Randomized controlled trials of 5- and 14-days primaquine therapy against relapses of vivax malaria in an Afghan refugee settlement in Pakistan.

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Abstract
Primaquine is the only drag available that can eliminate hypnoxoites from the liver and prevent relapses of vivax malaria. The World Health Organization recommends a course of 14–21 days depending on region and strain. The National Malaria Control and Eradication Programmes of Pakistan and India have adhered to a 5-day course as their standard as it is deemed more practical to implement and because facility for detecting glucose 6-phosphate dehydrogenase (G6PD) deficiency is seldom available at the periphery. Evidence for the efficacy of the 5-day regimen is controversial or lacking. Two, year-long, randomized controlled trials were undertaken in an Afghan refugee camp in north-western Pakistan using a process of passive case detection and treatment at the camp's clinic: the first trial compared treatment with chloroquine alone versus chloroquine plus 5-days primaquine, the second trial compared chloroquine alone versus chloroquine plus 14-days primaquine. Chloroquine is not hypnozoitocidal and was administered to eliminate the erythrocytic stages and to alleviate clinical symptoms. The daily primaquine dose was 0·25 mg/kg bodyweight and the total chloroquine dose was 25 mg/kg over 3 days. During the first trial 52% () of the non-primaquine group recorded a 2nd clinical-parasitaemic episode and 23% recorded a 3rd, whereas 51% () of the 5-days primaquine group reported a 2nd episode and 21% recorded a 3rd. During the second trial 49% () of the non-primaquine group recorded a 2nd episode and 25% recorded a 3rd, whereas only 32% () of the 14-days primaquine group recorded a 2nd and only 2% recorded a 3rd. The 5-days primaquine regimen has no value as an anti-relapse therapy and should be abandoned. In extended tests in vivo in which vivax cases (n = 3) were treated with chloroquine 25 mg/kg and 14-days primaquine, there was no parasite recrudescence within 28 days and hence no evidence of resistance to chloroquine.

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