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Review of key knowledge gaps in glucose-6-phosphate dehydrogenase deficiency detection with regard to the safe clinical deployment of 8-aminoquinoline treatment regimens: a workshop report

Lorenz von Seidlein1*, Sarah Auburn1, Fe Espino2, Dennis Shanks3, Qin Cheng3, James McCarthy4, Kevin Baird5, Catherine Moyes6, Rosalind Howes6, Didier Ménard7, Germana Bancone8, Ari Winasti-Satyahraha5, Lasse S Vestergaard9, Justin Green10, Gonzalo Domingo11, Shunmay Yeung12 and Ric Price113

Author Affiliations

1 Global and Tropical Health Division, Menzies School of Health Research, Charles Darwin University, Darwin, NT, Australia

2 Research Institute for Tropical Medicine, Manila, Philippines

3 Australian Army Malaria Institute, Enoggera, Australia

4 Queensland Institute of Medical Research, University of Queensland, 300 Herston Road, Herston, Brisbane, Queensland, 4006, Australia

5 Eijkman-Oxford Clinical Research Unit, Jakarta, Indonesia

6 Spatial Ecology and Epidemiology Group, Tinbergen Building, Department of Zoology, University of Oxford, Oxford, UK

7 Institut Pasteur of Cambodia, Phnom Penh, Cambodia

8 Shoklo Malaria Research Unit, Mae Sot, Thailand

9 WHO/WPRO, Manila, Philippines

10 GlaxoSmithKline, Stockley Park, Uxbridge, UK

11 PATH, Seattle, SE, USA

12 The Mahidol Oxford Tropical Medicine Research Unit, Bangkok, Thailand

13 Centre for Tropical Medicine, Nuffield Department of Medicine, University of Oxford, Oxford, UK

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Malaria Journal 2013, 12:112  doi:10.1186/1475-2875-12-112

Published: 27 March 2013

Abstract

The diagnosis and management of glucose-6-phosphate dehydrogenase (G6PD) deficiency is a crucial aspect in the current phases of malaria control and elimination, which will require the wider use of 8-aminoquinolines for both reducing Plasmodium falciparum transmission and achieving the radical cure of Plasmodium vivax. 8-aminoquinolines, such as primaquine, can induce severe haemolysis in G6PD-deficient individuals, potentially creating significant morbidity and undermining confidence in 8-aminoquinoline prescription. On the other hand, erring on the side of safety and excluding large numbers of people with unconfirmed G6PD deficiency from treatment with 8-aminoquinolines will diminish the impact of these drugs. Estimating the remaining G6PD enzyme activity is the most direct, accessible, and reliable assessment of the phenotype and remains the gold standard for the diagnosis of patients who could be harmed by the administration of primaquine. Genotyping seems an unambiguous technique, but its use is limited by cost and the large range of recognized G6PD genotypes. A number of enzyme activity assays diagnose G6PD deficiency, but they require a cold chain, specialized equipment, and laboratory skills. These assays are impractical for care delivery where most patients with malaria live. Improvements to the diagnosis of G6PD deficiency are required for the broader and safer use of 8-aminoquinolines to kill hypnozoites, while lower doses of primaquine may be safely used to kill gametocytes without testing. The discussions and conclusions of a workshop conducted in Incheon, Korea in May 2012 to review key knowledge gaps in G6PD deficiency are reported here.

Keywords:
Malaria; Vivax; Falciparum; 8-aminoquinolines; Primaquine; Tafenoquine; G6PD; Deficiency; Diagnostic tests