Dataset Information

Bacterial meningitis in Malawian adults, adolescents, and children during the era of antiretroviral scale-up and Haemophilus influenzae type b vaccination, 2000-2012.

ABSTRACT:

Background

We documented bacterial meningitis trends among adults and children presenting to a large teaching hospital in Malawi during introduction of Haemophilus influenzae type b (Hib) vaccination and the rollout of antiretroviral therapy (ART).

Methods

We analyzed data from 51 000 consecutive cerebrospinal fluid (CSF) samples obtained from adults, adolescents, and children with suspected meningitis admitted to the Queen Elizabeth Central Hospital, Blantyre, Malawi, between 2000 and 2012.

Results

There was a significant decline in the total number of CSF isolates over 12 years (incident rate ratio [IRR], 0.93; 95% CI, .92-.94; P < .001). This decline was entirely in children aged <5 years (IRR, 0.87; 95% CI, .85-.88; P < .001) and coincided with the introduction of Hib vaccination. The number of adult isolates has remained unchanged (IRR, 0.99; 95% CI, .97-1.0; P = .135) despite rapid scale-up of ART provision. In children aged <5 years, Streptococcus pneumoniae, nontyphoidal salmonellae (NTS), and Hib were the most frequently isolated pathogens, and have declined over this time period. Streptococcus pneumoniae was the most frequently isolated pathogen in older children and adults. Estimated incidence of bacterial meningitis in 2012 was 20 per 100,000 cases in children aged <14 years, 6 per 100,000 adolescents, and 10 per 100,000 adults.

Conclusions

Rates of bacterial meningitis have declined in children, but not adults, coinciding with the introduction of Hib vaccination. The highly successful rollout of ART has not yet resulted in a reduction in the incidence in adults where the burden remains high. Long-term surveillance of bacterial meningitis outside of the epidemic "meningitis belt" in Africa is essential.

SUBMITTER: Wall EC

PROVIDER: S-EPMC4001285 | biostudies-literature | 2014 May

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Bacterial meningitis in Malawian adults, adolescents, and children during the era of antiretroviral scale-up and Haemophilus influenzae type b vaccination, 2000-2012.

Wall Emma C EC Everett Dean B DB Mukaka Mavuto M Bar-Zeev Naor N Feasey Nicholas N Jahn Andreas A Moore Mike M van Oosterhout Joep J JJ Pensalo Paul P Baguimira Kenneth K Gordon Stephen B SB Molyneux Elizabeth M EM Carrol Enitan D ED French Neil N Molyneux Malcolm E ME Heyderman Robert S RS

Clinical infectious diseases : an official publication of the Infectious Diseases Society of America 20140204 10

<h4>Background</h4>We documented bacterial meningitis trends among adults and children presenting to a large teaching hospital in Malawi during introduction of Haemophilus influenzae type b (Hib) vaccination and the rollout of antiretroviral therapy (ART).<h4>Methods</h4>We analyzed data from 51 000 consecutive cerebrospinal fluid (CSF) samples obtained from adults, adolescents, and children with suspected meningitis admitted to the Queen Elizabeth Central Hospital, Blantyre, Malawi, between 200 ...[more]

PMID: 24496208

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Project description:BackgroundPneumococcal 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.

Project description:BackgroundTwo of the most prevalent causes of severe bacterial meningitis in children, Haemophilus influenzae type B (Hib) and Streptococcus pneumoniae, are preventable by existing vaccines increasingly available in developing countries. Our objective was to estimate the dose-specific effect of Hib and pneumococcal conjugate vaccines (PCV) on childhood meningitis mortality in low-income countries for use in the Lives Saved Tool (LiST).MethodsWe systematically searched and reviewed published vaccine efficacy trials and observational studies reporting the effect of Hib or PCV vaccines on organism-specific meningitis, bacterial meningitis and all-cause meningitis incidence and mortality among children less than five years old in low- and middle-income countries. Data collection and quality assessments were performed using standardized guidelines. For outcomes available across multiple studies (? 2) and approximating meningitis mortality, we pooled estimates reporting dose-specific effects using random effects meta-analytic methods, then combined these with meningitis etiology data to determine the preventable fraction of childhood meningitis mortality for inclusion in LiST.ResultsWe identified 18 studies of Hib conjugate vaccines reporting relevant meningitis morbidity and mortality outcomes (2 randomized controlled trials [RCTs], 16 observational studies) but few provided dose-specific effects. A meta-analysis of four case-control studies examined the dose-specific effect of Hib conjugate vaccines on Hib meningitis morbidity (1 dose: RR=0.64, 95% CI 0.38-1.06; 2 doses: RR=0.09, 95% CI 0.03-0.27; 3 doses: RR=0.06, 95% CI 0.02-0.22), consistent with results from single RCTs. Pooled estimates of two RCTs provided evidence for the effect of three doses of PCV on vaccine-serotype meningitis morbidity (RR=0.16, 95% CI 0.02-1.20). We considered these outcomes of severe disease as proxy estimates for meningitis mortality and combined the estimates of protective effects with meningitis etiology data to provide an estimate of the preventable fraction of childhood meningitis mortality with three doses of Hib (38-43%) and pneumococcal conjugate vaccines (28-35%) for use in LiST.ConclusionsFew RCTs or vaccine effectiveness studies evaluated the dose-specific impact of Hib and PCV vaccines on childhood meningitis mortality, necessitating use of proxy measures to estimate population impact in LiST. Our analysis indicates that approximately three-quarters of meningitis deaths are preventable with existing Hib and PCV vaccines.

Dataset Information

Bacterial meningitis in Malawian adults, adolescents, and children during the era of antiretroviral scale-up and Haemophilus influenzae type b vaccination, 2000-2012.

Background

Methods

Results

Conclusions

Publications

Bacterial meningitis in Malawian adults, adolescents, and children during the era of antiretroviral scale-up and Haemophilus influenzae type b vaccination, 2000-2012.

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