Quantification of glucose-6-phosphate dehydrogenase activity by spectrophotometry: A systematic review and meta-analysis

Pfeffer, Daniel; Ley, Benedikt; Howes, Rosalind E.; Adu, Patrick; Alam, Mohammad Shafiul; Bansil, Pooja; Boum, Yap; Brito, Marcelo Augusto Mota; Charoenkwan, Pimlak; Clements, Archie; Cui, Liwang; Deng, Zeshuai; Egesie, OJ; Espino, Fe Esperanza; Fricken, Michael E. von; Hamid, Muzamil Mahdi Abdel; He, Yongshu; Henriques, Gisela; Khan, Wasif Ali; Khim, Nimol; Kim, Saorin; Lacerda, Marcus; Lon, Chanthap; Mekuria, Asrat Hailu; Ménard, Didier; Monteiro, Wuelton Marcelo; Nosten, François; Oo, Nwe Nwe; Pal, Sampa; Palasuwan, Duangdao; Parikh, Sunil; Pasaribu, Ayodhia Pitaloka; Poespoprodjo, Jeanne Rini; Price, David J.; Roca-Feltrer, Arantxa; Roh, Michelle E.; Saunders, David; Spring, Michele; Sutanto, Inge; LeyThriemer, Kamala; Weppelmann, Thomas A.; Seidlein, Lorenz von; Satyagraha, Ari Winasti; Bancone, Germana; Domingo, Gonzalo J.; Price, Ric

doi:10.1371/journal.pmed.1003084

Cited by 43 publications

(48 citation statements)

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“…Although G6PD genotype is a key determinant of enzyme activity [ 43 ], we observed poor correlation between G6PD genotype and phenotype, a phenomenon that reflect both assay variability as well as host and environmental factors [ 44 – 49 ]. Almost 25% of females heterozygous for a known local G6PD variant had activities above 70%, likely due to lyonization patterns in favor of the G6PD normal allele [ 50 ].…”

Section: Discussionmentioning

confidence: 99%

“…Malaria status was not a significant predictor of G6PD activity irrespective of diagnostic assay applied, however our study was neither designed nor powered to this effect. Although G6PD genotype is a key determinant of enzyme activity [43], we observed poor correlation between G6PD genotype and phenotype, a phenomenon that reflect both assay variability as well as host and environmental factors [44][45][46][47][48][49]. Almost 25% of females heterozygous for a known local G6PD variant had activities above 70%, likely due to lyonization patterns in favor of the G6PD normal allele [50].…”

Section: Plos Neglected Tropical Diseasesmentioning

confidence: 96%

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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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Section: Discussionmentioning

confidence: 99%

Section: Plos Neglected Tropical Diseasesmentioning

confidence: 96%

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

et al. 2020

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“…A recent meta-analysis identified substantial inter-laboratory variation in measurements around the 70% threshold of G6PD activity using ultraviolet spectrophotometry, the most popular quantitative diagnostic method for G6PD deficiency. Measurements appear to be more robust at the 30% threshold ( Pfeffer et al, 2020 ). Hand-held biosensors for point-of-care quantification of G6PD activity, which are currently under development, are expected to become available in the near future in malaria clinics worldwide.…”

Section: Therapeutic Efficacy Trials Of Hypnozoitocidesmentioning

confidence: 99%

Monitoring Plasmodium vivax resistance to antimalarials: Persisting challenges and future directions

Ferreira

Sousa²,

Rangel

et al. 2021

International Journal for Parasitology: Drugs and Drug Resistan

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Emerging antimalarial drug resistance may undermine current efforts to control and eliminate Plasmodium vivax , the most geographically widespread yet neglected human malaria parasite. Endemic countries are expected to assess regularly the therapeutic efficacy of antimalarial drugs in use in order to adjust their malaria treatment policies, but proper funding and trained human resources are often lacking to execute relatively complex and expensive clinical studies, ideally complemented by ex vivo assays of drug resistance. Here we review the challenges for assessing in vivo P. vivax responses to commonly used antimalarials, especially chloroquine and primaquine, in the presence of confounding factors such as variable drug absorption, metabolism and interaction, and the risk of new infections following successful radical cure. We introduce a simple modeling approach to quantify the relative contribution of relapses and new infections to recurring parasitemias in clinical studies of hypnozoitocides. Finally, we examine recent methodological advances that may render ex vivo assays more practical and widely used to confirm P. vivax drug resistance phenotypes in endemic settings and review current approaches to the development of robust genetic markers for monitoring chloroquine resistance in P. vivax populations.

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“…G6PD activity is measured in U/gHb, but no universal cut-off for G6PDd has been defined, not least because standardization of the phenotypic reference method, spectrophotometry, is poor [ 55 ]. Instead, 100% activity is defined based on the adjusted male median (AMM) G6PD activity [ 56 ].…”

Section: Introductionmentioning

confidence: 99%

“…Quantitative UV-spectrophotometry, the phenotypic reference method, is costly and requires a well-established laboratory infrastructure ( Table 2 ) [ 55 , 56 , 58 ]. The spectrophotometry output requires calculation using the corresponding haemoglobin reading to derive a result in U/gHb, the necessary format to guide treatment.…”

Section: Introductionmentioning

confidence: 99%

Towards the elimination of Plasmodium vivax malaria: Implementing the radical cure

2021

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Quantification of glucose-6-phosphate dehydrogenase activity by spectrophotometry: A systematic review and meta-analysis

Abstract: Peer Review History: PLOS recognizes the benefits of transparency in the peer review process; therefore, we enable the publication of all of the content of peer review and author responses alongside final, published articles. The editorial history of this article is available here:

Cited by 43 publications

References 30 publications

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

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

Monitoring Plasmodium vivax resistance to antimalarials: Persisting challenges and future directions

Towards the elimination of Plasmodium vivax malaria: Implementing the radical cure

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