Molecular characterization and mapping of glucose-6-phosphate dehydrogenase (G6PD) mutations in the Greater Mekong Subregion.


Journal

Malaria journal
ISSN: 1475-2875
Titre abrégé: Malar J
Pays: England
ID NLM: 101139802

Informations de publication

Date de publication:
23 Jan 2019
Historique:
received: 22 08 2018
accepted: 16 01 2019
entrez: 25 1 2019
pubmed: 25 1 2019
medline: 8 2 2019
Statut: epublish

Résumé

Plasmodium vivax malaria elimination can only be achieved by the deployment of 8-aminoquinolines (primaquine and tafenoquine) in combination with ACT to kill both blood and liver-stage parasites. However, primaquine and the other 8-aminoquinolines cause dose-dependent haemolysis in subjects with G6PD deficiency, an X-linked disorder of red blood cells that is very common in populations living in tropical and subtropical areas. In order to inform safer use of 8-aminoquinolines in the Greater Mekong Subregion, a multi-centre study was carried out to assess the prevalence of G6PD deficiency and to identify the main G6PD variants in samples collected in Cambodia, Lao PDR, Myanmar, Thailand and Vietnam. Blood samples were collected in the five countries during National Malaria Surveys or during Population Surveys. During Population Surveys samples were characterized for G6PD phenotype using the Fluorescent Spot Test. Samples were then genotyped for a panel of G6PD mutations. G6PD deficiency was found to be common in the region with an overall mean prevalence of deficient or mutated hemizygous males of 14.0%, ranging from a mean 7.3% in Thailand, 8.1% in Lao PDR, 8.9% in Vietnam, 15.8% in Myanmar and 18.8% in Cambodia. Mahidol and Viangchan mutations were the most common and widespread variants found among the nine investigated. Owing to the high prevalence of G6PD deficiency in the Greater Mekong Subregion, strategies for vivax malaria elimination should include point-of-care G6PD testing (both qualitative and quantitative) to allow safe and wide treatment with 8-aminoquinolines.

Sections du résumé

BACKGROUND BACKGROUND
Plasmodium vivax malaria elimination can only be achieved by the deployment of 8-aminoquinolines (primaquine and tafenoquine) in combination with ACT to kill both blood and liver-stage parasites. However, primaquine and the other 8-aminoquinolines cause dose-dependent haemolysis in subjects with G6PD deficiency, an X-linked disorder of red blood cells that is very common in populations living in tropical and subtropical areas. In order to inform safer use of 8-aminoquinolines in the Greater Mekong Subregion, a multi-centre study was carried out to assess the prevalence of G6PD deficiency and to identify the main G6PD variants in samples collected in Cambodia, Lao PDR, Myanmar, Thailand and Vietnam.
METHODS METHODS
Blood samples were collected in the five countries during National Malaria Surveys or during Population Surveys. During Population Surveys samples were characterized for G6PD phenotype using the Fluorescent Spot Test. Samples were then genotyped for a panel of G6PD mutations.
RESULTS RESULTS
G6PD deficiency was found to be common in the region with an overall mean prevalence of deficient or mutated hemizygous males of 14.0%, ranging from a mean 7.3% in Thailand, 8.1% in Lao PDR, 8.9% in Vietnam, 15.8% in Myanmar and 18.8% in Cambodia. Mahidol and Viangchan mutations were the most common and widespread variants found among the nine investigated.
CONCLUSIONS CONCLUSIONS
Owing to the high prevalence of G6PD deficiency in the Greater Mekong Subregion, strategies for vivax malaria elimination should include point-of-care G6PD testing (both qualitative and quantitative) to allow safe and wide treatment with 8-aminoquinolines.

Identifiants

pubmed: 30674319
doi: 10.1186/s12936-019-2652-y
pii: 10.1186/s12936-019-2652-y
pmc: PMC6343352
doi:

Substances chimiques

G6PD protein, human EC 1.1.1.49
Glucosephosphate Dehydrogenase EC 1.1.1.49

Types de publication

Journal Article Multicenter Study

Langues

eng

Sous-ensembles de citation

IM

Pagination

20

Subventions

Organisme : France's 5% Initiative
ID : 12INI211

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Auteurs

Germana Bancone (G)

Shoklo Malaria Research Unit, Mahidol-Oxford Tropical Medicine Research Unit, Faculty of Tropical Medicine, Mahidol University, Mae Sot, Thailand. germana@tropmedres.ac.
Centre for Tropical Medicine & Global Health, Nuffield Department of Medicine, University of Oxford, Oxford, UK. germana@tropmedres.ac.

Didier Menard (D)

Malaria Molecular Epidemiology Unit, Institut Pasteur du Cambodge, Phnom Penh, Cambodia.
Malaria Genetics and Resistance Group, Institut Pasteur, Paris, France.

Nimol Khim (N)

Malaria Molecular Epidemiology Unit, Institut Pasteur du Cambodge, Phnom Penh, Cambodia.

Saorin Kim (S)

Malaria Molecular Epidemiology Unit, Institut Pasteur du Cambodge, Phnom Penh, Cambodia.

Lydie Canier (L)

Malaria Molecular Epidemiology Unit, Institut Pasteur du Cambodge, Phnom Penh, Cambodia.

Chea Nguong (C)

National Centre for Parasitology, Entomology and Malaria Control (CNM), Phnom Penh, Cambodia.

Koukeo Phommasone (K)

Microbiology Laboratory, Lao-Oxford-Mahosot Hospital-Wellcome Trust Research Unit (LOMWRU), Vientiane, Lao People's Democratic Republic.

Mayfong Mayxay (M)

Centre for Tropical Medicine & Global Health, Nuffield Department of Medicine, University of Oxford, Oxford, UK.
Microbiology Laboratory, Lao-Oxford-Mahosot Hospital-Wellcome Trust Research Unit (LOMWRU), Vientiane, Lao People's Democratic Republic.
Institute of Research and Education Development, University of Health Sciences, Ministry of Health, Vientiane, Lao People's Democratic Republic.

Sabine Dittrich (S)

Centre for Tropical Medicine & Global Health, Nuffield Department of Medicine, University of Oxford, Oxford, UK.
Microbiology Laboratory, Lao-Oxford-Mahosot Hospital-Wellcome Trust Research Unit (LOMWRU), Vientiane, Lao People's Democratic Republic.
Foundation for Innovative New Diagnostics (FIND), Geneva, Switzerland.

Malavanh Vongsouvath (M)

Microbiology Laboratory, Lao-Oxford-Mahosot Hospital-Wellcome Trust Research Unit (LOMWRU), Vientiane, Lao People's Democratic Republic.

Nadine Fievet (N)

UMR216-MERIT, French National Research Institute for Sustainable Development (IRD), Paris-5 University, Sorbonne Paris Cité, Paris, France.

Jean-Yves Le Hesran (JY)

UMR216-MERIT, French National Research Institute for Sustainable Development (IRD), Paris-5 University, Sorbonne Paris Cité, Paris, France.

Valerie Briand (V)

UMR216-MERIT, French National Research Institute for Sustainable Development (IRD), Paris-5 University, Sorbonne Paris Cité, Paris, France.

Sommay Keomany (S)

Salavan Provincial Hospital, Salavan, Lao People's Democratic Republic.

Paul N Newton (PN)

Centre for Tropical Medicine & Global Health, Nuffield Department of Medicine, University of Oxford, Oxford, UK.
Microbiology Laboratory, Lao-Oxford-Mahosot Hospital-Wellcome Trust Research Unit (LOMWRU), Vientiane, Lao People's Democratic Republic.

Gornpan Gorsawun (G)

Shoklo Malaria Research Unit, Mahidol-Oxford Tropical Medicine Research Unit, Faculty of Tropical Medicine, Mahidol University, Mae Sot, Thailand.

Kaelan Tardy (K)

Shoklo Malaria Research Unit, Mahidol-Oxford Tropical Medicine Research Unit, Faculty of Tropical Medicine, Mahidol University, Mae Sot, Thailand.

Cindy S Chu (CS)

Shoklo Malaria Research Unit, Mahidol-Oxford Tropical Medicine Research Unit, Faculty of Tropical Medicine, Mahidol University, Mae Sot, Thailand.
Centre for Tropical Medicine & Global Health, Nuffield Department of Medicine, University of Oxford, Oxford, UK.

Orpreeya Rattanapalroj (O)

Bureau of Vector Born Diseases, Bangkok, Thailand.

Le Thanh Dong (LT)

Institute of Malariology, Parasitology and Entomology - Ho Chi Minh City (IMPE-HCM), Ho Chi Minh City, Vietnam.

Huynh Hong Quang (HH)

Institute of Malariology, Parasitology and Entomology - Quy Nhon (IMPE-QN), Quy Nhon, Vietnam.

Nguyen Tam-Uyen (N)

Oxford University Clinical Research Unit, Wellcome Trust Asia Program, in partnership with Hospital For Tropical Diseases (HTD), Ho Chi Minh City, Vietnam.

Nguyen Thuy-Nhien (N)

Oxford University Clinical Research Unit, Wellcome Trust Asia Program, in partnership with Hospital For Tropical Diseases (HTD), Ho Chi Minh City, Vietnam.

Tran Tinh Hien (TT)

Centre for Tropical Medicine & Global Health, Nuffield Department of Medicine, University of Oxford, Oxford, UK.
Oxford University Clinical Research Unit, Wellcome Trust Asia Program, in partnership with Hospital For Tropical Diseases (HTD), Ho Chi Minh City, Vietnam.

Michael Kalnoky (M)

Diagnostics Program, PATH, Seattle, USA.

Francois Nosten (F)

Shoklo Malaria Research Unit, Mahidol-Oxford Tropical Medicine Research Unit, Faculty of Tropical Medicine, Mahidol University, Mae Sot, Thailand.
Centre for Tropical Medicine & Global Health, Nuffield Department of Medicine, University of Oxford, Oxford, UK.

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