Evaluation strategies for measuring pneumococcal conjugate vaccine impact in low-resource settings

ABSTRACT

Objectives: Pneumococcal conjugate vaccines (PCVs) are effective in reducing pneumococcal disease. We measured 13-valent PCV (PCV13) effect on different pneumococcal outcomes using diverse studies in Lao People’s Democratic Republic. Methods: Studies included: pre-PCV13 population-based record review of hospitalized childhood pneumonia cases; acute respiratory infection (ARI) study post-PCV13 to demonstrate effectiveness (VE) against hypoxic pneumonia; invasive pneumococcal disease (IPD) surveillance in all ages (2004–2018); carriage studies in children hospitalized with ARI (2013–2019); community carriage surveys pre- and post-PCV13. Results: Annual pneumonia incidence rate in children pre-PCV13 was 1,530 (95% confidence interval [CI] 1,477–1,584) per 100,000. Adjusted VE against hypoxic pneumonia was 37% (95% CI 6–57%). For IPD, 85% (11/13) of cases were due to vaccine-types pre-PCV13, and 43% (3/7) post-PCV13 in children aged <5 years; for ≥5 years, 61% (27/44) and 42% (17/40), respectively. For ARI cases, adjusted VE for vaccine-type carriage was 39% (95% CI 4–60) in <5 year olds; slightly higher than community surveys (23% [95% CI 4–39%] in 12–23 month olds). Conclusions: Despite limited baseline data, we found evidence of PCV13 impact on disease and carriage. Our approach could be used in similar settings to augment existing WHO PCV evaluation guidelines.

KEYWORDS:

• Children
• Laos
• lao pdr
• low-middle income country
• 13-valent pneumococcal conjugate vaccine
• vaccine impact
• surveillance

Supplementary material

Supplemental data for this article can be accessed here.

Declaration of interest

C von Mollendorf, C Satzke, EM Dunne, CD Nguyen and KE Mulholland are investigators on an unrelated collaborative research project funded by Pfizer. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript.

Reviewer disclosures

A reviewer on this manuscript acknowledges receiving consulting fees from Merck Sharp & Dohme, consulting and speaking fees, and funds for unrestricted research grants from Pfizer, and funds for unrestricted research grants from GlaxoSmithKline. All these fees and funds have been paid directly to her/his home institution. Peer reviewers on this manuscript have no other relevant financial or other relationships to disclose.

Author contributions

RL, MC, VS, KV, JYRL, SP, KAM, AG, MM, RP, SSD, KF, PNN, KEM, DABD and FMR supported the development of country-specific protocols and study implementation. CS and EMD devised the microbiological approach and protocols. BDO managed and conducted microbiological testing. CvM, RL, JYRL, JC, EMD, RW, CDN and CS conducted the analysis. CvM and RL drafted the manuscript. All authors provided feedback to the draft manuscript and have read and approved the final version.

Acknowledgments

We wish to acknowledge and thank all the patients and their families for participation in this study. We would also like to acknowledge the study and laboratory staff at: Centre for International Child Health, Dept. of Paediatrics, The University of Melbourne, Australia; Murdoch Children’s Research Institute, Australia; Expanded Programme of Immunization, Ministry of Health Lao PDR; Lao-Oxford-Mahosot Hospital-Wellcome Trust-Research Unit (LOMWRU), Vientiane; Lao PDR Centre for Tropical Medicine & Global Health, University of Oxford, Oxford, UK; London School of Hygiene and Tropical Medicine, London, UK; Lao PDR Infectious Disease Center and Microbiology Laboratory and the directors and staff of the district hospitals, for their help and support

In particular we are very grateful to Bounthaphany Bounxouei, previous Director of Mahosot Hospital; Bounnack Saysanasongkham, previous Director of Department of Health Care, Ministry of Health; H.E. Bounkong Syhavong, Previous Minister of Health, Lao PDR, and all the additional ARIVI/PneuCAPTIVE team members from LOMWRU (Melinda Morpeth, Chanthaphone Syladeth, Malisa Vongsakid, Toukta Bhounkhoun, Laddaphone Bounvilay, Rasamyvanh Vanthanouvong, Valin Chanthaluanglath, Soubanh Saysana, Parnthong Xaithilath and Chanthachone Khamsy). Lastly, we would like to thank the late Anonh Xeuatvongsa, National Immunization Programme manager at the Laos Ministry of Health, who supported the PCV evaluation programme since its inception.

Additional information

Funding

This study is funded by Gavi Alliance (PP34411213A1) and the Bill & Melinda Gates Foundation (OPP1115490), with support from the Victorian Government’s Operational Infrastructure Support Program. FR was supported by a NHMRC Early Career and TRIP Fellowships. CS was supported by a NHMRC Career Development Fellowship (1087957) and a veski Inspiring Women Fellowship. LOMWRU core support and for PNN and DABD were from the Wellcome Trust. This work was supported, in whole or in part, by the Bill & Melinda Gates Foundation [OPP1115490]. Under the grant conditions of the Foundation, a Creative Commons Attribution 4.0 Generic License has been assigned to the Author Accepted Manuscript version. This research was funded in part, by the Wellcome Trust [Grant number 106698/Z/14/Z]. For the purpose of open access, the author has applied a CC BY public copyright licence to any Author Accepted Manuscript version.