Efficacy of sulfadoxine-pyrimethamine with and without artesunate for the treatment of uncomplicated malaria in Mozambique : a randomised controlled trial
[Background and rationale] Malaria accounts for a large public health burden in Mozambique and a treatment policy with effective anti-malarials is a key component of their malaria control programme. Artemisinin-based combination therapies (ACTs) are now generally considered as the best treatment for uncomplicated falciparum malaria; the use of artesunate (AS) in combination with sulfadoxine-pyrimethamine (SP) is recommended by the World Health Organisation (WHO). Mozambique policy-makers recommended that an ACT be implemented and studied in 2003. Therefore this RCT was conducted to compare SP monotherapy with AS, plus SP in order to provide further evidence of available treatment options in the region. [Trial design and methods] A prospective multi-centre, open-label, parallel-group randomised clinical trial (RCT) was conducted at 4 public health facilities in Maputo Province, Mozambique during the malaria seasons of 2003 - 2004 and 2004 - 2005. Eligible patients were aged over 1 year with body weight over 10kg and uncomplicated Plasmodium falciparum malaria (parasitaemia less than 500 000 asexual parasites/ml blood with axillary temperature less than or equal to 37.5oC or a history of fever). Patients were excluded if they took other anti- malarials or folate within 7 days, had moderately severe/severe malaria, history of G6PD deficiency or allergy to study drugs, or serious underlying disease. Patients were randomly assigned to sulfadoxine-pyrimethamine (SP): a single oral 25/1.25mg per kg dose on Day 0, with a maximum of 3 tablets), or artesunate (AS) plus SP: SP as above, plus single oral doses of 4mg/kg AS on Days 0, 1 and 2 with a maximum daily dose of 4 tablets). The study aimed to compare the efficacy of SP monotherapy to SP in combination with AS as first line treatment of uncomplicated falciparum malaria. The primary objective was the comparison of the time to treatment failure (the relative hazard of treatment failure) between groups using standard WHO response to treatment definitions for low to moderate malaria transmission areas, modified to a 42 day follow up. Randomisation was computer-generated with sequential allocation concealed in opaque sealed envelopes. Treatments were open-label, however laboratory staff responsible for parasite density measurements (in order to determine the primary efficacy end point) were blinded to treatment allocation.
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Department of Public Health and Family Medicine