Journal article
Risk of pneumococcal bacteremia in Kenyan children with glucose-6-phosphate dehydrogenase deficiency
- Abstract:
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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.
- Publication status:
- Published
- Peer review status:
- Peer reviewed
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(Preview, Version of record, 1.1MB, Terms of use)
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- Publisher copy:
- 10.1186/s12916-020-01604-y
Authors
- Publisher:
- BioMed Central
- Journal:
- BMC Medicine More from this journal
- Volume:
- 18
- Article number:
- 148
- Publication date:
- 2020-06-15
- Acceptance date:
- 2020-04-23
- DOI:
- ISSN:
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1741-7015
- Language:
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English
- Keywords:
- Pubs id:
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1103700
- Local pid:
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pubs:1103700
- Deposit date:
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2020-05-09
Terms of use
- Copyright holder:
- Gilchrist et al.
- Copyright date:
- 2020
- Rights statement:
- © The Authors 2020. This 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.
- Licence:
- CC Attribution (CC BY)
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