Estimating the global and regional burden of meningitis in children caused by Haemophilus influenzae type b: A systematic review and meta-analysis.

Background: Haemophilus influenzae Type B (Hib) meningitis caused significant public health concern for children. Recent assessment in 2015 suggests vaccination has virtually eliminated invasive Hib diseases. However, many countries launched their programs after 2010, and few are yet to establish routine Hib immunisations. We therefore aimed to update the most recent global burden of Hib meningitis before the impact of COVID-19 pandemic, from 2010 to 2020, in order to aid future public health policies on disease management and prevention. Methods: Epidemiological data regarding Hib meningitis in children <5 years old were systematically searched and evaluated from PubMed and Scopus in August, 2020. We included studies published between 2010 and 2019 that reported incidence, prevalence, mortality, or case-fatality-ratio (CFR), and confirmation of meningitis by cerebrospinal fluid culture, with a minimum one year study period and ten cases. Each data was stratified by one study-year. Median study-year was used if information was not available. Quality of all studies were assessed using our adapted assessment criteria from Grading of Recommendations Assessment, Development and Evaluation (GRADE) and Study Quality Assessment Tool for Observational Cohort and Cross-Sectional Studies from National Heart, Lung and Blood Institute (NHLBI). We constructed and visually inspected a funnel plot of standard error by the incidence rate and performed an Egger's regression test to statistically assess publication bias. To ascertain incidence and CFR, we performed generalised linear mixed models on crude individual study estimates. Heterogeneity was assessed using I-squared statistics whilst further exploring heterogeneity by performing subgroup analysis. Results: 33 studies were identified. Pooled incidence of global Hib meningitis in children was 1.13 per 100 000-child-years (95% confidence interval (CI) = 0.80-1.59). Southeast Asian Region (SEAR) of World Health Organisation (WHO) region reported the highest incidence, and European Region (EUR) the lowest. Considering regions with three or more data, Western Pacific Region (WPR) had the highest incidence rate of 5.22 (95% CI = 3.12-8.72). Post-vaccination incidence (0.67 cases per 100 000-child-years, 95% CI = 0.48-0.94) was dramatically lower than Pre-vaccination incidence (4.84 cases per 100 000-child-years, 95% CI = 2.95-7.96). Pooled CFR in our meta-analysis was 11.21% (95% CI = 7.01-17.45). Eastern Mediterranean Region (EMR) had the highest CFR (26.92, 95% CI = 13.41-46.71) while EUR had the lowest (4.13, 95% CI = 1.73-9.54). However, considering regions with three or more data, African Region (AFR) had the highest CFR at 21.79% (95% CI = 13.65-32.92). Before the coronavirus disease 2019 (COVID-19) impact, the estimation for global Hib meningitis cases in 2020 is 7645 and 857 deaths. Conclusions: Global burden of Hib meningitis has markedly decreased, and most regions have implemented vaccination programs. Extrapolating population-at-risk from studies has possibly led to an underestimation. Continuous surveillance is necessary to monitor vaccination impact, resurgence, vaccine failures, strain variance, COVID-19 impact, and to track improvement of regional and global Hib meningitis mortality.

Haemophilus influenzae type b disease in the era of conjugate vaccines: critical factors for successful eradication.

INTRODUCTION: Prior to implementation of Haemophilus influenzae type b (Hib)-conjugate vaccination programs in the 1990s, Hib was the commonest cause of bacterial meningitis in children aged <5 years. While the burden of all Hib disease has significantly decreased in the post-vaccination era, Hib still accounted for >29,000 deaths worldwide in children aged <5 years in 2015. AREAS COVERED: We reviewed literature data on the most widely used Hib vaccines and vaccination strategies which led to the global prevention and control of Hib disease and aim to highlight important factors for continued disease control and elimination in the future. EXPERT COMMENTARY: More than 90% of countries worldwide have implemented Hib-conjugate vaccination in their national immunization programs. Vaccines containing Hib polyribosylribitol phosphate (PRP) conjugated with tetanus toxoid (Hib-TT) are the most commonly used. Neisseria meningitidis outer membrane protein complex of PRP (Hib-OMP) is also used. Although the kinetics of the immune response varies with Hib vaccine and schedule used, high control of Hib disease was observed in all settings/scenarios. Further improving global Hib vaccination coverage may result in disease elimination. Plain language summary What is the context? Haemophilus influenzae is causing a variety of diseases, from otitis media and sinusitis to invasive disease (e.g. meningitis and pneumonia). H. influenzae type b (Hib) was the most common cause of bacterial meningitis in children <5 years of age, and especially among <2-year-olds. Even with appropriate treatment, up to 40% of children with bacterial meningitis can suffer permanent disabilities and up to 5% will die. The development of vaccines to protect against Hib disease has started in the late 1970s and has culminated with the licensure of 4 Hib conjugate vaccines, of which 2 are currently widely used. What is new? In this review, we gathered evidence on the different Hib vaccines and vaccination strategies that have contributed to the global prevention and control of Hib disease. The review indicates: the incidence of Hib disease has decreased considerably due to the introduction of Hib vaccines in national immunization programs worldwide. However, Hib disease is not yet completely eradicated. the vaccines currently used offer protection against Hib over long periods of time. carriage of the pathogen by healthy individuals seem to be less frequent, but data are still needed to fully evaluate the impact of vaccination. other H. influenzae types are now more frequent. Why is this important? Despite the huge success of Hib vaccination, continuous surveillance is needed to anticipate potential re-emergences and devise the best strategies for prevention and control of disease. Hib vaccination should be considered in the few countries who have not yet implemented it, to decrease associated morbidity and mortality.

Impact of routine vaccination against Haemophilus influenzae type b in The Gambia: 20 years after its introduction.

BACKGROUND: In 1997, The Gambia introduced three primary doses of Haemophilus influenzae type b (Hib) conjugate vaccine without a booster in its infant immunisation programme along with establishment of a population-based surveillance on Hib meningitis in the West Coast Region (WCR). This surveillance was stopped in 2002 with reported elimination of Hib disease. This was re-established in 2008 but stopped again in 2010. We aimed to re-establish the surveillance in WCR and to continue surveillance in Basse Health and Demographic Surveillance System (BHDSS) in the east of the country to assess any shifts in the epidemiology of Hib disease in The Gambia. METHODS: In WCR, population-based surveillance for Hib meningitis was re-established in children aged under-10 years from 24 December 2014 to 31 March 2017, using conventional microbiology and Real Time Polymerase Chain Reaction (RT-PCR). In BHDSS, population-based surveillance for Hib disease was conducted in children aged 2-59 months from 12 May 2008 to 31 December 2017 using conventional microbiology only. Hib carriage survey was carried out in pre-school and school children from July 2015 to November 2016. RESULTS: In WCR, five Hib meningitis cases were detected using conventional microbiology while another 14 were detected by RT-PCR. Of the 19 cases, two (11%) were too young to be protected by vaccination while seven (37%) were unvaccinated. Using conventional microbiology, the incidence of Hib meningitis per 100 000-child-year (CY) in children aged 1-59 months was 0.7 in 2015 (95% confidence interval (CI) = 0.0-3.7) and 2.7 (95% CI = 0.7-7.0) in 2016. In BHDSS, 25 Hib cases were reported. Nine (36%) were too young to be protected by vaccination and five (20%) were under-vaccinated for age. Disease incidence peaked in 2012-2013 at 15 per 100 000 CY and fell to 5-8 per 100 000 CY over the subsequent four years. The prevalence of Hib carriage was 0.12% in WCR and 0.38% in BHDSS. CONCLUSIONS: After 20 years of using three primary doses of Hib vaccine without a booster Hib transmission continues in The Gambia, albeit at low rates. Improved coverage and timeliness of vaccination are of high priority for Hib disease in settings like Gambia, and there are currently no clear indications of a need for a booster dose.

Etiology of Pediatric Meningitis in West Africa Using Molecular Methods in the Era of Conjugate Vaccines against Pneumococcus, Meningococcus, and Haemophilus influenzae Type b.

Despite the implementation of effective conjugate vaccines against the three main bacterial pathogens that cause meningitis, Streptococcus pneumoniae, Haemophilus influenzae type b (Hib), and Neisseria meningitidis serogroup A, the burden of meningitis in West Africa remains high. The relative importance of other bacterial, viral, and parasitic pathogens in central nervous system infections is poorly characterized. Cerebrospinal fluid (CSF) specimens were collected from children younger than 5 years with suspected meningitis, presenting at pediatric teaching hospitals across West Africa in five countries including Senegal, Ghana, Togo, Nigeria, and Niger. Cerebrospinal fluid specimens were initially tested using bacteriologic culture and a triplex real-time polymerase chain reaction (PCR) assay for N. meningitidis, S. pneumoniae, and H. influenzae used in routine meningitis surveillance. A custom TaqMan Array Card (TAC) assay was later used to detect 35 pathogens including 15 bacteria, 17 viruses, one fungus, and two protozoans. Among 711 CSF specimens tested, the pathogen positivity rates were 2% and 20% by the triplex real-time PCR (three pathogens) and TAC (35 pathogens), respectively. TAC detected 10 bacterial pathogens, eight viral pathogens, and Plasmodium. Overall, Escherichia coli was the most prevalent (4.8%), followed by S. pneumoniae (3.5%) and Plasmodium (3.5%). Multiple pathogens were detected in 4.4% of the specimens. Children with human immunodeficiency virus (HIV) and Plasmodium detected in CSF had high mortality. Among 220 neonates, 17% had at least one pathogen detected, dominated by gram-negative bacteria. The meningitis TAC enhanced the detection of pathogens in children with meningitis and may be useful for case-based meningitis surveillance.

Immunogenicity and safety of a DTaP-IPV/Hib pentavalent vaccine given as primary and booster vaccinations in healthy infants and toddlers in Japan.

BACKGROUND: Globally, the use of single DTaP-IPV/Hib vaccines that combine DTaP-IPV and Hib is widespread, but in Japan vaccination is usually concomitant at separate sites. The immunogenicity and safety of a primary vaccination series and booster of a combined pentavalent DTaP-IPV/Hib vaccine were evaluated and compared to separate administration of DTaP-IPV and Hib in Japanese infants. METHODS: Healthy Japanese infants were administered DTaP-IPV/Hib (Group A: N = 207) or DTaP-IPV + Hib (Group B: N = 207) by the subcutaneous (SC) or DTaP-IPV/Hib by the intramuscular (IM) route (Group C: N = 10). All subjects received a 3-dose primary vaccination series and a booster. Non-inferiority (Group A versus Group B) was tested post-primary series and subsequent post hoc analyses were performed for anti-Hib. Safety was assessed by parental reports. RESULTS: Non-inferiority for SC administration of Group A versus Group B for the primary series was demonstrated for antibody responses to all antigens except Hib using the threshold of 1.0 µg/mL. Post hoc analyses for anti-Hib demonstrated non-inferiority for the primary series response using 0.15 µg/mL, and for pre-booster antibody persistence and the booster response using 0.15 µg/mL and 1.0 µg/mL. The immune response was similar for each antigen following SC or IM administration. There were no safety concerns in any group, and a lower incidence of injection sites for the IM route was observed as expected. CONCLUSIONS: These data show the good immunogenicity and safety profile of the DTaP-IPV/Hib vaccine as a 3-dose infant primary series followed by a booster in the second year of life in Japan.

Talk to Patients About: Hib.

Despite its name, Haemophilus influenzae type b - or Hib - doesn't cause influenza. In the 1890s, doctors thought this bacteria might cause flu and - despite later research showing flu is caused by a virus - the name stuck. But Hib does cause several severe illnesses, mostly among children under 5 years old. Meningitis is the most common.

Haemophilus influenzae type b vaccination and anthropometric, cognitive, and schooling outcomes among Indian children.

Haemophilus influenzae type b (Hib) affects 337,000 Indian children every year. A vaccine against Hib was introduced in 2011 as part of the pentavalent vaccine and scaled up nationwide. This study investigated the associations between Hib vaccination and child anthropometry, cognition, and schooling outcomes in India. We used longitudinal survey data and employed propensity score matching to control for observed systematic differences between children who reported receipt or nonreceipt of Hib vaccine before age 6 years (n = 1824). Z-scores of height-for-age (HAZ) and BMI-for-age (BMIZ), percentage scores of English, mathematics, reading, and Peabody Picture Vocabulary tests, and attained schooling grade of children were examined. Hib-vaccinated children had 0.25 higher HAZ, scored 4.09 percentage points (pp) higher on the English test and 4.78 pp higher on the mathematics test, and attained 0.16 more schooling grades than Hib-unvaccinated children at age 11-12 years. At age 14-15 years, they had 0.18 higher HAZ, scored 3.63 pp higher on the reading test and 3.22 pp higher on the mathematics test, and attained 0.15 more schooling grades than Hib-unvaccinated children. The findings indicate potential long-term health, cognitive, and schooling benefits of the Hib vaccine, subject to the effect of unobserved confounding factors.

Impact of the introduction of the Haemophilus influenzae type b conjugate vaccine in an urban setting in southern India.

INTRODUCTION: Haemophilus influenzae type b was the leading cause of bacterial meningitis in infants and children below the age of two years prior to the introduction of H. influenzae type b conjugate vaccines. In December 2011, the Indian government introduced H. influenzae b vaccine in the state of Tamilnadu. A prospective surveillance for bacterial meningitis was established at the Institute of Child Health in Chennai to evaluate the etiology of meningitis and impact of the vaccine. MATERIAL AND METHODS: Infants aged one to 23 months who were admitted to the hospital with symptoms of suspected bacterial meningitis were enrolled and lumbar puncture was performed. Cerebrospinal fluid samples were analyzed for white blood cells, protein, and glucose. Bacterial culture and a latex agglutination test for common bacterial pathogens were performed. RESULTS: Between January 2009 and March 2014, 4,770 children with suspected bacterial meningitis were enrolled. Prior to the introduction of the vaccine, an average of 11.7 cases of H. influenzae b meningitis and 31.1 cases of probable meningitis with no etiology were identified each year. After introduction, the number of cases were reduced by 79% and 44% respectively. The average H. influenzae b vaccine coverage after introduction was 69% among all children with clinically suspected meningitis. In contrast, the mean number of aseptic meningitis and pneumococcal meningitis cases remained stable throughout the pre and post vaccination period; 28.2 and 4.8 per year, respectively. CONCLUSIONS: H. influenzae b conjugate vaccine reduced the number of cases of H. influenzae b meningitis and probable meningitis within the first two years of its introduction. The impact against meningitis was higher than the vaccination rate, indicating indirect effects of the vaccine. India has recently scaled up the use of Hib conjugate vaccine throughout the country which should substantially reduce childhood meningitis rates further in the country.

A nationwide population-based surveillance of invasive Haemophilus influenzae diseases in children after the introduction of the Haemophilus influenzae type b vaccine in Japan.

BACKGROUND: Haemophilus influenzae type b (Hib) vaccine was introduced as a voluntary vaccine in December 2008 and was included in the national routine immunization program in April 2013 in Japan. Currently, no nationwide data are available to evaluate the effectiveness of Hib vaccine in Japan. METHODS: To evaluate the effectiveness of Hib vaccine in Japan, nationwide active population-based surveillance of culture-proven invasive infections caused by H. influenzae in children was performed in 2008-2017 in 10 prefectures in Japan (covering approximately 23% of the total Japanese population). Clinical data were recorded on a standardized case report form. Capsular type and antimicrobial susceptibility of the H. influenzae isolates were examined. The incidence rate ratio (IRR) and its confidence interval (CI) were calculated to compare data from 5 years before and that from after the introduction of the national routine Hib vaccine immunization program. RESULTS: During the 10-year study period, 566 invasive H. influenzae disease cases including 336 meningitis cases were identified. The average number of invasive H. influenzae disease cases among children <5 years of age during 2013-2017 decreased by 93% (IRR: 0.07, 95%CI 0.05-0.10, p < 0.001) compared with those occurring during 2008-2012. Hib strains have not been isolated from invasive H. influenzae disease cases since 2014; however, non-typeable H. influenzae and H. influenzae type f isolates have been noted as causes of invasive H. influenzae diseases among children <5 years in the post-Hib vaccine era. CONCLUSIONS: After the governmental subsidization of the Hib vaccine, invasive Hib disease cases decreased dramatically in the study population, as per our surveillance. Continuous surveillance is necessary to monitor the effectiveness of Hib vaccine and for detecting any emerging invasive capsular types.

Incidence and aetiology of bacterial meningitis among children aged 1-59 months in South Asia: systematic review and meta-analysis.

BACKGROUND: Bacterial meningitis is a significant cause of morbidity and mortality worldwide among children aged 1-59 months. We aimed to describe its burden in South Asia, focusing on vaccine-preventable aetiologies. METHODS: We searched five databases for studies published from January 1, 1990, to April 25, 2017. We estimated incidence and aetiology-specific proportions using random-effects meta-analysis. In secondary analyses, we described vaccine impact and pneumococcal meningitis serotypes. RESULTS: We included 48 articles cumulatively reporting 20,707 cases from 1987 to 2013. Mean annual incidence was 105 (95% confidence interval [CI], 53-173) cases per 100,000 children. On average, Haemophilus influenzae type b (Hib) accounted for 13% (95% CI, 8-19%) of cases, pneumococcus for 10% (95% CI, 6-15%), and meningococcus for 1% (95% CI, 0-2%). These meta-analyses had substantial between-study heterogeneity (I2 > 78%, P < 0.0001). Among studies reporting only confirmed cases, these three bacteria caused a median of 78% cases (IQR, 50-87%). Hib meningitis incidence declined by 72-83% at sentinel hospitals in Pakistan and Bangladesh, respectively, within two years of implementing nationwide vaccination. On average, PCV10 covered 49% (95% CI, 39-58%), PCV13 covered 51% (95% CI, 40-61%), and PPSV23 covered 74% (95% CI, 67-80%) of pneumococcal meningitis serotypes. Lower PCV10 and PCV13 serotype coverage in Bangladesh was associated with higher prevalence of serotype 2, compared to India and Pakistan. CONCLUSIONS: South Asia has relatively high incidence of bacterial meningitis among children aged 1-59 months, with vaccine-preventable bacteria causing a substantial proportion. These estimates are likely underestimates due to multiple epidemiological and microbiological factors. Further research on vaccine impact and distribution of pneumococcal serotypes will inform vaccine policymaking and implementation.

Cost-effectiveness of the Haemophilus influenzae type b vaccine for infants in mainland China.

OBJECTIVE: The aims of this study were to estimate the cost-effectiveness of the Haemophilus influenzae type b (Hib) vaccine for the prevention of childhood pneumonia, meningitis and other vaccine-preventable diseases in mainland China from a societal perspective and to provide information about the addition of the Hib vaccine to Chinese immunization programs. METHODS: A decision tree and the Markov model were used to estimate the costs and effectiveness of the Hib vaccine versus no Hib vaccine for a birth cohort of 100,000 children in 2016. The disease burden was estimated from the literature, statistical yearbooks and field surveys. Vaccine costs were calculated from government reports and the United Nations International Children's Emergency Fund (UNICEF) website. The WHO cost-effectiveness thresholds were used to evaluate the Hib vaccine intervention. A one-way sensitivity analysis and probabilistic sensitivity analysis were performed to evaluate the parameter uncertainties. RESULTS: Within the hypothetical cohort, under a vaccination coverage of 90%, the Hib vaccine could reduce 91.4% of Hib pneumonia and 88.3% of Hib meningitis; the Hib vaccine could also prevent 25 deaths, 24 meningitis sequelae cases and 9 hearing loss cases caused by Hib infection. From a societal perspective, the incremental cost-effectiveness ratio (ICER) of the Hib vaccine compared with no vaccination was US$ 13,640.1 at the market price, which was less than 3 times the GDP per capita of China in 2016. The ICER of the Hib vaccine was US$ -59,122.9 at the UNICEF price, indicating a cost savings. The largest portion of the uncertainty in the result was caused by the annual incidence of all-cause pneumonia, proportion of pneumonia caused by Hi, vaccine costs per dose, annual incidence of Hib meningitis and costs per episode of meningitis. The models were robust considering parameter uncertainties. CONCLUSION: The Hib vaccine is a cost-effective intervention among children in mainland China. The cost of Hib vaccine should be reduced, and it should be introduced into Chinese immunization programs.

Meningitis por Haemophilus influenzae b: ¿estamos ante una reemergencia? 24 años de experiencia en un hospital pediátrico / Haemophilus influenzae type B meningitis: Is there a re-emergence? 24 years of experience in a children's hospital

Introducción. Haemophilus influenzae b era la principal causa de meningitis bacteriana en menores de 5 años. Después de la introducción de la vacuna al calendario (1998), se observó un descenso significativo de la incidencia, pero, en los últimos años, hubo un aumento. Los objetivos de este estudio fueron describir las características y analizar la curva epidémica de los casos de meningitis por Haemophilus influenzae b (MHib) comparando los períodos pre- y posvacunación. Material y métodos. Estudio de series temporales. Se incluyeron todos los pacientes internados por MHib en el Hospital de Niños "R. Gutiérrez" (enero de 1992-mayo de 2016). Se compararon las tasas de hospitalización antes (prevacunación) y después (posvacunación) de la introducción de la vacuna. Se dividió la etapa posvacunación en tres períodos similares. Resultados. Fueron admitidos 85 pacientes con MHib (73,3% prevacunación). Las características clínicas y sociodemográficas de los casos en ambos períodos no mostraron diferencias. Prevacunación: 10,5 casos/año; y posvacunación: 0,7 casos/año. A partir de 2014, se observó un aumento. Tasa de letalidad: 4,8% (todos prevacunación). Datos posvacunación (n= 15): 40% del esquema primario completo, 40% del esquema atrasado para la edad. Reducción global de la tasa hospitalaria de MHib de 89,8% (IC 95%: -82,79-93,96%; p < 0,001) en el período posvacunación. Al analizar los diferentes períodos posvacunación, se observa una caída en la reducción a lo largo del tiempo. Conclusiones. Se observó una disminución muy importante de las hospitalizaciones por MHib pos introducción de la vacuna, pero, en los últimos años, se evidenció un aumento de estos casos sin modificaciones en las características de los pacientes.

Introduction. Haemophilus influenzae type B (Hib) used to be the main cause of bacterial meningitis in children younger than 5 years old. Following the introduction of the Hib vaccine in the immunization schedule (1998), its incidence reduced significantly but it has increased over the last years. The objectives of this study included describing the characteristics and analyzing the epidemic curve of Haemophilus influenzae type B (Hib) meningitis by comparing the pre- and postimmunization periods. Material and methods. Time-series study. All patients hospitalized with Hib meningitis at Hospital de Niños "R. Gutiérrez" (January 1992-May 2016). Hospitalization rates were compared before (pre-immunization) and after (post-immunization) the introduction of the Hib vaccine. The post-immunization period was divided into three similar periods. Results. Eighty-five patients with Hib meningitis were admitted (73.3% in the pre-immunization period). No differences were observed in relation to the clinical and sociodemographic characteristics of cases in both periods. Pre-immunization: 10.5 cases/year; postimmunization: 0.7 cases/year. As of 2014, the rate has increased. Lethality rate: 4.8% (all preimmunization). Post-immunization data (n= 15): 40% had completed their primary immunization schedule, 40% were delayed on the immunization schedule for their age. Overall reduction in the hospital rate of Hib meningitis by 89.8% (95% confidence interval: -82.79-93.96%, p < 0.001) in the post-immunization period. The analysis of the different post-immunization periods shows a decline in reduction over time. Conclusions. A very significant reduction in hospitalizations due to Hib meningitis was observed after the Hib vaccine was introduced; however, over the past years, the number of cases has increased although no changes have been observed in patient characteristics.

Haemophilus influenzae type B meningitis: Is there a re-emergence? 24 years of experience in a children's hospital. / Meningitis por Haemophilus influenzae b: ¿estamos ante una reemergencia? 24 años de experiencia en un hospital pediátrico.

INTRODUCTION: Haemophilus influenzae type B (Hib) used to be the main cause of bacterial meningitis in children younger than 5 years old. Following the introduction of the Hib vaccine in the immunization schedule (1998), its incidence reduced significantly but it has increased over the last years. The objectives of this study included describing the characteristics and analyzing the epidemic curve of Haemophilus influenzae type B (Hib) meningitis by comparing the pre- and postimmunization periods. MATERIALS AND METHODS: Time-series study. All patients hospitalized with Hib meningitis at Hospital de Niños "R. Gutiérrez" (January 1992-May 2016). Hospitalization rates were compared before (pre-immunization) and after (post-immunization) the introduction of the Hib vaccine. The post-immunization period was divided into three similar periods. RESULTS: Eighty-five patients with Hib meningitis were admitted (73.3% in the pre-immunization period). No differences were observed in relation to the clinical and sociodemographic characteristics of cases in both periods. Pre-immunization: 10.5 cases/year; postimmunization: 0.7 cases/year. As of 2014, the rate has increased. Lethality rate: 4.8% (all preimmunization). Post-immunization data (n= 15): 40% had completed their primary immunization schedule, 40% were delayed on the immunization schedule for their age. Overall reduction in the hospital rate of Hib meningitis by 89.8% (95% confidence interval: -82.79-93.96%, p < 0.001) in the post-immunization period. The analysis of the different post-immunization periods shows a decline in reduction over time. CONCLUSIONS: A very significant reduction in hospitalizations due to Hib meningitis was observed after the Hib vaccine was introduced; however, over the past years, the number of cases has increased although no changes have been observed in patient characteristics.

INTRODUCCIÓN: Haemophilus influenzae b era la principal causa de meningitis bacteriana en menores de 5 años. Después de la introducción de la vacuna al calendario (1998), se observó un descenso significativo de la incidencia, pero, en los últimos años, hubo un aumento. Los objetivos de este estudio fueron describir las características y analizar la curva epidémica de los casos de meningitis por Haemophilus influenzae b (MHib) comparando los períodos pre- y posvacunación. MATERIAL Y MÉTODOS: Estudio de series temporales. Se incluyeron todos los pacientes internados por MHib en el Hospital de Niños "R. Gutiérrez" (enero de 1992-mayo de 2016). Se compararon las tasas de hospitalización antes (prevacunación) y después (posvacunación) de la introducción de la vacuna. Se dividió la etapa posvacunación en tres períodos similares. RESULTADOS: Fueron admitidos 85 pacientes con MHib (73,3% prevacunación). Las características clínicas y sociodemográficas de los casos en ambos períodos no mostraron diferencias. Prevacunación: 10,5 casos/año; y posvacunación: 0,7 casos/año. A partir de 2014, se observó un aumento. Tasa de letalidad: 4,8% (todos prevacunación). Datos posvacunación (n= 15): 40% del esquema primario completo, 40% del esquema atrasado para la edad. Reducción global de la tasa hospitalaria de MHib de 89,8% (IC 95%: -82,79-93,96%; p < 0,001) en el período posvacunación. Al analizar los diferentes períodos posvacunación, se observa una caída en la reducción a lo largo del tiempo. CONCLUSIONES: Se observó una disminución muy importante de las hospitalizaciones por MHib pos introducción de la vacuna, pero, en los últimos años, se evidenció un aumento de estos casos sin modificaciones en las características de los pacientes.

Epidemiology of paediatric meningitis in central Côte d'Ivoire after the implementation of Haemophilus influenzae type b vaccination.

Infectious meningitis accounts for enormous morbidity worldwide, but there is a paucity of data on its regional epidemiology in resource-constrained settings of sub-Saharan Africa. Here, we present a study on the aetiology of paediatric meningitis in central Côte d'Ivoire. Between June 2012 and December 2013, all cerebrospinal fluid (CSF) samples drawn at the University Teaching Hospital Bouaké were examined for the presence of bacterial and fungal pathogens. A causative agent was detected in 31 out of 833 CSF specimens (3.7%), with the most prevalent pathogens being Streptococcus pneumoniae (n=15) and Neisseria meningitidis (n=5). With the exception of neonates, these two bacteria were the most common agents in all age groups. Of note, only a single case of Haemophilus influenzae meningitis was detected. Hence, this study reports a considerable shift in the epidemiology of paediatric meningitis in central Côte d'Ivoire. Following the implementation of a nation-wide childhood vaccination programme against H. influenzae type b, this pathogen was much less frequently reported than in previous studies. The integration of specific vaccines against S. pneumoniae and N. meningitidis into the childhood vaccination programme in Côted'Ivoire holds promise to further reduce the burden due to infectious meningitis.

Risk factors for community-acquired bacterial meningitis.

BACKGROUND: Bacterial meningitis is a significant burden of disease and mortality in all age groups worldwide despite the development of effective conjugated vaccines. The pathogenesis of bacterial meningitis is based on complex and incompletely understood host-pathogen interactions. Some of these are pathogen-specific, while some are shared between different bacteria. METHODS: We searched the database PubMed to identify host risk factors for bacterial meningitis caused by the pathogens Streptococcus pneumoniae, Neisseria meningitidis and Haemophilus influenzae type b, because they are three most common causative bacteria beyond the neonatal period. RESULTS: We describe a number of risk factors; including socioeconomic factors, age, genetic variation of the host and underlying medical conditions associated with increased susceptibility to invasive bacterial infections in both children and adults. CONCLUSIONS: As conjugated vaccines are available for these infections, it is of utmost importance to identify high risk patients to be able to prevent invasive disease.

Haemophilus influenzae type b meningitis in a vaccinated and immunocompetent child.

Invasive Haemophilus influenzae type b (Hib) disease decreased dramatically after the introduction of conjugate vaccine in routine immunization schedules. We report a case of a fifteen-months-old girl, previously healthy and vaccinated, admitted in the emergency room with fever and vomiting. She was irritable and the Brudzinski's sign was positive. The cerebrospinal fluid (CSF) analysis showed pleocytosis and high protein level. Empiric intravenous antibiotics (ceftriaxone and vancomycin) were administered for suspected bacterial meningitis during 10 days. Serotyping of the Haemophilus influenzae strain found in CSF revealed a serotype b. After one year of follow-up no Hib meningitis sequelae were noted. Despite vaccination compliance and absence of risk factors, invasive Hib disease can occur due to vaccine failure. Efforts to keep the low incidence of invasive Hib disease should be directed to the maintenance of high vaccination coverage rates, combined with the notification and surveillance strategies already implemented in each country.

Hib Vaccines: Past, Present, and Future Perspectives.

Haemophilus influenzae type b (Hib) causes many severe diseases, including epiglottitis, pneumonia, sepsis, and meningitis. In developed countries, the annual incidence of meningitis caused by bacteria is approximately 5-10 cases per population of 100,000. The Hib conjugate vaccine is considered protective and safe. Adjuvants, molecules that can enhance and/or regulate the fundamental immunogenicity of an antigen, comprise a wide range of diverse compounds. While earlier developments of adjuvants created effective products, there is still a need to create new generations, rationally designed based on recent discoveries in immunology, mainly in innate immunity. Many factors may play a role in the immunogenicity of Hib conjugate vaccines, such as the polysaccharides and proteins carrier used in vaccine construction, as well as the method of conjugation. A Hib conjugate vaccine has been constructed via chemical synthesis of a Hib saccharide antigen. Two models of carbohydrate-protein conjugate have been established, the single ended model (terminal amination-single method) and cross-linked lattice matrix (dual amination method). Increased knowledge in the fields of immunology, molecular biology, glycobiology, glycoimmunology, and the biology of infectious microorganisms has led to a dramatic increase in vaccine efficacy.

Glycoconjugate vaccines: an update.

INTRODUCTION: Globally, the three main pathogens causing serious infections are Haemophilus influenzae type b, Streptococcus pneumoniae and Neisseria meningitidis. Over the last 5 years, new vaccines protecting against these bacteria have been developed and introduced in various countries. AREAS COVERED: This review describes the recently licensed glycoconjugates being used to protect against these encapsulated bacteria. Immunogenicity and safety data that led to licensure or licensure expansion of these glycoconjugates are discussed in addition to the resultant impact on the disease burden. EXPERT OPINION: The maintenance of robust immunisation programmes with high uptake rates is important in maintaining low rates of disease. Epidemiological surveillance systems are essential in monitoring any changes in infectious disease trends and in identifying emerging infections such as from non-typeable H. influenzae, pneumococcal serotype replacement disease and changes in the epidemiology of meningococcal serogroups. This is important to guide future vaccine development. Accessibility of these glycoconjugate vaccines in resource poor regions, which bear the highest disease burden from these pathogens, remains challenging largely due to high vaccine pricing. Recent aids from public and private funding, tiered vaccine pricing and the transfer of vaccine technology have helped in introducing these vaccines where they are most needed.