Weekly primaquine for radical cure of patients with Plasmodium vivax malaria and glucose-6-phosphate dehydrogenase deficiency
Issued Date
2023-09-01
Resource Type
eISSN
19352735
Scopus ID
2-s2.0-85169998929
Pubmed ID
37672548
Journal Title
PLoS neglected tropical diseases
Volume
17
Issue
9
Rights Holder(s)
SCOPUS
Bibliographic Citation
PLoS neglected tropical diseases Vol.17 No.9 (2023) , e0011522
Suggested Citation
Taylor W.R.J., Meagher N., Ley B., Thriemer K., Bancone G., Satyagraha A., Assefa A., Chand K., Chau N.H., Dhorda M., Degaga T.S., Ekawati L.L., Hailu A., Hasanzai M.A., Naddim M.N., Pasaribu A.P., Rahim A.G., Sutanto I., Thanh N.V., Tuyet-Trinh N.T., Waithira N., Woyessa A., Dondorp A., von Seidlein L., Simpson J.A., White N.J., Baird J.K., Day N.P., Price R.N. Weekly primaquine for radical cure of patients with Plasmodium vivax malaria and glucose-6-phosphate dehydrogenase deficiency. PLoS neglected tropical diseases Vol.17 No.9 (2023) , e0011522. doi:10.1371/journal.pntd.0011522 Retrieved from: https://repository.li.mahidol.ac.th/handle/20.500.14594/90022
Title
Weekly primaquine for radical cure of patients with Plasmodium vivax malaria and glucose-6-phosphate dehydrogenase deficiency
Author(s)
Taylor W.R.J.
Meagher N.
Ley B.
Thriemer K.
Bancone G.
Satyagraha A.
Assefa A.
Chand K.
Chau N.H.
Dhorda M.
Degaga T.S.
Ekawati L.L.
Hailu A.
Hasanzai M.A.
Naddim M.N.
Pasaribu A.P.
Rahim A.G.
Sutanto I.
Thanh N.V.
Tuyet-Trinh N.T.
Waithira N.
Woyessa A.
Dondorp A.
von Seidlein L.
Simpson J.A.
White N.J.
Baird J.K.
Day N.P.
Price R.N.
Meagher N.
Ley B.
Thriemer K.
Bancone G.
Satyagraha A.
Assefa A.
Chand K.
Chau N.H.
Dhorda M.
Degaga T.S.
Ekawati L.L.
Hailu A.
Hasanzai M.A.
Naddim M.N.
Pasaribu A.P.
Rahim A.G.
Sutanto I.
Thanh N.V.
Tuyet-Trinh N.T.
Waithira N.
Woyessa A.
Dondorp A.
von Seidlein L.
Simpson J.A.
White N.J.
Baird J.K.
Day N.P.
Price R.N.
Author's Affiliation
Mahidol Oxford Tropical Medicine Research Unit
Ethiopian Public Health Institute
Oxford University Clinical Research Unit
Melbourne School of Population and Global Health
The Peter Doherty Institute for Infection and Immunity
Arba Minch University
Addis Ababa University
Universitas Sumatera Utara
Eijkman Institute for Molecular Biology
Universitas Indonesia
Menzies School of Health Research
Nuffield Department of Medicine
Nangarhar University
Health Protection and Research Organisation
Youth Health and Development Organization
Ethiopian Public Health Institute
Oxford University Clinical Research Unit
Melbourne School of Population and Global Health
The Peter Doherty Institute for Infection and Immunity
Arba Minch University
Addis Ababa University
Universitas Sumatera Utara
Eijkman Institute for Molecular Biology
Universitas Indonesia
Menzies School of Health Research
Nuffield Department of Medicine
Nangarhar University
Health Protection and Research Organisation
Youth Health and Development Organization
Other Contributor(s)
Abstract
BACKGROUND: The World Health Organization recommends that primaquine should be given once weekly for 8-weeks to patients with Plasmodium vivax malaria and glucose-6-phosphate dehydrogenase (G6PD) deficiency, but data on its antirelapse efficacy and safety are limited. METHODS: Within the context of a multicentre, randomised clinical trial of two primaquine regimens in P. vivax malaria, patients with G6PD deficiency were excluded and enrolled into a separate 12-month observational study. They were treated with a weekly dose of 0.75 mg/kg primaquine for 8 weeks (PQ8W) plus dihydroartemisinin piperaquine (Indonesia) or chloroquine (Afghanistan, Ethiopia, Vietnam). G6PD status was diagnosed using the fluorescent spot test and confirmed by genotyping for locally prevalent G6PD variants. The risk of P. vivax recurrence following PQ8W and the consequent haematological recovery were characterized in all patients and in patients with genotypically confirmed G6PD variants, and compared with the patients enrolled in the main randomised control trial. RESULTS: Between July 2014 and November 2017, 42 male and 8 female patients were enrolled in Afghanistan (6), Ethiopia (5), Indonesia (19), and Vietnam (20). G6PD deficiency was confirmed by genotyping in 31 patients: Viangchan (14), Mediterranean (4), 357A-G (3), Canton (2), Kaiping (2), and one each for A-, Chatham, Gaohe, Ludhiana, Orissa, and Vanua Lava. Two patients had recurrent P. vivax parasitaemia (days 68 and 207). The overall 12-month cumulative risk of recurrent P. vivax malaria was 5.1% (95% CI: 1.3-18.9) and the incidence rate of recurrence was 46.8 per 1000 person-years (95% CI: 11.7-187.1). The risk of P. vivax recurrence was lower in G6PD deficient patients treated with PQ8W compared to G6PD normal patients in all treatment arms of the randomised controlled trial. Two of the 26 confirmed hemizygous males had a significant fall in haemoglobin (>5g/dl) after the first dose but were able to complete their 8 week regimen. CONCLUSIONS: PQ8W was highly effective in preventing P. vivax recurrences. Whilst PQ8W was well tolerated in most patients across a range of different G6PD variants, significant falls in haemoglobin may occur after the first dose and require clinical monitoring. TRIAL REGISTRATION: This trial is registered at ClinicalTrials.gov (NCT01814683).