Safety and Efficacy of Adding a Single Low Dose of Primaquine to the Treatment of Adult Patients With Plasmodium falciparum Malaria in Senegal, to Reduce Gametocyte Carriage: A Randomized Controlled Trial.

Tine RC1, Sylla K1, Faye BT1, Poirot E2, Fall FB3, Sow D1, Wang D4, Ndiaye M1, Ndiaye JL1, Faye B1, Greenwood B5, Gaye O1, Milligan P6.

Author information

1

Department of Medical Parasitology, Faculty of Medicine, University Cheikh Anta Diop, Dakar, Senegal.

2

Malaria Elimination Initiative, Global Health Group, University of California, San Francisco.

3

National Malaria Control Programme, Ministère de la Santé et de l'Action sociale, Dakar, Senegal.

4

Liverpool School of Tropical Medicine.

5

Faculty of Infectious and Tropical Diseases, and.

6

Faculty of Epidemiology and Public Health, London School of Hygiene and Tropical Medicine, London, United Kingdom.

Abstract

INTRODUCTION.:

More information is needed about the safety of low-dose primaquine in populations where G6PD deficiency is common.

METHODS.:

Adults with Plasmodium falciparum malaria were randomized to receive 1 of 3 artemisinin combination therapies (ACTs) with or without primaquine (0.25 mg/kg). Glucose-6-phosphate dehydrogenase (G6PD) status was determined using a rapid test. Patients were followed for 28 days to record hemoglobin concentration, adverse events, and gametocyte carriage. The primary end point was the change in Hb at day 7.

RESULTS.:

In sum, 274 patients were randomized, 139 received an ACT alone, and 135 received an ACT + primaquine. The mean reduction in Hb at day 7 was similar in each group, a difference in the ACT + PQ versus the ACT alone group of -0.04 g/dL (95% confidence interval [CI] -0.23, 0.31), but the effect of primaquine differed according to G6PD status. In G6PD-deficient patients the drop in Hb was 0.63 g/dL (95% CI 0.03, 1.24) greater in those who received primaquine than in those who received an ACT alone. In G6PD-normal patients, the reduction in Hb was 0.22 g/dL (95% CI -0.08, 0.52) less in those who received primaquine (interaction P = .01). One G6PD normal patient who received primaquine developed moderately severe anaemia (Hb < 8 g/dL). Dark urine was more frequent in patients who received primaquine. Primaquine was associated with a 73% (95% CI 24-90) reduction in gametocyte carriage (P = .013).

CONCLUSION.:

Primaquine substantially reduced gametocyte carriage. However, the fall in Hb concentration at day 7 was greater in G6PD-deficient patients who received primaquine than in those who did not and one patient who received primaquine developed moderately severe anemia.