Pneumococcal Serotype Prevalence in Southeast Asia: A Systematic Review and Meta-Analysis

Background The prevalence of Streptococcus pneumoniae serotypes in the ASEAN region is not well studied despite severe pneumococcal infections being a major cause of death among children in the region. This information is crucial for understanding the epidemiology of the disease and guiding vaccine policies. Our study aimed to provide a thorough analysis of the pneumococcal serotypes in ASEAN prior to vaccine introduction to assist countries in formulating evidence-based vaccine policies. Methods We conducted a systematic review and meta-analysis of studies reporting S. pneumoniae serotypes from carriage, invasive disease (IPD) and non-invasive disease (non-IPD) published up until 31st December 2022 using PubMed, PubMed Central, Ovid MEDLINE and Scopus databases, reference lists and search engines. Data prior to the national introduction of conjugate vaccines in the ASEAN region were included. Non-English, animal, case studies, reviews, and studies on antibiotic resistance only were excluded. The quality of studies was examined using the CASP and the JBI’s Critical Appraisal Tools. The frequency of serogroups and serotypes was calculated, and vaccine coverage was estimated by the addition of vaccine serotypes as a fraction of the total number of isolates per age group. This study was registered with PROSPERO CRD42022243994. Findings A total of 940 studies were identified, and 99 and 84 relevant papers were included in the qualitative and quantitative analyses, respectively. A total of 16,396 isolates were identified, spread across all body sites and ages, with vaccine-covered serotypes 19F (n = 2,061, 12.57% [95%CI: 12.07 – 13.09]), 23F (n = 1,508, 9.20% [95%CI: 8.76 – 9.65]) and 6B (n = 1,160, 7.07% [95%CI: 6.69 – 7.48]) occurring most often. Non-vaccine types e.g ., 6AB (n = 617, 3.76% [95%CI: 3.48 – 4.07]), 15BC (n = 35, 2.57% [95%CI: 2.33 – 2.82]) and 34 (n = 260, 1.59% [95%CI: 1.40 – 1.79]) were also frequently observed. Interpretation The most common serotypes found in IPD, non-IPD, and carriage in ASEAN are covered by currently available conjugate vaccines. This underscores the importance of vaccination and predicts future success in reducing the burden of pneumococcal disease. The data gathered offers important insights into pneumococcal serotype epidemiology across the different countries belonging to ASEAN. ### Competing Interest Statement I have read the journal's policy and the authors of this manuscript have the following competing interests: SCC acts as principal investigator on studies conducted on behalf of University Hospital Southampton NHS Foundation Trust and the University of Southampton that are sponsored by vaccine manufacturers but receives no personal payments. SCC has received financial assistance from vaccine manufacturers to attend conferences. SCC has participated in advisory boards for vaccine manufacturers but receives no personal payments. DWC was a post-doctoral researcher on projects funded by Pfizer and GSK between April 2014 and 20th October 2017. All other authors have no conflicts of interest. ### Funding Statement Yes. This study was funded, in part, by a Global Partnership Award to SCC from the University of Southampton via the World Universities Network and a Pfizer GMG grant ID#69396685 to SCC. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. ### Author Declarations I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained. Yes The details of the IRB/oversight body that provided approval or exemption for the research described are given below: This research did not require ethical approval I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals. Yes I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance). Yes I have followed all appropriate research reporting guidelines, such as any relevant EQUATOR Network research reporting checklist(s) and other pertinent material, if applicable. Yes The data is available within the paper. * ASEAN : Association of Southeast Asian Nations IPD : Invasive Pneumococcal Disease LMIC : Low and Middle-Income Countries Non-IPD : Non-Invasive Pneumococcal Disease NT : Non-Typeable NVT : Non-Vaccine Type PCV : Pneumococcal Conjugate Vaccine VRT : Vaccine-Related Types VT : Vaccine Type