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2020-07-12
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THE EFFECT OF CHLOROQUINE DOSE AND PRIMAQUINE ON PLASMODIUM VIVAX RECURRENCE: A WORLDWIDE ANTIMALARIAL RESISTANCE NETWORK SYSTEMATIC REVIEW AND INDIVIDUAL PATIENT POOLED META-ANALYSIS
C. H. Sibley - Fundação Oswaldo Cruz. Instituto Nacional de Infectologia Evandro Chagas. Rio de Janeiro, RJ, Brasil.
A. Erhart - Fundação Oswaldo Cruz. Institute of Drug Technology (Farmanguinhos). Rio de Janeiro, RJ, Brasil.
A. Daher - Oswaldo Cruz Foundation. Vice-Presidency of Research and Reference Laboratories. Rio de Janeiro, RJ, Brazil.
Global Health Division, Menzies School of Health Research and Charles Darwin University, Darwin, NT, Australia (R J Commons FRACP, K Thriemer PhD, Prof N M Anstey PhD, B E Barber PhD, M J Grigg PhD, B Ley PhD, Prof R N Price FRCP); WorldWide Antimalarial Resistance Network, Clinical module, Darwin, NT, Australia (R J Commons, Prof R N Price); Department of Infectious Diseases, Royal Brisbane and Women’s Hospital, Herston, QLD, Australia (R J Commons); Centre for Epidemiology and Biostatistics, Melbourne School of Population and Global Health, The University of Melbourne, Melbourne, VIC, Australia (Prof J A Simpson PhD); WorldWide Antimalarial Resistance Network, Oxford, UK (G S Humphreys PhD, P Dahal MSc, Prof C H Sibley PhD, K Stepniewska PhD, Prof P J Guerin MD); Centre for Tropical Medicine, Nuffield Department of Clinical Medicine, University of Oxford, Oxford, UK (G S Humphreys, Prof J K Baird PhD, C S Chu MD, P Dahal, Prof F Nosten PhD, Prof H T Tran MD, Prof P J Guerin, Prof N J White FRS, Prof R N Price); ICAP, Columbia University Mailman School of Public Health, Addis Ababa, Ethiopia (T Abreha MPH); Department of Biology (T Ketema PhD), College of Natural Sciences (S G Alemu MSc), Addis Ababa University, Addis Ababa, Ethiopia; Armauer Hansen Research Institute, Addis Ababa, Ethiopia (S G Alemu); Departamento de Salud Pública, Universidad de Barcelona, Barcelona, Spain (A Añez PhD); Organización Panamericana de Salud, Oficina de país Bolivia, La Paz, Bolivia (A Añez); Mahidol-Oxford Tropical Medicine Research Unit, Faculty of Tropical Medicine, Mahidol University, Bangkok, Thailand (G R Awab PhD, W R J Taylor MD, C J Woodrow PhD, Prof N J White); Nangarhar Medical Faculty, Nangarhar University, Jalalabad Afghanistan (G R Awab); Eijkman-Oxford Clinical Research Unit, Jakarta, Indonesia (Prof J K Baird); Infectious Diseases Society Sabah-Menzies School of Health Research Clinical Research Unit, Kota Kinabalu, Sabah, Malaysia (B E Barber, M J Grigg, T William MRCP); Medicines for Malaria Venture, Geneva, Switzerland (I Borghini-Fuhrer PhD); Shoklo Malaria Research Unit, Mahidol-Oxford Tropical Medicine Research Unit, Faculty of Tropical Medicine, Mahidol University, Mae Sot, Thailand (C S Chu, Prof F Nosten, A P Phyo PhD); Unit of Malariology, Institute of Tropical Medicine, Antwerp, Belgium (U D’Alessandro PhD, A Erhart MD); Medical Research Council Unit, Fajara, The Gambia (U D’Alessandro, A Erhart); Institute of Drug Technology (Farmanguinhos) (A Daher MD), and Vice-Presidency of Research and Reference Laboratories (A Daher), Oswaldo Cruz Foundation, Rio de Janeiro, Brazil; Liverpool School of Tropical Medicine, Liverpool, UK (A Daher); Department of Internal Medicine, Tergooi Hospital, Hilversum, Netherlands (P J de Vries PhD); Global Health Institute, Faculty of Medicine and Health Sciences, University of Antwerp, Belgium (A Erhart); Superintendência de Vigilância em Saúde do Estado do Amapá -SVS/AP, Macapá, Amapá, Brazil (M S M Gomes PhD); Federal University of Amapá, Macapá, Amapá, Brazil (M S M Gomes); Regional Centre for Public Health Research, National Institute for Public Health, Tapachula, Chiapas, Mexico (L Gonzalez-Ceron PhD); Department of Medical Parasitology, School of Medicine, Alborz University of Medical Sciences, Karaj, Iran (A Heidari PhD); US President’s Malaria Initiative, Malaria Branch, US Centers for Disease Control and Prevention, Atlanta, GA, USA (J Hwang MD); Global Health Group,University of California San Francisco, San Francisco, CA, USA (J Hwang); Centre for Infection and Immunity Amsterdam (Prof P A Kager MD), Division of Infectious Diseases, Tropical Medicine and AIDS (G T Phan PhD), Academic Medical Center, Amsterdam, Netherlands; Department of Biology, Jimma University, Jimma, Ethiopia (T Ketema); International Centre for Diarrheal Diseases and Research, Dhaka, Bangladesh (W A Khan MHS); Fundação de Medicina Tropical Dr Heitor Vieira Dourado, Manaus, Brazil (Prof M V G Lacerda PhD, Prof W M Monteiro PhD, A M Siqueira PhD); Programa de Pós-graduação em Medicina Tropical, Universidade do Estado do Amazonas, Manaus, Brazil (Prof W M Monteiro, A M Siqueira); Fundação Oswaldo Cruz, Instituto Leônidas e Maria Deane (FIOCRUZ-Amazonas), Manaus, Brazil (Prof M V G Lacerda); Department of Infectious and Tropical Diseases, London School of Hygiene and Tropical Medicine, London, UK (T Leslie PhD, Prof M Rowland PhD); HealthNet-TPO, Kabul, Afghanistan (T Leslie); Department of Pharmacology and Therapy, Faculty of Medicine, Nusa Cendana University, Kupang, Indonesia (K Lidia MSc); Centro de Pesquisa em Medicina Tropical de Rondônia, Porto Velho, Rondônia, Brazil (Prof D B Pereira MD); Universidade Federal de Rondônia, Porto Velho, Rondônia, Brazil (Prof D B Pereira); Tropical Diseases Clinical Research Center, Cho Ray Hospital, Ho Chi Minh City, Vietnam (G T Phan, B Q Tran MD); Department of Medicine, Kasturba Medical College, (Prof K Saravu MD), and Manipal McGill Center for Infectious Diseases (Prof K Saravu), Manipal Academy of Higher Education, Manipal, Karnataka, India; Department of Genome Sciences, University of Washington, Seattle, WA, USA (Prof C H Sibley); Instituto Nacional de Infectologia Evandro Chagas, Fundação Oswaldo Cruz, Rio de Janeiro, Brazil (A M Siqueira); Department of Parasitology, Faculty of Medicine, University of Indonesia, Jakarta, Indonesia (Prof I Sutanto PhD); Oxford University Clinical Research Unit, Ho Chi Minh City, Vietnam (Prof G Thwaites FRCP, Prof H T Tran); Malaria Research Centre, Delhi, India (N Valecha MD); Federal University of Pará, Belém, Pará, Brazil (J L F Vieira PhD); Public Health Laboratory, Department of Public Health, Ministry of Health, Thimphu, Bhutan (S Wangchuk PhD); Infectious Diseases Unit, Clinical Research Centre, Queen Elizabeth Hospital, Kota Kinabalu, Sabah, Malaysia (T William); Division of Clinical Sciences, St George’s, University of London, London, UK (C J Woodrow); and Grupo Malaria, Facultad de Medicina, Universidad de Antioquia, Medellín, Colombia (L Zuluaga-Idarraga PhD).
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Abstract
Background Chloroquine 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.
Methods A 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. Findings Of 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). Interpretation Chloroquine 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.
Publisher
Elsevier
Citation
COMMONS, Robert J. et al. The effect of chloroquine dose and primaquine on Plasmodium vivax recurrence: a WorldWide Antimalarial Resistance Network systematic review and individual patient pooled meta-analysis. Lancet Infectious Diseases, v. 18, p. 1025-1034, Sept. 2018DOI
10.1016/S1473-3099(18)30348-7ISSN
1473-3099Notes
W. M. Monteiro, A. M. Siqueira - Fundação Oswaldo Cruz. Instituto Leônidas e Maria Deane. Manaus, AM, Brasil.C. H. Sibley - Fundação Oswaldo Cruz. Instituto Nacional de Infectologia Evandro Chagas. Rio de Janeiro, RJ, Brasil.
A. Erhart - Fundação Oswaldo Cruz. Institute of Drug Technology (Farmanguinhos). Rio de Janeiro, RJ, Brasil.
A. Daher - Oswaldo Cruz Foundation. Vice-Presidency of Research and Reference Laboratories. Rio de Janeiro, RJ, Brazil.
Global Health Division, Menzies School of Health Research and Charles Darwin University, Darwin, NT, Australia (R J Commons FRACP, K Thriemer PhD, Prof N M Anstey PhD, B E Barber PhD, M J Grigg PhD, B Ley PhD, Prof R N Price FRCP); WorldWide Antimalarial Resistance Network, Clinical module, Darwin, NT, Australia (R J Commons, Prof R N Price); Department of Infectious Diseases, Royal Brisbane and Women’s Hospital, Herston, QLD, Australia (R J Commons); Centre for Epidemiology and Biostatistics, Melbourne School of Population and Global Health, The University of Melbourne, Melbourne, VIC, Australia (Prof J A Simpson PhD); WorldWide Antimalarial Resistance Network, Oxford, UK (G S Humphreys PhD, P Dahal MSc, Prof C H Sibley PhD, K Stepniewska PhD, Prof P J Guerin MD); Centre for Tropical Medicine, Nuffield Department of Clinical Medicine, University of Oxford, Oxford, UK (G S Humphreys, Prof J K Baird PhD, C S Chu MD, P Dahal, Prof F Nosten PhD, Prof H T Tran MD, Prof P J Guerin, Prof N J White FRS, Prof R N Price); ICAP, Columbia University Mailman School of Public Health, Addis Ababa, Ethiopia (T Abreha MPH); Department of Biology (T Ketema PhD), College of Natural Sciences (S G Alemu MSc), Addis Ababa University, Addis Ababa, Ethiopia; Armauer Hansen Research Institute, Addis Ababa, Ethiopia (S G Alemu); Departamento de Salud Pública, Universidad de Barcelona, Barcelona, Spain (A Añez PhD); Organización Panamericana de Salud, Oficina de país Bolivia, La Paz, Bolivia (A Añez); Mahidol-Oxford Tropical Medicine Research Unit, Faculty of Tropical Medicine, Mahidol University, Bangkok, Thailand (G R Awab PhD, W R J Taylor MD, C J Woodrow PhD, Prof N J White); Nangarhar Medical Faculty, Nangarhar University, Jalalabad Afghanistan (G R Awab); Eijkman-Oxford Clinical Research Unit, Jakarta, Indonesia (Prof J K Baird); Infectious Diseases Society Sabah-Menzies School of Health Research Clinical Research Unit, Kota Kinabalu, Sabah, Malaysia (B E Barber, M J Grigg, T William MRCP); Medicines for Malaria Venture, Geneva, Switzerland (I Borghini-Fuhrer PhD); Shoklo Malaria Research Unit, Mahidol-Oxford Tropical Medicine Research Unit, Faculty of Tropical Medicine, Mahidol University, Mae Sot, Thailand (C S Chu, Prof F Nosten, A P Phyo PhD); Unit of Malariology, Institute of Tropical Medicine, Antwerp, Belgium (U D’Alessandro PhD, A Erhart MD); Medical Research Council Unit, Fajara, The Gambia (U D’Alessandro, A Erhart); Institute of Drug Technology (Farmanguinhos) (A Daher MD), and Vice-Presidency of Research and Reference Laboratories (A Daher), Oswaldo Cruz Foundation, Rio de Janeiro, Brazil; Liverpool School of Tropical Medicine, Liverpool, UK (A Daher); Department of Internal Medicine, Tergooi Hospital, Hilversum, Netherlands (P J de Vries PhD); Global Health Institute, Faculty of Medicine and Health Sciences, University of Antwerp, Belgium (A Erhart); Superintendência de Vigilância em Saúde do Estado do Amapá -SVS/AP, Macapá, Amapá, Brazil (M S M Gomes PhD); Federal University of Amapá, Macapá, Amapá, Brazil (M S M Gomes); Regional Centre for Public Health Research, National Institute for Public Health, Tapachula, Chiapas, Mexico (L Gonzalez-Ceron PhD); Department of Medical Parasitology, School of Medicine, Alborz University of Medical Sciences, Karaj, Iran (A Heidari PhD); US President’s Malaria Initiative, Malaria Branch, US Centers for Disease Control and Prevention, Atlanta, GA, USA (J Hwang MD); Global Health Group,University of California San Francisco, San Francisco, CA, USA (J Hwang); Centre for Infection and Immunity Amsterdam (Prof P A Kager MD), Division of Infectious Diseases, Tropical Medicine and AIDS (G T Phan PhD), Academic Medical Center, Amsterdam, Netherlands; Department of Biology, Jimma University, Jimma, Ethiopia (T Ketema); International Centre for Diarrheal Diseases and Research, Dhaka, Bangladesh (W A Khan MHS); Fundação de Medicina Tropical Dr Heitor Vieira Dourado, Manaus, Brazil (Prof M V G Lacerda PhD, Prof W M Monteiro PhD, A M Siqueira PhD); Programa de Pós-graduação em Medicina Tropical, Universidade do Estado do Amazonas, Manaus, Brazil (Prof W M Monteiro, A M Siqueira); Fundação Oswaldo Cruz, Instituto Leônidas e Maria Deane (FIOCRUZ-Amazonas), Manaus, Brazil (Prof M V G Lacerda); Department of Infectious and Tropical Diseases, London School of Hygiene and Tropical Medicine, London, UK (T Leslie PhD, Prof M Rowland PhD); HealthNet-TPO, Kabul, Afghanistan (T Leslie); Department of Pharmacology and Therapy, Faculty of Medicine, Nusa Cendana University, Kupang, Indonesia (K Lidia MSc); Centro de Pesquisa em Medicina Tropical de Rondônia, Porto Velho, Rondônia, Brazil (Prof D B Pereira MD); Universidade Federal de Rondônia, Porto Velho, Rondônia, Brazil (Prof D B Pereira); Tropical Diseases Clinical Research Center, Cho Ray Hospital, Ho Chi Minh City, Vietnam (G T Phan, B Q Tran MD); Department of Medicine, Kasturba Medical College, (Prof K Saravu MD), and Manipal McGill Center for Infectious Diseases (Prof K Saravu), Manipal Academy of Higher Education, Manipal, Karnataka, India; Department of Genome Sciences, University of Washington, Seattle, WA, USA (Prof C H Sibley); Instituto Nacional de Infectologia Evandro Chagas, Fundação Oswaldo Cruz, Rio de Janeiro, Brazil (A M Siqueira); Department of Parasitology, Faculty of Medicine, University of Indonesia, Jakarta, Indonesia (Prof I Sutanto PhD); Oxford University Clinical Research Unit, Ho Chi Minh City, Vietnam (Prof G Thwaites FRCP, Prof H T Tran); Malaria Research Centre, Delhi, India (N Valecha MD); Federal University of Pará, Belém, Pará, Brazil (J L F Vieira PhD); Public Health Laboratory, Department of Public Health, Ministry of Health, Thimphu, Bhutan (S Wangchuk PhD); Infectious Diseases Unit, Clinical Research Centre, Queen Elizabeth Hospital, Kota Kinabalu, Sabah, Malaysia (T William); Division of Clinical Sciences, St George’s, University of London, London, UK (C J Woodrow); and Grupo Malaria, Facultad de Medicina, Universidad de Antioquia, Medellín, Colombia (L Zuluaga-Idarraga PhD).
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