The risk of Plasmodium vivax parasitaemia after P. falciparum malaria: An individual patient data meta-analysis from the WorldWide Antimalarial Resistance Network
© 2020 Public Library of Science. All rights reserved. Background There is a high risk of Plasmodium vivax parasitaemia following treatment of falciparum malaria. Our study aimed to quantify this risk and the associated determinants using an individual patient data meta-analysis in order to identify...
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Medicine Mohammad S. Hossain Robert J. Commons Nicholas M. Douglas Kamala Thriemer Bereket H. Alemayehu Chanaki Amaratunga Anupkumar R. Anvikar Elizabeth A. Ashley Puji B.S. Asih Verena I. Carrara Chanthap Lon Umberto D’Alessandro Timothy M.E. Davis Arjen M. Dondorp Michael D. Edstein Rick M. Fairhurst Marcelo U. Ferreira Jimee Hwang Bart Janssens Harin Karunajeewa Jean R. Kiechel Simone Ladeia-Andrade Moses Laman Mayfong Mayxay Rose McGready Brioni R. Moore Ivo Mueller Paul N. Newton Nguyen T. Thuy-Nhien Harald Noedl Francois Nosten Aung P. Phyo Jeanne R. Poespoprodjo David L. Saunders Frank Smithuis Michele D. Spring Kasia Stepniewska Seila Suon Yupin Suputtamongkol Din Syafruddin Hien T. Tran Neena Valecha Michel van Herp Michele van Vugt Nicholas J. White Philippe J. Guerin Julie A. Simpson Ric N. Price The risk of Plasmodium vivax parasitaemia after P. falciparum malaria: An individual patient data meta-analysis from the WorldWide Antimalarial Resistance Network |
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© 2020 Public Library of Science. All rights reserved. Background There is a high risk of Plasmodium vivax parasitaemia following treatment of falciparum malaria. Our study aimed to quantify this risk and the associated determinants using an individual patient data meta-analysis in order to identify populations in which a policy of universal radical cure, combining artemisinin-based combination therapy (ACT) with a hypnozoitocidal antimalarial drug, would be beneficial. Methods and findings A systematic review of Medline, Embase, Web of Science, and the Cochrane Database of Systematic Reviews identified efficacy studies of uncomplicated falciparum malaria treated with ACT that were undertaken in regions coendemic for P. vivax between 1 January 1960 and 5 January 2018. Data from eligible studies were pooled using standardised methodology. The risk of P. vivax parasitaemia at days 42 and 63 and associated risk factors were investigated by multivariable Cox regression analyses. Study quality was assessed using a tool developed by the Joanna Briggs Institute. The study was registered in the International Prospective Register of Systematic Reviews (PROSPERO: CRD42018097400). In total, 42 studies enrolling 15,341 patients were included in the analysis, including 30 randomised controlled trials and 12 cohort studies. Overall, 14,146 (92.2%) patients had P. falciparum monoinfection and 1,195 (7.8%) mixed infection with P. falciparum and P. vivax. The median age was 17.0 years (interquartile range [IQR] = 9.0–29.0 years; range = 0–80 years), with 1,584 (10.3%) patients younger than 5 years. 2,711 (17.7%) patients were treated with artemether-lumefantrine (AL, 13 studies), 651 (4.2%) with artesunate-amodiaquine (AA, 6 studies), 7,340 (47.8%) with artesunate-mefloquine (AM, 25 studies), and 4,639 (30.2%) with dihydroartemisinin-piperaquine (DP, 16 studies). 14,537 patients (94.8%) were enrolled from the Asia-Pacific region, 684 (4.5%) from the Americas, and 120 (0.8%) from Africa. At day 42, the cumulative risk of vivax parasitaemia following treatment of P. falciparum was 31.1% (95% CI 28.9–33.4) after AL, 14.1% (95% CI 10.8–18.3) after AA, 7.4% (95% CI 6.7–8.1) after AM, and 4.5% (95% CI 3.9–5.3) after DP. By day 63, the risks had risen to 39.9% (95% CI 36.6–43.3), 42.4% (95% CI 34.7–51.2), 22.8% (95% CI 21.2–24.4), and 12.8% (95% CI 11.4–14.5), respectively. In multivariable analyses, the highest rate of P. vivax parasitaemia over 42 days of follow-up was in patients residing in areas of short relapse periodicity (adjusted hazard ratio [AHR] = 6.2, 95% CI 2.0–19.5; p = 0.002); patients treated with AL (AHR = 6.2, 95% CI 4.6–8.5; p < 0.001), AA (AHR = 2.3, 95% CI 1.4–3.7; p = 0.001), or AM (AHR = 1.4, 95% CI 1.0–1.9; p = 0.028) compared with DP; and patients who did not clear their initial parasitaemia within 2 days (AHR = 1.8, 95% CI 1.4–2.3; p < 0.001). The analysis was limited by heterogeneity between study populations and lack of data from very low transmission settings. Study quality was high. Conclusions In this meta-analysis, we found a high risk of P. vivax parasitaemia after treatment of P. falciparum malaria that varied significantly between studies. These P. vivax infections are likely attributable to relapses that could be prevented with radical cure including a hypnozoitocidal agent; however, the benefits of such a novel strategy will vary considerably between geographical areas. |
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Oxford University Clinical Research Unit |
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Oxford University Clinical Research Unit Mohammad S. Hossain Robert J. Commons Nicholas M. Douglas Kamala Thriemer Bereket H. Alemayehu Chanaki Amaratunga Anupkumar R. Anvikar Elizabeth A. Ashley Puji B.S. Asih Verena I. Carrara Chanthap Lon Umberto D’Alessandro Timothy M.E. Davis Arjen M. Dondorp Michael D. Edstein Rick M. Fairhurst Marcelo U. Ferreira Jimee Hwang Bart Janssens Harin Karunajeewa Jean R. Kiechel Simone Ladeia-Andrade Moses Laman Mayfong Mayxay Rose McGready Brioni R. Moore Ivo Mueller Paul N. Newton Nguyen T. Thuy-Nhien Harald Noedl Francois Nosten Aung P. Phyo Jeanne R. Poespoprodjo David L. Saunders Frank Smithuis Michele D. Spring Kasia Stepniewska Seila Suon Yupin Suputtamongkol Din Syafruddin Hien T. Tran Neena Valecha Michel van Herp Michele van Vugt Nicholas J. White Philippe J. Guerin Julie A. Simpson Ric N. Price |
format |
Article |
author |
Mohammad S. Hossain Robert J. Commons Nicholas M. Douglas Kamala Thriemer Bereket H. Alemayehu Chanaki Amaratunga Anupkumar R. Anvikar Elizabeth A. Ashley Puji B.S. Asih Verena I. Carrara Chanthap Lon Umberto D’Alessandro Timothy M.E. Davis Arjen M. Dondorp Michael D. Edstein Rick M. Fairhurst Marcelo U. Ferreira Jimee Hwang Bart Janssens Harin Karunajeewa Jean R. Kiechel Simone Ladeia-Andrade Moses Laman Mayfong Mayxay Rose McGready Brioni R. Moore Ivo Mueller Paul N. Newton Nguyen T. Thuy-Nhien Harald Noedl Francois Nosten Aung P. Phyo Jeanne R. Poespoprodjo David L. Saunders Frank Smithuis Michele D. Spring Kasia Stepniewska Seila Suon Yupin Suputtamongkol Din Syafruddin Hien T. Tran Neena Valecha Michel van Herp Michele van Vugt Nicholas J. White Philippe J. Guerin Julie A. Simpson Ric N. Price |
author_sort |
Mohammad S. Hossain |
title |
The risk of Plasmodium vivax parasitaemia after P. falciparum malaria: An individual patient data meta-analysis from the WorldWide Antimalarial Resistance Network |
title_short |
The risk of Plasmodium vivax parasitaemia after P. falciparum malaria: An individual patient data meta-analysis from the WorldWide Antimalarial Resistance Network |
title_full |
The risk of Plasmodium vivax parasitaemia after P. falciparum malaria: An individual patient data meta-analysis from the WorldWide Antimalarial Resistance Network |
title_fullStr |
The risk of Plasmodium vivax parasitaemia after P. falciparum malaria: An individual patient data meta-analysis from the WorldWide Antimalarial Resistance Network |
title_full_unstemmed |
The risk of Plasmodium vivax parasitaemia after P. falciparum malaria: An individual patient data meta-analysis from the WorldWide Antimalarial Resistance Network |
title_sort |
risk of plasmodium vivax parasitaemia after p. falciparum malaria: an individual patient data meta-analysis from the worldwide antimalarial resistance network |
publishDate |
2020 |
url |
https://repository.li.mahidol.ac.th/handle/123456789/60552 |
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1763491667760906240 |
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th-mahidol.605522020-12-28T13:07:10Z The risk of Plasmodium vivax parasitaemia after P. falciparum malaria: An individual patient data meta-analysis from the WorldWide Antimalarial Resistance Network Mohammad S. Hossain Robert J. Commons Nicholas M. Douglas Kamala Thriemer Bereket H. Alemayehu Chanaki Amaratunga Anupkumar R. Anvikar Elizabeth A. Ashley Puji B.S. Asih Verena I. Carrara Chanthap Lon Umberto D’Alessandro Timothy M.E. Davis Arjen M. Dondorp Michael D. Edstein Rick M. Fairhurst Marcelo U. Ferreira Jimee Hwang Bart Janssens Harin Karunajeewa Jean R. Kiechel Simone Ladeia-Andrade Moses Laman Mayfong Mayxay Rose McGready Brioni R. Moore Ivo Mueller Paul N. Newton Nguyen T. Thuy-Nhien Harald Noedl Francois Nosten Aung P. Phyo Jeanne R. Poespoprodjo David L. Saunders Frank Smithuis Michele D. Spring Kasia Stepniewska Seila Suon Yupin Suputtamongkol Din Syafruddin Hien T. Tran Neena Valecha Michel van Herp Michele van Vugt Nicholas J. White Philippe J. Guerin Julie A. Simpson Ric N. Price Oxford University Clinical Research Unit Melbourne Medical School Melbourne School of Population and Global Health Medecins Sans Frontieres, Brussels Papua New Guinea Institute of Medical Research Eijkman Institute for Molecular Biology Hasanuddin University Universitas Gadjah Mada Shoklo Malaria Research Unit The University of Western Australia Curtin University Sunshine Hospital Columbia University Irving Medical Center Walter and Eliza Hall Institute of Medical Research University of Melbourne Fundacao Oswaldo Cruz Menzies School of Health Research National Institute of Malaria Research India University of California, San Francisco Centers for Disease Control and Prevention National Institute of Allergy and Infectious Diseases (NIAID) Armed Forces Research Institute of Medical Sciences, Thailand Mahosot Hospital, Lao Mahidol University Ballarat Health Services Faculty of Medicine, Siriraj Hospital, Mahidol University International Centre for Diarrhoeal Disease Research Bangladesh Slotervaart Hospital Nuffield Department of Medicine United States Army Universidade de Sao Paulo - USP Institut Pasteur, Paris Drugs for Neglected Diseases initiative (DNDi) LSTMH Myanmar Oxford Clinical Research Unit University of Health Sciences Australian Defence Force Malaria and Infectious Disease Institute MARIB Mimika District Hospital Ministry of Health of Brazil Medical Action Myanmar Armed Forces Research Institute of Medical Sciences Papuan Health and Community Development Foundation WorldWide Antimalarial Resistance Network (WWARN) National Center for Parasitology, Entomology and Malaria Control Medicine © 2020 Public Library of Science. All rights reserved. Background There is a high risk of Plasmodium vivax parasitaemia following treatment of falciparum malaria. Our study aimed to quantify this risk and the associated determinants using an individual patient data meta-analysis in order to identify populations in which a policy of universal radical cure, combining artemisinin-based combination therapy (ACT) with a hypnozoitocidal antimalarial drug, would be beneficial. Methods and findings A systematic review of Medline, Embase, Web of Science, and the Cochrane Database of Systematic Reviews identified efficacy studies of uncomplicated falciparum malaria treated with ACT that were undertaken in regions coendemic for P. vivax between 1 January 1960 and 5 January 2018. Data from eligible studies were pooled using standardised methodology. The risk of P. vivax parasitaemia at days 42 and 63 and associated risk factors were investigated by multivariable Cox regression analyses. Study quality was assessed using a tool developed by the Joanna Briggs Institute. The study was registered in the International Prospective Register of Systematic Reviews (PROSPERO: CRD42018097400). In total, 42 studies enrolling 15,341 patients were included in the analysis, including 30 randomised controlled trials and 12 cohort studies. Overall, 14,146 (92.2%) patients had P. falciparum monoinfection and 1,195 (7.8%) mixed infection with P. falciparum and P. vivax. The median age was 17.0 years (interquartile range [IQR] = 9.0–29.0 years; range = 0–80 years), with 1,584 (10.3%) patients younger than 5 years. 2,711 (17.7%) patients were treated with artemether-lumefantrine (AL, 13 studies), 651 (4.2%) with artesunate-amodiaquine (AA, 6 studies), 7,340 (47.8%) with artesunate-mefloquine (AM, 25 studies), and 4,639 (30.2%) with dihydroartemisinin-piperaquine (DP, 16 studies). 14,537 patients (94.8%) were enrolled from the Asia-Pacific region, 684 (4.5%) from the Americas, and 120 (0.8%) from Africa. At day 42, the cumulative risk of vivax parasitaemia following treatment of P. falciparum was 31.1% (95% CI 28.9–33.4) after AL, 14.1% (95% CI 10.8–18.3) after AA, 7.4% (95% CI 6.7–8.1) after AM, and 4.5% (95% CI 3.9–5.3) after DP. By day 63, the risks had risen to 39.9% (95% CI 36.6–43.3), 42.4% (95% CI 34.7–51.2), 22.8% (95% CI 21.2–24.4), and 12.8% (95% CI 11.4–14.5), respectively. In multivariable analyses, the highest rate of P. vivax parasitaemia over 42 days of follow-up was in patients residing in areas of short relapse periodicity (adjusted hazard ratio [AHR] = 6.2, 95% CI 2.0–19.5; p = 0.002); patients treated with AL (AHR = 6.2, 95% CI 4.6–8.5; p < 0.001), AA (AHR = 2.3, 95% CI 1.4–3.7; p = 0.001), or AM (AHR = 1.4, 95% CI 1.0–1.9; p = 0.028) compared with DP; and patients who did not clear their initial parasitaemia within 2 days (AHR = 1.8, 95% CI 1.4–2.3; p < 0.001). The analysis was limited by heterogeneity between study populations and lack of data from very low transmission settings. Study quality was high. Conclusions In this meta-analysis, we found a high risk of P. vivax parasitaemia after treatment of P. falciparum malaria that varied significantly between studies. These P. vivax infections are likely attributable to relapses that could be prevented with radical cure including a hypnozoitocidal agent; however, the benefits of such a novel strategy will vary considerably between geographical areas. 2020-12-28T06:07:10Z 2020-12-28T06:07:10Z 2020-11-19 Article PLoS Medicine. Vol.17, No.11 (2020) 10.1371/journal.pmed.1003393 15491676 15491277 2-s2.0-85096458934 https://repository.li.mahidol.ac.th/handle/123456789/60552 Mahidol University SCOPUS https://www.scopus.com/inward/record.uri?partnerID=HzOxMe3b&scp=85096458934&origin=inward |