A pragmatic health centre-based evaluation comparing the effectiveness of a PCV13 schedule change from 3+0 to 2+1 in a high pneumococcal carriage and disease burden setting in Malawi: a study protocol

Todd D Swarthout, Ana Ibarz-Pavon, Gift Kawalazira, George Sinjani, James Chirombo, Andrea Gori, Peter Chalusa, Farouck Bonomali, Roseline Nyirenda, Edwin Bulla, Comfort Brown, Jacquline Msefula, Marjory Banda, Jean Kachala, Charles Mwansambo, Marc Yr Henrion, Stephen B Gordon, Neil French, Robert S Heyderman, Todd D Swarthout, Ana Ibarz-Pavon, Gift Kawalazira, George Sinjani, James Chirombo, Andrea Gori, Peter Chalusa, Farouck Bonomali, Roseline Nyirenda, Edwin Bulla, Comfort Brown, Jacquline Msefula, Marjory Banda, Jean Kachala, Charles Mwansambo, Marc Yr Henrion, Stephen B Gordon, Neil French, Robert S Heyderman

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.

Keywords: epidemiology; paediatric infectious disease & immunisation; public health.

Conflict of interest statement

Competing interests: None declared.

© Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY. Published by BMJ.

Figures

Figure 1
Figure 1
Map of Blantyre district with borders of health centre catchment areas. Red crosses (+) indicate location of health centres offering EPI vaccination. Areas shaded in green are non-inhabited (incl. mountains, industrial zones and other regions administratively declared not for habitation). EPI, Expanded Programme of Immunisations.
Figure 2
Figure 2
The PRagmatic-Explanatory Continuum Indicator Summary 2 wheel with study-specific scores.
Figure 3
Figure 3
Carriage surveillance sampling frame black dashed vertical line separates primary (left of dashed line) from secondary study objectives. ART, antiretroviral; M, months; PCV, pneumococcal conjugate; QECH, Queen Elizabeth Central Hospital.

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