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

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...

Descripción completa

Detalles Bibliográficos
Autores principales: 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
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2012
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3393623/
https://www.ncbi.nlm.nih.gov/pubmed/22546009
http://dx.doi.org/10.1186/1475-2875-11-139
_version_ 1782237737547464704
author 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
author_facet 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
author_sort Van Malderen, Carine
collection PubMed
description 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 frequently in children treated with CDA (56%) than in those treated with other ACT (29%), though the difference was not significant (p = 0.49). CONCLUSION: The use of CDA for treating uncomplicated malaria may increase the risk of haemolytic anaemia in G6PD-deficient children.
format Online
Article
Text
id pubmed-3393623
institution National Center for Biotechnology Information
language English
publishDate 2012
publisher BioMed Central
record_format MEDLINE/PubMed
spelling pubmed-33936232012-07-11 Glucose-6-phosphate dehydrogenase deficiency, chlorproguanil-dapsone with artesunate and post-treatment haemolysis in African children treated for uncomplicated malaria 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 Malar J Research 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 frequently in children treated with CDA (56%) than in those treated with other ACT (29%), though the difference was not significant (p = 0.49). CONCLUSION: The use of CDA for treating uncomplicated malaria may increase the risk of haemolytic anaemia in G6PD-deficient children. BioMed Central 2012-07-10 /pmc/articles/PMC3393623/ /pubmed/22546009 http://dx.doi.org/10.1186/1475-2875-11-139 Text en Copyright ©2012 Van Malderen et al.; licensee BioMed Central Ltd. http://creativecommons.org/licenses/by/2.0 This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Research
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
Glucose-6-phosphate dehydrogenase deficiency, chlorproguanil-dapsone with artesunate and post-treatment haemolysis in African children treated for uncomplicated malaria
title Glucose-6-phosphate dehydrogenase deficiency, chlorproguanil-dapsone with artesunate and post-treatment haemolysis in African children treated for uncomplicated malaria
title_full Glucose-6-phosphate dehydrogenase deficiency, chlorproguanil-dapsone with artesunate and post-treatment haemolysis in African children treated for uncomplicated malaria
title_fullStr Glucose-6-phosphate dehydrogenase deficiency, chlorproguanil-dapsone with artesunate and post-treatment haemolysis in African children treated for uncomplicated malaria
title_full_unstemmed Glucose-6-phosphate dehydrogenase deficiency, chlorproguanil-dapsone with artesunate and post-treatment haemolysis in African children treated for uncomplicated malaria
title_short Glucose-6-phosphate dehydrogenase deficiency, chlorproguanil-dapsone with artesunate and post-treatment haemolysis in African children treated for uncomplicated malaria
title_sort glucose-6-phosphate dehydrogenase deficiency, chlorproguanil-dapsone with artesunate and post-treatment haemolysis in african children treated for uncomplicated malaria
topic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3393623/
https://www.ncbi.nlm.nih.gov/pubmed/22546009
http://dx.doi.org/10.1186/1475-2875-11-139
work_keys_str_mv AT vanmalderencarine glucose6phosphatedehydrogenasedeficiencychlorproguanildapsonewithartesunateandposttreatmenthaemolysisinafricanchildrentreatedforuncomplicatedmalaria
AT vangeertruydenjeanpierre glucose6phosphatedehydrogenasedeficiencychlorproguanildapsonewithartesunateandposttreatmenthaemolysisinafricanchildrentreatedforuncomplicatedmalaria
AT machevosonia glucose6phosphatedehydrogenasedeficiencychlorproguanildapsonewithartesunateandposttreatmenthaemolysisinafricanchildrentreatedforuncomplicatedmalaria
AT gonzalezraquel glucose6phosphatedehydrogenasedeficiencychlorproguanildapsonewithartesunateandposttreatmenthaemolysisinafricanchildrentreatedforuncomplicatedmalaria
AT bassatquique glucose6phosphatedehydrogenasedeficiencychlorproguanildapsonewithartesunateandposttreatmenthaemolysisinafricanchildrentreatedforuncomplicatedmalaria
AT talisunaambrose glucose6phosphatedehydrogenasedeficiencychlorproguanildapsonewithartesunateandposttreatmenthaemolysisinafricanchildrentreatedforuncomplicatedmalaria
AT yekaadoke glucose6phosphatedehydrogenasedeficiencychlorproguanildapsonewithartesunateandposttreatmenthaemolysisinafricanchildrentreatedforuncomplicatedmalaria
AT nabasumbacarolyn glucose6phosphatedehydrogenasedeficiencychlorproguanildapsonewithartesunateandposttreatmenthaemolysisinafricanchildrentreatedforuncomplicatedmalaria
AT piolapatrice glucose6phosphatedehydrogenasedeficiencychlorproguanildapsonewithartesunateandposttreatmenthaemolysisinafricanchildrentreatedforuncomplicatedmalaria
AT danielatwine glucose6phosphatedehydrogenasedeficiencychlorproguanildapsonewithartesunateandposttreatmenthaemolysisinafricanchildrentreatedforuncomplicatedmalaria
AT turyakiraeleanor glucose6phosphatedehydrogenasedeficiencychlorproguanildapsonewithartesunateandposttreatmenthaemolysisinafricanchildrentreatedforuncomplicatedmalaria
AT forretpascale glucose6phosphatedehydrogenasedeficiencychlorproguanildapsonewithartesunateandposttreatmenthaemolysisinafricanchildrentreatedforuncomplicatedmalaria
AT vanovermeirchantal glucose6phosphatedehydrogenasedeficiencychlorproguanildapsonewithartesunateandposttreatmenthaemolysisinafricanchildrentreatedforuncomplicatedmalaria
AT vanloenharry glucose6phosphatedehydrogenasedeficiencychlorproguanildapsonewithartesunateandposttreatmenthaemolysisinafricanchildrentreatedforuncomplicatedmalaria
AT robertannie glucose6phosphatedehydrogenasedeficiencychlorproguanildapsonewithartesunateandposttreatmenthaemolysisinafricanchildrentreatedforuncomplicatedmalaria
AT dalessandroumberto glucose6phosphatedehydrogenasedeficiencychlorproguanildapsonewithartesunateandposttreatmenthaemolysisinafricanchildrentreatedforuncomplicatedmalaria