Control of malaria increasingly involves administration of 8-aminoquinolines, with accompanying risk of haemolysis in individuals with glucose-6-phosphate dehydrogenase (G6PD) deficiency. Few data on the prevalence and genotypic basis of G6PD deficiency are available from Bangladesh, where malaria remains a major problem in the South (Chittagong Division). The aim of this study was to determine the prevalence of G6PD deficiency, and associated G6PD genotypes, in adults with falciparum malaria in southern Bangladesh.
G6PD status was assessed via a combination of fluorescent spot testing (FST) and genotyping in 141 Bengali patients admitted with falciparum malaria to two centres in Chittagong Division from 2012 to 2014. In addition, an analysis of genomic data from 1000 Genomes Project was carried out among five healthy Indian subcontinent populations.
One male patient with uncomplicated malaria was found to have G6PD deficiency on FST and a genotype associated with deficiency (hemizygous Orissa variant). In addition, there were two female patients heterozygous for deficiency variants (Orissa and Kerala-Kalyan). These three patients had a relatively long duration of symptoms prior to admission compared to G6PD normal cases, possibly suggesting an interaction with parasite multiplication rate. In addition, one of 27 healthy local controls was deficient on FST and hemizygous for the Mahidol variant of G6PD deficiency. Examination of 1000 Genomes Project sequencing data across the Indian subcontinent showed that 19/723 chromosomes (2.63%) carried a variant associated with deficiency. In the Bengali from Bangladesh 1000 Genomes population, three of 130 chromosomes (2.31%) carried deficient alleles; this included single chromosomes carrying the Kerala-Kalyan and Orissa variants.
In line with other recent work, G6PD deficiency is uncommon in Bengalis in Bangladesh. Further studies of particular ethnic groups are needed to evaluate the potential risk of wide deployment of primaquine in malaria control efforts in Bangladesh.
Motulsky AG. Metabolic polymorphisms and the role of infectious diseases in human evolution. Hum Biol. 1960;32:28–62. PubMed
Uyoga S, Ndila CM, Macharia AW, Nyutu G, Shah S, Peshu N, et al. Glucose-6-phosphate dehydrogenase deficiency and the risk of malaria and other diseases in children in Kenya: a case–control and a cohort study. Lancet Haematol. 2015;2:437–44. CrossRef
Beutler E. The hemolytic effect of primaquine and related compounds: a review. Blood. 1959;14:103–39. PubMed
von Seidlein L, Auburn S, Espino F, Shanks D, Cheng Q, McCarthy J, et al. Review of key knowledge gaps in glucose-6-phosphate dehydrogenase deficiency detection with regard to the safe clinical deployment of 8-aminoquinoline treatment regimens: a workshop report. Malar J. 2013;12:112. CrossRef
Papiha SS, Roberts DF, Ali SG, Islam MM. Some hereditary blood factors of the Bengali Muslim of Bangladesh (red cell enzymes, haemoglobins, and serum proteins). Humangenetik. 1975;28:285–93. PubMed
World Health Organization. Guidelines for the treatment of malaria. 2nd ed. Geneva: World Health Organization; 2010.
Tang TK, Huang CS, Huang MJ, Tam KB, Yeh CH, Tang CJ. Diverse point mutations result in glucose-6-phosphate dehydrogenase (G6PD) polymorphism in Taiwan. Blood. 1992;79:2135–40. PubMed
Vulliamy TJ, Othman A, Town M, Nathwani A, Falusi AG, Mason PJ, et al. Polymorphic sites in the African population detected by sequence analysis of the glucose-6-phosphate dehydrogenase gene outline the evolution of the variants A and A. Proc Natl Acad Sci USA. 1991;88:8568–71. CrossRefPubMedPubMedCentral
Espino FE, Bibit JA, Sornillo JB, Tan A, von Seidlein L, Ley B. Comparison of three screening test kits for G6PD enzyme deficiency: implications for its use in the radical cure of vivax malaria in remote and resource-poor areas in the Philippines. PLoS ONE. 2016;11:e0148172. CrossRefPubMedPubMedCentral
Leiden Open Variation Database (LOVD). https://grenada.lumc.nl/LOVD2/MR/home.php. Accessed 9 Sept 2016.
Beutler E. A series of new screening procedures for pyruvate kinase deficiency, glucose-6-phosphate dehydrogenase deficiency, and glutathione reductase deficiency. Blood. 1966;28:553–62. PubMed
Ogo S, Focesi A Jr, Cashon R, Bonaventura J, Bonaventura C. Interactions of nicotinamide adenine dinucleotides with varied states and forms of hemoglobin. J Biol Chem. 1989;264:11302–6. PubMed
Panich V, Sungnate T, Na-Nakorn S. Acute intravascular hemolysis and renal failure in a new glucose-6-phosphate dehydrogenase variant: G-6-PD Siriraj. J Med Assoc Thail. 1972;55:726–31.
Tomar LR, Aggarwal A, Jain P, Rajpal S, Agarwal MP. Acute viral hepatitis E presenting with haemolytic anaemia and acute renal failure in a patient with glucose-6-phosphate dehydrogenase deficiency. Trop Dr. 2014;45:245–6. CrossRef
Balaka B, Agbere D, Bonkoungou P, Gnamey D, Kessie K, Assimadi K. Post-hemolytic renal failure in children with glucose-6-phosphate dehydrogenase deficiency at the University Hospital Center in Lome. Med Trop. 2003;63:151–4 (in French).
Zager RA, Gamelin LM. Pathogenetic mechanisms in experimental hemoglobinuric acute renal failure. Am J Physiol. 1989;256:F446–55. PubMed
Zager RA, Vijayan A, Johnson AC. Proximal tubule haptoglobin gene activation is an integral component of the acute kidney injury “stress response”. Am J Physiol. 2012;303:F139–48.
Zager RA, Johnson AC, Becker K. Renal cortical hemopexin accumulation in response to acute kidney injury. Am J Physiol. 2012;303:F1460–72.
- Genotypic and phenotypic characterization of G6PD deficiency in Bengali adults with severe and uncomplicated malaria
Hugh W. F. Kingston
M. Trent Herdman
Stije J. Leopold
Md. Abul Faiz
Nicholas M. Anstey
Nicholas P. J. Day
Md. Amir Hossain
Arjen M. Dondorp
Charles J. Woodrow
- BioMed Central
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