Evidence map›Paper›PMID 30033231›Full record

SynthesisThe Lancet. Infectious diseases2018

The effect of chloroquine dose and primaquine on Plasmodium vivax recurrence: a WorldWide Antimalarial Resistance Network systematic review and individual patient pooled meta-analysis.

Robert J Commons, Julie A Simpson, Kamala Thriemer, Georgina S Humphreys, Tesfay Abreha, Sisay G Alemu, Arletta Añez, Nicholas M Anstey, Ghulam R Awab, J Kevin Baird and 44 more

Open access · hybridAbstract readMeta-AnalysisSystematic Review
PubMed Full text at PMC Publisher
In one paragraph

Synthesis in The Lancet. Infectious diseases, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 67 papers, 7 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
67citing papers in PubMed, 7 pooled it
13.6field-weighted citation impact, top 1% of its field
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

67 citing papers in PubMed, 7 syntheses or guidelines pooled it, 110 citations in OpenAlex.

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  4. Estimating the Proportion ofThe American journal of tropical medicine and hygiene · 2020
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  13. Efficacy of primaquine-chloroquine combination onParasite epidemiology and control · 2026
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  20. Analysis of Severe and Relapse Risks of Imported Malaria in Five Provinces of China.The American journal of tropical medicine and hygiene · 2025
    Article

7 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

54 authors at 20 institutions in 20 countries.

Robert J CommonsGlobal Health Division, Menzies School of Health Research and Charles Darwin University, Darwin, NT, Australia; WorldWide Antimalarial Resistance Network, Clinical module, Darwin, NT, Australia; Department of Infectious Diseases, Royal Brisbane and Women's Hospital, Herston, QLD, Australia.
Julie A SimpsonCentre for Epidemiology and Biostatistics, Melbourne School of Population and Global Health, The University of Melbourne, Melbourne, VIC, Australia.
Kamala ThriemerGlobal Health Division, Menzies School of Health Research and Charles Darwin University, Darwin, NT, Australia.
Georgina S HumphreysWorldWide Antimalarial Resistance Network, Oxford, UK; Centre for Tropical Medicine, Nuffield Department of Clinical Medicine, University of Oxford, Oxford, UK.
Tesfay AbrehaICAP, Columbia University Mailman School of Public Health, Addis Ababa, Ethiopia.
Sisay G AlemuCollege of Natural Sciences, Addis Ababa University, Addis Ababa, Ethiopia; Armauer Hansen Research Institute, Addis Ababa, Ethiopia.
Arletta AñezDepartamento de Salud Pública, Universidad de Barcelona, Barcelona, Spain; Organización Panamericana de Salud, Oficina de país Bolivia, La Paz, Bolivia.
Nicholas M AnsteyGlobal Health Division, Menzies School of Health Research and Charles Darwin University, Darwin, NT, Australia.
Ghulam R AwabMahidol-Oxford Tropical Medicine Research Unit, Faculty of Tropical Medicine, Mahidol University, Bangkok, Thailand; Nangarhar Medical Faculty, Nangarhar University, Jalalabad Afghanistan.
J Kevin BairdCentre for Tropical Medicine, Nuffield Department of Clinical Medicine, University of Oxford, Oxford, UK; Eijkman-Oxford Clinical Research Unit, Jakarta, Indonesia.
Bridget E BarberGlobal Health Division, Menzies School of Health Research and Charles Darwin University, Darwin, NT, Australia; Infectious Diseases Society Sabah-Menzies School of Health Research Clinical Research Unit, Kota Kinabalu, Sabah, Malaysia.
Isabelle Borghini-FuhrerMedicines for Malaria Venture, Geneva, Switzerland.
Cindy S ChuCentre for Tropical Medicine, Nuffield Department of Clinical Medicine, University of Oxford, Oxford, UK; Shoklo Malaria Research Unit, Mahidol-Oxford Tropical Medicine Research Unit, Faculty of Tropical Medicine, Mahidol University, Mae Sot, Thailand.
Umberto D'AlessandroUnit of Malariology, Institute of Tropical Medicine, Antwerp, Belgium; Medical Research Council Unit, Fajara, The Gambia.
Prabin DahalWorldWide Antimalarial Resistance Network, Oxford, UK; Centre for Tropical Medicine, Nuffield Department of Clinical Medicine, University of Oxford, Oxford, UK.
André DaherInstitute of Drug Technology (Farmanguinhos), Oswaldo Cruz Foundation, Rio de Janeiro, Brazil; Vice-Presidency of Research and Reference Laboratories, Oswaldo Cruz Foundation, Rio de Janeiro, Brazil; Liverpool School of Tropical Medicine, Liverpool, UK.
Peter J de VriesDepartment of Internal Medicine, Tergooi Hospital, Hilversum, Netherlands.
Annette ErhartUnit of Malariology, Institute of Tropical Medicine, Antwerp, Belgium; Medical Research Council Unit, Fajara, The Gambia; Global Health Institute, Faculty of Medicine and Health Sciences, University of Antwerp, Belgium.
Margarete S M GomesSuperintendência de Vigilância em Saúde do Estado do Amapá -SVS/AP, Macapá, Amapá, Brazil; Federal University of Amapá, Macapá, Amapá, Brazil.
Lilia Gonzalez-CeronRegional Centre for Public Health Research, National Institute for Public Health, Tapachula, Chiapas, Mexico.
Matthew J GriggGlobal Health Division, Menzies School of Health Research and Charles Darwin University, Darwin, NT, Australia; Infectious Diseases Society Sabah-Menzies School of Health Research Clinical Research Unit, Kota Kinabalu, Sabah, Malaysia.
Aliehsan HeidariDepartment of Medical Parasitology, School of Medicine, Alborz University of Medical Sciences, Karaj, Iran.
Jimee HwangUS President's Malaria Initiative, Malaria Branch, US Centers for Disease Control and Prevention, Atlanta, GA, USA; Global Health Group, University of California San Francisco, San Francisco, CA, USA.
Piet A KagerCentre for Infection and Immunity Amsterdam, Academic Medical Center, Amsterdam, Netherlands.
Tsige KetemaDepartment of Biology, Addis Ababa University, Addis Ababa, Ethiopia; Department of Biology, Jimma University, Jimma, Ethiopia.
Wasif A KhanInternational Centre for Diarrheal Diseases and Research, Dhaka, Bangladesh.
Marcus V G LacerdaFundação de Medicina Tropical Dr Heitor Vieira Dourado, Manaus, Brazil; Fundação Oswaldo Cruz, Instituto Leônidas e Maria Deane (FIOCRUZ-Amazonas), Manaus, Brazil.
Toby LeslieDepartment of Infectious and Tropical Diseases, London School of Hygiene and Tropical Medicine, London, UK; HealthNet-TPO, Kabul, Afghanistan.
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, Nusa Cendana University, Kupang, Indonesia.
Wuelton M MonteiroFundação de Medicina Tropical Dr Heitor Vieira Dourado, Manaus, Brazil; Programa de Pós-graduação em Medicina Tropical, Universidade do Estado do Amazonas, Manaus, Brazil.
Francois NostenCentre for Tropical Medicine, Nuffield Department of Clinical Medicine, University of Oxford, Oxford, UK; Shoklo Malaria Research Unit, Mahidol-Oxford Tropical Medicine Research Unit, Faculty of Tropical Medicine, Mahidol University, Mae Sot, Thailand.
Dhelio B PereiraCentro de Pesquisa em Medicina Tropical de Rondônia, Porto Velho, Rondônia, Brazil; Universidade Federal de Rondônia, Porto Velho, Rondônia, Brazil.
Giao T PhanDivision of Infectious Diseases, Tropical Medicine and AIDS, Academic Medical Center, Amsterdam, Netherlands; Tropical Diseases Clinical Research Center, Cho Ray Hospital, Ho Chi Minh City, Vietnam.
Aung P PhyoShoklo Malaria Research Unit, Mahidol-Oxford Tropical Medicine Research Unit, Faculty of Tropical Medicine, Mahidol University, Mae Sot, Thailand.
Mark RowlandDepartment of Infectious and Tropical Diseases, London School of Hygiene and Tropical Medicine, London, UK.
Kavitha SaravuDepartment of Medicine, Kasturba Medical College, Manipal Academy of Higher Education, Manipal, Karnataka, India; Manipal McGill Center for Infectious Diseases, Manipal Academy of Higher Education, Manipal, Karnataka, India.
Carol H SibleyWorldWide Antimalarial Resistance Network, Oxford, UK; Department of Genome Sciences, University of Washington, Seattle, WA, USA.
André M SiqueiraFundação de Medicina Tropical Dr Heitor Vieira Dourado, Manaus, Brazil; Programa de Pós-graduação em Medicina Tropical, Universidade do Estado do Amazonas, Manaus, Brazil; Instituto Nacional de Infectologia Evandro Chagas, Fundação Oswaldo Cruz, Rio de Janeiro, Brazil.
Kasia StepniewskaWorldWide Antimalarial Resistance Network, Oxford, UK.
Inge SutantoDepartment of Parasitology, Faculty of Medicine, University of Indonesia, Jakarta, Indonesia.
Walter R J TaylorMahidol-Oxford Tropical Medicine Research Unit, Faculty of Tropical Medicine, Mahidol University, Bangkok, Thailand.
Guy ThwaitesOxford University Clinical Research Unit, Ho Chi Minh City, Vietnam.
Binh Q TranTropical Diseases Clinical Research Center, Cho Ray Hospital, Ho Chi Minh City, Vietnam.
Hien T TranCentre for Tropical Medicine, Nuffield Department of Clinical Medicine, University of Oxford, Oxford, UK; Oxford University Clinical Research Unit, Ho Chi Minh City, Vietnam.
Neena ValechaMalaria Research Centre, Delhi, India.
José Luiz F VieiraFederal University of Pará, Belém, Pará, Brazil.
Sonam WangchukPublic Health Laboratory, Department of Public Health, Ministry of Health, Thimphu, Bhutan.
Timothy WilliamInfectious Diseases Society Sabah-Menzies School of Health Research Clinical Research Unit, Kota Kinabalu, Sabah, Malaysia; Infectious Diseases Unit, Clinical Research Centre, Queen Elizabeth Hospital, Kota Kinabalu, Sabah, Malaysia.
Charles J WoodrowMahidol-Oxford Tropical Medicine Research Unit, Faculty of Tropical Medicine, Mahidol University, Bangkok, Thailand; Division of Clinical Sciences, St George's, University of London, London, UK.
Lina Zuluaga-IdarragaGrupo Malaria, Facultad de Medicina, Universidad de Antioquia, Medellín, Colombia.
Philippe J GuerinWorldWide Antimalarial Resistance Network, Oxford, UK; Centre for Tropical Medicine, Nuffield Department of Clinical Medicine, University of Oxford, Oxford, UK.
Nicholas J WhiteCentre for Tropical Medicine, Nuffield Department of Clinical Medicine, University of Oxford, Oxford, UK; Mahidol-Oxford Tropical Medicine Research Unit, Faculty of Tropical Medicine, Mahidol University, Bangkok, Thailand.
Ric N PriceGlobal Health Division, Menzies School of Health Research and Charles Darwin University, Darwin, NT, Australia; WorldWide Antimalarial Resistance Network, Clinical module, Darwin, NT, Australia; Centre for Tropical Medicine, Nuffield Department of Clinical Medicine, University of Oxford, Oxford, UK. Electronic address: rprice@menzies.edu.au.
Menzies School of Health Research · AUMahidol Oxford Tropical Medicine Research Unit · THNuffield Orthopaedic Centre · GBWorldwide Veterinary Service · GBAddis Ababa University · ETCho Ray Hospital · VNLondon School of Hygiene & Tropical Medicine · GBMahidol University · THAcademic Medical Center · NLAlborz University of Medical SciencesFundação de Medicina Tropical · BRFundação Oswaldo Cruz · BRInternational Centre for Diarrhoeal Disease Research · BDKasturba Medical College, Manipal · INLiverpool School of Tropical Medicine · GBMedicines for Malaria Venture · CHMRC Unit the Gambia · GMNational Institute of Malaria Research · INOxford University Clinical Research Unit · VNQueen Elizabeth Hospital · MY

Funding

Comparative incidence and clinical spectrum of Plasmodium knowlesi malaria, a longitudinal study in Sabah, MalaysiaR01AI116472 · NIAID · INFECTIOUS DISEASE SOCIETY KOTA KINABALU · PI WILLIAM, TIMOTHY · 2015 to 2019
$682k
Medical Research Council MC_UP_A900_1119NIAID NIH HHS R01 AI116472Wellcome Trust 107548/Z/15/ZWellcome Trust 200909Wellcome Trust 200909/Z/16/Z
6 · The paper itself

Abstract

backgroundChloroquine remains the mainstay of treatment for Plasmodium vivax malaria despite increasing reports of treatment failure. We did a systematic review and meta-analysis to investigate the effect of chloroquine dose and the addition of primaquine on the risk of recurrent vivax malaria across different settings.

methodsA systematic review done in MEDLINE, Web of Science, Embase, and Cochrane Database of Systematic Reviews identified P vivax clinical trials published between Jan 1, 2000, and March 22, 2017. Principal investigators were invited to share individual patient data, which were pooled using standardised methods. Cox regression analyses with random effects for study site were used to investigate the roles of chloroquine dose and primaquine use on rate of recurrence between day 7 and day 42 (primary outcome). The review protocol is registered in PROSPERO, number CRD42016053310.

findingsOf 134 identified chloroquine studies, 37 studies (from 17 countries) and 5240 patients were included. 2990 patients were treated with chloroquine alone, of whom 1041 (34·8%) received a dose below the target 25 mg/kg. The risk of recurrence was 32·4% (95% CI 29·8-35·1) by day 42. After controlling for confounders, a 5 mg/kg higher chloroquine dose reduced the rate of recurrence overall (adjusted hazard ratio [AHR] 0·82, 95% CI 0·69-0·97; p=0·021) and in children younger than 5 years (0·59, 0·41-0·86; p=0·0058). Adding primaquine reduced the risk of recurrence to 4·9% (95% CI 3·1-7·7) by day 42, which is lower than with chloroquine alone (AHR 0·10, 0·05-0·17; p<0·0001).

interpretationChloroquine is commonly under-dosed in the treatment of vivax malaria. Increasing the recommended dose to 30 mg/kg in children younger than 5 years could reduce substantially the risk of early recurrence when primaquine is not given. Radical cure with primaquine was highly effective in preventing early recurrence and may also improve blood schizontocidal efficacy against chloroquine-resistant P vivax.

fundingWellcome Trust, Australian National Health and Medical Research Council, and Bill & Melinda Gates Foundation.

Indexed as

Drug ResistanceAdolescentAdultAgedAged, 80 and overAntimalarialsChildChild, PreschoolChloroquineDrug Therapy, CombinationFemaleHumansInfantInfant, NewbornMalaria, VivaxMaleAntimalarialsChloroquinePrimaquine

Identifiers

PMID30033231
PMCPMC6105624
OpenAlexW2884033046

What OpenQuestion holds

Textmetadata
LicenceCC BY
Read underepoch 390

Registered trials

None linked

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.