scholarly journals Prevalence and distribution of G6PD deficiency: implication for the use of primaquine in malaria treatment in Ethiopia

2019 ◽  
Vol 18 (1) ◽  
Author(s):  
Eugenia Lo ◽  
Daibin Zhong ◽  
Beka Raya ◽  
Kareen Pestana ◽  
Cristian Koepfli ◽  
...  
Keyword(s):  
Plasmodium Vivax ◽  
G6pd Deficiency ◽  
Enzyme Level ◽  
Gene Mutations ◽  
Malaria Treatment ◽  
Fisher Exact Test ◽  
Radical Cure ◽  
Febrile Patient ◽  
South Ethiopia ◽  
G6pd Gene

Abstract Background G6PD enzyme deficiency is a common enzymatic X-linked disorder. Deficiency of the G6PD enzyme can cause free radical-mediated oxidative damage to red blood cells, leading to premature haemolysis. Treatment of Plasmodium vivax malaria with primaquine poses a potential risk of mild to severe acute haemolytic anaemia in G6PD deficient people. In this study, the prevalence and distribution of G6PD mutations were investigated across broad areas of Ethiopia, and tested the association between G6PD genotype and phenotype with the goal to provide additional information relevant to the use of primaquine in malaria treatment. Methods This study examined G6PD mutations in exons 3–11 for 344 febrile patient samples collected from seven sites across Ethiopia. In addition, the G6PD enzyme level of 400 febrile patient samples from Southwestern Ethiopia was determined by the CareStart™ biosensor. The association between G6PD phenotype and genotype was examined by Fisher exact test on a subset of 184 samples. Results Mutations were observed at three positions of the G6PD gene. The most common G6PD mutation across all sites was A376G, which was detected in 21 of 344 (6.1%) febrile patients. Thirteen of them were homozygous and eight were heterozygous for this mutation. The G267+119C/T mutation was found in 4 (1.2%) individuals in South Ethiopia, but absent in other sites. The G1116A mutation was also found in 4 (1.2%) individuals from East and South Ethiopia. For the 400 samples in the south, 17 (4.25%) were shown to be G6PD-deficient. G6PD enzyme level was not significantly different by age or gender. Among a subset of 202 febrile patients who were diagnosed with malaria, 11 (5.45%) were G6PD-deficient. These 11 infected samples were diagnosed with Plasmodium vivax by microscopy. Parasitaemia was not significantly different between the G6PD-deficient and G6PD-normal infections. Conclusions The prevalence of G6PD deficiency is modest among febrile patients in Ethiopia. G6PD deficiency testing is thus recommended before administrating primaquine for radical cure of P. vivax infected patients. The present study did not indicate a significant association between G6PD gene mutations and enzyme levels.

scholarly journals Protective effect of Mediterranean-type glucose-6-phosphate dehydrogenase deficiency against Plasmodium vivax malaria

eLife ◽  
2021 ◽  
Vol 10 ◽  
Author(s):  
Ghulam R Awab ◽  
Fahima Aaram ◽  
Natsuda Jamornthanyawat ◽  
Kanokon Suwannasin ◽  
Watcharee Pagornrat ◽  
...  
Keyword(s):  
Protective Effect ◽  
Plasmodium Vivax ◽  
G6pd Deficiency ◽  
Vivax Malaria ◽  
Malaria Incidence ◽  
Large Population ◽  
Credible Interval ◽  
Radical Cure ◽  
Plasmodium Vivax Malaria ◽  
Glucose 6 Phosphate Dehydrogenase

X-linked glucose-6-phosphate dehydrogenase (G6PD) deficiency is the most common human enzymopathy. The severe Mediterranean variant (G6PD Med) found across Europe and Asia is thought to confer protection against malaria, but its effect is unclear. We fitted a Bayesian statistical model to observed G6PD Med allele frequencies in 999 Pashtun patients presenting with acute Plasmodium vivax malaria and 1408 population controls. G6PD Med was associated with reductions in symptomatic P. vivax malaria incidence of 76% (95% credible interval [CI], 58–88) in hemizygous males and homozygous females combined and 55% (95% CI, 38–68) in heterozygous females. Unless there is very large population stratification within the Pashtun (confounding these results), the G6PD Med genotype confers a very large and gene-dose proportional protective effect against acute vivax malaria. The proportion of patients with vivax malaria at risk of haemolysis following 8-aminoquinoline radical cure is substantially overestimated by studies measuring G6PD deficiency prevalence in healthy subjects.

scholarly journals Prevalence and Genetic Characterization of Glucose-6-Phosphate Dehydrogenase Deficiency in Anemic Subjects from Uttar Pradesh, India

2019 ◽  
Vol 08 (02) ◽  
pp. 047-053 ◽  
Author(s):  
Poonam Tripathi ◽  
Sarita Agarwal ◽  
Srinivasan Muthuswamy
Keyword(s):  
G6pd Deficiency ◽  
Dehydrogenase Deficiency ◽  
Genetic Characterization ◽  
Gene Mutations ◽  
Uttar Pradesh ◽  
Chromosome X ◽  
G6pd Gene ◽  
Glucose 6 Phosphate Dehydrogenase ◽  
Fluorescent Spot

AbstractGlucose-6-phosphate dehydrogenase (G6PD) deficiency is caused by one or more mutations in the G6PD gene on chromosome X. It affects approximately 400 million people worldwide. The purpose of this study was to detect the prevalence of G6PD deficiency and G6PD gene mutations in the hospital-based settings in patients referred for suspected G6PD deficiency. A qualitative fluorescent spot test and dichlorophenol-indolphenol (DCIP) test were performed. G6PD-deficient, positive samples were further processed for mutation analysis by Sanger sequencing. Out of 1,069 cases, 95 (8.8%) were detected as G6PD deficient (by DCIP test) and were sent for molecular analysis. The G6PD Mediterranean mutation (563C > T) is the most common variant among G6PD-deficient individuals followed by the Coimbra (592C→T) and Orissa (131C→G) variants. We concluded that all symptomatic patients (anemic or jaundiced) should be investigated for G6PD deficiency. Our findings will inform our population screening approach and help provide better management for G6PD-deficient patients.

scholarly journals Optimizing G6PD testing for Plasmodium vivax case management: why sex, counseling, and community engagement matter

2020 ◽  
Vol 5 ◽  
pp. 21
Author(s):  
Cindy S Chu ◽  
Germana Bancone ◽  
Maureen Kelley ◽  
Nicole Advani ◽  
Gonzalo J Domingo ◽  
...  
Keyword(s):  
Plasmodium Vivax ◽  
G6pd Deficiency ◽  
Point Of Care ◽  
Genetic Disorder ◽  
Treatment Options ◽  
Radical Cure ◽  
Sex Counseling ◽  
Point Of Care Diagnostics ◽  
Genetic Test Results ◽  
Human Genetic Disorder

Safe access to the most effective treatment options for Plasmodium vivax malaria are limited by the absence of accurate point-of-care testing to detect glucose-6-phosphate dehydrogenase (G6PD) deficiency, the most common human genetic disorder. G6PD-deficient patients are at risk of life-threatening hemolysis when exposed to 8-aminoquinolines, the only class of drugs efficacious against P. vivax hypnozoites. Until recently, only qualitative tests were available in most settings. These accurately identify patients with severe G6PD deficiency (mostly male) but not patients with intermediate G6PD deficiency (always female). This has led to and reinforced a gap in awareness in clinical practice of the risks and implications of G6PD deficiency in females—who, unlike males, can have a heterozygous genotype for G6PD. Increasing recognition of the need for radical cure of P. vivax, first for patients’ health and then for malaria elimination, is driving the development of new point-of-care tests for G6PD deficiency and their accessibility to populations in low-resource settings. The availability of simple, affordable, and accurate point-of-care diagnostics for the precise classification of the three G6PD phenotypes can reduce sex-linked disparities by ensuring safe and effective malaria treatment, providing opportunities to develop supportive counseling to enhance understanding of genetic test results, and improving the detection of all G6PD deficiency phenotypes in newborns and their family members.

scholarly journals The Economics of Vivax Malaria Treatment

2018 ◽  
Author(s):  
Angela Devine
Keyword(s):  
Economic Burden ◽  
G6pd Deficiency ◽  
Vivax Malaria ◽  
Healthcare Providers ◽  
Malaria Treatment ◽  
Screening Tests ◽  
Radical Cure ◽  
Cost Component ◽  
Highly Effective ◽  
The Cost

The control and eventual elimination of malaria will require widescale adoption of strategies to ensure early diagnosis and highly effective treatment of infected individuals. In Plasmodium vivax, multiple relapse episodes can only be averted by treating the dormant liver stage of the parasite life cycle - a strategy known as radical cure. This thesis aims to investigate key factors determining treatment-seeking behaviour and costs associated with vivax malaria, how these influence healthcare decisions, the cost-effectiveness of screening tests and treatments for radical cure, and the cost-benefit implications of their global implementation.Treatment-seeking behaviour, assessed in Papua, Indonesia, demonstrated that household costs per person seeking treatment for vivax malaria were similar to those for falciparum malaria. Switching from ineffective to effective malaria treatment in the public sector improved the behaviour of patients and both public and private healthcare providers. Diagnostic strategies were investigated on the Thai-Myanmar border, where screening for glucose-6-phosphate-dehydrogenase (G6PD) deficiency prior to radical cure reduced the disease burden while being a cost-effective option for healthcare providers that do not use radical cure and a potentially cost-saving alternative where primaquine is prescribed without screening. The costs of implementing G6PD screening were collected in three countries, and highlighted that RDTs consistently reduced costs as compared to the widely-used fluorescent spot test. Across four countries, the indirect cost due to lost productivity was the largest cost component for households of patients with vivax malaria. After combining provider and patient costs with case estimates, the global economic burden of vivax malaria was estimated to be US\$330 million per year. Adopting a policy of screening for G6PD deficiency with delivery of highly effective radical cure was projected to save US\$45 million.P. vivax malaria causes a large economic burden that can be reduced substantially by delivering safe and effective radical cure.

scholarly journals Optimizing G6PD testing for Plasmodium vivax case management and beyond: why sex, counseling, and community engagement matter

2020 ◽  
Vol 5 ◽  
pp. 21
Author(s):  
Cindy S Chu ◽  
Germana Bancone ◽  
Maureen Kelley ◽  
Nicole Advani ◽  
Gonzalo J Domingo ◽  
...  
Keyword(s):  
Plasmodium Vivax ◽  
G6pd Deficiency ◽  
Point Of Care ◽  
Genetic Disorder ◽  
Treatment Options ◽  
Radical Cure ◽  
Sex Counseling ◽  
Point Of Care Diagnostics ◽  
Genetic Test Results ◽  
Human Genetic Disorder

Safe access to the most effective treatment options for Plasmodium vivax malaria are limited by the absence of accurate point-of-care testing to detect glucose-6-phosphate dehydrogenase (G6PD) deficiency, the most common human genetic disorder. G6PD-deficient patients are at risk of life-threatening hemolysis when exposed to 8-aminoquinolines, the only class of drugs efficacious against P. vivax hypnozoites. Until recently, only qualitative tests were available in most settings. These can identify patients with severe G6PD deficiency (mostly male) but not patients with intermediate G6PD deficiency (always female). This has led to and reinforced a gap in awareness in clinical practice of the risks and implications of G6PD deficiency in females—who, unlike males, can have a heterozygous genotype for G6PD. Increasing recognition of the need for radical cure of  P. vivax, first for patients’ health and then for malaria elimination, is driving the development of new point-of-care tests for G6PD deficiency and their accessibility to populations in low-resource settings. The availability of user-friendly, affordable, and accurate quantitative point-of-care diagnostics for the precise classification of the three G6PD phenotypes can reduce sex-linked disparities by ensuring safe and effective malaria treatment, providing opportunities to develop supportive counseling to enhance understanding of genetic test results, and improving the detection of all G6PD deficiency phenotypes in newborns and their family members.

Molecular Characterization of Glucose-6-Phosphate Dehydrogenase Deficiency in the Shenzhen Population

2021 ◽  
pp. 1-7
Author(s):  
Jian Gao ◽  
Sheng Lin ◽  
Shiguo Chen ◽  
Qunyan Wu ◽  
Kaifeng Zheng ◽  
...  
Keyword(s):  
G6pd Deficiency ◽  
Amplification Refractory Mutation System ◽  
Gene Variants ◽  
Coding Region ◽  
G6pd Gene ◽  
Mutation System ◽  
Hotspot Mutations ◽  
Glucose 6 Phosphate Dehydrogenase ◽  
Generation Sequencing

<b><i>Background:</i></b> Glucose-6-phosphate dehydrogenase (G6PD) deficiency is caused by one or more mutations in the G6PD gene on chromosome X. This study aimed to characterize the G6PD gene variant distribution in Shenzhen of Guangdong province. <b><i>Methods:</i></b> A total of 33,562 individuals were selected at the hospital for retrospective analysis, of which 1,213 cases with enzymatic activity-confirmed G6PD deficiency were screened for G6PD gene variants. Amplification refractory mutation system PCR was first used to screen the 6 dominant mutants in the Chinese population (c.1376G&#x3e;T, c.1388G&#x3e;A, c.95A&#x3e;G, c.1024C&#x3e;T, c.392G&#x3e;T, and c.871G&#x3e;A). If the 6 hotspot variants were not found, next-generation sequencing was then performed. Finally, Sanger sequencing was used to verify all the mutations. <b><i>Results:</i></b> The incidence of G6PD deficiency in this study was 3.54%. A total of 26 kinds of mutants were found in the coding region, except for c.-8-624T&#x3e;C, which was in the noncoding region. c.1376G&#x3e;T and c.1388G&#x3e;A, both located in exon 12, were the top 2 mutants, accounting for 68.43% of all individuals. The 6 hotspot mutations had a cumulative proportion of 94.02%. <b><i>Conclusions:</i></b> This study provided detailed characteristics of G6PD gene variants in Shenzhen, and the results would be valuable to enrich the knowledge of G6PD deficiency.

scholarly journals G6PD deficiency among malaria-infected national groups at the western part of Myanmar with implications for primaquine use in malaria elimination

2021 ◽  
Vol 49 (1) ◽  
Author(s):  
Kay Thwe Han ◽  
Zay Yar Han ◽  
Kyin Hla Aye ◽  
Khin Thet Wai ◽  
Aung Thi ◽  
...  
Keyword(s):  
Enzyme Activity ◽  
Malaria Elimination ◽  
G6pd Deficiency ◽  
Control Program ◽  
Cross Sectional Study ◽  
Diagnostic Tools ◽  
Asymptomatic Malaria ◽  
Radical Cure ◽  
Readiness Assessment ◽  
Cross Sectional

Abstract Background Glucose 6-phosphate dehydrogenase deficiency (G6PDd) plays a central role in readiness assessment for malaria elimination in Myanmar by 2030 that includes primaquine (PQ) use. The risk of hemolysis in G6PDd individuals hampers the widespread use of primaquine safely in malaria-infected patients. In the pre-elimination era, it is important to screen initially for asymptomatic malaria in combination with G6PD deficiency by applying more sensitive diagnostic tools. Therefore, this study examined the proportion of G6PDd and the distribution of G6PD genotypes among malaria-infected national groups in Myanmar before initiation of malaria elimination strategies. Methods A cross-sectional study in one township each with high malaria burden from two states in the western part of Myanmar, was conducted during 2016-2018, and 320 participants (164 Rakhine and 156 Chin National groups) were recruited. We used RDT and ultrasensitive polymerase chain reaction (us PCR) method to confirm malaria infection, and a G6PD RDT(CareStart) to detect G6PDd and PCR/restriction fragment length polymorphism (RFLP) method to confirm the variant of G6PDd for genotyping. G6PD enzyme activity was measured by G6PD Biosensor (CareStart). Results Malaria positivity rates detected by RDT were lower than those detected by us PCR in the combined samples [13% (42/320) vs. 21% (67/320)] as well as in the Rakhine samples [17% (28/164) vs. 25% (41/164)] and in Chin samples [9% (14/156) vs. 17% (26/156)]. G6PD deficiency rates were approximately 10% in both the combined samples and specific national groups. For G6PD enzyme activity in the combined samples, G6PDd (defined as < 30% of adjusted male median) was 10% (31/320) and severe G6PDd (< 10% of AMM) was 3% (9/320). Among malaria-infected patients with positive by both RDT and usPCR, G6PDd was less than 20% in each national group. G6PD genotyping showed that the G6PD Mahidol (G487A) was the major variant. Conclusions The varying degree of G6PDd detected among malaria-infected national groups by advanced diagnostic tools, strongly support the recommend G6PD testing by the National Malaria Control Program and the subsequent safe treatment of P. vivax by primaquine for radical cure. Establishing a field monitoring system to achieve timely malaria elimination is mandatory to observe the safety of patients after PQ treatment.

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