title: 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 drug available that can eliminate hypnozoites 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 = 31) 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.
authors.affiliation: HealthNet International, University Town, Peshawar, Pakistan. m.rowland@lshtm.ac.uk
authors.forename: M
authors.initials: M
authors.lastname: Rowland
authors.forename: N
authors.initials: N
authors.lastname: Durrani
mesh_terms: D000293:Adolescent; D000346:Afghanistan / Q000208:ethnology; D000962:Antimalarials / Q000008:administration & dosage*; D002648:Child; D005260:Female; D006801:Humans; D016780:Malaria, Vivax / Q000188:drug therapy* / Q000208:ethnology; D008297:Male; D010154:Pakistan; D011319:Primaquine / Q000008:administration & dosage*; D012008:Recurrence; D012036:Refugees
chemical_list: D000962:Antimalarials; D011319:Primaquine