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

English version

Autoři: Daniel A. Pfeffer ^aff001; Benedikt Ley ^aff001; Rosalind E. Howes ^aff002; Patrick Adu ^aff004; Mohammad Shafiul Alam ^aff005; Pooja Bansil ^aff006; Yap Boum, II ^aff007; Marcelo Brito ^aff009; Pimlak Charoenkwan ^aff010; Archie Clements ^aff011; Liwang Cui ^aff013; Zeshuai Deng ^aff014; Ochaka Julie Egesie ^aff015; Fe Esperanza Espino ^aff016; Michael E. von Fricken ^aff017; Muzamil Mahdi Abdel Hamid ^aff018; Yongshu He ^aff014; Gisela Henriques ^aff019; Wasif Ali Khan ^aff005; Nimol Khim ^aff020; Saorin Kim ^aff020; Marcus Lacerda ^aff009; Chanthap Lon ^aff021; Asrat Hailu Mekuria ^aff022; Didier Menard ^aff023; Wuelton Monteiro ^aff009; Francois Nosten ^aff024; Nwe Nwe Oo ^aff026; Sampa Pal ^aff006; Duangdao Palasuwan ^aff027; Sunil Parikh ^aff028; Ayodhia Pitaloka Pasaribu ^aff029; Jeanne Rini Poespoprodjo ^aff030; David J. Price ^aff031; Arantxa Roca-Feltrer ^aff033; Michelle E. Roh ^aff034; David L. Saunders ^aff021; Michele D. Spring ^aff021; Inge Sutanto ^aff037; Kamala Ley-Thriemer ^aff001; Thomas A. Weppelmann ^aff038; Lorenz von Seidlein ^aff024; Ari Winasti Satyagraha ^aff040; Germana Bancone ^aff024; Gonzalo J. Domingo ^aff006; Ric N. Price ^aff001
Působiště autorů: Global and Tropical Health Division, Menzies School of Health Research and Charles Darwin University, Darwin, Australia ^aff001; Malaria Atlas Project, Big Data Institute, Nuffield Department of Medicine, University of Oxford, Oxford, United Kingdom ^aff002; Foundation for Innovative New Diagnostics, Geneva, Switzerland ^aff003; Department of Medical Laboratory Sciences, School of Allied Health Sciences, University of Cape Coast, Cape Coast, Ghana ^aff004; Infectious Diseases Division, International Centre for Diarrheal Diseases Research, Bangladesh, Mohakhali, Dhaka, Bangladesh ^aff005; Diagnostics Program, PATH, Seattle, Washington, United States of America ^aff006; Médecins sans Frontières Epicentre, Mbarara Research Centre, Mbarara, Uganda ^aff007; Mbarara University of Science and Technology, Mbarara, Uganda ^aff008; Fundação de Medicina Tropical Dr. Heitor Vieira Dourado, Manaus, Amazonas, Brasil ^aff009; Division of Hematology and Oncology, Department of Pediatrics, Faculty of Medicine, Chiang Mai University, Chiang Mai, Thailand ^aff010; Faculty of Health Sciences, Curtin University, Bentley, Australia ^aff011; Telethon Kids Institute, Nedlands, Australia ^aff012; Department of Entomology, Pennsylvania State University, University Park, Pennsylvania, United States of America ^aff013; Department of Cell Biology and Medical Genetics, Kunming Medical University, Kunming, Yunnan Province, China ^aff014; Department of Hematology and Blood Transfusion, Faculty of Medical Sciences, University of Jos and Jos University Teaching Hospital, Jos, Plateau State, Nigeria ^aff015; Department of Parasitology, Research Institute for Tropical Medicine, Department of Health, Alabang, Muntinlupa City, Philippines ^aff016; Department of Global and Community Health, George Mason University, Fairfax, Virginia, United States of America ^aff017; Department of Parasitology and Medical Entomology, Institute of Endemic Diseases, University of Khartoum, Khartoum, Republic of the Sudan ^aff018; Faculty of Infectious and Tropical Diseases, London School of Hygiene & Tropical Medicine, London, United Kingdom ^aff019; Malaria Molecular Epidemiology Unit, Institut Pasteur du Cambodge, Phnom Penh, Cambodia ^aff020; Armed Forces Research Institute of Medical Sciences, Bangkok, Thailand ^aff021; School of Medicine, Addis Ababa University, Addis Ababa, Ethiopia ^aff022; Malaria Genetics and Resistance Group, Institut Pasteur, Paris, France ^aff023; Shoklo Malaria Research Unit, Mahidol–Oxford Tropical Medicine Research Unit, Faculty of Tropical Medicine, Mahidol University, Mae Sot, Thailand ^aff024; Centre for Tropical Medicine & Global Health, Nuffield Department of Medicine, University of Oxford, Oxford, United Kingdom ^aff025; Department of Medical Research, Lower Myanmar, Yangon, Myanmar ^aff026; Oxidation in Red Cell Disorders and Health Research Unit, Department of Clinical Microscopy, Faculty of Allied Health Sciences, Chulalongkorn University, Bangkok, Thailand ^aff027; Yale School of Public Health, New Haven, Connecticut, United States of America ^aff028; Faculty of Medicine, Universitas Sumatera Utara, Medan, Indonesia ^aff029; Yayasan Pengembangan Kesehatan dan Masyarakat Papua (YPKMP), Papua, Indonesia ^aff030; Centre for Epidemiology and Biostatistics, Melbourne School of Population and Global Health, University of Melbourne, Melbourne, Australia ^aff031; The Peter Doherty Institute for Infection and Immunity, The University of Melbourne and Royal Melbourne Hospital, Melbourne, Australia ^aff032; Malaria Consortium, Phnom Penh, Cambodia ^aff033; Global Health Group, Malaria Elimination Initiative, University of California, San Francisco, San Francisco, United States of America ^aff034; F. Edward Hebert School of Medicine, Uniformed Services University of the Health Sciences, Bethesda, Maryland, United States of America ^aff035; US Army Medical Materiel Development Activity, Fort Detrick, Maryland, United States of America ^aff036; University of Indonesia, Jakarta, Indonesia ^aff037; Herbert Wertheim College of Medicine, Florida International University, Miami, Florida, United States of America ^aff038; Mahidol Oxford Tropical Medicine Research Unit, Faculty of Tropical Medicine, Mahidol University, Bangkok, Thailand ^aff039; Eijkman Institute for Molecular Biology, Jakarta, Indonesia ^aff040
Vyšlo v časopise: Quantification of glucose-6-phosphate dehydrogenase activity by spectrophotometry: A systematic review and meta-analysis. PLoS Med 17(5): e32767. doi:10.1371/journal.pmed.1003084
Kategorie: Research Article
doi: https://doi.org/10.1371/journal.pmed.1003084

Souhrn

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.

Klíčová slova:

Antimalarials – Glucose-6-phosphate dehydrogenase deficiency – Hematology – Malaria – Plasmodium – Primaquine – Quality control – Spectrophotometry

Zdroje

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