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1. Louis K. Thaler Concert Violinist Series [concert program]

Author

Kirk-Evan Billet, JungEun Kim, Ithaca College, Kirk-Evan Billet, JungEun Kim, and Ithaca College

Abstract

Program folder for recital on February 8, 2005, by Leon Fleisher and Jaime Laredo. Schubert: Sonatina for violin and piano in A minor, D. 385 -- Brahms: Violin sonata in D minor, op. 108 -- Schubert: Violin sonata in A major, D. 574. Includes biographical notes, photographs. 4 pages.

Published
2005

4. Louis K. Liggett

Author

Liggett, Louis K., E. B. Bird, Bird, Elisha Brown, Liggett, Louis K., E. B. Bird, and Bird, Elisha Brown

Published
1921

7. Louis K. Church portrait

Abstract

Louis K. Church stands posed for a formal portrait. he wears a dark suit and a striped tie.

9. Capt. Louis K. Wilde

Author

United States. Navy--Women and United States. Navy--Women

Abstract

Handwritten description on reverse: "Fourth Director of Navy WAVES 1953-1957"

Published
1953

10. 'In memoriam' resolutions. Dr Louis K. Knight

Author

Cooper, H.K.; McMullen, Ellsworth, Cooper, H.K.; McMullen, Ellsworth, Cooper, H.K.; McMullen, Ellsworth, and Cooper, H.K.; McMullen, Ellsworth

Abstract

Editors: Aug. 1859-July 1865, J. D. White, J. H. McQuillen, G. J. Ziegler.--Aug. 1865-Dec. 1871, J. H. McQuillen, G. J. Ziegler.--Jan. 1872-May 1891, J. W. White.--July 1891-Apr. 1930, E. C. Kirk (with L. P. Anthony, Dec. 1917-Apr. 1930).--May 1930-Dec. 1936, L. P. Anthony., Vols. 1-13 are called "new series.", Merged in Jan. 1937 with: Journal of the American Dental Association, ISSN 1048-6364, to form: Journal of the American Dental Association and dental cosmos, ISSN 0375-8451., The Dental cosmos; a monthly record of dental science. [Vol. 69] : Vol 69 : Issue 12, Page(s) 1318, (dlps) volume: 0527912.0069.001, (dlps) article: 0527912.0069.001:914, http://quod.lib.umich.edu/t/text/accesspolicy.html

11. Green Lawn Cemetery interment card Harding, Louis K.

Author

Green Lawn Cemetery and Green Lawn Cemetery

Abstract

This grave registration card was created by Green Lawn Cemetery. Images are digitized from the microfilm in the collection of the Columbus Metropolitan Library.

12. Variability in white blood cell count during uncomplicated malaria and implications for parasite density estimation : a WorldWide Antimalarial Resistance Network individual patient data meta-analysis

Author

Wynberg, Elke, Commons, Robert J., Humphreys, Georgina, Ashurst, Hazel, Burrow, Rebekah, Adjei, George O., Adjuik, Martin, Anstey, Nicholas M., Anvikar, Anup, Baird, Kevin J., Barber, Bridget E., Barennes, Hubert, Baudin, Elisabeth, Bell, David J., Bethell, Delia, Binh, Tran Quang, Borghini, Isabelle, Chu, Cindy S., Daher, Andre, D'Alessandro, Umberto, Das, Debashish, Davis, Timothy Me, de Vries, Peter J., Djimde, Abdoulaye A., Dondorp, Arjen M., Dorsey, Grant, Faucher, Jean-Francois F., Fogg, Carole, Gaye, Oumar, Grigg, Matthew, Hatz, Christoph, Kager, Piet A., Lacerda, Marcus, Laman, Moses, Mårtensson, Andreas, Menan, Herve Ignace Eby, Monteiro, Wuelton M., Moore, Brioni R., Nosten, Francois, Ogutu, Bernhards, Osorio, Lyda, Penali, Louis K., Pereira, Dhelio B., Rahim, Awab G., Ramharter, Michael, Sagara, Issaka, Schramm, Birgit, Seidlein, Lorenz, Siqueira, Andre M., Sirima, Sodiomon B., Starzengruber, Peter, Sutanto, Inge, Taylor, Walter R., Toure, Offianan A., Utzinger, Jurg, Valea, Innocent, Valentini, Giovanni, White, Nicholas J., William, Timothy, Woodrow, Charles J., Richmond, Caitlin L., Guerin, Philippe J., Price, Ric N., Stepniewska, Kasia, Wynberg, Elke, Commons, Robert J., Humphreys, Georgina, Ashurst, Hazel, Burrow, Rebekah, Adjei, George O., Adjuik, Martin, Anstey, Nicholas M., Anvikar, Anup, Baird, Kevin J., Barber, Bridget E., Barennes, Hubert, Baudin, Elisabeth, Bell, David J., Bethell, Delia, Binh, Tran Quang, Borghini, Isabelle, Chu, Cindy S., Daher, Andre, D'Alessandro, Umberto, Das, Debashish, Davis, Timothy Me, de Vries, Peter J., Djimde, Abdoulaye A., Dondorp, Arjen M., Dorsey, Grant, Faucher, Jean-Francois F., Fogg, Carole, Gaye, Oumar, Grigg, Matthew, Hatz, Christoph, Kager, Piet A., Lacerda, Marcus, Laman, Moses, Mårtensson, Andreas, Menan, Herve Ignace Eby, Monteiro, Wuelton M., Moore, Brioni R., Nosten, Francois, Ogutu, Bernhards, Osorio, Lyda, Penali, Louis K., Pereira, Dhelio B., Rahim, Awab G., Ramharter, Michael, Sagara, Issaka, Schramm, Birgit, Seidlein, Lorenz, Siqueira, Andre M., Sirima, Sodiomon B., Starzengruber, Peter, Sutanto, Inge, Taylor, Walter R., Toure, Offianan A., Utzinger, Jurg, Valea, Innocent, Valentini, Giovanni, White, Nicholas J., William, Timothy, Woodrow, Charles J., Richmond, Caitlin L., Guerin, Philippe J., Price, Ric N., and Stepniewska, Kasia

Abstract

Background: The World Health Organization (WHO) recommends that when peripheral malarial parasitaemia is quantified by thick film microscopy, an actual white blood cell (WBC) count from a concurrently collected blood sample is used in calculations. However, in resource-limited settings an assumed WBC count is often used instead. The aim of this study was to describe the variability in WBC count during acute uncomplicated malaria, and estimate the impact of using an assumed value of WBC on estimates of parasite density and clearance. Methods: Uncomplicated malaria drug efficacy studies that measured WBC count were selected from the WorldWide Antimalarial Resistance Network data repository for an individual patient data meta-analysis of WBC counts. Regression models with random intercepts for study-site were used to assess WBC count variability at presentation and during follow-up. Inflation factors for parasitaemia density, and clearance estimates were calculated for methods using assumed WBC counts (8000 cells/mu L and age-stratified values) using estimates derived from the measured WBC value as reference. Results: Eighty-four studies enrolling 27,656 patients with clinically uncomplicated malaria were included. Geometric mean WBC counts (x 1000 cells/mu L) in age groups < 1, 1-4, 5-14 and >= 15 years were 10.5, 8.3, 7.1, 5.7 and 7.5, 7.0, 6.5, 6.0 for individuals with falciparum (n = 24,978) and vivax (n = 2678) malaria, respectively. At presentation, higher WBC counts were seen among patients with higher parasitaemia, severe anaemia and, for individuals with vivax malaria, in regions with shorter regional relapse periodicity. Among falciparum malaria patients, using an assumed WBC count of 8000 cells/mu L resulted in parasite density underestimation by a median (IQR) of 26% (4-41%) in infants < 1 year old but an overestimation by 50% (16-91%) in adults aged = 15 years. Use of age-stratified assumed WBC values removed systematic bias but did not improve pr

Published
2023
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13. Variability in white blood cell count during uncomplicated malaria and implications for parasite density estimation : a WorldWide Antimalarial Resistance Network individual patient data meta-analysis

Author

Wynberg, Elke, Commons, Robert J., Humphreys, Georgina, Ashurst, Hazel, Burrow, Rebekah, Adjei, George O., Adjuik, Martin, Anstey, Nicholas M., Anvikar, Anup, Baird, Kevin J., Barber, Bridget E., Barennes, Hubert, Baudin, Elisabeth, Bell, David J., Bethell, Delia, Binh, Tran Quang, Borghini, Isabelle, Chu, Cindy S., Daher, Andre, D'Alessandro, Umberto, Das, Debashish, Davis, Timothy Me, de Vries, Peter J., Djimde, Abdoulaye A., Dondorp, Arjen M., Dorsey, Grant, Faucher, Jean-Francois F., Fogg, Carole, Gaye, Oumar, Grigg, Matthew, Hatz, Christoph, Kager, Piet A., Lacerda, Marcus, Laman, Moses, Mårtensson, Andreas, Menan, Herve Ignace Eby, Monteiro, Wuelton M., Moore, Brioni R., Nosten, Francois, Ogutu, Bernhards, Osorio, Lyda, Penali, Louis K., Pereira, Dhelio B., Rahim, Awab G., Ramharter, Michael, Sagara, Issaka, Schramm, Birgit, Seidlein, Lorenz, Siqueira, Andre M., Sirima, Sodiomon B., Starzengruber, Peter, Sutanto, Inge, Taylor, Walter R., Toure, Offianan A., Utzinger, Jurg, Valea, Innocent, Valentini, Giovanni, White, Nicholas J., William, Timothy, Woodrow, Charles J., Richmond, Caitlin L., Guerin, Philippe J., Price, Ric N., Stepniewska, Kasia, Wynberg, Elke, Commons, Robert J., Humphreys, Georgina, Ashurst, Hazel, Burrow, Rebekah, Adjei, George O., Adjuik, Martin, Anstey, Nicholas M., Anvikar, Anup, Baird, Kevin J., Barber, Bridget E., Barennes, Hubert, Baudin, Elisabeth, Bell, David J., Bethell, Delia, Binh, Tran Quang, Borghini, Isabelle, Chu, Cindy S., Daher, Andre, D'Alessandro, Umberto, Das, Debashish, Davis, Timothy Me, de Vries, Peter J., Djimde, Abdoulaye A., Dondorp, Arjen M., Dorsey, Grant, Faucher, Jean-Francois F., Fogg, Carole, Gaye, Oumar, Grigg, Matthew, Hatz, Christoph, Kager, Piet A., Lacerda, Marcus, Laman, Moses, Mårtensson, Andreas, Menan, Herve Ignace Eby, Monteiro, Wuelton M., Moore, Brioni R., Nosten, Francois, Ogutu, Bernhards, Osorio, Lyda, Penali, Louis K., Pereira, Dhelio B., Rahim, Awab G., Ramharter, Michael, Sagara, Issaka, Schramm, Birgit, Seidlein, Lorenz, Siqueira, Andre M., Sirima, Sodiomon B., Starzengruber, Peter, Sutanto, Inge, Taylor, Walter R., Toure, Offianan A., Utzinger, Jurg, Valea, Innocent, Valentini, Giovanni, White, Nicholas J., William, Timothy, Woodrow, Charles J., Richmond, Caitlin L., Guerin, Philippe J., Price, Ric N., and Stepniewska, Kasia

Abstract

Background: The World Health Organization (WHO) recommends that when peripheral malarial parasitaemia is quantified by thick film microscopy, an actual white blood cell (WBC) count from a concurrently collected blood sample is used in calculations. However, in resource-limited settings an assumed WBC count is often used instead. The aim of this study was to describe the variability in WBC count during acute uncomplicated malaria, and estimate the impact of using an assumed value of WBC on estimates of parasite density and clearance. Methods: Uncomplicated malaria drug efficacy studies that measured WBC count were selected from the WorldWide Antimalarial Resistance Network data repository for an individual patient data meta-analysis of WBC counts. Regression models with random intercepts for study-site were used to assess WBC count variability at presentation and during follow-up. Inflation factors for parasitaemia density, and clearance estimates were calculated for methods using assumed WBC counts (8000 cells/mu L and age-stratified values) using estimates derived from the measured WBC value as reference. Results: Eighty-four studies enrolling 27,656 patients with clinically uncomplicated malaria were included. Geometric mean WBC counts (x 1000 cells/mu L) in age groups < 1, 1-4, 5-14 and >= 15 years were 10.5, 8.3, 7.1, 5.7 and 7.5, 7.0, 6.5, 6.0 for individuals with falciparum (n = 24,978) and vivax (n = 2678) malaria, respectively. At presentation, higher WBC counts were seen among patients with higher parasitaemia, severe anaemia and, for individuals with vivax malaria, in regions with shorter regional relapse periodicity. Among falciparum malaria patients, using an assumed WBC count of 8000 cells/mu L resulted in parasite density underestimation by a median (IQR) of 26% (4-41%) in infants < 1 year old but an overestimation by 50% (16-91%) in adults aged = 15 years. Use of age-stratified assumed WBC values removed systematic bias but did not improve pr

Published
2023
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14. Variability in white blood cell count during uncomplicated malaria and implications for parasite density estimation : a WorldWide Antimalarial Resistance Network individual patient data meta-analysis

Author

Wynberg, Elke, Commons, Robert J., Humphreys, Georgina, Ashurst, Hazel, Burrow, Rebekah, Adjei, George O., Adjuik, Martin, Anstey, Nicholas M., Anvikar, Anup, Baird, Kevin J., Barber, Bridget E., Barennes, Hubert, Baudin, Elisabeth, Bell, David J., Bethell, Delia, Binh, Tran Quang, Borghini, Isabelle, Chu, Cindy S., Daher, Andre, D'Alessandro, Umberto, Das, Debashish, Davis, Timothy Me, de Vries, Peter J., Djimde, Abdoulaye A., Dondorp, Arjen M., Dorsey, Grant, Faucher, Jean-Francois F., Fogg, Carole, Gaye, Oumar, Grigg, Matthew, Hatz, Christoph, Kager, Piet A., Lacerda, Marcus, Laman, Moses, Mårtensson, Andreas, Menan, Herve Ignace Eby, Monteiro, Wuelton M., Moore, Brioni R., Nosten, Francois, Ogutu, Bernhards, Osorio, Lyda, Penali, Louis K., Pereira, Dhelio B., Rahim, Awab G., Ramharter, Michael, Sagara, Issaka, Schramm, Birgit, Seidlein, Lorenz, Siqueira, Andre M., Sirima, Sodiomon B., Starzengruber, Peter, Sutanto, Inge, Taylor, Walter R., Toure, Offianan A., Utzinger, Jurg, Valea, Innocent, Valentini, Giovanni, White, Nicholas J., William, Timothy, Woodrow, Charles J., Richmond, Caitlin L., Guerin, Philippe J., Price, Ric N., Stepniewska, Kasia, Wynberg, Elke, Commons, Robert J., Humphreys, Georgina, Ashurst, Hazel, Burrow, Rebekah, Adjei, George O., Adjuik, Martin, Anstey, Nicholas M., Anvikar, Anup, Baird, Kevin J., Barber, Bridget E., Barennes, Hubert, Baudin, Elisabeth, Bell, David J., Bethell, Delia, Binh, Tran Quang, Borghini, Isabelle, Chu, Cindy S., Daher, Andre, D'Alessandro, Umberto, Das, Debashish, Davis, Timothy Me, de Vries, Peter J., Djimde, Abdoulaye A., Dondorp, Arjen M., Dorsey, Grant, Faucher, Jean-Francois F., Fogg, Carole, Gaye, Oumar, Grigg, Matthew, Hatz, Christoph, Kager, Piet A., Lacerda, Marcus, Laman, Moses, Mårtensson, Andreas, Menan, Herve Ignace Eby, Monteiro, Wuelton M., Moore, Brioni R., Nosten, Francois, Ogutu, Bernhards, Osorio, Lyda, Penali, Louis K., Pereira, Dhelio B., Rahim, Awab G., Ramharter, Michael, Sagara, Issaka, Schramm, Birgit, Seidlein, Lorenz, Siqueira, Andre M., Sirima, Sodiomon B., Starzengruber, Peter, Sutanto, Inge, Taylor, Walter R., Toure, Offianan A., Utzinger, Jurg, Valea, Innocent, Valentini, Giovanni, White, Nicholas J., William, Timothy, Woodrow, Charles J., Richmond, Caitlin L., Guerin, Philippe J., Price, Ric N., and Stepniewska, Kasia

Abstract

Background: The World Health Organization (WHO) recommends that when peripheral malarial parasitaemia is quantified by thick film microscopy, an actual white blood cell (WBC) count from a concurrently collected blood sample is used in calculations. However, in resource-limited settings an assumed WBC count is often used instead. The aim of this study was to describe the variability in WBC count during acute uncomplicated malaria, and estimate the impact of using an assumed value of WBC on estimates of parasite density and clearance. Methods: Uncomplicated malaria drug efficacy studies that measured WBC count were selected from the WorldWide Antimalarial Resistance Network data repository for an individual patient data meta-analysis of WBC counts. Regression models with random intercepts for study-site were used to assess WBC count variability at presentation and during follow-up. Inflation factors for parasitaemia density, and clearance estimates were calculated for methods using assumed WBC counts (8000 cells/mu L and age-stratified values) using estimates derived from the measured WBC value as reference. Results: Eighty-four studies enrolling 27,656 patients with clinically uncomplicated malaria were included. Geometric mean WBC counts (x 1000 cells/mu L) in age groups < 1, 1-4, 5-14 and >= 15 years were 10.5, 8.3, 7.1, 5.7 and 7.5, 7.0, 6.5, 6.0 for individuals with falciparum (n = 24,978) and vivax (n = 2678) malaria, respectively. At presentation, higher WBC counts were seen among patients with higher parasitaemia, severe anaemia and, for individuals with vivax malaria, in regions with shorter regional relapse periodicity. Among falciparum malaria patients, using an assumed WBC count of 8000 cells/mu L resulted in parasite density underestimation by a median (IQR) of 26% (4-41%) in infants < 1 year old but an overestimation by 50% (16-91%) in adults aged = 15 years. Use of age-stratified assumed WBC values removed systematic bias but did not improve pr

Published
2023
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15. Variability in white blood cell count during uncomplicated malaria and implications for parasite density estimation : a WorldWide Antimalarial Resistance Network individual patient data meta-analysis

Author

Wynberg, Elke, Commons, Robert J., Humphreys, Georgina, Ashurst, Hazel, Burrow, Rebekah, Adjei, George O., Adjuik, Martin, Anstey, Nicholas M., Anvikar, Anup, Baird, Kevin J., Barber, Bridget E., Barennes, Hubert, Baudin, Elisabeth, Bell, David J., Bethell, Delia, Binh, Tran Quang, Borghini, Isabelle, Chu, Cindy S., Daher, Andre, D'Alessandro, Umberto, Das, Debashish, Davis, Timothy Me, de Vries, Peter J., Djimde, Abdoulaye A., Dondorp, Arjen M., Dorsey, Grant, Faucher, Jean-Francois F., Fogg, Carole, Gaye, Oumar, Grigg, Matthew, Hatz, Christoph, Kager, Piet A., Lacerda, Marcus, Laman, Moses, Mårtensson, Andreas, Menan, Herve Ignace Eby, Monteiro, Wuelton M., Moore, Brioni R., Nosten, Francois, Ogutu, Bernhards, Osorio, Lyda, Penali, Louis K., Pereira, Dhelio B., Rahim, Awab G., Ramharter, Michael, Sagara, Issaka, Schramm, Birgit, Seidlein, Lorenz, Siqueira, Andre M., Sirima, Sodiomon B., Starzengruber, Peter, Sutanto, Inge, Taylor, Walter R., Toure, Offianan A., Utzinger, Jurg, Valea, Innocent, Valentini, Giovanni, White, Nicholas J., William, Timothy, Woodrow, Charles J., Richmond, Caitlin L., Guerin, Philippe J., Price, Ric N., Stepniewska, Kasia, Wynberg, Elke, Commons, Robert J., Humphreys, Georgina, Ashurst, Hazel, Burrow, Rebekah, Adjei, George O., Adjuik, Martin, Anstey, Nicholas M., Anvikar, Anup, Baird, Kevin J., Barber, Bridget E., Barennes, Hubert, Baudin, Elisabeth, Bell, David J., Bethell, Delia, Binh, Tran Quang, Borghini, Isabelle, Chu, Cindy S., Daher, Andre, D'Alessandro, Umberto, Das, Debashish, Davis, Timothy Me, de Vries, Peter J., Djimde, Abdoulaye A., Dondorp, Arjen M., Dorsey, Grant, Faucher, Jean-Francois F., Fogg, Carole, Gaye, Oumar, Grigg, Matthew, Hatz, Christoph, Kager, Piet A., Lacerda, Marcus, Laman, Moses, Mårtensson, Andreas, Menan, Herve Ignace Eby, Monteiro, Wuelton M., Moore, Brioni R., Nosten, Francois, Ogutu, Bernhards, Osorio, Lyda, Penali, Louis K., Pereira, Dhelio B., Rahim, Awab G., Ramharter, Michael, Sagara, Issaka, Schramm, Birgit, Seidlein, Lorenz, Siqueira, Andre M., Sirima, Sodiomon B., Starzengruber, Peter, Sutanto, Inge, Taylor, Walter R., Toure, Offianan A., Utzinger, Jurg, Valea, Innocent, Valentini, Giovanni, White, Nicholas J., William, Timothy, Woodrow, Charles J., Richmond, Caitlin L., Guerin, Philippe J., Price, Ric N., and Stepniewska, Kasia

Abstract

Background: The World Health Organization (WHO) recommends that when peripheral malarial parasitaemia is quantified by thick film microscopy, an actual white blood cell (WBC) count from a concurrently collected blood sample is used in calculations. However, in resource-limited settings an assumed WBC count is often used instead. The aim of this study was to describe the variability in WBC count during acute uncomplicated malaria, and estimate the impact of using an assumed value of WBC on estimates of parasite density and clearance. Methods: Uncomplicated malaria drug efficacy studies that measured WBC count were selected from the WorldWide Antimalarial Resistance Network data repository for an individual patient data meta-analysis of WBC counts. Regression models with random intercepts for study-site were used to assess WBC count variability at presentation and during follow-up. Inflation factors for parasitaemia density, and clearance estimates were calculated for methods using assumed WBC counts (8000 cells/mu L and age-stratified values) using estimates derived from the measured WBC value as reference. Results: Eighty-four studies enrolling 27,656 patients with clinically uncomplicated malaria were included. Geometric mean WBC counts (x 1000 cells/mu L) in age groups < 1, 1-4, 5-14 and >= 15 years were 10.5, 8.3, 7.1, 5.7 and 7.5, 7.0, 6.5, 6.0 for individuals with falciparum (n = 24,978) and vivax (n = 2678) malaria, respectively. At presentation, higher WBC counts were seen among patients with higher parasitaemia, severe anaemia and, for individuals with vivax malaria, in regions with shorter regional relapse periodicity. Among falciparum malaria patients, using an assumed WBC count of 8000 cells/mu L resulted in parasite density underestimation by a median (IQR) of 26% (4-41%) in infants < 1 year old but an overestimation by 50% (16-91%) in adults aged = 15 years. Use of age-stratified assumed WBC values removed systematic bias but did not improve pr

Published
2023
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16. Variability in white blood cell count during uncomplicated malaria and implications for parasite density estimation : a WorldWide Antimalarial Resistance Network individual patient data meta-analysis

Author

Wynberg, Elke, Commons, Robert J., Humphreys, Georgina, Ashurst, Hazel, Burrow, Rebekah, Adjei, George O., Adjuik, Martin, Anstey, Nicholas M., Anvikar, Anup, Baird, Kevin J., Barber, Bridget E., Barennes, Hubert, Baudin, Elisabeth, Bell, David J., Bethell, Delia, Binh, Tran Quang, Borghini, Isabelle, Chu, Cindy S., Daher, Andre, D'Alessandro, Umberto, Das, Debashish, Davis, Timothy Me, de Vries, Peter J., Djimde, Abdoulaye A., Dondorp, Arjen M., Dorsey, Grant, Faucher, Jean-Francois F., Fogg, Carole, Gaye, Oumar, Grigg, Matthew, Hatz, Christoph, Kager, Piet A., Lacerda, Marcus, Laman, Moses, Mårtensson, Andreas, Menan, Herve Ignace Eby, Monteiro, Wuelton M., Moore, Brioni R., Nosten, Francois, Ogutu, Bernhards, Osorio, Lyda, Penali, Louis K., Pereira, Dhelio B., Rahim, Awab G., Ramharter, Michael, Sagara, Issaka, Schramm, Birgit, Seidlein, Lorenz, Siqueira, Andre M., Sirima, Sodiomon B., Starzengruber, Peter, Sutanto, Inge, Taylor, Walter R., Toure, Offianan A., Utzinger, Jurg, Valea, Innocent, Valentini, Giovanni, White, Nicholas J., William, Timothy, Woodrow, Charles J., Richmond, Caitlin L., Guerin, Philippe J., Price, Ric N., Stepniewska, Kasia, Wynberg, Elke, Commons, Robert J., Humphreys, Georgina, Ashurst, Hazel, Burrow, Rebekah, Adjei, George O., Adjuik, Martin, Anstey, Nicholas M., Anvikar, Anup, Baird, Kevin J., Barber, Bridget E., Barennes, Hubert, Baudin, Elisabeth, Bell, David J., Bethell, Delia, Binh, Tran Quang, Borghini, Isabelle, Chu, Cindy S., Daher, Andre, D'Alessandro, Umberto, Das, Debashish, Davis, Timothy Me, de Vries, Peter J., Djimde, Abdoulaye A., Dondorp, Arjen M., Dorsey, Grant, Faucher, Jean-Francois F., Fogg, Carole, Gaye, Oumar, Grigg, Matthew, Hatz, Christoph, Kager, Piet A., Lacerda, Marcus, Laman, Moses, Mårtensson, Andreas, Menan, Herve Ignace Eby, Monteiro, Wuelton M., Moore, Brioni R., Nosten, Francois, Ogutu, Bernhards, Osorio, Lyda, Penali, Louis K., Pereira, Dhelio B., Rahim, Awab G., Ramharter, Michael, Sagara, Issaka, Schramm, Birgit, Seidlein, Lorenz, Siqueira, Andre M., Sirima, Sodiomon B., Starzengruber, Peter, Sutanto, Inge, Taylor, Walter R., Toure, Offianan A., Utzinger, Jurg, Valea, Innocent, Valentini, Giovanni, White, Nicholas J., William, Timothy, Woodrow, Charles J., Richmond, Caitlin L., Guerin, Philippe J., Price, Ric N., and Stepniewska, Kasia

Abstract

Background: The World Health Organization (WHO) recommends that when peripheral malarial parasitaemia is quantified by thick film microscopy, an actual white blood cell (WBC) count from a concurrently collected blood sample is used in calculations. However, in resource-limited settings an assumed WBC count is often used instead. The aim of this study was to describe the variability in WBC count during acute uncomplicated malaria, and estimate the impact of using an assumed value of WBC on estimates of parasite density and clearance. Methods: Uncomplicated malaria drug efficacy studies that measured WBC count were selected from the WorldWide Antimalarial Resistance Network data repository for an individual patient data meta-analysis of WBC counts. Regression models with random intercepts for study-site were used to assess WBC count variability at presentation and during follow-up. Inflation factors for parasitaemia density, and clearance estimates were calculated for methods using assumed WBC counts (8000 cells/mu L and age-stratified values) using estimates derived from the measured WBC value as reference. Results: Eighty-four studies enrolling 27,656 patients with clinically uncomplicated malaria were included. Geometric mean WBC counts (x 1000 cells/mu L) in age groups < 1, 1-4, 5-14 and >= 15 years were 10.5, 8.3, 7.1, 5.7 and 7.5, 7.0, 6.5, 6.0 for individuals with falciparum (n = 24,978) and vivax (n = 2678) malaria, respectively. At presentation, higher WBC counts were seen among patients with higher parasitaemia, severe anaemia and, for individuals with vivax malaria, in regions with shorter regional relapse periodicity. Among falciparum malaria patients, using an assumed WBC count of 8000 cells/mu L resulted in parasite density underestimation by a median (IQR) of 26% (4-41%) in infants < 1 year old but an overestimation by 50% (16-91%) in adults aged = 15 years. Use of age-stratified assumed WBC values removed systematic bias but did not improve pr

Published
2023
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17. Haematological consequences of acute uncomplicated falciparum malaria : a WorldWide Antimalarial Resistance Network pooled analysis of individual patient data

Author

Mansoor, Rashid, Commons, Robert J., Douglas, Nicholas M., Abuaku, Benjamin, Achan, Jane, Adam, Ishag, Adjei, George O., Adjuik, Martin, Alemayehu, Bereket H., Allan, Richard, Allen, Elizabeth N., Anvikar, Anupkumar R., Arinaitwe, Emmanuel, Ashley, Elizabeth A., Ashurst, Hazel, Asih, Puji B. S., Bakyaita, Nathan, Barennes, Hubert, Barnes, Karen, I, Basco, Leonardo, Bassat, Quique, Baudin, Elisabeth, Bell, David J., Bethell, Delia, Bjorkman, Anders, Boulton, Caroline, Bousema, Teun, Brasseur, Philippe, Bukirwa, Hasifa, Burrow, Rebekah, Carrara, Verena, I, Cot, Michel, D'Alessandro, Umberto, Das, Debashish, Das, Sabyasachi, Davis, Timothy M. E., Desai, Meghna, Djimde, Abdoulaye A., Dondorp, Arjen M., Dorsey, Grant, Drakeley, Chris J., Duparc, Stephan, Espie, Emmanuelle, Etard, Jean-Francois, Falade, Catherine, Faucher, Jean Francois, Filler, Scott, Fogg, Carole, Fukuda, Mark, Gaye, Oumar, Genton, Blaise, Rahim, Awab Ghulam, Gilayeneh, Julius, Gonzalez, Raquel, Grais, Rebecca F., Grandesso, Francesco, Greenwood, Brian, Grivoyannis, Anastasia, Hatz, Christoph, Hodel, Eva Maria, Humphreys, Georgina S., Hwang, Jimee, Ishengoma, Deus, Juma, Elizabeth, Kachur, S. Patrick, Kager, Piet A., Kamugisha, Erasmus, Kamya, Moses R., Karema, Corine, Kayentao, Kassoum, Kazienga, Adama, Kiechel, Jean-Rene, Kofoed, Poul-Erik, Koram, Kwadwo, Kremsner, Peter G., Lalloo, David G., Laman, Moses, Lee, Sue J., Lell, Bertrand, Maiga, Amelia W., Mårtensson, Andreas, Mayxay, Mayfong, Mbacham, Wilfred, McGready, Rose, Menan, Herve, Menard, Didier, Mockenhaupt, Frank, Moore, Brioni R., Muller, Olaf, Nahum, Alain, Ndiaye, Jean-Louis, Newton, Paul N., Ngasala, Billy E., Nikiema, Frederic, Nji, Akindeh M., Noedl, Harald, Nosten, Francois, Ogutu, Bernhards R., Ojurongbe, Olusola, Osorio, Lyda, Ouedraogo, Jean-Bosco, Owusu-Agyei, Seth, Pareek, Anil, Penali, Louis K., Piola, Patrice, Plucinski, Mateusz, Premji, Zul, Ramharter, Michael, Richmond, Caitlin L., Rombo, Lars, Rosenthal, Philip J., Salman, Sam, Same-Ekobo, Albert, Sibley, Carol, Sirima, Sodiomon B., Smithuis, Frank M., Some, Fabrice A., Staedke, Sarah G., Starzengruber, Peter, Strub-Wourgaft, Nathalie, Sutanto, Inge, Swarthout, Todd D., Syafruddin, Din, Talisuna, Ambrose O., Taylor, Walter R., Temu, Emmanuel A., Thwing, Julie, I, Tinto, Halidou, Tjitra, Emiliana, Toure, Offianan A., Tran, T. Hien, Ursing, Johan, Valea, Innocent, Valentini, Giovanni, van Vugt, Michele, von Seidlein, Lorenz, Ward, Stephen A., Were, Vincent, White, Nicholas J., Woodrow, Charles J., Yavo, William, Yeka, Adoke, Zongo, Issaka, Simpson, Julie A., Guerin, Philippe J., Stepniewska, Kasia, Price, Ric N., Roper, Cally, Mansoor, Rashid, Commons, Robert J., Douglas, Nicholas M., Abuaku, Benjamin, Achan, Jane, Adam, Ishag, Adjei, George O., Adjuik, Martin, Alemayehu, Bereket H., Allan, Richard, Allen, Elizabeth N., Anvikar, Anupkumar R., Arinaitwe, Emmanuel, Ashley, Elizabeth A., Ashurst, Hazel, Asih, Puji B. S., Bakyaita, Nathan, Barennes, Hubert, Barnes, Karen, I, Basco, Leonardo, Bassat, Quique, Baudin, Elisabeth, Bell, David J., Bethell, Delia, Bjorkman, Anders, Boulton, Caroline, Bousema, Teun, Brasseur, Philippe, Bukirwa, Hasifa, Burrow, Rebekah, Carrara, Verena, I, Cot, Michel, D'Alessandro, Umberto, Das, Debashish, Das, Sabyasachi, Davis, Timothy M. E., Desai, Meghna, Djimde, Abdoulaye A., Dondorp, Arjen M., Dorsey, Grant, Drakeley, Chris J., Duparc, Stephan, Espie, Emmanuelle, Etard, Jean-Francois, Falade, Catherine, Faucher, Jean Francois, Filler, Scott, Fogg, Carole, Fukuda, Mark, Gaye, Oumar, Genton, Blaise, Rahim, Awab Ghulam, Gilayeneh, Julius, Gonzalez, Raquel, Grais, Rebecca F., Grandesso, Francesco, Greenwood, Brian, Grivoyannis, Anastasia, Hatz, Christoph, Hodel, Eva Maria, Humphreys, Georgina S., Hwang, Jimee, Ishengoma, Deus, Juma, Elizabeth, Kachur, S. Patrick, Kager, Piet A., Kamugisha, Erasmus, Kamya, Moses R., Karema, Corine, Kayentao, Kassoum, Kazienga, Adama, Kiechel, Jean-Rene, Kofoed, Poul-Erik, Koram, Kwadwo, Kremsner, Peter G., Lalloo, David G., Laman, Moses, Lee, Sue J., Lell, Bertrand, Maiga, Amelia W., Mårtensson, Andreas, Mayxay, Mayfong, Mbacham, Wilfred, McGready, Rose, Menan, Herve, Menard, Didier, Mockenhaupt, Frank, Moore, Brioni R., Muller, Olaf, Nahum, Alain, Ndiaye, Jean-Louis, Newton, Paul N., Ngasala, Billy E., Nikiema, Frederic, Nji, Akindeh M., Noedl, Harald, Nosten, Francois, Ogutu, Bernhards R., Ojurongbe, Olusola, Osorio, Lyda, Ouedraogo, Jean-Bosco, Owusu-Agyei, Seth, Pareek, Anil, Penali, Louis K., Piola, Patrice, Plucinski, Mateusz, Premji, Zul, Ramharter, Michael, Richmond, Caitlin L., Rombo, Lars, Rosenthal, Philip J., Salman, Sam, Same-Ekobo, Albert, Sibley, Carol, Sirima, Sodiomon B., Smithuis, Frank M., Some, Fabrice A., Staedke, Sarah G., Starzengruber, Peter, Strub-Wourgaft, Nathalie, Sutanto, Inge, Swarthout, Todd D., Syafruddin, Din, Talisuna, Ambrose O., Taylor, Walter R., Temu, Emmanuel A., Thwing, Julie, I, Tinto, Halidou, Tjitra, Emiliana, Toure, Offianan A., Tran, T. Hien, Ursing, Johan, Valea, Innocent, Valentini, Giovanni, van Vugt, Michele, von Seidlein, Lorenz, Ward, Stephen A., Were, Vincent, White, Nicholas J., Woodrow, Charles J., Yavo, William, Yeka, Adoke, Zongo, Issaka, Simpson, Julie A., Guerin, Philippe J., Stepniewska, Kasia, Price, Ric N., and Roper, Cally

Abstract

Background Plasmodium falciparum malaria is associated with anaemia-related morbidity, attributable to host, parasite and drug factors. We quantified the haematological response following treatment of uncomplicated P. falciparum malaria to identify the factors associated with malarial anaemia. Methods Individual patient data from eligible antimalarial efficacy studies of uncomplicated P. falciparum malaria, available through the WorldWide Antimalarial Resistance Network data repository prior to August 2015, were pooled using standardised methodology. The haematological response over time was quantified using a multivariable linear mixed effects model with nonlinear terms for time, and the model was then used to estimate the mean haemoglobin at day of nadir and day 7. Multivariable logistic regression quantified risk factors for moderately severe anaemia (haemoglobin < 7 g/dL) at day 0, day 3 and day 7 as well as a fractional fall >= 25% at day 3 and day 7. Results A total of 70,226 patients, recruited into 200 studies between 1991 and 2013, were included in the analysis: 50,859 (72.4%) enrolled in Africa, 18,451 (26.3%) in Asia and 916 (1.3%) in South America. The median haemoglobin concentration at presentation was 9.9 g/dL (range 5.0-19.7 g/dL) in Africa, 11.6 g/dL (range 5.0-20.0 g/dL) in Asia and 12.3 g/dL (range 6.9-17.9 g/dL) in South America. Moderately severe anaemia (Hb < 7g/dl) was present in 8.4% (4284/50,859) of patients from Africa, 3.3% (606/18,451) from Asia and 0.1% (1/916) from South America. The nadir haemoglobin occurred on day 2 post treatment with a mean fall from baseline of 0.57 g/dL in Africa and 1.13 g/dL in Asia. Independent risk factors for moderately severe anaemia on day 7, in both Africa and Asia, included moderately severe anaemia at baseline (adjusted odds ratio (AOR) = 16.10 and AOR = 23.00, respectively), young age (age < 1 compared to >= 12 years AOR = 12.81 and AOR = 6.79, respectively), high parasitaemia (AOR = 1.7

Published
2022
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18. Haematological consequences of acute uncomplicated falciparum malaria : a WorldWide Antimalarial Resistance Network pooled analysis of individual patient data

Author

Mansoor, Rashid, Commons, Robert J., Douglas, Nicholas M., Abuaku, Benjamin, Achan, Jane, Adam, Ishag, Adjei, George O., Adjuik, Martin, Alemayehu, Bereket H., Allan, Richard, Allen, Elizabeth N., Anvikar, Anupkumar R., Arinaitwe, Emmanuel, Ashley, Elizabeth A., Ashurst, Hazel, Asih, Puji B. S., Bakyaita, Nathan, Barennes, Hubert, Barnes, Karen, I, Basco, Leonardo, Bassat, Quique, Baudin, Elisabeth, Bell, David J., Bethell, Delia, Bjorkman, Anders, Boulton, Caroline, Bousema, Teun, Brasseur, Philippe, Bukirwa, Hasifa, Burrow, Rebekah, Carrara, Verena, I, Cot, Michel, D'Alessandro, Umberto, Das, Debashish, Das, Sabyasachi, Davis, Timothy M. E., Desai, Meghna, Djimde, Abdoulaye A., Dondorp, Arjen M., Dorsey, Grant, Drakeley, Chris J., Duparc, Stephan, Espie, Emmanuelle, Etard, Jean-Francois, Falade, Catherine, Faucher, Jean Francois, Filler, Scott, Fogg, Carole, Fukuda, Mark, Gaye, Oumar, Genton, Blaise, Rahim, Awab Ghulam, Gilayeneh, Julius, Gonzalez, Raquel, Grais, Rebecca F., Grandesso, Francesco, Greenwood, Brian, Grivoyannis, Anastasia, Hatz, Christoph, Hodel, Eva Maria, Humphreys, Georgina S., Hwang, Jimee, Ishengoma, Deus, Juma, Elizabeth, Kachur, S. Patrick, Kager, Piet A., Kamugisha, Erasmus, Kamya, Moses R., Karema, Corine, Kayentao, Kassoum, Kazienga, Adama, Kiechel, Jean-Rene, Kofoed, Poul-Erik, Koram, Kwadwo, Kremsner, Peter G., Lalloo, David G., Laman, Moses, Lee, Sue J., Lell, Bertrand, Maiga, Amelia W., Mårtensson, Andreas, Mayxay, Mayfong, Mbacham, Wilfred, McGready, Rose, Menan, Herve, Menard, Didier, Mockenhaupt, Frank, Moore, Brioni R., Muller, Olaf, Nahum, Alain, Ndiaye, Jean-Louis, Newton, Paul N., Ngasala, Billy E., Nikiema, Frederic, Nji, Akindeh M., Noedl, Harald, Nosten, Francois, Ogutu, Bernhards R., Ojurongbe, Olusola, Osorio, Lyda, Ouedraogo, Jean-Bosco, Owusu-Agyei, Seth, Pareek, Anil, Penali, Louis K., Piola, Patrice, Plucinski, Mateusz, Premji, Zul, Ramharter, Michael, Richmond, Caitlin L., Rombo, Lars, Rosenthal, Philip J., Salman, Sam, Same-Ekobo, Albert, Sibley, Carol, Sirima, Sodiomon B., Smithuis, Frank M., Some, Fabrice A., Staedke, Sarah G., Starzengruber, Peter, Strub-Wourgaft, Nathalie, Sutanto, Inge, Swarthout, Todd D., Syafruddin, Din, Talisuna, Ambrose O., Taylor, Walter R., Temu, Emmanuel A., Thwing, Julie, I, Tinto, Halidou, Tjitra, Emiliana, Toure, Offianan A., Tran, T. Hien, Ursing, Johan, Valea, Innocent, Valentini, Giovanni, van Vugt, Michele, von Seidlein, Lorenz, Ward, Stephen A., Were, Vincent, White, Nicholas J., Woodrow, Charles J., Yavo, William, Yeka, Adoke, Zongo, Issaka, Simpson, Julie A., Guerin, Philippe J., Stepniewska, Kasia, Price, Ric N., Roper, Cally, Mansoor, Rashid, Commons, Robert J., Douglas, Nicholas M., Abuaku, Benjamin, Achan, Jane, Adam, Ishag, Adjei, George O., Adjuik, Martin, Alemayehu, Bereket H., Allan, Richard, Allen, Elizabeth N., Anvikar, Anupkumar R., Arinaitwe, Emmanuel, Ashley, Elizabeth A., Ashurst, Hazel, Asih, Puji B. S., Bakyaita, Nathan, Barennes, Hubert, Barnes, Karen, I, Basco, Leonardo, Bassat, Quique, Baudin, Elisabeth, Bell, David J., Bethell, Delia, Bjorkman, Anders, Boulton, Caroline, Bousema, Teun, Brasseur, Philippe, Bukirwa, Hasifa, Burrow, Rebekah, Carrara, Verena, I, Cot, Michel, D'Alessandro, Umberto, Das, Debashish, Das, Sabyasachi, Davis, Timothy M. E., Desai, Meghna, Djimde, Abdoulaye A., Dondorp, Arjen M., Dorsey, Grant, Drakeley, Chris J., Duparc, Stephan, Espie, Emmanuelle, Etard, Jean-Francois, Falade, Catherine, Faucher, Jean Francois, Filler, Scott, Fogg, Carole, Fukuda, Mark, Gaye, Oumar, Genton, Blaise, Rahim, Awab Ghulam, Gilayeneh, Julius, Gonzalez, Raquel, Grais, Rebecca F., Grandesso, Francesco, Greenwood, Brian, Grivoyannis, Anastasia, Hatz, Christoph, Hodel, Eva Maria, Humphreys, Georgina S., Hwang, Jimee, Ishengoma, Deus, Juma, Elizabeth, Kachur, S. Patrick, Kager, Piet A., Kamugisha, Erasmus, Kamya, Moses R., Karema, Corine, Kayentao, Kassoum, Kazienga, Adama, Kiechel, Jean-Rene, Kofoed, Poul-Erik, Koram, Kwadwo, Kremsner, Peter G., Lalloo, David G., Laman, Moses, Lee, Sue J., Lell, Bertrand, Maiga, Amelia W., Mårtensson, Andreas, Mayxay, Mayfong, Mbacham, Wilfred, McGready, Rose, Menan, Herve, Menard, Didier, Mockenhaupt, Frank, Moore, Brioni R., Muller, Olaf, Nahum, Alain, Ndiaye, Jean-Louis, Newton, Paul N., Ngasala, Billy E., Nikiema, Frederic, Nji, Akindeh M., Noedl, Harald, Nosten, Francois, Ogutu, Bernhards R., Ojurongbe, Olusola, Osorio, Lyda, Ouedraogo, Jean-Bosco, Owusu-Agyei, Seth, Pareek, Anil, Penali, Louis K., Piola, Patrice, Plucinski, Mateusz, Premji, Zul, Ramharter, Michael, Richmond, Caitlin L., Rombo, Lars, Rosenthal, Philip J., Salman, Sam, Same-Ekobo, Albert, Sibley, Carol, Sirima, Sodiomon B., Smithuis, Frank M., Some, Fabrice A., Staedke, Sarah G., Starzengruber, Peter, Strub-Wourgaft, Nathalie, Sutanto, Inge, Swarthout, Todd D., Syafruddin, Din, Talisuna, Ambrose O., Taylor, Walter R., Temu, Emmanuel A., Thwing, Julie, I, Tinto, Halidou, Tjitra, Emiliana, Toure, Offianan A., Tran, T. Hien, Ursing, Johan, Valea, Innocent, Valentini, Giovanni, van Vugt, Michele, von Seidlein, Lorenz, Ward, Stephen A., Were, Vincent, White, Nicholas J., Woodrow, Charles J., Yavo, William, Yeka, Adoke, Zongo, Issaka, Simpson, Julie A., Guerin, Philippe J., Stepniewska, Kasia, Price, Ric N., and Roper, Cally

Abstract

Background Plasmodium falciparum malaria is associated with anaemia-related morbidity, attributable to host, parasite and drug factors. We quantified the haematological response following treatment of uncomplicated P. falciparum malaria to identify the factors associated with malarial anaemia. Methods Individual patient data from eligible antimalarial efficacy studies of uncomplicated P. falciparum malaria, available through the WorldWide Antimalarial Resistance Network data repository prior to August 2015, were pooled using standardised methodology. The haematological response over time was quantified using a multivariable linear mixed effects model with nonlinear terms for time, and the model was then used to estimate the mean haemoglobin at day of nadir and day 7. Multivariable logistic regression quantified risk factors for moderately severe anaemia (haemoglobin < 7 g/dL) at day 0, day 3 and day 7 as well as a fractional fall >= 25% at day 3 and day 7. Results A total of 70,226 patients, recruited into 200 studies between 1991 and 2013, were included in the analysis: 50,859 (72.4%) enrolled in Africa, 18,451 (26.3%) in Asia and 916 (1.3%) in South America. The median haemoglobin concentration at presentation was 9.9 g/dL (range 5.0-19.7 g/dL) in Africa, 11.6 g/dL (range 5.0-20.0 g/dL) in Asia and 12.3 g/dL (range 6.9-17.9 g/dL) in South America. Moderately severe anaemia (Hb < 7g/dl) was present in 8.4% (4284/50,859) of patients from Africa, 3.3% (606/18,451) from Asia and 0.1% (1/916) from South America. The nadir haemoglobin occurred on day 2 post treatment with a mean fall from baseline of 0.57 g/dL in Africa and 1.13 g/dL in Asia. Independent risk factors for moderately severe anaemia on day 7, in both Africa and Asia, included moderately severe anaemia at baseline (adjusted odds ratio (AOR) = 16.10 and AOR = 23.00, respectively), young age (age < 1 compared to >= 12 years AOR = 12.81 and AOR = 6.79, respectively), high parasitaemia (AOR = 1.7

Published
2022
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19. Haematological consequences of acute uncomplicated falciparum malaria : a WorldWide Antimalarial Resistance Network pooled analysis of individual patient data

Author

Mansoor, Rashid, Commons, Robert J., Douglas, Nicholas M., Abuaku, Benjamin, Achan, Jane, Adam, Ishag, Adjei, George O., Adjuik, Martin, Alemayehu, Bereket H., Allan, Richard, Allen, Elizabeth N., Anvikar, Anupkumar R., Arinaitwe, Emmanuel, Ashley, Elizabeth A., Ashurst, Hazel, Asih, Puji B. S., Bakyaita, Nathan, Barennes, Hubert, Barnes, Karen, I, Basco, Leonardo, Bassat, Quique, Baudin, Elisabeth, Bell, David J., Bethell, Delia, Bjorkman, Anders, Boulton, Caroline, Bousema, Teun, Brasseur, Philippe, Bukirwa, Hasifa, Burrow, Rebekah, Carrara, Verena, I, Cot, Michel, D'Alessandro, Umberto, Das, Debashish, Das, Sabyasachi, Davis, Timothy M. E., Desai, Meghna, Djimde, Abdoulaye A., Dondorp, Arjen M., Dorsey, Grant, Drakeley, Chris J., Duparc, Stephan, Espie, Emmanuelle, Etard, Jean-Francois, Falade, Catherine, Faucher, Jean Francois, Filler, Scott, Fogg, Carole, Fukuda, Mark, Gaye, Oumar, Genton, Blaise, Rahim, Awab Ghulam, Gilayeneh, Julius, Gonzalez, Raquel, Grais, Rebecca F., Grandesso, Francesco, Greenwood, Brian, Grivoyannis, Anastasia, Hatz, Christoph, Hodel, Eva Maria, Humphreys, Georgina S., Hwang, Jimee, Ishengoma, Deus, Juma, Elizabeth, Kachur, S. Patrick, Kager, Piet A., Kamugisha, Erasmus, Kamya, Moses R., Karema, Corine, Kayentao, Kassoum, Kazienga, Adama, Kiechel, Jean-Rene, Kofoed, Poul-Erik, Koram, Kwadwo, Kremsner, Peter G., Lalloo, David G., Laman, Moses, Lee, Sue J., Lell, Bertrand, Maiga, Amelia W., Mårtensson, Andreas, Mayxay, Mayfong, Mbacham, Wilfred, McGready, Rose, Menan, Herve, Menard, Didier, Mockenhaupt, Frank, Moore, Brioni R., Muller, Olaf, Nahum, Alain, Ndiaye, Jean-Louis, Newton, Paul N., Ngasala, Billy E., Nikiema, Frederic, Nji, Akindeh M., Noedl, Harald, Nosten, Francois, Ogutu, Bernhards R., Ojurongbe, Olusola, Osorio, Lyda, Ouedraogo, Jean-Bosco, Owusu-Agyei, Seth, Pareek, Anil, Penali, Louis K., Piola, Patrice, Plucinski, Mateusz, Premji, Zul, Ramharter, Michael, Richmond, Caitlin L., Rombo, Lars, Rosenthal, Philip J., Salman, Sam, Same-Ekobo, Albert, Sibley, Carol, Sirima, Sodiomon B., Smithuis, Frank M., Some, Fabrice A., Staedke, Sarah G., Starzengruber, Peter, Strub-Wourgaft, Nathalie, Sutanto, Inge, Swarthout, Todd D., Syafruddin, Din, Talisuna, Ambrose O., Taylor, Walter R., Temu, Emmanuel A., Thwing, Julie, I, Tinto, Halidou, Tjitra, Emiliana, Toure, Offianan A., Tran, T. Hien, Ursing, Johan, Valea, Innocent, Valentini, Giovanni, van Vugt, Michele, von Seidlein, Lorenz, Ward, Stephen A., Were, Vincent, White, Nicholas J., Woodrow, Charles J., Yavo, William, Yeka, Adoke, Zongo, Issaka, Simpson, Julie A., Guerin, Philippe J., Stepniewska, Kasia, Price, Ric N., Roper, Cally, Mansoor, Rashid, Commons, Robert J., Douglas, Nicholas M., Abuaku, Benjamin, Achan, Jane, Adam, Ishag, Adjei, George O., Adjuik, Martin, Alemayehu, Bereket H., Allan, Richard, Allen, Elizabeth N., Anvikar, Anupkumar R., Arinaitwe, Emmanuel, Ashley, Elizabeth A., Ashurst, Hazel, Asih, Puji B. S., Bakyaita, Nathan, Barennes, Hubert, Barnes, Karen, I, Basco, Leonardo, Bassat, Quique, Baudin, Elisabeth, Bell, David J., Bethell, Delia, Bjorkman, Anders, Boulton, Caroline, Bousema, Teun, Brasseur, Philippe, Bukirwa, Hasifa, Burrow, Rebekah, Carrara, Verena, I, Cot, Michel, D'Alessandro, Umberto, Das, Debashish, Das, Sabyasachi, Davis, Timothy M. E., Desai, Meghna, Djimde, Abdoulaye A., Dondorp, Arjen M., Dorsey, Grant, Drakeley, Chris J., Duparc, Stephan, Espie, Emmanuelle, Etard, Jean-Francois, Falade, Catherine, Faucher, Jean Francois, Filler, Scott, Fogg, Carole, Fukuda, Mark, Gaye, Oumar, Genton, Blaise, Rahim, Awab Ghulam, Gilayeneh, Julius, Gonzalez, Raquel, Grais, Rebecca F., Grandesso, Francesco, Greenwood, Brian, Grivoyannis, Anastasia, Hatz, Christoph, Hodel, Eva Maria, Humphreys, Georgina S., Hwang, Jimee, Ishengoma, Deus, Juma, Elizabeth, Kachur, S. Patrick, Kager, Piet A., Kamugisha, Erasmus, Kamya, Moses R., Karema, Corine, Kayentao, Kassoum, Kazienga, Adama, Kiechel, Jean-Rene, Kofoed, Poul-Erik, Koram, Kwadwo, Kremsner, Peter G., Lalloo, David G., Laman, Moses, Lee, Sue J., Lell, Bertrand, Maiga, Amelia W., Mårtensson, Andreas, Mayxay, Mayfong, Mbacham, Wilfred, McGready, Rose, Menan, Herve, Menard, Didier, Mockenhaupt, Frank, Moore, Brioni R., Muller, Olaf, Nahum, Alain, Ndiaye, Jean-Louis, Newton, Paul N., Ngasala, Billy E., Nikiema, Frederic, Nji, Akindeh M., Noedl, Harald, Nosten, Francois, Ogutu, Bernhards R., Ojurongbe, Olusola, Osorio, Lyda, Ouedraogo, Jean-Bosco, Owusu-Agyei, Seth, Pareek, Anil, Penali, Louis K., Piola, Patrice, Plucinski, Mateusz, Premji, Zul, Ramharter, Michael, Richmond, Caitlin L., Rombo, Lars, Rosenthal, Philip J., Salman, Sam, Same-Ekobo, Albert, Sibley, Carol, Sirima, Sodiomon B., Smithuis, Frank M., Some, Fabrice A., Staedke, Sarah G., Starzengruber, Peter, Strub-Wourgaft, Nathalie, Sutanto, Inge, Swarthout, Todd D., Syafruddin, Din, Talisuna, Ambrose O., Taylor, Walter R., Temu, Emmanuel A., Thwing, Julie, I, Tinto, Halidou, Tjitra, Emiliana, Toure, Offianan A., Tran, T. Hien, Ursing, Johan, Valea, Innocent, Valentini, Giovanni, van Vugt, Michele, von Seidlein, Lorenz, Ward, Stephen A., Were, Vincent, White, Nicholas J., Woodrow, Charles J., Yavo, William, Yeka, Adoke, Zongo, Issaka, Simpson, Julie A., Guerin, Philippe J., Stepniewska, Kasia, Price, Ric N., and Roper, Cally

Abstract

Background Plasmodium falciparum malaria is associated with anaemia-related morbidity, attributable to host, parasite and drug factors. We quantified the haematological response following treatment of uncomplicated P. falciparum malaria to identify the factors associated with malarial anaemia. Methods Individual patient data from eligible antimalarial efficacy studies of uncomplicated P. falciparum malaria, available through the WorldWide Antimalarial Resistance Network data repository prior to August 2015, were pooled using standardised methodology. The haematological response over time was quantified using a multivariable linear mixed effects model with nonlinear terms for time, and the model was then used to estimate the mean haemoglobin at day of nadir and day 7. Multivariable logistic regression quantified risk factors for moderately severe anaemia (haemoglobin < 7 g/dL) at day 0, day 3 and day 7 as well as a fractional fall >= 25% at day 3 and day 7. Results A total of 70,226 patients, recruited into 200 studies between 1991 and 2013, were included in the analysis: 50,859 (72.4%) enrolled in Africa, 18,451 (26.3%) in Asia and 916 (1.3%) in South America. The median haemoglobin concentration at presentation was 9.9 g/dL (range 5.0-19.7 g/dL) in Africa, 11.6 g/dL (range 5.0-20.0 g/dL) in Asia and 12.3 g/dL (range 6.9-17.9 g/dL) in South America. Moderately severe anaemia (Hb < 7g/dl) was present in 8.4% (4284/50,859) of patients from Africa, 3.3% (606/18,451) from Asia and 0.1% (1/916) from South America. The nadir haemoglobin occurred on day 2 post treatment with a mean fall from baseline of 0.57 g/dL in Africa and 1.13 g/dL in Asia. Independent risk factors for moderately severe anaemia on day 7, in both Africa and Asia, included moderately severe anaemia at baseline (adjusted odds ratio (AOR) = 16.10 and AOR = 23.00, respectively), young age (age < 1 compared to >= 12 years AOR = 12.81 and AOR = 6.79, respectively), high parasitaemia (AOR = 1.7

Published
2022
Full Text
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20. Haematological consequences of acute uncomplicated falciparum malaria : a WorldWide Antimalarial Resistance Network pooled analysis of individual patient data

Author

Mansoor, Rashid, Commons, Robert J., Douglas, Nicholas M., Abuaku, Benjamin, Achan, Jane, Adam, Ishag, Adjei, George O., Adjuik, Martin, Alemayehu, Bereket H., Allan, Richard, Allen, Elizabeth N., Anvikar, Anupkumar R., Arinaitwe, Emmanuel, Ashley, Elizabeth A., Ashurst, Hazel, Asih, Puji B. S., Bakyaita, Nathan, Barennes, Hubert, Barnes, Karen, I, Basco, Leonardo, Bassat, Quique, Baudin, Elisabeth, Bell, David J., Bethell, Delia, Bjorkman, Anders, Boulton, Caroline, Bousema, Teun, Brasseur, Philippe, Bukirwa, Hasifa, Burrow, Rebekah, Carrara, Verena, I, Cot, Michel, D'Alessandro, Umberto, Das, Debashish, Das, Sabyasachi, Davis, Timothy M. E., Desai, Meghna, Djimde, Abdoulaye A., Dondorp, Arjen M., Dorsey, Grant, Drakeley, Chris J., Duparc, Stephan, Espie, Emmanuelle, Etard, Jean-Francois, Falade, Catherine, Faucher, Jean Francois, Filler, Scott, Fogg, Carole, Fukuda, Mark, Gaye, Oumar, Genton, Blaise, Rahim, Awab Ghulam, Gilayeneh, Julius, Gonzalez, Raquel, Grais, Rebecca F., Grandesso, Francesco, Greenwood, Brian, Grivoyannis, Anastasia, Hatz, Christoph, Hodel, Eva Maria, Humphreys, Georgina S., Hwang, Jimee, Ishengoma, Deus, Juma, Elizabeth, Kachur, S. Patrick, Kager, Piet A., Kamugisha, Erasmus, Kamya, Moses R., Karema, Corine, Kayentao, Kassoum, Kazienga, Adama, Kiechel, Jean-Rene, Kofoed, Poul-Erik, Koram, Kwadwo, Kremsner, Peter G., Lalloo, David G., Laman, Moses, Lee, Sue J., Lell, Bertrand, Maiga, Amelia W., Mårtensson, Andreas, Mayxay, Mayfong, Mbacham, Wilfred, McGready, Rose, Menan, Herve, Menard, Didier, Mockenhaupt, Frank, Moore, Brioni R., Muller, Olaf, Nahum, Alain, Ndiaye, Jean-Louis, Newton, Paul N., Ngasala, Billy E., Nikiema, Frederic, Nji, Akindeh M., Noedl, Harald, Nosten, Francois, Ogutu, Bernhards R., Ojurongbe, Olusola, Osorio, Lyda, Ouedraogo, Jean-Bosco, Owusu-Agyei, Seth, Pareek, Anil, Penali, Louis K., Piola, Patrice, Plucinski, Mateusz, Premji, Zul, Ramharter, Michael, Richmond, Caitlin L., Rombo, Lars, Rosenthal, Philip J., Salman, Sam, Same-Ekobo, Albert, Sibley, Carol, Sirima, Sodiomon B., Smithuis, Frank M., Some, Fabrice A., Staedke, Sarah G., Starzengruber, Peter, Strub-Wourgaft, Nathalie, Sutanto, Inge, Swarthout, Todd D., Syafruddin, Din, Talisuna, Ambrose O., Taylor, Walter R., Temu, Emmanuel A., Thwing, Julie, I, Tinto, Halidou, Tjitra, Emiliana, Toure, Offianan A., Tran, T. Hien, Ursing, Johan, Valea, Innocent, Valentini, Giovanni, van Vugt, Michele, von Seidlein, Lorenz, Ward, Stephen A., Were, Vincent, White, Nicholas J., Woodrow, Charles J., Yavo, William, Yeka, Adoke, Zongo, Issaka, Simpson, Julie A., Guerin, Philippe J., Stepniewska, Kasia, Price, Ric N., Roper, Cally, Mansoor, Rashid, Commons, Robert J., Douglas, Nicholas M., Abuaku, Benjamin, Achan, Jane, Adam, Ishag, Adjei, George O., Adjuik, Martin, Alemayehu, Bereket H., Allan, Richard, Allen, Elizabeth N., Anvikar, Anupkumar R., Arinaitwe, Emmanuel, Ashley, Elizabeth A., Ashurst, Hazel, Asih, Puji B. S., Bakyaita, Nathan, Barennes, Hubert, Barnes, Karen, I, Basco, Leonardo, Bassat, Quique, Baudin, Elisabeth, Bell, David J., Bethell, Delia, Bjorkman, Anders, Boulton, Caroline, Bousema, Teun, Brasseur, Philippe, Bukirwa, Hasifa, Burrow, Rebekah, Carrara, Verena, I, Cot, Michel, D'Alessandro, Umberto, Das, Debashish, Das, Sabyasachi, Davis, Timothy M. E., Desai, Meghna, Djimde, Abdoulaye A., Dondorp, Arjen M., Dorsey, Grant, Drakeley, Chris J., Duparc, Stephan, Espie, Emmanuelle, Etard, Jean-Francois, Falade, Catherine, Faucher, Jean Francois, Filler, Scott, Fogg, Carole, Fukuda, Mark, Gaye, Oumar, Genton, Blaise, Rahim, Awab Ghulam, Gilayeneh, Julius, Gonzalez, Raquel, Grais, Rebecca F., Grandesso, Francesco, Greenwood, Brian, Grivoyannis, Anastasia, Hatz, Christoph, Hodel, Eva Maria, Humphreys, Georgina S., Hwang, Jimee, Ishengoma, Deus, Juma, Elizabeth, Kachur, S. Patrick, Kager, Piet A., Kamugisha, Erasmus, Kamya, Moses R., Karema, Corine, Kayentao, Kassoum, Kazienga, Adama, Kiechel, Jean-Rene, Kofoed, Poul-Erik, Koram, Kwadwo, Kremsner, Peter G., Lalloo, David G., Laman, Moses, Lee, Sue J., Lell, Bertrand, Maiga, Amelia W., Mårtensson, Andreas, Mayxay, Mayfong, Mbacham, Wilfred, McGready, Rose, Menan, Herve, Menard, Didier, Mockenhaupt, Frank, Moore, Brioni R., Muller, Olaf, Nahum, Alain, Ndiaye, Jean-Louis, Newton, Paul N., Ngasala, Billy E., Nikiema, Frederic, Nji, Akindeh M., Noedl, Harald, Nosten, Francois, Ogutu, Bernhards R., Ojurongbe, Olusola, Osorio, Lyda, Ouedraogo, Jean-Bosco, Owusu-Agyei, Seth, Pareek, Anil, Penali, Louis K., Piola, Patrice, Plucinski, Mateusz, Premji, Zul, Ramharter, Michael, Richmond, Caitlin L., Rombo, Lars, Rosenthal, Philip J., Salman, Sam, Same-Ekobo, Albert, Sibley, Carol, Sirima, Sodiomon B., Smithuis, Frank M., Some, Fabrice A., Staedke, Sarah G., Starzengruber, Peter, Strub-Wourgaft, Nathalie, Sutanto, Inge, Swarthout, Todd D., Syafruddin, Din, Talisuna, Ambrose O., Taylor, Walter R., Temu, Emmanuel A., Thwing, Julie, I, Tinto, Halidou, Tjitra, Emiliana, Toure, Offianan A., Tran, T. Hien, Ursing, Johan, Valea, Innocent, Valentini, Giovanni, van Vugt, Michele, von Seidlein, Lorenz, Ward, Stephen A., Were, Vincent, White, Nicholas J., Woodrow, Charles J., Yavo, William, Yeka, Adoke, Zongo, Issaka, Simpson, Julie A., Guerin, Philippe J., Stepniewska, Kasia, Price, Ric N., and Roper, Cally

Abstract

Background Plasmodium falciparum malaria is associated with anaemia-related morbidity, attributable to host, parasite and drug factors. We quantified the haematological response following treatment of uncomplicated P. falciparum malaria to identify the factors associated with malarial anaemia. Methods Individual patient data from eligible antimalarial efficacy studies of uncomplicated P. falciparum malaria, available through the WorldWide Antimalarial Resistance Network data repository prior to August 2015, were pooled using standardised methodology. The haematological response over time was quantified using a multivariable linear mixed effects model with nonlinear terms for time, and the model was then used to estimate the mean haemoglobin at day of nadir and day 7. Multivariable logistic regression quantified risk factors for moderately severe anaemia (haemoglobin < 7 g/dL) at day 0, day 3 and day 7 as well as a fractional fall >= 25% at day 3 and day 7. Results A total of 70,226 patients, recruited into 200 studies between 1991 and 2013, were included in the analysis: 50,859 (72.4%) enrolled in Africa, 18,451 (26.3%) in Asia and 916 (1.3%) in South America. The median haemoglobin concentration at presentation was 9.9 g/dL (range 5.0-19.7 g/dL) in Africa, 11.6 g/dL (range 5.0-20.0 g/dL) in Asia and 12.3 g/dL (range 6.9-17.9 g/dL) in South America. Moderately severe anaemia (Hb < 7g/dl) was present in 8.4% (4284/50,859) of patients from Africa, 3.3% (606/18,451) from Asia and 0.1% (1/916) from South America. The nadir haemoglobin occurred on day 2 post treatment with a mean fall from baseline of 0.57 g/dL in Africa and 1.13 g/dL in Asia. Independent risk factors for moderately severe anaemia on day 7, in both Africa and Asia, included moderately severe anaemia at baseline (adjusted odds ratio (AOR) = 16.10 and AOR = 23.00, respectively), young age (age < 1 compared to >= 12 years AOR = 12.81 and AOR = 6.79, respectively), high parasitaemia (AOR = 1.7

Published
2022
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21. Haematological consequences of acute uncomplicated falciparum malaria : a WorldWide Antimalarial Resistance Network pooled analysis of individual patient data

Author

Mansoor, Rashid, Commons, Robert J., Douglas, Nicholas M., Abuaku, Benjamin, Achan, Jane, Adam, Ishag, Adjei, George O., Adjuik, Martin, Alemayehu, Bereket H., Allan, Richard, Allen, Elizabeth N., Anvikar, Anupkumar R., Arinaitwe, Emmanuel, Ashley, Elizabeth A., Ashurst, Hazel, Asih, Puji B. S., Bakyaita, Nathan, Barennes, Hubert, Barnes, Karen, I, Basco, Leonardo, Bassat, Quique, Baudin, Elisabeth, Bell, David J., Bethell, Delia, Bjorkman, Anders, Boulton, Caroline, Bousema, Teun, Brasseur, Philippe, Bukirwa, Hasifa, Burrow, Rebekah, Carrara, Verena, I, Cot, Michel, D'Alessandro, Umberto, Das, Debashish, Das, Sabyasachi, Davis, Timothy M. E., Desai, Meghna, Djimde, Abdoulaye A., Dondorp, Arjen M., Dorsey, Grant, Drakeley, Chris J., Duparc, Stephan, Espie, Emmanuelle, Etard, Jean-Francois, Falade, Catherine, Faucher, Jean Francois, Filler, Scott, Fogg, Carole, Fukuda, Mark, Gaye, Oumar, Genton, Blaise, Rahim, Awab Ghulam, Gilayeneh, Julius, Gonzalez, Raquel, Grais, Rebecca F., Grandesso, Francesco, Greenwood, Brian, Grivoyannis, Anastasia, Hatz, Christoph, Hodel, Eva Maria, Humphreys, Georgina S., Hwang, Jimee, Ishengoma, Deus, Juma, Elizabeth, Kachur, S. Patrick, Kager, Piet A., Kamugisha, Erasmus, Kamya, Moses R., Karema, Corine, Kayentao, Kassoum, Kazienga, Adama, Kiechel, Jean-Rene, Kofoed, Poul-Erik, Koram, Kwadwo, Kremsner, Peter G., Lalloo, David G., Laman, Moses, Lee, Sue J., Lell, Bertrand, Maiga, Amelia W., Mårtensson, Andreas, Mayxay, Mayfong, Mbacham, Wilfred, McGready, Rose, Menan, Herve, Menard, Didier, Mockenhaupt, Frank, Moore, Brioni R., Muller, Olaf, Nahum, Alain, Ndiaye, Jean-Louis, Newton, Paul N., Ngasala, Billy E., Nikiema, Frederic, Nji, Akindeh M., Noedl, Harald, Nosten, Francois, Ogutu, Bernhards R., Ojurongbe, Olusola, Osorio, Lyda, Ouedraogo, Jean-Bosco, Owusu-Agyei, Seth, Pareek, Anil, Penali, Louis K., Piola, Patrice, Plucinski, Mateusz, Premji, Zul, Ramharter, Michael, Richmond, Caitlin L., Rombo, Lars, Rosenthal, Philip J., Salman, Sam, Same-Ekobo, Albert, Sibley, Carol, Sirima, Sodiomon B., Smithuis, Frank M., Some, Fabrice A., Staedke, Sarah G., Starzengruber, Peter, Strub-Wourgaft, Nathalie, Sutanto, Inge, Swarthout, Todd D., Syafruddin, Din, Talisuna, Ambrose O., Taylor, Walter R., Temu, Emmanuel A., Thwing, Julie, I, Tinto, Halidou, Tjitra, Emiliana, Toure, Offianan A., Tran, T. Hien, Ursing, Johan, Valea, Innocent, Valentini, Giovanni, van Vugt, Michele, von Seidlein, Lorenz, Ward, Stephen A., Were, Vincent, White, Nicholas J., Woodrow, Charles J., Yavo, William, Yeka, Adoke, Zongo, Issaka, Simpson, Julie A., Guerin, Philippe J., Stepniewska, Kasia, Price, Ric N., Roper, Cally, Mansoor, Rashid, Commons, Robert J., Douglas, Nicholas M., Abuaku, Benjamin, Achan, Jane, Adam, Ishag, Adjei, George O., Adjuik, Martin, Alemayehu, Bereket H., Allan, Richard, Allen, Elizabeth N., Anvikar, Anupkumar R., Arinaitwe, Emmanuel, Ashley, Elizabeth A., Ashurst, Hazel, Asih, Puji B. S., Bakyaita, Nathan, Barennes, Hubert, Barnes, Karen, I, Basco, Leonardo, Bassat, Quique, Baudin, Elisabeth, Bell, David J., Bethell, Delia, Bjorkman, Anders, Boulton, Caroline, Bousema, Teun, Brasseur, Philippe, Bukirwa, Hasifa, Burrow, Rebekah, Carrara, Verena, I, Cot, Michel, D'Alessandro, Umberto, Das, Debashish, Das, Sabyasachi, Davis, Timothy M. E., Desai, Meghna, Djimde, Abdoulaye A., Dondorp, Arjen M., Dorsey, Grant, Drakeley, Chris J., Duparc, Stephan, Espie, Emmanuelle, Etard, Jean-Francois, Falade, Catherine, Faucher, Jean Francois, Filler, Scott, Fogg, Carole, Fukuda, Mark, Gaye, Oumar, Genton, Blaise, Rahim, Awab Ghulam, Gilayeneh, Julius, Gonzalez, Raquel, Grais, Rebecca F., Grandesso, Francesco, Greenwood, Brian, Grivoyannis, Anastasia, Hatz, Christoph, Hodel, Eva Maria, Humphreys, Georgina S., Hwang, Jimee, Ishengoma, Deus, Juma, Elizabeth, Kachur, S. Patrick, Kager, Piet A., Kamugisha, Erasmus, Kamya, Moses R., Karema, Corine, Kayentao, Kassoum, Kazienga, Adama, Kiechel, Jean-Rene, Kofoed, Poul-Erik, Koram, Kwadwo, Kremsner, Peter G., Lalloo, David G., Laman, Moses, Lee, Sue J., Lell, Bertrand, Maiga, Amelia W., Mårtensson, Andreas, Mayxay, Mayfong, Mbacham, Wilfred, McGready, Rose, Menan, Herve, Menard, Didier, Mockenhaupt, Frank, Moore, Brioni R., Muller, Olaf, Nahum, Alain, Ndiaye, Jean-Louis, Newton, Paul N., Ngasala, Billy E., Nikiema, Frederic, Nji, Akindeh M., Noedl, Harald, Nosten, Francois, Ogutu, Bernhards R., Ojurongbe, Olusola, Osorio, Lyda, Ouedraogo, Jean-Bosco, Owusu-Agyei, Seth, Pareek, Anil, Penali, Louis K., Piola, Patrice, Plucinski, Mateusz, Premji, Zul, Ramharter, Michael, Richmond, Caitlin L., Rombo, Lars, Rosenthal, Philip J., Salman, Sam, Same-Ekobo, Albert, Sibley, Carol, Sirima, Sodiomon B., Smithuis, Frank M., Some, Fabrice A., Staedke, Sarah G., Starzengruber, Peter, Strub-Wourgaft, Nathalie, Sutanto, Inge, Swarthout, Todd D., Syafruddin, Din, Talisuna, Ambrose O., Taylor, Walter R., Temu, Emmanuel A., Thwing, Julie, I, Tinto, Halidou, Tjitra, Emiliana, Toure, Offianan A., Tran, T. Hien, Ursing, Johan, Valea, Innocent, Valentini, Giovanni, van Vugt, Michele, von Seidlein, Lorenz, Ward, Stephen A., Were, Vincent, White, Nicholas J., Woodrow, Charles J., Yavo, William, Yeka, Adoke, Zongo, Issaka, Simpson, Julie A., Guerin, Philippe J., Stepniewska, Kasia, Price, Ric N., and Roper, Cally

Abstract

Background Plasmodium falciparum malaria is associated with anaemia-related morbidity, attributable to host, parasite and drug factors. We quantified the haematological response following treatment of uncomplicated P. falciparum malaria to identify the factors associated with malarial anaemia. Methods Individual patient data from eligible antimalarial efficacy studies of uncomplicated P. falciparum malaria, available through the WorldWide Antimalarial Resistance Network data repository prior to August 2015, were pooled using standardised methodology. The haematological response over time was quantified using a multivariable linear mixed effects model with nonlinear terms for time, and the model was then used to estimate the mean haemoglobin at day of nadir and day 7. Multivariable logistic regression quantified risk factors for moderately severe anaemia (haemoglobin < 7 g/dL) at day 0, day 3 and day 7 as well as a fractional fall >= 25% at day 3 and day 7. Results A total of 70,226 patients, recruited into 200 studies between 1991 and 2013, were included in the analysis: 50,859 (72.4%) enrolled in Africa, 18,451 (26.3%) in Asia and 916 (1.3%) in South America. The median haemoglobin concentration at presentation was 9.9 g/dL (range 5.0-19.7 g/dL) in Africa, 11.6 g/dL (range 5.0-20.0 g/dL) in Asia and 12.3 g/dL (range 6.9-17.9 g/dL) in South America. Moderately severe anaemia (Hb < 7g/dl) was present in 8.4% (4284/50,859) of patients from Africa, 3.3% (606/18,451) from Asia and 0.1% (1/916) from South America. The nadir haemoglobin occurred on day 2 post treatment with a mean fall from baseline of 0.57 g/dL in Africa and 1.13 g/dL in Asia. Independent risk factors for moderately severe anaemia on day 7, in both Africa and Asia, included moderately severe anaemia at baseline (adjusted odds ratio (AOR) = 16.10 and AOR = 23.00, respectively), young age (age < 1 compared to >= 12 years AOR = 12.81 and AOR = 6.79, respectively), high parasitaemia (AOR = 1.7

Published
2022
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22. RANS simulations of terrain-disrupted turbulent airflow at Hong Kong International Airport

Author

Tse, Louis K. S., Guan, Yu, Li, Larry K.B., Tse, Louis K. S., Guan, Yu, and Li, Larry K.B.

Abstract

During a tropical cyclone, windshear can occur at Hong Kong International Airport (HKIA) owing to interactions between strong winds and the complex topography of the neighboring Lantau Island. For aviation safety, it is crucial to understand how such interactions arise under realistic but controlled meteorological conditions. In this study, we numerically simulate the turbulent airflow over Lantau Island and HKIA using OpenFOAM, an open-source platform for computational fluid dynamics. We use the platform to solve the Reynolds-averaged Navier–Stokes equations via the finite volume method of discretization. We impose a neutrally stratified atmospheric boundary layer as the upwind condition, which is initialized with a logarithmic velocity profile in three different wind directions: southerly, southeasterly and easterly. For all three directions, we find multiple high-speed ∨-shaped jets emanating from the mountain gaps of Lantau Island, giving rise to headwind and crosswind variations along the glide paths of HKIA. However, we find that it is primarily the southerly and southeasterly winds that are the most conducive to windshear. For these two wind directions, we find that windshear is most likely to occur along the glide paths of the two existing runways because these are the closest to Lantau Island itself. The third runway, which is currently under construction, is the least likely to suffer from windshear. By showing how airflow disturbances arise from the complex topography of Lantau Island, this study contributes to safer and more efficient flight operations at HKIA.

Published
2021

23. RANS simulations of terrain-disrupted turbulent airflow at Hong Kong International Airport

Author

Tse, Louis K. S., Guan, Yu, Li, Larry K.B., Tse, Louis K. S., Guan, Yu, and Li, Larry K.B.

Abstract

During a tropical cyclone, windshear can occur at Hong Kong International Airport (HKIA) owing to interactions between strong winds and the complex topography of the neighboring Lantau Island. For aviation safety, it is crucial to understand how such interactions arise under realistic but controlled meteorological conditions. In this study, we numerically simulate the turbulent airflow over Lantau Island and HKIA using OpenFOAM, an open-source platform for computational fluid dynamics. We use the platform to solve the Reynolds-averaged Navier–Stokes equations via the finite volume method of discretization. We impose a neutrally stratified atmospheric boundary layer as the upwind condition, which is initialized with a logarithmic velocity profile in three different wind directions: southerly, southeasterly and easterly. For all three directions, we find multiple high-speed ∨-shaped jets emanating from the mountain gaps of Lantau Island, giving rise to headwind and crosswind variations along the glide paths of HKIA. However, we find that it is primarily the southerly and southeasterly winds that are the most conducive to windshear. For these two wind directions, we find that windshear is most likely to occur along the glide paths of the two existing runways because these are the closest to Lantau Island itself. The third runway, which is currently under construction, is the least likely to suffer from windshear. By showing how airflow disturbances arise from the complex topography of Lantau Island, this study contributes to safer and more efficient flight operations at HKIA.

Published
2021

24. RANS simulations of terrain-disrupted turbulent airflow at Hong Kong International Airport

Author

Tse, Louis K. S., Guan, Yu, Li, Larry K.B., Tse, Louis K. S., Guan, Yu, and Li, Larry K.B.

Abstract

During a tropical cyclone, windshear can occur at Hong Kong International Airport (HKIA) owing to interactions between strong winds and the complex topography of the neighboring Lantau Island. For aviation safety, it is crucial to understand how such interactions arise under realistic but controlled meteorological conditions. In this study, we numerically simulate the turbulent airflow over Lantau Island and HKIA using OpenFOAM, an open-source platform for computational fluid dynamics. We use the platform to solve the Reynolds-averaged Navier–Stokes equations via the finite volume method of discretization. We impose a neutrally stratified atmospheric boundary layer as the upwind condition, which is initialized with a logarithmic velocity profile in three different wind directions: southerly, southeasterly and easterly. For all three directions, we find multiple high-speed ∨-shaped jets emanating from the mountain gaps of Lantau Island, giving rise to headwind and crosswind variations along the glide paths of HKIA. However, we find that it is primarily the southerly and southeasterly winds that are the most conducive to windshear. For these two wind directions, we find that windshear is most likely to occur along the glide paths of the two existing runways because these are the closest to Lantau Island itself. The third runway, which is currently under construction, is the least likely to suffer from windshear. By showing how airflow disturbances arise from the complex topography of Lantau Island, this study contributes to safer and more efficient flight operations at HKIA.

Published
2021

25. Automatic Speech Recognition And Limited Vocabulary: A Survey

Author

Fendji, Jean Louis K. E., Tala, Diane C. M., Yenke, Blaise O., Atemkeng, Marcellin, Fendji, Jean Louis K. E., Tala, Diane C. M., Yenke, Blaise O., and Atemkeng, Marcellin

Abstract

Automatic Speech Recognition (ASR) is an active field of research due to its large number of applications and the proliferation of interfaces or computing devices that can support speech processing. However, the bulk of applications are based on well-resourced languages that overshadow under-resourced ones. Yet, ASR represents an undeniable means to promote such languages, especially when designing human-to-human or human-to-machine systems involving illiterate people. An approach to design an ASR system targeting under-resourced languages is to start with a limited vocabulary. ASR using a limited vocabulary is a subset of the speech recognition problem that focuses on the recognition of a small number of words or sentences. This paper aims to provide a comprehensive view of mechanisms behind ASR systems as well as techniques, tools, projects, recent contributions, and possible future directions in ASR using a limited vocabulary. This work consequently provides a way forward when designing an ASR system using limited vocabulary. Although an emphasis is put on limited vocabulary, most of the tools and techniques reported in this survey can be applied to ASR systems in general., Comment: 24 pages, 9 figures, 6 tables, submitted to Elsevier for possible publication

Published
2021

26. A connectome and analysis of the adult Drosophila central brain

Author

Scheffer, Louis K., Xu, C. Shan, Januszewski, Michal, Lu, Zhiyuan, Takemura, Shin-ya, Hayworth, Kenneth J., Huang, Gary B., Shinomiya, Kazunori, Maitlin-Shepard, Jeremy, Berg, Stuart, Clements, Jody, Hubbard, Philip M., Katz, William T., Umayam, Lowell, Zhao, Ting, Ackerman, David, Blakely, Tim, Bogovic, John, Dolafi, Tom, Kainmueller, Dagmar, Kawase, Takashi, Khairy, Khaled A., Leavitt, Laramie, Li, Peter H., Lindsey, Larry, Neubarth, Nicole, Olbris, Donald J., Otsuna, Hideo, Trautman, Eric T., Ito, Masayoshi, Bates, Alexander S., Goldammer, Jens, Wolff, Tanya, Svirskas, Robert, Schlegel, Philipp, Neace, Erika, Knecht, Christopher J., Alvarado, Chelsea X., Bailey, Dennis A., Ballinger, Samantha, Borycz, Jolanta A., Canino, Brandon S., Cheatham, Natasha, Cook, Michael, Dreher, Marisa, Duclos, Octave, Eubanks, Bryon, Fairbanks, Kelli, Finley, Samantha, Forknall, Nora, Francis, Audrey, Hopkins, Gary Patrick, Joyce, Emily M., Kim, SungJin, Kirk, Nicole A., Kovalyak, Julie, Lauchie, Shirley A., Lohff, Alanna, Maldonado, Charli, Manley, Emily A., McLin, Sari, Mooney, Caroline, Ndama, Miatta, Ogundeyi, Omotara, Okeoma, Nneoma, Ordish, Christopher, Padilla, Nicholas, Patrick, Christopher M., Paterson, Tyler, Phillips, Elliott E., Phillips, Emily M., Rampally, Neha, Ribeiro, Caitlin, Robertson, Madelaine K., Rymer, Jon Thomson, Ryan, Sean M., Sammons, Megan, Scott, Anne K., Scott, Ashley L., Shinomiya, Aya, Smith, Claire, Smith, Kelsey, Smith, Natalie L., Sobeski, Margaret A., Suleiman, Alia, Swift, Jackie, Takemura, Satoko, Talebi, Iris, Tarnogorska, Dorota, Tenshaw, Emily, Tokhi, Temour, Walsh, John J., Yang, Tansy, Horne, Jane Anne, Li, Feng, Parekh, Ruchi, Rivlin, Patricia K., Jayaraman, Vivek, Costa, Marta, Jefferis, Gregory S. X. E., Ito, Kei, Saalfeld, Stephan, George, Reed, Meinertzhagen, Ian A., Rubin, Gerald M., Hess, Harald F., Jain, Viren, Plaza, Stephen M., Scheffer, Louis K., Xu, C. Shan, Januszewski, Michal, Lu, Zhiyuan, Takemura, Shin-ya, Hayworth, Kenneth J., Huang, Gary B., Shinomiya, Kazunori, Maitlin-Shepard, Jeremy, Berg, Stuart, Clements, Jody, Hubbard, Philip M., Katz, William T., Umayam, Lowell, Zhao, Ting, Ackerman, David, Blakely, Tim, Bogovic, John, Dolafi, Tom, Kainmueller, Dagmar, Kawase, Takashi, Khairy, Khaled A., Leavitt, Laramie, Li, Peter H., Lindsey, Larry, Neubarth, Nicole, Olbris, Donald J., Otsuna, Hideo, Trautman, Eric T., Ito, Masayoshi, Bates, Alexander S., Goldammer, Jens, Wolff, Tanya, Svirskas, Robert, Schlegel, Philipp, Neace, Erika, Knecht, Christopher J., Alvarado, Chelsea X., Bailey, Dennis A., Ballinger, Samantha, Borycz, Jolanta A., Canino, Brandon S., Cheatham, Natasha, Cook, Michael, Dreher, Marisa, Duclos, Octave, Eubanks, Bryon, Fairbanks, Kelli, Finley, Samantha, Forknall, Nora, Francis, Audrey, Hopkins, Gary Patrick, Joyce, Emily M., Kim, SungJin, Kirk, Nicole A., Kovalyak, Julie, Lauchie, Shirley A., Lohff, Alanna, Maldonado, Charli, Manley, Emily A., McLin, Sari, Mooney, Caroline, Ndama, Miatta, Ogundeyi, Omotara, Okeoma, Nneoma, Ordish, Christopher, Padilla, Nicholas, Patrick, Christopher M., Paterson, Tyler, Phillips, Elliott E., Phillips, Emily M., Rampally, Neha, Ribeiro, Caitlin, Robertson, Madelaine K., Rymer, Jon Thomson, Ryan, Sean M., Sammons, Megan, Scott, Anne K., Scott, Ashley L., Shinomiya, Aya, Smith, Claire, Smith, Kelsey, Smith, Natalie L., Sobeski, Margaret A., Suleiman, Alia, Swift, Jackie, Takemura, Satoko, Talebi, Iris, Tarnogorska, Dorota, Tenshaw, Emily, Tokhi, Temour, Walsh, John J., Yang, Tansy, Horne, Jane Anne, Li, Feng, Parekh, Ruchi, Rivlin, Patricia K., Jayaraman, Vivek, Costa, Marta, Jefferis, Gregory S. X. E., Ito, Kei, Saalfeld, Stephan, George, Reed, Meinertzhagen, Ian A., Rubin, Gerald M., Hess, Harald F., Jain, Viren, and Plaza, Stephen M.

Abstract

The neural circuits responsible for animal behavior remain largely unknown. We summarize new methods and present the circuitry of a large fraction of the brain of the fruit fly Drosophila melanogaster. Improved methods include new procedures to prepare, image, align, segment, find synapses in, and proofread such large data sets. We define cell types, refine computational compartments, and provide an exhaustive atlas of cell examples and types, many of them novel. We provide detailed circuits consisting of neurons and their chemical synapses for most of the central brain. We make the data public and simplify access, reducing the effort needed eLife digest Animal brains of all sizes, from the smallest to the largest, work in broadly similar ways. Studying the brain of any one animal in depth can thus reveal the general principles behind the workings of all brains. The fruit fly Drosophila is a popular choice for such research. With about 100,000 neurons - compared to some 86 billion in humans - the fly brain is small enough to study at the level of individual cells. But it nevertheless supports a range of complex behaviors, including navigation, courtship and learning. Thanks to decades of research, scientists now have a good understanding of which parts of the fruit fly brain support particular behaviors. But exactly how they do this is often unclear. This is because previous studies showing the connections between cells only covered small areas of the brain. This is like trying to understand a novel when all you can see is a few isolated paragraphs. To solve this problem, Scheffer, Xu, Januszewski, Lu, Takemura, Hayworth, Huang, Shinomiya et al. prepared the first complete map of the entire central region of the fruit fly brain. The central brain consists of approximately 25,000 neurons and around 20 million connections. To prepare the map - or connectome - the brain was cut into very thin 8nm slices and photographed with an electron microscope. A three-dimensional

Published
2020

27. A connectome and analysis of the adult Drosophila central brain

Author

Scheffer, Louis K., Xu, C. Shan, Januszewski, Michal, Lu, Zhiyuan, Takemura, Shin-ya, Hayworth, Kenneth J., Huang, Gary B., Shinomiya, Kazunori, Maitlin-Shepard, Jeremy, Berg, Stuart, Clements, Jody, Hubbard, Philip M., Katz, William T., Umayam, Lowell, Zhao, Ting, Ackerman, David, Blakely, Tim, Bogovic, John, Dolafi, Tom, Kainmueller, Dagmar, Kawase, Takashi, Khairy, Khaled A., Leavitt, Laramie, Li, Peter H., Lindsey, Larry, Neubarth, Nicole, Olbris, Donald J., Otsuna, Hideo, Trautman, Eric T., Ito, Masayoshi, Bates, Alexander S., Goldammer, Jens, Wolff, Tanya, Svirskas, Robert, Schlegel, Philipp, Neace, Erika, Knecht, Christopher J., Alvarado, Chelsea X., Bailey, Dennis A., Ballinger, Samantha, Borycz, Jolanta A., Canino, Brandon S., Cheatham, Natasha, Cook, Michael, Dreher, Marisa, Duclos, Octave, Eubanks, Bryon, Fairbanks, Kelli, Finley, Samantha, Forknall, Nora, Francis, Audrey, Hopkins, Gary Patrick, Joyce, Emily M., Kim, SungJin, Kirk, Nicole A., Kovalyak, Julie, Lauchie, Shirley A., Lohff, Alanna, Maldonado, Charli, Manley, Emily A., McLin, Sari, Mooney, Caroline, Ndama, Miatta, Ogundeyi, Omotara, Okeoma, Nneoma, Ordish, Christopher, Padilla, Nicholas, Patrick, Christopher M., Paterson, Tyler, Phillips, Elliott E., Phillips, Emily M., Rampally, Neha, Ribeiro, Caitlin, Robertson, Madelaine K., Rymer, Jon Thomson, Ryan, Sean M., Sammons, Megan, Scott, Anne K., Scott, Ashley L., Shinomiya, Aya, Smith, Claire, Smith, Kelsey, Smith, Natalie L., Sobeski, Margaret A., Suleiman, Alia, Swift, Jackie, Takemura, Satoko, Talebi, Iris, Tarnogorska, Dorota, Tenshaw, Emily, Tokhi, Temour, Walsh, John J., Yang, Tansy, Horne, Jane Anne, Li, Feng, Parekh, Ruchi, Rivlin, Patricia K., Jayaraman, Vivek, Costa, Marta, Jefferis, Gregory S. X. E., Ito, Kei, Saalfeld, Stephan, George, Reed, Meinertzhagen, Ian A., Rubin, Gerald M., Hess, Harald F., Jain, Viren, Plaza, Stephen M., Scheffer, Louis K., Xu, C. Shan, Januszewski, Michal, Lu, Zhiyuan, Takemura, Shin-ya, Hayworth, Kenneth J., Huang, Gary B., Shinomiya, Kazunori, Maitlin-Shepard, Jeremy, Berg, Stuart, Clements, Jody, Hubbard, Philip M., Katz, William T., Umayam, Lowell, Zhao, Ting, Ackerman, David, Blakely, Tim, Bogovic, John, Dolafi, Tom, Kainmueller, Dagmar, Kawase, Takashi, Khairy, Khaled A., Leavitt, Laramie, Li, Peter H., Lindsey, Larry, Neubarth, Nicole, Olbris, Donald J., Otsuna, Hideo, Trautman, Eric T., Ito, Masayoshi, Bates, Alexander S., Goldammer, Jens, Wolff, Tanya, Svirskas, Robert, Schlegel, Philipp, Neace, Erika, Knecht, Christopher J., Alvarado, Chelsea X., Bailey, Dennis A., Ballinger, Samantha, Borycz, Jolanta A., Canino, Brandon S., Cheatham, Natasha, Cook, Michael, Dreher, Marisa, Duclos, Octave, Eubanks, Bryon, Fairbanks, Kelli, Finley, Samantha, Forknall, Nora, Francis, Audrey, Hopkins, Gary Patrick, Joyce, Emily M., Kim, SungJin, Kirk, Nicole A., Kovalyak, Julie, Lauchie, Shirley A., Lohff, Alanna, Maldonado, Charli, Manley, Emily A., McLin, Sari, Mooney, Caroline, Ndama, Miatta, Ogundeyi, Omotara, Okeoma, Nneoma, Ordish, Christopher, Padilla, Nicholas, Patrick, Christopher M., Paterson, Tyler, Phillips, Elliott E., Phillips, Emily M., Rampally, Neha, Ribeiro, Caitlin, Robertson, Madelaine K., Rymer, Jon Thomson, Ryan, Sean M., Sammons, Megan, Scott, Anne K., Scott, Ashley L., Shinomiya, Aya, Smith, Claire, Smith, Kelsey, Smith, Natalie L., Sobeski, Margaret A., Suleiman, Alia, Swift, Jackie, Takemura, Satoko, Talebi, Iris, Tarnogorska, Dorota, Tenshaw, Emily, Tokhi, Temour, Walsh, John J., Yang, Tansy, Horne, Jane Anne, Li, Feng, Parekh, Ruchi, Rivlin, Patricia K., Jayaraman, Vivek, Costa, Marta, Jefferis, Gregory S. X. E., Ito, Kei, Saalfeld, Stephan, George, Reed, Meinertzhagen, Ian A., Rubin, Gerald M., Hess, Harald F., Jain, Viren, and Plaza, Stephen M.

Abstract

The neural circuits responsible for animal behavior remain largely unknown. We summarize new methods and present the circuitry of a large fraction of the brain of the fruit fly Drosophila melanogaster. Improved methods include new procedures to prepare, image, align, segment, find synapses in, and proofread such large data sets. We define cell types, refine computational compartments, and provide an exhaustive atlas of cell examples and types, many of them novel. We provide detailed circuits consisting of neurons and their chemical synapses for most of the central brain. We make the data public and simplify access, reducing the effort needed eLife digest Animal brains of all sizes, from the smallest to the largest, work in broadly similar ways. Studying the brain of any one animal in depth can thus reveal the general principles behind the workings of all brains. The fruit fly Drosophila is a popular choice for such research. With about 100,000 neurons - compared to some 86 billion in humans - the fly brain is small enough to study at the level of individual cells. But it nevertheless supports a range of complex behaviors, including navigation, courtship and learning. Thanks to decades of research, scientists now have a good understanding of which parts of the fruit fly brain support particular behaviors. But exactly how they do this is often unclear. This is because previous studies showing the connections between cells only covered small areas of the brain. This is like trying to understand a novel when all you can see is a few isolated paragraphs. To solve this problem, Scheffer, Xu, Januszewski, Lu, Takemura, Hayworth, Huang, Shinomiya et al. prepared the first complete map of the entire central region of the fruit fly brain. The central brain consists of approximately 25,000 neurons and around 20 million connections. To prepare the map - or connectome - the brain was cut into very thin 8nm slices and photographed with an electron microscope. A three-dimensional

Published
2020

28. Comparative efficacy of uncontrolled and controlled intermittent preventive treatment during pregnancy (IPTp) with combined use of LLTNs in high resistance area to sulfadoxine-pyrimethamine in Côte d’Ivoire

Author

Offianan,A Toure, Penali,Louis K, Coulibaly,MA, Tiacoh,NL, Ako,AAB, Adji,EG, Coulibaly ,B, Koffi,D, Sarr,D, Jambou,R, Kone,M, Offianan,A Toure, Penali,Louis K, Coulibaly,MA, Tiacoh,NL, Ako,AAB, Adji,EG, Coulibaly ,B, Koffi,D, Sarr,D, Jambou,R, and Kone,M

Abstract

A Toure Offianan1, Louis K Penali1, MA Coulibaly1, NL Tiacoh1, AAB Ako1, EG Adji1, B Coulibaly1, D Koffi1, D Sarr2, R Jambou3, M Kone41Department of Malariology, Institut Pasteur of Côte d’Ivoire, 2Department of Infectious Diseases, University of Georgia, Athens, GA, 3Department of Immunology, Institut Pasteur of Madagascar, Tananarive, Madagascar, 4UFR Sciences Pharmaceutiques et Biologiques, University of Cocody, Abidjan, Côte d’IvoireIntroduction: In recent years, intermittent preventive treatment for pregnancy (IPTp) with sulfadoxine-pyrimethamine (SP) has become policy in much of sub-Saharan Africa. But resistance to SP has been spreading across sub-Saharan Africa and thus the effectiveness of IPTp-SP has been questioned. The present study therefore sought to assess the incidence of placental malaria, low birth weight, and anemia of two IPTp-SP approaches (directly observed treatment scheme versus no directly observed treatment) in Anonkoua-Kouté and Samo, Côte d’Ivoire where the reported prevalence of dfr single mutant 108 was 62% and 52.2%, respectively.Methods: The study was a longitudinal design involving pregnant women and was conducted in Anonkoua-Kouté, a suburban area, and Samo, a rural area, from January 2008 through March 2009. Women of a pregnancy less than 28 weeks duration were randomized to receive SP (1.5 g/0.075 g SP) in a single intake twice and were followed up monthly until delivery. Doses were administered under supervision in the controlled IPTp group, while SP was given free to women in the uncontrolled IPTp group with a recommendation to take it at home. The primary end point was the proportion of low birth weight infants (body weight < 2500 g) and the secondary end point was the rate of severe anemia and placental malaria detected at delivery.Results: A total of 420 pregnant women were enrolled (212 and 208, respectively, in the controlled and uncont

Published
2012

29. Impending anterior ischemic optic neuropathy with elements of retinal vein occlusion in a patient on interferon for polycythemia vera

Author

Rue,Kelly S, Hirsch,Louis K, Sadun,Alfredo A, Rue,Kelly S, Hirsch,Louis K, and Sadun,Alfredo A

Abstract

Kelly S Rue, Louis K Hirsch, Alfredo A SadunDepartment of Neuro-Ophthalmology, Doheny Eye Institute and Keck School of Medicine, University of Southern California, Los Angeles, CA, USAAbstract: We describe the course and likely pathophysiology of impending anterior ischemic optic neuropathy (AION) and retinal vein occlusion in a 56-year-old man with polycythemia vera managed with interferon alpha for 2 years. Our patient presented with decreased vision, scintillating scotomata, and floaters. Fundus examination findings and results of a fluorescein angiogram led to the diagnosis of impending AION and retinal vein occlusion. Considering that both polycythemia vera and interferon have possible influences on vascular occlusion and optic disc edema, we stopped interferon treatment and immediately attempted to treat the polycythemia vera empirically with pentoxifylline and any interferon-associated inflammation with prednisone. Our patient experienced complete resolution of fundus abnormalities and return of normal vision within 3 weeks, which may be attributed to our successful treatment of both etiologies. Thus, further study is warranted to elucidate the treatment of both polycythemia vera and interferon-induced impending AION.Keywords: optic disc edema, interferon alpha, vascular occlusion, Roth spot, autoantibody, pentoxifylline

Published
2012

30. Assessment of the efficacy of first-line antimalarial drugs after 5 years of deployment by the National Malaria Control Programme in Côte d'Ivoire

Author

Offianan,Andre T, Assi,Serge B, Coulibaly,Aristide MA, N'guessan,Landry T, Ako,Aristide A, Kadjo,Florence K, San,Moïse K, Penali,Louis K, Offianan,Andre T, Assi,Serge B, Coulibaly,Aristide MA, N'guessan,Landry T, Ako,Aristide A, Kadjo,Florence K, San,Moïse K, and Penali,Louis K

Abstract

Andre T Offianan1, Serge B Assi2, Aristide MA Coulibaly1, Landry T N'guessan1, Aristide A Ako1, Florence K Kadjo2, Moïse K San2, Louis K Penali2 1Malariology Department, Institut Pasteur de Côte d'Ivoire, Abidjan, Côte d'Ivoire; 2National Malaria Control Programme, Abidjan, Côte d'Ivoire Background: The emergence of artemisinin resistance has raised concerns that the most potent antimalarial drug may be under threat. Artesunate + amodiaquine (ASAQ) and artemether-lumefantrine (AL) are respectively the first- and second-line treatments for uncomplicated falciparum malaria in Côte d'Ivoire. A comparison of the efficacy and safety of these two drug combinations was necessary to make evidence-based drug treatment policies. Methods: In an open-label, non inferiority, randomized, controlled clinical trial, children aged 6–59 months were randomized to receive ASAQ or AL. Both drug regimens were given for 3 days, and follow-up was for 28 days. The primary endpoint was the 28-day cure rates and was defined as proportion of patients with polymerase chain reaction (PCR)-corrected cure rate after 28 days of follow-up. Findings: A total of 251 patients who were attending the Ayame and Dabakala hospitals and presenting with symptomatic acute uncomplicated falciparum malaria were randomized to receive ASAQ (128) and AL (123). The intention-to-treat analysis showed effectiveness rates of 94.5% and 93.5% for ASAQ and AL, respectively on day 28. After adjustment for PCR results, these rates were 96.1% and 96.8%, respectively. On day 28, the per-protocol analysis showed effectiveness rates of 98.4% and 96.6% for ASAQ and AL, respectively. After adjustment by PCR for reinfection, these rates were 100% for each drug, and both regimens were well tolerated. Conclusion: ASAQ and AL remain efficacious treatments of uncomplicated falciparum malaria in Ivorian children 5 years after adoption. Th

Published
2011

31. Current and future approaches in the prevention and treatment of diabetic retinopathy

Author

Chang,Louis K, Sarraf,David, Chang,Louis K, and Sarraf,David

Abstract

Louis K Chang1, David Sarraf1,21Jules Stein Eye Institute, Department of Ophthalmology, University of California, Los Angeles, Los Angeles, CA, USA; 2Department of Ophthalmology, Greater LA VA Healthcare Center, Los Angeles, CAAbstract: Diabetic retinopathy (DR) is a major cause of blindness worldwide and is the number one cause of blindness in working-age individuals in developed countries. We review the current literature and discuss the pathogenesis, modifying risk factors, genetics, and treatment of DR. Special focus is placed on the rationale and effectiveness of therapeutic modalities, both current and future.

Published
2008

32. Systemic over-release of interleukin-17 in acute kidney injury after septic shock: Clinical and experimental evidence

Author

Maravitsa, P., Adamopoulou, M., Pistiki, A., Netea, M.G., Louis, K., Giamarellos-Bourboulis, E.J., Maravitsa, P., Adamopoulou, M., Pistiki, A., Netea, M.G., Louis, K., and Giamarellos-Bourboulis, E.J.

Abstract

Item does not contain fulltext, In order to investigate the role of T-helper 17 (Th17) cell activation in acute kidney injury (AKI) after septic shock, a two-stage approach was used. Firstly, peripheral blood mononuclear cells (PBMCs) and CD4-lymphocytes were isolated the first 24h after septic shock from 26 patients with AKI and 18 patients with chronic renal disease (CRD) without AKI and stimulated for the release of tumour necrosis factor-alpha (TNFalpha), interleukin (IL)-10, IL-17, IL-22 and interferon-gamma (IFNgamma). Results were compared with 15 healthy volunteers and 13 patients with uncomplicated sepsis. Secondly, a murine model of multiple organ dysfunction (MODS) complicated with AKI and bacterial gut translocation was studied, and IL-10, IL-17, IL-22 and IFNgamma were measured in kidney homogenates. IL-17 was the only cytokine produced at greater quantities from PBMCs and CD4-lymphocytes of patients with septic shock and AKI than comparators. When PBMCs of patients with septic shock and AKI were ex-vivo stimulated, intracellular staining for IL-17 was greater in CD3(+)/CD4(+)/CD196(+) cells compared to patients with septic shock and CRD. IL-17 was released at greater amounts from PBMCs of non-survivors by septic shock and AKI but not of septic shock and CRD. In the murine model of MODS, a gradual decrease of IL-17, but not of IL-10, IL-22 and IFNgamma, of kidney homogenates was found indicating over-consumption. These results suggest that AKI after septic shock is driven through IL-17 release by Th17 cells; this is gradually consumed in the kidney.

Published
2016

33. Systemic over-release of interleukin-17 in acute kidney injury after septic shock: Clinical and experimental evidence

Author

Maravitsa, P., Adamopoulou, M., Pistiki, A., Netea, M.G., Louis, K., Giamarellos-Bourboulis, E.J., Maravitsa, P., Adamopoulou, M., Pistiki, A., Netea, M.G., Louis, K., and Giamarellos-Bourboulis, E.J.

Abstract

Item does not contain fulltext, In order to investigate the role of T-helper 17 (Th17) cell activation in acute kidney injury (AKI) after septic shock, a two-stage approach was used. Firstly, peripheral blood mononuclear cells (PBMCs) and CD4-lymphocytes were isolated the first 24h after septic shock from 26 patients with AKI and 18 patients with chronic renal disease (CRD) without AKI and stimulated for the release of tumour necrosis factor-alpha (TNFalpha), interleukin (IL)-10, IL-17, IL-22 and interferon-gamma (IFNgamma). Results were compared with 15 healthy volunteers and 13 patients with uncomplicated sepsis. Secondly, a murine model of multiple organ dysfunction (MODS) complicated with AKI and bacterial gut translocation was studied, and IL-10, IL-17, IL-22 and IFNgamma were measured in kidney homogenates. IL-17 was the only cytokine produced at greater quantities from PBMCs and CD4-lymphocytes of patients with septic shock and AKI than comparators. When PBMCs of patients with septic shock and AKI were ex-vivo stimulated, intracellular staining for IL-17 was greater in CD3(+)/CD4(+)/CD196(+) cells compared to patients with septic shock and CRD. IL-17 was released at greater amounts from PBMCs of non-survivors by septic shock and AKI but not of septic shock and CRD. In the murine model of MODS, a gradual decrease of IL-17, but not of IL-10, IL-22 and IFNgamma, of kidney homogenates was found indicating over-consumption. These results suggest that AKI after septic shock is driven through IL-17 release by Th17 cells; this is gradually consumed in the kidney.

Published
2016

34. Systemic over-release of interleukin-17 in acute kidney injury after septic shock: Clinical and experimental evidence

Author

Maravitsa, P., Adamopoulou, M., Pistiki, A., Netea, M.G., Louis, K., Giamarellos-Bourboulis, E.J., Maravitsa, P., Adamopoulou, M., Pistiki, A., Netea, M.G., Louis, K., and Giamarellos-Bourboulis, E.J.

Abstract

Item does not contain fulltext, In order to investigate the role of T-helper 17 (Th17) cell activation in acute kidney injury (AKI) after septic shock, a two-stage approach was used. Firstly, peripheral blood mononuclear cells (PBMCs) and CD4-lymphocytes were isolated the first 24h after septic shock from 26 patients with AKI and 18 patients with chronic renal disease (CRD) without AKI and stimulated for the release of tumour necrosis factor-alpha (TNFalpha), interleukin (IL)-10, IL-17, IL-22 and interferon-gamma (IFNgamma). Results were compared with 15 healthy volunteers and 13 patients with uncomplicated sepsis. Secondly, a murine model of multiple organ dysfunction (MODS) complicated with AKI and bacterial gut translocation was studied, and IL-10, IL-17, IL-22 and IFNgamma were measured in kidney homogenates. IL-17 was the only cytokine produced at greater quantities from PBMCs and CD4-lymphocytes of patients with septic shock and AKI than comparators. When PBMCs of patients with septic shock and AKI were ex-vivo stimulated, intracellular staining for IL-17 was greater in CD3(+)/CD4(+)/CD196(+) cells compared to patients with septic shock and CRD. IL-17 was released at greater amounts from PBMCs of non-survivors by septic shock and AKI but not of septic shock and CRD. In the murine model of MODS, a gradual decrease of IL-17, but not of IL-10, IL-22 and IFNgamma, of kidney homogenates was found indicating over-consumption. These results suggest that AKI after septic shock is driven through IL-17 release by Th17 cells; this is gradually consumed in the kidney.

Published
2016

35. Systemic over-release of interleukin-17 in acute kidney injury after septic shock: Clinical and experimental evidence

Author

Maravitsa, P., Adamopoulou, M., Pistiki, A., Netea, M.G., Louis, K., Giamarellos-Bourboulis, E.J., Maravitsa, P., Adamopoulou, M., Pistiki, A., Netea, M.G., Louis, K., and Giamarellos-Bourboulis, E.J.

Abstract

Item does not contain fulltext, In order to investigate the role of T-helper 17 (Th17) cell activation in acute kidney injury (AKI) after septic shock, a two-stage approach was used. Firstly, peripheral blood mononuclear cells (PBMCs) and CD4-lymphocytes were isolated the first 24h after septic shock from 26 patients with AKI and 18 patients with chronic renal disease (CRD) without AKI and stimulated for the release of tumour necrosis factor-alpha (TNFalpha), interleukin (IL)-10, IL-17, IL-22 and interferon-gamma (IFNgamma). Results were compared with 15 healthy volunteers and 13 patients with uncomplicated sepsis. Secondly, a murine model of multiple organ dysfunction (MODS) complicated with AKI and bacterial gut translocation was studied, and IL-10, IL-17, IL-22 and IFNgamma were measured in kidney homogenates. IL-17 was the only cytokine produced at greater quantities from PBMCs and CD4-lymphocytes of patients with septic shock and AKI than comparators. When PBMCs of patients with septic shock and AKI were ex-vivo stimulated, intracellular staining for IL-17 was greater in CD3(+)/CD4(+)/CD196(+) cells compared to patients with septic shock and CRD. IL-17 was released at greater amounts from PBMCs of non-survivors by septic shock and AKI but not of septic shock and CRD. In the murine model of MODS, a gradual decrease of IL-17, but not of IL-10, IL-22 and IFNgamma, of kidney homogenates was found indicating over-consumption. These results suggest that AKI after septic shock is driven through IL-17 release by Th17 cells; this is gradually consumed in the kidney.

Published
2016

36. Fully-Automatic Synapse Prediction and Validation on a Large Data Set

Author

Huang, Gary B., Scheffer, Louis K., Plaza, Stephen M., Huang, Gary B., Scheffer, Louis K., and Plaza, Stephen M.

Abstract

Extracting a connectome from an electron microscopy (EM) data set requires identification of neurons and determination of synapses between neurons. As manual extraction of this information is very time-consuming, there has been extensive research effort to automatically segment the neurons to help guide and eventually replace manual tracing. Until recently, there has been comparatively less research on automatically detecting the actual synapses between neurons. This discrepancy can, in part, be attributed to several factors: obtaining neuronal shapes is a prerequisite first step in extracting a connectome, manual tracing is much more time-consuming than annotating synapses, and neuronal contact area can be used as a proxy for synapses in determining connections. However, recent research has demonstrated that contact area alone is not a sufficient predictor of synaptic connection. Moreover, as segmentation has improved, we have observed that synapse annotation is consuming a more significant fraction of overall reconstruction time. This ratio will only get worse as segmentation improves, gating overall possible speed-up. Therefore, we address this problem by developing algorithms that automatically detect pre-synaptic neurons and their post-synaptic partners. In particular, pre-synaptic structures are detected using a Deep and Wide Multiscale Recursive Network, and post-synaptic partners are detected using a MLP with features conditioned on the local segmentation. This work is novel because it requires minimal amount of training, leverages advances in image segmentation directly, and provides a complete solution for polyadic synapse detection. We further introduce novel metrics to evaluate our algorithm on connectomes of meaningful size. These metrics demonstrate that complete automatic prediction can be used to effectively characterize most connectivity correctly.

Published
2016

37. The effect of dosing strategies on the therapeutic efficacy of artesunate-amodiaquine for uncomplicated malaria : a meta-analysis of individual patient data

Author

Adjuik, Martin A., Allan, Richard, Anvikar, Anupkumar R., Ashley, Elizabeth A., Ba, Mamadou S., Barennes, Hubert, Barnes, Karen I., Bassat, Quique, Baudin, Elisabeth, Bjorkman, Anders, Bompart, Francois, Bonnet, Maryline, Borrmann, Steffen, Brasseur, Philippe, Bukirwa, Hasifa, Checchi, Francesco, Cot, Michel, Dahal, Prabin, D'Alessandro, Umberto, Deloron, Philippe, Desai, Meghna, Diap, Graciela, Djimde, Abdoulaye A., Dorsey, Grant, Doumbo, Ogobara K., Espie, Emmanuelle, Etard, Jean-Francois, Fanello, Caterina I., Faucher, Jean-Francois, Faye, Babacar, Flegg, Jennifer A., Gaye, Oumar, Gething, Peter W., Gonzalez, Raquel, Grandesso, Francesco, Guerin, Philippe J., Guthmann, Jean-Paul, Hamour, Sally, Hasugian, Armedy Ronny, Hay, Simon I., Humphreys, Georgina S., Jullien, Vincent, Juma, Elizabeth, Kamya, Moses R., Karema, Corine, Kiechel, Jean R., Kremsner, Peter G., Krishna, Sanjeev, Lameyre, Valerie, Ibrahim, Laminou M., Lee, Sue J., Lell, Bertrand, Martensson, Andreas, Massougbodji, Achille, Menan, Herve, Menard, Didier, Menendez, Clara, Meremikwu, Martin, Moreira, Clarissa, Nabasumba, Carolyn, Nambozi, Michael, Ndiaye, Jean-Louis, Nikiema, Frederic, Nsanzabana, Christian, Ntoumi, Francine, Ogutu, Bernhards R., Olliaro, Piero, Osorio, Lyda, Ouedraogo, Jean-Bosco, Penali, Louis K., Pene, Mbaye, Pinoges, Loretxu, Piola, Patrice, Price, Ric N., Roper, Cally, Rosenthal, Philip J., Rwagacondo, Claude Emile, Same-Ekobo, Albert, Schramm, Birgit, Seck, Amadou, Sharma, Bhawna, Sibley, Carol Hopkins, Sinou, Veronique, Sirima, Sodiomon B., Smith, Jeffery J., Smithuis, Frank, Some, Fabrice A., Sow, Doudou, Staedke, Sarah G., Stepniewska, Kasia, Swarthout, Todd D., Sylla, Khadime, Talisuna, Ambrose O., Tarning, Joel, Taylor, Walter R. J., Temu, Emmanuel A., Thwing, Julie I., Tjitra, Emiliana, Tine, Roger C. K., Tinto, Halidou, Vaillant, Michel T., Valecha, Neena, Van den Broek, Ingrid, White, Nicholas J., Yeka, Adoke, Zongo, Issaka, Adjuik, Martin A., Allan, Richard, Anvikar, Anupkumar R., Ashley, Elizabeth A., Ba, Mamadou S., Barennes, Hubert, Barnes, Karen I., Bassat, Quique, Baudin, Elisabeth, Bjorkman, Anders, Bompart, Francois, Bonnet, Maryline, Borrmann, Steffen, Brasseur, Philippe, Bukirwa, Hasifa, Checchi, Francesco, Cot, Michel, Dahal, Prabin, D'Alessandro, Umberto, Deloron, Philippe, Desai, Meghna, Diap, Graciela, Djimde, Abdoulaye A., Dorsey, Grant, Doumbo, Ogobara K., Espie, Emmanuelle, Etard, Jean-Francois, Fanello, Caterina I., Faucher, Jean-Francois, Faye, Babacar, Flegg, Jennifer A., Gaye, Oumar, Gething, Peter W., Gonzalez, Raquel, Grandesso, Francesco, Guerin, Philippe J., Guthmann, Jean-Paul, Hamour, Sally, Hasugian, Armedy Ronny, Hay, Simon I., Humphreys, Georgina S., Jullien, Vincent, Juma, Elizabeth, Kamya, Moses R., Karema, Corine, Kiechel, Jean R., Kremsner, Peter G., Krishna, Sanjeev, Lameyre, Valerie, Ibrahim, Laminou M., Lee, Sue J., Lell, Bertrand, Martensson, Andreas, Massougbodji, Achille, Menan, Herve, Menard, Didier, Menendez, Clara, Meremikwu, Martin, Moreira, Clarissa, Nabasumba, Carolyn, Nambozi, Michael, Ndiaye, Jean-Louis, Nikiema, Frederic, Nsanzabana, Christian, Ntoumi, Francine, Ogutu, Bernhards R., Olliaro, Piero, Osorio, Lyda, Ouedraogo, Jean-Bosco, Penali, Louis K., Pene, Mbaye, Pinoges, Loretxu, Piola, Patrice, Price, Ric N., Roper, Cally, Rosenthal, Philip J., Rwagacondo, Claude Emile, Same-Ekobo, Albert, Schramm, Birgit, Seck, Amadou, Sharma, Bhawna, Sibley, Carol Hopkins, Sinou, Veronique, Sirima, Sodiomon B., Smith, Jeffery J., Smithuis, Frank, Some, Fabrice A., Sow, Doudou, Staedke, Sarah G., Stepniewska, Kasia, Swarthout, Todd D., Sylla, Khadime, Talisuna, Ambrose O., Tarning, Joel, Taylor, Walter R. J., Temu, Emmanuel A., Thwing, Julie I., Tjitra, Emiliana, Tine, Roger C. K., Tinto, Halidou, Vaillant, Michel T., Valecha, Neena, Van den Broek, Ingrid, White, Nicholas J., Yeka, Adoke, and Zongo, Issaka

Abstract

Background: Artesunate-amodiaquine (AS-AQ) is one of the most widely used artemisinin-based combination therapies (ACTs) to treat uncomplicated Plasmodium falciparum malaria in Africa. We investigated the impact of different dosing strategies on the efficacy of this combination for the treatment of falciparum malaria. Methods: Individual patient data from AS-AQ clinical trials were pooled using the WorldWide Antimalarial Resistance Network (WWARN) standardised methodology. Risk factors for treatment failure were identified using a Cox regression model with shared frailty across study sites. Results: Forty-three studies representing 9,106 treatments from 1999-2012 were included in the analysis; 4,138 (45.4%) treatments were with a fixed dose combination with an AQ target dose of 30 mg/kg (FDC), 1,293 (14.2%) with a non-fixed dose combination with an AQ target dose of 25 mg/kg (loose NFDC-25), 2,418 (26.6%) with a non-fixed dose combination with an AQ target dose of 30 mg/kg (loose NFDC-30), and the remaining 1,257 (13.8%) with a co-blistered non-fixed dose combination with an AQ target dose of 30 mg/kg (co-blistered NFDC). The median dose of AQ administered was 32.1 mg/kg [IQR: 25.9-38.2], the highest dose being administered to patients treated with co-blistered NFDC (median = 35.3 mg/kg [IQR: 30.6-43.7]) and the lowest to those treated with loose NFDC-25 (median = 25.0 mg/kg [IQR: 22.7-25.0]). Patients treated with FDC received a median dose of 32.4 mg/kg [IQR: 27-39.0]. After adjusting for reinfections, the corrected antimalarial efficacy on day 28 after treatment was similar for co-blistered NFDC (97.9% [95% confidence interval (CI): 97.0-98.8%]) and FDC (98.1% [95% CI: 97.6%-98.5%]; P = 0.799), but significantly lower for the loose NFDC-25 (93.4% [95% CI: 91.9%-94.9%]), and loose NFDC-30 (95.0% [95% CI: 94.1%-95.9%]) (P < 0.001 for all comparisons). After controlling for age, AQ dose, baseline parasitemia and region; treatment with loose NFDC-25 was associated

Published
2015
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38. Clinical determinants of early parasitological response to ACTs in African patients with uncomplicated falciparum malaria : a literature review and meta-analysis of individual patient data

Author

Abdulla, Salim, Adam, Ishag, Adjei, George O., Adjuik, Martin A., Alemayehu, Bereket, Allan, Richard, Arinaitwe, Emmanuel, Ashley, Elizabeth A., Ba, Mamadou S., Barennes, Hubert, Barnes, Karen I., Bassat, Quique, Baudin, Elisabeth, Berens-Riha, Nicole, Bjoerkman, Anders, Bompart, Francois, Bonnet, Maryline, Borrmann, Steffen, Bousema, Teun, Brasseur, Philippe, Bukirwa, Hasifa, Checchi, Francesco, Dahal, Prabin, D'Alessandro, Umberto, Desai, Meghna, Dicko, Alassane, Djimde, Abdoulaye A., Dorsey, Grant, Doumbo, Ogobara K., Drakeley, Chris J., Duparc, Stephan, Eshetu, Teferi, Espie, Emmanuelle, Etard, Jean-Francois, Faiz, Abul M., Falade, Catherine O., Fanello, Caterina I., Faucher, Jean-Francois, Faye, Babacar, Faye, Oumar, Filler, Scott, Flegg, Jennifer A., Fofana, Bakary, Fogg, Carole, Gadalla, Nahla B., Gaye, Oumar, Genton, Blaise, Gething, Peter W., Gil, Jose P., Gonzalez, Raquel, Grandesso, Francesco, Greenhouse, Bryan, Greenwood, Brian, Grivoyannis, Anastasia, Guerin, Philippe J., Guthmann, Jean-Paul, Hamed, Kamal, Hamour, Sally, Hay, Simon I., Hodel, Eva Maria, Humphreys, Georgina S., Hwang, Jimee, Ibrahim, Maman L., Jima, Daddi, Jones, Joel J., Jullien, Vincent, Juma, Elizabeth, Kachur, Patrick S., Kager, Piet A., Kamugisha, Erasmus, Kamya, Moses R., Karema, Corine, Kayentao, Kassoum, Kiechel, Jean-Rene, Kironde, Fred, Kofoed, Poul-Erik, Kremsner, Peter G., Krishna, Sanjeev, Lameyre, Valerie, Lell, Bertrand, Lima, Angeles, Makanga, Michael, Malik, ElFatih M., Marsh, Kevin, Mårtensson, Andreas, Massougbodji, Achille, Menan, Herve, Menard, Didier, Menendez, Clara, Mens, Petra F., Meremikwu, Martin, Moreira, Clarissa, Nabasumba, Carolyn, Nambozi, Michael, Ndiaye, Jean-Louis, Ngasala, Billy E., Nikiema, Frederic, Nsanzabana, Christian, Ntoumi, Francine, Oguike, Mary, Ogutu, Bernhards R., Olliaro, Piero, Omar, Sabah A., Ouedraogo, Jean-Bosco, Owusu-Agyei, Seth, Penali, Louis K., Pene, Mbaye, Peshu, Judy, Piola, Patrice, Plowe, Christopher V., Premji, Zul, Price, Ric N., Randrianarivelojosia, Milijaona, Rombo, Lars, Roper, Cally, Rosenthal, Philip J., Sagara, Issaka, Same-Ekobo, Albert, Sawa, Patrick, Schallig, Henk D. F. H., Schramm, Birgit, Seck, Amadou, Shekalaghe, Seif A., Sibley, Carol H., Sinou, Vronique, Sirima, Sodiomon B., Som, Fabrice A., Sow, Doudou, Staedke, Sarah G., Stepniewska, Kasia, Sutherland, Colin J., Swarthout, Todd D., Sylla, Khadime, Talisuna, Ambrose O., Taylor, Walter R. J., Temu, Emmanuel A., Thwing, Julie I., Tine, Roger C. K., Tinto, Halidou, Tommasini, Silva, Toure, Offianan A., Ursing, Johan, Vaillant, Michel T., Valentini, Giovanni, Van den Broek, Ingrid, Van Vugt, Michele, Ward, Stephen A., Winstanley, Peter A., Yavo, William, Yeka, Adoke, Zolia, Yah M., Zongo, Issaka, Abdulla, Salim, Adam, Ishag, Adjei, George O., Adjuik, Martin A., Alemayehu, Bereket, Allan, Richard, Arinaitwe, Emmanuel, Ashley, Elizabeth A., Ba, Mamadou S., Barennes, Hubert, Barnes, Karen I., Bassat, Quique, Baudin, Elisabeth, Berens-Riha, Nicole, Bjoerkman, Anders, Bompart, Francois, Bonnet, Maryline, Borrmann, Steffen, Bousema, Teun, Brasseur, Philippe, Bukirwa, Hasifa, Checchi, Francesco, Dahal, Prabin, D'Alessandro, Umberto, Desai, Meghna, Dicko, Alassane, Djimde, Abdoulaye A., Dorsey, Grant, Doumbo, Ogobara K., Drakeley, Chris J., Duparc, Stephan, Eshetu, Teferi, Espie, Emmanuelle, Etard, Jean-Francois, Faiz, Abul M., Falade, Catherine O., Fanello, Caterina I., Faucher, Jean-Francois, Faye, Babacar, Faye, Oumar, Filler, Scott, Flegg, Jennifer A., Fofana, Bakary, Fogg, Carole, Gadalla, Nahla B., Gaye, Oumar, Genton, Blaise, Gething, Peter W., Gil, Jose P., Gonzalez, Raquel, Grandesso, Francesco, Greenhouse, Bryan, Greenwood, Brian, Grivoyannis, Anastasia, Guerin, Philippe J., Guthmann, Jean-Paul, Hamed, Kamal, Hamour, Sally, Hay, Simon I., Hodel, Eva Maria, Humphreys, Georgina S., Hwang, Jimee, Ibrahim, Maman L., Jima, Daddi, Jones, Joel J., Jullien, Vincent, Juma, Elizabeth, Kachur, Patrick S., Kager, Piet A., Kamugisha, Erasmus, Kamya, Moses R., Karema, Corine, Kayentao, Kassoum, Kiechel, Jean-Rene, Kironde, Fred, Kofoed, Poul-Erik, Kremsner, Peter G., Krishna, Sanjeev, Lameyre, Valerie, Lell, Bertrand, Lima, Angeles, Makanga, Michael, Malik, ElFatih M., Marsh, Kevin, Mårtensson, Andreas, Massougbodji, Achille, Menan, Herve, Menard, Didier, Menendez, Clara, Mens, Petra F., Meremikwu, Martin, Moreira, Clarissa, Nabasumba, Carolyn, Nambozi, Michael, Ndiaye, Jean-Louis, Ngasala, Billy E., Nikiema, Frederic, Nsanzabana, Christian, Ntoumi, Francine, Oguike, Mary, Ogutu, Bernhards R., Olliaro, Piero, Omar, Sabah A., Ouedraogo, Jean-Bosco, Owusu-Agyei, Seth, Penali, Louis K., Pene, Mbaye, Peshu, Judy, Piola, Patrice, Plowe, Christopher V., Premji, Zul, Price, Ric N., Randrianarivelojosia, Milijaona, Rombo, Lars, Roper, Cally, Rosenthal, Philip J., Sagara, Issaka, Same-Ekobo, Albert, Sawa, Patrick, Schallig, Henk D. F. H., Schramm, Birgit, Seck, Amadou, Shekalaghe, Seif A., Sibley, Carol H., Sinou, Vronique, Sirima, Sodiomon B., Som, Fabrice A., Sow, Doudou, Staedke, Sarah G., Stepniewska, Kasia, Sutherland, Colin J., Swarthout, Todd D., Sylla, Khadime, Talisuna, Ambrose O., Taylor, Walter R. J., Temu, Emmanuel A., Thwing, Julie I., Tine, Roger C. K., Tinto, Halidou, Tommasini, Silva, Toure, Offianan A., Ursing, Johan, Vaillant, Michel T., Valentini, Giovanni, Van den Broek, Ingrid, Van Vugt, Michele, Ward, Stephen A., Winstanley, Peter A., Yavo, William, Yeka, Adoke, Zolia, Yah M., and Zongo, Issaka

Abstract

Background: Artemisinin-resistant Plasmodium falciparum has emerged in the Greater Mekong sub-region and poses a major global public health threat. Slow parasite clearance is a key clinical manifestation of reduced susceptibility to artemisinin. This study was designed to establish the baseline values for clearance in patients from Sub-Saharan African countries with uncomplicated malaria treated with artemisinin-based combination therapies (ACTs). Methods: A literature review in PubMed was conducted in March 2013 to identify all prospective clinical trials (uncontrolled trials, controlled trials and randomized controlled trials), including ACTs conducted in Sub-Saharan Africa, between 1960 and 2012. Individual patient data from these studies were shared with the WorldWide Antimalarial Resistance Network (WWARN) and pooled using an a priori statistical analytical plan. Factors affecting early parasitological response were investigated using logistic regression with study sites fitted as a random effect. The risk of bias in included studies was evaluated based on study design, methodology and missing data. Results: In total, 29,493 patients from 84 clinical trials were included in the analysis, treated with artemether-lumefantrine (n = 13,664), artesunate-amodiaquine (n = 11,337) and dihydroartemisinin-piperaquine (n = 4,492). The overall parasite clearance rate was rapid. The parasite positivity rate (PPR) decreased from 59.7 % (95 % CI: 54.5-64.9) on day 1 to 6.7 % (95 % CI: 4.8-8.7) on day 2 and 0.9 % (95 % CI: 0.5-1.2) on day 3. The 95th percentile of observed day 3 PPR was 5.3 %. Independent risk factors predictive of day 3 positivity were: high baseline parasitaemia (adjusted odds ratio (AOR) = 1.16 (95 % CI: 1.08-1.25); per 2-fold increase in parasite density, P <0.001); fever (>37.5 degrees C) (AOR = 1.50 (95 % CI: 1.06-2.13), P = 0.022); severe anaemia (AOR = 2.04 (95 % CI: 1.21-3.44), P = 0.008); areas of low/moderate transmission setting (AOR = 2.71 (

Published
2015
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39. The effect of dosing strategies on the therapeutic efficacy of artesunate-amodiaquine for uncomplicated malaria : a meta-analysis of individual patient data

Author

Adjuik, Martin A., Allan, Richard, Anvikar, Anupkumar R., Ashley, Elizabeth A., Ba, Mamadou S., Barennes, Hubert, Barnes, Karen I., Bassat, Quique, Baudin, Elisabeth, Bjorkman, Anders, Bompart, Francois, Bonnet, Maryline, Borrmann, Steffen, Brasseur, Philippe, Bukirwa, Hasifa, Checchi, Francesco, Cot, Michel, Dahal, Prabin, D'Alessandro, Umberto, Deloron, Philippe, Desai, Meghna, Diap, Graciela, Djimde, Abdoulaye A., Dorsey, Grant, Doumbo, Ogobara K., Espie, Emmanuelle, Etard, Jean-Francois, Fanello, Caterina I., Faucher, Jean-Francois, Faye, Babacar, Flegg, Jennifer A., Gaye, Oumar, Gething, Peter W., Gonzalez, Raquel, Grandesso, Francesco, Guerin, Philippe J., Guthmann, Jean-Paul, Hamour, Sally, Hasugian, Armedy Ronny, Hay, Simon I., Humphreys, Georgina S., Jullien, Vincent, Juma, Elizabeth, Kamya, Moses R., Karema, Corine, Kiechel, Jean R., Kremsner, Peter G., Krishna, Sanjeev, Lameyre, Valerie, Ibrahim, Laminou M., Lee, Sue J., Lell, Bertrand, Martensson, Andreas, Massougbodji, Achille, Menan, Herve, Menard, Didier, Menendez, Clara, Meremikwu, Martin, Moreira, Clarissa, Nabasumba, Carolyn, Nambozi, Michael, Ndiaye, Jean-Louis, Nikiema, Frederic, Nsanzabana, Christian, Ntoumi, Francine, Ogutu, Bernhards R., Olliaro, Piero, Osorio, Lyda, Ouedraogo, Jean-Bosco, Penali, Louis K., Pene, Mbaye, Pinoges, Loretxu, Piola, Patrice, Price, Ric N., Roper, Cally, Rosenthal, Philip J., Rwagacondo, Claude Emile, Same-Ekobo, Albert, Schramm, Birgit, Seck, Amadou, Sharma, Bhawna, Sibley, Carol Hopkins, Sinou, Veronique, Sirima, Sodiomon B., Smith, Jeffery J., Smithuis, Frank, Some, Fabrice A., Sow, Doudou, Staedke, Sarah G., Stepniewska, Kasia, Swarthout, Todd D., Sylla, Khadime, Talisuna, Ambrose O., Tarning, Joel, Taylor, Walter R. J., Temu, Emmanuel A., Thwing, Julie I., Tjitra, Emiliana, Tine, Roger C. K., Tinto, Halidou, Vaillant, Michel T., Valecha, Neena, Van den Broek, Ingrid, White, Nicholas J., Yeka, Adoke, Zongo, Issaka, Adjuik, Martin A., Allan, Richard, Anvikar, Anupkumar R., Ashley, Elizabeth A., Ba, Mamadou S., Barennes, Hubert, Barnes, Karen I., Bassat, Quique, Baudin, Elisabeth, Bjorkman, Anders, Bompart, Francois, Bonnet, Maryline, Borrmann, Steffen, Brasseur, Philippe, Bukirwa, Hasifa, Checchi, Francesco, Cot, Michel, Dahal, Prabin, D'Alessandro, Umberto, Deloron, Philippe, Desai, Meghna, Diap, Graciela, Djimde, Abdoulaye A., Dorsey, Grant, Doumbo, Ogobara K., Espie, Emmanuelle, Etard, Jean-Francois, Fanello, Caterina I., Faucher, Jean-Francois, Faye, Babacar, Flegg, Jennifer A., Gaye, Oumar, Gething, Peter W., Gonzalez, Raquel, Grandesso, Francesco, Guerin, Philippe J., Guthmann, Jean-Paul, Hamour, Sally, Hasugian, Armedy Ronny, Hay, Simon I., Humphreys, Georgina S., Jullien, Vincent, Juma, Elizabeth, Kamya, Moses R., Karema, Corine, Kiechel, Jean R., Kremsner, Peter G., Krishna, Sanjeev, Lameyre, Valerie, Ibrahim, Laminou M., Lee, Sue J., Lell, Bertrand, Martensson, Andreas, Massougbodji, Achille, Menan, Herve, Menard, Didier, Menendez, Clara, Meremikwu, Martin, Moreira, Clarissa, Nabasumba, Carolyn, Nambozi, Michael, Ndiaye, Jean-Louis, Nikiema, Frederic, Nsanzabana, Christian, Ntoumi, Francine, Ogutu, Bernhards R., Olliaro, Piero, Osorio, Lyda, Ouedraogo, Jean-Bosco, Penali, Louis K., Pene, Mbaye, Pinoges, Loretxu, Piola, Patrice, Price, Ric N., Roper, Cally, Rosenthal, Philip J., Rwagacondo, Claude Emile, Same-Ekobo, Albert, Schramm, Birgit, Seck, Amadou, Sharma, Bhawna, Sibley, Carol Hopkins, Sinou, Veronique, Sirima, Sodiomon B., Smith, Jeffery J., Smithuis, Frank, Some, Fabrice A., Sow, Doudou, Staedke, Sarah G., Stepniewska, Kasia, Swarthout, Todd D., Sylla, Khadime, Talisuna, Ambrose O., Tarning, Joel, Taylor, Walter R. J., Temu, Emmanuel A., Thwing, Julie I., Tjitra, Emiliana, Tine, Roger C. K., Tinto, Halidou, Vaillant, Michel T., Valecha, Neena, Van den Broek, Ingrid, White, Nicholas J., Yeka, Adoke, and Zongo, Issaka

Abstract

Background: Artesunate-amodiaquine (AS-AQ) is one of the most widely used artemisinin-based combination therapies (ACTs) to treat uncomplicated Plasmodium falciparum malaria in Africa. We investigated the impact of different dosing strategies on the efficacy of this combination for the treatment of falciparum malaria. Methods: Individual patient data from AS-AQ clinical trials were pooled using the WorldWide Antimalarial Resistance Network (WWARN) standardised methodology. Risk factors for treatment failure were identified using a Cox regression model with shared frailty across study sites. Results: Forty-three studies representing 9,106 treatments from 1999-2012 were included in the analysis; 4,138 (45.4%) treatments were with a fixed dose combination with an AQ target dose of 30 mg/kg (FDC), 1,293 (14.2%) with a non-fixed dose combination with an AQ target dose of 25 mg/kg (loose NFDC-25), 2,418 (26.6%) with a non-fixed dose combination with an AQ target dose of 30 mg/kg (loose NFDC-30), and the remaining 1,257 (13.8%) with a co-blistered non-fixed dose combination with an AQ target dose of 30 mg/kg (co-blistered NFDC). The median dose of AQ administered was 32.1 mg/kg [IQR: 25.9-38.2], the highest dose being administered to patients treated with co-blistered NFDC (median = 35.3 mg/kg [IQR: 30.6-43.7]) and the lowest to those treated with loose NFDC-25 (median = 25.0 mg/kg [IQR: 22.7-25.0]). Patients treated with FDC received a median dose of 32.4 mg/kg [IQR: 27-39.0]. After adjusting for reinfections, the corrected antimalarial efficacy on day 28 after treatment was similar for co-blistered NFDC (97.9% [95% confidence interval (CI): 97.0-98.8%]) and FDC (98.1% [95% CI: 97.6%-98.5%]; P = 0.799), but significantly lower for the loose NFDC-25 (93.4% [95% CI: 91.9%-94.9%]), and loose NFDC-30 (95.0% [95% CI: 94.1%-95.9%]) (P < 0.001 for all comparisons). After controlling for age, AQ dose, baseline parasitemia and region; treatment with loose NFDC-25 was associated

Published
2015
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40. Clinical determinants of early parasitological response to ACTs in African patients with uncomplicated falciparum malaria : a literature review and meta-analysis of individual patient data

Author

Abdulla, Salim, Adam, Ishag, Adjei, George O., Adjuik, Martin A., Alemayehu, Bereket, Allan, Richard, Arinaitwe, Emmanuel, Ashley, Elizabeth A., Ba, Mamadou S., Barennes, Hubert, Barnes, Karen I., Bassat, Quique, Baudin, Elisabeth, Berens-Riha, Nicole, Bjoerkman, Anders, Bompart, Francois, Bonnet, Maryline, Borrmann, Steffen, Bousema, Teun, Brasseur, Philippe, Bukirwa, Hasifa, Checchi, Francesco, Dahal, Prabin, D'Alessandro, Umberto, Desai, Meghna, Dicko, Alassane, Djimde, Abdoulaye A., Dorsey, Grant, Doumbo, Ogobara K., Drakeley, Chris J., Duparc, Stephan, Eshetu, Teferi, Espie, Emmanuelle, Etard, Jean-Francois, Faiz, Abul M., Falade, Catherine O., Fanello, Caterina I., Faucher, Jean-Francois, Faye, Babacar, Faye, Oumar, Filler, Scott, Flegg, Jennifer A., Fofana, Bakary, Fogg, Carole, Gadalla, Nahla B., Gaye, Oumar, Genton, Blaise, Gething, Peter W., Gil, Jose P., Gonzalez, Raquel, Grandesso, Francesco, Greenhouse, Bryan, Greenwood, Brian, Grivoyannis, Anastasia, Guerin, Philippe J., Guthmann, Jean-Paul, Hamed, Kamal, Hamour, Sally, Hay, Simon I., Hodel, Eva Maria, Humphreys, Georgina S., Hwang, Jimee, Ibrahim, Maman L., Jima, Daddi, Jones, Joel J., Jullien, Vincent, Juma, Elizabeth, Kachur, Patrick S., Kager, Piet A., Kamugisha, Erasmus, Kamya, Moses R., Karema, Corine, Kayentao, Kassoum, Kiechel, Jean-Rene, Kironde, Fred, Kofoed, Poul-Erik, Kremsner, Peter G., Krishna, Sanjeev, Lameyre, Valerie, Lell, Bertrand, Lima, Angeles, Makanga, Michael, Malik, ElFatih M., Marsh, Kevin, Mårtensson, Andreas, Massougbodji, Achille, Menan, Herve, Menard, Didier, Menendez, Clara, Mens, Petra F., Meremikwu, Martin, Moreira, Clarissa, Nabasumba, Carolyn, Nambozi, Michael, Ndiaye, Jean-Louis, Ngasala, Billy E., Nikiema, Frederic, Nsanzabana, Christian, Ntoumi, Francine, Oguike, Mary, Ogutu, Bernhards R., Olliaro, Piero, Omar, Sabah A., Ouedraogo, Jean-Bosco, Owusu-Agyei, Seth, Penali, Louis K., Pene, Mbaye, Peshu, Judy, Piola, Patrice, Plowe, Christopher V., Premji, Zul, Price, Ric N., Randrianarivelojosia, Milijaona, Rombo, Lars, Roper, Cally, Rosenthal, Philip J., Sagara, Issaka, Same-Ekobo, Albert, Sawa, Patrick, Schallig, Henk D. F. H., Schramm, Birgit, Seck, Amadou, Shekalaghe, Seif A., Sibley, Carol H., Sinou, Vronique, Sirima, Sodiomon B., Som, Fabrice A., Sow, Doudou, Staedke, Sarah G., Stepniewska, Kasia, Sutherland, Colin J., Swarthout, Todd D., Sylla, Khadime, Talisuna, Ambrose O., Taylor, Walter R. J., Temu, Emmanuel A., Thwing, Julie I., Tine, Roger C. K., Tinto, Halidou, Tommasini, Silva, Toure, Offianan A., Ursing, Johan, Vaillant, Michel T., Valentini, Giovanni, Van den Broek, Ingrid, Van Vugt, Michele, Ward, Stephen A., Winstanley, Peter A., Yavo, William, Yeka, Adoke, Zolia, Yah M., Zongo, Issaka, Abdulla, Salim, Adam, Ishag, Adjei, George O., Adjuik, Martin A., Alemayehu, Bereket, Allan, Richard, Arinaitwe, Emmanuel, Ashley, Elizabeth A., Ba, Mamadou S., Barennes, Hubert, Barnes, Karen I., Bassat, Quique, Baudin, Elisabeth, Berens-Riha, Nicole, Bjoerkman, Anders, Bompart, Francois, Bonnet, Maryline, Borrmann, Steffen, Bousema, Teun, Brasseur, Philippe, Bukirwa, Hasifa, Checchi, Francesco, Dahal, Prabin, D'Alessandro, Umberto, Desai, Meghna, Dicko, Alassane, Djimde, Abdoulaye A., Dorsey, Grant, Doumbo, Ogobara K., Drakeley, Chris J., Duparc, Stephan, Eshetu, Teferi, Espie, Emmanuelle, Etard, Jean-Francois, Faiz, Abul M., Falade, Catherine O., Fanello, Caterina I., Faucher, Jean-Francois, Faye, Babacar, Faye, Oumar, Filler, Scott, Flegg, Jennifer A., Fofana, Bakary, Fogg, Carole, Gadalla, Nahla B., Gaye, Oumar, Genton, Blaise, Gething, Peter W., Gil, Jose P., Gonzalez, Raquel, Grandesso, Francesco, Greenhouse, Bryan, Greenwood, Brian, Grivoyannis, Anastasia, Guerin, Philippe J., Guthmann, Jean-Paul, Hamed, Kamal, Hamour, Sally, Hay, Simon I., Hodel, Eva Maria, Humphreys, Georgina S., Hwang, Jimee, Ibrahim, Maman L., Jima, Daddi, Jones, Joel J., Jullien, Vincent, Juma, Elizabeth, Kachur, Patrick S., Kager, Piet A., Kamugisha, Erasmus, Kamya, Moses R., Karema, Corine, Kayentao, Kassoum, Kiechel, Jean-Rene, Kironde, Fred, Kofoed, Poul-Erik, Kremsner, Peter G., Krishna, Sanjeev, Lameyre, Valerie, Lell, Bertrand, Lima, Angeles, Makanga, Michael, Malik, ElFatih M., Marsh, Kevin, Mårtensson, Andreas, Massougbodji, Achille, Menan, Herve, Menard, Didier, Menendez, Clara, Mens, Petra F., Meremikwu, Martin, Moreira, Clarissa, Nabasumba, Carolyn, Nambozi, Michael, Ndiaye, Jean-Louis, Ngasala, Billy E., Nikiema, Frederic, Nsanzabana, Christian, Ntoumi, Francine, Oguike, Mary, Ogutu, Bernhards R., Olliaro, Piero, Omar, Sabah A., Ouedraogo, Jean-Bosco, Owusu-Agyei, Seth, Penali, Louis K., Pene, Mbaye, Peshu, Judy, Piola, Patrice, Plowe, Christopher V., Premji, Zul, Price, Ric N., Randrianarivelojosia, Milijaona, Rombo, Lars, Roper, Cally, Rosenthal, Philip J., Sagara, Issaka, Same-Ekobo, Albert, Sawa, Patrick, Schallig, Henk D. F. H., Schramm, Birgit, Seck, Amadou, Shekalaghe, Seif A., Sibley, Carol H., Sinou, Vronique, Sirima, Sodiomon B., Som, Fabrice A., Sow, Doudou, Staedke, Sarah G., Stepniewska, Kasia, Sutherland, Colin J., Swarthout, Todd D., Sylla, Khadime, Talisuna, Ambrose O., Taylor, Walter R. J., Temu, Emmanuel A., Thwing, Julie I., Tine, Roger C. K., Tinto, Halidou, Tommasini, Silva, Toure, Offianan A., Ursing, Johan, Vaillant, Michel T., Valentini, Giovanni, Van den Broek, Ingrid, Van Vugt, Michele, Ward, Stephen A., Winstanley, Peter A., Yavo, William, Yeka, Adoke, Zolia, Yah M., and Zongo, Issaka

Abstract

Background: Artemisinin-resistant Plasmodium falciparum has emerged in the Greater Mekong sub-region and poses a major global public health threat. Slow parasite clearance is a key clinical manifestation of reduced susceptibility to artemisinin. This study was designed to establish the baseline values for clearance in patients from Sub-Saharan African countries with uncomplicated malaria treated with artemisinin-based combination therapies (ACTs). Methods: A literature review in PubMed was conducted in March 2013 to identify all prospective clinical trials (uncontrolled trials, controlled trials and randomized controlled trials), including ACTs conducted in Sub-Saharan Africa, between 1960 and 2012. Individual patient data from these studies were shared with the WorldWide Antimalarial Resistance Network (WWARN) and pooled using an a priori statistical analytical plan. Factors affecting early parasitological response were investigated using logistic regression with study sites fitted as a random effect. The risk of bias in included studies was evaluated based on study design, methodology and missing data. Results: In total, 29,493 patients from 84 clinical trials were included in the analysis, treated with artemether-lumefantrine (n = 13,664), artesunate-amodiaquine (n = 11,337) and dihydroartemisinin-piperaquine (n = 4,492). The overall parasite clearance rate was rapid. The parasite positivity rate (PPR) decreased from 59.7 % (95 % CI: 54.5-64.9) on day 1 to 6.7 % (95 % CI: 4.8-8.7) on day 2 and 0.9 % (95 % CI: 0.5-1.2) on day 3. The 95th percentile of observed day 3 PPR was 5.3 %. Independent risk factors predictive of day 3 positivity were: high baseline parasitaemia (adjusted odds ratio (AOR) = 1.16 (95 % CI: 1.08-1.25); per 2-fold increase in parasite density, P <0.001); fever (>37.5 degrees C) (AOR = 1.50 (95 % CI: 1.06-2.13), P = 0.022); severe anaemia (AOR = 2.04 (95 % CI: 1.21-3.44), P = 0.008); areas of low/moderate transmission setting (AOR = 2.71 (

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2015
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41. The effect of dosing strategies on the therapeutic efficacy of artesunate-amodiaquine for uncomplicated malaria : a meta-analysis of individual patient data

Author

Adjuik, Martin A., Allan, Richard, Anvikar, Anupkumar R., Ashley, Elizabeth A., Ba, Mamadou S., Barennes, Hubert, Barnes, Karen I., Bassat, Quique, Baudin, Elisabeth, Bjorkman, Anders, Bompart, Francois, Bonnet, Maryline, Borrmann, Steffen, Brasseur, Philippe, Bukirwa, Hasifa, Checchi, Francesco, Cot, Michel, Dahal, Prabin, D'Alessandro, Umberto, Deloron, Philippe, Desai, Meghna, Diap, Graciela, Djimde, Abdoulaye A., Dorsey, Grant, Doumbo, Ogobara K., Espie, Emmanuelle, Etard, Jean-Francois, Fanello, Caterina I., Faucher, Jean-Francois, Faye, Babacar, Flegg, Jennifer A., Gaye, Oumar, Gething, Peter W., Gonzalez, Raquel, Grandesso, Francesco, Guerin, Philippe J., Guthmann, Jean-Paul, Hamour, Sally, Hasugian, Armedy Ronny, Hay, Simon I., Humphreys, Georgina S., Jullien, Vincent, Juma, Elizabeth, Kamya, Moses R., Karema, Corine, Kiechel, Jean R., Kremsner, Peter G., Krishna, Sanjeev, Lameyre, Valerie, Ibrahim, Laminou M., Lee, Sue J., Lell, Bertrand, Martensson, Andreas, Massougbodji, Achille, Menan, Herve, Menard, Didier, Menendez, Clara, Meremikwu, Martin, Moreira, Clarissa, Nabasumba, Carolyn, Nambozi, Michael, Ndiaye, Jean-Louis, Nikiema, Frederic, Nsanzabana, Christian, Ntoumi, Francine, Ogutu, Bernhards R., Olliaro, Piero, Osorio, Lyda, Ouedraogo, Jean-Bosco, Penali, Louis K., Pene, Mbaye, Pinoges, Loretxu, Piola, Patrice, Price, Ric N., Roper, Cally, Rosenthal, Philip J., Rwagacondo, Claude Emile, Same-Ekobo, Albert, Schramm, Birgit, Seck, Amadou, Sharma, Bhawna, Sibley, Carol Hopkins, Sinou, Veronique, Sirima, Sodiomon B., Smith, Jeffery J., Smithuis, Frank, Some, Fabrice A., Sow, Doudou, Staedke, Sarah G., Stepniewska, Kasia, Swarthout, Todd D., Sylla, Khadime, Talisuna, Ambrose O., Tarning, Joel, Taylor, Walter R. J., Temu, Emmanuel A., Thwing, Julie I., Tjitra, Emiliana, Tine, Roger C. K., Tinto, Halidou, Vaillant, Michel T., Valecha, Neena, Van den Broek, Ingrid, White, Nicholas J., Yeka, Adoke, Zongo, Issaka, Adjuik, Martin A., Allan, Richard, Anvikar, Anupkumar R., Ashley, Elizabeth A., Ba, Mamadou S., Barennes, Hubert, Barnes, Karen I., Bassat, Quique, Baudin, Elisabeth, Bjorkman, Anders, Bompart, Francois, Bonnet, Maryline, Borrmann, Steffen, Brasseur, Philippe, Bukirwa, Hasifa, Checchi, Francesco, Cot, Michel, Dahal, Prabin, D'Alessandro, Umberto, Deloron, Philippe, Desai, Meghna, Diap, Graciela, Djimde, Abdoulaye A., Dorsey, Grant, Doumbo, Ogobara K., Espie, Emmanuelle, Etard, Jean-Francois, Fanello, Caterina I., Faucher, Jean-Francois, Faye, Babacar, Flegg, Jennifer A., Gaye, Oumar, Gething, Peter W., Gonzalez, Raquel, Grandesso, Francesco, Guerin, Philippe J., Guthmann, Jean-Paul, Hamour, Sally, Hasugian, Armedy Ronny, Hay, Simon I., Humphreys, Georgina S., Jullien, Vincent, Juma, Elizabeth, Kamya, Moses R., Karema, Corine, Kiechel, Jean R., Kremsner, Peter G., Krishna, Sanjeev, Lameyre, Valerie, Ibrahim, Laminou M., Lee, Sue J., Lell, Bertrand, Martensson, Andreas, Massougbodji, Achille, Menan, Herve, Menard, Didier, Menendez, Clara, Meremikwu, Martin, Moreira, Clarissa, Nabasumba, Carolyn, Nambozi, Michael, Ndiaye, Jean-Louis, Nikiema, Frederic, Nsanzabana, Christian, Ntoumi, Francine, Ogutu, Bernhards R., Olliaro, Piero, Osorio, Lyda, Ouedraogo, Jean-Bosco, Penali, Louis K., Pene, Mbaye, Pinoges, Loretxu, Piola, Patrice, Price, Ric N., Roper, Cally, Rosenthal, Philip J., Rwagacondo, Claude Emile, Same-Ekobo, Albert, Schramm, Birgit, Seck, Amadou, Sharma, Bhawna, Sibley, Carol Hopkins, Sinou, Veronique, Sirima, Sodiomon B., Smith, Jeffery J., Smithuis, Frank, Some, Fabrice A., Sow, Doudou, Staedke, Sarah G., Stepniewska, Kasia, Swarthout, Todd D., Sylla, Khadime, Talisuna, Ambrose O., Tarning, Joel, Taylor, Walter R. J., Temu, Emmanuel A., Thwing, Julie I., Tjitra, Emiliana, Tine, Roger C. K., Tinto, Halidou, Vaillant, Michel T., Valecha, Neena, Van den Broek, Ingrid, White, Nicholas J., Yeka, Adoke, and Zongo, Issaka

Abstract

Background: Artesunate-amodiaquine (AS-AQ) is one of the most widely used artemisinin-based combination therapies (ACTs) to treat uncomplicated Plasmodium falciparum malaria in Africa. We investigated the impact of different dosing strategies on the efficacy of this combination for the treatment of falciparum malaria. Methods: Individual patient data from AS-AQ clinical trials were pooled using the WorldWide Antimalarial Resistance Network (WWARN) standardised methodology. Risk factors for treatment failure were identified using a Cox regression model with shared frailty across study sites. Results: Forty-three studies representing 9,106 treatments from 1999-2012 were included in the analysis; 4,138 (45.4%) treatments were with a fixed dose combination with an AQ target dose of 30 mg/kg (FDC), 1,293 (14.2%) with a non-fixed dose combination with an AQ target dose of 25 mg/kg (loose NFDC-25), 2,418 (26.6%) with a non-fixed dose combination with an AQ target dose of 30 mg/kg (loose NFDC-30), and the remaining 1,257 (13.8%) with a co-blistered non-fixed dose combination with an AQ target dose of 30 mg/kg (co-blistered NFDC). The median dose of AQ administered was 32.1 mg/kg [IQR: 25.9-38.2], the highest dose being administered to patients treated with co-blistered NFDC (median = 35.3 mg/kg [IQR: 30.6-43.7]) and the lowest to those treated with loose NFDC-25 (median = 25.0 mg/kg [IQR: 22.7-25.0]). Patients treated with FDC received a median dose of 32.4 mg/kg [IQR: 27-39.0]. After adjusting for reinfections, the corrected antimalarial efficacy on day 28 after treatment was similar for co-blistered NFDC (97.9% [95% confidence interval (CI): 97.0-98.8%]) and FDC (98.1% [95% CI: 97.6%-98.5%]; P = 0.799), but significantly lower for the loose NFDC-25 (93.4% [95% CI: 91.9%-94.9%]), and loose NFDC-30 (95.0% [95% CI: 94.1%-95.9%]) (P < 0.001 for all comparisons). After controlling for age, AQ dose, baseline parasitemia and region; treatment with loose NFDC-25 was associated

Published
2015
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42. The effect of dosing strategies on the therapeutic efficacy of artesunate-amodiaquine for uncomplicated malaria : a meta-analysis of individual patient data

Author

Adjuik, Martin A., Allan, Richard, Anvikar, Anupkumar R., Ashley, Elizabeth A., Ba, Mamadou S., Barennes, Hubert, Barnes, Karen I., Bassat, Quique, Baudin, Elisabeth, Bjorkman, Anders, Bompart, Francois, Bonnet, Maryline, Borrmann, Steffen, Brasseur, Philippe, Bukirwa, Hasifa, Checchi, Francesco, Cot, Michel, Dahal, Prabin, D'Alessandro, Umberto, Deloron, Philippe, Desai, Meghna, Diap, Graciela, Djimde, Abdoulaye A., Dorsey, Grant, Doumbo, Ogobara K., Espie, Emmanuelle, Etard, Jean-Francois, Fanello, Caterina I., Faucher, Jean-Francois, Faye, Babacar, Flegg, Jennifer A., Gaye, Oumar, Gething, Peter W., Gonzalez, Raquel, Grandesso, Francesco, Guerin, Philippe J., Guthmann, Jean-Paul, Hamour, Sally, Hasugian, Armedy Ronny, Hay, Simon I., Humphreys, Georgina S., Jullien, Vincent, Juma, Elizabeth, Kamya, Moses R., Karema, Corine, Kiechel, Jean R., Kremsner, Peter G., Krishna, Sanjeev, Lameyre, Valerie, Ibrahim, Laminou M., Lee, Sue J., Lell, Bertrand, Martensson, Andreas, Massougbodji, Achille, Menan, Herve, Menard, Didier, Menendez, Clara, Meremikwu, Martin, Moreira, Clarissa, Nabasumba, Carolyn, Nambozi, Michael, Ndiaye, Jean-Louis, Nikiema, Frederic, Nsanzabana, Christian, Ntoumi, Francine, Ogutu, Bernhards R., Olliaro, Piero, Osorio, Lyda, Ouedraogo, Jean-Bosco, Penali, Louis K., Pene, Mbaye, Pinoges, Loretxu, Piola, Patrice, Price, Ric N., Roper, Cally, Rosenthal, Philip J., Rwagacondo, Claude Emile, Same-Ekobo, Albert, Schramm, Birgit, Seck, Amadou, Sharma, Bhawna, Sibley, Carol Hopkins, Sinou, Veronique, Sirima, Sodiomon B., Smith, Jeffery J., Smithuis, Frank, Some, Fabrice A., Sow, Doudou, Staedke, Sarah G., Stepniewska, Kasia, Swarthout, Todd D., Sylla, Khadime, Talisuna, Ambrose O., Tarning, Joel, Taylor, Walter R. J., Temu, Emmanuel A., Thwing, Julie I., Tjitra, Emiliana, Tine, Roger C. K., Tinto, Halidou, Vaillant, Michel T., Valecha, Neena, Van den Broek, Ingrid, White, Nicholas J., Yeka, Adoke, Zongo, Issaka, Adjuik, Martin A., Allan, Richard, Anvikar, Anupkumar R., Ashley, Elizabeth A., Ba, Mamadou S., Barennes, Hubert, Barnes, Karen I., Bassat, Quique, Baudin, Elisabeth, Bjorkman, Anders, Bompart, Francois, Bonnet, Maryline, Borrmann, Steffen, Brasseur, Philippe, Bukirwa, Hasifa, Checchi, Francesco, Cot, Michel, Dahal, Prabin, D'Alessandro, Umberto, Deloron, Philippe, Desai, Meghna, Diap, Graciela, Djimde, Abdoulaye A., Dorsey, Grant, Doumbo, Ogobara K., Espie, Emmanuelle, Etard, Jean-Francois, Fanello, Caterina I., Faucher, Jean-Francois, Faye, Babacar, Flegg, Jennifer A., Gaye, Oumar, Gething, Peter W., Gonzalez, Raquel, Grandesso, Francesco, Guerin, Philippe J., Guthmann, Jean-Paul, Hamour, Sally, Hasugian, Armedy Ronny, Hay, Simon I., Humphreys, Georgina S., Jullien, Vincent, Juma, Elizabeth, Kamya, Moses R., Karema, Corine, Kiechel, Jean R., Kremsner, Peter G., Krishna, Sanjeev, Lameyre, Valerie, Ibrahim, Laminou M., Lee, Sue J., Lell, Bertrand, Martensson, Andreas, Massougbodji, Achille, Menan, Herve, Menard, Didier, Menendez, Clara, Meremikwu, Martin, Moreira, Clarissa, Nabasumba, Carolyn, Nambozi, Michael, Ndiaye, Jean-Louis, Nikiema, Frederic, Nsanzabana, Christian, Ntoumi, Francine, Ogutu, Bernhards R., Olliaro, Piero, Osorio, Lyda, Ouedraogo, Jean-Bosco, Penali, Louis K., Pene, Mbaye, Pinoges, Loretxu, Piola, Patrice, Price, Ric N., Roper, Cally, Rosenthal, Philip J., Rwagacondo, Claude Emile, Same-Ekobo, Albert, Schramm, Birgit, Seck, Amadou, Sharma, Bhawna, Sibley, Carol Hopkins, Sinou, Veronique, Sirima, Sodiomon B., Smith, Jeffery J., Smithuis, Frank, Some, Fabrice A., Sow, Doudou, Staedke, Sarah G., Stepniewska, Kasia, Swarthout, Todd D., Sylla, Khadime, Talisuna, Ambrose O., Tarning, Joel, Taylor, Walter R. J., Temu, Emmanuel A., Thwing, Julie I., Tjitra, Emiliana, Tine, Roger C. K., Tinto, Halidou, Vaillant, Michel T., Valecha, Neena, Van den Broek, Ingrid, White, Nicholas J., Yeka, Adoke, and Zongo, Issaka

Abstract

Background: Artesunate-amodiaquine (AS-AQ) is one of the most widely used artemisinin-based combination therapies (ACTs) to treat uncomplicated Plasmodium falciparum malaria in Africa. We investigated the impact of different dosing strategies on the efficacy of this combination for the treatment of falciparum malaria. Methods: Individual patient data from AS-AQ clinical trials were pooled using the WorldWide Antimalarial Resistance Network (WWARN) standardised methodology. Risk factors for treatment failure were identified using a Cox regression model with shared frailty across study sites. Results: Forty-three studies representing 9,106 treatments from 1999-2012 were included in the analysis; 4,138 (45.4%) treatments were with a fixed dose combination with an AQ target dose of 30 mg/kg (FDC), 1,293 (14.2%) with a non-fixed dose combination with an AQ target dose of 25 mg/kg (loose NFDC-25), 2,418 (26.6%) with a non-fixed dose combination with an AQ target dose of 30 mg/kg (loose NFDC-30), and the remaining 1,257 (13.8%) with a co-blistered non-fixed dose combination with an AQ target dose of 30 mg/kg (co-blistered NFDC). The median dose of AQ administered was 32.1 mg/kg [IQR: 25.9-38.2], the highest dose being administered to patients treated with co-blistered NFDC (median = 35.3 mg/kg [IQR: 30.6-43.7]) and the lowest to those treated with loose NFDC-25 (median = 25.0 mg/kg [IQR: 22.7-25.0]). Patients treated with FDC received a median dose of 32.4 mg/kg [IQR: 27-39.0]. After adjusting for reinfections, the corrected antimalarial efficacy on day 28 after treatment was similar for co-blistered NFDC (97.9% [95% confidence interval (CI): 97.0-98.8%]) and FDC (98.1% [95% CI: 97.6%-98.5%]; P = 0.799), but significantly lower for the loose NFDC-25 (93.4% [95% CI: 91.9%-94.9%]), and loose NFDC-30 (95.0% [95% CI: 94.1%-95.9%]) (P < 0.001 for all comparisons). After controlling for age, AQ dose, baseline parasitemia and region; treatment with loose NFDC-25 was associated

Published
2015
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43. The effect of dosing strategies on the therapeutic efficacy of artesunate-amodiaquine for uncomplicated malaria: a meta-analysis of individual patient data.

Author

WorldWide Antimalarial Resistance Network (WWARN) AS-AQ Study Group, WorldWide Antimalarial Resistance Network (WWARN) AS-AQ Study Group, Adjuik, Martin A, Allan, Richard, Anvikar, Anupkumar R, Ashley, Elizabeth A, Ba, Mamadou S, Barennes, Hubert, Barnes, Karen I, Bassat, Quique, Baudin, Elisabeth, Björkman, Anders, Bompart, François, Bonnet, Maryline, Borrmann, Steffen, Brasseur, Philippe, Bukirwa, Hasifa, Checchi, Francesco, Cot, Michel, Dahal, Prabin, D'Alessandro, Umberto, Deloron, Philippe, Desai, Meghna, Diap, Graciela, Djimde, Abdoulaye A, Dorsey, Grant, Doumbo, Ogobara K, Espié, Emmanuelle, Etard, Jean-Francois, Fanello, Caterina I, Faucher, Jean-François, Faye, Babacar, Flegg, Jennifer A, Gaye, Oumar, Gething, Peter W, González, Raquel, Grandesso, Francesco, Guerin, Philippe J, Guthmann, Jean-Paul, Hamour, Sally, Hasugian, Armedy Ronny, Hay, Simon I, Humphreys, Georgina S, Jullien, Vincent, Juma, Elizabeth, Kamya, Moses R, Karema, Corine, Kiechel, Jean R, Kremsner, Peter G, Krishna, Sanjeev, Lameyre, Valérie, Ibrahim, Laminou M, Lee, Sue J, Lell, Bertrand, Mårtensson, Andreas, Massougbodji, Achille, Menan, Hervé, Ménard, Didier, Menéndez, Clara, Meremikwu, Martin, Moreira, Clarissa, Nabasumba, Carolyn, Nambozi, Michael, Ndiaye, Jean-Louis, Nikiema, Frederic, Nsanzabana, Christian, Ntoumi, Francine, Ogutu, Bernhards R, Olliaro, Piero, Osorio, Lyda, Ouédraogo, Jean-Bosco, Penali, Louis K, Pene, Mbaye, Pinoges, Loretxu, Piola, Patrice, Price, Ric N, Roper, Cally, Rosenthal, Philip J, Rwagacondo, Claude Emile, Same-Ekobo, Albert, Schramm, Birgit, Seck, Amadou, Sharma, Bhawna, Sibley, Carol Hopkins, Sinou, Véronique, Sirima, Sodiomon B, Smith, Jeffery J, Smithuis, Frank, Somé, Fabrice A, Sow, Doudou, Staedke, Sarah G, Stepniewska, Kasia, Swarthout, Todd D, Sylla, Khadime, Talisuna, Ambrose O, Tarning, Joel, Taylor, Walter RJ, Temu, Emmanuel A, Thwing, Julie I, Tjitra, Emiliana, Tine, Roger CK, WorldWide Antimalarial Resistance Network (WWARN) AS-AQ Study Group, WorldWide Antimalarial Resistance Network (WWARN) AS-AQ Study Group, Adjuik, Martin A, Allan, Richard, Anvikar, Anupkumar R, Ashley, Elizabeth A, Ba, Mamadou S, Barennes, Hubert, Barnes, Karen I, Bassat, Quique, Baudin, Elisabeth, Björkman, Anders, Bompart, François, Bonnet, Maryline, Borrmann, Steffen, Brasseur, Philippe, Bukirwa, Hasifa, Checchi, Francesco, Cot, Michel, Dahal, Prabin, D'Alessandro, Umberto, Deloron, Philippe, Desai, Meghna, Diap, Graciela, Djimde, Abdoulaye A, Dorsey, Grant, Doumbo, Ogobara K, Espié, Emmanuelle, Etard, Jean-Francois, Fanello, Caterina I, Faucher, Jean-François, Faye, Babacar, Flegg, Jennifer A, Gaye, Oumar, Gething, Peter W, González, Raquel, Grandesso, Francesco, Guerin, Philippe J, Guthmann, Jean-Paul, Hamour, Sally, Hasugian, Armedy Ronny, Hay, Simon I, Humphreys, Georgina S, Jullien, Vincent, Juma, Elizabeth, Kamya, Moses R, Karema, Corine, Kiechel, Jean R, Kremsner, Peter G, Krishna, Sanjeev, Lameyre, Valérie, Ibrahim, Laminou M, Lee, Sue J, Lell, Bertrand, Mårtensson, Andreas, Massougbodji, Achille, Menan, Hervé, Ménard, Didier, Menéndez, Clara, Meremikwu, Martin, Moreira, Clarissa, Nabasumba, Carolyn, Nambozi, Michael, Ndiaye, Jean-Louis, Nikiema, Frederic, Nsanzabana, Christian, Ntoumi, Francine, Ogutu, Bernhards R, Olliaro, Piero, Osorio, Lyda, Ouédraogo, Jean-Bosco, Penali, Louis K, Pene, Mbaye, Pinoges, Loretxu, Piola, Patrice, Price, Ric N, Roper, Cally, Rosenthal, Philip J, Rwagacondo, Claude Emile, Same-Ekobo, Albert, Schramm, Birgit, Seck, Amadou, Sharma, Bhawna, Sibley, Carol Hopkins, Sinou, Véronique, Sirima, Sodiomon B, Smith, Jeffery J, Smithuis, Frank, Somé, Fabrice A, Sow, Doudou, Staedke, Sarah G, Stepniewska, Kasia, Swarthout, Todd D, Sylla, Khadime, Talisuna, Ambrose O, Tarning, Joel, Taylor, Walter RJ, Temu, Emmanuel A, Thwing, Julie I, Tjitra, Emiliana, and Tine, Roger CK

Abstract

BackgroundArtesunate-amodiaquine (AS-AQ) is one of the most widely used artemisinin-based combination therapies (ACTs) to treat uncomplicated Plasmodium falciparum malaria in Africa. We investigated the impact of different dosing strategies on the efficacy of this combination for the treatment of falciparum malaria.MethodsIndividual patient data from AS-AQ clinical trials were pooled using the WorldWide Antimalarial Resistance Network (WWARN) standardised methodology. Risk factors for treatment failure were identified using a Cox regression model with shared frailty across study sites.ResultsForty-three studies representing 9,106 treatments from 1999-2012 were included in the analysis; 4,138 (45.4%) treatments were with a fixed dose combination with an AQ target dose of 30 mg/kg (FDC), 1,293 (14.2%) with a non-fixed dose combination with an AQ target dose of 25 mg/kg (loose NFDC-25), 2,418 (26.6%) with a non-fixed dose combination with an AQ target dose of 30 mg/kg (loose NFDC-30), and the remaining 1,257 (13.8%) with a co-blistered non-fixed dose combination with an AQ target dose of 30 mg/kg (co-blistered NFDC). The median dose of AQ administered was 32.1 mg/kg [IQR: 25.9-38.2], the highest dose being administered to patients treated with co-blistered NFDC (median = 35.3 mg/kg [IQR: 30.6-43.7]) and the lowest to those treated with loose NFDC-25 (median = 25.0 mg/kg [IQR: 22.7-25.0]). Patients treated with FDC received a median dose of 32.4 mg/kg [IQR: 27-39.0]. After adjusting for reinfections, the corrected antimalarial efficacy on day 28 after treatment was similar for co-blistered NFDC (97.9% [95% confidence interval (CI): 97.0-98.8%]) and FDC (98.1% [95% CI: 97.6%-98.5%]; P = 0.799), but significantly lower for the loose NFDC-25 (93.4% [95% CI: 91.9%-94.9%]), and loose NFDC-30 (95.0% [95% CI: 94.1%-95.9%]) (P < 0.001 for all comparisons). After controlling for age, AQ dose, baseline parasitemia and region; treatment with loose NFDC-25 was associated with a

Published
2015

44. Immune responses in relation to the type and time of thermal injury: An experimental study

Author

Alexis, A., Carrer, D.P., Droggiti, D.I., Louis, K., Pistiki, A., Netea, M.G., Kapessidou, Y., Giamarellos-Bourboulis, E.J., Alexis, A., Carrer, D.P., Droggiti, D.I., Louis, K., Pistiki, A., Netea, M.G., Kapessidou, Y., and Giamarellos-Bourboulis, E.J.

Abstract

Item does not contain fulltext, BACKGROUND: Thermal injuries are followed by a complex immune response, but the relationship between the severity of burn injury and the time exposure to the thermal injury on the extent of the immune response is still not known. OBJECTIVE: This study focuses on characterising the effect of temperature and time exposure on the post-burn immune response. METHODS: We used 120 C57BL/6 male mice divided equally in 5 burn groups and one sham operated group (groups A-E and sham). Ten mice per group were sacrificed at 24 and 48h after burn injury and whole blood was collected; specimens of liver, lung, spleen, kidney and bowel were excised. Apoptosis and TREM-1 expression on circulating blood cells were measured. Splenocytes were isolated and stimulated for cytokine production; the rate of apoptosis of splenocytes was also measured. RESULTS: Production of IL-17 from splenocytes of mice group D was enhanced. Considerable effects were shown on the apoptosis of circulating lymphocytes and of spleen cells. The apoptotic rates varied between groups and also evolved after 24 and 48h. To examine the origin of this differential response, quantitative bacterial cultures of liver, lung and kidney were made but no differences were observed compared with sham-operated animals. LIMITATIONS: This study was based on an experimental murine model. CONCLUSION: There is a unique response for each type of injury depending on the temperature of the thermal source and the exposure time.

Published
2015

45. Graphene Sails with Phased Array Optical Drive - Towards More Practical Interstellar Probes

Author

Scheffer, Louis K. and Scheffer, Louis K.

Abstract

A spacecraft pushed by radiation has the major advantage that the power source is not included in the accelerated mass, making it the preferred technique for reaching relativistic speeds. There are two main technical challenges. First, to get significant acceleration, the sail must be both extremely light weight and capable of operating at high intensities of the incident beam and the resulting high temperatures. Second, the transmitter must emit high power beams through huge apertures, many kilometers in diameter, in order to focus radiation on the sail across the long distances needed to achieve high final speeds. Existing proposals for the sail use carbon or aluminum films, but aluminum is limited by a low melting point, and both have low mechanical strength requiring either a distributed payload or complex rigging. We propose here a graphene sail, which offers high absorption per unit weight, high temperature operation, and the mechanical strength to support simple rigging to a lumped mass payload. For the transmitter, existing proposals use a compact high power source, and focus the energy with a large (hundreds to thousands of km) space-based lens. Existing optical drive proposals also require launch from the outer solar system, have severe pointing restrictions, and require difficult maneuvering of the beam source. Instead we propose an active Fresnel lens, allowing smaller apertures of less mass, easier pointing with fewer restrictions, and probe launch from the inner solar system. The technologies for both the sail and the transmitter are already under development for other reasons. Worked examples, physically smaller and less massive than those suggested so far, range from a 1kg payload launched to 10\% of the speed of light by a transmitter only 25 times the mass of ISS, to a larger system that can launch a 1000 kg payload to 50\% of the speed of light., Comment: 14 pages, 6 figures, 3 tables. V2 includes additional references

Published
2015

46. The effect of dosing strategies on the therapeutic efficacy of artesunate-amodiaquine for uncomplicated malaria: a meta-analysis of individual patient data.

Author

WorldWide Antimalarial Resistance Network (WWARN) AS-AQ Study Group, WorldWide Antimalarial Resistance Network (WWARN) AS-AQ Study Group, Adjuik, Martin A, Allan, Richard, Anvikar, Anupkumar R, Ashley, Elizabeth A, Ba, Mamadou S, Barennes, Hubert, Barnes, Karen I, Bassat, Quique, Baudin, Elisabeth, Björkman, Anders, Bompart, François, Bonnet, Maryline, Borrmann, Steffen, Brasseur, Philippe, Bukirwa, Hasifa, Checchi, Francesco, Cot, Michel, Dahal, Prabin, D'Alessandro, Umberto, Deloron, Philippe, Desai, Meghna, Diap, Graciela, Djimde, Abdoulaye A, Dorsey, Grant, Doumbo, Ogobara K, Espié, Emmanuelle, Etard, Jean-Francois, Fanello, Caterina I, Faucher, Jean-François, Faye, Babacar, Flegg, Jennifer A, Gaye, Oumar, Gething, Peter W, González, Raquel, Grandesso, Francesco, Guerin, Philippe J, Guthmann, Jean-Paul, Hamour, Sally, Hasugian, Armedy Ronny, Hay, Simon I, Humphreys, Georgina S, Jullien, Vincent, Juma, Elizabeth, Kamya, Moses R, Karema, Corine, Kiechel, Jean R, Kremsner, Peter G, Krishna, Sanjeev, Lameyre, Valérie, Ibrahim, Laminou M, Lee, Sue J, Lell, Bertrand, Mårtensson, Andreas, Massougbodji, Achille, Menan, Hervé, Ménard, Didier, Menéndez, Clara, Meremikwu, Martin, Moreira, Clarissa, Nabasumba, Carolyn, Nambozi, Michael, Ndiaye, Jean-Louis, Nikiema, Frederic, Nsanzabana, Christian, Ntoumi, Francine, Ogutu, Bernhards R, Olliaro, Piero, Osorio, Lyda, Ouédraogo, Jean-Bosco, Penali, Louis K, Pene, Mbaye, Pinoges, Loretxu, Piola, Patrice, Price, Ric N, Roper, Cally, Rosenthal, Philip J, Rwagacondo, Claude Emile, Same-Ekobo, Albert, Schramm, Birgit, Seck, Amadou, Sharma, Bhawna, Sibley, Carol Hopkins, Sinou, Véronique, Sirima, Sodiomon B, Smith, Jeffery J, Smithuis, Frank, Somé, Fabrice A, Sow, Doudou, Staedke, Sarah G, Stepniewska, Kasia, Swarthout, Todd D, Sylla, Khadime, Talisuna, Ambrose O, Tarning, Joel, Taylor, Walter RJ, Temu, Emmanuel A, Thwing, Julie I, Tjitra, Emiliana, Tine, Roger CK, WorldWide Antimalarial Resistance Network (WWARN) AS-AQ Study Group, WorldWide Antimalarial Resistance Network (WWARN) AS-AQ Study Group, Adjuik, Martin A, Allan, Richard, Anvikar, Anupkumar R, Ashley, Elizabeth A, Ba, Mamadou S, Barennes, Hubert, Barnes, Karen I, Bassat, Quique, Baudin, Elisabeth, Björkman, Anders, Bompart, François, Bonnet, Maryline, Borrmann, Steffen, Brasseur, Philippe, Bukirwa, Hasifa, Checchi, Francesco, Cot, Michel, Dahal, Prabin, D'Alessandro, Umberto, Deloron, Philippe, Desai, Meghna, Diap, Graciela, Djimde, Abdoulaye A, Dorsey, Grant, Doumbo, Ogobara K, Espié, Emmanuelle, Etard, Jean-Francois, Fanello, Caterina I, Faucher, Jean-François, Faye, Babacar, Flegg, Jennifer A, Gaye, Oumar, Gething, Peter W, González, Raquel, Grandesso, Francesco, Guerin, Philippe J, Guthmann, Jean-Paul, Hamour, Sally, Hasugian, Armedy Ronny, Hay, Simon I, Humphreys, Georgina S, Jullien, Vincent, Juma, Elizabeth, Kamya, Moses R, Karema, Corine, Kiechel, Jean R, Kremsner, Peter G, Krishna, Sanjeev, Lameyre, Valérie, Ibrahim, Laminou M, Lee, Sue J, Lell, Bertrand, Mårtensson, Andreas, Massougbodji, Achille, Menan, Hervé, Ménard, Didier, Menéndez, Clara, Meremikwu, Martin, Moreira, Clarissa, Nabasumba, Carolyn, Nambozi, Michael, Ndiaye, Jean-Louis, Nikiema, Frederic, Nsanzabana, Christian, Ntoumi, Francine, Ogutu, Bernhards R, Olliaro, Piero, Osorio, Lyda, Ouédraogo, Jean-Bosco, Penali, Louis K, Pene, Mbaye, Pinoges, Loretxu, Piola, Patrice, Price, Ric N, Roper, Cally, Rosenthal, Philip J, Rwagacondo, Claude Emile, Same-Ekobo, Albert, Schramm, Birgit, Seck, Amadou, Sharma, Bhawna, Sibley, Carol Hopkins, Sinou, Véronique, Sirima, Sodiomon B, Smith, Jeffery J, Smithuis, Frank, Somé, Fabrice A, Sow, Doudou, Staedke, Sarah G, Stepniewska, Kasia, Swarthout, Todd D, Sylla, Khadime, Talisuna, Ambrose O, Tarning, Joel, Taylor, Walter RJ, Temu, Emmanuel A, Thwing, Julie I, Tjitra, Emiliana, and Tine, Roger CK

Abstract

BackgroundArtesunate-amodiaquine (AS-AQ) is one of the most widely used artemisinin-based combination therapies (ACTs) to treat uncomplicated Plasmodium falciparum malaria in Africa. We investigated the impact of different dosing strategies on the efficacy of this combination for the treatment of falciparum malaria.MethodsIndividual patient data from AS-AQ clinical trials were pooled using the WorldWide Antimalarial Resistance Network (WWARN) standardised methodology. Risk factors for treatment failure were identified using a Cox regression model with shared frailty across study sites.ResultsForty-three studies representing 9,106 treatments from 1999-2012 were included in the analysis; 4,138 (45.4%) treatments were with a fixed dose combination with an AQ target dose of 30 mg/kg (FDC), 1,293 (14.2%) with a non-fixed dose combination with an AQ target dose of 25 mg/kg (loose NFDC-25), 2,418 (26.6%) with a non-fixed dose combination with an AQ target dose of 30 mg/kg (loose NFDC-30), and the remaining 1,257 (13.8%) with a co-blistered non-fixed dose combination with an AQ target dose of 30 mg/kg (co-blistered NFDC). The median dose of AQ administered was 32.1 mg/kg [IQR: 25.9-38.2], the highest dose being administered to patients treated with co-blistered NFDC (median = 35.3 mg/kg [IQR: 30.6-43.7]) and the lowest to those treated with loose NFDC-25 (median = 25.0 mg/kg [IQR: 22.7-25.0]). Patients treated with FDC received a median dose of 32.4 mg/kg [IQR: 27-39.0]. After adjusting for reinfections, the corrected antimalarial efficacy on day 28 after treatment was similar for co-blistered NFDC (97.9% [95% confidence interval (CI): 97.0-98.8%]) and FDC (98.1% [95% CI: 97.6%-98.5%]; P = 0.799), but significantly lower for the loose NFDC-25 (93.4% [95% CI: 91.9%-94.9%]), and loose NFDC-30 (95.0% [95% CI: 94.1%-95.9%]) (P < 0.001 for all comparisons). After controlling for age, AQ dose, baseline parasitemia and region; treatment w

Published
2015

47. Immune responses in relation to the type and time of thermal injury: An experimental study

Author

Alexis, A., Carrer, D.P., Droggiti, D.I., Louis, K., Pistiki, A., Netea, M.G., Kapessidou, Y., Giamarellos-Bourboulis, E.J., Alexis, A., Carrer, D.P., Droggiti, D.I., Louis, K., Pistiki, A., Netea, M.G., Kapessidou, Y., and Giamarellos-Bourboulis, E.J.

Abstract

Item does not contain fulltext, BACKGROUND: Thermal injuries are followed by a complex immune response, but the relationship between the severity of burn injury and the time exposure to the thermal injury on the extent of the immune response is still not known. OBJECTIVE: This study focuses on characterising the effect of temperature and time exposure on the post-burn immune response. METHODS: We used 120 C57BL/6 male mice divided equally in 5 burn groups and one sham operated group (groups A-E and sham). Ten mice per group were sacrificed at 24 and 48h after burn injury and whole blood was collected; specimens of liver, lung, spleen, kidney and bowel were excised. Apoptosis and TREM-1 expression on circulating blood cells were measured. Splenocytes were isolated and stimulated for cytokine production; the rate of apoptosis of splenocytes was also measured. RESULTS: Production of IL-17 from splenocytes of mice group D was enhanced. Considerable effects were shown on the apoptosis of circulating lymphocytes and of spleen cells. The apoptotic rates varied between groups and also evolved after 24 and 48h. To examine the origin of this differential response, quantitative bacterial cultures of liver, lung and kidney were made but no differences were observed compared with sham-operated animals. LIMITATIONS: This study was based on an experimental murine model. CONCLUSION: There is a unique response for each type of injury depending on the temperature of the thermal source and the exposure time.

Published
2015

48. Immune responses in relation to the type and time of thermal injury: An experimental study

Author

Alexis, A., Carrer, D.P., Droggiti, D.I., Louis, K., Pistiki, A., Netea, M.G., Kapessidou, Y., Giamarellos-Bourboulis, E.J., Alexis, A., Carrer, D.P., Droggiti, D.I., Louis, K., Pistiki, A., Netea, M.G., Kapessidou, Y., and Giamarellos-Bourboulis, E.J.

Abstract

Item does not contain fulltext, BACKGROUND: Thermal injuries are followed by a complex immune response, but the relationship between the severity of burn injury and the time exposure to the thermal injury on the extent of the immune response is still not known. OBJECTIVE: This study focuses on characterising the effect of temperature and time exposure on the post-burn immune response. METHODS: We used 120 C57BL/6 male mice divided equally in 5 burn groups and one sham operated group (groups A-E and sham). Ten mice per group were sacrificed at 24 and 48h after burn injury and whole blood was collected; specimens of liver, lung, spleen, kidney and bowel were excised. Apoptosis and TREM-1 expression on circulating blood cells were measured. Splenocytes were isolated and stimulated for cytokine production; the rate of apoptosis of splenocytes was also measured. RESULTS: Production of IL-17 from splenocytes of mice group D was enhanced. Considerable effects were shown on the apoptosis of circulating lymphocytes and of spleen cells. The apoptotic rates varied between groups and also evolved after 24 and 48h. To examine the origin of this differential response, quantitative bacterial cultures of liver, lung and kidney were made but no differences were observed compared with sham-operated animals. LIMITATIONS: This study was based on an experimental murine model. CONCLUSION: There is a unique response for each type of injury depending on the temperature of the thermal source and the exposure time.

Published
2015

49. The effect of dosing strategies on the therapeutic efficacy of artesunate-amodiaquine for uncomplicated malaria : a meta-analysis of individual patient data

Author

Adjuik, Martin A., Allan, Richard, Anvikar, Anupkumar R., Ashley, Elizabeth A., Ba, Mamadou S., Barennes, Hubert, Barnes, Karen I., Bassat, Quique, Baudin, Elisabeth, Bjorkman, Anders, Bompart, Francois, Bonnet, Maryline, Borrmann, Steffen, Brasseur, Philippe, Bukirwa, Hasifa, Checchi, Francesco, Cot, Michel, Dahal, Prabin, D'Alessandro, Umberto, Deloron, Philippe, Desai, Meghna, Diap, Graciela, Djimde, Abdoulaye A., Dorsey, Grant, Doumbo, Ogobara K., Espie, Emmanuelle, Etard, Jean-Francois, Fanello, Caterina I., Faucher, Jean-Francois, Faye, Babacar, Flegg, Jennifer A., Gaye, Oumar, Gething, Peter W., Gonzalez, Raquel, Grandesso, Francesco, Guerin, Philippe J., Guthmann, Jean-Paul, Hamour, Sally, Hasugian, Armedy Ronny, Hay, Simon I., Humphreys, Georgina S., Jullien, Vincent, Juma, Elizabeth, Kamya, Moses R., Karema, Corine, Kiechel, Jean R., Kremsner, Peter G., Krishna, Sanjeev, Lameyre, Valerie, Ibrahim, Laminou M., Lee, Sue J., Lell, Bertrand, Martensson, Andreas, Massougbodji, Achille, Menan, Herve, Menard, Didier, Menendez, Clara, Meremikwu, Martin, Moreira, Clarissa, Nabasumba, Carolyn, Nambozi, Michael, Ndiaye, Jean-Louis, Nikiema, Frederic, Nsanzabana, Christian, Ntoumi, Francine, Ogutu, Bernhards R., Olliaro, Piero, Osorio, Lyda, Ouedraogo, Jean-Bosco, Penali, Louis K., Pene, Mbaye, Pinoges, Loretxu, Piola, Patrice, Price, Ric N., Roper, Cally, Rosenthal, Philip J., Rwagacondo, Claude Emile, Same-Ekobo, Albert, Schramm, Birgit, Seck, Amadou, Sharma, Bhawna, Sibley, Carol Hopkins, Sinou, Veronique, Sirima, Sodiomon B., Smith, Jeffery J., Smithuis, Frank, Some, Fabrice A., Sow, Doudou, Staedke, Sarah G., Stepniewska, Kasia, Swarthout, Todd D., Sylla, Khadime, Talisuna, Ambrose O., Tarning, Joel, Taylor, Walter R. J., Temu, Emmanuel A., Thwing, Julie I., Tjitra, Emiliana, Tine, Roger C. K., Tinto, Halidou, Vaillant, Michel T., Valecha, Neena, Van den Broek, Ingrid, White, Nicholas J., Yeka, Adoke, Zongo, Issaka, Adjuik, Martin A., Allan, Richard, Anvikar, Anupkumar R., Ashley, Elizabeth A., Ba, Mamadou S., Barennes, Hubert, Barnes, Karen I., Bassat, Quique, Baudin, Elisabeth, Bjorkman, Anders, Bompart, Francois, Bonnet, Maryline, Borrmann, Steffen, Brasseur, Philippe, Bukirwa, Hasifa, Checchi, Francesco, Cot, Michel, Dahal, Prabin, D'Alessandro, Umberto, Deloron, Philippe, Desai, Meghna, Diap, Graciela, Djimde, Abdoulaye A., Dorsey, Grant, Doumbo, Ogobara K., Espie, Emmanuelle, Etard, Jean-Francois, Fanello, Caterina I., Faucher, Jean-Francois, Faye, Babacar, Flegg, Jennifer A., Gaye, Oumar, Gething, Peter W., Gonzalez, Raquel, Grandesso, Francesco, Guerin, Philippe J., Guthmann, Jean-Paul, Hamour, Sally, Hasugian, Armedy Ronny, Hay, Simon I., Humphreys, Georgina S., Jullien, Vincent, Juma, Elizabeth, Kamya, Moses R., Karema, Corine, Kiechel, Jean R., Kremsner, Peter G., Krishna, Sanjeev, Lameyre, Valerie, Ibrahim, Laminou M., Lee, Sue J., Lell, Bertrand, Martensson, Andreas, Massougbodji, Achille, Menan, Herve, Menard, Didier, Menendez, Clara, Meremikwu, Martin, Moreira, Clarissa, Nabasumba, Carolyn, Nambozi, Michael, Ndiaye, Jean-Louis, Nikiema, Frederic, Nsanzabana, Christian, Ntoumi, Francine, Ogutu, Bernhards R., Olliaro, Piero, Osorio, Lyda, Ouedraogo, Jean-Bosco, Penali, Louis K., Pene, Mbaye, Pinoges, Loretxu, Piola, Patrice, Price, Ric N., Roper, Cally, Rosenthal, Philip J., Rwagacondo, Claude Emile, Same-Ekobo, Albert, Schramm, Birgit, Seck, Amadou, Sharma, Bhawna, Sibley, Carol Hopkins, Sinou, Veronique, Sirima, Sodiomon B., Smith, Jeffery J., Smithuis, Frank, Some, Fabrice A., Sow, Doudou, Staedke, Sarah G., Stepniewska, Kasia, Swarthout, Todd D., Sylla, Khadime, Talisuna, Ambrose O., Tarning, Joel, Taylor, Walter R. J., Temu, Emmanuel A., Thwing, Julie I., Tjitra, Emiliana, Tine, Roger C. K., Tinto, Halidou, Vaillant, Michel T., Valecha, Neena, Van den Broek, Ingrid, White, Nicholas J., Yeka, Adoke, and Zongo, Issaka

Abstract

Background: Artesunate-amodiaquine (AS-AQ) is one of the most widely used artemisinin-based combination therapies (ACTs) to treat uncomplicated Plasmodium falciparum malaria in Africa. We investigated the impact of different dosing strategies on the efficacy of this combination for the treatment of falciparum malaria. Methods: Individual patient data from AS-AQ clinical trials were pooled using the WorldWide Antimalarial Resistance Network (WWARN) standardised methodology. Risk factors for treatment failure were identified using a Cox regression model with shared frailty across study sites. Results: Forty-three studies representing 9,106 treatments from 1999-2012 were included in the analysis; 4,138 (45.4%) treatments were with a fixed dose combination with an AQ target dose of 30 mg/kg (FDC), 1,293 (14.2%) with a non-fixed dose combination with an AQ target dose of 25 mg/kg (loose NFDC-25), 2,418 (26.6%) with a non-fixed dose combination with an AQ target dose of 30 mg/kg (loose NFDC-30), and the remaining 1,257 (13.8%) with a co-blistered non-fixed dose combination with an AQ target dose of 30 mg/kg (co-blistered NFDC). The median dose of AQ administered was 32.1 mg/kg [IQR: 25.9-38.2], the highest dose being administered to patients treated with co-blistered NFDC (median = 35.3 mg/kg [IQR: 30.6-43.7]) and the lowest to those treated with loose NFDC-25 (median = 25.0 mg/kg [IQR: 22.7-25.0]). Patients treated with FDC received a median dose of 32.4 mg/kg [IQR: 27-39.0]. After adjusting for reinfections, the corrected antimalarial efficacy on day 28 after treatment was similar for co-blistered NFDC (97.9% [95% confidence interval (CI): 97.0-98.8%]) and FDC (98.1% [95% CI: 97.6%-98.5%]; P = 0.799), but significantly lower for the loose NFDC-25 (93.4% [95% CI: 91.9%-94.9%]), and loose NFDC-30 (95.0% [95% CI: 94.1%-95.9%]) (P < 0.001 for all comparisons). After controlling for age, AQ dose, baseline parasitemia and region; treatment with loose NFDC-25 was associated

Published
2015
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50. Clinical determinants of early parasitological response to ACTs in African patients with uncomplicated falciparum malaria : a literature review and meta-analysis of individual patient data

Author

Abdulla, Salim, Adam, Ishag, Adjei, George O., Adjuik, Martin A., Alemayehu, Bereket, Allan, Richard, Arinaitwe, Emmanuel, Ashley, Elizabeth A., Ba, Mamadou S., Barennes, Hubert, Barnes, Karen I., Bassat, Quique, Baudin, Elisabeth, Berens-Riha, Nicole, Bjoerkman, Anders, Bompart, Francois, Bonnet, Maryline, Borrmann, Steffen, Bousema, Teun, Brasseur, Philippe, Bukirwa, Hasifa, Checchi, Francesco, Dahal, Prabin, D'Alessandro, Umberto, Desai, Meghna, Dicko, Alassane, Djimde, Abdoulaye A., Dorsey, Grant, Doumbo, Ogobara K., Drakeley, Chris J., Duparc, Stephan, Eshetu, Teferi, Espie, Emmanuelle, Etard, Jean-Francois, Faiz, Abul M., Falade, Catherine O., Fanello, Caterina I., Faucher, Jean-Francois, Faye, Babacar, Faye, Oumar, Filler, Scott, Flegg, Jennifer A., Fofana, Bakary, Fogg, Carole, Gadalla, Nahla B., Gaye, Oumar, Genton, Blaise, Gething, Peter W., Gil, Jose P., Gonzalez, Raquel, Grandesso, Francesco, Greenhouse, Bryan, Greenwood, Brian, Grivoyannis, Anastasia, Guerin, Philippe J., Guthmann, Jean-Paul, Hamed, Kamal, Hamour, Sally, Hay, Simon I., Hodel, Eva Maria, Humphreys, Georgina S., Hwang, Jimee, Ibrahim, Maman L., Jima, Daddi, Jones, Joel J., Jullien, Vincent, Juma, Elizabeth, Kachur, Patrick S., Kager, Piet A., Kamugisha, Erasmus, Kamya, Moses R., Karema, Corine, Kayentao, Kassoum, Kiechel, Jean-Rene, Kironde, Fred, Kofoed, Poul-Erik, Kremsner, Peter G., Krishna, Sanjeev, Lameyre, Valerie, Lell, Bertrand, Lima, Angeles, Makanga, Michael, Malik, ElFatih M., Marsh, Kevin, Mårtensson, Andreas, Massougbodji, Achille, Menan, Herve, Menard, Didier, Menendez, Clara, Mens, Petra F., Meremikwu, Martin, Moreira, Clarissa, Nabasumba, Carolyn, Nambozi, Michael, Ndiaye, Jean-Louis, Ngasala, Billy E., Nikiema, Frederic, Nsanzabana, Christian, Ntoumi, Francine, Oguike, Mary, Ogutu, Bernhards R., Olliaro, Piero, Omar, Sabah A., Ouedraogo, Jean-Bosco, Owusu-Agyei, Seth, Penali, Louis K., Pene, Mbaye, Peshu, Judy, Piola, Patrice, Plowe, Christopher V., Premji, Zul, Price, Ric N., Randrianarivelojosia, Milijaona, Rombo, Lars, Roper, Cally, Rosenthal, Philip J., Sagara, Issaka, Same-Ekobo, Albert, Sawa, Patrick, Schallig, Henk D. F. H., Schramm, Birgit, Seck, Amadou, Shekalaghe, Seif A., Sibley, Carol H., Sinou, Vronique, Sirima, Sodiomon B., Som, Fabrice A., Sow, Doudou, Staedke, Sarah G., Stepniewska, Kasia, Sutherland, Colin J., Swarthout, Todd D., Sylla, Khadime, Talisuna, Ambrose O., Taylor, Walter R. J., Temu, Emmanuel A., Thwing, Julie I., Tine, Roger C. K., Tinto, Halidou, Tommasini, Silva, Toure, Offianan A., Ursing, Johan, Vaillant, Michel T., Valentini, Giovanni, Van den Broek, Ingrid, Van Vugt, Michele, Ward, Stephen A., Winstanley, Peter A., Yavo, William, Yeka, Adoke, Zolia, Yah M., Zongo, Issaka, Abdulla, Salim, Adam, Ishag, Adjei, George O., Adjuik, Martin A., Alemayehu, Bereket, Allan, Richard, Arinaitwe, Emmanuel, Ashley, Elizabeth A., Ba, Mamadou S., Barennes, Hubert, Barnes, Karen I., Bassat, Quique, Baudin, Elisabeth, Berens-Riha, Nicole, Bjoerkman, Anders, Bompart, Francois, Bonnet, Maryline, Borrmann, Steffen, Bousema, Teun, Brasseur, Philippe, Bukirwa, Hasifa, Checchi, Francesco, Dahal, Prabin, D'Alessandro, Umberto, Desai, Meghna, Dicko, Alassane, Djimde, Abdoulaye A., Dorsey, Grant, Doumbo, Ogobara K., Drakeley, Chris J., Duparc, Stephan, Eshetu, Teferi, Espie, Emmanuelle, Etard, Jean-Francois, Faiz, Abul M., Falade, Catherine O., Fanello, Caterina I., Faucher, Jean-Francois, Faye, Babacar, Faye, Oumar, Filler, Scott, Flegg, Jennifer A., Fofana, Bakary, Fogg, Carole, Gadalla, Nahla B., Gaye, Oumar, Genton, Blaise, Gething, Peter W., Gil, Jose P., Gonzalez, Raquel, Grandesso, Francesco, Greenhouse, Bryan, Greenwood, Brian, Grivoyannis, Anastasia, Guerin, Philippe J., Guthmann, Jean-Paul, Hamed, Kamal, Hamour, Sally, Hay, Simon I., Hodel, Eva Maria, Humphreys, Georgina S., Hwang, Jimee, Ibrahim, Maman L., Jima, Daddi, Jones, Joel J., Jullien, Vincent, Juma, Elizabeth, Kachur, Patrick S., Kager, Piet A., Kamugisha, Erasmus, Kamya, Moses R., Karema, Corine, Kayentao, Kassoum, Kiechel, Jean-Rene, Kironde, Fred, Kofoed, Poul-Erik, Kremsner, Peter G., Krishna, Sanjeev, Lameyre, Valerie, Lell, Bertrand, Lima, Angeles, Makanga, Michael, Malik, ElFatih M., Marsh, Kevin, Mårtensson, Andreas, Massougbodji, Achille, Menan, Herve, Menard, Didier, Menendez, Clara, Mens, Petra F., Meremikwu, Martin, Moreira, Clarissa, Nabasumba, Carolyn, Nambozi, Michael, Ndiaye, Jean-Louis, Ngasala, Billy E., Nikiema, Frederic, Nsanzabana, Christian, Ntoumi, Francine, Oguike, Mary, Ogutu, Bernhards R., Olliaro, Piero, Omar, Sabah A., Ouedraogo, Jean-Bosco, Owusu-Agyei, Seth, Penali, Louis K., Pene, Mbaye, Peshu, Judy, Piola, Patrice, Plowe, Christopher V., Premji, Zul, Price, Ric N., Randrianarivelojosia, Milijaona, Rombo, Lars, Roper, Cally, Rosenthal, Philip J., Sagara, Issaka, Same-Ekobo, Albert, Sawa, Patrick, Schallig, Henk D. F. H., Schramm, Birgit, Seck, Amadou, Shekalaghe, Seif A., Sibley, Carol H., Sinou, Vronique, Sirima, Sodiomon B., Som, Fabrice A., Sow, Doudou, Staedke, Sarah G., Stepniewska, Kasia, Sutherland, Colin J., Swarthout, Todd D., Sylla, Khadime, Talisuna, Ambrose O., Taylor, Walter R. J., Temu, Emmanuel A., Thwing, Julie I., Tine, Roger C. K., Tinto, Halidou, Tommasini, Silva, Toure, Offianan A., Ursing, Johan, Vaillant, Michel T., Valentini, Giovanni, Van den Broek, Ingrid, Van Vugt, Michele, Ward, Stephen A., Winstanley, Peter A., Yavo, William, Yeka, Adoke, Zolia, Yah M., and Zongo, Issaka

Abstract

Background: Artemisinin-resistant Plasmodium falciparum has emerged in the Greater Mekong sub-region and poses a major global public health threat. Slow parasite clearance is a key clinical manifestation of reduced susceptibility to artemisinin. This study was designed to establish the baseline values for clearance in patients from Sub-Saharan African countries with uncomplicated malaria treated with artemisinin-based combination therapies (ACTs). Methods: A literature review in PubMed was conducted in March 2013 to identify all prospective clinical trials (uncontrolled trials, controlled trials and randomized controlled trials), including ACTs conducted in Sub-Saharan Africa, between 1960 and 2012. Individual patient data from these studies were shared with the WorldWide Antimalarial Resistance Network (WWARN) and pooled using an a priori statistical analytical plan. Factors affecting early parasitological response were investigated using logistic regression with study sites fitted as a random effect. The risk of bias in included studies was evaluated based on study design, methodology and missing data. Results: In total, 29,493 patients from 84 clinical trials were included in the analysis, treated with artemether-lumefantrine (n = 13,664), artesunate-amodiaquine (n = 11,337) and dihydroartemisinin-piperaquine (n = 4,492). The overall parasite clearance rate was rapid. The parasite positivity rate (PPR) decreased from 59.7 % (95 % CI: 54.5-64.9) on day 1 to 6.7 % (95 % CI: 4.8-8.7) on day 2 and 0.9 % (95 % CI: 0.5-1.2) on day 3. The 95th percentile of observed day 3 PPR was 5.3 %. Independent risk factors predictive of day 3 positivity were: high baseline parasitaemia (adjusted odds ratio (AOR) = 1.16 (95 % CI: 1.08-1.25); per 2-fold increase in parasite density, P <0.001); fever (>37.5 degrees C) (AOR = 1.50 (95 % CI: 1.06-2.13), P = 0.022); severe anaemia (AOR = 2.04 (95 % CI: 1.21-3.44), P = 0.008); areas of low/moderate transmission setting (AOR = 2.71 (

Published
2015
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