High risk of severe anaemia after chlorproguanil-dapsone+artesunate antimalarial treatment in patients with G6PD (A-) deficiency.
BACKGROUND
Glucose-6-phosphate dehydrogenase (G6PD) deficiency is the most common inherited human enzyme defect. This deficiency provides some protection from clinical malaria, but it can also cause haemolysis after administration of drugs with oxidant properties.


METHODS
The safety of chlorproguanil-dapsone+artesunate (CD+A) and amodiaquine+sulphadoxine-pyrimethamine (AQ+SP) for the treatment of uncomplicated P. falciparum malaria was evaluated according to G6PD deficiency in a secondary analysis of an open-label, randomized clinical trial. 702 children, treated with CD+A or AQ+SP and followed for 28 days after treatment were genotyped for G6PD A- deficiency.


RESULTS
In the first 4 days following CD+A treatment, mean haematocrit declined on average 1.94% (95% CI 1.54 to 2.33) and 1.05% per day (95% CI 0.95 to 1.15) respectively in patients with G6PD deficiency and normal patients; a mean reduction of 1.3% per day was observed among patients who received AQ+SP regardless of G6PD status (95% CI 1.25 to 1.45). Patients with G6PD deficiency recipients of CD+A had significantly lower haematocrit than the other groups until day 7 (p = 0.04). In total, 10 patients had severe post-treatment haemolysis requiring blood transfusion. Patients with G6PD deficiency showed a higher risk of severe anaemia following treatment with CD+A (RR = 10.2; 95% CI 1.8 to 59.3) or AQ+SP (RR = 5.6; 95% CI 1.0 to 32.7).


CONCLUSIONS
CD+A showed a poor safety profile in individuals with G6PD deficiency most likely as a result of dapsone induced haemolysis. Screening for G6PD deficiency before drug administration of potentially pro-oxidants drugs, like dapsone-containing combinations, although seldom available, is necessary.
Fanello
Caterina I
CI
Centre for Vaccinology and Tropical Medicine, Nuffield Department of Medicine, Oxford University, Oxford, United Kingdom. Caterina.Fanello@ndm.ox.ac.uk
Karema
Corine
C
Avellino
Pamela
P
Bancone
Germana
G
Uwimana
Aline
A
Lee
Sue J
SJ
d'Alessandro
Umberto
U
Modiano
David
D
D000655:Amodiaquine / Q000008:administration & dosage; D000962:Antimalarials / Q000008:administration & dosage*; D037621:Artemisinins / Q000008:administration & dosage*; D000077332:Artesunate; D002648:Child; D002675:Child, Preschool; D003622:Dapsone / Q000008:administration & dosage*; D004338:Drug Combinations; D004359:Drug Therapy, Combination; D005260:Female; D005955:Glucosephosphate Dehydrogenase Deficiency / Q000188:drug therapy* / Q000235:genetics*; D006801:Humans; D007223:Infant; D016778:Malaria, Falciparum / Q000188:drug therapy*; D008297:Male; D016877:Oxidants / Q000009:adverse effects; D011110:Polymorphism, Genetic; D002727:Proguanil / Q000008:administration & dosage / Q000031:analogs & derivatives*; D011739:Pyrimethamine / Q000008:administration & dosage; D013413:Sulfadoxine / Q000008:administration & dosage
D000962:Antimalarials; D037621:Artemisinins; D004338:Drug Combinations; D016877:Oxidants; D000655:Amodiaquine; C001205:fanasil, pyrimethamine drug combination; D000077332:Artesunate; D013413:Sulfadoxine; C007030:chlorproguanil; D003622:Dapsone; D002727:Proguanil; D011739:Pyrimethamine