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 Bjorkman, Francois Bompart, Maryline Bonnet, Steffen Borrmann, Teun Bousema, Philippe Brasseur & 133 others 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 François Etard, Abul M. Faiz, Catherine O. Falade, Caterina I. Fanello, Jean François 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 González, Francesco Grandesso, Bryan Greenhouse, Brian Greenwood, Anastasia Grivoyannis, Philippe J. Guerin, Jean Paul Guthmann, Kamal Hamed, Sally Hamour, Simon I. Hay, Eva Maria Hode, 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 Kieche, Fred Kironde, Poul Erik Kofoed, Peter G. Kremsner, Sanjeev Krishna, Valerie Lameyre, Bertrand Lell, Angeles Lima, Michael Makanga, El Fatih 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, Veronique Sinou, Sodiomon B. Sirima, Fabrice A. Some, 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, Artemisinin based Combination Therapy (ACT) Africa Baseline Study Group WWARN Artemisinin based Combination Therapy (ACT) Africa Baseline Study Group

    Research output: Contribution to journalArticleResearchpeer-review

    2 Downloads (Pure)

    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 °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 languageEnglish
    Article number212
    Pages (from-to)1-16
    Number of pages16
    JournalBMC Medicine
    Volume13
    Issue number1
    DOIs
    Publication statusPublished - 7 Sep 2015

    Fingerprint

    Falciparum Malaria
    Meta-Analysis
    dihydroartemisinin
    Parasites
    Therapeutics
    Clinical Trials
    Benchmarking
    Parasitemia
    Africa South of the Sahara
    Antimalarials
    Plasmodium falciparum
    PubMed
    Malaria
    artemisinine
    Anemia
    Randomized Controlled Trials
    Public Health

    Cite this

    Abdulla, S., Adam, I., Adjei, G. O., Adjuik, M. A., Alemayehu, B., Allan, R., ... WWARN Artemisinin based Combination Therapy (ACT) Africa Baseline Study Group, A. B. C. T. ACT. A. B. S. G. (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(1), 1-16. [212]. https://doi.org/10.1186/s12916-015-0445-x
    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 ; Bjorkman, 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 François ; Faiz, Abul M. ; Falade, Catherine O. ; Fanello, Caterina I. ; Faucher, Jean François ; 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. ; González, Raquel ; Grandesso, Francesco ; Greenhouse, Bryan ; Greenwood, Brian ; Grivoyannis, Anastasia ; Guerin, Philippe J. ; Guthmann, Jean Paul ; Hamed, Kamal ; Hamour, Sally ; Hay, Simon I. ; Hode, 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 ; Kieche, Jean Rene ; Kironde, Fred ; Kofoed, Poul Erik ; Kremsner, Peter G. ; Krishna, Sanjeev ; Lameyre, Valerie ; Lell, Bertrand ; Lima, Angeles ; Makanga, Michael ; Malik, El Fatih M. ; Marsh, Kevin ; Martensson, 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, Veronique ; Sirima, Sodiomon B. ; Some, 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 ; Vugt, Michele Van ; Ward, Stephen A. ; Winstanley, Peter A. ; Yavo, William ; Yeka, Adoke ; Zolia, Yah M. ; Zongo, Issaka ; WWARN Artemisinin based Combination Therapy (ACT) Africa Baseline Study Group, Artemisinin based Combination Therapy (ACT) Africa Baseline Study Group. / 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. In: BMC Medicine. 2015 ; Vol. 13, No. 1. pp. 1-16.
    @article{38aa86b873384d74999d82b4c3bac962,
    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 °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.",
    keywords = "amodiaquine, amodiaquine plus artesunate, arteether, artemether, artemether plus benflumetol, artemisinin, artesunate, atovaquone, atovaquone plus proguanil, azithromycin, benflumetol, chloroquine, chlorproguanil, clindamycin, cycloguanil, dapsone, dihydroartemisinin, dihydroartemisinin plus piperaquine, doxycycline, halofantrine, mefloquine, naphthoquinone, piperaquine, primaquine, proguanil, pyrimethamine, pyronaridine, quinidine, quinine, unindexed drug, Africa south of the Sahara, African, anemia, Article, disease severity, drug response, factorial analysis, fever, human, malaria falciparum, meta analysis, nonhuman, outcome assessment, parasite clearance, parasitemia, patient information, prospective study, randomized controlled trial (topic), risk assessment, risk factor, statistical analysis, systematic review",
    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 Bjorkman 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 Etard, {Jean Fran{\cc}ois} and Faiz, {Abul M.} and Falade, {Catherine O.} and Fanello, {Caterina I.} and Faucher, {Jean Fran{\cc}ois} 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 Gonz{\'a}lez and Francesco Grandesso and Bryan Greenhouse and Brian Greenwood and Anastasia Grivoyannis and Guerin, {Philippe J.} and Guthmann, {Jean Paul} and Kamal Hamed and Sally Hamour and Hay, {Simon I.} and Hode, {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 Kieche, {Jean Rene} and Fred Kironde and Kofoed, {Poul Erik} and Kremsner, {Peter G.} and Sanjeev Krishna and Valerie Lameyre and Bertrand Lell and Angeles Lima and Michael Makanga and Malik, {El Fatih 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 Ndiaye, {Jean Louis} 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 Ouedraogo, {Jean Bosco} 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 Veronique Sinou and Sirima, {Sodiomon B.} and Some, {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 Vugt, {Michele Van} and Ward, {Stephen A.} and Winstanley, {Peter A.} and William Yavo and Adoke Yeka and Zolia, {Yah M.} and Issaka Zongo and {WWARN Artemisinin based Combination Therapy (ACT) Africa Baseline Study Group}, {Artemisinin based Combination Therapy (ACT) Africa Baseline Study Group}",
    year = "2015",
    month = "9",
    day = "7",
    doi = "10.1186/s12916-015-0445-x",
    language = "English",
    volume = "13",
    pages = "1--16",
    journal = "BMC Medicine",
    issn = "1741-7015",
    publisher = "BioMed Central",
    number = "1",

    }

    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, Bjorkman, 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, JF, Faiz, AM, Falade, CO, Fanello, CI, Faucher, JF, Faye, B, Faye, O, Filler, S, Flegg, JA, Fofana, B, Fogg, C, Gadalla, NB, Gaye, O, Genton, B, Gething, PW, Gil, JP, González, R, Grandesso, F, Greenhouse, B, Greenwood, B, Grivoyannis, A, Guerin, PJ, Guthmann, JP, Hamed, K, Hamour, S, Hay, SI, Hode, 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, Kieche, JR, Kironde, F, Kofoed, PE, Kremsner, PG, Krishna, S, Lameyre, V, Lell, B, Lima, A, Makanga, M, Malik, EFM, Marsh, K, Martensson, A, Massougbodji, A, Menan, H, Menard, D, Menendez, C, Mens, PF, Meremikwu, M, Moreira, C, Nabasumba, C, Nambozi, M, Ndiaye, JL, Ngasala, BE, Nikiema, F, Nsanzabana, C, Ntoumi, F, Oguike, M, Ogutu, BR, Olliaro, P, Omar, SA, Ouedraogo, JB, 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, Some, 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, Vugt, MV, Ward, SA, Winstanley, PA, Yavo, W, Yeka, A, Zolia, YM, Zongo, I & WWARN Artemisinin based Combination Therapy (ACT) Africa Baseline Study Group, ABCTACTABSG 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, no. 1, 212, pp. 1-16. 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.; 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; Bjorkman, 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 François; Faiz, Abul M.; Falade, Catherine O.; Fanello, Caterina I.; Faucher, Jean François; 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.; González, Raquel; Grandesso, Francesco; Greenhouse, Bryan; Greenwood, Brian; Grivoyannis, Anastasia; Guerin, Philippe J.; Guthmann, Jean Paul; Hamed, Kamal; Hamour, Sally; Hay, Simon I.; Hode, 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; Kieche, Jean Rene; Kironde, Fred; Kofoed, Poul Erik; Kremsner, Peter G.; Krishna, Sanjeev; Lameyre, Valerie; Lell, Bertrand; Lima, Angeles; Makanga, Michael; Malik, El Fatih M.; Marsh, Kevin; Martensson, 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, Veronique; Sirima, Sodiomon B.; Some, 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; Vugt, Michele Van; Ward, Stephen A.; Winstanley, Peter A.; Yavo, William; Yeka, Adoke; Zolia, Yah M.; Zongo, Issaka; WWARN Artemisinin based Combination Therapy (ACT) Africa Baseline Study Group, Artemisinin based Combination Therapy (ACT) Africa Baseline Study Group.

    In: BMC Medicine, Vol. 13, No. 1, 212, 07.09.2015, p. 1-16.

    Research output: Contribution to journalArticleResearchpeer-review

    TY - JOUR

    T1 - Clinical determinants of early parasitological response to ACTs in African patients with uncomplicated falciparum malaria

    T2 - 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 - Bjorkman, 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 François

    AU - Faiz, Abul M.

    AU - Falade, Catherine O.

    AU - Fanello, Caterina I.

    AU - Faucher, Jean François

    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 - González, 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 - Hode, 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 - Kieche, 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, El Fatih 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, Veronique

    AU - Sirima, Sodiomon B.

    AU - Some, 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 - Vugt, Michele Van

    AU - Ward, Stephen A.

    AU - Winstanley, Peter A.

    AU - Yavo, William

    AU - Yeka, Adoke

    AU - Zolia, Yah M.

    AU - Zongo, Issaka

    AU - WWARN Artemisinin based Combination Therapy (ACT) Africa Baseline Study Group, Artemisinin based Combination Therapy (ACT) Africa Baseline Study Group

    PY - 2015/9/7

    Y1 - 2015/9/7

    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 °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 °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.

    KW - amodiaquine

    KW - amodiaquine plus artesunate

    KW - arteether

    KW - artemether

    KW - artemether plus benflumetol

    KW - artemisinin

    KW - artesunate

    KW - atovaquone

    KW - atovaquone plus proguanil

    KW - azithromycin

    KW - benflumetol

    KW - chloroquine

    KW - chlorproguanil

    KW - clindamycin

    KW - cycloguanil

    KW - dapsone

    KW - dihydroartemisinin

    KW - dihydroartemisinin plus piperaquine

    KW - doxycycline

    KW - halofantrine

    KW - mefloquine

    KW - naphthoquinone

    KW - piperaquine

    KW - primaquine

    KW - proguanil

    KW - pyrimethamine

    KW - pyronaridine

    KW - quinidine

    KW - quinine

    KW - unindexed drug

    KW - Africa south of the Sahara

    KW - African

    KW - anemia

    KW - Article

    KW - disease severity

    KW - drug response

    KW - factorial analysis

    KW - fever

    KW - human

    KW - malaria falciparum

    KW - meta analysis

    KW - nonhuman

    KW - outcome assessment

    KW - parasite clearance

    KW - parasitemia

    KW - patient information

    KW - prospective study

    KW - randomized controlled trial (topic)

    KW - risk assessment

    KW - risk factor

    KW - statistical analysis

    KW - systematic review

    UR - http://www.scopus.com/inward/record.url?scp=84941618712&partnerID=8YFLogxK

    U2 - 10.1186/s12916-015-0445-x

    DO - 10.1186/s12916-015-0445-x

    M3 - Article

    VL - 13

    SP - 1

    EP - 16

    JO - BMC Medicine

    JF - BMC Medicine

    SN - 1741-7015

    IS - 1

    M1 - 212

    ER -