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

Malaria Journal

Research

Sonia Machevo¹  Quique Bassat²  Raquel González²  Adoke Yeka³  Ambrose Talisuna⁴  Atwine Daniel⁵  Carolyn Nabasumba⁵  Patrice Piola⁵  Eleanor Turyakira⁵  Carine Van Malderen⁶  Chantal Van Overmeir⁷  Umberto D’ Alessandro⁷  Harry Van Loen⁷  Pascale Forret⁷  Jean-Pierre Van Geertruyden⁸  Annie Robert⁹ 

[1] Centro de Investigação em Saúde da Manhiça (CISM), Maputo, Mozambique;Centro de Investigação em Saúde da Manhiça (CISM), Maputo, Mozambique;Barcelona Centre for International Health Research (CRESIB), Hospital Clínic-Universitat de Barcelona, Barcelona, Spain;Department of Epidemiology and Biostatistics, Makerere University School of Public Health, P.O Box 7072, Kampala, Uganda;Department of Epidemiology and Biostatistics, Makerere University School of Public Health, P.O Box 7072, Kampala, Uganda;Malaria Public Health and Epidemiology Group (MPHEG), University of Oxford-KEMRI-Wellcome Trust Research Program, Nairobi, Kenya;Epicentre Mbarara Research Base, Mbarara, Uganda;Faculté de pharmacie et des sciences biomédicales, Université catholique de Louvain, Brussels, Belgium;Institute of Tropical Medicine, Antwerp, Belgium;Institute of Tropical Medicine, Antwerp, Belgium;International Health Unit, University of Antwerp, Antwerp, Belgium;Université catholique de Louvain. Brussels Health Sector – Institut de recherche expérimentale et clinique Pôle, Epidémiologie et biostatistique B1.30.13, Brussels, Belgium;

关键词: Malaria;    Artemisinin-based combination therapy;    Chlorproguanil-dapsone;    Artesunate;    Glucose-6-phosphate dehydrogenase deficiency;    Uganda;    Mozambique;    Restriction fragment length polymorphisms;    Conditional logistic regression;   

DOI  :  10.1186/1475-2875-11-139

 received in 2012-01-17, accepted in 2012-04-30,  发布年份 2012

来源: Springer

【 摘 要 】

BackgroundMalaria 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.MethodsThis 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.ResultsG6PD 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 frequently in children treated with CDA (56%) than in those treated with other ACT (29%), though the difference was not significant (p = 0.49).ConclusionThe use of CDA for treating uncomplicated malaria may increase the risk of haemolytic anaemia in G6PD-deficient children.

【 授权许可】

CC BY   
© Van Malderen et al.; licensee BioMed Central Ltd. 2012