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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 chlorprogua...

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Autores principales: Fanello, Caterina I., Karema, Corine, Avellino, Pamela, Bancone, Germana, Uwimana, Aline, Lee, Sue J., d'Alessandro, Umberto, Modiano, David
Formato: Texto
Lenguaje:English
Publicado: Public Library of Science 2008
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2603295/
https://www.ncbi.nlm.nih.gov/pubmed/19112496
http://dx.doi.org/10.1371/journal.pone.0004031
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author Fanello, Caterina I.
Karema, Corine
Avellino, Pamela
Bancone, Germana
Uwimana, Aline
Lee, Sue J.
d'Alessandro, Umberto
Modiano, David
author_facet Fanello, Caterina I.
Karema, Corine
Avellino, Pamela
Bancone, Germana
Uwimana, Aline
Lee, Sue J.
d'Alessandro, Umberto
Modiano, David
author_sort Fanello, Caterina I.
collection PubMed
description 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 [1]. 702 children, treated with CD+A or AQ+SP and followed for 28 days after treatment were genotyped for G6PD A- deficiency. FINDINGS: 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. TRIAL REGISTRATION: ClinicalTrials.gov NCT00461578
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spelling pubmed-26032952008-12-29 High Risk of Severe Anaemia after Chlorproguanil-Dapsone+Artesunate Antimalarial Treatment in Patients with G6PD (A-) Deficiency Fanello, Caterina I. Karema, Corine Avellino, Pamela Bancone, Germana Uwimana, Aline Lee, Sue J. d'Alessandro, Umberto Modiano, David PLoS One Research Article 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 [1]. 702 children, treated with CD+A or AQ+SP and followed for 28 days after treatment were genotyped for G6PD A- deficiency. FINDINGS: 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. TRIAL REGISTRATION: ClinicalTrials.gov NCT00461578 Public Library of Science 2008-12-29 /pmc/articles/PMC2603295/ /pubmed/19112496 http://dx.doi.org/10.1371/journal.pone.0004031 Text en Fanello et al. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited.
spellingShingle Research Article
Fanello, Caterina I.
Karema, Corine
Avellino, Pamela
Bancone, Germana
Uwimana, Aline
Lee, Sue J.
d'Alessandro, Umberto
Modiano, David
High Risk of Severe Anaemia after Chlorproguanil-Dapsone+Artesunate Antimalarial Treatment in Patients with G6PD (A-) Deficiency
title High Risk of Severe Anaemia after Chlorproguanil-Dapsone+Artesunate Antimalarial Treatment in Patients with G6PD (A-) Deficiency
title_full High Risk of Severe Anaemia after Chlorproguanil-Dapsone+Artesunate Antimalarial Treatment in Patients with G6PD (A-) Deficiency
title_fullStr High Risk of Severe Anaemia after Chlorproguanil-Dapsone+Artesunate Antimalarial Treatment in Patients with G6PD (A-) Deficiency
title_full_unstemmed High Risk of Severe Anaemia after Chlorproguanil-Dapsone+Artesunate Antimalarial Treatment in Patients with G6PD (A-) Deficiency
title_short High Risk of Severe Anaemia after Chlorproguanil-Dapsone+Artesunate Antimalarial Treatment in Patients with G6PD (A-) Deficiency
title_sort high risk of severe anaemia after chlorproguanil-dapsone+artesunate antimalarial treatment in patients with g6pd (a-) deficiency
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2603295/
https://www.ncbi.nlm.nih.gov/pubmed/19112496
http://dx.doi.org/10.1371/journal.pone.0004031
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