Randomised Placebo-controlled Trial of Primaquine for Prophylaxis of Falciparum and Vivax Malaria

Drug resistance has made malaria prevention difficult and the new agents are too expensive for widespread use. Primaquine, an established drug for treatment, is potentially useful for prevention. Malaria prophylaxis with primaquine was evaluated in Irian Jaya during one year in Javanese men who were not deficient in glucose-6-phosphate dehydrogenase (G-6-PD). 126 volunteers were randomised to receive 0.5 mg/kg primaquine base or placebo daily (double-blinded), or 300 mg chloroquine base weekly (open). The protective efficacy of primaquine relative to placebo was 94.5% (95% confidence interval 57-99) for Plasmodium falciparum and 90.4% (95% CI 58-98) for P vivax. Attack rates for either parasite did not differ significantly between the chloroquine and placebo groups. Incidence density of physical complaints not associated with parasitaemia was low (17-18 complaints/person-year) and was about the same in all groups except for cough, which was increased in the primaquine group. Complete blood counts were normal and no evidence of hepatic or renal dysfunction was found with primaquine. However, at 50 weeks the primaquine group had a mean methaemoglobin of 5.8% (range 1.4-13%), which declined by half within 7 days of ending prophylaxis. When used daily for one year by men with normal G-6-PD activity, primaquine was well tolerated and effective for prevention of malaria.