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
Issued Date
2023-12-01
Resource Type
eISSN
14752875
Scopus ID
2-s2.0-85173698545
Pubmed ID
37817240
Journal Title
Malaria Journal
Volume
22
Issue
1
Rights Holder(s)
SCOPUS
Bibliographic Citation
Malaria Journal Vol.22 No.1 (2023)
Suggested Citation
Mehdipour P., Rajasekhar M., Dini S., Zaloumis S., Abreha T., Adam I., Awab G.R., Baird J.K., Brasil L.W., Chu C.S., Cui L., Daher A., do Socorro M Gomes M., Gonzalez‑Ceron L., Hwang J., Karunajeewa H., Lacerda M.V.G., Ladeia-Andrade S., Leslie T., Ley B., Lidia K., Llanos-Cuentas A., Longley R.J., Monteiro W.M., Pereira D.B., Rijal K.R., Saravu K., Sutanto I., Taylor W.R.J., Thanh P.V., Thriemer K., Vieira J.L.F., White N.J., Zuluaga-Idarraga L.M., Guerin P.J., Price R.N., Simpson J.A., Commons R.J. 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. Malaria Journal Vol.22 No.1 (2023). doi:10.1186/s12936-023-04725-w Retrieved from: https://repository.li.mahidol.ac.th/handle/20.500.14594/90657
Title
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
Author(s)
Mehdipour P.
Rajasekhar M.
Dini S.
Zaloumis S.
Abreha T.
Adam I.
Awab G.R.
Baird J.K.
Brasil L.W.
Chu C.S.
Cui L.
Daher A.
do Socorro M Gomes M.
Gonzalez‑Ceron L.
Hwang J.
Karunajeewa H.
Lacerda M.V.G.
Ladeia-Andrade S.
Leslie T.
Ley B.
Lidia K.
Llanos-Cuentas A.
Longley R.J.
Monteiro W.M.
Pereira D.B.
Rijal K.R.
Saravu K.
Sutanto I.
Taylor W.R.J.
Thanh P.V.
Thriemer K.
Vieira J.L.F.
White N.J.
Zuluaga-Idarraga L.M.
Guerin P.J.
Price R.N.
Simpson J.A.
Commons R.J.
Rajasekhar M.
Dini S.
Zaloumis S.
Abreha T.
Adam I.
Awab G.R.
Baird J.K.
Brasil L.W.
Chu C.S.
Cui L.
Daher A.
do Socorro M Gomes M.
Gonzalez‑Ceron L.
Hwang J.
Karunajeewa H.
Lacerda M.V.G.
Ladeia-Andrade S.
Leslie T.
Ley B.
Lidia K.
Llanos-Cuentas A.
Longley R.J.
Monteiro W.M.
Pereira D.B.
Rijal K.R.
Saravu K.
Sutanto I.
Taylor W.R.J.
Thanh P.V.
Thriemer K.
Vieira J.L.F.
White N.J.
Zuluaga-Idarraga L.M.
Guerin P.J.
Price R.N.
Simpson J.A.
Commons R.J.
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
Melbourne Medical School
Melbourne School of Population and Global Health
Health Works, Amsterdam
Universidad Peruana Cayetano Heredia, Instituto de Medicina Tropical Alexander von Humboldt
Tribhuvan University
National Institute of Malariology, Parasitology and Entomology Hanoi
Fundacao de Medicina Tropical do Amazonas
Universitas Nusa Cendana
Universitas Indonesia
Instituto de Higiene e Medicina Tropical
Universidad de Antioquia
London School of Hygiene & Tropical Medicine
Walter and Eliza Hall Institute of Medical Research
University of Melbourne
Fundacao Oswaldo Cruz
Menzies School of Health Research
Al Qassim University
Fundacao Universidade Federal de Rondonia
University of California, San Francisco
Instituto Nacional de Salud Pública. México
Centers for Disease Control and Prevention
Universidade Federal do Amapa
Fiocruz Amazônia
Kasturba Medical College, Manipal
UT Medical Branch at Galveston
Mailman School of Public Health
Morsani College of Medicine
Nuffield Department of Medicine
Universidade do Estado do Amazonas
Universidade Federal do Pará
Superintendência de Vigilância em Saúde do Estado do Amapá
Nangarhar University
Grampians Health
Fundação de Medicina Tropical Dr. Heitor Vieira Dourado
Centro de Pesquisa em Medicina Tropical de Rondônia
WorldWide Antimalarial Resistance Network
Prasanna School of Public Health
Faculty of Tropical Medicine, Mahidol University
Mahidol Oxford Tropical Medicine Research Unit
Melbourne Medical School
Melbourne School of Population and Global Health
Health Works, Amsterdam
Universidad Peruana Cayetano Heredia, Instituto de Medicina Tropical Alexander von Humboldt
Tribhuvan University
National Institute of Malariology, Parasitology and Entomology Hanoi
Fundacao de Medicina Tropical do Amazonas
Universitas Nusa Cendana
Universitas Indonesia
Instituto de Higiene e Medicina Tropical
Universidad de Antioquia
London School of Hygiene & Tropical Medicine
Walter and Eliza Hall Institute of Medical Research
University of Melbourne
Fundacao Oswaldo Cruz
Menzies School of Health Research
Al Qassim University
Fundacao Universidade Federal de Rondonia
University of California, San Francisco
Instituto Nacional de Salud Pública. México
Centers for Disease Control and Prevention
Universidade Federal do Amapa
Fiocruz Amazônia
Kasturba Medical College, Manipal
UT Medical Branch at Galveston
Mailman School of Public Health
Morsani College of Medicine
Nuffield Department of Medicine
Universidade do Estado do Amazonas
Universidade Federal do Pará
Superintendência de Vigilância em Saúde do Estado do Amapá
Nangarhar University
Grampians Health
Fundação de Medicina Tropical Dr. Heitor Vieira Dourado
Centro de Pesquisa em Medicina Tropical de Rondônia
Other Contributor(s)
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.