Genotypic and phenotypic characterization of G6PD deficiency in Bengali adults with severe and uncomplicated malaria

Plewes, Katherine; Soontarawirat, Ingfar; Ghose, Aniruddha; Bancone, Germana; Hwf., Kingston; Herdman,; Leopold, Stije J.; Ishioka, Haruhiko; Faiz, M. Abul; Anstey, Nicholas M.; Npj., Day; Hossain, Md. Amir; Imwong, Mallika; Dondorp, Arjen M.; Woodrow, Charles J.

doi:10.1186/s12936-017-1788-x

Cited by 13 publications

(11 citation statements)

References 55 publications

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“…Neonates were followed up and after one month of age a capillary blood sample was tested with the FST by a locally trained laboratory technician. Samples with discrepant QC results at birth, and with different results at birth versus after one month of age were genotyped using established PCR-RFLP protocols for Mahidol, Chinese-4, Canton, Viangchan, Mediterranean and Kaiping mutations 25 .…”

Section: Methodsmentioning

confidence: 99%

Diagnostic performances of the fluorescent spot test for G6PD deficiency in newborns along the Thailand-Myanmar border: A cohort study

Thielemans¹,

Gornsawun²,

Hanboonkunupakarn³

et al. 2018

Wellcome Open Res

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Background: Glucose-6-phosphate dehydrogenase (G6PD) deficiency is an inherited enzymatic disorder associated with severe neonatal hyperbilirubinemia and acute haemolysis after exposure to certain drugs or infections. The disorder can be diagnosed phenotypically with a fluorescent spot test (FST), which is a simple test that requires training and basic laboratory equipment. This study aimed to assess the diagnostic performances of the FST used on umbilical cord blood by locally-trained staff and to compare test results of the neonates at birth with the results after one month of age. Methods: We conducted a cohort study on newborns at the Shoklo Malaria Research Unit, along the Thai-Myanmar border between January 2015 and May 2016. The FST was performed at birth on the umbilical cord blood by locally-trained staff and quality controlled by specialised technicians at the central laboratory. The FST was repeated after one month of age. Genotyping for common local G6PD mutations was carried out for all discrepant results. Results: FST was performed on 1521 umbilical cord blood samples. Quality control and genotyping revealed 10 misdiagnoses. After quality control, 10.7% of the males (84/786) and 1.2% of the females (9/735) were phenotypically G6PD deficient at birth. The FST repeated at one month of age or later diagnosed 8 additional G6PD deficient infants who were phenotypically normal at birth. Conclusions: This study shows the short-comings of the G6PD FST in neonatal routine screening and highlights the importance of training and quality control. A more conservative interpretation of the FST in male newborns could increase the diagnostic performances. Quantitative point-of-care tests might show higher sensitivity and specificity for diagnosis of G6PD deficiency on umbilical cord blood and should be investigated.

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Section: Methodsmentioning

confidence: 99%

Diagnostic performances of the fluorescent spot test for G6PD deficiency in newborns along the Thailand-Myanmar border: A cohort study

Thielemans¹,

Gornsawun²,

Hanboonkunupakarn³

et al. 2018

Wellcome Open Res

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“…The study had some inherent limitations. The panel of five G6PD variants that were genotyped was based on earlier reports from the area [8,26,52]. However, a known G6PD variant was only present in 42% of patients with less than 70% G6PD activity.…”

Section: Plos Neglected Tropical Diseasesmentioning

confidence: 99%

“…vivax , but patients are not tested for G6PDd to guide treatment and no systematic assessment of the prevalence of G6PDd within the country has been conducted. Anecdotal reports from the CHT estimate the G6PDd prevalence between 20% and 40% (Khan, personal communication), however in hospital based surveys in the same region only 0.6% to 1.4% of patients were G6PDd [ 25 , 26 ]. The significant differences in these estimates may reflect study populations with different ethnic backgrounds, and associated differences in G6PD genetic profiles, or an underlying difference in G6PD activity in patients with and without malaria [ 15 , 27 ].…”

Section: Introductionmentioning

confidence: 99%

Wide range of G6PD activities found among ethnic groups of the Chittagong Hill Tracts, Bangladesh

et al. 2020

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The proportion of Plasmodium vivax malaria among all malarias is increasing worldwide. Treatment with 8-aminoquinolines remain the only radical cure. However, 8-aminoquinolines can cause severe hemolysis in glucose-6-phosphate dehydrogenase (G6PD) deficient patients. The population of the multi-ethnic Chittagong Hill Tracts (CHT) carry the highest malaria burden within Bangladesh. As in many countries the national treatment guidelines recommend 8-aminoquinoline based radical cure without routine G6PD deficiency (G6PDd) testing to guide treatment. Aim of this study was to determine the need for routine testing within a multi-ethnic population by assessing the prevalence of G6PDd among the local population. Participants from 11 ethnicities were randomly selected and malaria status was assessed by microscopy, rapid diagnostic test (RDT) and polymerase chain reaction (PCR). G6PD status was determined by spectrophotometry and G6PD genotyping. The adjusted male median (AMM) was defined as 100% G6PD activity, participants were categorized as G6PD deficient (<30% activity), G6PD intermediate (30% to 70% activity) or G6PD normal (>70% activity). Median G6PD activities between ethnicities were compared and the association between G6PD activity and malaria status was assessed. 1002 participants were enrolled and tested for malaria. G6PD activity was measured by spectrophotometry in 999 participants and host G6PD genotyping undertaken in 323 participants. Seven participants (0.7%) had peripheral parasitaemia detected by microscopy or RDT and 42 by PCR (4.2%). Among 106 participants (32.8%) with confirmed genotype, 99 (93.4%) had the Mahidol variant. The AMM was 7.03U/gHb with 90 (9.0%) G6PD deficient participants and 133 (13.3%) with intermediate G6PD activity. Median G6PD activity differed significantly between ethnicities (p<0.001), proportions of G6PD deficient individuals ranged from 2% to 26% but did not differ between participants with and without malaria. The high G6PDd prevalence and PLOS NEGLECTED TROPICAL DISEASES

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“…Seven of the nine studies were in South East Asian populations (dominant G6PDd genotypes: Viangchan, Mahidol and Vanua Lava); one study was from Bangladesh (likely dominant genotypes Orissa, Kalyan-Kerala [ 32 ] and Mahidol); and one study was in African Americans (dominant genotype: A-) ( Table 1 ).…”

Section: Resultsmentioning

confidence: 99%

Implications of current therapeutic restrictions for primaquine and tafenoquine in the radical cure of vivax malaria

et al. 2018

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BackgroundThe 8-aminoquinoline antimalarials, the only drugs which prevent relapse of vivax and ovale malaria (radical cure), cause dose-dependent oxidant haemolysis in individuals with glucose-6-phosphate dehydrogenase (G6PD) deficiency. Patients with <30% and <70% of normal G6PD activity are not given standard regimens of primaquine and tafenoquine, respectively. Both drugs are currently considered contraindicated in pregnant and lactating women.MethodsQuantitative G6PD enzyme activity data from 5198 individuals were used to estimate the proportions of heterozygous females who would be ineligible for treatment at the 30% and 70% activity thresholds, and the relationship with the severity of the deficiency. This was used to construct a simple model relating allele frequency in males to the potential population coverage of tafenoquine and primaquine under current prescribing restrictions.FindingsIndependent of G6PD deficiency, the current pregnancy and lactation restrictions will exclude ~13% of females from radical cure treatment. This could be reduced to ~4% if 8-aminoquinolines can be prescribed to women breast-feeding infants older than 1 month. At a 30% activity threshold, approximately 8–19% of G6PD heterozygous women are ineligible for primaquine treatment; at a 70% threshold, 50–70% of heterozygous women and approximately 5% of G6PD wild type individuals are ineligible for tafenoquine treatment. Thus, overall in areas where the G6PDd allele frequency is >10% more than 15% of men and more than 25% of women would be unable to receive tafenoquine. In vivax malaria infected patients these proportions will be lowered by any protective effect against P. vivax conferred by G6PD deficiency.ConclusionIf tafenoquine is deployed for radical cure, primaquine will still be needed to obtain high population coverage. Better radical cure antimalarial regimens are needed.

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Genotypic and phenotypic characterization of G6PD deficiency in Bengali adults with severe and uncomplicated malaria

Cited by 13 publications

References 55 publications

Diagnostic performances of the fluorescent spot test for G6PD deficiency in newborns along the Thailand-Myanmar border: A cohort study

Diagnostic performances of the fluorescent spot test for G6PD deficiency in newborns along the Thailand-Myanmar border: A cohort study

Wide range of G6PD activities found among ethnic groups of the Chittagong Hill Tracts, Bangladesh

Implications of current therapeutic restrictions for primaquine and tafenoquine in the radical cure of vivax malaria

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