Safety of single low-dose primaquine in glucose-6-phosphate dehydrogenase deficient falciparum-infected African males: Two open-label, randomized, safety trials.
Safety of single low-dose primaquine in glucose-6-phosphate dehydrogenase deficient falciparum-infected African males: Two open-label, randomized, safety trials.
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DOI：
10.1371/journal.pone.0190272
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发表时间：
2018
期刊：
影响因子：
3.7
通讯作者：
Drakeley C
中科院分区：
文献类型：
--
作者：
Bastiaens GJH;Tiono AB;Okebe J;Pett HE;Coulibaly SA;Gonçalves BP;Affara M;Ouédraogo A;Bougouma EC;Sanou GS;Nébié I;Bradley J;Lanke KHW;Niemi M;Sirima SB;d'Alessandro U;Bousema T;Drakeley C
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. 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. 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. Clinicaltrials.gov NCT02174900 Clinicaltrials.gov NCT02654730
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DOI：
10.1038/ejhg.2009.8
发表时间：
2009-08
期刊：
European journal of human genetics : EJHG
影响因子：
--
作者：
通讯作者：
--
影响因子：
4.3
作者：
Johnston GL;Gething PW;Hay SI;Smith DL;Fidock DA
通讯作者：
Fidock DA
影响因子：
4.9
作者：
Eziefula, Alice C.;Pett, Helmi;Drakeley, Chris
通讯作者：
Drakeley, Chris
影响因子：
6.7
作者：
Gaedigk, A.;Simon, S. D.;Leeder, J. S.
通讯作者：
Leeder, J. S.
影响因子：
15.8
作者：
malERA Consultative Group on Vaccines
通讯作者：
malERA Consultative Group on Vaccines