Increased Risk of Long-Term Disabilities Following Childhood Bacterial Meningitis in Sweden.

Importance: Few studies have examined the incidence of long-term disabilities due to bacterial meningitis in childhood with extended follow-up time and a nationwide cohort. Objective: To describe the long-term risks of disabilities following a childhood diagnosis of bacterial meningitis in Sweden. Design, Setting, and Participants: This nationwide retrospective registry-based cohort study included individuals diagnosed with bacterial meningitis (younger than 18 years) and general population controls matched (1:9) by age, sex, and place of residence. Data were retrieved from the Swedish National Patient Register from January 1, 1987, to December 31, 2021. Data were analyzed from July 13, 2022, to November 30, 2023. Exposure: A diagnosis of bacterial meningitis in childhood recorded in the National Patient Register between 1987 and 2021. Main Outcomes and Measures: Cumulative incidence of 7 disabilities (cognitive disabilities, seizures, hearing loss, motor function disorders, visual disturbances, behavioral and emotional disorders, and intracranial structural injuries) after bacterial meningitis in childhood. Results: The cohort included 3623 individuals diagnosed with bacterial meningitis during childhood and 32 607 controls from the general population (median age at diagnosis, 1.5 [IQR, 0.4-6.2] years; 44.2% female and 55.8% male, median follow-up time, 23.7 [IQR, 12.2-30.4] years). Individuals diagnosed with bacterial meningitis had higher cumulative incidence of all 7 disabilities, and 1052 (29.0%) had at least 1 disability. The highest absolute risk of disabilities was found for behavioral and emotional disorders, hearing loss, and visual disturbances. The estimated adjusted hazard ratios (HRs) showed a significant increased relative risk for cases compared with controls for all 7 disabilities, with the largest adjusted HRs for intracranial structural injuries (26.04 [95% CI, 15.50-43.74]), hearing loss (7.90 [95% CI, 6.68-9.33]), and motor function disorders (4.65 [95% CI, 3.72-5.80]). The adjusted HRs for cognitive disabilities, seizures, hearing loss, and motor function disorders were significantly higher for Streptococcus pneumoniae infection (eg, 7.89 [95% CI, 5.18-12.02] for seizure) compared with Haemophilus influenzae infection (2.46 [95% CI, 1.63-3.70]) or Neisseria meningitidis infection (1.38 [95% CI, 0.65-2.93]). The adjusted HRs for cognitive disabilities, seizures, behavioral and emotional disorders, and intracranial structural injuries were significantly higher for children diagnosed with bacterial meningitis at an age below the median. Conclusions and Relevance: The findings of this cohort study of individuals diagnosed with bacterial meningitis during childhood suggest that exposed individuals may have had an increased risk for long-term disabilities (particularly when diagnosed with pneumococcal meningitis or when diagnosed at a young age), highlighting the need to detect disabilities among surviving children.

Postmeningitic pediatric hearing loss from non-type b Haemophilus influenzae.

BACKGROUND: Postmeningitic hearing loss from Haemophilus influenzae (H. influenzae) is increasingly due to encapsulated serotypes other than type b (Hib) and nontypeable strains (collectively, nHiB H. influenzae). Pediatric hearing loss after nHib H. influenzae meningitis remains poorly described. METHODS: Retrospecive case series of nHiB H. influenzae meningitis cases identified from a microbiologic database at Children's Hospital Colorado from 2000 to 2020. Literature regarding nHiB H. influenzae and H. influenzae postmeningitic hearing loss was also reviewed. RESULTS: Eleven cases of nHib H. influenzae meningitis (median age 15.9 months) were identified due to serotype f (36 %), serotype a (27 %), and nontypable strains (36 %). Seven (64 %) patients were male, 55 % were white and 18 % were Hispanic or Latino. Hearing loss was initially identified in 4 children (40 %), with two patients with moderate conductive hearing loss (CHL) and one child with unilateral moderate sensorineural (SNHL) hearing loss patients recovering normal hearing. One patient with bilateral profound sensorineural hearing loss and associated labyrinthitis ossificans required cochlear implantation. All children (4) with identified hearing loss were noted to have additional intracranial sequelae, which included empyema (2), sinus thrombosis (2), and seizures (2). Of patients receiving steroids, 25 % had hearing loss on initial testing, compared to 66 % of those who did not receive steroids. CONCLUSIONS: nHib H. influenzae can cause both transient and permanent postmeningitic hearing loss. Steroids may offer otoprotection in nHib H. influenzae meningitis similar to Hib meningitis. Given the limited literature, further study is needed to better characterize hearing outcomes after nHib H. influenzae meningitis.

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.

Community-acquired Haemophilus influenzae meningitis in adults.

BACKGROUND: Haemophilus influenzae is an uncommon cause of meningitis in adults. METHODS: We analyzed episodes of community-acquired H. influenzae meningitis in adults included in a prospective nationwide cohort study in the Netherlands. RESULTS: From 2006 to July 2018, 82 of 2272 (4%) bacterial meningitis episodes were caused by H. influenzae (mean annual incidence 0.5 patients per 1,000,000). Median age was 61 years (IQR 46-68), and 48 episodes (59%) occurred in woman. Predisposing factors were otitis and/or sinusitis in 33 of 76 patients (49%), immunocompromising conditions in 19 of 75 patients (25%) and cerebrospinal fluid leak in 13 of 79 patients (17%). Serotyping showed 63 of 80 isolates (79%) were non-typeable (NTHi). Three patients (4%) died and 14 patients (17%) had an unfavorable outcome (Glasgow Outcome Scale score < 5 at discharge). Pneumonia (odds ratio [OR] 5.8, 95% confidence interval [95%CI] 1.1-30.8), presence of immunocompromising conditions (OR 6.0, 95%CI 1.5-24.4), and seizures on admission (OR 10.7, 95%CI 1.6-72.8) were associated with an unfavorable outcome, while NTHi was associated with a favorable outcome (OR 5.6, 95%CI 1.6-19.5). CONCLUSION: H. influenzae is an uncommon cause of adult bacterial meningitis patients mainly causing disease in those with predisposing factors, such as CSF leakage, ENT infections, and immunocompromised state. In adult patients the majority of H. influenzae meningitis is caused by non-typeable strains.

Epidemiology and antibiotic resistance profile of bacterial meningitis in Morocco from 2015 to 2018.

Over a 4-year study period from 2015 to 2018, altogether 183 isolates of bacterial meningitis were collected from 12 hospitals covering the entire Moroccan territory. Neisseria meningitidis represented 58.5%, Streptococcus pneumoniae 35.5%, and Haemophilus influenzae type b 6%. H. influenzae type b mainly affected 5-year-olds and unvaccinated adults. N. meningitidis serogroup B represented 90.7% followed by serogroup W135 with 6.5%. Decreased susceptibility to penicillin G (DSPG) for all isolates accounted for 15.7%, with 11.6% being resistant to penicillin G (PG) and 4.1% decreased susceptibility. Cumulative results of all strains showed 2.7% decreased susceptibility to amoxicillin and 3.3% resistant, 2.2% of isolates were resistant to third-generation cephalosporin and 2.2% were decreased susceptible, 5.5% were resistant to chloramphenicol and 2.7% were resistant to rifampin. The frequency of DSPG observed in our study is more common in S. pneumoniae than in N. meningitidis (P < 0.05). These isolates have been found to be highly susceptible to antibiotics used for treatment and prophylaxis chemotherapy and the observed resistance remains rare. The impact of introduction of conjugate vaccines against H. influenzae type b and S. pneumoniae (PCVs) is an advantage in reducing meningitis cases due to these two species.

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.

Meningitis trends in Niger 2008-2015: a secondary data analysis.

INTRODUCTION: Niger, located in the meningitis belt, faces recurrent epidemics of magnitudes that vary with the year. The objective of this study was to describe the trends in meningitis and identify the profile of the microbes implicated in meningitis epidemics in Niger. METHODS: We conducted a descriptive study (a secondary analysis) of meningitis data from 2008 through 2015. The study population comprised patients with suspected and confirmed meningitis. We conducted an exhaustive sampling of all suspected and confirmed meningitis cases reported in Niger from 2008 to 2015. RESULTS: A total of 6167 (40.6 %) confirmed cases of meningitis were identified. Among them, 5,507 (89.3 %) were attributable to Neisseria meningitidis, 593 (9.6 %) to Streptococcus pneumoniae, and 66 (1.1 %) to Haemophilus influenzae respectively. Among the Neisseria meningitidis cases, 2,984 (54.2 %) were caused by serogroup A, 1,333 (24.2 %) by serogroup W, 1,165 (21.1 %) by serogroup C, 23 (0.4 %) by serogroup X, and 2 (0.03 %) by the serogroup B. CONCLUSION: This study enabled us to describe meningitis trends and identify the profile of the bacteria implicated in its epidemics in Niger. We observed the emergence of Neisseria meningitidis C and recommend vaccination against this serogroup.

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.

Causes of Pediatric Meningitis in Botswana: Results From a 16-Year National Meningitis Audit.

BACKGROUND: Central nervous system infections are an important cause of childhood morbidity and mortality in high HIV-prevalence settings of Africa. We evaluated the epidemiology of pediatric meningitis in Botswana during the rollout of antiretroviral therapy, pneumococcal conjugate vaccine and Haemophilus influenzae type B (HiB) vaccine. METHODS: We performed a cross-sectional study of children (<15 years old) evaluated for meningitis by cerebrospinal fluid (CSF) examination from 2000 to 2015, with complete national records for 2013-2014. Clinical and laboratory characteristics of microbiologically confirmed and culture-negative meningitis were described and incidence of Streptococcus pneumoniae, H. influenzae and cryptococcal meningitis was estimated for 2013-2014. RESULTS: A total of 6796 unique cases were identified. Median age was 1 year [interquartile range 0-3]; 10.4% (435/4186) of children with available HIV-related records were known HIV-infected. Overall, 30.4% (2067/6796) had abnormal CSF findings (positive microbiologic testing or CSF pleocytosis). Ten percent (651/6796) had a confirmed microbiologic diagnosis; including 26.9% (175/651) Cryptococcus, 18.9% (123/651) S. pneumoniae, 20.3% (132/651) H. influenzae and 1.1% (7/651) Mycobacterium tuberculosis. During 2013-2014, national cryptococcal meningitis incidence was 1.3 cases per 100,000 person-years (95% confidence interval, 0.8-2.1) and pneumococcal meningitis incidence 0.7 per 100,000 person-years (95% confidence interval, 0.3-1.3), with no HiB meningitis diagnosed. CONCLUSIONS: Following HiB vaccination, a marked decline in microbiologically confirmed cases of H. influenzae meningitis occurred. Cryptococcal meningitis remains the most common confirmed etiology, demonstrating gaps in prevention-of-mother-to-child transmission and early HIV diagnosis. The high proportion of abnormal CSF samples with no microbiologic diagnosis highlights limitation in available diagnostics.

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.

[Acute meningitis and encephalitis syndrome surveillance disease burden in four China prefectures].

Objectives: To explore acute meningitis and encephalitis syndrome (AMES) surveillance in 4 China prefectures, to understand the epidemiological features and disease burden of neisseria meningitides (Nm) meningitis, streptococcus pneumoniae (Sp) meningitis, haemophilus influenza type b (Hib) meningitis and Japanese encephalitis and provide evidence for related disease prevention and control. Methods: AMES surveillance were conducted in Jinan, Shandong Province and Yichang, Hubei Province in September 2006, and in 13 districts of Shijiazhuang, Hebei Province and Guigang City, Guangxi Zhuang Autonomous Region in April 2007. Six hospitals in each city were selected as monitoring pilot hospitals to carry out reports of suspected cases of acute meningitis and encephalitis, case investigation, blood specimens and cerebrospinal fluid specimen collection, anti-JEV IgM antibody enzyme-linked immunosorbent assay, Nm, Sp and Hib culture and polymerase chain reaction detection, etc. According to the age group, the incidence of bacterial meningitis and Japanese encephalitis in local residents <20 years old was estimated. Results: From 2006 to 2013, a total of 19 423 surveillance cases were reported in four cities, of which 11 071 (56.99%) were reported in the pilot hospitals. Of the 11 071 cases, 5 315 were tested for bacteriology and 9 180 were tested for anti-JEV IgM antibodies. Among the bacteriological tests, 176 cases were positive, including 75 cases of Nm positive, 91 cases of Sp positive and 10 cases of Hib positive. The incidence of three bacterial meningitis is estimated for people under 20 years old, with estimated incidence of Nm, Sp and Hib meningitis in children <5 years old was 0.46/100 000-0.71/100 000, 0.34/100 000-0.83/100 000 and 0.32/100 000-0.57/100 000 respectively; the estimated incidence of Nm and Sp meningitis in children aged 5-9 years was 0.59/100 000-1.14/100 000 and 0.50/100 000-1.66/100 000 respectively. In 732 cases of positive JE cases, the positive detection rates of <5 years old, 40-49 years old and ≥50 years old were 9.51% (95/999), 28.09% (66/235) and 33.85% (130/384), respectively. The estimated annual incidence rate of JE was 0.12/100 000-0.79/100 000.ratio of cases 1.19∶1. Most of cases (27.30%) were children and adolescents aged 5-14 years and those (26.84%) aged over 45 year. Conclusion: The study found that primary and secondary school students are the key population of Nm meningitis, suggesting that it is necessary to explore the enhanced immunization study of meningococcal vaccine in this population; Sp has the possibility of occurrence in all age groups; <5 years old children are the main population of Hib meningitis.

Vaccine preventable invasive bacterial diseases in Italy: A comparison between the national surveillance system and recorded hospitalizations, 2007-2016.

BACKGROUND: Vaccine-preventable invasive bacterial diseases (IBDs) caused by Neisseria meningitidis (Nm), Streptococcus pneumoniae (Sp), and Haemophilus influenzae (Hi) have been notified in Italy since 2007 without assessing reporting completeness. METHODS: Our study compared the number of cases of IBDs identified from the Italian Hospital Discharge Records (HDRs), using specific diagnostic ICD-9-CM codes, with those notified to the National Surveillance System (NSS) from 2007 to 2016. A multinomial logistic regression model was used to impute the aetiology of all discharges with a diagnosis of unspecified bacterial meningitis. RESULTS: Over a 10-year period, 14,243 hospital discharges with diagnosis of IBD were estimated in Italy (12,671 with specified aetiology and 1,572 with imputed aetiology). Among those, 2,513 (17.6%) were caused by Nm, 10,441 (73.3%) by Sp, and 1289 (9.1%) by Hi. Most invasive meningococcal diseases were coded as meningitis (72.3%), while Hi and Sp were more frequently coded as septicaemia (51.6% and 60.4%, respectively). The highest mean annual incidence rate was found for IBD caused by Sp (1.74 per 100,000), followed by Nm (0.42 per 100,000) and by Hi (0.21 per 100,000). Comparing NSS with HDR data, we found an initially high underreporting of all IBDs, and particularly for Hi. Data from the two systems overlapped in more recent years, due to an improved reporting completeness. The increasing IBD incidence observed in NSS data was not confirmed by HDR data trends, although with pathogen-related differences with Hi cases rising in both data sources, suggesting that is mainly due to an improved disease notification rather than to a true incidence increase. CONCLUSIONS: Comparing surveillance data with other data sources is useful to better interpret observed trends of notifiable diseases.

Bacterial meningitis in Niger: an analysis of national surveillance data, 2003-2015.

INTRODUCTION: Bacterial meningitis (BM) is one of the most severe infectious disease in Niger republic. To best describe the trends of BM disease, meningitis surveillance data from the Centre de Recherche Medicale et Sanitaire (CERMES) and the Direction of Surveillance and Response to Epidemics (DSRE) were reviewed and analyzed. METHODS: Data on number of notified cases of BM and on pathogens were analyzed during 2003-2015. Excel 2013 was used for trend analysis on the etiology of BM prevalence and incidence. RESULTS: A total of 10051 cerebrospinal fluid (CSF) samples collected were confirmed by laboratory methods. The main etiologies of meningitis detected were N. meningitidis (82.1%), S. pneumonia (12.1%) and H. influenza (3.4%). N. meningitidis mostly affected children in the age groups of 5-9 years (32.9%) and 10-14 years (24.9%) with respective mean incidence of 14.9 and 11.3. The percentage estimate of N. meningitidis serogroup A (NmA) meningitis fell to 0% in 2015 while during the same year that of N. meningitidis serogroup C (NmC) and N. meningitidis serogroup W (NmW) reached 82.9% and 17% respectively. CONCLUSION: Overall, the epidemiological trends of the BM in Niger were dynamic. The emergence of NmC strains suggests that there may be an urgent need for serogroup C containing vaccines in Niger in the coming years.

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.

Invasive Haemophilus influenzae Serotype a Infection in Children: Clinical Description of an Emerging Pathogen-Alaska, 2002-2014.

BACKGROUND: Invasive infections from Haemophilus influenzae serotype a (Hia) have been reported with increasing frequency, especially among indigenous populations. However, there are limited population-based studies of clinical severity. We studied invasive Hia infections in Alaska to determine clinical characteristics, mortality and sequelae. METHODS: We defined an invasive Hia infection as the first detection of Hia from a usually sterile site in a child <10 years of age from Alaska. We identified cases using the Alaska Invasive Bacterial Diseases Surveillance System and reviewed medical charts up to 2 years after reported illness. RESULTS: We identified invasive Hia infections in 36 children, 28 (78%) <1 year old, 34 (94%) living in an Alaskan village and 25 (69%) without documented underlying illness. Overlapping clinical presentations included meningitis in 15 children (42%); bacteremia and pneumonia in 10 children (28%); and bone, joint or soft tissue infections in 10 children (22%). In 4 other children, no source of invasive infection was identified. Intensive care was provided for 11 children (31%); 12 children (33%) required surgical intervention. One year after infection, 4 children (11%) had died from Hia, and 5 children (14%) had ongoing neurologic sequelae. CONCLUSIONS: Invasive Hia infections in Alaska occurred predominantly in Alaska Native infants in rural communities. Although one-third of children had preexisting conditions, most cases occurred without known comorbidity. Clinical syndromes were frequently severe. One year after infection, 1 in 4 children had either died or had neurologic sequelae. An effective vaccine would prevent significant morbidity and mortality in affected populations.

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.

Impact of Haemophilus influenzae type b conjugate vaccination on hospitalization for invasive disease in children fifteen years after its introduction in Italy.

In Italy, Hib conjugate vaccine was introduced for infants in 1999 and included in the DTaP-HBV-IPV-Hib combination in 2001, with an uptake of 83.4% in 2002, >90% by 2005, and >95% by 2011. We estimated the impact of Hib vaccination on hospitalizations for H. influenzae invasive disease in children <5years. Age-specific hospitalization rates and hospitalization risk ratios (HRRs) with 95%CI during 2001-2013 were calculated performing time-series analysis. The number of cases reported to the national surveillance of invasive bacterial diseases was compared to the number of hospitalizations between 2007-2013. Hospitalization rates declined from 2.3 in 2001 to 0.9×100,000 in 2002 (HRR=0.4, 95%CI=0.3-0.6, p<0.05) among children 1-4years and from 5.4 in 2001 to 2.4×100,000 in 2005 (HRR=0.4, 95%CI=0.2-0.9, p<0.05) among infants. During 2007-2013: 401 cases were reported, 242 were typed, 12.4% were by serotype b; 861 hospital admissions were recorded. Applying the percentage of typed b strains retrieved from the surveillance to the number of hospitalizations for invasive H. influenzae disease, an estimated 107 episodes could be attributable to serotype b. These findings provided reassuring data on the impact of Hib vaccination on the burden of hospitalization for invasive disease in Italian children.

Haemophilus influenzae Type a Meningitis in Immunocompetent Child, Oman, 2015.

Meningitis caused by Haemophilus influenzae type b (Hib) was eliminated in Oman after the introduction of Hib vaccine in 2001. However, a case of H. influenzae type a meningitis was diagnosed in a child from Oman in 2015, which highlights the need to monitor the incidence of invasive non-Hib H. influenzae disease.