scholarly journals Protective effect of Mediterranean-type glucose-6-phosphate dehydrogenase deficiency against Plasmodium vivax malaria

eLife ◽  
2021 ◽  
Vol 10 ◽  
Author(s):  
Ghulam R Awab ◽  
Fahima Aaram ◽  
Natsuda Jamornthanyawat ◽  
Kanokon Suwannasin ◽  
Watcharee Pagornrat ◽  
...  
Keyword(s):  
Protective Effect ◽  
Plasmodium Vivax ◽  
G6pd Deficiency ◽  
Vivax Malaria ◽  
Malaria Incidence ◽  
Large Population ◽  
Credible Interval ◽  
Radical Cure ◽  
Plasmodium Vivax Malaria ◽  
Glucose 6 Phosphate Dehydrogenase

X-linked glucose-6-phosphate dehydrogenase (G6PD) deficiency is the most common human enzymopathy. The severe Mediterranean variant (G6PD Med) found across Europe and Asia is thought to confer protection against malaria, but its effect is unclear. We fitted a Bayesian statistical model to observed G6PD Med allele frequencies in 999 Pashtun patients presenting with acute Plasmodium vivax malaria and 1408 population controls. G6PD Med was associated with reductions in symptomatic P. vivax malaria incidence of 76% (95% credible interval [CI], 58–88) in hemizygous males and homozygous females combined and 55% (95% CI, 38–68) in heterozygous females. Unless there is very large population stratification within the Pashtun (confounding these results), the G6PD Med genotype confers a very large and gene-dose proportional protective effect against acute vivax malaria. The proportion of patients with vivax malaria at risk of haemolysis following 8-aminoquinoline radical cure is substantially overestimated by studies measuring G6PD deficiency prevalence in healthy subjects.

scholarly journals Strong gene dose dependent protective effect of Mediterranean type glucose-6-phosphate dehydrogenase deficiency against Plasmodium vivax malaria

2020 ◽  
Author(s):  
Ghulam R Awab ◽  
Fahima Aaram ◽  
Natsuda Jamornthanyawat ◽  
Kanokon Suwannasin ◽  
Watcharee Pagornrat ◽  
...  
Keyword(s):  
Protective Effect ◽  
Plasmodium Vivax ◽  
Vivax Malaria ◽  
Large Population ◽  
Epidemiological Studies ◽  
Radical Cure ◽  
Gene Dose ◽  
Plasmodium Vivax Malaria ◽  
Glucose 6 Phosphate Dehydrogenase ◽  
Dose Dependent

X-linked glucose-6-phosphate dehydrogenase (G6PD) deficiency is the most common human enzymopathy. The severe Mediterranean variant (G6PD Med) is common across Europe and Asia, and is thought to confer protection against malaria but its effect is unclear. We fit a Bayesian statistical model to observed G6PD Med allele frequencies in 999 Pashtun patients with acute Plasmodium vivax malaria and 1408 population controls. G6PD Med was associated with a reduction in the incidence of symptomatic P. vivax malaria of 76% (95% CI 58-88) in hemizygous males and homozygous females combined, and of 55% (95% CI 38-68) in heterozygous females. Thus, in absence of very large population stratification (i.e. confounding) the G6PD Med genotype confers a very large and gene dose proportional protective effect against acute vivax malaria. The proportion of patients with vivax malaria at risk of haemolysis following 8-aminoquinoline radical cure is substantially overestimated by epidemiological studies in healthy subjects.

scholarly journals Determinants of primaquine and carboxyprimaquine exposures in children and adults with Plasmodium vivax malaria

2021 ◽  
Author(s):  
Cindy S Chu ◽  
James Andrew Watson ◽  
Aung Pyae Phyo ◽  
Htun Htun Win ◽  
Widi Yotyingaphiram ◽  
...  
Keyword(s):  
Young Children ◽  
Plasmodium Vivax ◽  
Vivax Malaria ◽  
Plasma Concentrations ◽  
Radical Cure ◽  
Pharmacokinetic Properties ◽  
Plasmodium Vivax Malaria ◽  
Glucose 6 Phosphate Dehydrogenase ◽  
To Receive ◽  
Cyp 2D6

Background: Primaquine is the only widely available drug for radical cure of Plasmodium vivax malaria. There is uncertainty whether the pharmacokinetic properties of primaquine are altered significantly in childhood or not. Methods: Glucose-6-phosphate dehydrogenase normal patients with uncomplicated P. vivax malaria were randomized to receive either chloroquine (25mg base/kg) or dihydroartemisinin-piperaquine (dihydroartemisinin 7mg/kg and piperaquine 55mg/kg) plus primaquine; plus either 0.5 mg base/kg/day for 14 days or 1 mg/kg/day for 7 days. Pre-dose day 7 venous plasma concentrations of chloroquine, desethylchloroquine, piperaquine, primaquine and carboxyprimaquine were measured. Methemoglobin levels were measured on days 1, 4, 7. Results: Day 7 primaquine and carboxyprimaquine concentrations were available for 641 patients. After adjustment for the primaquine mg/kg daily dose, day of sampling, partner drug, and fever clearance, there was a significant non-linear relationship between age and trough primaquine and carboxyprimaquine concentrations, and day methemoglobin levels. Compared to adults 30 years of age, children 5 years of age had trough primaquine concentrations 0.55 (95% CI: 0.39- 0.78) fold lower, trough carboxyprimaquine concentrations 0.43 (95% CI: 0.34- 0.55) fold lower, and day 7 methemoglobin levels 0.87 (95% CI: 0.58-1.27) fold lower. Increasing concentrations of piperaquine and chloroquine and poor metabolizer CYP 2D6 alleles were also associated with higher day 7 primaquine and carboxyprimaquine concentrations. Increased methemoglobin concentrations were associated with a lower risk of recurrence. Conclusion: Young children have lower primaquine and carboxyprimaquine exposures, and lower levels of methemoglobinemia, than adults. Young children may need higher weight adjusted primaquine doses than adults.

scholarly journals A Comparison of Two Short-Course Primaquine Regimens for the Treatment and Radical Cure of Plasmodium vivax Malaria in Thailand

2010 ◽  
Vol 82 (4) ◽  
pp. 542-547 ◽  
Author(s):  
Sasithon Pukrittayakamee ◽  
Nicholas J. White ◽  
Kesinee Chotivanich ◽  
Nicholas P. J. Day ◽  
Mallika Imwong ◽  
...  
Keyword(s):  
Plasmodium Vivax ◽  
Vivax Malaria ◽  
Radical Cure ◽  
Short Course ◽  
Plasmodium Vivax Malaria

scholarly journals G6PD deficiency in male individuals infected by Plasmodium vivax malaria in the Brazilian Amazon: a cost study

2015 ◽  
Vol 14 (1) ◽  
Author(s):  
Henry M Peixoto ◽  
Marcelo AM Brito ◽  
Gustavo AS Romero ◽  
Wuelton M Monteiro ◽  
Marcus VG de Lacerda ◽  
...  
Keyword(s):  
Plasmodium Vivax ◽  
G6pd Deficiency ◽  
Vivax Malaria ◽  
Brazilian Amazon ◽  
Cost Study ◽  
Plasmodium Vivax Malaria

scholarly journals Towards the elimination of Plasmodium vivax malaria: Implementing the radical cure

PLoS Medicine ◽  
2021 ◽  
Vol 18 (4) ◽  
pp. e1003494
Author(s):  
Kamala Thriemer ◽  
Benedikt Ley ◽  
Lorenz von Seidlein
Keyword(s):  
Plasmodium Vivax ◽  
Vivax Malaria ◽  
Radical Cure ◽  
Plasmodium Vivax Malaria

scholarly journals The risk of adverse clinical outcomes following treatment of Plasmodium vivax malaria with and without primaquine in Papua, Indonesia

2020 ◽  
Vol 14 (11) ◽  
pp. e0008838
Author(s):  
Kamala Thriemer ◽  
Jeanne-Rini Poespoprodjo ◽  
Enny Kenangalem ◽  
Nicholas M. Douglas ◽  
Paulus Sugiarto ◽  
...  
Keyword(s):  
Clinical Outcomes ◽  
G6pd Deficiency ◽  
Cox Regression ◽  
Artemisinin Combination Therapy ◽  
Morbidity And Mortality ◽  
Radical Cure ◽  
Drug Induced ◽  
Routine Administration ◽  
Plasmodium Vivax Malaria ◽  
Glucose 6 Phosphate Dehydrogenase

The widespread use of primaquine (PQ) radical cure for P. vivax, is constrained by concerns over its safety. We used routinely collected patient data to compare the overall morbidity and mortality in patients treated with and without PQ without prior testing of Glucose-6-Phosphate-Dehydrogenase (G6PD) deficiency in Papua, Indonesia, where there is a low prevalence of G6PD deficiency. Records were collated from patients older than 1 year, with P. vivax infection, who were treated with an artemisinin combination therapy (ACT). The risks of re-presentation, hospitalization, major fall in haemoglobin and death within 30 days were quantified and compared between patients treated with and without PQ using a Cox regression model. In total 26,216 patients with P. vivax malaria presented to the hospital with malaria during the study period. Overall 27.56% (95% Confidence Interval (95%CI): 26.96–28.16) of 21,344 patients treated with PQ re-presented with any illness within 30 days and 1.69% (1.51–1.88) required admission to hospital. The corresponding risks were higher in the 4,872 patients not treated with PQ; Adjusted Hazard Ratio (AHR) = 0.84 (0.79–0.91; p<0.001) and 0.54 (0.41–0.70; p<0.001) respectively. By day 30, 14.15% (12.45–16.05) of patients who had received PQ had a fall in haemoglobin (Hb) below 7g/dl compared to 20.43% (16.67–24.89) of patients treated without PQ; AHR = 0.66 (0.45–0.97; p = 0.033). A total of 75 (0.3%) patients died within 30 days of treatment with a mortality risk of 0.27% (0.21–0.35) in patients treated with PQ, compared to 0.38% (0.24–0.60) without PQ; AHR = 0.79 (0.43–1.45; p = 0.448). In Papua, Indonesia routine administration of PQ radical cure without prior G6PD testing, was associated with lower risk of all cause hospitalization and other serious adverse clinical outcomes. In areas where G6PD testing is not available or cannot be delivered reliably, the risks of drug induced haemolysis should be balanced against the potential benefits of reducing recurrent P. vivax malaria and its associated morbidity and mortality.

Sign in / Sign up

Export Citation Format

Share Document