Glucose-6-phosphate dehydrogenase deficiency and susceptibility to childhood diseases in Kilifi, Kenya
Open Access
- 4 December 2020
- journal article
- research article
- Published by American Society of Hematology in Blood Advances
- Vol. 4 (23), 5942-5950
- https://doi.org/10.1182/bloodadvances.2020003015
Abstract
Few previous studies have reported the effects of glucose-6-phosphate dehydrogenase (G6PD)–deficiency on child health in Africa. We conducted a case-control study in which cases (n = 6829) were children admitted, for any reason, to Kilifi County Hospital, Kenya, while controls (n = 10 179) were recruited from the surrounding community. Cases were subclassified based on their clinical and laboratory findings at admission. We calculated the prevalence of specific diseases by G6PD c.202 genotype, the only significant cause of G6PD-deficiency in this area, then estimated the association between genotype and admission with specific conditions using logistic regression. Among neonates, the prevalence of jaundice was higher in both G6PD c.202T heterozygotes (40/88; 45.5%; P = .004) and homo/hemizygotes (81/134; 60.5%; P < .0001) than in wild-type homozygotes (157/526; 29.9%). Median bilirubin levels also increased across the groups, being highest (239 mmol/L; interquartile range 96-390 mmol/L) in G6PD c.202T homo/hemizygotes. No differences were seen in admission hemoglobin concentrations or the prevalence of anemia or severe anemia by G6PD c.202 genotype. On case control analysis, G6PD heterozygosity was negatively associated with all-cause hospital admission (odds ratio 0.81; 95% confidence interval 0.73-0.90; P < .0001) and, specifically, admission with either pneumonia or Plasmodium falciparum parasitemia; while, conversely, it was positively associated with Gram-positive bacteremia. G6PD c.202T homo/heterozygosity was positively associated with neonatal jaundice, severe pneumonia, the receipt of a transfusion, and in-patient death. Our study supports the conclusion that G6PD c.202T is a balanced polymorphism in which a selective advantage afforded to heterozygous females against malaria is counterbalanced by increased risks of neonatal jaundice, invasive bacterial infections, and anemia.This publication has 41 references indexed in Scilit:
- Spatial distribution of G6PD deficiency variants across malaria-endemic regionsMalaria Journal, 2013
- G6PD Deficiency Prevalence and Estimates of Affected Populations in Malaria Endemic Countries: A Geostatistical Model-Based MapPLoS Medicine, 2012
- Profile: The Kilifi Health and Demographic Surveillance System (KHDSS)International Journal of Epidemiology, 2012
- The Definition of Pneumonia, the Assessment of Severity, and Clinical Standardization in the Pneumonia Etiology Research for Child Health StudyClinical Infectious Diseases, 2012
- Relation between falciparum malaria and bacteraemia in Kenyan children: a population-based, case-control study and a longitudinal studyThe Lancet, 2011
- Changing trends in blood transfusion in children and neonates admitted in Kilifi District Hospital, KenyaMalaria Journal, 2010
- X-Linked G6PD Deficiency Protects Hemizygous Males but Not Heterozygous Females against Severe MalariaPLoS Medicine, 2007
- Both heterozygous and homozygous α+ thalassemias protect against severe and fatal Plasmodium falciparum malaria on the coast of KenyaBlood, 2005
- Conjugated bilirubin in neonates with glucose-6-phosphate dehydrogenase deficiencyThe Journal of Pediatrics, 1996
- SEVERE MALARIA AND GLUCOSE-6-PHOSPHATE-DEHYDROGENASE DEFICIENCY: A REAPPRAISAL OF THE MALARIA/G-6-P.D. HYPOTHESISThe Lancet, 1979