Characterization of G6PD Genotypes and Phenotypes on the Northwestern Thailand-Myanmar Border

Bancone, Germana; Chu, Cindy S.; Somsakchaicharoen, Raweewan; Chowwiwat, Nongnud; Parker, Daniel M.; Charunwatthana, Prakaykaew; White, Nicholas J.; Nosten, François

doi:10.1371/journal.pone.0116063

Cited by 85 publications

(102 citation statements)

References 29 publications

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“…AHA induced by 15 mg of daily PQ alone was well tolerated in healthy Cambodian Air Force men who had a mean baseline haemoglobin concentration of approximately 14 g/dL and which fell by a mean of 21 % on day (D)7, persisting to D15 [37]. Data in vivax-infected patients, with Hb concentrations ≥ 10 g/dL, showed that weekly-administered 0.75 mg base/kg of PQ resulted in a greater Hb level decline in G6PDd compared to G6PD normal patients.…”

Section: Introductionmentioning

confidence: 99%

An optimised age-based dosing regimen for single low-dose primaquine for blocking malaria transmission in Cambodia

Leang

Khu

Mukaka

et al. 2016

BMC Med

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BackgroundIn 2012, the World Health Organization recommended the addition of single low-dose primaquine (SLDPQ, 0.25 mg base/kg body weight) to artemisinin combination therapies to block the transmission of Plasmodium falciparum without testing for glucose-6-phosphate dehydrogenase deficiency. The targeted group was non-pregnant patients aged ≥ 1 year (later changed to ≥ 6 months) with acute uncomplicated falciparum malaria, primarily in countries with artemisinin-resistant P. falciparum (ARPf). No dosing regimen was suggested, leaving malaria control programmes and clinicians in limbo. Therefore, we designed a user-friendly, age-based SLDPQ regimen for Cambodia, the country most affected by ARPf.MethodsBy reviewing primaquine’s pharmacology, we defined a therapeutic dose range of 0.15–0.38 mg base/kg (9–22.5 mg in a 60-kg adult) for a therapeutic index of 2.5. Primaquine doses (1–20 mg) were tested using a modelled, anthropometric database of 28,138 Cambodian individuals (22,772 healthy, 4119 with malaria and 1247 with other infections); age distributions were: 0.5–4 years (20.0 %, n = 5640), 5–12 years (9.1 %, n = 2559), 13–17 years (9.1 %, n = 2550), and ≥ 18 years (61.8 %, n = 17,389). Optimal age-dosing groups were selected according to calculated mg base/kg doses and proportions of individuals receiving a therapeutic dose.ResultsFour age-dosing bands were defined: (1) 0.5–4 years, (2) 5–9 years, (3) 10–14 years, and (4) ≥15 years to receive 2.5, 5, 7.5, and 15 mg of primaquine base, resulting in therapeutic doses in 97.4 % (5494/5640), 90.5 % (1511/1669), 97.7 % (1473/1508), and 95.7 % (18,489/19,321) of individuals, respectively. Corresponding median (1st–99th centiles) mg base/kg doses of primaquine were (1) 0.23 (0.15–0.38), (2) 0.29 (0.18–0.45), (3) 0.27 (0.15–0.39), and (4) 0.29 (0.20–0.42).ConclusionsThis age-based SLDPQ regimen could contribute substantially to malaria elimination and requires urgent evaluation in Cambodia and other countries with similar anthropometric characteristics. It guides primaquine manufacturers on suitable tablet strengths and doses for paediatric-friendly formulations. Development of similar age-based dosing recommendations for Africa is needed.Electronic supplementary materialThe online version of this article (doi:10.1186/s12916-016-0701-8) contains supplementary material, which is available to authorized users.

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Section: Introductionmentioning

confidence: 99%

An optimised age-based dosing regimen for single low-dose primaquine for blocking malaria transmission in Cambodia

Leang

Khu

Mukaka

et al. 2016

BMC Med

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“…G6PD-deficiency is very common among the refugee and migrant populations living on the Thai-Myanmar border [20]. This study will quantify the contribution of G6PD-deficiency to the incidence and severity of NH in these populations.…”

Section: Discussionmentioning

confidence: 99%

Neonatal Hyperbilirubinemia in a Marginalized Population on the Thai-Myanmar Border: a study protocol

et al. 2017

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BackgroundThis study aims to identify risk factors and the neurodevelopmental impact of neonatal hyperbilirubinemia in a limited-resource setting among a refugee and migrant population residing along the Thai-Myanmar border, an area with a high prevalence of glucose-6-phosphate dehydrogenase-deficiency.MethodsThis is an analytic, observational, prospective birth cohort study including all infants of estimated gestational age equal to or greater than 28 weeks from mothers who followed antenatal care in the Shoklo Malaria Research Unit clinics. At birth, a series of clinical exams and laboratory investigations on cord blood will be carried out. Serum bilirubin will be measured in all infants during their first week of life. All the infants of the cohort will be clinically followed until the age of one year, including monitoring of their neurodevelopment.DiscussionThe strength of this study is the prospective cohort design. It will allow us to collect information about the pregnancy and detect all infants with neonatal hyperbilirubinemia, to observe their clinical response under treatment and to compare their neurodevelopment with infants who did not develop neonatal hyperbilirubinemia. Our study design has some limitations in particular the generalizability of our findings will be limited to infants born after the gestational age of 28 weeks onwards and neurodevelopment to the end of the first year of life.Trial registrationClinicalTrials.gov ID NCT02361788, registration date September 1st, 2014.

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“…G6PD Mahidol is the most common deficient variant (occurs in 88–96% of G6PD-deficient subjects) in Thai-Myanmar border area [26–28]. This variant provides selective advantage against Plasmodium vivax but not against Plasmodium falciparum , which stipulates Plasmodium vivax has been the driving force for selective advantage conferred by Mahidol variant [29].…”

Section: Discussionmentioning

confidence: 99%

Molecular Analysis of Glucose-6-Phosphate Dehydrogenase Gene Mutations in Bangladeshi Individuals

et al. 2016

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Glucose-6-phosphate dehydrogenase (G6PD) deficiency is a common X-linked human enzyme defect of red blood cells (RBCs). Individuals with this gene defect appear normal until exposed to oxidative stress which induces hemolysis. Consumption of certain foods such as fava beans, legumes; infection with bacteria or virus; and use of certain drugs such as primaquine, sulfa drugs etc. may result in lysis of RBCs in G6PD deficient individuals. The genetic defect that causes G6PD deficiency has been identified mostly as single base missense mutations. One hundred and sixty G6PD gene mutations, which lead to amino acid substitutions, have been described worldwide. The purpose of this study was to detect G6PD gene mutations in hospital-based settings in the local population of Dhaka city, Bangladesh. Qualitative fluorescent spot test and quantitative enzyme activity measurement using RANDOX G6PDH kit were performed for analysis of blood specimens and detection of G6PD-deficient participants. For G6PD-deficient samples, PCR was done with six sets of primers specific for G6PD gene. Automated Sanger sequencing of the PCR products was performed to identify the mutations in the gene. Based on fluorescence spot test and quantitative enzyme assay followed by G6PD gene sequencing, 12 specimens (11 males and one female) among 121 clinically suspected patient-specimens were found to be deficient, suggesting a frequency of 9.9% G6PD deficiency. Sequencing of the G6PD-deficient samples revealed c.C131G substitution (exon-3: Ala44Gly) in six samples, c.G487A substitution (exon-6:Gly163Ser) in five samples and c.G949A substitution (exon-9: Glu317Lys) of coding sequence in one sample. These mutations either affect NADP binding or disrupt protein structure. From the study it appears that Ala44Gly and Gly163Ser are the most common G6PD mutations in Dhaka, Bangladesh. This is the first study of G6PD mutations in Bangladesh.

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Characterization of G6PD Genotypes and Phenotypes on the Northwestern Thailand-Myanmar Border

Cited by 85 publications

References 29 publications

An optimised age-based dosing regimen for single low-dose primaquine for blocking malaria transmission in Cambodia

An optimised age-based dosing regimen for single low-dose primaquine for blocking malaria transmission in Cambodia

Neonatal Hyperbilirubinemia in a Marginalized Population on the Thai-Myanmar Border: a study protocol

Molecular Analysis of Glucose-6-Phosphate Dehydrogenase Gene Mutations in Bangladeshi Individuals

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