Eintrag weiter verarbeiten
author_facet Hossain, Mohammad S.
Commons, Robert J.
Douglas, Nicholas M.
Thriemer, Kamala
Alemayehu, Bereket H.
Amaratunga, Chanaki
Anvikar, Anupkumar R.
Ashley, Elizabeth A.
Asih, Puji B. S.
Carrara, Verena I.
Lon, Chanthap
D’Alessandro, Umberto
Davis, Timothy M. E.
Dondorp, Arjen M.
Edstein, Michael D.
Fairhurst, Rick M.
Ferreira, Marcelo U.
Hwang, Jimee
Janssens, Bart
Karunajeewa, Harin
Kiechel, Jean R.
Ladeia-Andrade, Simone
Laman, Moses
Mayxay, Mayfong
McGready, Rose
Moore, Brioni R.
Mueller, Ivo
Newton, Paul N.
Thuy-Nhien, Nguyen T.
Noedl, Harald
Nosten, Francois
Phyo, Aung P.
Poespoprodjo, Jeanne R.
Saunders, David L.
Smithuis, Frank
Spring, Michele D.
Stepniewska, Kasia
Suon, Seila
Suputtamongkol, Yupin
Syafruddin, Din
Tran, Hien T.
Valecha, Neena
Van Herp, Michel
Van Vugt, Michele
White, Nicholas J.
Guerin, Philippe J.
Simpson, Julie A.
Price, Ric N.
Hossain, Mohammad S.
Commons, Robert J.
Douglas, Nicholas M.
Thriemer, Kamala
Alemayehu, Bereket H.
Amaratunga, Chanaki
Anvikar, Anupkumar R.
Ashley, Elizabeth A.
Asih, Puji B. S.
Carrara, Verena I.
Lon, Chanthap
D’Alessandro, Umberto
Davis, Timothy M. E.
Dondorp, Arjen M.
Edstein, Michael D.
Fairhurst, Rick M.
Ferreira, Marcelo U.
Hwang, Jimee
Janssens, Bart
Karunajeewa, Harin
Kiechel, Jean R.
Ladeia-Andrade, Simone
Laman, Moses
Mayxay, Mayfong
McGready, Rose
Moore, Brioni R.
Mueller, Ivo
Newton, Paul N.
Thuy-Nhien, Nguyen T.
Noedl, Harald
Nosten, Francois
Phyo, Aung P.
Poespoprodjo, Jeanne R.
Saunders, David L.
Smithuis, Frank
Spring, Michele D.
Stepniewska, Kasia
Suon, Seila
Suputtamongkol, Yupin
Syafruddin, Din
Tran, Hien T.
Valecha, Neena
Van Herp, Michel
Van Vugt, Michele
White, Nicholas J.
Guerin, Philippe J.
Simpson, Julie A.
Price, Ric N.
author Hossain, Mohammad S.
Commons, Robert J.
Douglas, Nicholas M.
Thriemer, Kamala
Alemayehu, Bereket H.
Amaratunga, Chanaki
Anvikar, Anupkumar R.
Ashley, Elizabeth A.
Asih, Puji B. S.
Carrara, Verena I.
Lon, Chanthap
D’Alessandro, Umberto
Davis, Timothy M. E.
Dondorp, Arjen M.
Edstein, Michael D.
Fairhurst, Rick M.
Ferreira, Marcelo U.
Hwang, Jimee
Janssens, Bart
Karunajeewa, Harin
Kiechel, Jean R.
Ladeia-Andrade, Simone
Laman, Moses
Mayxay, Mayfong
McGready, Rose
Moore, Brioni R.
Mueller, Ivo
Newton, Paul N.
Thuy-Nhien, Nguyen T.
Noedl, Harald
Nosten, Francois
Phyo, Aung P.
Poespoprodjo, Jeanne R.
Saunders, David L.
Smithuis, Frank
Spring, Michele D.
Stepniewska, Kasia
Suon, Seila
Suputtamongkol, Yupin
Syafruddin, Din
Tran, Hien T.
Valecha, Neena
Van Herp, Michel
Van Vugt, Michele
White, Nicholas J.
Guerin, Philippe J.
Simpson, Julie A.
Price, Ric N.
spellingShingle Hossain, Mohammad S.
Commons, Robert J.
Douglas, Nicholas M.
Thriemer, Kamala
Alemayehu, Bereket H.
Amaratunga, Chanaki
Anvikar, Anupkumar R.
Ashley, Elizabeth A.
Asih, Puji B. S.
Carrara, Verena I.
Lon, Chanthap
D’Alessandro, Umberto
Davis, Timothy M. E.
Dondorp, Arjen M.
Edstein, Michael D.
Fairhurst, Rick M.
Ferreira, Marcelo U.
Hwang, Jimee
Janssens, Bart
Karunajeewa, Harin
Kiechel, Jean R.
Ladeia-Andrade, Simone
Laman, Moses
Mayxay, Mayfong
McGready, Rose
Moore, Brioni R.
Mueller, Ivo
Newton, Paul N.
Thuy-Nhien, Nguyen T.
Noedl, Harald
Nosten, Francois
Phyo, Aung P.
Poespoprodjo, Jeanne R.
Saunders, David L.
Smithuis, Frank
Spring, Michele D.
Stepniewska, Kasia
Suon, Seila
Suputtamongkol, Yupin
Syafruddin, Din
Tran, Hien T.
Valecha, Neena
Van Herp, Michel
Van Vugt, Michele
White, Nicholas J.
Guerin, Philippe J.
Simpson, Julie A.
Price, Ric N.
PLOS Medicine
The risk of Plasmodium vivax parasitaemia after P. falciparum malaria: An individual patient data meta-analysis from the WorldWide Antimalarial Resistance Network
General Medicine
author_sort hossain, mohammad s.
spelling Hossain, Mohammad S. Commons, Robert J. Douglas, Nicholas M. Thriemer, Kamala Alemayehu, Bereket H. Amaratunga, Chanaki Anvikar, Anupkumar R. Ashley, Elizabeth A. Asih, Puji B. S. Carrara, Verena I. Lon, Chanthap D’Alessandro, Umberto Davis, Timothy M. E. Dondorp, Arjen M. Edstein, Michael D. Fairhurst, Rick M. Ferreira, Marcelo U. Hwang, Jimee Janssens, Bart Karunajeewa, Harin Kiechel, Jean R. Ladeia-Andrade, Simone Laman, Moses Mayxay, Mayfong McGready, Rose Moore, Brioni R. Mueller, Ivo Newton, Paul N. Thuy-Nhien, Nguyen T. Noedl, Harald Nosten, Francois Phyo, Aung P. Poespoprodjo, Jeanne R. Saunders, David L. Smithuis, Frank Spring, Michele D. Stepniewska, Kasia Suon, Seila Suputtamongkol, Yupin Syafruddin, Din Tran, Hien T. Valecha, Neena Van Herp, Michel Van Vugt, Michele White, Nicholas J. Guerin, Philippe J. Simpson, Julie A. Price, Ric N. 1549-1676 Public Library of Science (PLoS) General Medicine http://dx.doi.org/10.1371/journal.pmed.1003393 <jats:sec id="sec001"> <jats:title>Background</jats:title> <jats:p>There is a high risk of <jats:italic>Plasmodium vivax</jats:italic> 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.</jats:p> </jats:sec> <jats:sec id="sec002"> <jats:title>Methods and findings</jats:title> <jats:p>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 <jats:italic>P</jats:italic>. <jats:italic>vivax</jats:italic> between 1 January 1960 and 5 January 2018. Data from eligible studies were pooled using standardised methodology. The risk of <jats:italic>P</jats:italic>. <jats:italic>vivax</jats:italic> 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 <jats:italic>P</jats:italic>. <jats:italic>falciparum</jats:italic> monoinfection and 1,195 (7.8%) mixed infection with <jats:italic>P</jats:italic>. <jats:italic>falciparum</jats:italic> and <jats:italic>P</jats:italic>. <jats:italic>vivax</jats:italic>. 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 <jats:italic>P</jats:italic>. <jats:italic>falciparum</jats:italic> 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 <jats:italic>P</jats:italic>. <jats:italic>vivax</jats:italic> 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 &lt; 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 &lt; 0.001). The analysis was limited by heterogeneity between study populations and lack of data from very low transmission settings. Study quality was high.</jats:p> </jats:sec> <jats:sec id="sec003"> <jats:title>Conclusions</jats:title> <jats:p>In this meta-analysis, we found a high risk of <jats:italic>P</jats:italic>. <jats:italic>vivax</jats:italic> parasitaemia after treatment of <jats:italic>P</jats:italic>. <jats:italic>falciparum</jats:italic> malaria that varied significantly between studies. These <jats:italic>P</jats:italic>. <jats:italic>vivax</jats:italic> 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.</jats:p> </jats:sec> The risk of Plasmodium vivax parasitaemia after P. falciparum malaria: An individual patient data meta-analysis from the WorldWide Antimalarial Resistance Network PLOS Medicine
doi_str_mv 10.1371/journal.pmed.1003393
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title The risk of Plasmodium vivax parasitaemia after P. falciparum malaria: An individual patient data meta-analysis from the WorldWide Antimalarial Resistance Network
title_unstemmed 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_short The risk of Plasmodium vivax parasitaemia after P. falciparum malaria: An individual patient data meta-analysis from the WorldWide Antimalarial Resistance Network
title_sort the risk of plasmodium vivax parasitaemia after p. falciparum malaria: an individual patient data meta-analysis from the worldwide antimalarial resistance network
topic General Medicine
url http://dx.doi.org/10.1371/journal.pmed.1003393
publishDate 2020
physical e1003393
description <jats:sec id="sec001"> <jats:title>Background</jats:title> <jats:p>There is a high risk of <jats:italic>Plasmodium vivax</jats:italic> 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.</jats:p> </jats:sec> <jats:sec id="sec002"> <jats:title>Methods and findings</jats:title> <jats:p>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 <jats:italic>P</jats:italic>. <jats:italic>vivax</jats:italic> between 1 January 1960 and 5 January 2018. Data from eligible studies were pooled using standardised methodology. The risk of <jats:italic>P</jats:italic>. <jats:italic>vivax</jats:italic> 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 <jats:italic>P</jats:italic>. <jats:italic>falciparum</jats:italic> monoinfection and 1,195 (7.8%) mixed infection with <jats:italic>P</jats:italic>. <jats:italic>falciparum</jats:italic> and <jats:italic>P</jats:italic>. <jats:italic>vivax</jats:italic>. 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 <jats:italic>P</jats:italic>. <jats:italic>falciparum</jats:italic> 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 <jats:italic>P</jats:italic>. <jats:italic>vivax</jats:italic> 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 &lt; 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 &lt; 0.001). The analysis was limited by heterogeneity between study populations and lack of data from very low transmission settings. Study quality was high.</jats:p> </jats:sec> <jats:sec id="sec003"> <jats:title>Conclusions</jats:title> <jats:p>In this meta-analysis, we found a high risk of <jats:italic>P</jats:italic>. <jats:italic>vivax</jats:italic> parasitaemia after treatment of <jats:italic>P</jats:italic>. <jats:italic>falciparum</jats:italic> malaria that varied significantly between studies. These <jats:italic>P</jats:italic>. <jats:italic>vivax</jats:italic> 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.</jats:p> </jats:sec>
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author Hossain, Mohammad S., Commons, Robert J., Douglas, Nicholas M., Thriemer, Kamala, Alemayehu, Bereket H., Amaratunga, Chanaki, Anvikar, Anupkumar R., Ashley, Elizabeth A., Asih, Puji B. S., Carrara, Verena I., Lon, Chanthap, D’Alessandro, Umberto, Davis, Timothy M. E., Dondorp, Arjen M., Edstein, Michael D., Fairhurst, Rick M., Ferreira, Marcelo U., Hwang, Jimee, Janssens, Bart, Karunajeewa, Harin, Kiechel, Jean R., Ladeia-Andrade, Simone, Laman, Moses, Mayxay, Mayfong, McGready, Rose, Moore, Brioni R., Mueller, Ivo, Newton, Paul N., Thuy-Nhien, Nguyen T., Noedl, Harald, Nosten, Francois, Phyo, Aung P., Poespoprodjo, Jeanne R., Saunders, David L., Smithuis, Frank, Spring, Michele D., Stepniewska, Kasia, Suon, Seila, Suputtamongkol, Yupin, Syafruddin, Din, Tran, Hien T., Valecha, Neena, Van Herp, Michel, Van Vugt, Michele, White, Nicholas J., Guerin, Philippe J., Simpson, Julie A., Price, Ric N.
author_facet Hossain, Mohammad S., Commons, Robert J., Douglas, Nicholas M., Thriemer, Kamala, Alemayehu, Bereket H., Amaratunga, Chanaki, Anvikar, Anupkumar R., Ashley, Elizabeth A., Asih, Puji B. S., Carrara, Verena I., Lon, Chanthap, D’Alessandro, Umberto, Davis, Timothy M. E., Dondorp, Arjen M., Edstein, Michael D., Fairhurst, Rick M., Ferreira, Marcelo U., Hwang, Jimee, Janssens, Bart, Karunajeewa, Harin, Kiechel, Jean R., Ladeia-Andrade, Simone, Laman, Moses, Mayxay, Mayfong, McGready, Rose, Moore, Brioni R., Mueller, Ivo, Newton, Paul N., Thuy-Nhien, Nguyen T., Noedl, Harald, Nosten, Francois, Phyo, Aung P., Poespoprodjo, Jeanne R., Saunders, David L., Smithuis, Frank, Spring, Michele D., Stepniewska, Kasia, Suon, Seila, Suputtamongkol, Yupin, Syafruddin, Din, Tran, Hien T., Valecha, Neena, Van Herp, Michel, Van Vugt, Michele, White, Nicholas J., Guerin, Philippe J., Simpson, Julie A., Price, Ric N., Hossain, Mohammad S., Commons, Robert J., Douglas, Nicholas M., Thriemer, Kamala, Alemayehu, Bereket H., Amaratunga, Chanaki, Anvikar, Anupkumar R., Ashley, Elizabeth A., Asih, Puji B. S., Carrara, Verena I., Lon, Chanthap, D’Alessandro, Umberto, Davis, Timothy M. E., Dondorp, Arjen M., Edstein, Michael D., Fairhurst, Rick M., Ferreira, Marcelo U., Hwang, Jimee, Janssens, Bart, Karunajeewa, Harin, Kiechel, Jean R., Ladeia-Andrade, Simone, Laman, Moses, Mayxay, Mayfong, McGready, Rose, Moore, Brioni R., Mueller, Ivo, Newton, Paul N., Thuy-Nhien, Nguyen T., Noedl, Harald, Nosten, Francois, Phyo, Aung P., Poespoprodjo, Jeanne R., Saunders, David L., Smithuis, Frank, Spring, Michele D., Stepniewska, Kasia, Suon, Seila, Suputtamongkol, Yupin, Syafruddin, Din, Tran, Hien T., Valecha, Neena, Van Herp, Michel, Van Vugt, Michele, White, Nicholas J., Guerin, Philippe J., Simpson, Julie A., Price, Ric N.
author_sort hossain, mohammad s.
container_issue 11
container_start_page 0
container_title PLOS Medicine
container_volume 17
description <jats:sec id="sec001"> <jats:title>Background</jats:title> <jats:p>There is a high risk of <jats:italic>Plasmodium vivax</jats:italic> 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.</jats:p> </jats:sec> <jats:sec id="sec002"> <jats:title>Methods and findings</jats:title> <jats:p>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 <jats:italic>P</jats:italic>. <jats:italic>vivax</jats:italic> between 1 January 1960 and 5 January 2018. Data from eligible studies were pooled using standardised methodology. The risk of <jats:italic>P</jats:italic>. <jats:italic>vivax</jats:italic> 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 <jats:italic>P</jats:italic>. <jats:italic>falciparum</jats:italic> monoinfection and 1,195 (7.8%) mixed infection with <jats:italic>P</jats:italic>. <jats:italic>falciparum</jats:italic> and <jats:italic>P</jats:italic>. <jats:italic>vivax</jats:italic>. 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 <jats:italic>P</jats:italic>. <jats:italic>falciparum</jats:italic> 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 <jats:italic>P</jats:italic>. <jats:italic>vivax</jats:italic> 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 &lt; 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 &lt; 0.001). The analysis was limited by heterogeneity between study populations and lack of data from very low transmission settings. Study quality was high.</jats:p> </jats:sec> <jats:sec id="sec003"> <jats:title>Conclusions</jats:title> <jats:p>In this meta-analysis, we found a high risk of <jats:italic>P</jats:italic>. <jats:italic>vivax</jats:italic> parasitaemia after treatment of <jats:italic>P</jats:italic>. <jats:italic>falciparum</jats:italic> malaria that varied significantly between studies. These <jats:italic>P</jats:italic>. <jats:italic>vivax</jats:italic> 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.</jats:p> </jats:sec>
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spelling Hossain, Mohammad S. Commons, Robert J. Douglas, Nicholas M. Thriemer, Kamala Alemayehu, Bereket H. Amaratunga, Chanaki Anvikar, Anupkumar R. Ashley, Elizabeth A. Asih, Puji B. S. Carrara, Verena I. Lon, Chanthap D’Alessandro, Umberto Davis, Timothy M. E. Dondorp, Arjen M. Edstein, Michael D. Fairhurst, Rick M. Ferreira, Marcelo U. Hwang, Jimee Janssens, Bart Karunajeewa, Harin Kiechel, Jean R. Ladeia-Andrade, Simone Laman, Moses Mayxay, Mayfong McGready, Rose Moore, Brioni R. Mueller, Ivo Newton, Paul N. Thuy-Nhien, Nguyen T. Noedl, Harald Nosten, Francois Phyo, Aung P. Poespoprodjo, Jeanne R. Saunders, David L. Smithuis, Frank Spring, Michele D. Stepniewska, Kasia Suon, Seila Suputtamongkol, Yupin Syafruddin, Din Tran, Hien T. Valecha, Neena Van Herp, Michel Van Vugt, Michele White, Nicholas J. Guerin, Philippe J. Simpson, Julie A. Price, Ric N. 1549-1676 Public Library of Science (PLoS) General Medicine http://dx.doi.org/10.1371/journal.pmed.1003393 <jats:sec id="sec001"> <jats:title>Background</jats:title> <jats:p>There is a high risk of <jats:italic>Plasmodium vivax</jats:italic> 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.</jats:p> </jats:sec> <jats:sec id="sec002"> <jats:title>Methods and findings</jats:title> <jats:p>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 <jats:italic>P</jats:italic>. <jats:italic>vivax</jats:italic> between 1 January 1960 and 5 January 2018. Data from eligible studies were pooled using standardised methodology. The risk of <jats:italic>P</jats:italic>. <jats:italic>vivax</jats:italic> 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 <jats:italic>P</jats:italic>. <jats:italic>falciparum</jats:italic> monoinfection and 1,195 (7.8%) mixed infection with <jats:italic>P</jats:italic>. <jats:italic>falciparum</jats:italic> and <jats:italic>P</jats:italic>. <jats:italic>vivax</jats:italic>. 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 <jats:italic>P</jats:italic>. <jats:italic>falciparum</jats:italic> 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 <jats:italic>P</jats:italic>. <jats:italic>vivax</jats:italic> 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 &lt; 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 &lt; 0.001). The analysis was limited by heterogeneity between study populations and lack of data from very low transmission settings. Study quality was high.</jats:p> </jats:sec> <jats:sec id="sec003"> <jats:title>Conclusions</jats:title> <jats:p>In this meta-analysis, we found a high risk of <jats:italic>P</jats:italic>. <jats:italic>vivax</jats:italic> parasitaemia after treatment of <jats:italic>P</jats:italic>. <jats:italic>falciparum</jats:italic> malaria that varied significantly between studies. These <jats:italic>P</jats:italic>. <jats:italic>vivax</jats:italic> 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.</jats:p> </jats:sec> The risk of Plasmodium vivax parasitaemia after P. falciparum malaria: An individual patient data meta-analysis from the WorldWide Antimalarial Resistance Network PLOS Medicine
spellingShingle Hossain, Mohammad S., Commons, Robert J., Douglas, Nicholas M., Thriemer, Kamala, Alemayehu, Bereket H., Amaratunga, Chanaki, Anvikar, Anupkumar R., Ashley, Elizabeth A., Asih, Puji B. S., Carrara, Verena I., Lon, Chanthap, D’Alessandro, Umberto, Davis, Timothy M. E., Dondorp, Arjen M., Edstein, Michael D., Fairhurst, Rick M., Ferreira, Marcelo U., Hwang, Jimee, Janssens, Bart, Karunajeewa, Harin, Kiechel, Jean R., Ladeia-Andrade, Simone, Laman, Moses, Mayxay, Mayfong, McGready, Rose, Moore, Brioni R., Mueller, Ivo, Newton, Paul N., Thuy-Nhien, Nguyen T., Noedl, Harald, Nosten, Francois, Phyo, Aung P., Poespoprodjo, Jeanne R., Saunders, David L., Smithuis, Frank, Spring, Michele D., Stepniewska, Kasia, Suon, Seila, Suputtamongkol, Yupin, Syafruddin, Din, Tran, Hien T., Valecha, Neena, Van Herp, Michel, Van Vugt, Michele, White, Nicholas J., Guerin, Philippe J., Simpson, Julie A., Price, Ric N., PLOS Medicine, The risk of Plasmodium vivax parasitaemia after P. falciparum malaria: An individual patient data meta-analysis from the WorldWide Antimalarial Resistance Network, General Medicine
title 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_short The risk of Plasmodium vivax parasitaemia after P. falciparum malaria: An individual patient data meta-analysis from the WorldWide Antimalarial Resistance Network
title_sort the risk of plasmodium vivax parasitaemia after p. falciparum malaria: an individual patient data meta-analysis from the worldwide antimalarial resistance network
title_unstemmed The risk of Plasmodium vivax parasitaemia after P. falciparum malaria: An individual patient data meta-analysis from the WorldWide Antimalarial Resistance Network
topic General Medicine
url http://dx.doi.org/10.1371/journal.pmed.1003393