib meningitis, the effectiveness of Hib vaccine with a case-control design, and the number of vaccine-preventable cases and deaths of Hib disease in Uganda. Of the 13 978 children from 17 districts with suspected bacterial meningitis, 269 had confirmed Hib meningitis, declining from 69 patients in the prevaccine year (2001-2002) to three in 2006-2007. Hib meningitis incidence dropped from 88 cases per 100,000 children aged < 5 years in the year before vaccine introduction to 13 within 4 years, and to near zero in the fifth year. Vaccine effectiveness for 2 or more doses was 93% (95% confidence interval, CI: 69-99) against confirmed Hib meningitis and 53% (95% CI: 11-68) against purulent meningitis of unknown cause. In Uganda, Hib vaccine prevents an estimated 28 000 cases of pneumonia and meningitis, 5000 deaths and 1000 severe meningitis sequelae each year. Infant immunization with Hib vaccine has virtually eliminated Hib meningitis in Uganda within 5 years. Ensuring long-term benefits of Hib vaccine urgently requires sustainable vaccine financing, high-quality ongoing surveillance, and a health sector able to deliver a robust immunization programme.

Progress in vaccination against Haemophilus influenzae type b in the Americas.

Worldwide, Haemophilus influenzae type b (Hib) causes at least 3 million cases of severe disease each year. Approximately 400,000 children die annually due to pneumonia or meningitis caused by Hib [1]. Severe neurological sequelae occur in 15% to 30% of those who survive Hib meningitis [2]. Other, less frequent, manifestations of Hib are epiglottitis, septic arthritis, osteomyelitis, and septicemia [1–3]. Current polysaccharide–protein conjugate Hib vaccines are highly efficacious and safe. Primary series of two or three doses protect approximately 95% of infants [4–8]. Universal infant Hib immunization has proven to dramatically reduce Hib invasive disease [9–13] through direct vaccine protection and an important herd effect related to the reduction in Hib nasopharyngeal carriage in the community [12,14–16]. Adverse events are rare, and Hib vaccine is contraindicated only for persons with hypersensitivity to any of the vaccine's components [8,17]. The World Health Organization (WHO) recommends the introduction of Hib vaccines worldwide [1]. Furthermore, the Global Alliance for Vaccines and Immunization (GAVI Alliance)—an organization that aligns public and private resources in a global effort to create greater access to the benefits of immunization—considers Hib vaccine introduction in the world's poorest countries to be a top priority [18]. Prior to vaccine introduction, an estimated 20,000 cases of Hib meningitis were estimated to occur in countries of Latin America and the Caribbean (LAC) annually, based on an overall Hib meningitis incidence of 35 per 100,000 children aged 0–4 years [19]. Another 20,000 cases of invasive Hib disease were estimated to occur in the United States annually [20]. Most cases occurred in children aged less than 24 months, with at least 60% of cases occurring in children aged 0–11 months in half of the studies. The annual mortality rate for Hib meningitis in children aged less than five years was estimated to be around two per 100,000 in the Western Hemisphere [21]. Summary Points Hib vaccine introduction in countries of Latin America and the Caribbean has substantially reduced morbidity and mortality due to invasive Hib infections. All Latin American and Caribbean countries but one include Hib vaccine in their routine immunization schedule for infants. Factors that favored this region-wide Hib vaccine adoption include strong political will, data supporting Hib disease burden and impact in early adopting countries, and experience exchange among countries. Financial sustainability when introducing the more expensive Hib vaccine was critical for ensuring successful vaccine introduction in all countries. Efforts are still needed to improve vaccination coverage and to strengthen invasive bacterial disease surveillance in developing countries. In this article, we review the progress of vaccine introduction, lessons learned, and remaining challenges regarding Hib vaccination in the Americas, with emphasis on LAC countries. We expect that this updated and summarized information on Hib vaccination will serve as a useful reference to public health officials and policy makers from other regions who face the challenge of introducing Hib and other new or underutilized vaccines.

Haemophilus influenzae type b conjugate vaccine is highly effective in the Ugandan routine immunization program: a case–control study

To study the effectiveness of the Haemophilus influenzae type b (Hib) vaccination program in Uganda. Case-control study of Hib vaccine effectiveness against Hib meningitis. Cases were children hospitalized with Hib meningitis confirmed by culture and/or latex agglutination. Cases were identified retrospectively from July 2002 to July 2004, and prospectively from July 2004 to July 2005. Each case-patient was matched by age to three neighbourhood and three hospital controls; all children were eligible to receive Hib vaccine through the routine schedule. Vaccine effectiveness was evaluated by conditional logistic regression, controlling for confounding variables. We enrolled 41 cases; their median age was 6 months. Only six (15%) cases, all HIV-negative, had received >/=2 doses of Hib vaccine, compared with 64% of neighbourhood controls and 70% of hospital controls. Controlling for maternal education, the only variable which remained in the multivariable model, vaccine effectiveness for two or three doses vs. no dose was 99% [95% confidence intervals (CI) 92-100%] and 96% (95% CI 80-100%) when cases were compared with neighbourhood and hospital controls, respectively. In Uganda, Hib vaccine was highly effective in the context of the routine immunization schedule. Sustained routine use of Hib vaccine will contribute to the prevention of childhood morbidity and mortality.

Epidemiology and outcomes of bacterial meningitis in Mexican children: 10-year experience (1993–2003)

Acute bacterial meningitis remains an important cause of morbidity, neurologic sequelae, and mortality in children in Latin America. We retrospectively reviewed the hospital-based medical records of children diagnosed with acute bacterial meningitis, aged 1 month to 18 years, at a large inner city referral Hospital in Mexico City, for a 10-year period (1993-2003). To characterize the epidemiology, clinical features, and outcomes of acute bacterial meningitis, we subdivided our study into two time periods: the period prior to the routine use of Haemophilus influenzae type b (Hib) vaccine (1993-1998) and the period after the vaccine became available (1999-2003). A total of 218 cases of acute bacterial meningitis were identified during the study period. The most frequently affected age group was that of children aged between 1 and 6 months. Hib was the most commonly isolated pathogen, found in 50% of cases. However, its incidence declined significantly after the introduction of the combined diphtheria, tetanus, pertussis, hepatitis B, and conjugated Hib (DTP-HB/Hib) pentavalent vaccine into the universal vaccination schedule for children in 1998. Streptococcus pneumoniae followed as the second most commonly isolated bacterial pathogen. Neisseria meningitidis was isolated in only a few cases, confirming the historically low incidence of this pathogen in Mexico. Identified risk factors for death were found to include the presence of septic shock and intracranial hypertension, but were not attributable to any particular bacterial pathogen. In our hospital, acute bacterial meningitis remains a severe disease with important sequelae and mortality. The incidence of Hib meningitis cases has declined since the introduction of the Hib vaccine. However, S. pneumoniae persists as an important cause of bacterial meningitis, highlighting the need for the implementation of vaccination policies against this pathogen.

Direct Detection of the Multidrug Resistance Genome of Haemophilus influenzae in Cerebrospinal Fluid of Children

Multidrug resistance (MDR), specifically to ampicillin and chloramphenicol, has complicated the treatment of Haemophilus influenzae type b (Hib) meningitis. This is worsened by use of prior antibiotics, which limits identification of the causative agent by culture and increases reliance on antigen detection. We aimed to develop a PCR assay for detecting the family of Haemophilus integrating and conjugative elements (ICEs) represented by ICEHin1056 among antibiotic resistant Hib, and then apply this directly to CSF to diagnose Hib meningitis and predict organism susceptibility, irrespective of culture results. Primers specific for orf 51 of ICEHin1056 were designed and multiplexed with Bex primers, specific for H. influenzae, and tested on culture positive and negative cases. Of 73 Hib isolates, orf 51 PCR amplicons, predicting the presence of ICEs, were found in all 33 MDR isolates while only in 1 of 33 sensitive strains. The remaining 7 ampicillin susceptible, chloramphenicol and tetracycline resistant strains did not produce a PCR product to orf 51. PCR amplification from CSF specimens of these culture positive cases produced identical results with 100% and 97% positive and negative predictive values, respectively. Multiplex PCR to detect Bex and orf 51 identified another 16 MDR Hib cases among 81 culture-negative CSF samples. Direct PCR for orf 51 in CSF identified resistance pattern of 51% more Hib strains than culture alone (110 versus 73). The ability to detect MDR, in culture negative Hib meningitis cases has significant implications for better directing antibiotic treatment of meningitis cases and thus for preventing disability and death.

Vaccination policy and programs in the circumpolar world

In Canada the introduction of the Haemophilus influenzae type b (Hib) capsular polysaccharide-protein conjugate vaccines in 1988 led to a reduction in the annual incidence of Hib meningitis in children less than 5 years of age from approximately 44/100,000 in 1985 to &1/100,000 by 1994 (1). This reduction in morbidity and mortality was particularly dramatic among the Canadian Inuit, who had suffered the highest reported incidence of Hib meningitis (530/100,000 children less than 5 years) among indigenous populations worldwide (2).

Haemophilus influenzae type b conjugate vaccine impact against purulent meningitis in Rwanda

Rwanda introduced Haemophilus influenzae type b (Hib) conjugate vaccine in January 2002 and simultaneously implemented pediatric bacterial meningitis surveillance at a major referral hospital in the capital Kigali. We reviewed clinical and laboratory information collected during January 2002 to June 2006. Due to a variety of laboratory limitations, only eight confirmed Hib cases were identified, all before 2004. However, the proportion of cerebrospinal fluid with purulence decreased from 26.0% during 2002, to 15.9% during 2003, 9.7% during 2004 and 8.4% in 2005 (p<0.001). Vaccine effectiveness of two or three doses of Hib vaccine against purulent meningitis was 52% (95% confidence interval, 5-75%). In an African setting with few resources and in which few confirmed Hib meningitis cases were identified, Hib vaccine impact nevertheless could be demonstrated against the outcome of purulent meningitis and was found to be high.

Effectiveness of Haemophilus influenzae Type B Conjugate Vaccine on Prevention of Pneumonia and Meningitis in Bangladeshi Children

Few Asian countries have introduced Haemophilus influenzae type b (Hib) conjugate vaccine because of its cost and uncertainty regarding disease burden. 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. 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%). The study documented that significant fractions of pneumonia and meningitis in Bangladeshi children age <2 years can be prevented by the Hib conjugate vaccine.

Economic evaluation of delivering Haemophilus influenzae type b vaccine in routine immunization services in Kenya.

Haemophilus influenzae type b (Hib) vaccine was introduced into routine immunization services in Kenya in 2001. We aimed to estimate the cost-effectiveness of Hib vaccine delivery. A model was developed to follow the Kenyan 2004 birth cohort until death, with and without Hib vaccine. Incidence of invasive Hib disease was estimated at Kilifi District Hospital and in the surrounding demographic surveillance system in coastal Kenya. National Hib disease incidence was estimated by adjusting incidence observed by passive hospital surveillance using assumptions about access to care. Case fatality rates were also assumed dependent on access to care. A price of US$ 3.65 per dose of pentavalent diphtheria-tetanus-pertussis-hep B-Hib vaccine was used. Multivariate Monte Carlo simulations were performed in order to assess the impact on the cost-effectiveness ratios of uncertainty in parameter values. The introduction of Hib vaccine reduced the estimated incidence of Hib meningitis per 100,000 children aged < 5 years from 71 to 8; of Hib non-meningitic invasive disease from 61 to 7; and of non-bacteraemic Hib pneumonia from 296 to 34. The costs per discounted disability adjusted life year (DALY) and per discounted death averted were US$ 38 (95% confidence interval, CI: 26-63) and US$ 1197 (95% CI: 814-2021) respectively. Most of the uncertainty in the results was due to uncertain access to care parameters. The break-even pentavalent vaccine price--where incremental Hib vaccination costs equal treatment costs averted from Hib disease--was US$ 1.82 per dose. Hib vaccine is a highly cost-effective intervention in Kenya. It would be cost-saving if the vaccine price was below half of its present level.

Vaccine: The Controversial Story of Medicine's Greatest Lifesaver

In his comprehensive survey of vaccination controversies past and present, Arthur Allen quotes US vaccine chief Walter Orenstein's recollection that ‘for those trained in pediatrics in the 1970s, Hib (Haemophilus influenzae type b) was a horror.’ It was indeed. I recall a mother whose infant died of Hib meningitis, secondary to an apparently trivial otitis media, within minutes of arriving in hospital. Already at an advanced stage of her second pregnancy, she promptly went into labour and had an uncomplicated delivery. The way her grief at the loss of one child overwhelmed her joy at the arrival of another is my enduring memory of the horror of Hib, which was still killing 60 children every year in Britain in the 1980s. Thanks to the introduction of routine Hib immunization in 1992, this disease has now become a rarity. Yet, as Orenstein points out, when the immunization was introduced there was much uncertainty about its impact on the ecology of Haemophilus and the long term consequences. As he observes, some things are ‘only knowable in the long run;’ in the meantime, ‘we have to take our chances and then follow up.’ One of the themes of Allen's book is that this courageous and enterprising approach to vaccination policy—vindicated by its historic achievements in the conquest of disease—is now threatened by the contemporary climate of risk aversion. Allen does not ignore the history of vaccine disasters. He includes the fiasco in the US military in 1942, when yellow fever vaccine contaminated with hepatitis B caused 100 deaths, and the mass vaccination against smallpox in New York in 1947 that caused six deaths (four more than the outbreak itself). In the Cutter incident in the 1950s, inadequately inactivated polio vaccine caused 164 cases of paralysis and 10 deaths. While acknowledging these failures, Allen pays tribute to immunization authorities—such as Henry Kempe and Bob Chen—who have campaigned to improve vaccine safety. The great irony underlying current vaccination controversies is that, as vaccines have become more effective and safer than ever before, an anti-vaccine world view, reflecting a combination of nostalgia and cultural pessimism, has become more prevalent. Allen reports how one family with an autistic child described ‘going down the rabbit hole’ into a ‘spooky realm of herbalists and populist mavericks and—not to put too fine a point on it—conspiracy kooks, who view America as a toxic hell.’ Recognizing that parents' anger and inclination to blame vaccines reflect difficulties in coming to terms with their children's disabilities, Allen has himself bravely challenged anti-vaccine campaigners who have had such a damaging impact on the world of autism. Allen concludes with Orenstein's prescient warning that a precautionary approach, reflecting corporate concerns about a low profit, high risk area of investment and government sensitivities to public anxieties, ‘could paralyze’ innovation in vaccines.

Haemophilus influenzae meningitis 5 years after introduction of the Haemophilus influenzae type b conjugate vaccine in Brazil

The long-term impact of Haemophilus influenzae type b (Hib) conjugate vaccine, introduced throughout Latin America in the late 1990s, has not been evaluated. Active surveillance for H. influenzae meningitis was performed from August 9, 1996 to August 8, 2004 in Metropolitan Salvador, Brazil. Five years after the introduction of Hib conjugate vaccine, Hib meningitis incidence decreased from 2.39 to 0.06 cases per 100,000 population (98%) overall, and from 60.9 to 3.1 cases per 100,000 population (95%) in children <1 year of age. A transient serotype replacement phenomenon was observed associated with a small increase of meningitis due to two H. influenzae type a clonal groups. These findings indicate that Hib immunization campaign has led to the virtual elimination of Hib disease in this region.

Incidence of bacterial meningitis in Asia using enhanced CSF testing: polymerase chain reaction, latex agglutination and culture

To enhance the detection of bacterial meningitis in an East Asian surveillance study, we employed cerebrospinal fluid (CSF) bacterial culture, latex agglutination (LA) and polymerase chain reaction-enzyme immunoassay (PCR-EIA) testing for Haemophilus influenzae type b (Hib) and Streptococcus pneumoniae (Sp). The sensitivity and specificity of CSF PCR-EIA testing was compared to LA and culture. A meningitis case was defined by one positive result for any of the three tests. The sensitivity of H. influenzae CSF PCR-EIA, LA, and culture was 100%, 40% and 57.5% respectively; and for Sp CSF PCR-EIA, LA and culture, the sensitivity was 100%, 58.3% and 66.7%, respectively. Hib and Sp specificity was 100% by each method. CSF PCR-EIA was more sensitive than culture or LA for the detection of Hib and Sp meningitis cases increasing their incidence by 74% and 50% compared to culture respectively. CSF PCR-EIA should be included for the detection of bacterial meningitis in surveillance studies.

小児インフルエンザ菌性髄膜炎の抗菌療法に関する検討

We summarize 41 cases of bacterial meningitis in the last 11 years caused by Haemophilus influenzae. All isolates were serotype b strain (Hib). Initial chemotherapy was started with ceftriaxone (CTRX) in 22 cases, ampicillin plus cefotaxime (CTX) in 9, CTRX plus panipenem/betamipron in 5, and CTX in 2. Some 31 cases were treated mainly with CTRX. Although therapeutic antibiotics showed good susceptibility for isolates, 8 complicated cases (19.5%) occurred. Sequalae were observed in 7 (17.1%) but none were fatal. Five strains with elevated MIC of CTX (0.12 to 1 microg/mL) recovered after 2001, and 3 of 5 strains also showed elevated MIC of CTRX (0.12 to 0.5 microg/mL), but all were cured completely with CTRX. At present, no treatment failures due to antibiotic resistance have been observed, and CTRX remains suitable as initial therapy for Hib meningitis. A decline in susceptibility for third-generation cephalosporin against beta-lactamase-nonproducing ampicillin-resistant H. influenzae is emerging, however, so it will be necessary to consider combination therapy with CTRX given the foreseeable trend in MICs.

Prevalence of β-lactamase-nonproducing ampicillin-resistant Haemophilus influenzae and Haemophilus influenzae type b strains obtained from children with lower respiratory tract infections

The prevalence of strains with ampicillin (ABPC) resistance among Haemophilus influenzae strains isolated from the nasopharynx of children with lower respiratory tract infections has increased significantly during the 6 years from 2000, when it was 41.9%, to 2005, when it reached 60.1%. From 2002, the prevalence exceeded 50%, and the prevalence of beta-lactamase-nonproducing ABPC-resistant (BLNAR) strains with a minimum inhibitory concentration (MIC) of ABPC of over 4 microg/ml doubled, from 28.2% in 2002 to 54.7% in 2005. In H. influenzae strains obtained from the nasopharynx of children with lower respiratory tract infections between April 2004 and March 2006, identification of serotype b was defined, using the slide agglutination method. The frequency of isolation of H. influenzae type b (Hib) strains was then measured and the ABPC resistance conditions of the Hib strains were also evaluated. The frequency of the Hib strains was found to be 30 out of 479 strains, 6.3%. Of these 30 strains, BLNAR accounted for 53.3% (16 strains), approximately the same frequency of isolation as that of the BLNAR isolated from all H. influenzae strains during the same period. In Japan, the prevalence of BLNAR strains among clinically isolated H. influenzae strains has continued to increase, and the frequency of isolation of BLNAR strains among Hib strains has also continued to rise. As a countermeasure, attempts at improving resistance have been made through judicious antibiotic use, but concern that the choice of antibiotics for Hib meningitis may become complicated has sparked a keen interest in the introduction of Hib conjugate vaccine.

Detection of antigenuria for diagnosis of invasiveHaemophilus influenzaetype b disease

Haemophilus influenzae type b (Hib) diseases are responsible for an estimated 400,000 childhood deaths, mostly in developing countries. To determine the value of the Wellcogen quantitative latex agglutination test (LA) in urine for the diagnosis of Hib pneumonia and meningitis. 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. 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=1:4 for healthy children. In addition to the ten cases of culture-proven Hib, the test detected an additional 16 Hib pneumonia cases among children diagnosed as pneumonia, based on the presence of antigenuria >or=1:8 dilutions. The Wellcogen LA test for Hib using boiled and non-concentrated urine is more sensitive than blood culture alone and is highly specific.

The impact of routine infant immunization with Haemophilus influenzae type b conjugate vaccine in Malawi, a country with high human immunodeficiency virus prevalence

Malawi has extreme poverty and a high-human immunodeficiency virus (HIV) prevalence. Following Haemophilus influenzae type b (Hib) conjugate vaccine introduction during 2002, we evaluated vaccine impact by reviewing hospital surveillance data for acute bacterial meningitis in Blantyre district among children age 1–59 months admitted during 1997–2005. Documented annual Hib meningitis incidence rates decreased from 20–40/100,000 to near zero among both rural and urban residents despite no change in pneumococcal meningitis incidence rates. Before vaccine introduction, an average of 10 children/year had Hib meningitis and HIV infection compared to 2/year during 2003–2004 and none during 2005. Vaccine effectiveness was high following two or more doses of vaccine. The most urgent future need is for a sustainable routine infant immunization program, including a less expensive vaccine that preferably is delivered in a multivalent form.

The Epidemiology of Haemophilus influenzae Type b Meningitis in Burkina Faso

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. 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. 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. 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.