A Randomised Open Label Study Comparing the Efficacy of Chloroquine/Primaquine, Chloroquine and Artesunate in the Treatment of Vivax Malaria Along the Thai-Burmese Border

Considerably less attention has been paid to Plasmodium vivax epidemiology than Plasmodium falciparum. In areas of relatively low unstable transmission, which comprise the majority of P.vivax affected areas, vivax malaria is predominantly a disease of children (Luxemburger et al 1999). Chloroquine has long been the standard treatment for vivax malaria. Primaquine is recommended for radical cure of vivax malaria, but is difficult to administer due to dosing duration and side effects.

This study aims to characterize the epidemiologic history comparing the efficacy of 3 antimalarial regimens (chloroquine, artesunate, and chloroquine/primaquine) for plasmodium vivax in western Thailand. Chloroquine is currently the standard of treatment for Plasmodium vivax. Due to the long half-life or chloroquine, the first relapse of vivax malaria may be delayed. In contrast, artesunate has a very short half-life, thus, having no impact on first relapse. It is not known whether chloroquine reduces the overall number of relapses, or only delays the first relapse. There are many important questions about the biology of vivax malaria of relevance to treatment that remain unanswered. For example is the number of relapses per infection (i.e. per successful inoculation) predetermined or adaptive? If it is predetermined then suppression of the first relapse (as with chloroquine, mefloquine or piperaquine) will reduce the total number of relapses and this is a clear benefit. If it is adaptive then these drugs will simply delay the relapses and there is less clear benefit. These various uncertainties illustrate the importance of detailed comparative longitudinal evaluations. In order to characterize the biology of vivax malaria, it will be necessary to compare regimens with and without primaquine. Because of the challenges that face primaquine prescription (side effects, toxicity in G6PD deficient patients and duration of treatment), it is not commonly deployed along the Thai Burma border. In effect, we will be comparing usual practice (non primaquine regimens) with the recommended WHO and Thai MOPH practice (use of primaquine for 14 days). The information we will gather is crucial to the understanding of chloroquine and its effect on the vivax parasite. This will lead to future studies and invariably change the way we treat vivax malaria.