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Risk of pneumococcal bacteremia in Kenyan children with glucose-6-phosphate dehydrogenase deficiency

BACKGROUND: Glucose-6-phosphate dehydrogenase (G6PD) deficiency is the most common enzyme deficiency state in humans. The clinical phenotype is variable and includes asymptomatic individuals, episodic hemolysis induced by oxidative stress, and chronic hemolysis. G6PD deficiency is common in malaria-...

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Autores principales: Gilchrist, James J., Uyoga, Sophie, Pirinen, Matti, Rautanen, Anna, Mwarumba, Salim, Njuguna, Patricia, Mturi, Neema, Hill, Adrian V. S., Scott, J. Anthony G., Williams, Thomas N.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7294654/
https://www.ncbi.nlm.nih.gov/pubmed/32536341
http://dx.doi.org/10.1186/s12916-020-01604-y
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author Gilchrist, James J.
Uyoga, Sophie
Pirinen, Matti
Rautanen, Anna
Mwarumba, Salim
Njuguna, Patricia
Mturi, Neema
Hill, Adrian V. S.
Scott, J. Anthony G.
Williams, Thomas N.
author_facet Gilchrist, James J.
Uyoga, Sophie
Pirinen, Matti
Rautanen, Anna
Mwarumba, Salim
Njuguna, Patricia
Mturi, Neema
Hill, Adrian V. S.
Scott, J. Anthony G.
Williams, Thomas N.
author_sort Gilchrist, James J.
collection PubMed
description BACKGROUND: Glucose-6-phosphate dehydrogenase (G6PD) deficiency is the most common enzyme deficiency state in humans. The clinical phenotype is variable and includes asymptomatic individuals, episodic hemolysis induced by oxidative stress, and chronic hemolysis. G6PD deficiency is common in malaria-endemic regions, an observation hypothesized to be due to balancing selection at the G6PD locus driven by malaria. G6PD deficiency increases risk of severe malarial anemia, a key determinant of invasive bacterial disease in malaria-endemic settings. The pneumococcus is a leading cause of invasive bacterial infection and death in African children. The effect of G6PD deficiency on risk of pneumococcal disease is undefined. We hypothesized that G6PD deficiency increases pneumococcal disease risk and that this effect is dependent upon malaria. METHODS: We performed a genetic case-control study of pneumococcal bacteremia in Kenyan children stratified across a period of falling malaria transmission between 1998 and 2010. RESULTS: Four hundred twenty-nine Kenyan children with pneumococcal bacteremia and 2677 control children were included in the study. Among control children, G6PD deficiency, secondary to the rs1050828 G>A mutation, was common, with 11.2% (n = 301 of 2677) being hemi- or homozygotes and 33.3% (n = 442 of 1329) of girls being heterozygotes. We found that G6PD deficiency increased the risk of pneumococcal bacteremia, but only during a period of high malaria transmission (P = 0.014; OR 2.33, 95% CI 1.19–4.57). We estimate that the population attributable fraction of G6PD deficiency on risk of pneumococcal bacteremia in areas under high malaria transmission is 0.129. CONCLUSIONS: Our data demonstrate that G6PD deficiency increases risk of pneumococcal bacteremia in a manner dependent on malaria. At the population level, the impact of G6PD deficiency on invasive pneumococcal disease risk in malaria-endemic regions is substantial. Our study highlights the infection-associated morbidity and mortality conferred by G6PD deficiency in malaria-endemic settings and adds to our understanding of the potential indirect health benefits of improved malaria control.
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spelling pubmed-72946542020-06-16 Risk of pneumococcal bacteremia in Kenyan children with glucose-6-phosphate dehydrogenase deficiency Gilchrist, James J. Uyoga, Sophie Pirinen, Matti Rautanen, Anna Mwarumba, Salim Njuguna, Patricia Mturi, Neema Hill, Adrian V. S. Scott, J. Anthony G. Williams, Thomas N. BMC Med Research Article BACKGROUND: Glucose-6-phosphate dehydrogenase (G6PD) deficiency is the most common enzyme deficiency state in humans. The clinical phenotype is variable and includes asymptomatic individuals, episodic hemolysis induced by oxidative stress, and chronic hemolysis. G6PD deficiency is common in malaria-endemic regions, an observation hypothesized to be due to balancing selection at the G6PD locus driven by malaria. G6PD deficiency increases risk of severe malarial anemia, a key determinant of invasive bacterial disease in malaria-endemic settings. The pneumococcus is a leading cause of invasive bacterial infection and death in African children. The effect of G6PD deficiency on risk of pneumococcal disease is undefined. We hypothesized that G6PD deficiency increases pneumococcal disease risk and that this effect is dependent upon malaria. METHODS: We performed a genetic case-control study of pneumococcal bacteremia in Kenyan children stratified across a period of falling malaria transmission between 1998 and 2010. RESULTS: Four hundred twenty-nine Kenyan children with pneumococcal bacteremia and 2677 control children were included in the study. Among control children, G6PD deficiency, secondary to the rs1050828 G>A mutation, was common, with 11.2% (n = 301 of 2677) being hemi- or homozygotes and 33.3% (n = 442 of 1329) of girls being heterozygotes. We found that G6PD deficiency increased the risk of pneumococcal bacteremia, but only during a period of high malaria transmission (P = 0.014; OR 2.33, 95% CI 1.19–4.57). We estimate that the population attributable fraction of G6PD deficiency on risk of pneumococcal bacteremia in areas under high malaria transmission is 0.129. CONCLUSIONS: Our data demonstrate that G6PD deficiency increases risk of pneumococcal bacteremia in a manner dependent on malaria. At the population level, the impact of G6PD deficiency on invasive pneumococcal disease risk in malaria-endemic regions is substantial. Our study highlights the infection-associated morbidity and mortality conferred by G6PD deficiency in malaria-endemic settings and adds to our understanding of the potential indirect health benefits of improved malaria control. BioMed Central 2020-06-15 /pmc/articles/PMC7294654/ /pubmed/32536341 http://dx.doi.org/10.1186/s12916-020-01604-y Text en © The Author(s) 2020 Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data.
spellingShingle Research Article
Gilchrist, James J.
Uyoga, Sophie
Pirinen, Matti
Rautanen, Anna
Mwarumba, Salim
Njuguna, Patricia
Mturi, Neema
Hill, Adrian V. S.
Scott, J. Anthony G.
Williams, Thomas N.
Risk of pneumococcal bacteremia in Kenyan children with glucose-6-phosphate dehydrogenase deficiency
title Risk of pneumococcal bacteremia in Kenyan children with glucose-6-phosphate dehydrogenase deficiency
title_full Risk of pneumococcal bacteremia in Kenyan children with glucose-6-phosphate dehydrogenase deficiency
title_fullStr Risk of pneumococcal bacteremia in Kenyan children with glucose-6-phosphate dehydrogenase deficiency
title_full_unstemmed Risk of pneumococcal bacteremia in Kenyan children with glucose-6-phosphate dehydrogenase deficiency
title_short Risk of pneumococcal bacteremia in Kenyan children with glucose-6-phosphate dehydrogenase deficiency
title_sort risk of pneumococcal bacteremia in kenyan children with glucose-6-phosphate dehydrogenase deficiency
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7294654/
https://www.ncbi.nlm.nih.gov/pubmed/32536341
http://dx.doi.org/10.1186/s12916-020-01604-y
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