Chloroquine-Primaquine versus Chloroquine Alone to Treat Vivax Malaria in Afghanistan: An Open Randomized Superiority Trial.

Ghulam Rahim Awab,Mallika Imwong,Nicholas J White,Nicholas P J Day,Germana Bancone,Charles J Woodrow,Atthanee Jeeyapant

doi:10.4269/ajtmh.17-0290

Abstract

.Afghanistan’s national guidelines recommend primaquine (PQ) for radical treatment of Plasmodium vivax malaria, but this is rarely implemented because of concerns over potential hemolysis in patients who have G6PD deficiency. Between August 2009 and February 2014, we conducted an open-label, randomized controlled trial of chloroquine (CQ) alone versus chloroquine plus primaquine (0.25 mg base/kg/day for 14 days) (CQ+PQ) in patients aged 6 months and older with microscopy confirmed P. vivax infection. In the CQ+PQ group, G6PD deficiency was excluded by fluorescent spot testing. The primary outcome was P. vivax recurrence assessed by survival analysis over one year follow-up. Of 593 patients enrolled, 570 attended at or after 14 days of follow-up. Plasmodium vivax recurrences occurred in 37 (13.1%) of 282 patients in the CQ+PQ arm versus 86 (29.9%) of 288 in the CQ arm (Cox proportional hazard ratio [HR] 0.37, 95% confidence interval [CI] 0.25–0.54) (intention-to-treat analysis). Protection against recurrence was greater in the first 6 months of follow-up (HR 0.082; 95% CI 0.029–0.23) than later (HR 0.65, 95% CI 0.41–1.03). Five of seven patients requiring hospital admission were considered possible cases of PQ-related hemolysis, and PQ was stopped in a further six; however, in none of these cases did hemoglobin fall by ≥ 2 g/dL or to below 7 g/dL, and genotyping did not detect any cases of Mediterranean variant G6PD deficiency. PQ 0.25 mg/kg/day for 14 days prevents relapse of P. vivax in Afghanistan. Patient visits during the first week may improve adherence. Implementation will require deployment of point-of-care phenotypic tests for G6PD deficiency.

Highlights

Malaria remains a significant problem in Afghanistan where cases are caused by Plasmodium vivax.[1,2]
Trials of primaquine (PQ), the only widely available radical therapy, in Afghan refugees living in Pakistan documented good efficacy for PQ 0.25 or 0.5 mg/kg/day given over 14 days[4,5] or 0.75 mg/kg/week for 8 weeks,[5] compared with a 5-day PQ regimen.[6]
In Afghanistan, malaria is confined to the northern plains, the Jalalabad basin, and valleys fringing the central mountains to the west and south.[10,11]

Summary

Introduction

Malaria remains a significant problem in Afghanistan where cases are caused by Plasmodium vivax.[1,2] Limited resources and security challenges hamper control efforts.[2] Control of vivax malaria is challenging because the dormant liver stages cause multiple relapses providing a source for new transmission.[3] Trials of primaquine (PQ), the only widely available radical therapy, in Afghan refugees living in Pakistan documented good efficacy for PQ 0.25 or 0.5 mg/kg/day given over 14 days[4,5] or 0.75 mg/kg/week for 8 weeks,[5] compared with a 5-day PQ regimen.[6] adherence to the 14-day treatment course is a concern, efficacy was preserved with an unsupervised regimen accompanied by appropriate instructions.[4]. The national treatment policy for vivax malaria in Afghanistan is chloroquine (CQ) plus 0.25 mg/kg/day PQ for 14 days. PQ causes hemolysis in individuals with G6PD deficiency, a common red cell enzyme deficiency in malaria endemic regions.[7,8,9] G6PD phenotypic tests are generally unavailable in Afghanistan as in many other tropical regions. Administration of PQ according to the national guideline is rarely undertaken

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Conclusion