ReviewIncidence and aetiology of bacterial meningitis among children aged 1–59 months in South Asia: systematic review and meta-analysis
Introduction
Bacterial meningitis a significant cause of death among children aged 1–59 months, with an estimated 115,000 deaths worldwide in 2015 [1]. Disease burden is high in South Asia, with over 21,000 deaths in 2015 in India alone [1]. Among survivors, up to half have permanent neuropsychological sequelae such as hearing loss or developmental delay [2].
Three bacteria account for most cases in infants and young children: Haemophilus influenzae type b (Hib), Streptococcus pneumoniae (pneumococcus), and Neisseria meningitidis (meningococcus) [3], [4]. Although safe and effective vaccines have existed for years [5], vaccination rates remain suboptimal in South Asia [6], [7], [8], [9], [10]. Yet the impact of vaccine implementation has been substantial among low- and middle-income countries (LMICs) that have achieved high levels of coverage [11], [12], [13], [14], [15].
South Asian countries have only recently incorporated conjugate Hib and pneumococcal vaccines into their immunisation programs. All countries have introduced the pentavalent conjugate Hib vaccine, with routine nationwide vaccination first implemented by Sri Lanka in 2008 [16], and most recently by India (which completed its phased introduction in September 2016); Bangladesh, Bhutan, Nepal and Pakistan implemented the pentavalent vaccine in the interim [17]. For pneumococcus, only three countries in the region have implemented a protein-conjugate vaccine (PCV10)—Pakistan (2012), Nepal (2015), and Bangladesh (2015) [17]; India began rolling out PCV13 in May 2017 [18]. No country in the region has incorporated any meningococcal vaccine into their routine immunisation programs [17], [19].
Since robust nation- or region-wide routine surveillance systems for bacterial meningitis do not exist in South Asia, we aimed to synthesise evidence within the published literature on the incidence and aetiology of bacterial meningitis among children aged 1–59 months in the region. Synthesising data on disease burden and vaccine impact may identify areas for future research and guide vaccine policymaking and implementation in South Asia.
Section snippets
Search strategy and study selection
We searched five databases (Embase®, Global Health®, Medline®, Scopus®, and Web of Science®) without language restrictions for studies published between January 1, 1990, and April 25, 2017, that described the incidence or aetiology of bacterial meningitis among children aged 1–59 months in South Asia, defined as Bangladesh, Bhutan, India, Nepal, Pakistan, and Sri Lanka (see supplementary appendix for search strategy). Two authors (MA and BC) independently screened titles, abstracts, and
Study characteristics
Among 2569 records identified, 47 articles met eligibility criteria (Fig. 1). After reviewing bibliographies of included articles, we identified one additional study, totalling 48 articles cumulatively reporting 20,707 meningitis cases.
There were 26 sentinel surveillance studies, 19 case series, four population-based surveillance studies, and one randomised controlled trial (Table 1) [23], [24], [25], [26], [27], [28], [29], [30], [31], [32], [33], [34], [35], [36], [37], [38], [39], [40], [41]
Discussion
We synthesised data from 48 studies cumulatively reporting 20,707 cases of bacterial meningitis to describe its incidence and aetiology among children aged 1–59 months in South Asia. These cases occurred over a 27-year period (1987–2013) and were reported in articles published from January 1, 1990, through April 25, 2017. To our knowledge, ours is the first systematic review and meta-analysis of this topic. In random-effects meta-analysis, mean annual incidence was 105 (95% CI, 53–173) cases
Conclusions
In summary, we synthesised data from 48 studies cumulatively reporting 20,707 cases of bacterial meningitis over a 27-year period (1987–2013) among children aged 1–59 months in South Asia. Mean annual incidence was 105 (95% CI, 53–173) cases per 100,000 children, the second-highest regional incidence in the world during this time period [73]. On average, almost one-quarter of cases were caused by two vaccine-preventable bacteria, Hib and pneumococcus, though, among studies reporting only
Funding
None.
Disclosures
The authors report no conflict of interest concerning the materials or methods used in this study or the findings reported in this paper. The corresponding author (SKM) had full access to all the data in the study and had final responsibility for the decision to submit for publication.
Authors’ contributions
MA and SKM conceived and designed the study. MA and BC independently conducted the literature review, screened articles, and abstracted data. MA and KWJ independently performed all the statistical analyses. All authors interpreted the findings. MA and BC drafted the article and all authors critically revised the article. SKM supervised the study and is the guarantor.
Acknowledgements
We are grateful to Cheri Nickel, research librarian at the Hospital for Sick Children, for assistance with the literature search; Brenda Bishop, Jenna Craig, and Nadine Francis for administrative support; Dr. Stephen Sharp at the MRC Epidemiology Unit, University of Cambridge, for guidance about stratified meta-analysis and meta-regression; and the following colleagues, mentors, and supervisors for critical feedback on an earlier version of this manuscripts: Nathan Boin and Alice Shen (Icahn
Conflicts of interest
The authors report no conflict of interest concerning the materials or methods used in this study or the findings reported in this paper.
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Equal contributors.