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

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

doi:https://doi.org/10.1186/s12916-015-0445-x

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

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

Research output: Contribution to journal › Review article › Academic › peer-review

55 Citations (Scopus)

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 (95 % CI: 1.38-5.36), P = 0.004); and treatment with the loose formulation of artesunate-amodiaquine (AOR = 2.27 (95 % CI: 1.14-4.51), P = 0.020, compared to dihydroartemisinin-piperaquine). Conclusions: The three ACTs assessed in this analysis continue to achieve rapid early parasitological clearance across the sites assessed in Sub-Saharan Africa. A threshold of 5 % day 3 parasite positivity from a minimum sample size of 50 patients provides a more sensitive benchmark in Sub-Saharan Africa compared to the current recommended threshold of 10 % to trigger further investigation of artemisinin susceptibility

Original language	English
Pages (from-to)	212
Journal	BMC medicine
Volume	13
DOIs	https://doi.org/10.1186/s12916-015-0445-x
Publication status	Published - 2015

Access to Document

https://doi.org/10.1186/s12916-015-0445-x

Cite this

Abdulla, S., Adam, I., Adjei, G. O., Adjuik, M. A., Alemayehu, B., Allan, R., Arinaitwe, E., Ashley, E. A., Ba, M. S., Barennes, H., Barnes, K. I., Bassat, Q., Baudin, E., Berens-Riha, N., Bjoerkman, A., Bompart, F., Bonnet, M., Borrmann, S., Bousema, T., ... Zongo, I. (2015). 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. BMC medicine, 13, 212. https://doi.org/10.1186/s12916-015-0445-x

@article{5fdeaa69adf8485687dc8336adbbbb3f,

title = "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",

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 (95 % CI: 1.38-5.36), P = 0.004); and treatment with the loose formulation of artesunate-amodiaquine (AOR = 2.27 (95 % CI: 1.14-4.51), P = 0.020, compared to dihydroartemisinin-piperaquine). Conclusions: The three ACTs assessed in this analysis continue to achieve rapid early parasitological clearance across the sites assessed in Sub-Saharan Africa. A threshold of 5 % day 3 parasite positivity from a minimum sample size of 50 patients provides a more sensitive benchmark in Sub-Saharan Africa compared to the current recommended threshold of 10 % to trigger further investigation of artemisinin susceptibility",

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

year = "2015",

doi = "https://doi.org/10.1186/s12916-015-0445-x",

language = "English",

volume = "13",

pages = "212",

journal = "BMC medicine",

issn = "1464-2662",

publisher = "BioMed Central",

}

Abdulla, S, Adam, I, Adjei, GO, Adjuik, MA, Alemayehu, B, Allan, R, Arinaitwe, E, Ashley, EA, Ba, MS, Barennes, H, Barnes, KI, Bassat, Q, Baudin, E, Berens-Riha, N, Bjoerkman, A, Bompart, F, Bonnet, M, Borrmann, S, Bousema, T, Brasseur, P, Bukirwa, H, Checchi, F, Dahal, P, d'Alessandro, U, Desai, M, Dicko, A, Djimde, AA, Dorsey, G, Doumbo, OK, Drakeley, CJ, Duparc, S, Eshetu, T, Espie, E, Etard, J-F, Faiz, AM, Falade, CO, Fanello, CI, Faucher, J-F, Faye, B, Faye, O, Filler, S, Flegg, JA, Fofana, B, Fogg, C, Gadalla, NB, Gaye, O, Genton, B, Gething, PW, Gil, JP, Gonzalez, R, Grandesso, F, Greenhouse, B, Greenwood, B, Grivoyannis, A, Guerin, PJ, Guthmann, J-P, Hamed, K, Hamour, S, Hay, SI, Hodel, EM, Humphreys, GS, Hwang, J, Ibrahim, ML, Jima, D, Jones, JJ, Jullien, V, Juma, E, Kachur, PS, Kager, PA, Kamugisha, E, Kamya, MR, Karema, C, Kayentao, K, Kiechel, J-R, Kironde, F, Kofoed, P-E, Kremsner, PG, Krishna, S, Lameyre, V, Lell, B, Lima, A, Makanga, M, Malik, EM, Marsh, K, Martensson, A, Massougbodji, A, Menan, H, Menard, D, Menendez, C, Mens, PF, Meremikwu, M, Moreira, C, Nabasumba, C, Nambozi, M, Ndiaye, J-L, Ngasala, BE, Nikiema, F, Nsanzabana, C, Ntoumi, F, Oguike, M, Ogutu, BR, Olliaro, P, Omar, SA, Ouedraogo, J-B, Owusu-Agyei, S, Penali, LK, Pene, M, Peshu, J, Piola, P, Plowe, CV, Premji, Z, Price, RN, Randrianarivelojosia, M, Rombo, L, Roper, C, Rosenthal, PJ, Sagara, I, Same-Ekobo, A, Sawa, P, Schallig, HDFH, Schramm, B, Seck, A, Shekalaghe, SA, Sibley, CH, Sinou, V, Sirima, SB, Som, FA, Sow, D, Staedke, SG, Stepniewska, K, Sutherland, CJ, Swarthout, TD, Sylla, K, Talisuna, AO, Taylor, WRJ, Temu, EA, Thwing, JI, Tine, RCK, Tinto, H, Tommasini, S, Toure, OA, Ursing, J, Vaillant, MT, Valentini, G, van den Broek, I, van Vugt, M, Ward, SA, Winstanley, PA, Yavo, W, Yeka, A, Zolia, YM & Zongo, I 2015, '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', BMC medicine, vol. 13, pp. 212. https://doi.org/10.1186/s12916-015-0445-x

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. / Abdulla, Salim; Adam, Ishag; Adjei, George O. et al.
In: BMC medicine, Vol. 13, 2015, p. 212.

Research output: Contribution to journal › Review article › Academic › peer-review

TY - JOUR

T1 - 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

AU - Abdulla, Salim

AU - Adam, Ishag

AU - Adjei, George O.

AU - Adjuik, Martin A.

AU - Alemayehu, Bereket

AU - Allan, Richard

AU - Arinaitwe, Emmanuel

AU - Ashley, Elizabeth A.

AU - Ba, Mamadou S.

AU - Barennes, Hubert

AU - Barnes, Karen I.

AU - Bassat, Quique

AU - Baudin, Elisabeth

AU - Berens-Riha, Nicole

AU - Bjoerkman, Anders

AU - Bompart, Francois

AU - Bonnet, Maryline

AU - Borrmann, Steffen

AU - Bousema, Teun

AU - Brasseur, Philippe

AU - Bukirwa, Hasifa

AU - Checchi, Francesco

AU - Dahal, Prabin

AU - d'Alessandro, Umberto

AU - Desai, Meghna

AU - Dicko, Alassane

AU - Djimde, Abdoulaye A.

AU - Dorsey, Grant

AU - Doumbo, Ogobara K.

AU - Drakeley, Chris J.

AU - Duparc, Stephan

AU - Eshetu, Teferi

AU - Espie, Emmanuelle

AU - Etard, Jean-Francois

AU - Faiz, Abul M.

AU - Falade, Catherine O.

AU - Fanello, Caterina I.

AU - Faucher, Jean-Francois

AU - Faye, Babacar

AU - Faye, Oumar

AU - Filler, Scott

AU - Flegg, Jennifer A.

AU - Fofana, Bakary

AU - Fogg, Carole

AU - Gadalla, Nahla B.

AU - Gaye, Oumar

AU - Genton, Blaise

AU - Gething, Peter W.

AU - Gil, Jose P.

AU - Gonzalez, Raquel

AU - Grandesso, Francesco

AU - Greenhouse, Bryan

AU - Greenwood, Brian

AU - Grivoyannis, Anastasia

AU - Guerin, Philippe J.

AU - Guthmann, Jean-Paul

AU - Hamed, Kamal

AU - Hamour, Sally

AU - Hay, Simon I.

AU - Hodel, Eva Maria

AU - Humphreys, Georgina S.

AU - Hwang, Jimee

AU - Ibrahim, Maman L.

AU - Jima, Daddi

AU - Jones, Joel J.

AU - Jullien, Vincent

AU - Juma, Elizabeth

AU - Kachur, Patrick S.

AU - Kager, Piet A.

AU - Kamugisha, Erasmus

AU - Kamya, Moses R.

AU - Karema, Corine

AU - Kayentao, Kassoum

AU - Kiechel, Jean-Rene

AU - Kironde, Fred

AU - Kofoed, Poul-Erik

AU - Kremsner, Peter G.

AU - Krishna, Sanjeev

AU - Lameyre, Valerie

AU - Lell, Bertrand

AU - Lima, Angeles

AU - Makanga, Michael

AU - Malik, Elfatih M.

AU - Marsh, Kevin

AU - Martensson, Andreas

AU - Massougbodji, Achille

AU - Menan, Herve

AU - Menard, Didier

AU - Menendez, Clara

AU - Mens, Petra F.

AU - Meremikwu, Martin

AU - Moreira, Clarissa

AU - Nabasumba, Carolyn

AU - Nambozi, Michael

AU - Ndiaye, Jean-Louis

AU - Ngasala, Billy E.

AU - Nikiema, Frederic

AU - Nsanzabana, Christian

AU - Ntoumi, Francine

AU - Oguike, Mary

AU - Ogutu, Bernhards R.

AU - Olliaro, Piero

AU - Omar, Sabah A.

AU - Ouedraogo, Jean-Bosco

AU - Owusu-Agyei, Seth

AU - Penali, Louis K.

AU - Pene, Mbaye

AU - Peshu, Judy

AU - Piola, Patrice

AU - Plowe, Christopher V.

AU - Premji, Zul

AU - Price, Ric N.

AU - Randrianarivelojosia, Milijaona

AU - Rombo, Lars

AU - Roper, Cally

AU - Rosenthal, Philip J.

AU - Sagara, Issaka

AU - Same-Ekobo, Albert

AU - Sawa, Patrick

AU - Schallig, Henk D. F. H.

AU - Schramm, Birgit

AU - Seck, Amadou

AU - Shekalaghe, Seif A.

AU - Sibley, Carol H.

AU - Sinou, Vronique

AU - Sirima, Sodiomon B.

AU - Som, Fabrice A.

AU - Sow, Doudou

AU - Staedke, Sarah G.

AU - Stepniewska, Kasia

AU - Sutherland, Colin J.

AU - Swarthout, Todd D.

AU - Sylla, Khadime

AU - Talisuna, Ambrose O.

AU - Taylor, Walter R. J.

AU - Temu, Emmanuel A.

AU - Thwing, Julie I.

AU - Tine, Roger C. K.

AU - Tinto, Halidou

AU - Tommasini, Silva

AU - Toure, Offianan A.

AU - Ursing, Johan

AU - Vaillant, Michel T.

AU - Valentini, Giovanni

AU - van den Broek, Ingrid

AU - van Vugt, Michele

AU - Ward, Stephen A.

AU - Winstanley, Peter A.

AU - Yavo, William

AU - Yeka, Adoke

AU - Zolia, Yah M.

AU - Zongo, Issaka

PY - 2015

Y1 - 2015

N2 - 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 (95 % CI: 1.38-5.36), P = 0.004); and treatment with the loose formulation of artesunate-amodiaquine (AOR = 2.27 (95 % CI: 1.14-4.51), P = 0.020, compared to dihydroartemisinin-piperaquine). Conclusions: The three ACTs assessed in this analysis continue to achieve rapid early parasitological clearance across the sites assessed in Sub-Saharan Africa. A threshold of 5 % day 3 parasite positivity from a minimum sample size of 50 patients provides a more sensitive benchmark in Sub-Saharan Africa compared to the current recommended threshold of 10 % to trigger further investigation of artemisinin susceptibility

AB - 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 (95 % CI: 1.38-5.36), P = 0.004); and treatment with the loose formulation of artesunate-amodiaquine (AOR = 2.27 (95 % CI: 1.14-4.51), P = 0.020, compared to dihydroartemisinin-piperaquine). Conclusions: The three ACTs assessed in this analysis continue to achieve rapid early parasitological clearance across the sites assessed in Sub-Saharan Africa. A threshold of 5 % day 3 parasite positivity from a minimum sample size of 50 patients provides a more sensitive benchmark in Sub-Saharan Africa compared to the current recommended threshold of 10 % to trigger further investigation of artemisinin susceptibility

U2 - https://doi.org/10.1186/s12916-015-0445-x

DO - https://doi.org/10.1186/s12916-015-0445-x

M3 - Review article

C2 - 26343145

SN - 1464-2662

VL - 13

SP - 212

JO - BMC medicine

JF - BMC medicine

ER -