Effectiveness of seasonal malaria chemoprevention (SMC) treatments when SMC is implemented at scale: Case-control studies in 5 countries

BackgroundSeasonal malaria chemoprevention (SMC) has shown high protective efficacy against clinical malaria and severe malaria in a series of clinical trials. We evaluated the effectiveness of SMC treatments against clinical malaria when delivered at scale through national malaria control programmes in 2015 and 2016. Methods and findingsCase-control studies were carried out in Mali and The Gambia in 2015, and in Burkina Faso, Chad, Mali, Nigeria, and The Gambia in 2016. Children aged 3-59 months presenting at selected health facilities with microscopically confirmed clinical malaria were recruited as cases. Two controls per case were recruited concurrently (on or shortly after the day the case was detected) from the neighbourhood in which the case lived. The primary exposure was the time since the most recent course of SMC treatment, determined from SMC recipient cards, caregiver recall, and administrative records. Conditional logistic regression was used to estimate the odds ratio (OR) associated with receipt of SMC within the previous 28 days, and SMC 29 to 42 days ago, compared with no SMC in the past 42 days. These ORs, which are equivalent to incidence rate ratios, were used to calculate the percentage reduction in clinical malaria incidence in the corresponding time periods. Results from individual countries were pooled in a random-effects meta-analysis. In total, 2,126 cases and 4,252 controls were included in the analysis. Across the 7 studies, the mean age ranged from 1.7 to 2.4 years and from 2.1 to 2.8 years among controls and cases, respectively; 42.2%-50.9% and 38.9%-46.9% of controls and cases, respectively, were male. In all 7 individual case-control studies, a high degree of personal protection from SMC against clinical malaria was observed, ranging from 73% in Mali in 2016 to 98% in Mali in 2015. The overall OR for SMC within 28 days was 0.12 (95% CI: 0.06, 0.21; p < 0.001), indicating a protective effectiveness of 88% (95% CI: 79%, 94%). Effectiveness against clinical malaria for SMC 29-42 days ago was 61% (95% CI: 47%, 72%). Similar results were obtained when the analysis was restricted to cases with parasite density in excess of 5,000 parasites per microlitre: OR 0.90 (95% CI: 0.79, 0.96; p < 0.001) and 0.59 (95% CI: 0.34, 0.74; p < 0.001) for SMC 0-28 days and 29-42 days ago, respectively. Potential limitations include the possibility of residual confounding due to an association between exposure to malaria and access to SMC, or differences in access to SMC between patients attending a clinic and community controls; however, neighbourhood matching of cases and controls, and covariate adjustment, attempted to control for these aspects, and the observed decline in protection over time, consistent with expected trends, argues against a major bias from these sources. ConclusionsSMC administered as part of routine national malaria control activities provided a very high level of personal protection against clinical malaria over 28 days post-treatment, similar to the efficacy observed in clinical trials. The case-control design used in this study can be used at intervals to ensure SMC treatments remain effective. Author summary Why was this study done? Seasonal malaria chemoprevention (SMC) consists of monthly administration of 2 antimalarial drugs, sulphadoxine-pyrimethamine and amodiaquine, to children 3-59 months of age during the peak months of malaria transmission.SMC provided a high level of protection against clinical malaria in clinical trials, and has been recommended by the World Health Organization since 2012 for areas of the Sahel and sub-Sahel regions of Africa with seasonal transmission. This study was done to determine whether the efficacy observed in the trials translated into effectiveness when SMC was deployed at scale. What did the researchers do and find? The researchers carried out case-control studies in Burkina Faso, Chad, Mali, Nigeria, and The Gambia to estimate the protective effectiveness of SMC treatments against clinical malaria.Cases were children with confirmed malaria at a health facility. For each case, 2 controls were chosen from the neighbourhood where the case lived. Dates of SMC treatments were determined from SMC record cards and by asking caregivers. The effectiveness of monthly SMC treatment in preventing clinical malaria was estimated by comparison of when cases and controls had most recently received SMC.In all 7 case-control studies (2 in 2015 and 5 in 2016), SMC provided a high level of protection against clinical malaria. Protection was highest in the first 4 weeks after treatment. Pooling estimates across the 7 studies, clinical malaria incidence during the first 4 weeks after SMC treatment was reduced on average by 88%. Protection from SMC was lower in the period 5-6 weeks post-administration. What do these findings mean? SMC was highly effective in preventing clinical malaria when delivered at scale through national malaria control programmes, with protection comparable to that observed during clinical trials. This case-control design can be used by national malaria control programmes at intervals to confirm that SMC remains effective.