Importance of Drug Concentrations and Nutritional Status During Fixed-Dose Chloroquine and Sulfadoxine/Pyrimethamine Combination Treatment of Malaria

Abstract

The importance of drug concentrations, nutritional status and other host factors were explored in uncomplicated falciparum malaria therapy with fixed-dose chloroquine+sulfadoxine/pyrimethamine (CQ+SP). A total of 83 children were treated. Younger children (6-24months) were given half-strength (HS) and older children (2-5years) full-strength (FS) CQ+SP as recommended. The concentrations of CQ and sulfadoxine (S) were determined by HPLC in 100μl of capillary blood on filter paper. Multiple logistic regressions were used to determine associations with outcomes. Stunting (height-for-age <-2 Z-scores) was more common (27.7%) compared to underweight (wt-for-age <-2 Z-scores, 19.3%) and wasting (wt-for-ht <-2 Z-scores, 9.6%). The mean given doses of CQ and S (mg/kg) were higher in the FS than HS dose groups (p<0.001). Day 1 concentrations of S were also higher in the FS compared to the HS dose group. Nearly all children with day 1 S concentrations above 319μmol/l (the population mean) were cured. Significant explanatory covariates for cure were day 1 S concentration (p=0.004), day 3 CQ concentration (p=0.037), and stunting (p=0.046). Importantly, there were higher odds for cure among the non-stunted than the stunted children. To improve treatment outcomes, narrower graded age-dose intervals should be considered to minimize the effects of anthropometric variations.

Keywords: Malaria, treatment, nutritional status, chloroquine, sulfadoxine, fixed-dose combination

West African Journal of Pharmacology and Drug Research Vol. 22/23 2007: pp. 1-9