A comparison of the efficacy of artesunate plus sulfadoxine–pyrimethamine with that of sulfadoxine–pyrimethamine alone, in the treatment of uncomplicated,Plasmodiumfalciparummalaria in eastern Sudan

Abstract

In an open, randomized, clinical trial, conducted in New Halfa, eastern Sudan, in September-October 2004, the efficacies and adverse effects of artesunate plus sulfadoxine-pyrimethamine (SP), in the treatment of uncomplicated, Plasmodium falciparum malaria, were compared with those of SP alone. Patients were randomized to receive either artesunate (4 mg/kg. day) on days 0-2 plus SP (25 mg sulfadoxine/kg) on day 0 or the SP alone, and then followed-up for 28 days. Sixty patients completed follow-up. Compared with the 30 given artesunate plus SP (ASP), the 30 given SP alone were much more likely to be febrile (30% v. 3.3%; P=0.006) and parasitaemic (50% v. 6.7%; P<00001) on day 1. By day 3, 16.7% of the patients given SP alone were still febrile and 6.7% of them were still parasitaemic, although all the patients given ASP were then afebrile (P=0.02) and aparasitaemic (P=0.1). Five (16.7%) of the patients treated with SP alone but none of those given ASP appeared to be treatment failures (P<0.05). Parasite genotyping revealed that four of the five apparent treatment failures were true recrudescences but the other represented a re-infection detected on day 28. The true frequencies of cure by day 28 were therefore 100% for ASP and 86.7% for SP alone (P=0.02). Adverse effects of treatment (nausea, itching and giddiness) were observed with similar frequencies in the two treatment arms (10.0% of the patients given ASP v. 13.3% of the patients given SP alone; P>0.05). The frequencies of gametocytaemia during follow-up were, however, much lower in the ASP arm than in the SP-only (0.0% v. 23.3%; P=0.005).Thus, although the problems posed by adverse effects were similar in the two treatment arms, ASP appeared markedly better, in terms of fever- and parasite-clearance times and the prevalence of post-treatment gametocytaemia, than SP alone.

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

“…The addition of artesunate to standard antimalarial treatments substantially reduces treatment failure, recrudescence and gametocyte carriage, preventing the emergence and spread of drug resistance and interrupting the transmission of P. falciparum . Coupled with early detection and confirmed diagnosis, this strategy represents the only way forward in the chemotherapy of malaria [4-8]. …”

“…Due to the spread of multidrug-resistant P. falciparum malaria in Sudan [10,11], artesunate plus sulfadoxine-pyrimethamine is recommended as the first-line treatment for uncomplicated P. falciparum malaria. The study aimed to investigate the efficacy of AS plus SP, as there is little published data in Sudan [8,12]. …”

The efficacies of artesunate–sulfadoxine–pyrimethamine and artemether–lumefantrine in the treatment of uncomplicated,Plasmodium falciparummalaria, in an area of low transmission in central Sudan

“…In general, ASP appears more effective and no less safe than SP alone (Anon., 2004;Adam et al, 2005). It is unclear why ASP apparently caused no adverse effects in central Sudan (present study) when about 10% of the patients recently given the same combination (or SP alone) in eastern Sudan reported nausea, itching and/or giddiness (Adam et al, 2005). Artesunate can kill most malarial parasites very quickly, leading to rapid improvement in malaria cases given the drug (Olliaro and Taylor, 2004).…”

“…In the present study, ASP and AL appeared both efficacious and safe in the treatment of uncomplicated malaria in central Sudan. In general, ASP appears more effective and no less safe than SP alone (Anon., 2004;Adam et al, 2005). It is unclear why ASP apparently caused no adverse effects in central Sudan (present study) when about 10% of the patients recently given the same combination (or SP alone) in eastern Sudan reported nausea, itching and/or giddiness (Adam et al, 2005).…”

“…The results of the present and previous investigations (Anon., 2004;Olliaro and Taylor, 2004;Adam et al, 2005) indicate that, if fully implemented, the recent change in the national policy for the treatment of malaria in Sudan, from CQ or SP used alone to ACT for both first-and second-line treatments, should greatly reduce malariaattributable morbidity and mortality in the country. In the present study, ASP and AL appeared both efficacious and safe in the treatment of uncomplicated malaria in central Sudan.…”