Seasonal Malaria Chemoprevention Drug Levels and Drug Resistance Markers in Children With or Without Malaria in Burkina Faso: A Case-Control Study

Abstract Background Despite scale-up of seasonal malaria chemoprevention (SMC) with sulfadoxine-pyrimethamine and amodiaquine (SP-AQ) in children 3–59 months of age in Burkina Faso, malaria incidence remains high, raising concerns regarding SMC effectiveness and selection of drug resistance. Using a case-control design, we determined associations between SMC drug levels, drug resistance markers, and presentation with malaria. Methods We enrolled 310 children presenting at health facilities in Bobo-Dioulasso. Cases were SMC-eligible children 6–59 months of age diagnosed with malaria. Two controls were enrolled per case: SMC-eligible children without malaria; and older (5–10 years old), SMC-ineligible children with malaria. We measured SP-AQ drug levels among SMC-eligible children and SP-AQ resistance markers among parasitemic children. Conditional logistic regression was used to compute odds ratios (ORs) comparing drug levels between cases and controls. Results Compared to SMC-eligible controls, children with malaria were less likely to have any detectable SP or AQ (OR, 0.33 [95% confidence interval, .16–.67]; P = .002) and have lower drug levels (P < .05). Prevalences of mutations mediating high-level SP resistance were rare (0%–1%) and similar between cases and SMC-ineligible controls (P > .05). Conclusions Incident malaria among SMC-eligible children was likely due to suboptimal levels of SP-AQ, resulting from missed cycles rather than increased antimalarial resistance to SP-AQ. In this case-control study assessing drug levels and resistance markers for seasonal malaria chemoprevention (SMC) with sulfadoxine-pyrimethamine-amodiaquine in children in Burkina Faso, suboptimal drug levels and not increased prevalence of resistance markers was associated with incident malaria in SMC-eligible children.