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

Issued Date

2020-05-01

Resource Type

Article

ISSN

15491676

DOI

10.1371/journal.pmed.1003084

Other identifier(s)

2-s2.0-85084787376

Rights

Mahidol University

Rights Holder(s)

SCOPUS

Bibliographic Citation

PLoS medicine. Vol.17, No.5 (2020), e1003084

Suggested Citation

Daniel A. Pfeffer, Benedikt Ley, Rosalind E. Howes, Patrick Adu, Mohammad Shafiul Alam, Pooja Bansil, Yap Boum, Marcelo Brito, Pimlak Charoenkwan, Archie Clements, Liwang Cui, Zeshuai Deng, Ochaka Julie Egesie, Fe Esperanza Espino, Michael E. von Fricken, Muzamil Mahdi Abdel Hamid, Yongshu He, Gisela Henriques, Wasif Ali Khan, Nimol Khim, Saorin Kim, Marcus Lacerda, Chanthap Lon, Asrat Hailu Mekuria, Didier Menard, Wuelton Monteiro, François Nosten, Nwe Nwe Oo, Sampa Pal, Duangdao Palasuwan, Sunil Parikh, Ayodhia Pitaloka Pasaribu, Jeanne Rini Poespoprodjo, David J. Price, Arantxa Roca-Feltrer, Michelle E. Roh, David L. Saunders, Michele D. Spring, Inge Sutanto, Kamala Ley-Thriemer, Thomas A. Weppelmann, Lorenz von Seidlein, Ari Winasti Satyagraha, Germana Bancone, Gonzalo J. Domingo, Ric N. Price Quantification of glucose-6-phosphate dehydrogenase activity by spectrophotometry: A systematic review and meta-analysis. PLoS medicine. Vol.17, No.5 (2020), e1003084. doi:10.1371/journal.pmed.1003084 Retrieved from: https://repository.li.mahidol.ac.th/handle/123456789/56249

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Title

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

Author(s)

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

Other Contributor(s)

Herbert Wertheim College of Medicine
 Melbourne School of Population and Global Health
 Foundation for Innovative New Diagnostics, Switzerland
 Institut Pasteur du Cambodge
 University of Cape Coast Ghana
 Institute of Endemic Diseases Sudan
 Mbarara University of Science and Technology
 Gokila
 Addis Ababa University
 Fundacao de Medicina Tropical do Amazonas
 Universitas Sumatera Utara
 Eijkman Institute for Molecular Biology
 Universitas Indonesia
 Shoklo Malaria Research Unit
 London School of Hygiene & Tropical Medicine
 Curtin University
 PATH Seattle
 University of Jos
 Chulalongkorn University
 University of Melbourne
 Menzies School of Health Research
 University of California, San Francisco
 George Mason University, Fairfax Campus
 Armed Forces Research Institute of Medical Sciences, Thailand
 Kunming Medical University
 Mahidol University
 International Centre for Diarrhoeal Disease Research Bangladesh
 Nuffield Department of Clinical Medicine
 Uniformed Services University of the Health Sciences
 Medecins Sans Frontieres
 Yale University
 Institut Pasteur, Paris
 Pennsylvania State University
 Chiang Mai University
 Telethon Kids Institute
 Papua
 Malaria Consortium
 US Army Medical Materiel Development Activity

Abstract

BACKGROUND: The radical cure of Plasmodium vivax and P. ovale requires treatment with primaquine or tafenoquine to clear dormant liver stages. Either drug can induce haemolysis in individuals with glucose-6-phosphate dehydrogenase (G6PD) deficiency, necessitating screening. The reference diagnostic method for G6PD activity is ultraviolet (UV) spectrophotometry; however, a universal G6PD activity threshold above which these drugs can be safely administered is not yet defined. Our study aimed to quantify assay-based variation in G6PD spectrophotometry and to explore the diagnostic implications of applying a universal threshold. METHODS AND FINDINGS: Individual-level data were pooled from studies that used G6PD spectrophotometry. Studies were identified via PubMed search (25 April 2018) and unpublished contributions from contacted authors (PROSPERO: CRD42019121414). Studies were excluded if they assessed only individuals with known haematological conditions, were family studies, or had insufficient details. Studies of malaria patients were included but analysed separately. Included studies were assessed for risk of bias using an adapted form of the Quality Assessment of Diagnostic Accuracy Studies-2 (QUADAS-2) tool. Repeatability and intra- and interlaboratory variability in G6PD activity measurements were compared between studies and pooled across the dataset. A universal threshold for G6PD deficiency was derived, and its diagnostic performance was compared to site-specific thresholds. Study participants (n = 15,811) were aged between 0 and 86 years, and 44.4% (7,083) were women. Median (range) activity of G6PD normal (G6PDn) control samples was 10.0 U/g Hb (6.3-14.0) for the Trinity assay and 8.3 U/g Hb (6.8-15.6) for the Randox assay. G6PD activity distributions varied significantly between studies. For the 13 studies that used the Trinity assay, the adjusted male median (AMM; a standardised metric of 100% G6PD activity) varied from 5.7 to 12.6 U/g Hb (p < 0.001). Assay precision varied between laboratories, as assessed by variance in control measurements (from 0.1 to 1.5 U/g Hb; p < 0.001) and study-wise mean coefficient of variation (CV) of replicate measures (from 1.6% to 14.9%; p < 0.001). A universal threshold of 100% G6PD activity was defined as 9.4 U/g Hb, yielding diagnostic thresholds of 6.6 U/g Hb (70% activity) and 2.8 U/g Hb (30% activity). These thresholds diagnosed individuals with less than 30% G6PD activity with study-wise sensitivity from 89% (95% CI: 81%-94%) to 100% (95% CI: 96%-100%) and specificity from 96% (95% CI: 89%-99%) to 100% (100%-100%). However, when considering intermediate deficiency (<70% G6PD activity), sensitivity fell to a minimum of 64% (95% CI: 52%-75%) and specificity to 35% (95% CI: 24%-46%). Our ability to identify underlying factors associated with study-level heterogeneity was limited by the lack of availability of covariate data and diverse study contexts and methodologies. CONCLUSIONS: Our findings indicate that there is substantial variation in G6PD measurements by spectrophotometry between sites. This is likely due to variability in laboratory methods, with possible contribution of unmeasured population factors. While an assay-specific, universal quantitative threshold offers robust diagnosis at the 30% level, inter-study variability impedes performance of universal thresholds at the 70% level. Caution is advised in comparing findings based on absolute G6PD activity measurements across studies. Novel handheld quantitative G6PD diagnostics may allow greater standardisation in the future.

Keyword(s)

Medicine

Availability

URI

https://repository.li.mahidol.ac.th/handle/123456789/56249

Collections

Scopus 2020