Publication:
The haematological consequences of Plasmodium vivax malaria after chloroquine treatment with and without primaquine: A WorldWide Antimalarial Resistance Network systematic review and individual patient data meta-analysis

2

Issued Date

2019-08-01

Resource Type

Review

ISSN

17417015

DOI

10.1186/s12916-019-1386-6

Other identifier(s)

2-s2.0-85070892819

Rights

Mahidol University

Rights Holder(s)

SCOPUS

Bibliographic Citation

BMC Medicine. Vol.17, No.1 (2019)

Suggested Citation

Robert J. Commons, Julie A. Simpson, Kamala Thriemer, Cindy S. Chu, Nicholas M. Douglas, Tesfay Abreha, Sisay G. Alemu, Arletta Añez, Nicholas M. Anstey, Abraham Aseffa, Ashenafi Assefa, Ghulam R. Awab, J. Kevin Baird, Bridget E. Barber, Isabelle Borghini-Fuhrer, Umberto D'Alessandro, Prabin Dahal, André Daher, Peter J. De Vries, Annette Erhart, Margarete S.M. Gomes, Matthew J. Grigg, Jimee Hwang, Piet A. Kager, Tsige Ketema, Wasif A. Khan, Marcus V.G. Lacerda, Toby Leslie, Benedikt Ley, Kartini Lidia, Wuelton M. Monteiro, Dhelio B. Pereira, Giao T. Phan, Aung P. Phyo, Mark Rowland, Kavitha Saravu, Carol H. Sibley, André M. Siqueira, Kasia Stepniewska, Walter R.J. Taylor, Guy Thwaites, Binh Q. Tran, Tran T. Hien, José Luiz F. Vieira, Sonam Wangchuk, James Watson, Timothy William, Charles J. Woodrow, Francois Nosten, Philippe J. Guerin, Nicholas J. White, Ric N. Price The haematological consequences of Plasmodium vivax malaria after chloroquine treatment with and without primaquine: A WorldWide Antimalarial Resistance Network systematic review and individual patient data meta-analysis. BMC Medicine. Vol.17, No.1 (2019). doi:10.1186/s12916-019-1386-6 Retrieved from: https://repository.li.mahidol.ac.th/handle/123456789/51523

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Title

The haematological consequences of Plasmodium vivax malaria after chloroquine treatment with and without primaquine: A WorldWide Antimalarial Resistance Network systematic review and individual patient data meta-analysis

Author(s)

Robert J. Commons
 Julie A. Simpson
 Kamala Thriemer
 Cindy S. Chu
 Nicholas M. Douglas
 Tesfay Abreha
 Sisay G. Alemu
 Arletta Añez
 Nicholas M. Anstey
 Abraham Aseffa
 Ashenafi Assefa
 Ghulam R. Awab
 J. Kevin Baird
 Bridget E. Barber
 Isabelle Borghini-Fuhrer
 Umberto D'Alessandro
 Prabin Dahal
 André Daher
 Peter J. De Vries
 Annette Erhart
 Margarete S.M. Gomes
 Matthew J. Grigg
 Jimee Hwang
 Piet A. Kager
 Tsige Ketema
 Wasif A. Khan
 Marcus V.G. Lacerda
 Toby Leslie
 Benedikt Ley
 Kartini Lidia
 Wuelton M. Monteiro
 Dhelio B. Pereira
 Giao T. Phan
 Aung P. Phyo
 Mark Rowland
 Kavitha Saravu
 Carol H. Sibley
 André M. Siqueira
 Kasia Stepniewska
 Walter R.J. Taylor
 Guy Thwaites
 Binh Q. Tran
 Tran T. Hien
 José Luiz F. Vieira
 Sonam Wangchuk
 James Watson
 Timothy William
 Charles J. Woodrow
 Francois Nosten
 Philippe J. Guerin
 Nicholas J. White
 Ric N. Price

Other Contributor(s)

Melbourne School of Population and Global Health
 Health Works, Amsterdam
 Tergooiziekenhuizen
 Cho Ray Hospital
 Jimma University
 Armauer Hansen Research Institute
 Addis Ababa University
 London School of Hygiene & Tropical Medicine
 Columbia University Irving Medical Center
 Fundacao Oswaldo Cruz
 Menzies School of Health Research
 Fundacao Universidade Federal de Rondonia
 University of California, San Francisco
 Centers for Disease Control and Prevention
 Liverpool School of Tropical Medicine
 Universidade Federal do Amapa
 Manipal Academy of Higher Education
 Kasturba Medical College, Manipal
 University of Washington, Seattle
 Mahidol University
 Nuffield Department of Clinical Medicine
 Universidade do Estado do Amazonas
 Universidade Federal do Para
 Universitat de Barcelona
 Amsterdam UMC - University of Amsterdam
 LSTMH
 Medicines for Malaria Venture
 Gleneagles Hospital
 Ethiopian Public Health Institute
 Nangarhar University
 WorldWide Antimalarial Resistance Network (WWARN)
 Nusa Cendana University
 Infectious Diseases Society Sabah-Menzies School of Health Research Clinical Research Unit
 Organización Panamericana de Salud
 Eijkman-Oxford Clinical Research Unit
 Fundação de Medicina Tropical Dr. Heitor Vieira Dourado
 WorldWide Antimalarial Resistance Network (WWARN)
 International Centre for Diarrheal Diseases and Research
 Centro de Pesquisa em Medicina Tropical de Rondônia (CEPEM)
 Ministry of Health
 Secretaria de Saúde do Estado do Amapá
 Oxford University Clinical Research Unit

Abstract

© 2019 The Author(s). Background: Malaria causes a reduction in haemoglobin that is compounded by primaquine, particularly in patients with glucose-6-phosphate dehydrogenase (G6PD) deficiency. The aim of this study was to determine the relative contributions to red cell loss of malaria and primaquine in patients with uncomplicated Plasmodium vivax. Methods: A systematic review identified P. vivax efficacy studies of chloroquine with or without primaquine published between January 2000 and March 2017. Individual patient data were pooled using standardised methodology, and the haematological response versus time was quantified using a multivariable linear mixed effects model with non-linear terms for time. Mean differences in haemoglobin between treatment groups at day of nadir and day 42 were estimated from this model. Results: In total, 3421 patients from 29 studies were included: 1692 (49.5%) with normal G6PD status, 1701 (49.7%) with unknown status and 28 (0.8%) deficient or borderline individuals. Of 1975 patients treated with chloroquine alone, the mean haemoglobin fell from 12.22 g/dL [95% CI 11.93, 12.50] on day 0 to a nadir of 11.64 g/dL [11.36, 11.93] on day 2, before rising to 12.88 g/dL [12.60, 13.17] on day 42. In comparison to chloroquine alone, the mean haemoglobin in 1446 patients treated with chloroquine plus primaquine was - 0.13 g/dL [- 0.27, 0.01] lower at day of nadir (p = 0.072), but 0.49 g/dL [0.28, 0.69] higher by day 42 (p < 0.001). On day 42, patients with recurrent parasitaemia had a mean haemoglobin concentration - 0.72 g/dL [- 0.90, - 0.54] lower than patients without recurrence (p < 0.001). Seven days after starting primaquine, G6PD normal patients had a 0.3% (1/389) risk of clinically significant haemolysis (fall in haemoglobin > 25% to < 7 g/dL) and a 1% (4/389) risk of a fall in haemoglobin > 5 g/dL. Conclusions: Primaquine has the potential to reduce malaria-related anaemia at day 42 and beyond by preventing recurrent parasitaemia. Its widespread implementation will require accurate diagnosis of G6PD deficiency to reduce the risk of drug-induced haemolysis in vulnerable individuals. Trial registration: This trial was registered with PROSPERO: CRD42016053312. The date of the first registration was 23 December 2016.

Keyword(s)

Medicine

Availability

URI

https://repository.li.mahidol.ac.th/handle/123456789/51523

Collections

Scopus 2019