Hib Meningitis Research Articles

PREVALENCE AND RISK FACTORS OF HEMOPHILUS INFLUENZA TYPE B MENINGITIS: ROLE OF VACCINATION AND SOCIAL DEMOGRAPHY IN THE PATHOGENESIS

Bacterial meningitis is a condition caused by a bacterial infection in the meninges that results in inflammation. The causative agent varies according to age and other related factors. Hemophilus Influenza type B (Hib) is the most common cause of meningitis in children. This study aimed to determine the prevalence of H. influenza meningitis, the role of vaccination, and demographic factors in the etiology of Hib meningitis. Using a cross-sectional design, the study was conducted at the Pediatrics department of Ayub Teaching Hospital, Abbottabad, for six months, from 19-9-2023 to 19-3-2024. After obtaining ethical approval from the IRB of Ayub Teaching Hospital Abbottabad, a cross-sectional study was conducted, and 143 patients who met the inclusion criteria were included in the study. Hib vaccination status was confirmed by history and the presence of a vaccination card. Cerebrospinal fluid (CSF) was collected and sent for analysis, including microscopy and culture. The mean age of the patients was 44.92±51.48 months, with a male-to-female ratio of 1.38:1. Seventy (49.65%) patients were fully vaccinated against the Hib virus. The study results showed that H. influenza growth on CSF culture was noted in 14 (9.79%) patients. The Hib positive status of these cases was significantly associated with gender, residential area, and socioeconomic class of the patient at p values of 0.005, 0.047, and 0.041. In conclusion, despite the use of conjugate vaccine, Hib remains a cause of meningitis, and the pathogenesis of Hib meningitis is associated with gender, residential category, and socioeconomic class of the patient.

Postmeningitic pediatric hearing loss from non-type b Haemophilus influenzae

BackgroundPostmeningitic 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. MethodsRetrospecive 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. ResultsEleven 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. ConclusionsnHib 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.

HAEMOPHILUSINFLUENZAE TYPE B MENINGITIS REVEALING HYPOGAMMAGLOBULINEMIA IN A VACCINATED CHILD

Haemophilusinfluenzae type b (Hib) meningitis is a major therapeutic emergency, and its incidence has been significantly reduced by vaccination.We report the case of a 4-year-old girl vaccinated against Hib, hospitalized for Haemophilus influenza type b meningitis revealed by a febrile meningeal syndrome and having revealed a hypogammaglobulinemia. The child was treated with antibiotic therapy associated with corticosteroid therapy and immunoglobulin substitution with a good evolution. Through this observation we conclude that the assessment of the immune deficiency must be systematically proposed in front of a neuromeningeal infection with Hib.

Haemophilus influenzae meningitis: A rare etiology of bacterial meningitis in adults! A case report

Invasive Haemophilus influenzae infections can occur as a sepsis, an invasive pneumonia, an epiglottitis and an acute bacterial meningitis. H. influenzae meningitis accounts for about 4% of community-acquired bacterial meningitis in adults. We report a case of Haemophilus influenzae serotype b (Hib) meningitis in a 37-year-old patient having an osteomeningeal breach as a predisposing factor. The diagnosis was established by lumbar puncture. The course was satisfactory with antibiotic treatment. The systematic search for an osteomeningeal breach as well as other risk factors is crucial in any adult patient presenting with an episode of confirmed H. influenzae meningitis. The quick performance of bacteriological samples is primordial in order to obtain an early diagnosis and to ensure a good clinical outcome.

Clinical-epidemiological characteristics of acute bacterial meningitis in children of Khmelnitskyi region (Podilsky region, Ukraine): fifteen-year-long

Acute bacterial meningitis (ABM) leads to a significant number of complications and high mortality. The aim - to analyze the etiological structure, epidemiological, socio-demographic features and complications in ABM in children of Khmelnitskyi region during 2004-2018. Materials and methods. The analysis of 346 cases of ABM, of which 217 boys and 129 girls was conducted. The etiology of meningitis was determined by bacterioscopy, bacteriological sowing, latex agglutination and polymerase chain reaction. Complications were revealed based on the clinical picture and computed tomography and мagnetic resonance imaging. The processing of the results was carried out using analytical method, t-criterion and constructing 95% confidence interval. Results. The disease started with fever 346 (100%), neck stiffness 289 (83.5%) and vomiting 273 (78.9%), less common, alteration of consciousness 28 (8.1%) and seizures 9 (2.6%). The high level of the cytosis were observed in meningococcal (5801.3±4856.7 cells/mm3) and Hib meningitis (5152.6±4153.1 cells/mm3), the lowest level was in pneumococcal meningitis (2601.0±1839.6 cells/mm3). The highest level of liquor protein was in pneumococcal meningitis (179.0±51.0 mg/dl), and the lowest level was in meningococcal meningitis (102.0±49.0 mg/dl) and Hib meningitis (112.0±56.0 mg/dl). The etiological factor was established in 121 (35.0%) of patients. 52 (15.4%) of patients had neurological complications. Conclusions. The majority (58.1%) of ABM are in children under the age of 3. The main causative agent remains N. meningitidis - 57.9%, the second place is S. pneumoniae - 21.5%, the third Hib - 9.9% of cases. Frequent complications were brain edema 32 (61.5%), seizures 19 (36.5%) and hydrocephalus 8 (15.4%). The study was conducted in accordance with the principles of the Declaration of Helsinki. The research protocol was approved by the Local Ethics Committee of the institution mentioned in the work. Informed consent of the children’s parents was obtained for the research. No conflict of interests was declared by the authors.

Clinical and laboratory characteristics of haemophilus influenza type b Infection with central nervous system Involvement in young children

Introduction. Invasive Haemophilus influenza type b (Hib) infection often manifests as severe and complicated forms of purulent meningitis in children from birth to 6 years of age. Hib meningitis is the most commonly diagnosed invasive form, with a severe course. There is no generally accepted clinical classification of Hib infection. Along with meningitis, the infection is often manifested with purulent inflammatory foci of different localization.The objective was to characterize the course of purulent Hib meningitis, including in combination with purulent foci, in young children.Methods and materials. We analyzed 45 case histories of children (under the age of 3 years) who had an invasive Haemophilus infection with purulent meningitis. Hib meningitis (Group-1) was diagnosed in 17 patients and meningitis in combination with specific purulent foci was diagnosed in 28 patients (Group-2). The diagnosis in all patients was confirmed bacteriologically or serologically (Latex Agglutination Test).Results. The combination of meningitis with purulent foci of Hib infection was characterized by late hospitalization (36 %), longer recovery of cerebrospinal fluid, longer duration of the disease, and the prevalence of severe and complicated disease, and often required surgical treatment (46.4 %). A burdened premorbid background is traditionally considered a condition for the development of invasive Hib infection. According to our data, only 40 % of children had a burdened premorbid background, which is confirmed by clinical cases.Conclusion. Since Hib infection in young children is often combined with meningitis with purulent foci, is characterized by a severe and complicated course, and often requires surgical treatment, it is advisable to consider this form of infection separately.

Global Epidemiology of Vaccine-preventable Bacterial Meningitis.

Global Epidemiology of Vaccine-preventable Bacterial Meningitis.

Impact of a Single-Tube PCR Assay for the Detection of Haemophilus influenzae Serotypes a, c, d, e and f on the Epidemiological Surveillance in Greece.

Background: The decrease in the rate of meningitis due to Haemophilus influenzae type b after vaccine introduction and a possible change in epidemiology of H. influenzae disease highlights the need for continuous serotype surveillance. Methods: A single-tube multiplex PCR assay for serotyping of H. influenzae was developed and deployed. Results: During 2003–2020, 108 meningitis cases due to H. influenzae were notified; 86 (80%) were confirmed and serotyped by molecular methods. The overall specificity and sensitivity of the assay were estimated (100% PPV and NPV respectively). The overall mean annual reported incidence for H. influenzae was 0.02, while for Hib and non-b meningitis equaled 0.02 and 0.03 per 100 000, respectively. Analysis by age group revealed that H. influenzae peaks in toddlers and children 0–4 years and in adults >45 years old. Among the serotyped cases, 39.8% were identified as Hib, 46.3% as NTHi, and 0.9% and 2.8% as serotypes a (Hia) and f (Hif)) respectively. Conclusions: Low incidence due to Hib was observed while non-typeable H. influenzae (NTHi) and serotypes Hia and Hif seem to emerge. The application of the current assay discloses the ongoing change of invasive H. influenzae disease trends during the Hib post-vaccine era.

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

BackgroundHaemophilus 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.MethodsEpidemiological 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.Results33 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.ConclusionsGlobal 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.

Profound Sensorineural Hearing Loss Following Adjuvant Steroid Delay in Pediatric Bacterial Meningitis

Streptococcus pneumonia is a gram positive, polysaccharide-encapsulated diplococcus associated with various pulmonary and extra-pulmonary clinical presentations including invasive diseases such as acute meningitis. It can be associated with high rates of morbidity and mortality in both the pediatric and the adult populations. The introduction of the pneumococcal conjugate vaccine which expanded to cover 13 strains allowed remarkable protection against these invasive infections. In addition, the use of adjuvant corticosteroid therapy in the last few years; in particular dexamethasone, for the management of acute bacterial meningitis reduced the incidence of severe hearing loss in both Hib and other bacterial meningitis. The IDS guidelines recommend administering the first dose of steroids just before or with the start of antibiotics due to its decreased effectiveness with the late presentations of meningitis. We present the case of a 14-year-old female adolescent refugee, with incomplete vaccination status prior to relocating to Lebanon presenting with pneumococcal meningitis. Her hospitalization was complicated by bilateral profound sensorineural hearing loss (SNHL) following a delay in steroid administration. The aim of this article is to highlight the role of vaccines in decreasing morbidity of vaccine-preventable illnesses, and the importance of early administration of steroids as adjuvant to therapy for prevention of neurologic sequeleae.

M174 HAEMOPHILUS INFLUENZAE TYPE B MENINGITIS – A CASE OF VACCINE FAILURE

Haemophilus influenzae is a pleomorphic gram-negative bacteria commonly found within the respiratory tract. Haemophilus influenzae serotype b (Hib) is a typeable (encapsulated) strain known to cause invasive disease. Hib polysaccharide-protein conjugate vaccines stimulate a highly immunogenic T-cell dependent response which has dramatically decreased the incidence of invasive disease. Here we present a case of Hib meningitis resulting in sensorineural hearing loss in an immunized infant, presumed to be secondary to vaccine failure.

Long Term Impact of Conjugate Vaccines on Haemophilus influenzae Meningitis: Narrative Review.

H. influenzae serotype b (Hib) used to be the commonest cause of bacterial meningitis in young children. The widespread use of Hib conjugate vaccine has profoundly altered the epidemiology of H. influenzae meningitis. This short review reports on the spectrum of H. influenzae meningitis thirty years after Hib conjugate vaccine was first introduced into a National Immunization Program (NIP). Hib meningitis is now uncommon, but meningitis caused by other capsulated serotypes of H. influenzae and non-typeable strains (NTHi) should be considered. H. influenzae serotype a (Hia) has emerged as a significant cause of meningitis in Indigenous children in North America, which may necessitate a Hia conjugate vaccine. Cases of Hie, Hif, and NTHi meningitis are predominantly seen in young children and less common in older age groups. This short review reports on the spectrum of H. influenzae meningitis thirty years after Hib conjugate vaccine was first introduced into a NIP.

Bacterial Meningitis in Children: Neurological Complications, Associated Risk Factors, and Prevention.

Bacterial meningitis is a devastating infection, with a case fatality rate of up to 30% and 50% of survivors developing neurological complications. These include short-term complications such as focal neurological deficit and subdural effusion, and long-term complications such as hearing loss, seizures, cognitive impairment and hydrocephalus. Complications develop due to bacterial toxin release and the host immune response, which lead to neuronal damage. Factors associated with increased risk of developing neurological complications include young age, delayed presentation and Streptococcus pneumoniae as an etiologic agent. Vaccination is the primary method of preventing bacterial meningitis and therefore its complications. There are three vaccine preventable causes: Haemophilus influenzae type b (Hib), S. pneumoniae, and Neisseria meningitidis. Starting antibiotics without delay is also critical to reduce the risk of neurological complications. Additionally, early adjuvant corticosteroid use in Hib meningitis reduces the risk of hearing loss and severe neurological complications.

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

BackgroundIn 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.MethodsIn 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.ResultsIn 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.ConclusionsAfter 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.

National, regional, and state-level burden of Streptococcus pneumoniae and Haemophilus influenzae type b disease in children in India: modelled estimates for 2000–15

SummaryBackgroundIndia accounts for a disproportionate burden of global childhood illnesses. To inform policies and measure progress towards achieving child health targets, we estimated the annual national and state-specific childhood mortality and morbidity attributable to Streptococcus pneumoniae and Haemophilus influenzae type b (Hib) between 2000 and 2015.MethodsIn this modelling study, we used vaccine clinical trial data to estimate the proportion of pneumonia deaths attributable to pneumococcus and Hib. The proportion of meningitis deaths attributable to each pathogen was derived from pathogen-specific meningitis case fatality and bacterial meningitis case data from surveillance studies. We applied these proportions to modelled state-specific pneumonia and meningitis deaths from 2000 to 2015 prepared by the WHO Maternal and Child Epidemiology Estimation collaboration (WHO/MCEE) on the basis of verbal autopsy studies from India. The burden of clinical and severe pneumonia cases attributable to pneumococcus and Hib was ascertained with vaccine clinical trial data and state-specific all-cause pneumonia case estimates prepared by WHO/MCEE by use of risk factor prevalence data from India. Pathogen-specific meningitis cases were derived from state-level modelled pathogen-specific meningitis deaths and state-level meningitis case fatality estimates. Pneumococcal and Hib morbidity due to non-pneumonia, non-meningitis (NPNM) invasive syndromes were derived by applying the ratio of pathogen-specific NPNM cases to pathogen-specific meningitis cases to the state-level pathogen-specific meningitis cases. Mortality due to pathogen-specific NPNM was calculated with the ratio of pneumococcal and Hib meningitis case fatality to pneumococcal and Hib meningitis NPNM case fatality. Census data from India provided the population at risk.FindingsBetween 2000 and 2015, estimates of pneumococcal deaths in Indian children aged 1–59 months fell from 166 000 (uncertainty range [UR] 110 000–198 000) to 68 700 (44 600–86 000), while Hib deaths fell from 82 600 (52 300–112 000) to 15 600 (9800–21 500), representing a 58% (UR 22–78) decline in pneumococcal deaths and an 81% (59–91) decline in Hib deaths. In 2015, national mortality rates in children aged 1–59 months were 56 (UR 37–71) per 100 000 for pneumococcal infection and 13 (UR 8–18) per 100 000 for Hib. Uttar Pradesh (18 900 [UR 12 300–23 600]) and Bihar (8600 [5600–10 700]) had the highest numbers of pneumococcal deaths in 2015. Uttar Pradesh (9300 [UR 5900–12 700]) and Odisha (1100 [700–1500]) had the highest numbers of Hib deaths in 2015. Less conservative assumptions related to the proportion of pneumonia deaths attributable to pneumococcus indicate that as many as 118 000 (UR 69 000–140 000) total pneumococcal deaths could have occurred in 2015 in India.InterpretationPneumococcal and Hib mortality have declined in children aged 1–59 months in India since 2000, even before nationwide implementation of conjugate vaccines. Introduction of the Hib vaccine in several states corresponded with a more rapid reduction in morbidity and mortality associated with Hib infection. Rapid scale-up and widespread use of the pneumococcal conjugate vaccine and sustained use of the Hib vaccine could help accelerate achievement of child survival targets in India.FundingBill & Melinda Gates Foundation.

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.

Burden of Streptococcus pneumoniae and Haemophilus influenzae type b disease in children in the era of conjugate vaccines: global, regional, and national estimates for 2000-15.

SummaryBackgroundPneumococcal conjugate vaccine (PCV) and Haemophilus influenzae type b (Hib) vaccine are now used in most countries. To monitor global and regional progress towards improving child health and to inform national policies for disease prevention and treatment, we prepared global, regional, and national disease burden estimates for these pathogens in children from 2000 to 2015.MethodsUsing WHO and Maternal and Child Epidemiology Estimation collaboration country-specific estimates of pneumonia and meningitis mortality and pneumonia morbidity from 2000 to 2015, we applied pneumococcal and Hib cause-specific proportions to estimate pathogen-specific deaths and cases. Summary estimates of the proportion of pneumonia deaths and cases attributable to these pathogens were derived from four Hib vaccine and six PCV efficacy and effectiveness study values. The proportion of meningitis deaths due to each pathogen was derived from bacterial meningitis aetiology and adjusted pathogen-specific meningitis case–fatality data. Pneumococcal and Hib meningitis cases were inferred from modelled pathogen-specific meningitis deaths and literature-derived case–fatality estimates. Cases of pneumococcal and Hib syndromes other than pneumonia and meningitis were estimated using the ratio of pathogen-specific non-pneumonia, non-meningitis cases to pathogen-specific meningitis cases from the literature. We accounted for annual HIV infection prevalence, access to care, and vaccine use.FindingsWe estimated that there were 294 000 pneumococcal deaths (uncertainty range [UR] 192 000–366 000) and 29 500 Hib deaths (18 400–40 700) in HIV-uninfected children aged 1–59 months in 2015. An additional 23 300 deaths (15 300–28 700) associated with pneumococcus and fewer than 1000 deaths associated Hib were estimated to have occurred in children infected with HIV. We estimate that pneumococcal deaths declined by 51% (7–74) and Hib deaths by 90% (78–96) from 2000 to 2015. Most children who died of pneumococcus (81%) and Hib (76%) presented with pneumonia. Less conservative assumptions result in pneumococcccal death estimates that could be as high as 515 000 deaths (302 000–609 000) in 2015. Approximately 50% of all pneumococcal deaths in 2015 occurred in four countries in Africa and Asia: India (68 700 deaths, UR 44 600–86 100), Nigeria (49 000 deaths, 32 400–59 000), the Democratic Republic of the Congo (14 500 deaths, 9300–18 700), and Pakistan (14 400 deaths, 9700–17 000]). India (15 600 deaths, 9800–21 500), Nigeria (3600 deaths, 2200–5100), China (3400 deaths, 2300–4600), and South Sudan (1000 deaths, 600–1400) had the greatest number of Hib deaths in 2015. We estimated 3·7 million episodes (UR 2·7 million–4·3 million) of severe pneumococcus and 340 000 episodes (196 000–669 000) of severe Hib globally in children in 2015.InterpretationThe widespread use of Hib vaccine and the recent introduction of PCV in countries with high child mortality is associated with reductions in Hib and pneumococcal cases and deaths. Uncertainties in the burden of pneumococcal disease are largely driven by the fraction of pneumonia deaths attributable to pneumococcus. Progress towards further reducing the global burden of Hib and pneumococcal disease burden will depend on the efforts of a few large countries in Africa and Asia.FundingBill & Melinda Gates Foundation.

Haemophilus influenzae type b (Hib) seroprevalence and current epidemiology in England and Wales

IntroductionThe implementation of the Hib conjugate vaccine in the United Kingdom in 1992 resulted in a rapid decline in invasive Hib disease across all age groups. However, a resurgence in 2000–2002 prompted the introduction of additional control measures, including a routine 12-month booster in 2006. Here we describe results from a national serosurvey in children eligible for the 12-month booster and recent Haemophilus influenzae epidemiology in England and Wales. MethodsA national serosurvey was performed to determine the prevalence of anti-polyribosyl-phosphate (anti-PRP) IgG antibodies in 1000 residual samples from children up to 8 years of age in 2013–2014. Data were compared to previous national serosurveys performed by the same laboratory. Current epidemiology of invasive H. influenzae disease in England and Wales is also reported. ResultsMedian anti-PRP IgG concentrations were highest among 1 year olds at 4.4 µg/mL (IQR, 1.3–14.9; n = 99) and then declined rapidly but remained ≥1.0 µg/mL across the age-groups in the cohort eligible for the 12-month booster. Overall, 89% of children (719/817) had anti-PRP concentrations ≥0.15 µg/mL, the putative threshold for short-term protection against invasive Hib disease. During 2012–2016, annual Hib disease incidence remained below one case per million population, responsible for only 67 of 3523 laboratory-confirmed H. influenzae cases, including one case of Hib meningitis during the 5-year period. There were only two deaths within 30 days over the five-year period (case fatality rate, 3.0%). ConclusionsHib control in England and Wales is currently the best achieved since the vaccine was introduced more than two decades ago. However, Hib antibodies wane rapidly after the 12 months booster. Although most children remain protected against disease, antibody levels may not be high enough to prevent carriage among toddlers. Ongoing monitoring is essential to inform future vaccination policy.

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

ABSTRACTObjective: 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.

Haemophilus influenzae type B meningitis: Is there a re-emergence? 24 years of experience in a children's hospital.

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. 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. 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. 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.