Symptomatic Plasmodium Falciparum Malaria Following Administration of Artemether-Lumefantrine in Healthy Children Living in Western Kenya: A Time Analysis

Abstract

Sulphadoxine-Pyremethamine (SP) has been an ideal choice of drug for Intermittent Preventive Treatment (IPT) of malaria; however, due to widespread resistance of the malaria parasite to this drug, there has arisen need to find alternative anti-malarial drugs for IPT to replace it. It has been suggested that short-acting drugs are unsuitable for IPT. A longitudinal cohort study of the epidemiology of pediatric malaria was conducted in Kombewa Division, Western Kenya between 2003 and 2004, in which 270 healthy children were randomized to receive either Artemether-Lumefantrine (AL), a short acting anti-malarial, or placebo at the beginning of the study, and then followed up for one year. Data generated from this study was used to assess the effect of AL on the time to first clinical malaria episode and the risk of multiple clinical malaria episodes and thus evaluate the evidence against the use of short-acting drugs for IPT, and also assess the risk for rebound of clinical malaria episodes. There was no significant difference in the time to first clinical malaria episode in the treatment groups (5.29 weeks (95% CI 2.86 to 11.14 weeks) for the placebo arm versus 5.43 weeks (95% CI 4.86 to 6.43 weeks), and no significant protective effect of AL against the first episode observed beyond 3 weeks post randomization. No rebound of clinical malaria episodes was observed in the treatment groups after 52 weeks of follow up – the rate ratio for multiple malaria episodes (AL/placebo) was 0.90 (95% CI 0.76 to 1.06, p-value=0.205) AL administered in healthy children therefore has little influence on the time to first clinical malaria episode and the risk of multiple clinical malaria episodes. Its short duration of protection makes it unsuitable for IPT.