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

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% ( 129 250 ) of the non-primaquine group recorded a 2nd clinical-parasitaemic episode and 23% recorded a 3rd, whereas 51% ( 128 250 ) of the 5-days primaquine group reported a 2nd episode and 21% recorded a 3rd. During the second trial 49% ( 49 100 ) of the non-primaquine group recorded a 2nd episode and 25% recorded a 3rd, whereas only 32% ( 32 100 ) 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.