Data from: Safety of single low-dose primaquine in glucose-6-phosphate dehydrogenase deficient falciparum-infected African males: two open-label, randomized, safety trials
Primaquine (PQ) actively clears mature Plasmodium falciparum gametocytes but in glucose-6-phosphate dehydrogenase deficient (G6PDd) individuals can cause hemolysis. We assessed the safety of low-dose PQ in combination with artemether-lumefantrine (AL) or dihydroartemisinin-piperaquine (DP) in G6PDd African males with asymptomatic P. falciparum malaria. Methods and findings: In Burkina Faso, G6PDd adult males were randomized to treatment with AL alone (n = 10) or with PQ at 0.25 (n = 20) or 0.40 mg/kg (n = 20) dosage; G6PD-normal males received AL plus 0.25 (n = 10) or 0.40 mg/kg (n = 10) PQ. In The Gambia, G6PDd adult males and boys received DP alone (n = 10) or with 0.25 mg/kg PQ (n = 20); G6PD-normal males received DP plus 0.25 (n = 10) or 0.40 mg/kg (n = 10) PQ. The primary study endpoint was change in hemoglobin concentration during the 28-day follow-up. Cytochrome P-450 isoenzyme 2D6 (CYP2D6) metabolizer status, gametocyte carriage, haptoglobin, lactate dehydrogenase levels and reticulocyte counts were also determined. In Burkina Faso, the mean maximum absolute change in hemoglobin was -2.13 g/dL (95% confidence interval [CI], -2.78, -1.49) in G6PDd individuals randomized to 0.25 PQ mg/kg and -2.29 g/dL (95% CI, -2.79, -1.79) in those receiving 0.40 PQ mg/kg. In The Gambia, the mean maximum absolute change in hemoglobin concentration was -1.83 g/dL (95% CI, -2.19, -1.47) in G6PDd individuals receiving 0.25 PQ mg/kg. After adjustment for baseline concentrations, hemoglobin reductions in G6PDd individuals in Burkina Faso were more pronounced compared to those in G6PD-normal individuals receiving the same PQ doses (P = 0.062 and P = 0.022, respectively). Hemoglobin levels normalized during follow-up. Abnormal haptoglobin and lactate dehydrogenase levels provided additional evidence of mild transient hemolysis post-PQ. Conclusions: Single low-dose PQ in combination with AL and DP was associated with mild and transient reductions in hemoglobin. None of the study participants developed moderate or severe anemia; there were no severe adverse events. This indicates that single low-dose PQ is safe in G6PDd African males when used with artemisinin-based combination therapy.
Keywords
Plasmodium falciparum, Haemoglobin, Primaquine, Haemolysis, Safety, Gametocyte, Reticulocytes, MalariaItem Type | Dataset |
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Capture method | Unknown |
Date | 18 December 2018 |
Language(s) of written materials | English |
Creator(s) |
Bastiaens, GJH, Tiono, AB, Okebe, J, Pett, HE, Coulibaly, SA, Gonçalves, BP, Affara, M, Ouédraogo, A, Bougouma, EC, Sanou, GS, Nébié, I, Bradley, J |
LSHTM Faculty/Department | Faculty of Epidemiology and Population Health > Dept of Infectious Disease Epidemiology (-2023) |
Participating Institutions | London School of Hygiene & Tropical Medicine, London, United Kingdom |
Funders |
Project Funder Grant Number Funder URI |
Date Deposited | 10 Oct 2019 11:21 |
Last Modified | 17 Mar 2022 16:12 |
Publisher | Dryad |