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Abstract
Introduction Streptococcus pneumoniae (the pneumococcus) is commonly carried as a commensal bacterium in the nasopharynx but can cause life-threatening disease. Transmission occurs by human respiratory droplets and interruption of this process provides herd immunity. A 2017 WHO Consultation on Optimisation of pneumococcal conjugate vaccines (PCV) Impact highlighted a substantial research gap in investigating why the impact of PCV vaccines in low-income countries has been lower than expected. Malawi introduced the 13-valent PCV (PCV13) into the national Expanded Programme of Immunisations in 2011, using a 3+0 (3 primary +0 booster doses) schedule. With evidence of greater impact of a 2+1 (2 primary +1 booster dose) schedule in other settings, including South Africa, Malawi’s National Immunisations Technical Advisory Group is seeking evidence of adequate superiority of a 2+1 schedule to inform vaccine policy.
Methods A pragmatic health centre-based evaluation comparing impact of a PCV13 schedule change from 3+0 to 2+1 in Blantyre district, Malawi. Twenty government health centres will be randomly selected, with ten implementing a 2+1 and 10 to continue with the 3+0 schedule. Health centres implementing 3+0 will serve as the direct comparator in evaluating 2+1 providing superior direct and indirect protection against pneumococcal carriage. Pneumococcal carriage surveys will evaluate carriage prevalence among children 15–24 months, randomised at household level, and schoolgoers 5–10 years of age, randomly selected from school registers. Carriage surveys will be conducted 18 and 33 months following 2+1 implementation.
Analysis The primary endpoint is powered to detect an effect size of 50% reduction in vaccine serotype (VT) carriage among vaccinated children 15–24 months old, expecting a 14% and 7% VT carriage prevalence in the 3+0 and 2+1 arms, respectively.
Ethics and dissemination The study has been approved by the Malawi College of Medicine Research Ethics Committee (COMREC; Ref: P05.19.2680), the University College London Research Ethics Committee (Ref: 8603.002) and the University of Liverpool Research Ethics Committee (Ref: 5439). The results from this study will be actively disseminated through manuscript publications and conference presentations.
Trial registration number NCT04078997.
- epidemiology
- epidemiology
- public health
- paediatric infectious disease & immunisation
- public health
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Footnotes
TDS and AI-P are joint first authors.
NF and RSH are joint senior authors.
Contributors Contributors TDS, GK, CM, NF and RSH conceived the study. TDS, GK, CM, NF and RSH designed the study with contributions from AI-P, JC, JK, MB, MH and SBG. TDS, CB and JM oversaw development of laboratory methods. TDS, AI-P, AG, PC, FB, RN, EB and GS designed study documents. TDS and AI-P jointly wrote the first draft. All authors have commented on the manuscript. All authors have read and approved the final manuscript.
Funding This work was funded by Bill & Melinda Gates Foundation, USA (Ref: OPP1185516) to RSH; National Institute for Health Research (NIHR) Global Health Research Unit on Mucosal Pathogens using UK aid from the UK Government (Project number 16/136/46) to RSH. The MLW Clinical Research Programme is supported by a Strategic Award from the Wellcome Trust, UK (206545/Z/17/Z) to SBG. The corresponding author will have full access to the study data and, together with the senior authors, will have final responsibility for the decision to submit for publication.
Disclaimer The funders had no role in study design. The funders will have no role in collection, analysis, data interpretation, writing of the report or in the decision to submit the paper for publication. The views expressed in this publication are those of the authors and not necessarily those of the NIHR or the Department of Health and Social Care.
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Competing interests None declared.
Patient and public involvement Patients and/or the public were involved in the design, or conduct, or reporting, or dissemination plans of this research. Refer to the Methods section for further details.
Provenance and peer review Not commissioned; peer reviewed for ethical and funding approval prior to submission.