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Published in: Malaria Journal 1/2018

Open Access 01-12-2018 | Research

Glucose-6-phosphate dehydrogenase (G6PD) deficiency in Ethiopia: absence of common African and Mediterranean allelic variants in a nationwide study

Authors: Ashenafi Assefa, Ahmed Ali, Wakgari Deressa, Wendimagegn Tsegaye, Getachew Abebe, Heven Sime, Amha Kebede, Daddi Jima, Moges Kassa, Tesfay Abreha, Hiwot Teka, Hiwot Solomon, Joseph Malone, Ya Ping Shi, Zhiyong Zhou, Richard Reithinger, Jimee Hwang

Published in: Malaria Journal | Issue 1/2018

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Abstract

Background

Building on the declining trend of malaria in Ethiopia, the Federal Ministry of Health aims to eliminate malaria by 2030. As Plasmodium falciparum and Plasmodium vivax are co-endemic in Ethiopia, the use of primaquine is indicated for both transmission interruption and radical cure, respectively. However, the limited knowledge of the local prevalence of glucose-6-phosphate dehydrogenase (G6PD) deficiency and its associated variants has hindered the use of primaquine.

Methods

Some 11,138 dried blood spot (DBS) samples were collected in 2011 as part of a national, household Malaria Indicator Survey, a multi-stage nationally representative survey of all malaria-endemic areas of Ethiopia. A randomly selected sub-set of 1414 DBS samples was successfully genotyped by polymerase chain reaction–restriction fragment length polymorphism (PCR–RFLP) technique. Considering the geographical position and ethnic mix of the country, three common variants: G6PD*A (A376G), G6PD*A− (G202A) and Mediterranean (C563T) were investigated.

Results

Of the 1998 randomly selected individuals, 1429 (71.5%) DBS samples were genotyped and merged to the database, of which 53.5% were from females. G6PD*A (A376G) was the only genotype detected. No sample was positive for either G6PD*A− (G202A) or Mediterranean (C563T) variants. The prevalence of G6PD*A (A376G) was 8.9% [95% confidence interval (CI) 6.7–11.2] ranging from 12.2% in the Southern Nations, Nationalities and Peoples’ (95% CI 5.7–18.7) to none in Dire Dawa/Harari Region.

Conclusion

The common G6PD*A− (G202A) or Mediterranean (C563T) variants were not observed in this nationwide study. The observed G6PD*A (A376G) mutation has little or no clinical significance. These findings supported the adoption of primaquine for P. falciparum transmission interruption and radical cure of P. vivax in Ethiopia. As the presence of other clinically important, less common variants cannot be ruled out, the implementation of radical cure will be accompanied by active haematological and adverse events monitoring in Ethiopia.
Literature
2.
go back to reference Federal Ministry of Ethiopia (FMOH). National Malaria Elimination Roadmap. National Malaria prevention, control and elimination programme; Disease Prevention and Control Directorate; 2016. Federal Ministry of Ethiopia (FMOH). National Malaria Elimination Roadmap. National Malaria prevention, control and elimination programme; Disease Prevention and Control Directorate; 2016.
3.
go back to reference Beutler E, Duparc S, G6PD Deficiency Working Group. Glucose-6-phosphate dehydrogenase deficiency and antimalarial drug development. Am J Trop Med Hyg. 2007;77:779–89.CrossRef Beutler E, Duparc S, G6PD Deficiency Working Group. Glucose-6-phosphate dehydrogenase deficiency and antimalarial drug development. Am J Trop Med Hyg. 2007;77:779–89.CrossRef
4.
go back to reference Howes RE, Dewi M, Piel FB, Monteiro WM, Battle KE, Messina JP, et al. Spatial distribution of G6PD deficiency variants across malaria-endemic regions. Malar J. 2013;12:418.CrossRef Howes RE, Dewi M, Piel FB, Monteiro WM, Battle KE, Messina JP, et al. Spatial distribution of G6PD deficiency variants across malaria-endemic regions. Malar J. 2013;12:418.CrossRef
7.
go back to reference Howes RE, Battle KE, Satyagraha AW, Baird JK, Hay SI. G6PD deficiency: global distribution, genetic variants and primaquine therapy. Adv Parasitol. 2013;81:133–201.CrossRef Howes RE, Battle KE, Satyagraha AW, Baird JK, Hay SI. G6PD deficiency: global distribution, genetic variants and primaquine therapy. Adv Parasitol. 2013;81:133–201.CrossRef
8.
go back to reference Adam A, Bat-miriam M, Barnicot N A, Lehmann H, Mourant AE, Ramot B, et al. A survey of some genetical characters in Ethiopian Tribes. Report on an expedition to Ethiopia during the last quarter of 1959 planned by the Tel Habshomer Government Hospital, Israel, and the Israel Institute for Biological Research in Ness Ziona and financed by AJDC (American Joint Distribution Committee); 1959. Adam A, Bat-miriam M, Barnicot N A, Lehmann H, Mourant AE, Ramot B, et al. A survey of some genetical characters in Ethiopian Tribes. Report on an expedition to Ethiopia during the last quarter of 1959 planned by the Tel Habshomer Government Hospital, Israel, and the Israel Institute for Biological Research in Ness Ziona and financed by AJDC (American Joint Distribution Committee); 1959.
9.
go back to reference Adam A, Bat-miriam M, Lehmann H, Mourant AE, Ramot B, Sheba CH, et al. A survey of some genetical characters in Ethiopian tribes. In: Excerta medica international congress series: second international conference of Human Genetics. September 7–12, 1961. Rome, Italy; 1961. Adam A, Bat-miriam M, Lehmann H, Mourant AE, Ramot B, Sheba CH, et al. A survey of some genetical characters in Ethiopian tribes. In: Excerta medica international congress series: second international conference of Human Genetics. September 7–12, 1961. Rome, Italy; 1961.
10.
go back to reference Perine PL, Mebrahtu Tesfa M. A preliminary survey for glucose-6-phosphate dehydrogenase deficiency and haemoglobin S in Ethiopia. Ethiop Med J. 1974;12:179.PubMed Perine PL, Mebrahtu Tesfa M. A preliminary survey for glucose-6-phosphate dehydrogenase deficiency and haemoglobin S in Ethiopia. Ethiop Med J. 1974;12:179.PubMed
11.
go back to reference Tsegaye A, Golassa L, Mamo H, Erko B. Glucose-6-phosphate dehydrogenase deficiency among malaria suspects attending Gambella hospital, southwest Ethiopia. Malar J. 2014;13:438.CrossRef Tsegaye A, Golassa L, Mamo H, Erko B. Glucose-6-phosphate dehydrogenase deficiency among malaria suspects attending Gambella hospital, southwest Ethiopia. Malar J. 2014;13:438.CrossRef
12.
go back to reference Federal Ministry of Health Ethiopia (FMOH). National Strategic plan 2014–2020 (Draft). 2014. Federal Ministry of Health Ethiopia (FMOH). National Strategic plan 2014–2020 (Draft). 2014.
13.
go back to reference Aregawi M, Lynch M, Bekele W, Kebede H, Jima D, Taffese HS, et al. Time series analysis of trends in malaria cases and deaths at hospitals and the effect of antimalarial interventions, 2001–2011, Ethiopia. PLoS ONE. 2014;9:e106359.CrossRef Aregawi M, Lynch M, Bekele W, Kebede H, Jima D, Taffese HS, et al. Time series analysis of trends in malaria cases and deaths at hospitals and the effect of antimalarial interventions, 2001–2011, Ethiopia. PLoS ONE. 2014;9:e106359.CrossRef
14.
go back to reference Federal Ministry of Health Ethiopia (FMOH). Ethiopia National Malaria strategic plan: 2017–2020. 2017. Federal Ministry of Health Ethiopia (FMOH). Ethiopia National Malaria strategic plan: 2017–2020. 2017.
17.
go back to reference Carter N, Pamba A, Duparc S, Waitumbi JN. Frequency of glucose-6-phosphate dehydrogenase deficiency in malaria patients from six African countries enrolled in two randomized anti-malarial clinical trials. Malar J. 2011;10:241.CrossRef Carter N, Pamba A, Duparc S, Waitumbi JN. Frequency of glucose-6-phosphate dehydrogenase deficiency in malaria patients from six African countries enrolled in two randomized anti-malarial clinical trials. Malar J. 2011;10:241.CrossRef
18.
go back to reference Alfadhli S, Kaaba S, Elshafey A, Salim M, AlAwadi A, Bastaki L. Molecular characterization of glucose-6-phosphate dehydrogenase gene defect in the Kuwaiti population. Arch Pathol Lab Med. 2005;129:1144–7.PubMed Alfadhli S, Kaaba S, Elshafey A, Salim M, AlAwadi A, Bastaki L. Molecular characterization of glucose-6-phosphate dehydrogenase gene defect in the Kuwaiti population. Arch Pathol Lab Med. 2005;129:1144–7.PubMed
19.
go back to reference Samilchuk E, D’Souza B, Al-Awadi S. Population study of common glucose-6-phosphate dehydrogenase mutations in Kuwait. Hum Hered. 1999;49:41–4.CrossRef Samilchuk E, D’Souza B, Al-Awadi S. Population study of common glucose-6-phosphate dehydrogenase mutations in Kuwait. Hum Hered. 1999;49:41–4.CrossRef
20.
go back to reference Phompradit P, Kuesap J, Chaijaroenkul W, Rueangweerayut R, Hongkaew Y, Yamnuan R, et al. Prevalence and distribution of glucose-6-phosphate dehydrogenase (G6PD) variants in Thai and Burmese populations in malaria endemic areas of Thailand. Malar J. 2011;10:368.CrossRef Phompradit P, Kuesap J, Chaijaroenkul W, Rueangweerayut R, Hongkaew Y, Yamnuan R, et al. Prevalence and distribution of glucose-6-phosphate dehydrogenase (G6PD) variants in Thai and Burmese populations in malaria endemic areas of Thailand. Malar J. 2011;10:368.CrossRef
21.
go back to reference Hirono A, Beutler E. Molecular cloning and nucleotide sequence of cDNA for human glucose-6-phosphate dehydrogenase variant A(−). Proc Natl Acad Sci USA. 1988;85:3951–4.CrossRef Hirono A, Beutler E. Molecular cloning and nucleotide sequence of cDNA for human glucose-6-phosphate dehydrogenase variant A(−). Proc Natl Acad Sci USA. 1988;85:3951–4.CrossRef
22.
go back to reference Carter TE, Mekonnen SK, Lopez K, Bonnell V, Damodaran L, Aseffa A, et al. Glucose-6-phosphate dehydrogenase deficiency genetic variants in malaria patients in Southwestern Ethiopia. Am J Trop Med Hyg. 2018;98:83–7.CrossRef Carter TE, Mekonnen SK, Lopez K, Bonnell V, Damodaran L, Aseffa A, et al. Glucose-6-phosphate dehydrogenase deficiency genetic variants in malaria patients in Southwestern Ethiopia. Am J Trop Med Hyg. 2018;98:83–7.CrossRef
23.
go back to reference Saunders MA, Hammer MF, Nachman MW. Nucleotide variability at G6pd and the signature of malarial selection in humans. Genetics. 2002;162:1849–61.PubMedPubMedCentral Saunders MA, Hammer MF, Nachman MW. Nucleotide variability at G6pd and the signature of malarial selection in humans. Genetics. 2002;162:1849–61.PubMedPubMedCentral
24.
go back to reference Ruwende C, Khoo SC, Snow RW, Yates SN, Kwiatkowski D, Gupta S, et al. Natural selection of hemi- and heterozygotes for G6PD deficiency in Africa by resistance to severe malaria. Nature. 1995;376:246–9.CrossRef Ruwende C, Khoo SC, Snow RW, Yates SN, Kwiatkowski D, Gupta S, et al. Natural selection of hemi- and heterozygotes for G6PD deficiency in Africa by resistance to severe malaria. Nature. 1995;376:246–9.CrossRef
25.
go back to reference Beutler E, Vulliamy TJ. Hematologically important mutations: glucose-6-phosphate dehydrogenase. Blood Cells Mol Dis. 2002;28:93–103.CrossRef Beutler E, Vulliamy TJ. Hematologically important mutations: glucose-6-phosphate dehydrogenase. Blood Cells Mol Dis. 2002;28:93–103.CrossRef
26.
go back to reference LaRue N, Kahn M, Murray M, Leader BT, Bansil P, McGray S, et al. Comparison of quantitative and qualitative tests for glucose-6-phosphate dehydrogenase deficiency. Am J Trop Med Hyg. 2014;91:854–61.CrossRef LaRue N, Kahn M, Murray M, Leader BT, Bansil P, McGray S, et al. Comparison of quantitative and qualitative tests for glucose-6-phosphate dehydrogenase deficiency. Am J Trop Med Hyg. 2014;91:854–61.CrossRef
28.
go back to reference Monteiro WM, Val FF, Siqueira AM, Franca GP, Sampaio VS, Melo GC, et al. G6PD deficiency in Latin America: systematic review on prevalence and variants. Mem Inst Oswaldo Cruz. 2014;109:553–68.CrossRef Monteiro WM, Val FF, Siqueira AM, Franca GP, Sampaio VS, Melo GC, et al. G6PD deficiency in Latin America: systematic review on prevalence and variants. Mem Inst Oswaldo Cruz. 2014;109:553–68.CrossRef
29.
go back to reference Zein ZA, Koos H. The ecology of health and disease in Ethiopia. Ministry of Health; 1993. Zein ZA, Koos H. The ecology of health and disease in Ethiopia. Ministry of Health; 1993.
30.
go back to reference Iancovici-Kidon M, Sthoeger D, Abrahamov A, Wolach B, Beutler E, Gelbart T, et al. A new exon 9 glucose-6-phosphate dehydrogenase mutation (G6PD “Rehovot”) in a Jewish Ethiopian family with variable phenotypes. Blood Cells Mol Dis. 2000;26:567–71.CrossRef Iancovici-Kidon M, Sthoeger D, Abrahamov A, Wolach B, Beutler E, Gelbart T, et al. A new exon 9 glucose-6-phosphate dehydrogenase mutation (G6PD “Rehovot”) in a Jewish Ethiopian family with variable phenotypes. Blood Cells Mol Dis. 2000;26:567–71.CrossRef
31.
go back to reference Tadesse FG, Helmi P, Amrish B, et al. Submicroscopic carriage of Plasmodium falciparum and Plasmodium vivax in a low endemic area in Ethiopia where no parasitaemia was detected by microscopy or rapid diagnostic test. Malar J. 2015;14:303.CrossRef Tadesse FG, Helmi P, Amrish B, et al. Submicroscopic carriage of Plasmodium falciparum and Plasmodium vivax in a low endemic area in Ethiopia where no parasitaemia was detected by microscopy or rapid diagnostic test. Malar J. 2015;14:303.CrossRef
32.
go back to reference Federal Ministry of Health Ethiopia (FMOH). Updates on Malaria Diagnosis and Treatment, Ethiopia. 2016. Federal Ministry of Health Ethiopia (FMOH). Updates on Malaria Diagnosis and Treatment, Ethiopia. 2016.
33.
go back to reference Poirot E, Soble A, Ntshalintshali N, Mwandemele A, Mkhonta N, Malambe C, et al. Development of a pharmacovigilance safety monitoring tool for the rollout of single low-dose primaquine and artemether-lumefantrine to treat Plasmodium falciparum infections in Swaziland: a pilot study. Malar J. 2016;15:384.CrossRef Poirot E, Soble A, Ntshalintshali N, Mwandemele A, Mkhonta N, Malambe C, et al. Development of a pharmacovigilance safety monitoring tool for the rollout of single low-dose primaquine and artemether-lumefantrine to treat Plasmodium falciparum infections in Swaziland: a pilot study. Malar J. 2016;15:384.CrossRef
34.
go back to reference Abreha T, Hwang J, Thriemer K, Tadesse Y, Girma S, Melaku Z, et al. Comparison of artemether-lumefantrine and chloroquine with and without primaquine for the treatment of Plasmodium vivax infection in Ethiopia: a randomized controlled trial. PLoS Med. 2017;14:e1002299.CrossRef Abreha T, Hwang J, Thriemer K, Tadesse Y, Girma S, Melaku Z, et al. Comparison of artemether-lumefantrine and chloroquine with and without primaquine for the treatment of Plasmodium vivax infection in Ethiopia: a randomized controlled trial. PLoS Med. 2017;14:e1002299.CrossRef
35.
go back to reference IMPROV Study Group. Improving the radical cure of vivax malaria (IMPROV): a study protocol for a multicentre randomised, placebo-controlled comparison of short and long course primaquine regimens. BMC Infect Dis. 2015;15:558.CrossRef IMPROV Study Group. Improving the radical cure of vivax malaria (IMPROV): a study protocol for a multicentre randomised, placebo-controlled comparison of short and long course primaquine regimens. BMC Infect Dis. 2015;15:558.CrossRef
Metadata
Title
Glucose-6-phosphate dehydrogenase (G6PD) deficiency in Ethiopia: absence of common African and Mediterranean allelic variants in a nationwide study
Authors
Ashenafi Assefa
Ahmed Ali
Wakgari Deressa
Wendimagegn Tsegaye
Getachew Abebe
Heven Sime
Amha Kebede
Daddi Jima
Moges Kassa
Tesfay Abreha
Hiwot Teka
Hiwot Solomon
Joseph Malone
Ya Ping Shi
Zhiyong Zhou
Richard Reithinger
Jimee Hwang
Publication date
01-12-2018
Publisher
BioMed Central
Published in
Malaria Journal / Issue 1/2018
Electronic ISSN: 1475-2875
DOI
https://doi.org/10.1186/s12936-018-2538-4

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