Dynamics of G6PD activity in patients receiving weekly primaquine for therapy of Plasmodium vivax malaria.

<h4>Background</h4>Acute Plasmodium vivax malaria is associated with haemolysis, bone marrow suppression, reticulocytopenia, and post-treatment reticulocytosis leading to haemoglobin recovery. Little is known how malaria affects glucose-6-phosphate dehydrogenase (G6PD) activity and wheth...

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Autores principales:	Walter R J Taylor, Saorin Kim, Sim Kheng, Sinoun Muth, Pety Tor, Eva Christophel, Mavuto Mukaka, Alexandra Kerleguer, Lucio Luzzatto, J Kevin Baird, Didier Menard
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2021
Materias:	Arctic medicine. Tropical medicine RC955-962 Public aspects of medicine RA1-1270
Acceso en línea:	https://doaj.org/article/1541e051e5744381a2d41c6987f91de7
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id	oai:doaj.org-article:1541e051e5744381a2d41c6987f91de7
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spelling	oai:doaj.org-article:1541e051e5744381a2d41c6987f91de72021-12-02T20:24:10ZDynamics of G6PD activity in patients receiving weekly primaquine for therapy of Plasmodium vivax malaria.1935-27271935-273510.1371/journal.pntd.0009690https://doaj.org/article/1541e051e5744381a2d41c6987f91de72021-09-01T00:00:00Zhttps://doi.org/10.1371/journal.pntd.0009690https://doaj.org/toc/1935-2727https://doaj.org/toc/1935-2735<h4>Background</h4>Acute Plasmodium vivax malaria is associated with haemolysis, bone marrow suppression, reticulocytopenia, and post-treatment reticulocytosis leading to haemoglobin recovery. Little is known how malaria affects glucose-6-phosphate dehydrogenase (G6PD) activity and whether changes in activity when patients present may lead qualitative tests, like the fluorescent spot test (FST), to misdiagnose G6PD deficient (G6PDd) patients as G6PD normal (G6PDn). Giving primaquine or tafenoquine to such patients could result in severe haemolysis.<h4>Methods</h4>We investigated the G6PD genotype, G6PD enzyme activity over time and the baseline FST phenotype in Cambodians with acute P. vivax malaria treated with 3-day dihydroartemisinin piperaquine and weekly primaquine, 0·75 mg/kg x8 doses.<h4>Results</h4>Of 75 recruited patients (males 63), aged 5-63 years (median 24), 15 were G6PDd males (14 Viangchan, 1 Canton), 3 were G6PD Viangchan heterozygous females, and 57 were G6PDn; 6 patients had α/β-thalassaemia and 26 had HbE. Median (range) Day0 G6PD activities were 0·85 U/g Hb (0·10-1·36) and 11·4 U/g Hb (6·67-16·78) in G6PDd and G6PDn patients, respectively, rising significantly to 1·45 (0·36-5·54, p<0.01) and 12·0 (8·1-17·4, p = 0.04) U/g Hb on Day7, then falling to ~Day0 values by Day56. Day0 G6PD activity did not correlate (p = 0.28) with the Day0 reticulocyte counts but both correlated over time. The FST diagnosed correctly 17/18 G6PDd patients, misclassifying one heterozygous female as G6PDn.<h4>Conclusions</h4>In Cambodia, acute P. vivax malaria did not elevate G6PD activities in our small sample of G6PDd patients to levels that would result in a false normal qualitative test. Low G6PDd enzyme activity at disease presentation increases upon parasite clearance, parallel to reticulocytosis. More work is needed in G6PDd heterozygous females to ascertain the effect of P. vivax on their G6PD activities.<h4>Trial registration</h4>The trial was registered (ACTRN12613000003774) with the Australia New Zealand Clinical trials (https://www.anzctr.org.au/Trial/Registration/TrialReview.aspx?id=363399&isReview=true).Walter R J TaylorSaorin KimSim KhengSinoun MuthPety TorEva ChristophelMavuto MukakaAlexandra KerleguerLucio LuzzattoJ Kevin BairdDidier MenardPublic Library of Science (PLoS)articleArctic medicine. Tropical medicineRC955-962Public aspects of medicineRA1-1270ENPLoS Neglected Tropical Diseases, Vol 15, Iss 9, p e0009690 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Arctic medicine. Tropical medicine RC955-962 Public aspects of medicine RA1-1270
spellingShingle	Arctic medicine. Tropical medicine RC955-962 Public aspects of medicine RA1-1270 Walter R J Taylor Saorin Kim Sim Kheng Sinoun Muth Pety Tor Eva Christophel Mavuto Mukaka Alexandra Kerleguer Lucio Luzzatto J Kevin Baird Didier Menard Dynamics of G6PD activity in patients receiving weekly primaquine for therapy of Plasmodium vivax malaria.
description	<h4>Background</h4>Acute Plasmodium vivax malaria is associated with haemolysis, bone marrow suppression, reticulocytopenia, and post-treatment reticulocytosis leading to haemoglobin recovery. Little is known how malaria affects glucose-6-phosphate dehydrogenase (G6PD) activity and whether changes in activity when patients present may lead qualitative tests, like the fluorescent spot test (FST), to misdiagnose G6PD deficient (G6PDd) patients as G6PD normal (G6PDn). Giving primaquine or tafenoquine to such patients could result in severe haemolysis.<h4>Methods</h4>We investigated the G6PD genotype, G6PD enzyme activity over time and the baseline FST phenotype in Cambodians with acute P. vivax malaria treated with 3-day dihydroartemisinin piperaquine and weekly primaquine, 0·75 mg/kg x8 doses.<h4>Results</h4>Of 75 recruited patients (males 63), aged 5-63 years (median 24), 15 were G6PDd males (14 Viangchan, 1 Canton), 3 were G6PD Viangchan heterozygous females, and 57 were G6PDn; 6 patients had α/β-thalassaemia and 26 had HbE. Median (range) Day0 G6PD activities were 0·85 U/g Hb (0·10-1·36) and 11·4 U/g Hb (6·67-16·78) in G6PDd and G6PDn patients, respectively, rising significantly to 1·45 (0·36-5·54, p<0.01) and 12·0 (8·1-17·4, p = 0.04) U/g Hb on Day7, then falling to ~Day0 values by Day56. Day0 G6PD activity did not correlate (p = 0.28) with the Day0 reticulocyte counts but both correlated over time. The FST diagnosed correctly 17/18 G6PDd patients, misclassifying one heterozygous female as G6PDn.<h4>Conclusions</h4>In Cambodia, acute P. vivax malaria did not elevate G6PD activities in our small sample of G6PDd patients to levels that would result in a false normal qualitative test. Low G6PDd enzyme activity at disease presentation increases upon parasite clearance, parallel to reticulocytosis. More work is needed in G6PDd heterozygous females to ascertain the effect of P. vivax on their G6PD activities.<h4>Trial registration</h4>The trial was registered (ACTRN12613000003774) with the Australia New Zealand Clinical trials (https://www.anzctr.org.au/Trial/Registration/TrialReview.aspx?id=363399&isReview=true).
format	article
author	Walter R J Taylor Saorin Kim Sim Kheng Sinoun Muth Pety Tor Eva Christophel Mavuto Mukaka Alexandra Kerleguer Lucio Luzzatto J Kevin Baird Didier Menard
author_facet	Walter R J Taylor Saorin Kim Sim Kheng Sinoun Muth Pety Tor Eva Christophel Mavuto Mukaka Alexandra Kerleguer Lucio Luzzatto J Kevin Baird Didier Menard
author_sort	Walter R J Taylor
title	Dynamics of G6PD activity in patients receiving weekly primaquine for therapy of Plasmodium vivax malaria.
title_short	Dynamics of G6PD activity in patients receiving weekly primaquine for therapy of Plasmodium vivax malaria.
title_full	Dynamics of G6PD activity in patients receiving weekly primaquine for therapy of Plasmodium vivax malaria.
title_fullStr	Dynamics of G6PD activity in patients receiving weekly primaquine for therapy of Plasmodium vivax malaria.
title_full_unstemmed	Dynamics of G6PD activity in patients receiving weekly primaquine for therapy of Plasmodium vivax malaria.
title_sort	dynamics of g6pd activity in patients receiving weekly primaquine for therapy of plasmodium vivax malaria.
publisher	Public Library of Science (PLoS)
publishDate	2021
url	https://doaj.org/article/1541e051e5744381a2d41c6987f91de7
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Dynamics of G6PD activity in patients receiving weekly primaquine for therapy of Plasmodium vivax malaria.

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