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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.
Mehdipour, Parinaz; Rajasekhar, Megha; Dini, Saber; Zaloumis, Sophie; Abreha, Tesfay; Adam, Ishag; Awab, Ghulam Rahim; Baird, J Kevin; Brasil, Larissa W; Chu, Cindy S; Cui, Liwang; Daher, André; do Socorro M Gomes, Margarete; Gonzalez-Ceron, Lilia; Hwang, Jimee; Karunajeewa, Harin; Lacerda, Marcus V G; Ladeia-Andrade, Simone; Leslie, Toby; Ley, Benedikt; Lidia, Kartini; Llanos-Cuentas, Alejandro; Longley, Rhea J; Monteiro, Wuelton Marcelo; Pereira, Dhelio B; Rijal, Komal Raj; Saravu, Kavitha; Sutanto, Inge; Taylor, Walter R J; Thanh, Pham Vinh; Thriemer, Kamala; Vieira, José Luiz F; White, Nicholas J; Zuluaga-Idarraga, Lina M; Guerin, Philippe J; Price, Ric N; Simpson, Julie A; Commons, Robert J.
Affiliation
  • Mehdipour P; Centre for Epidemiology and Biostatistics, Melbourne School of Population and Global Health, The University of Melbourne, Melbourne, Australia.
  • Rajasekhar M; Centre for Epidemiology and Biostatistics, Melbourne School of Population and Global Health, The University of Melbourne, Melbourne, Australia.
  • Dini S; Centre for Epidemiology and Biostatistics, Melbourne School of Population and Global Health, The University of Melbourne, Melbourne, Australia.
  • Zaloumis S; Centre for Epidemiology and Biostatistics, Melbourne School of Population and Global Health, The University of Melbourne, Melbourne, Australia.
  • Abreha T; ICAP, Columbia University Mailman School of Public Health, Addis Ababa, Ethiopia.
  • Adam I; Department of Obstetrics and Gynecology, Unaizah College of Medicine and Medical Sciences, Qassim University, Unaizah, Saudi Arabia.
  • Awab GR; Mahidol Oxford Tropical Medicine Research Unit (MORU), Faculty of Tropical Medicine, Mahidol University, Bangkok, Thailand.
  • Baird JK; Nangarhar Medical Faculty, Nangarhar University, Jalalabad, Afghanistan.
  • Brasil LW; Oxford University Clinical Research Unit Indonesia, Faculty of Medicine, Universitas Indonesia, Jakarta, Indonesia.
  • Chu CS; Centre for Tropical Medicine and Global Health, Nuffield Department of Medicine, Oxford University, Oxford, UK.
  • Cui L; Diretoria de Ensino E Pesquisa, Fundação de Medicina Tropical Dr. Heitor Vieira Dourado, Manaus, AM, Brazil.
  • Daher A; Programa de Pós­Graduação em Medicina Tropical, Universidade Do Estado Do Amazonas, Manaus, AM, Brazil.
  • do Socorro M Gomes M; Centre for Tropical Medicine and Global Health, Nuffield Department of Medicine, Oxford University, Oxford, UK.
  • Gonzalez-Ceron L; Shoklo Malaria Research Unit, Mahidol Oxford Tropical Medicine Research Unit, Faculty of Tropical Medicine, Mahidol University, Mae Sot, Thailand.
  • Hwang J; Department of Internal Medicine, Morsani College of Medicine, University of South Florida, Tampa, FL, USA.
  • Karunajeewa H; Fiocruz Clinical Research Platform, Vice-Presidency of Research and Biological Collections, Oswaldo Cruz Foundation (FIOCRUZ), Rio de Janeiro, Brazil.
  • Lacerda MVG; Superintendência de Vigilância Em Saúde Do Estado Do Amapá - SVS/AP, Macapá, Amapá, Brazil.
  • Ladeia-Andrade S; Federal University of aMAPA, Universidade Federal Do Amapá - UNIFAP), Macapá, Amapá, Brazil.
  • Leslie T; Regional Centre for Public Health Research, National Institute for Public Health, Tapachula, Chiapas, Mexico.
  • Ley B; U.S. President's Malaria Initiative, Malaria Branch, U.S. Centers for Disease Control and Prevention, Atlanta, GA, USA.
  • Lidia K; Global Health Group, University of California San Francisco, San Francisco, USA.
  • Llanos-Cuentas A; Department of Medicine-Western Health, Melbourne Medical School, The University of Melbourne, St. Albans, VIC, Australia.
  • Longley RJ; Fundação de Medicina Tropical Dr Heitor Vieira Dourado, Manaus, Brazil.
  • Monteiro WM; Instituto Leônidas & Maria Deane, Fiocruz, Manaus, Brazil.
  • Pereira DB; University of Texas Medical Branch, Galveston, USA.
  • Rijal KR; Laboratory of Parasitic Diseases, Oswaldo Cruz Institute, Fiocruz, Rio de Janeiro, Brazil.
  • Saravu K; Global Health and Tropical Medicine, Institute of Hygiene and Tropical Medicine, Nova University of Lisbon, Lisbon, Portugal.
  • Sutanto I; Department of Infectious and Tropical Diseases, London School of Hygiene and Tropical Medicine, London, UK.
  • Taylor WRJ; HealthNet-TPO, Kabul, Afghanistan.
  • Thanh PV; Global Health Division, Menzies School of Health Research and Charles Darwin University, Darwin, NT, Australia.
  • Thriemer K; Department of Pharmacology and Therapy, Faculty of Medicine and Veterinary Medicine, Universitas Nusa Cendana, Kupang, Indonesia.
  • Vieira JLF; Unit of Leishmaniasis and Malaria, Instituto de Medicina Tropical "Alexander Von Humboldt", Universidad Peruana Cayetano Heredia, Lima, Peru.
  • White NJ; Mahidol Vivax Research Unit, Faculty of Tropical Medicine, Mahidol University, Bangkok, Thailand.
  • Zuluaga-Idarraga LM; Population Health and Immunity Division, Walter and Eliza Hall Institute of Medical Research, Melbourne, Australia.
  • Guerin PJ; Department of Medical Biology, University of Melbourne, Melbourne, Australia.
  • Price RN; Universidade Do Estado Do Amazonas, Manaus, Brazil.
  • Simpson JA; Centro de Pesquisa Em Medicina Tropical de Rondonia (CEPEM), Porto Velho, Brazil.
  • Commons RJ; Fundação Universidade Federal de Rondonia (UNIR), Porto Velho, Brazil.
Malar J ; 22(1): 306, 2023 Oct 10.
Article in En | MEDLINE | ID: mdl-37817240
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.
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Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: Malaria, Vivax / Folic Acid Antagonists / Antimalarials Type of study: Etiology_studies / Guideline / Risk_factors_studies / Systematic_reviews Limits: Humans Language: En Journal: Malar J Journal subject: MEDICINA TROPICAL Year: 2023 Document type: Article Affiliation country: Australia
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Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: Malaria, Vivax / Folic Acid Antagonists / Antimalarials Type of study: Etiology_studies / Guideline / Risk_factors_studies / Systematic_reviews Limits: Humans Language: En Journal: Malar J Journal subject: MEDICINA TROPICAL Year: 2023 Document type: Article Affiliation country: Australia