Evidence map›Paper›PMID 37817240›Full record

SynthesisMalaria journal2023

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 and 29 more

Abstract readSystematic ReviewMeta-Analysis
PubMed Full text at PMC Publisher
In one paragraph

Synthesis in Malaria journal, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
25citing papers in PubMed, 1 pooled it
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

25 citing papers in PubMed, 1 synthesis or guideline pooled it.

  1. Pooled it
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  7. Health-care provider compliance with a revisedLancet regional health. Americas · 2026
    Article
  8. Effect of higher dose primaquine for the radical cure ofThe Lancet regional health. Western Pacific · 2026
    Article
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  13. Review
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  15. Review
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  20. Observational
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

39 authors.

Parinaz MehdipourCentre for Epidemiology and Biostatistics, Melbourne School of Population and Global Health, The University of Melbourne, Melbourne, Australia.
Megha RajasekharCentre for Epidemiology and Biostatistics, Melbourne School of Population and Global Health, The University of Melbourne, Melbourne, Australia.
Saber DiniCentre for Epidemiology and Biostatistics, Melbourne School of Population and Global Health, The University of Melbourne, Melbourne, Australia.
Sophie ZaloumisCentre for Epidemiology and Biostatistics, Melbourne School of Population and Global Health, The University of Melbourne, Melbourne, Australia.
Tesfay AbrehaICAP, Columbia University Mailman School of Public Health, Addis Ababa, Ethiopia.
Ishag AdamDepartment of Obstetrics and Gynecology, Unaizah College of Medicine and Medical Sciences, Qassim University, Unaizah, Saudi Arabia.
Ghulam Rahim AwabMahidol Oxford Tropical Medicine Research Unit (MORU), Faculty of Tropical Medicine, Mahidol University, Bangkok, Thailand.
J Kevin BairdOxford University Clinical Research Unit Indonesia, Faculty of Medicine, Universitas Indonesia, Jakarta, Indonesia.
Larissa W BrasilDiretoria de Ensino E Pesquisa, Fundação de Medicina Tropical Dr. Heitor Vieira Dourado, Manaus, AM, Brazil.
Cindy S ChuCentre for Tropical Medicine and Global Health, Nuffield Department of Medicine, Oxford University, Oxford, UK.
Liwang CuiDepartment of Internal Medicine, Morsani College of Medicine, University of South Florida, Tampa, FL, USA.
André DaherFiocruz Clinical Research Platform, Vice-Presidency of Research and Biological Collections, Oswaldo Cruz Foundation (FIOCRUZ), Rio de Janeiro, Brazil.
Margarete do Socorro M GomesSuperintendência de Vigilância Em Saúde Do Estado Do Amapá - SVS/AP, Macapá, Amapá, Brazil.
Lilia Gonzalez-CeronRegional Centre for Public Health Research, National Institute for Public Health, Tapachula, Chiapas, Mexico.
Jimee HwangU.S. President's Malaria Initiative, Malaria Branch, U.S. Centers for Disease Control and Prevention, Atlanta, GA, USA.
Harin KarunajeewaDepartment of Medicine-Western Health, Melbourne Medical School, The University of Melbourne, St. Albans, VIC, Australia.
Marcus V G LacerdaFundação de Medicina Tropical Dr Heitor Vieira Dourado, Manaus, Brazil.
Simone Ladeia-AndradeLaboratory of Parasitic Diseases, Oswaldo Cruz Institute, Fiocruz, Rio de Janeiro, Brazil.
Toby LeslieDepartment of Infectious and Tropical Diseases, London School of Hygiene and Tropical Medicine, London, UK.
Benedikt LeyGlobal Health Division, Menzies School of Health Research and Charles Darwin University, Darwin, NT, Australia.
Kartini LidiaDepartment of Pharmacology and Therapy, Faculty of Medicine and Veterinary Medicine, Universitas Nusa Cendana, Kupang, Indonesia.
Alejandro Llanos-CuentasUnit of Leishmaniasis and Malaria, Instituto de Medicina Tropical "Alexander Von Humboldt", Universidad Peruana Cayetano Heredia, Lima, Peru.
Rhea J LongleyMahidol Vivax Research Unit, Faculty of Tropical Medicine, Mahidol University, Bangkok, Thailand.
Wuelton Marcelo MonteiroUniversidade Do Estado Do Amazonas, Manaus, Brazil.
Dhelio B PereiraCentro de Pesquisa Em Medicina Tropical de Rondonia (CEPEM), Porto Velho, Brazil.
Komal Raj RijalCentral Department of Microbiology, Tribhuvan University, Kirtipur, Kathmandu, Nepal.
Kavitha SaravuDepartment of Infectious Diseases, Kasturba Medical College Manipal, Manipal Academy of Higher Education, Madhava Nagar, Manipal, Karnataka, India.
Inge SutantoDepartment of Parasitology, Faculty of Medicine, University of Indonesia, Jakarta, Indonesia.
Walter R J TaylorMahidol Oxford Tropical Medicine Research Unit (MORU), Faculty of Tropical Medicine, Mahidol University, Bangkok, Thailand.
Pham Vinh ThanhNational Institute of Malariology, Parasitology and Entomology, Hanoi, Vietnam.
Kamala ThriemerGlobal Health Division, Menzies School of Health Research and Charles Darwin University, Darwin, NT, Australia.
José Luiz F VieiraFederal University of Pará, Universidade Federal Do Pará - UFPA), Belém, Pará, Brazil.
Nicholas J WhiteMahidol Oxford Tropical Medicine Research Unit (MORU), Faculty of Tropical Medicine, Mahidol University, Bangkok, Thailand.
Lina M Zuluaga-IdarragaGrupo Malaria, Facultad de Medicina, Universidad de Antioquia, Medellín, Colombia.
Philippe J GuerinCentre for Tropical Medicine and Global Health, Nuffield Department of Medicine, Oxford University, Oxford, UK.
Ric N PriceCentre for Tropical Medicine and Global Health, Nuffield Department of Medicine, Oxford University, Oxford, UK.
Julie A SimpsonCentre for Epidemiology and Biostatistics, Melbourne School of Population and Global Health, The University of Melbourne, Melbourne, Australia.
Robert J CommonsGlobal Health Division, Menzies School of Health Research and Charles Darwin University, Darwin, NT, Australia. robert.commons@gmail.com.
WWARN Vivax Adherence Study Group

Funding

Wellcome TrustWellcome Trust 089179
6 · The paper itself

Abstract

backgroundImperfect 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.

methodsEfficacy 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.

resultsOf 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.

conclusionReduced adherence, including less supervision, increases the risk of vivax recurrence.

Indexed as

AntimalarialsFolic Acid AntagonistsMalaria, VivaxHumansPlasmodium vivaxPrimaquineRecurrenceAntimalarialsFolic Acid AntagonistsPrimaquineAdherenceMalariaPlasmodium vivaxPrimaquineRate of recurrenceSupervision

Identifiers

PMID37817240
PMCPMC10563365

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.