Safety and efficacy of primaquine in patients with Plasmodium vivax malaria from South Asia: A systematic review and individual patient data meta-analysis
Issued Date
2023-12-20
Resource Type
eISSN
20597908
Scopus ID
2-s2.0-85181945747
Journal Title
BMJ Global Health
Volume
8
Issue
12
Rights Holder(s)
SCOPUS
Bibliographic Citation
BMJ Global Health Vol.8 No.12 (2023)
Suggested Citation
Verma R., Commons R.J., Gupta A., Rahi M., Nitika, Bharti P.K., Thriemer K., Rajasekhar M., Singh-Phulgenda S., Adhikari B., Alam M.S., Ghimire P., Khan W.A., Kumar R., Leslie T., Ley B., Llanos-Cuentas A., Pukrittayakamee S., Rijal K.R., Rowland M., Saravu K., Simpson J.A., Guerin P.J., Price R.N., Sharma A. Safety and efficacy of primaquine in patients with Plasmodium vivax malaria from South Asia: A systematic review and individual patient data meta-analysis. BMJ Global Health Vol.8 No.12 (2023). doi:10.1136/bmjgh-2023-012675 Retrieved from: https://repository.li.mahidol.ac.th/handle/20.500.14594/95731
Title
Safety and efficacy of primaquine in patients with Plasmodium vivax malaria from South Asia: A systematic review and individual patient data meta-analysis
Author's Affiliation
Infectious Diseases Data Observatory
WorldWide Antimalarial Resistance Network
Prasanna School of Public Health
Faculty of Tropical Medicine, Mahidol University
Mahidol Oxford Tropical Medicine Research Unit
Academy of Scientific and Innovative Research (AcSIR)
Melbourne School of Population and Global Health
Health Works, Amsterdam
Universidad Peruana Cayetano Heredia, Instituto de Medicina Tropical Alexander von Humboldt
Tribhuvan University
Rajendra Memorial Research Institute of Medical Sciences
International Centre for Genetic Engineering and Biotechnology
London School of Hygiene & Tropical Medicine
Menzies School of Health Research
Indian Council of Medical Research
National Institute of Malaria Research India
Kasturba Medical College, Manipal
International Centre for Diarrhoeal Disease Research Bangladesh
Nuffield Department of Medicine
WorldWide Antimalarial Resistance Network
Grampians Health
WorldWide Antimalarial Resistance Network
Prasanna School of Public Health
Faculty of Tropical Medicine, Mahidol University
Mahidol Oxford Tropical Medicine Research Unit
Academy of Scientific and Innovative Research (AcSIR)
Melbourne School of Population and Global Health
Health Works, Amsterdam
Universidad Peruana Cayetano Heredia, Instituto de Medicina Tropical Alexander von Humboldt
Tribhuvan University
Rajendra Memorial Research Institute of Medical Sciences
International Centre for Genetic Engineering and Biotechnology
London School of Hygiene & Tropical Medicine
Menzies School of Health Research
Indian Council of Medical Research
National Institute of Malaria Research India
Kasturba Medical College, Manipal
International Centre for Diarrhoeal Disease Research Bangladesh
Nuffield Department of Medicine
WorldWide Antimalarial Resistance Network
Grampians Health
Corresponding Author(s)
Other Contributor(s)
Abstract
Background The optimal dosing of primaquine to prevent relapsing Plasmodium vivax malaria in South Asia remains unclear. We investigated the efficacy and safety of different primaquine regimens to prevent P. vivax relapse. Methods A systematic review identified P. vivax efficacy studies from South Asia published between 1 January 2000 and 23 August 2021. In a one-stage meta-analysis of available individual patient data, the cumulative risks of P. vivax recurrence at day 42 and 180 were assessed by primaquine total mg/kg dose and duration. The risk of recurrence by day 180 was also determined in a two-stage meta-analysis. Patients with a >25% drop in haemoglobin to <70 g/L, or an absolute drop of >50 g/L between days 1 and 14 were categorised by daily mg/kg primaquine dose. Results In 791 patients from 7 studies in the one-stage meta-analysis, the day 180 cumulative risk of recurrence was 61.1% (95% CI 42.2% to 80.4%; 201 patients; 25 recurrences) after treatment without primaquine, 28.8% (95% CI 8.2% to 74.1%; 398 patients; 4 recurrences) following low total (2 to <5 mg/kg) and 0% (96 patients; 0 recurrences) following high total dose primaquine (=5 mg/kg). In the subsequent two-stage meta-analysis of nine studies (3529 patients), the pooled proportions of P. vivax recurrences by day 180 were 12.1% (95% CI 7.7% to 17.2%), 2.3% (95% CI 0.3% to 5.4%) and 0.7% (95% CI 0% to 6.1%), respectively. No patients had a >25% drop in haemoglobin to <70 g/L. Conclusions Primaquine treatment led to a marked decrease in P. vivax recurrences following low (~3.5 mg/ kg) and high (~7 mg/kg) total doses, with no reported severe haemolytic events. PROSPERO registration number CRD42022313730.