The duration of protection against clinical malaria provided by the combination of seasonal RTS,S/AS01E vaccination and seasonal malaria chemoprevention versus either intervention given alone

Abstract

Background A 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. Methods In 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. Results The 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. Conclusions The 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 registration The RTS,S-SMC trial in which these data were collected was registered at clinicaltrials.gov: NCT03143218

Trends in Uncomplicated and Severe Malaria following Seasonal Malaria Chemoprevention Administration in Nouna, Burkina Faso

“…Previous studies have shown that the effectiveness of SMC was highest in the rst 28 days after administration, 12,34 which was short duration but slightly longer than that observed here. The shorter duration observed, compared to that previously documented in RCT, 35 may indicate that the period of protection could be even shorter at the population level in areas with gaps in coverage. Furthermore, this may signal a growing resistance to SP, as shorter duration of protection of chemoprophylaxis has been previously associated with increasing resistance.…”

Evidence from Madagascar shows that vaccination could mitigate climate-driven disruptions to malaria control

“…Current operational plans for high malaria burden countries, including Madagascar ( 45 ), recommend implementing or expanding interventions using anti-malaria drugs to reduce burden in targeted populations, as a supplement to existing base activities (i.e., bednet distribution). Approaches use the regular administration of either a standard first-line antimalarial with a short half-life (protective against reinfection for 13-15 days ( 46 )) to clear existing infections (mass drug administration, MDA, or mass testing and treatment, MTaT) or a longer lasting antimalarial (protective for 21-42 days ( 47, 48 )) to also prevent new infections (seasonal or perennial malaria chemoprophylaxis, SMC, PMC, or intermittent preventive treatment of malaria in pregnancy, IPTp) (see Table S1 ).…”

Malaria prevention in children: an update

“…For example, seasonal administration of RTS,S plus SMC improves upon the efficacy of either alone by almost 60% [47 && ]. A sub-study from this trial did note that RTS,S efficacy in this setting declined rapidly after six months, highlighting the importance of correctly timing interventions for the malaria season [48].…”