Glucose-6-phosphate dehydrogenase deficiency, chlorproguanil-dapsone with artesunate and post-treatment haemolysis in African children treated for uncomplicated malaria

• Published in: Malaria Journal
• Main Authors: Van Malderen Carine, Van Geertruyden Jean-Pierre, Machevo Sonia, González Raquel, Bassat Quique, Talisuna Ambrose, Yeka Adoke, Nabasumba Carolyn, Piola Patrice, Daniel Atwine, Turyakira Eleanor, Forret Pascale, Van Overmeir Chantal, Van Loen Harry, Robert Annie, D’ Alessandro Umberto
• Format: Article in Journal/Newspaper
• Language: English
• Published: BMC 2012
• Subjects: Malaria; Artemisinin-based combination therapy; Chlorproguanil-dapsone; Artesunate; Glucose-6-phosphate dehydrogenase deficiency; Uganda; Mozambique; Restriction fragment length polymorphisms; Conditional logistic regression; Arctic medicine. Tropical medicine; RC955-962; Infectious and parasitic diseases; RC109-216; Arctic
• Online Access: https://doi.org/10.1186/1475-2875-11-139; https://doaj.org/article/77d4505f1dbe411e809c6ce54ded1448

Abstract Background Malaria is a leading cause of mortality, particularly in sub-Saharan African children. Prompt and efficacious treatment is important as patients may progress within a few hours to severe and possibly fatal disease. Chlorproguanil-dapsone-artesunate (CDA) was a promising artemisinin-based combination therapy (ACT), but its development was prematurely stopped because of safety concerns secondary to its associated risk of haemolytic anaemia in glucose-6-phosphate dehydrogenase (G6PD)-deficient individuals. The objective of the study was to assess whether CDA treatment and G6PD deficiency are risk factors for a post-treatment haemoglobin drop in African children <5 years of age with uncomplicated malaria. Methods This case–control study was performed in the context of a larger multicentre randomized clinical trial comparing safety and efficacy of four different ACT in children with uncomplicated malaria. Children, who after treatment experienced a haemoglobin drop ≥2 g/dl (cases) within the first four days (days 0, 1, 2, and 3), were compared with those without an Hb drop (controls). Cases and controls were matched for study site, sex, age and baseline haemoglobin measurements. Data were analysed using a conditional logistic regression model. Results G6PD deficiency prevalence, homo- or hemizygous, was 8.5% (10/117) in cases and 6.8% (16/234) in controls (p = 0.56). The risk of a Hb drop ≥2 g/dl was not associated with either G6PD deficiency (adjusted odds ratio (AOR): 0.81; p = 0.76) or CDA treatment (AOR: 1.28; p = 0.37) alone. However, patients having both risk factors tended to have higher odds (AOR: 11.13; p = 0.25) of experiencing a Hb drop ≥2 g/dl within the first four days after treatment, however this finding was not statistically significant, mainly because G6PD deficient patients treated with CDA were very few. In non-G6PD deficient individuals, the proportion of cases was similar between treatment groups while in G6PD-deficient individuals, haemolytic anaemia occurred more ...