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Risk of hemolysis in Plasmodium vivax malaria patients receiving standard primaquine treatment in a population with high prevalence of G6PD deficiency

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Abstract

Background

Primaquine is essential for the radical cure of Plasmodium vivax malaria, but it poses a potential danger of severe hemolysis in G6PD-deficient (G6PDd) patients. This study aimed to determine whether primaquine is safe in a population with high G6PD prevalence but lacking G6PD diagnosis capacity.

Methods

In Myanmar, 152 vivax patients were gender- and age-matched at 1:3 for G6PDd versus G6PD-normal (G6PDn). Their risk of acute hemolysis was followed for 28 days after treatment with the standard chloroquine and 14-day primaquine (0.25 mg/kg/day) regimen.

Results

Patients anemic and non-anemic at enrollment showed a rising and declining trend in the mean hemoglobin level, respectively. In males, the G6PDd group showed substantially larger magnitudes of hemoglobin reduction and lower hemoglobin nadir levels than the G6PDn group, but this trend was not evident in females. Almost 1/3 of the patients experienced clinically concerning declines in hemoglobin, with five requiring blood transfusion.

Conclusions

The standard 14-day primaquine regimen carries a significant risk of acute hemolytic anemia (AHA) in vivax patients without G6PD testing in a population with a high prevalence of G6PD deficiency and anemia. G6PD testing would avoid most of the clinically significant Hb reductions and AHA in male patients.

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Acknowledgements

We want to thank the medical staff at the study clinics for assisting with the study.

Funding

This study was supported by the National Institute of Allergy and Infectious Diseases, and National Institutes of Health USA (U19AI089672). ZY was also supported by the National Natural Science Foundation of China (31860604 and U1802286), the Science and Technology Project of Yunnan (2018ZF0081), and International Science and Technology Cooperation-Yunnan International Science and Technology Cooperation Base (202003AE140004). WZ was supported by the Education Department Fund of Yunnan Province (2019J1184). HL was supported by the High-level Health Talents Project of Yunnan Province (H-2017071).

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Author notes

  1. Pallavi Malla

    Present address: Center for Disease Control and Prevention, 1825 Century Center Blvd, Atlanta, GA, 30345, USA

  2. Huaie Liu and Weilin Zeng have contributed equally to this work.

Authors and Affiliations

  1. Department of Pathogen Biology and Immunology, Kunming Medical University, Kunming, 650500, Yunnan Province, China

    Huaie Liu, Weilin Zeng & Zhaoqing Yang

  2. Department of Internal Medicine, Morsani College of Medicine, University of South Florida, 3720 Spectrum Boulevard, Suite 304, Tampa, FL, 33612, USA

    Pallavi Malla, Seetha Lakshmi, Kami Kim, Lynette Menezes & Liwang Cui

  3. Center for Global Health and Infectious Diseases, University of South Florida, 3720 Spectrum Boulevard, Suite 404, Tampa, FL, 33612, USA

    Chengqi Wang, Kami Kim & Liwang Cui

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  1. Huaie Liu
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Contributions

ZY and LC conceived the design of this study. HL and WZ facilitated sample collection and data curation. HZ, ZY, PM, CW, SL, KK, LM, and LC performed data analysis and drafted the manuscript. HL, LM, ZY, KK, and LC reviewed and revised the manuscript. All authors read and approved the final manuscript.

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Correspondence to Zhaoqing Yang or Liwang Cui.

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Liu, H., Zeng, W., Malla, P. et al. Risk of hemolysis in Plasmodium vivax malaria patients receiving standard primaquine treatment in a population with high prevalence of G6PD deficiency. Infection 51, 213–222 (2023). https://doi.org/10.1007/s15010-022-01905-9

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