• Matthew Cairns, Amadou Barry, Issaka Zongo, Issaka Sagara, Serge R Yerbanga, Modibo Diarra, Charles Zoungrana, Djibrilla Issiaka, Abdoul Aziz Sienou, Amadou Tapily, Koualy Sanogo, Mahamadou Kaya, Seydou Traore, Kalifa Diarra, Hama Yalcouye, Youssoufa Sidibe, Alassane Haro, Ismaila Thera, Paul Snell, Jane Grant, Halidou Tinto, Paul Milligan, Daniel Chandramohan, Brian Greenwood, Alassane Dicko, and Jean Bosco Ouedraogo.
• International Statistics and Epidemiology Group, Department of Infectious Disease Epidemiology, London School of Hygiene and Tropical Medicine, London, UK. matthew.cairns@lshtm.ac.uk.
• Bmc Med. 2022 Oct 7; 20 (1): 352352.

BackgroundA recent trial of 5920 children in Burkina Faso and Mali showed that the combination of seasonal vaccination with the RTS,S/AS01E malaria vaccine (primary series and two seasonal boosters) and seasonal malaria chemoprevention (four monthly cycles per year) was markedly more effective than either intervention given alone in preventing clinical malaria, severe malaria, and deaths from malaria.MethodsIn order to help optimise the timing of these two interventions, trial data were reanalysed to estimate the duration of protection against clinical malaria provided by RTS,S/AS01E when deployed seasonally, by comparing the group who received the combination of SMC and RTS,S/AS01E with the group who received SMC alone. The duration of protection from SMC was also estimated comparing the combined intervention group with the group who received RTS,S/AS01E alone. Three methods were used: Piecewise Cox regression, Flexible parametric survival models and Smoothed Schoenfeld residuals from Cox models, stratifying on the study area and using robust standard errors to control for within-child clustering of multiple episodes.ResultsThe overall protective efficacy from RTS,S/AS01E over 6 months was at least 60% following the primary series and the two seasonal booster doses and remained at a high level over the full malaria transmission season. Beyond 6 months, protective efficacy appeared to wane more rapidly, but the uncertainty around the estimates increases due to the lower number of cases during this period (coinciding with the onset of the dry season). Protection from SMC exceeded 90% in the first 2-3 weeks post-administration after several cycles, but was not 100%, even immediately post-administration. Efficacy begins to decline from approximately day 21 and then declines more sharply after day 28, indicating the importance of preserving the delivery interval for SMC cycles at a maximum of four weeks.ConclusionsThe efficacy of both interventions was highest immediately post-administration. Understanding differences between these interventions in their peak efficacy and how rapidly efficacy declines over time will help to optimise the scheduling of SMC, malaria vaccination and the combination in areas of seasonal transmission with differing epidemiology, and using different vaccine delivery systems.Trial RegistrationThe RTS,S-SMC trial in which these data were collected was registered at clinicaltrials.gov: NCT03143218.© 2022. The Author(s).

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