Kinetics of glucose-6-phosphate dehydrogenase (G6PD) activity during Plasmodium vivax infection: implications for early radical malaria treatment

Abstract

Background: Plasmodium vivax relapses due to dormant liver hypnozoites can be prevented with primaquine. However, the dose must be adjusted in individuals with glucose-6-phosphate-dehydrogenase (G6PD) deficiency. In French Guiana, assessment of G6PD activity is typically delayed until day (D)14 to avoid the risk if misclassification. This study assessed the kinetics of G6PD activity throughout P. vivax infection to inform the timing of treatment.

Methods: For this retrospective monocentric study, data on G6PD activity between D1 and D28 after treatment initiation with chloroquine or artemisinin-based combination therapy were collected for patients followed at Cayenne Hospital, French Guiana, between January 2018 and December 2020. Patients were divided into three groups based on the number of available G6PD activity assessments: (i) at least two measurements during the P. vivax malaria infection; (ii) two measurements: one during the current infection and one previously; (iii) only one measurement during the malaria infection.

Results: In total, 210 patients were included (80, 20 and 110 in groups 1, 2 and 3, respectively). Data from group 1 showed that G6PD activity remained stable in each patient over time (D1, D3, D7, D14, D21, D28). None of the patients with normal G6PD activity during the initial phase (D1-D3) of the malaria episode (n = 44) was categorized as G6PD-deficient at D14. Patients with G6PD activity < 80% at D1 or D3 showed normal activity at D14. Sex and reticulocyte count were statistically associated with G6PD activity variation. In the whole sample (n = 210), no patient had severe G6PD deficiency (< 10%) and only three between 10 and 30%, giving a G6PD deficiency prevalence of 1.4%. Among the 100 patients from group 1 and 2, 30 patients (26.5%) were lost to follow-up before primaquine initiation.

Conclusions: In patients treated for P. vivax infection, G6PD activity did not vary over time. Therefore, G6PD activity on D1 instead of D14 could be used for primaquine dose-adjustment. This could allow earlier radical treatment with primaquine, that could have a public health impact by decreasing early recurrences and patients lost to follow-up before primaquine initiation. This hypothesis needs to be confirmed in larger prospective studies.

Keywords: Plasmodium vivax; French Guiana; G6PD/Glucose-6-phosphase dehydrogenase; Malaria; Primaquine.

Fig. 1

Study flowchart. N_A = Number of Plasmodium vivax attacks; N_P = Number of patients (one or more malaria episodes). (Asterisk) Duplicates: multiple results for the same malaria episode. G6PD glucose-6-phosphate dehydrogenase

Fig. 2

Box plots (median, interquartile range, full range) showing the distribution of the indicated laboratory parameter values in group 1 (N_A = 93) at different time points. The line indicates the median, crosses indicate the mean. D, day after treatment (chloroquine or artemisinin-based combination) initiation

Fig. 3

G6PD activity (U/g Hb) changes in the 44 patients from group 1 with G6PD activity measurements at day 1 or day 3 and at day 14 after treatment initiation (chloroquine or artemisinin-based combination). Dashed black line and black line: 30% and 80% of G6PD activity, respectively. D day

Fig. 4

Scatterplot (black points) and smoothing line (blue line and its 95% confidence intervals) showing the relationship between G6PD activity and reticulocyte count by sex group. Reticulocyte count (G/L), G6PD (U/g Hb)

Fig. 5

G6PD activity kinetics over time. Prevalence of patients in each G6PD activity category (< 10%, 10–30%, 30–80%, and > 80%). G6PD (U/g Hb). Day 1: n = 37, Day 3: n = 62, Day 7: n = 67, Day 14: 113, Day 21: n = 69, Day 28: n = 71

Fig. 6

Optimization of P. vivax infection management using different diagnostic and treatment levers