Artesunate plus sulfadoxine-pyrimethamine for uncomplicated malaria in Kenyan children: A randomized, double-blind, placebo-controlled trial

Abstract

Plasmodium falciparum has developed resistance to almost all routinely used antimalarial drugs. Sulfadoxine-pyrimethamine (SP) has replaced chloroquine as first-line treatment of uncomplicated malaria infection in Kenya but resistance to SP is already reported. The addition of artemisinin derivatives to SP may delay the development of drug resistance, improve cure rates, and reduce transmission. The efficacy and safety of artesunate plus SP in the treatment of uncomplicated P. falciparum malaria was evaluated in a randomized trial of 600 children at Siaya District Hospital, western Kenya between October 1999 and March 2000. Children aged < 5 years were randomly assigned to receive SP alone (1.25 mg/kg based on pyrimethamine), or in combination with artesunate (4 mg/kg/d) for either 1 or 3 d. Parasitological failure by days 14 and 28 (polymerase chain reaction [PCR]-corrected for new infections) were the primary endpoints. Treatment failure rates by day 14 were 25.5% in the SP alone group, 16.2% (risk difference [delta]-9.3%, 95% CI -17.3 to -1.2%, P= 0.027) in the 1-dose artesunate group, and 9.4% (delta-16.2%, 95% CI -23.6 to -8.7%, P< 0.001) in the 3-dose artesunate group. Corresponding rates by day 28 were 46.0% in the SP alone group, 38.2% (delta-7.8%, 95% CI -17.7 to 2.1%, P= 0.16) in the 1-dose artesunate group, and 26.0% (delta-20.0%, 95% CI -29.4 to -10.6%, P < 0.001) in the 3-dose artesunate group. The artesunate and SP combination was well tolerated. There were no serious drug-related adverse events. Parasite clearance and gametocyte carriage were reduced significantly in both combination groups compared with SP alone. Three days of artesunate were required to reduce significantly the risk of treatment failure by day 28. However, the high background rate of parasitological failure with SP may make this combination unsuitable for widespread use in Kenya.

Artesunate plus sulfadoxine-pyrimethamine for treatment of uncomplicated Plasmodium falciparum malaria in Sudan

“…Hundred percent efficacy of AS plus SP was recently reported from eastern Sudan [8] and 99% from southern Sudan [12]. The high cure rate in this study is comparable to that reported from neighbouring African countries [5,6]. However, the highest drug resistant P. falciparum strains were reported from eastern Sudan [11,16].…”

Effect of artesunate plus sulfadoxine–pyrimethamine on haematological recovery and anaemia, in Kenyan children with uncomplicated,Plasmodium falciparummalaria

“…Children with a high prevalence of malaria-associated anaemia, arising probably from chronic asymptomatic parasitaemia, may need repeated doses of an effective antimalarial therapy, combined with vector control. The efficacy of an ACT depends strongly on the efficacy of the partner drug used with the artemisinin derivative Obonyo et al, 2003). In the present study, it was almost certainly the high prevalence of SP resistance that compromised the efficacy of the AS1 and AS3 combinations, in terms of both parasitological cure and haematological recovery.…”

A Reversal in Reductions of Child Mortality in Western Kenya, 2003–2009

“…Drawing from the standard health facility formulary, the health worker had the option of providing quinine, which is bitter and can be difficult to administer for the full seven-day treatment regimen, sulfadoxine-pyrimethamine, which is well tolerated and easily administered, but has poor treatment efficacy in Kenya because of high levels of resistance, 24 or a prescription, which may not be filled as prescribed in this rural setting with few licensed pharmacies, and an impoverished population. Thus, the increase in malaria-specific mortality may have been caused by lack of access to any effective antimalarial drug during times of AL stock-out.…”