A randomized trial of chloroquine, amodiaquine and pyrimethamine‐sulphadoxine in Gambian children with uncomplicated malaria

Abstract

SummaryThe increasing occurrence of chloroquine-resistant Plasmodium falciparum in sub-Saharan Africa makes it essential to reconsider current recommendations for the treatment of uncornplicated P. falciparum malaria. In an open, randomized trial, we have compared chloroquine (CQ), amodiaquine (AQ), and pyrimethamine-sulphadoxine (PS) in rural Gambian children with uncomplicated P. falciparum malaria. Three hundred children were randomly assigned at the time of consultation (Do) to oral treatment with 25 mg/kg CQ, 2 j mg/kg AQ (both given over 3 days), or 1.2j/25 mg/kg PS. They were reviewed on day 7 (D7) and day 28 (D28) for symptoms, malaria parasitaemia, and packed cell volume (PCV). Significantly more children treated with PS compared to C Q (17 vs 7%, P=0.03) or AQ (17 vs 3%, P=O.OOI) returned with clinical complaints during the first 3 days after treatment. Five of these patients had a generalized convulsion ( I from the AQ group, 4 from the PS group), of whom 4 developed cerebral malaria. At D7, significantly more patients treated with C Q compared to AQ ( 2 5 vs 7%, P=0.0009) or PS (25 vs 4%, P=o.oooI) were parasitaemic. By D28, the cumulative number of parasitological failures was significantly higher in the C Q group compared to the AQ group (65 us 3 5 % , P=O.OOOI), and significantly higher in the AQ group compared to the PS group (3 j vs 14%, P=o.ooI). Overall, 91% of parasitological failures observed during the study period were symptomatic and were consequently treated with an alternative antimalarial drug. Over the 28-day study period the mean PCV increased significantly less in the C Q group than in the PS group (1.2 vs 3.8%, P=o.o16) and was lower in the C Q group than in the AQ group (1.2 us 2.7%, P=o.Iz, not significant). These results suggest that PS acts more slowly than 4-aminoquinolines in controlling the clinical features of malaria, and that A Q can be considered as an interim alternative to C Q in the first-line therapy of uncomplicated malaria in African areas of high C Q resistance.

Combination of Drug Level Measurement and Parasite Genotyping Data for Improved Assessment of Amodiaquine and Sulfadoxine-Pyrimethamine Efficacies in Treating Plasmodium falciparum Malaria in Gabonese Children

“…A similar level of resistance to SP was reported in Cameroon in 1997 and 1999 (30). Indeed, Central Africa seems to exhibit an intermediate prevalence of resistance to SP, between East Africa, where the resistance rate is around 30% in Uganda, Kenya, and Tanzania (18,19,22), and West Africa, where the rate of resistance remains lower, in the 0 to 10% range (5,21). Our study revealed a worsening of the treatment efficacy of AQ, with more than 30% treatment failures.…”

Antipyretic, Parasitologic, and Immunologic Effects of Combining Sulfadoxine/Pyrimethamine With Chloroquine or Paracetamol for Treating Uncomplicated Plasmodium Falciparum Malaria

“…The relatively slow fever recovery effect by SP treatment alone confirms previous similar preliminary findings. 3 However, the anti-parasitic effect brings about a reduction of fever during the second day, but an antipyretic drug is still required up to 48 hours if clearance of fever is to be achieved.…”

“…3 An optimal treatment regimen may therefore be to combine SP and chloroquine, thus optimizing both the anti-parasitic and clinical effects.…”

Gambian children successfully treated with chloroquine can harbor and transmit Plasmodium falciparum gametocytes carrying resistance genes.

“…However, there is evidence of an increase in the prevalence of CQ-resistant parasites in the last decade, [1][2][3] and in neighboring Senegal, an increase in the number of CQresistant infections has been associated with increased child mortality. 4 It is crucial that the frequency of failures with CQ treatment is monitored carefully, since a change in malaria treatment policy may soon become necessary in The Gambia and other west African countries.…”