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.

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.

Clinical Trial registration:

PACTR201411000937373 (www.pactr.org).

• Authors: Roger C Tine, Khadime Sylla, Babacar T Faye, Eugenie Poirot, Fatou B Fall, Doudou Sow, Duolao Wang, Magatte Ndiaye, Jean Louis Ndiaye, Babacar Faye, Brian Greenwood, Oumar Gaye, Paul Milligan
• Journal: Clinical infectious diseases : an official publication of the Infectious Diseases Society of America (Clin Infect Dis) Vol. 65 Issue 4 Pg. 535-543 (08 15 2017) ISSN: 1537-6591 [Electronic] United States
• PMID: 28605472 (Publication Type: Journal Article, Randomized Controlled Trial)
• Copyright: © The Author 2017. Published by Oxford University Press for the Infectious Diseases Society of America.

Chemical References

• Antimalarials
• Hemoglobins
• Primaquine

Topics

• Adolescent
• Adult
• Aged
• Antimalarials (administration & dosage, adverse effects, therapeutic use)
• Female
• Hemoglobins
• Humans
• Malaria, Falciparum (blood, drug therapy, parasitology, physiopathology)
• Male
• Middle Aged
• Parasitemia
• Plasmodium falciparum
• Primaquine (administration & dosage, adverse effects, therapeutic use)
• Senegal
• Young Adult