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

Autor: Bastiaens GJH; Department of Medical Microbiology, Radboud University Medical Center, Nijmegen, the Netherlands., Tiono AB; Department of Biomedical Sciences, Centre National de Recherche et de Formation sur le Paludisme, Ouagadougou, Burkina Faso., Okebe J; Disease Control & Elimination Theme, Medical Research Council Unit, Fajara, The Gambia., Pett HE; Department of Medical Microbiology, Radboud University Medical Center, Nijmegen, the Netherlands.; Department of Clinical Pharmacology, University of Helsinki and Helsinki University Hospital, Helsinki, Finland., Coulibaly SA; Department of Biomedical Sciences, Centre National de Recherche et de Formation sur le Paludisme, Ouagadougou, Burkina Faso., Gonçalves BP; Department of Immunology and Infection, London School of Hygiene and Tropical Medicine, London, United Kingdom., Affara M; Disease Control & Elimination Theme, Medical Research Council Unit, Fajara, The Gambia., Ouédraogo A; Department of Biomedical Sciences, Centre National de Recherche et de Formation sur le Paludisme, Ouagadougou, Burkina Faso., Bougouma EC; Department of Biomedical Sciences, Centre National de Recherche et de Formation sur le Paludisme, Ouagadougou, Burkina Faso., Sanou GS; Department of Biomedical Sciences, Centre National de Recherche et de Formation sur le Paludisme, Ouagadougou, Burkina Faso., Nébié I; Department of Biomedical Sciences, Centre National de Recherche et de Formation sur le Paludisme, Ouagadougou, Burkina Faso., Bradley J; MRC Tropical Epidemiology Group, London School of Hygiene & Tropical Medicine, London, United Kingdom., Lanke KHW; Department of Medical Microbiology, Radboud University Medical Center, Nijmegen, the Netherlands., Niemi M; Department of Clinical Pharmacology, University of Helsinki and Helsinki University Hospital, Helsinki, Finland., Sirima SB; Department of Biomedical Sciences, Centre National de Recherche et de Formation sur le Paludisme, Ouagadougou, Burkina Faso., d'Alessandro U; Disease Control & Elimination Theme, Medical Research Council Unit, Fajara, The Gambia.; Department of Disease Control, Faculty of infectious and Tropical Diseases, London School of Hygiene and Tropical Medicine, London, United Kingdom., Bousema T; Department of Medical Microbiology, Radboud University Medical Center, Nijmegen, the Netherlands.; Department of Immunology and Infection, London School of Hygiene and Tropical Medicine, London, United Kingdom., Drakeley C; Department of Immunology and Infection, London School of Hygiene and Tropical Medicine, London, United Kingdom.
Jazyk: angličtina
Zdroj: PloS one [PLoS One] 2018 Jan 11; Vol. 13 (1), pp. e0190272. Date of Electronic Publication: 2018 Jan 11 (Print Publication: 2018).
DOI: 10.1371/journal.pone.0190272
Abstrakt: 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.
Trial Registration: Clinicaltrials.gov NCT02174900 Clinicaltrials.gov NCT02654730.
Databáze: MEDLINE
Externí odkaz:
Nepřihlášeným uživatelům se plný text nezobrazuje