Malaria Journal (Oct 2023)
Effect of adherence to primaquine on the risk of Plasmodium vivax recurrence: a WorldWide Antimalarial Resistance Network systematic review and individual patient data meta-analysis
- Parinaz Mehdipour,
- Megha Rajasekhar,
- Saber Dini,
- Sophie Zaloumis,
- Tesfay Abreha,
- Ishag Adam,
- Ghulam Rahim Awab,
- J. Kevin Baird,
- Larissa W. Brasil,
- Cindy S. Chu,
- Liwang Cui,
- André Daher,
- Margarete do Socorro M Gomes,
- Lilia Gonzalez‑Ceron,
- Jimee Hwang,
- Harin Karunajeewa,
- Marcus V. G. Lacerda,
- Simone Ladeia-Andrade,
- Toby Leslie,
- Benedikt Ley,
- Kartini Lidia,
- Alejandro Llanos-Cuentas,
- Rhea J. Longley,
- Wuelton Marcelo Monteiro,
- Dhelio B. Pereira,
- Komal Raj Rijal,
- Kavitha Saravu,
- Inge Sutanto,
- Walter R. J. Taylor,
- Pham Vinh Thanh,
- Kamala Thriemer,
- José Luiz F. Vieira,
- Nicholas J. White,
- Lina M. Zuluaga-Idarraga,
- Philippe J. Guerin,
- Ric N. Price,
- Julie A. Simpson,
- Robert J. Commons,
- the WWARN Vivax Adherence Study Group
Affiliations
- Parinaz Mehdipour
- Centre for Epidemiology and Biostatistics, Melbourne School of Population and Global Health, The University of Melbourne
- Megha Rajasekhar
- Centre for Epidemiology and Biostatistics, Melbourne School of Population and Global Health, The University of Melbourne
- Saber Dini
- Centre for Epidemiology and Biostatistics, Melbourne School of Population and Global Health, The University of Melbourne
- Sophie Zaloumis
- Centre for Epidemiology and Biostatistics, Melbourne School of Population and Global Health, The University of Melbourne
- Tesfay Abreha
- ICAP, Columbia University Mailman School of Public Health
- Ishag Adam
- Department of Obstetrics and Gynecology, Unaizah College of Medicine and Medical Sciences, Qassim University
- Ghulam Rahim Awab
- Mahidol Oxford Tropical Medicine Research Unit (MORU), Faculty of Tropical Medicine, Mahidol University
- J. Kevin Baird
- Oxford University Clinical Research Unit Indonesia, Faculty of Medicine, Universitas Indonesia
- Larissa W. Brasil
- Diretoria de Ensino E Pesquisa
- Cindy S. Chu
- Centre for Tropical Medicine and Global Health, Nuffield Department of Medicine, Oxford University
- Liwang Cui
- Department of Internal Medicine, Morsani College of Medicine, University of South Florida
- André Daher
- Fiocruz Clinical Research Platform, Vice-Presidency of Research and Biological Collections, Oswaldo Cruz Foundation (FIOCRUZ)
- Margarete do Socorro M Gomes
- Superintendência de Vigilância Em Saúde Do Estado Do Amapá - SVS/AP
- Lilia Gonzalez‑Ceron
- Regional Centre for Public Health Research, National Institute for Public Health
- Jimee Hwang
- U.S. President’s Malaria Initiative, Malaria Branch, U.S. Centers for Disease Control and Prevention
- Harin Karunajeewa
- Department of Medicine-Western Health, Melbourne Medical School, The University of Melbourne
- Marcus V. G. Lacerda
- Fundação de Medicina Tropical Dr Heitor Vieira Dourado
- Simone Ladeia-Andrade
- Laboratory of Parasitic Diseases, Oswaldo Cruz Institute
- Toby Leslie
- Department of Infectious and Tropical Diseases, London School of Hygiene and Tropical Medicine
- Benedikt Ley
- Global Health Division, Menzies School of Health Research and Charles Darwin University
- Kartini Lidia
- Department of Pharmacology and Therapy, Faculty of Medicine and Veterinary Medicine, Universitas Nusa Cendana
- Alejandro Llanos-Cuentas
- Unit of Leishmaniasis and Malaria, Instituto de Medicina Tropical “Alexander Von Humboldt”, Universidad Peruana Cayetano Heredia
- Rhea J. Longley
- Mahidol Vivax Research Unit, Faculty of Tropical Medicine, Mahidol University
- Wuelton Marcelo Monteiro
- Universidade Do Estado Do Amazonas
- Dhelio B. Pereira
- Centro de Pesquisa Em Medicina Tropical de Rondonia (CEPEM)
- Komal Raj Rijal
- Central Department of Microbiology, Tribhuvan University
- Kavitha Saravu
- Department of Infectious Diseases, Kasturba Medical College Manipal, Manipal Academy of Higher Education
- Inge Sutanto
- Department of Parasitology, Faculty of Medicine, University of Indonesia
- Walter R. J. Taylor
- Mahidol Oxford Tropical Medicine Research Unit (MORU), Faculty of Tropical Medicine, Mahidol University
- Pham Vinh Thanh
- National Institute of Malariology, Parasitology and Entomology
- Kamala Thriemer
- Global Health Division, Menzies School of Health Research and Charles Darwin University
- José Luiz F. Vieira
- Federal University of Pará, Universidade Federal Do Pará - UFPA)
- Nicholas J. White
- Mahidol Oxford Tropical Medicine Research Unit (MORU), Faculty of Tropical Medicine, Mahidol University
- Lina M. Zuluaga-Idarraga
- Grupo Malaria, Facultad de Medicina, Universidad de Antioquia
- Philippe J. Guerin
- Centre for Tropical Medicine and Global Health, Nuffield Department of Medicine, Oxford University
- Ric N. Price
- Centre for Tropical Medicine and Global Health, Nuffield Department of Medicine, Oxford University
- Julie A. Simpson
- Centre for Epidemiology and Biostatistics, Melbourne School of Population and Global Health, The University of Melbourne
- Robert J. Commons
- Global Health Division, Menzies School of Health Research and Charles Darwin University
- the WWARN Vivax Adherence Study Group
- DOI
- https://doi.org/10.1186/s12936-023-04725-w
- Journal volume & issue
-
Vol. 22,
no. 1
pp. 1 – 14
Abstract
Abstract Background Imperfect adherence is a major barrier to effective primaquine radical cure of Plasmodium vivax. This study investigated the effect of reduced adherence on the risk of P. vivax recurrence. Methods Efficacy studies of patients with uncomplicated P. vivax malaria, including a treatment arm with daily primaquine, published between January 1999 and March 2020 were identified. Individual patient data from eligible studies were pooled using standardized methodology. Adherence to primaquine was inferred from i) the percentage of supervised doses and ii) the total mg/kg dose received compared to the target total mg/kg dose per protocol. The effect of adherence to primaquine on the incidence of P. vivax recurrence between days 7 and 90 was investigated by Cox regression analysis. Results Of 82 eligible studies, 32 were available including 6917 patients from 18 countries. For adherence assessed by percentage of supervised primaquine, 2790 patients (40.3%) had poor adherence (≤ 50%) and 4127 (59.7%) had complete adherence. The risk of recurrence by day 90 was 14.0% [95% confidence interval: 12.1–16.1] in patients with poor adherence compared to 5.8% [5.0–6.7] following full adherence; p = 0.014. After controlling for age, sex, baseline parasitaemia, and total primaquine dose per protocol, the rate of the first recurrence was higher following poor adherence compared to patients with full adherence (adjusted hazard ratio (AHR) = 2.3 [1.8–2.9]). When adherence was quantified by total mg/kg dose received among 3706 patients, 347 (9.4%) had poor adherence, 88 (2.4%) had moderate adherence, and 3271 (88.2%) had complete adherence to treatment. The risks of recurrence by day 90 were 8.2% [4.3–15.2] in patients with poor adherence and 4.9% [4.1–5.8] in patients with full adherence; p < 0.001. Conclusion Reduced adherence, including less supervision, increases the risk of vivax recurrence.
Keywords
