Safety of single low-dose primaquine in glucose-6-phosphate dehydrogenase deficient falciparum-infected African males : Two open-label, randomized, safety trials

Show full item record



Permalink

http://hdl.handle.net/10138/233433

Citation

Bastiaens , G J H , Tiono , A B , Okebe , J , Pett , H E , Coulibaly , S A , Goncalves , B P , Affara , M , Ouedraogo , A , Bougouma , E C , Sanou , G S , Nebie , I , Bradley , J , Lanke , K H W , Niemi , M , Sirima , S B , d'Alessandro , U , Bousema , T & Drakeley , C 2018 , ' Safety of single low-dose primaquine in glucose-6-phosphate dehydrogenase deficient falciparum-infected African males : Two open-label, randomized, safety trials ' , PLoS One , vol. 13 , no. 1 , 0190272 . https://doi.org/10.1371/journal.pone.0190272

Title: Safety of single low-dose primaquine in glucose-6-phosphate dehydrogenase deficient falciparum-infected African males : Two open-label, randomized, safety trials
Author: Bastiaens, Guido J. H.; Tiono, Alfred B.; Okebe, Joseph; Pett, Helmi E.; Coulibaly, Sam A.; Goncalves, Bronner P.; Affara, Muna; Ouedraogo, Alphonse; Bougouma, Edith C.; Sanou, Guillaume S.; Nebie, Issa; Bradley, John; Lanke, Kjerstin H. W.; Niemi, Mikko; Sirima, Sodiomon B.; d'Alessandro, Umberto; Bousema, Teun; Drakeley, Chris
Other contributor: University of Helsinki, Clinicum
University of Helsinki, Medicum




Date: 2018-01-11
Language: eng
Number of pages: 20
Belongs to series: PLoS One
ISSN: 1932-6203
DOI: https://doi.org/10.1371/journal.pone.0190272
URI: http://hdl.handle.net/10138/233433
Abstract: Background 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.
Subject: REDUCE GAMETOCYTE CARRIAGE
PLASMODIUM-VIVAX MALARIA
ARTEMETHER-LUMEFANTRINE
DIHYDROARTEMISININ-PIPERAQUINE
DRUG DEVELOPMENT
G6PD DEFICIENCY
DOUBLE-BLIND
CYP 2D6
TRANSMISSION
CHILDREN
3111 Biomedicine
3121 General medicine, internal medicine and other clinical medicine
Rights:


Files in this item

Total number of downloads: Loading...

Files Size Format View
journal.pone.0190272.pdf 3.014Mb PDF View/Open

This item appears in the following Collection(s)

Show full item record