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
Year: 2019
Type: review
Study designs: Systematic Review, Meta-Analysis
Abstract: 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.
Source: BMC Medicine
Authors: 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
Institutions: Charles Darwin University, Menzies School of Health Research, The University of Melbourne, Mahidol University, University of Oxford, Shoklo Malaria Research Unit, Mahidol Oxford Tropical Medicine Research Unit, Columbia University, Armauer Hansen Research Institute, Addis Ababa University, World Health Organization Regional Office for the Americas, Universitat de Barcelona, Ethiopian Public Health Institute, Nangarhar University, Oxford University Clinical Research Unit Indonesia, Medicines for Malaria Venture, MRC Unit the Gambia, Liverpool School of Tropical Medicine, Instituto de Tecnologia em Fármacos, Fundação Oswaldo Cruz, Tergooi, Universidade Federal do Amapá, Centers for Disease Control and Prevention, University of California, San Francisco, U.S. President's Malaria Initiative, Amsterdam UMC Location University of Amsterdam, Jimma University, International Centre for Diarrhoeal Disease Research, Fundação de Medicina Tropical, Fiocruz Amazônia, HealthNet TPO, London School of Hygiene & Tropical Medicine, University of Nusa Cendana, Universidade do Estado do Amazonas, Universidade Federal de Rondônia, Cho Ray Hospital, Manipal Academy of Higher Education, Kasturba Medical College Hospital, Kasturba Medical College, Manipal, University of Washington, Instituto Nacional de Infectologia Evandro Chagas, Oxford University Clinical Research Unit, Universidade Federal do Pará, Ministry of Health
Language: English
Topic: Malaria Research and Control
Field: Medicine
Domain: Health Sciences
Open Access status: gold
Estimated APC paid: $2,825
Funders: Bill and Melinda Gates Foundation, Exxon Mobil Corporation, Wellcome Trust, University of Oxford, Royal Australasian College of Physicians, Conselho Nacional de Desenvolvimento Científico e Tecnológico, Centers for Disease Control and Prevention, Medical Research Council, National Health and Medical Research Council, National Institute of Allergy and Infectious Diseases
Awards: G1617459808, Pathophysiology and treatment of malaria in our region, G3253273863, G3350072673, Impact of malaria elimination on immunity and risk of malaria rebound in Myanmar, Integration of biostatistics and mathematical modelling to improve the control of infectious diseases, Comparative incidence and clinical spectrum of Plasmodium knowlesi malaria, a longitudinal study in Sabah, Malaysia, Improving the treatment of Plasmodium vivax, G690355535, G730015249, Risk factors, mechanisms, and treatment of knowlesi malaria, G7597818247, Improving the treatment of Plasmodium vivax, G8654089671, Centre for Research Excellence in Malaria Elimination, Improving the treatment of malaria.
OpenAlex ID: W2966250344