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

Abstract

BackgroundPlasmodium 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.MethodsBlood 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.ResultsG6PD 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.ConclusionsOwing 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.Electronic supplementary materialThe online version of this article (10.1186/s12936-019-2652-y) contains supplementary material, which is available to authorized users.

Molecular Characterization of G6PD Mutations Reveals the High Frequency of G6PD Aures in the Mon-Khmer Population

“…A comparison of the G6PD mutation data collected in this and previous studies of non-speci ed Lao ethnic populations is summarized in Table 2. The most common G6PD mutation in the Mon-Khmer population was G6PD Aures c.143T > C (6.75%); this result is different from that in a previous report, which found that the G6PD Viangchan mutation was the most common mutation in the Laotian population (1.21-6.76%) (20,26,27,(29)(30)(31). The G6PD Jammu mutation is an 871G > A mutation identical to the G6PD Viangchan mutation but different from the polymorphism at nucleotide 1311 (nt1311C) detected in this study, whereas the previous report found only G6PD Viangchan in the Laotian population (30).…”

“…The present study is the rst to report the prevalence of G6PD de ciency and G6PD mutations in the Mon-Khmer or Lao Theung ethnic group. The prevalence of G6PD de ciency reported in this study (8.73%) is higher than that previously reported for unspeci ed ethnic Lao populations (6.21% and 4.40%) (26,27) (Table 2). However, the prevalence of G6PD de ciency in Lao populations was lower than that reported in neighboring Southeast Asian populations, including Mon (12%) (17), Karen and Burman (13.7%) (28), Thai (11.1%) (18), and Cambodian (26.1%) (19) populations.…”

“…In the beginning of G6PD mutation screening, the study of G6PD mutations focused only on the detection of the G6PD Viangchan mutation or identi ed the G6PD mutation only in males that presented with severe hemolytic anemia (20,26,29). Only six previous studies ( Table 2) have revealed that the prevalence of G6PD de ciency in the Lao population ranges from 3.30-21.98% in males and 2.50-11.24% in females (20,26,27,(29)(30)(31). Our study revealed severe G6PD de ciency more frequently in males than in females, whereas moderate and mild G6PD de ciencies were more common in females than in males.…”

“…These data imply that the Mon-Khmer or Lao Theung and Lao Loum groups have different origins. For neighboring Southeast Asian countries, G6PD Mahidol is commonly found in Burmese (18.21%) (27), while G6PD Viangchan is commonly found in Thais (6.0%) (18), Cambodians (17.72%) (27) and Vietnamese (26.7%) (33) but not in the Mon-Khmer population. In addition, we rarely detected the G6PD Canton, G6PD Kaiping and G6PD Union mutations, which are prevalent in South China (34).…”

Tools to accelerate falciparum malaria elimination in Cambodia: a meeting report

“…Like primaquine, the other licensed 8-aminoquinoline, tafenoquine carries a risk of triggering haemolysis in G6PD-deficient individuals. The prevalence of G6PD deficiency is highly heterogeneous, between 2 and 16% of residents in the GMS may have sufficiently severe G6PD deficiency to exclude them from any exposure to 8-aminoquinolines [65][66][67]. To use tafenoquine safely as a prophylaxis in the GMS it would be essential to have access to robust diagnostic tools which identify G6PD deficient individuals.…”