Modelling primaquine-induced haemolysis in G6PD deficiency.
Primaquine is the only drug available to prevent relapse in vivax malaria. The main adverse effect of primaquine is erythrocyte age and dose-dependent acute haemolytic anaemia in individuals with glucose-6-phosphate dehydrogenase deficiency (G6PDd). As testing for G6PDd is often unavailable, this limits the use of primaquine for radical cure. A compartmental model of the dynamics of red blood cell production and destruction was designed to characterise primaquine-induced haemolysis using a holistic Bayesian analysis of all published data and was used to predict a safer alternative to the currently recommended once weekly 0.75 mg/kg regimen for G6PDd. The model suggests that a step-wise increase in daily administered primaquine dose would be relatively safe in G6PDd. If this is confirmed, then were this regimen to be recommended for radical cure patients would not require testing for G6PDd in areas where G6PDd Viangchan or milder variants are prevalent.
Mahidol Oxford Tropical Medicine Research Unit, Faculty of Tropical Medicine, Mahidol University, Bangkok, Thailand.|Centre for Tropical Medicine and Global Health, Nuffield Department of Medicine, University of Oxford, Oxford, United Kingdom.
James
0000-0001-5524-0325
J
Watson
Mahidol Oxford Tropical Medicine Research Unit, Faculty of Tropical Medicine, Mahidol University, Bangkok, Thailand.|Centre for Tropical Medicine and Global Health, Nuffield Department of Medicine, University of Oxford, Oxford, United Kingdom.
Walter Rj
WR
Taylor
Unité d'Epidémiologie Moléculaire du Paludisme, Institut Pasteur du Cambodge, Phnom Penh, Cambodia.
Didier
0000-0003-1357-4495
D
Menard
National Center for Parasitology, Entomology and Malaria Control, Phnom Penh, Cambodia.
Sim
S
Kheng
Mahidol Oxford Tropical Medicine Research Unit, Faculty of Tropical Medicine, Mahidol University, Bangkok, Thailand.|Centre for Tropical Medicine and Global Health, Nuffield Department of Medicine, University of Oxford, Oxford, United Kingdom.
Nicholas J
0000-0002-1897-1978
NJ
White
D000743:Anemia, Hemolytic / Q000139:chemically induced / Q000175:diagnosis / Q000517:prevention & control*; D000962:Antimalarials / Q000008:administration & dosage / Q000009:adverse effects*; D001499:Bayes Theorem; D016923:Cell Death / Q000187:drug effects; D004912:Erythrocytes / Q000187:drug effects; D005260:Female; D005955:Glucosephosphate Dehydrogenase Deficiency / Q000150:complications / Q000188:drug therapy* / Q000469:parasitology / Q000473:pathology; D006461:Hemolysis / Q000187:drug effects; D006801:Humans; D016780:Malaria, Vivax / Q000150:complications / Q000188:drug therapy* / Q000469:parasitology / Q000473:pathology; D008297:Male; D015233:Models, Statistical; D010966:Plasmodium vivax / Q000187:drug effects / Q000254:growth & development; D011319:Primaquine / Q000008:administration & dosage / Q000009:adverse effects*; D012008:Recurrence
D000962:Antimalarials; D011319:Primaquine
G6PD deficiency; computational biology; epidemiology; global health; human; in silico modelling; primaquine; radical cure; systems biology