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Clinical Trial
. 2021 Sep 8;15(9):e0009690.
doi: 10.1371/journal.pntd.0009690. eCollection 2021 Sep.

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

Walter R J Taylor  1   2   3 , Saorin Kim  4 , Sim Kheng  1 , Sinoun Muth  1 , Pety Tor  4 , Eva Christophel  5 , Mavuto Mukaka  3   6 , Alexandra Kerleguer  4 , Lucio Luzzatto  7   8 , J Kevin Baird  6   9 , Didier Menard  10   11   12   13
Affiliations
Clinical Trial

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

Walter R J Taylor et al. PLoS Negl Trop Dis. .

Abstract

Background: 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.

Methods: 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.

Results: 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.

Conclusions: 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.

Trial registration: 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).

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Conflict of interest statement

The authors have declared that no competing interests exist.

Figures

Fig 1
Fig 1. Time course of G6PD activity and reticulocyte counts in male vivax-infected patients given weekly primaquine.
Panel A: G6PD activity. Panel B: reticulocyte counts.
Fig 2
Fig 2. Time course of G6PD activity and reticulocyte counts in female vivax-infected patients given weekly primaquine.
Panel A: G6PD activity. Panel B: reticulocyte counts.
Fig 3
Fig 3. Relationship between the percentage changes in G6PD activity and percentage changes in reticulocyte counts between Day 7 and baseline in the two G6PD groups.
Panel A: G6PD normal patients: the Pearson correlation coefficient, r, was 0.14, adjusted R2 0.34 (p<0.001). Panel B: G6PD deficient patients: r = 0.063, aR2 = -0.063 (p = 0.64).
See this image and copyright information in PMC

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