Tafenoquine, an analogue of primaquine, is effective and well tolerated for prophylaxis against malaria, a Smithkline Beecham sponsored study has found.
Dr Betrand Lell (Institute for Tropical Medicine, University of Tüblingen, Germany) and colleagues explain that the advantage of both primaquine and tafenoquine is that they are active against the liver stages of malaria which means that, unlike antimalarials active against blood stages, they do not need to be continued after exposure ends. However, the short half life and toxicity of primaquine has restricted its use, they say, adding that tafenoquine has an improved safety profile and a longer half life (14 days compared with six hours).
Dr Lell and colleagues conducted a randomised, double-blind study of 426 participants aged 12-20 to assess the safety and efficacy of tafenoquine in Gabon, a malaria-endemic area. After receiving radical cure for malaria (halofantrine) and being assessed as aparasitaemic, the trial participants were randomised to receive tafenoquine or placebo for three days. Tafenoquine was given in one of four doses - 31.25mg, 62.5mg, 125mg and 250mg. Participants were then followed up to day 77.
At day 56, four participants in the placebo group and four in the tafenoquine 31.25mg group had positive smears for the malarial parasite. At higher doses, the first positive smear was found on day 70. At day 77, no participants in the 250mg tafenoquine group had positive smears. The protective efficacy for tafenoquine at day 77 was 0 per cent for 31.25mg, 80 per cent for 62.5mg, 93 per cent for 125mg and 100 per cent for 250mg. The drug was well tolerated, say the researchers. But as it is related to primaquine, it should not be used in individuals with deficiency of glucose-6-phosphate dehydrogenase until its haemolytic potential has been assessed, they add.
Antimalarial regimens requiring daily intake are associated with low compliance among short-term visitors to malarial areas, the authors say. They conclude: "At this stage, a three-day course of 250mg seems a reasonable dose regimen for chemoprophylaxis in a population such as that studied." If the required duration of protection is a few weeks, then tafenoquine has the potential to become the drug of choice, they say (Lancet 2000;355:2041).