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

Abstract

Background Seasonal 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 findings Case–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. Conclusions SMC 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.

Effectiveness of seasonal malaria chemoprevention administered in a mass campaign in the Kedougou region of Senegal in 2016: a case-control study

“…In this case-control study chosen to evaluate the effectiveness of SMC administered in a mass campaign in Senegal, the same difficulties as those described by Cairns et al, and related to the rigor required for this type of study, were encountered 9 . The usefulness of case-control studies for determining the efficacy of SMC as well as that of a vaccine has been reported.…”

Introducing field digital data collection systems into seasonal malaria chemoprevention campaigns: opportunities for robust evidence development and national e-health strategies

“…12 Pooled estimates across seven studies in SSA indicate that SMC implementation reduces the incidence of clinical malaria during the first 4 weeks by about 88%. 13 Since 2012, 13 countries in the Sahel region of Africa have implemented SMC and over 33 million children were protected by the intervention in 2020 alone. 14 For SMC, caregivers administer three doses of the drug, sulfadoxine-pyrimethamine plus amodiaquine, over a 3-day period for up to 5 months of the rainy season.…”

“…To protect children from malaria, in 2012, the WHO recommended seasonal malaria chemoprevention (SMC) in areas of highly seasonal malaria transmission during the rainy season, during periods when malaria incidence is at the highest 12. Pooled estimates across seven studies in SSA indicate that SMC implementation reduces the incidence of clinical malaria during the first 4 weeks by about 88% 13. Since 2012, 13 countries in the Sahel region of Africa have implemented SMC and over 33 million children were protected by the intervention in 2020 alone 14…”

Sub-national tailoring of seasonal malaria chemoprevention in Mali based on malaria surveillance and rainfall data

“…In accordance with WHO recommendations, malaria prevention in Mali involves vector control using LLINs and IRS and chemoprevention in children and pregnant women [ 10 ]. A major control intervention is seasonal malaria chemoprevention (SMC) [ 11 ], which consists of the monthly administration of antimalarial drugs to children aged 3–59 months during the high malaria transmission season [ 12 ]. Since 2016, the NMCP has been implementing SMC interventions in all health districts on the basis of historical national data on malaria incidence or prevalence [ 13 ].…”