Please use this identifier to cite or link to this item:
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
André Daher. Fundação Oswaldo Cruz. Instituto de Tecnologia em Fármacos / Fundação Oswaldo Cruz. Presidência. Vice-Presidência de Pesquisa. Documento produzido em parceria ou por autor vinculado à Fiocruz, mas não consta a informação no documento.
Marcus V. G. Lacerda. Fundação Oswaldo Cruz. Instituto Leônidas e Maria Deane. Documento produzido em parceria ou por autor vinculado à Fiocruz, mas não consta a informação no documento.
1 Global Health Division, Menzies School of Health Research and Charles Darwin University, Darwin, Northern Territory, Australia. 2 WorldWide Antimalarial Resistance Network (WWARN), Clinical Module, Darwin, Northern Territory, Australia. 3 Centre for Epidemiology and Biostatistics, Melbourne School of Population and Global Health, The University of Melbourne, Melbourne, Victoria, Australia. 4 Centre for Tropical Medicine and Global Health, Nuffield Department of Clinical Medicine, University of Oxford, Oxford, UK. 5 Shoklo Malaria Research Unit, Mahidol-Oxford Tropical Medicine Research Unit, Faculty of Tropical Medicine, Mahidol University, Mae Sot, Thailand. 6 ICAP, Columbia University Mailman School of Public Health, Addis Ababa, Ethiopia. 7 Addis Ababa University, Addis Ababa, Ethiopia. 8 Armauer Hansen Research Institute, Addis Ababa, Ethiopia. 9 Departamento de Salud Pública, Universidad de Barcelona, Barcelona, Spain. 10Organización Panamericana de Salud, Oficina de País Bolivia, La Paz, Bolivia. 11Malaria and Neglected Tropical Diseases Research Team, Bacterial, Parasitic, Zoonotic Diseases Research Directorate, Ethiopian Public Health Institute, Addis Ababa, Ethiopia. 12Mahidol-Oxford Tropical Medicine Research Unit (MORU), Faculty of Tropical Medicine, Mahidol University, Bangkok, Thailand. 13Nangarhar Medical Faculty, Nangarhar University, Jalalabad, Afghanistan. 14Eijkman-Oxford Clinical Research Unit, Jakarta, Indonesia. 15Infectious Diseases Society Sabah-Menzies School of Health Research Clinical Research Unit, Kota Kinabalu, Sabah, Malaysia. 16Medicines for Malaria Venture, Geneva, Switzerland. 17Medical Research Council Unit The Gambia at LSTMH, Fajara, The Gambia. 18WorldWide Antimalarial Resistance Network (WWARN), Oxford, UK. 19Institute of Drug Technology (Farmanguinhos), Oswaldo Cruz Foundation (FIOCRUZ), Rio de Janeiro, Brazil. 20Vice-presidency of Research and Reference Laboratories, Oswaldo Cruz Foundation (FIOCRUZ), Rio de Janeiro, Brazil. 21Liverpool School of Tropical Medicine, Liverpool, UK. 22Department of Internal Medicine, Tergooi Hospital, Hilversum, the Netherlands. 23Superintendência de Vigilância em Saúde do Estado do Amapá - SVS/AP, Macapá, Amapá, Brazil. 24Universidade Federal do Amapá – UNIFAP, Macapá, Amapá, Brazil. 25U.S. President’s Malaria Initiative, Malaria Branch, U.S. Centers for Disease Control and Prevention, Atlanta, USA. 26Global Health Group, University of California San Francisco, San Francisco, USA. 27Centre for Infection and Immunity Amsterdam (CINEMA), Division of Infectious Diseases, Tropical Medicine and AIDS, Academic Medical Centre, Amsterdam, the Netherlands. 28Department of Biology, Addis Ababa University, Addis Ababa, Ethiopia. 29Department of Biology, Jimma University, Jimma, Ethiopia. 30International Centre for Diarrheal Diseases and Research, Dhaka, Bangladesh. 31Fundação de Medicina Tropical Dr. Heitor Vieira Dourado, Manaus, Brazil. 32Universidade do Estado do Amazonas, Manaus, Brazil. 33Fundação Oswaldo Cruz, Instituto Leônidas e Maria Deane (FIOCRUZ-Amazonas), Manaus, Brazil. 34Department of Infectious and Tropical Diseases, London School of Hygiene and Tropical Medicine, London, UK. 35HealthNet-TPO, Kabul, Afghanistan. 36The Department of Pharmacology and Therapy, Faculty of Medicine, Nusa Cendana University, Kupang, Indonesia. 37Centro de Pesquisa em Medicina Tropical de Rondônia (CEPEM), Porto Velho, Rondônia, Brazil. 38Universidade Federal de Rondônia (UNIR), Porto Velho, Rondônia, Brazil. 39Division of Infectious Diseases, Tropical Commons et al. BMC Medicine (2019) 17:151 Page 11 of 13 Medicine and AIDS, Academic Medical Center, Amsterdam, the Netherlands. 40Tropical Diseases Clinical Research Center, Cho Ray Hospital, Ho Chi Minh City, Vietnam. 41Department of Medicine, Kasturba Medical College, Manipal Academy of Higher Education, Madhav Nagar, Manipal, Karnataka, India. 42Manipal McGill Center for Infectious Diseases, Manipal Academy of Higher Education, Manipal, Karnataka, India. 43Department of Genome Sciences, University of Washington, Seattle, USA. 44Programa de Pós-graduação em Medicina Tropical, Universidade do Estado do Amazonas, Manaus, Brazil. 45Instituto Nacional de Infectologia Evandro Chagas, Fundação Oswaldo Cruz, Rio de Janeiro, Brazil. 46Oxford University Clinical Research Unit, Ho Chi Minh City, Vietnam. 47Federal University of Pará (Universidade Federal do Pará - UFPA), Belém, Pará, Brazil. 48Public Health Laboratory, Department of Public Health, Ministry of Health, Thimphu, Bhutan. 49Gleneagles Hospital, Kota Kinabalu, Sabah, Malaysia.
Author
Affilliation
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. n 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.
Publisher
BioMed Central
Citation
COMMONS, Robert J. et al. 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, v. 17, n. 1, p. 1-13, Aug. 2019.DOI
10.1186/s12916-019-1386-6ISSN
1741-7015Notes
André M. Siqueira. Fundação Oswaldo Cruz. Instituto Nacional de Infectologia Evandro Chagas. Documento produzido em parceria ou por autor vinculado à Fiocruz, mas não consta a informação no documento.André Daher. Fundação Oswaldo Cruz. Instituto de Tecnologia em Fármacos / Fundação Oswaldo Cruz. Presidência. Vice-Presidência de Pesquisa. Documento produzido em parceria ou por autor vinculado à Fiocruz, mas não consta a informação no documento.
Marcus V. G. Lacerda. Fundação Oswaldo Cruz. Instituto Leônidas e Maria Deane. Documento produzido em parceria ou por autor vinculado à Fiocruz, mas não consta a informação no documento.
1 Global Health Division, Menzies School of Health Research and Charles Darwin University, Darwin, Northern Territory, Australia. 2 WorldWide Antimalarial Resistance Network (WWARN), Clinical Module, Darwin, Northern Territory, Australia. 3 Centre for Epidemiology and Biostatistics, Melbourne School of Population and Global Health, The University of Melbourne, Melbourne, Victoria, Australia. 4 Centre for Tropical Medicine and Global Health, Nuffield Department of Clinical Medicine, University of Oxford, Oxford, UK. 5 Shoklo Malaria Research Unit, Mahidol-Oxford Tropical Medicine Research Unit, Faculty of Tropical Medicine, Mahidol University, Mae Sot, Thailand. 6 ICAP, Columbia University Mailman School of Public Health, Addis Ababa, Ethiopia. 7 Addis Ababa University, Addis Ababa, Ethiopia. 8 Armauer Hansen Research Institute, Addis Ababa, Ethiopia. 9 Departamento de Salud Pública, Universidad de Barcelona, Barcelona, Spain. 10Organización Panamericana de Salud, Oficina de País Bolivia, La Paz, Bolivia. 11Malaria and Neglected Tropical Diseases Research Team, Bacterial, Parasitic, Zoonotic Diseases Research Directorate, Ethiopian Public Health Institute, Addis Ababa, Ethiopia. 12Mahidol-Oxford Tropical Medicine Research Unit (MORU), Faculty of Tropical Medicine, Mahidol University, Bangkok, Thailand. 13Nangarhar Medical Faculty, Nangarhar University, Jalalabad, Afghanistan. 14Eijkman-Oxford Clinical Research Unit, Jakarta, Indonesia. 15Infectious Diseases Society Sabah-Menzies School of Health Research Clinical Research Unit, Kota Kinabalu, Sabah, Malaysia. 16Medicines for Malaria Venture, Geneva, Switzerland. 17Medical Research Council Unit The Gambia at LSTMH, Fajara, The Gambia. 18WorldWide Antimalarial Resistance Network (WWARN), Oxford, UK. 19Institute of Drug Technology (Farmanguinhos), Oswaldo Cruz Foundation (FIOCRUZ), Rio de Janeiro, Brazil. 20Vice-presidency of Research and Reference Laboratories, Oswaldo Cruz Foundation (FIOCRUZ), Rio de Janeiro, Brazil. 21Liverpool School of Tropical Medicine, Liverpool, UK. 22Department of Internal Medicine, Tergooi Hospital, Hilversum, the Netherlands. 23Superintendência de Vigilância em Saúde do Estado do Amapá - SVS/AP, Macapá, Amapá, Brazil. 24Universidade Federal do Amapá – UNIFAP, Macapá, Amapá, Brazil. 25U.S. President’s Malaria Initiative, Malaria Branch, U.S. Centers for Disease Control and Prevention, Atlanta, USA. 26Global Health Group, University of California San Francisco, San Francisco, USA. 27Centre for Infection and Immunity Amsterdam (CINEMA), Division of Infectious Diseases, Tropical Medicine and AIDS, Academic Medical Centre, Amsterdam, the Netherlands. 28Department of Biology, Addis Ababa University, Addis Ababa, Ethiopia. 29Department of Biology, Jimma University, Jimma, Ethiopia. 30International Centre for Diarrheal Diseases and Research, Dhaka, Bangladesh. 31Fundação de Medicina Tropical Dr. Heitor Vieira Dourado, Manaus, Brazil. 32Universidade do Estado do Amazonas, Manaus, Brazil. 33Fundação Oswaldo Cruz, Instituto Leônidas e Maria Deane (FIOCRUZ-Amazonas), Manaus, Brazil. 34Department of Infectious and Tropical Diseases, London School of Hygiene and Tropical Medicine, London, UK. 35HealthNet-TPO, Kabul, Afghanistan. 36The Department of Pharmacology and Therapy, Faculty of Medicine, Nusa Cendana University, Kupang, Indonesia. 37Centro de Pesquisa em Medicina Tropical de Rondônia (CEPEM), Porto Velho, Rondônia, Brazil. 38Universidade Federal de Rondônia (UNIR), Porto Velho, Rondônia, Brazil. 39Division of Infectious Diseases, Tropical Commons et al. BMC Medicine (2019) 17:151 Page 11 of 13 Medicine and AIDS, Academic Medical Center, Amsterdam, the Netherlands. 40Tropical Diseases Clinical Research Center, Cho Ray Hospital, Ho Chi Minh City, Vietnam. 41Department of Medicine, Kasturba Medical College, Manipal Academy of Higher Education, Madhav Nagar, Manipal, Karnataka, India. 42Manipal McGill Center for Infectious Diseases, Manipal Academy of Higher Education, Manipal, Karnataka, India. 43Department of Genome Sciences, University of Washington, Seattle, USA. 44Programa de Pós-graduação em Medicina Tropical, Universidade do Estado do Amazonas, Manaus, Brazil. 45Instituto Nacional de Infectologia Evandro Chagas, Fundação Oswaldo Cruz, Rio de Janeiro, Brazil. 46Oxford University Clinical Research Unit, Ho Chi Minh City, Vietnam. 47Federal University of Pará (Universidade Federal do Pará - UFPA), Belém, Pará, Brazil. 48Public Health Laboratory, Department of Public Health, Ministry of Health, Thimphu, Bhutan. 49Gleneagles Hospital, Kota Kinabalu, Sabah, Malaysia.
Share