Abstract
Folic acid supplementation may potentially alter the efficacy of sulfadoxine-pyrimethamine (SP) treatment in children with malaria. However, there is lack of evidence from randomized controlled trials and effects of folic acid supplementation on clinical efficacy of SP therapy remain moderately understood among children. In a double masked, placebo-controlled trial among preschool children in Pemba Island (Tanzania), iron and folic acid supplementation (Fe/FA) showed an increased risk of hospitalizations and death. In the present paper, we evaluated if folic acid supplementation reduced the efficacy of malaria treatment and thereby contributed to observed adverse effects. During the study, 1648 children had confirmed malarial episodes and received either sulphadoxine-pyrimethamine (SP) treatment and iron folic acid or SP treatment and placebo. These children were evaluated for recovery and incidence of hospitalization during the next 15, 30, and 140 days. Two groups did not differ in malarial episode or hospitalization rate on subsequent 15, 30, and 140 days. Altered efficacy of SP by folic acid was not observed and did not contribute to adverse events in the previous trial. This trial is registered with Controlled-trials.com ISRCTN59549825.
Highlights
Malaria affects approximately 219 million people each year with an estimated 660,000 deaths
It has been suggested that folic acid (FA) supplementation during SP treatment could adversely affect the inhibitory effect of SP on parasite growth, by providing folate to the parasite [4]
The relative risk of treated malarial episode extending beyond 4 days or beyond 7 days among those receiving FA as compared to the placebo was 1.03 and 0.99, respectively
Summary
Malaria affects approximately 219 million people each year (range 154–289 million) with an estimated 660,000 deaths. Children during this study were receiving sulfadoxine-pyrimethamine (SP), an antifolate antimalarial drug as a first-line treatment for malaria. Sulfadoxine is known to act by inhibition of dihydropteroate synthetase while pyrimethamine competitively inhibits dihydrofolate reductase thereby blocking the endogenous pathway whereby plasmodium parasites produce folate de novo. It blocks uptake of and/or utilization by malaria parasites of exogenous folic acid that may transiently occur in circulation following ingestion of high supplemental doses. It has been suggested that FA supplementation (at least in higher doses) during SP treatment could adversely affect the inhibitory effect of SP on parasite growth, by providing folate to the parasite [4].
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