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.

Keywords: amodiaquine; antimalarial resistance; malaria; seasonal malaria chemoprevention; sulfadoxine-pyrimethamine.

Figure 1.

Prevalence of detectable drug levels (A) and distribution of drug concentrations (B) in children presenting with and without malaria. A, P values comparing prevalence of children with detectable drug levels between cases and controls were computed using Pearson χ² test. B, In the boxplots, the thick black horizontal line indicates median, the upper and lower bounds of the box indicate the 25th and 75th percentiles, the upper and lower bounds of the whiskers indicate the value 1.5 times the interquartile range (IQR), and black points indicate outliers. Median (IQR) of concentrations is provided in Table 2. Mann–Whitney tests were used to compute P values comparing differences in drug distributions between cases and controls.

Figure 2.

Prevalence of detectable drug levels (A) and distribution of drug concentrations (B) in children presenting with and without malaria, stratified by time since the most recent seasonal malaria chemoprevention drug administration. A, Prevalence of cases and controls with detectable drug levels is provided above each barplot. B, In each boxplot, the thick black horizontal line indicates median, the upper and lower bounds of the box indicate the 25th and 75th percentiles, the upper and lower bounds of the whiskers indicate the value 1.5 times the interquartile range, and black points indicate outliers.

Figure 3.

Prevalence of detectable drug levels (A) and distribution of drug concentrations (B) in children presenting with and without malaria, stratified by malnutrition status. A, Prevalence of cases and controls with detectable drug levels is provided above each barplot. B, For each boxplot, the thick black horizontal line indicates median, the upper and lower bounds of the box indicate the 25th and 75th percentiles, the upper and lower bounds of the whiskers indicate the value 1.5 times the interquartile range, and black points indicate outliers.

Figure 4.

Prevalence of detectable drug levels (A) and distribution of concentrations in those with detectable levels of sulfadoxine and pyrimethamine (B) in children presenting with and without malaria within the first week after scheduled seasonal malaria chemoprevention administration. A, Prevalence of cases and controls with detectable drug levels is provided above each barplot and reported P values were computed using Pearson χ² test. B, Only children with detectable levels of sulfadoxine-pyrimethamine contributed to the data presented on the distributions of concentrations. B, For each boxplot, the thick black horizontal line indicates median, the upper and lower bounds of the box indicate the 25th and 75th percentiles, the upper and lower bounds of the whiskers indicate the value 1.5 times the interquartile range, and black points indicate outliers. Median (range) is provided in text above each boxplot. Mann–Whitney tests were used to compute P values comparing differences in drug distributions between cases and controls.