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1. Prevalence of asymptomatic parasitaemia among household members of children under seasonal malaria chemoprevention coverage and comparison of the performance of standard rapid diagnostic tests versus ultrasensitive RDT for the detection of asymptomatic parasitaemia in Nanoro, Burkina Faso

Author

Kambou, Sié A. Elisée, Millogo, Kié Solange, Sondo, Paul, Kabore, Bérenger, Kouevi, Amélé Fifi Chantal, Bouda, Ismaila, Rouamba, Toussaint, Derra, Karim, Tahita, Mark Christian, Ilboudo, Hamidou, Rouamba, Eli, Tougri, Gauthier, Otienoburu, Sabina Dahlström, Dhorda, Mehul, Bamba, Sanata, Guerin, Philippe J, and Tinto, Halidou

Published
2024
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2. A randomised controlled trial to compare the efficacy, safety, and tolerability of low dose, short course primaquine in adults with uncomplicated P. vivax malaria in two hospitals in India

Author

Ahmad, Sundus Shafat, Verma, Reena, Commons, Robert J., Nitika, Singh-Phulgenda, Sauman, Chhajed, Rutuja, Bharti, Praveen K., Behera, Beauty, Naser, Syed Mohammad, Pal, Salil Kumar, Ranjit, Parinita Halder, Baharia, Rajendra Kumar, Solanki, Bhavin, Upadhyay, K. J., Guerin, Philippe J., Sharma, Amit, Price, Ric N., Rahi, Manju, and Thriemer, Kamala

Published
2024
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3. Primaquine for uncomplicated Plasmodium vivax malaria in children younger than 15 years: a systematic review and individual patient data meta-analysis

Author

Adhikari, Bipin, Alam, Mohammad Shafiul, Anstey, Nicholas M, Assefa, Ashenafi, Baird, J Kevin, Boyd, Sarah C, Chau, Nguyen H, Day, Nicholas PJ, Degaga, Tamiru Shibiru, Dondorp, Arjen M, Erhart, Annette, Ferreira, Marcelo U, Ghimire, Prakash, Khan, Wasif A, Ley, Benedikt, Mekuria, Asrat H, Mueller, Ivo, Naadim, Mohammad N, Nosten, Francois, Price, David J, Pukrittayakamee, Sasithon, Rowland, Mark, Sattabongkot, Jetsumon, SuarezKurtz, Guilherme, Sutanto, Inge, von Seidlein, Lorenz, William, Timothy, Woodrow, Charles J, Woyessa, Adugna, Commons, Robert J, Rajasekhar, Megha, Allen, Elizabeth N, Yilma, Daniel, Chotsiri, Palang, Abreha, Tesfay, Adam, Ishag, Awab, Ghulam Rahim, Barber, Bridget E, Brasil, Larissa W, Chu, Cindy S, Cui, Liwang, Edler, Peta, Gomes, Margarete do Socorro M, Gonzalez‑Ceron, Lilia, Grigg, Matthew J, Hamid, Muzamil Mahdi Abdel, Hwang, Jimee, Karunajeewa, Harin, Lacerda, Marcus V G, Ladeia-Andrade, Simone, Leslie, Toby, Longley, Rhea J, Monteiro, Wuelton Marcelo, Pasaribu, Ayodhia Pitaloka, Poespoprodjo, Jeanne Rini, Richmond, Caitlin L, Rijal, Komal Raj, Taylor, Walter R J, Thanh, Pham Vinh, Thriemer, Kamala, Vieira, José Luiz F, White, Nicholas J, Zuluaga-Idarraga, Lina M, Workman, Lesley J, Tarning, Joel, Stepniewska, Kasia, Guerin, Philippe J, Simpson, Julie A, Barnes, Karen I, and Price, Ric N

Published
2024
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4. Effect of adherence to primaquine on the risk of Plasmodium vivax recurrence: a WorldWide Antimalarial Resistance Network systematic review and individual patient data meta-analysis

Author

Mehdipour, Parinaz, Rajasekhar, Megha, Dini, Saber, Zaloumis, Sophie, Abreha, Tesfay, Adam, Ishag, Awab, Ghulam Rahim, Baird, J. Kevin, Brasil, Larissa W., Chu, Cindy S., Cui, Liwang, Daher, André, do Socorro M Gomes, Margarete, Gonzalez‑Ceron, Lilia, Hwang, Jimee, Karunajeewa, Harin, Lacerda, Marcus V. G., Ladeia-Andrade, Simone, Leslie, Toby, Ley, Benedikt, Lidia, Kartini, Llanos-Cuentas, Alejandro, Longley, Rhea J., Monteiro, Wuelton Marcelo, Pereira, Dhelio B., Rijal, Komal Raj, Saravu, Kavitha, Sutanto, Inge, Taylor, Walter R. J., Thanh, Pham Vinh, Thriemer, Kamala, Vieira, José Luiz F., White, Nicholas J., Zuluaga-Idarraga, Lina M., Guerin, Philippe J., Price, Ric N., Simpson, Julie A., and Commons, Robert J.

Published
2023
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5. Does acute malnutrition in young children increase the risk of treatment failure following artemisinin-based combination therapy? A WWARN individual patient data meta-analysis

Author

Stepniewska, Kasia, Allan, Richard, Anvikar, Anupkumar R, Anyorigiya, Thomas A, Ashley, Elizabeth A, Bassat, Quique, Baudin, Elisabeth, Bjorkman, Anders, Bonnet, Maryline, Boulton, Caroline, Bousema, Teun, Carn, Gwenaelle, Carrara, Verena I, D'Alessandro, Umberto, Davis, Timothy ME, Denoeud-Ndam, Lise, Desai, Meghna, Djimde, Abdoulaye A, Dorsey, Grant, Etard, Jean-François, Falade, Catherine, Fanello, Caterina, Gaye, Oumar, Gonzalez, Raquel, Grandesso, Francesco, Grivoyannis, Anastasia D, Grais, Rebecca F, Humphreys, Georgina S, Ishengoma, Deus S, Karema, Corine, Kayentao, Kassoum, Kennon, Kalynn, Kremsner, PeterG, Laman, Moses, Laminou, Ibrahim M, Macete, Eusebio, Martensson, Andreas, Mayxay, Mayfong, Menan, Hervé IB, Menéndez, Clara, Moore, Brioni R, Nabasumba, Carolyn, Ndiaye, Jean-Louis, Nhama, Abel, Nosten, Francois, Onyamboko, Marie, Phyo, Aung Pyae, Ramharter, Michael, Rosenthal, Philip J, Schramm, Birgit, Sharma, Yagya D, Sirima, Sodiomon B, Strub-Wourgaft, Nathalie, Sylla, Khadime, Talisuna, Ambrose O, Temu, Emmanuel A, Thwing, Julie I, Tinto, Halidou, Valentini, Giovanni, White, Nicholas J, Yeka, Adoke, Isanaka, Sheila, Barnes, Karen I, and Guerin, Philippe J

Published
2024
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7. Effect of primaquine dose on the risk of recurrence in patients with uncomplicated Plasmodium vivax: a systematic review and individual patient data meta-analysis

Author

Adhikari, Bipin, Anstey, Nicholas M, Assefa, Ashenafi, Boyd, Sarah C, Chau, Nguyen Hoang, Day, Nicholas PJ, Degaga, Tamiru Shibiru, Dondorp, Arjen M, Erhart, Annette, Ferreira, Marcelo Urbano, Ghimire, Prakash, Green, Justin A, Koh, Gavin CKW, Mekuria, Asrat Hailu, Mueller, Ivo, Naadim, Mohammad Nader, Nelwan, Erni J, Nosten, Francois, Price, David J, Sattabongkot, Jetsumon, Stepniewska, Kasia, von Seidlein, Lorenz, William, Timothy, Woodrow, Charles J, Woyessa, Adugna, Commons, Robert J, Rajasekhar, Megha, Edler, Peta, Abreha, Tesfay, Awab, Ghulam R, Baird, J Kevin, Barber, Bridget E, Chu, Cindy S, Cui, Liwang, Daher, André, Gonzalez-Ceron, Lilia, Grigg, Matthew J, Hwang, Jimee, Karunajeewa, Harin, Lacerda, Marcus V G, Ladeia-Andrade, Simone, Lidia, Kartini, Llanos-Cuentas, Alejandro, Longley, Rhea J, Pereira, Dhelio B, Pasaribu, Ayodhia P, Pukrittayakamee, Sasithon, Rijal, Komal R, Sutanto, Inge, Taylor, Walter R J, Thanh, Pham V, Thriemer, Kamala, Vieira, José Luiz F, Watson, James A, Zuluaga-Idarraga, Lina M, White, Nicholas J, Guerin, Philippe J, Simpson, Julie A, and Price, Ric N

Published
2024
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8. Primaquine dose and the risk of haemolysis in patients with uncomplicated Plasmodium vivax malaria: a systematic review and individual patient data meta-analysis

Author

Adhikari, Bipin, Alam, Mohammad Shafiul, Anstey, Nicholas M, Assefa, Ashenafi, Boyd, Sarah C, Chau, Nguyen Hoang, Day, Nicholas PJ, Degaga, Tamiru Shibiru, Dondorp, Arjen M, Ferreira, Marcelo Urbano, Ghimire, Prakash, Green, Justin A, Khan, Wasif Ali, Koh, Gavin CKW, Mekuria, Asrat Hailu, Naadim, Mohammad Nader, Nelwan, Erni J, Nosten, Francois, Pasaribu, Ayodhia Pitaloka, Price, David J, Stepniewska, Kasia, von Seidlein, Lorenz, William, Timothy, Woodrow, Charles J, Woyessa, Adugna, Rajasekhar, Megha, Simpson, Julie A, Ley, Benedikt, Edler, Peta, Chu, Cindy S, Abreha, Tesfay, Awab, Ghulam R, Baird, J Kevin, Bancone, Germana, Barber, Bridget E, Grigg, Matthew J, Hwang, Jimee, Karunajeewa, Harin, Lacerda, Marcus V G, Ladeia-Andrade, Simone, Llanos-Cuentas, Alejandro, Pukrittayakamee, Sasithon, Rijal, Komal R, Saravu, Kavitha, Sutanto, Inge, Taylor, Walter R J, Thriemer, Kamala, Watson, James A, Guerin, Philippe J, White, Nicholas J, Price, Ric N, and Commons, Robert J

Published
2024
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9. Pregnancy outcomes after first-trimester treatment with artemisinin derivatives versus non-artemisinin antimalarials: a systematic review and individual patient data meta-analysis

Author

Saito, Makoto, McGready, Rose, Tinto, Halidou, Rouamba, Toussaint, Mosha, Dominic, Rulisa, Stephen, Kariuki, Simon, Desai, Meghna, Manyando, Christine, Njunju, Eric M, Sevene, Esperanca, Vala, Anifa, Augusto, Orvalho, Clerk, Christine, Were, Edwin, Mrema, Sigilbert, Kisinza, William, Byamugisha, Josaphat, Kagawa, Mike, Singlovic, Jan, Yore, Mackensie, van Eijk, Anna Maria, Mehta, Ushma, Stergachis, Andy, Hill, Jenny, Stepniewska, Kasia, Gomes, Melba, Guérin, Philippe J, Nosten, Francois, ter Kuile, Feiko O, and Dellicour, Stephanie

Published
2023
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10. Factors Affecting Integration of an Early Warning System for Antimalarial Drug Resistance within a Routine Surveillance System in a Pre-elimination Setting in Sub-Saharan Africa.

Author

Kagoro, Frank M, primary, Allen, Elizabeth, additional, Raman, Jaishree, additional, Mabuza, Aaron, additional, Magagula, Ray, additional, Kok, Gerdalize, additional, Malatje, Gillian, additional, Guerin, Philippe J, additional, Dhorda, Mehul, additional, Maude, Richard J, additional, and Barnes, Karen I, additional

Published
2024
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11. Antimicrobial resistance patterns in bacteria causing febrile illness in Africa, South Asia, and Southeast Asia: a systematic review of published etiological studies from 1980-2015

Author

Roberts, Tamalee, Dahal, Prabin, Shrestha, Poojan, Schilling, William, Shrestha, Rujan, Ngu, Roland, Huong, Vu Thi Lan, van Doorn, H Rogier, Phimolsarnnousith, Vilayouth, Miliya, Thyl, Crump, John A, Bell, David, Newton, Paul N, Dittrich, Sabine, Hopkins, Heidi, Stepniewska, Kasia, Guerin, Philippe J, Ashley, Elizabeth A, and Turner, Paul

Published
2022
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12. Safety of single-dose primaquine as a Plasmodium falciparum gametocytocide: a systematic review and meta-analysis of individual patient data

Author

Stepniewska, Kasia, Allen, Elizabeth N., Humphreys, Georgina S., Poirot, Eugenie, Craig, Elaine, Kennon, Kalynn, Yilma, Daniel, Bousema, Teun, Guerin, Philippe J., White, Nicholas J., Price, Ric N., Raman, Jaishree, Martensson, Andreas, Mwaiswelo, Richard O., Bancone, Germana, Bastiaens, Guido J. H., Bjorkman, Anders, Brown, Joelle M., D’Alessandro, Umberto, Dicko, Alassane A., El-Sayed, Badria, Elzaki, Salah-Eldin, Eziefula, Alice C., Gonçalves, Bronner P., Hamid, Muzamil Mahdi Abdel, Kaneko, Akira, Kariuki, Simon, Khan, Wasif, Kwambai, Titus K., Ley, Benedikt, Ngasala, Billy E., Nosten, Francois, Okebe, Joseph, Samuels, Aaron M., Smit, Menno R., Stone, Will J. R., Sutanto, Inge, Ter Kuile, Feiko, Tine, Roger C., Tiono, Alfred B., Drakeley, Chris J., Gosling, Roly, Stergachis, Andy, Barnes, Karen I., and Chen, Ingrid

Published
2022
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15. Post-kala-azar dermal leishmaniasis (PKDL) drug efficacy study landscape: A systematic scoping review of clinical trials and observational studies to assess the feasibility of establishing an individual participant-level data (IPD) platform

Author

Singh-Phulgenda, Sauman, primary, Kumar, Rishikesh, additional, Dahal, Prabin, additional, Munir, Abdalla, additional, Rashan, Sumayyah, additional, Chhajed, Rutuja, additional, Naylor, Caitlin, additional, Maguire, Brittany J., additional, Siddiqui, Niyamat Ali, additional, Harriss, Eli, additional, Rahi, Manju, additional, Alves, Fabiana, additional, Sundar, Shyam, additional, Stepniewska, Kasia, additional, Musa, Ahmed, additional, Guerin, Philippe J., additional, and Pandey, Krishna, additional

Published
2024
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17. Systematic Review and Geospatial Modeling of Molecular Markers of Resistance to Artemisinins and Sulfadoxine–Pyrimethamine in Plasmodium falciparum in India

Author

Nain, Minu, primary, Dhorda, Mehul, additional, Flegg, Jennifer A., additional, Gupta, Apoorv, additional, Harrison, Lucinda E., additional, Singh-Phulgenda, Sauman, additional, Otienoburu, Sabina D., additional, Harriss, Eli, additional, Bharti, Praveen K., additional, Behera, Beauty, additional, Rahi, Manju, additional, Guerin, Philippe J., additional, and Sharma, Amit, additional

Published
2024
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18. Primaquine for uncomplicated Plasmodium vivaxmalaria in children younger than 15 years: a systematic review and individual patient data meta-analysis

Author

Commons, Robert J, Rajasekhar, Megha, Allen, Elizabeth N, Yilma, Daniel, Chotsiri, Palang, Abreha, Tesfay, Adam, Ishag, Awab, Ghulam Rahim, Barber, Bridget E, Brasil, Larissa W, Chu, Cindy S, Cui, Liwang, Edler, Peta, Gomes, Margarete do Socorro M, Gonzalez‑Ceron, Lilia, Grigg, Matthew J, Hamid, Muzamil Mahdi Abdel, Hwang, Jimee, Karunajeewa, Harin, Lacerda, Marcus V G, Ladeia-Andrade, Simone, Leslie, Toby, Longley, Rhea J, Monteiro, Wuelton Marcelo, Pasaribu, Ayodhia Pitaloka, Poespoprodjo, Jeanne Rini, Richmond, Caitlin L, Rijal, Komal Raj, Taylor, Walter R J, Thanh, Pham Vinh, Thriemer, Kamala, Vieira, José Luiz F, White, Nicholas J, Zuluaga-Idarraga, Lina M, Workman, Lesley J, Tarning, Joel, Stepniewska, Kasia, Guerin, Philippe J, Simpson, Julie A, Barnes, Karen I, Price, Ric N, Adhikari, Bipin, Alam, Mohammad Shafiul, Anstey, Nicholas M, Assefa, Ashenafi, Baird, J Kevin, Boyd, Sarah C, Chau, Nguyen H, Day, Nicholas PJ, Degaga, Tamiru Shibiru, Dondorp, Arjen M, Erhart, Annette, Ferreira, Marcelo U, Ghimire, Prakash, Khan, Wasif A, Ley, Benedikt, Mekuria, Asrat H, Mueller, Ivo, Naadim, Mohammad N, Nosten, Francois, Price, David J, Pukrittayakamee, Sasithon, Rowland, Mark, Sattabongkot, Jetsumon, SuarezKurtz, Guilherme, Sutanto, Inge, von Seidlein, Lorenz, William, Timothy, Woodrow, Charles J, and Woyessa, Adugna

Abstract

Primaquine, the only widely available treatment to prevent relapsing Plasmodium vivaxmalaria, is produced as 15 mg tablets, and new paediatric formulations are being developed. To inform the optimal primaquine dosing regimen for children, we aimed to determine the efficacy and safety of different primaquine dose strategies in children younger than 15 years.

Published
2024
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20. Efficacy and tolerability of artemisinin-based and quinine-based treatments for uncomplicated falciparum malaria in pregnancy: a systematic review and individual patient data meta-analysis

Author

Saito, Makoto, Mansoor, Rashid, Kennon, Kalynn, Anvikar, Anupkumar R, Ashley, Elizabeth A, Chandramohan, Daniel, Cohee, Lauren M, D'Alessandro, Umberto, Genton, Blaise, Gilder, Mary Ellen, Juma, Elizabeth, Kalilani-Phiri, Linda, Kuepfer, Irene, Laufer, Miriam K, Lwin, Khin Maung, Meshnick, Steven R, Mosha, Dominic, Mwapasa, Victor, Mwebaza, Norah, Nambozi, Michael, Ndiaye, Jean-Louis A, Nosten, François, Nyunt, Myaing, Ogutu, Bernhards, Parikh, Sunil, Paw, Moo Kho, Phyo, Aung Pyae, Pimanpanarak, Mupawjay, Piola, Patrice, Rijken, Marcus J, Sriprawat, Kanlaya, Tagbor, Harry K, Tarning, Joel, Tinto, Halidou, Valéa, Innocent, Valecha, Neena, White, Nicholas J, Wiladphaingern, Jacher, Stepniewska, Kasia, McGready, Rose, and Guérin, Philippe J

Published
2020
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22. 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

WWARN Artemisinin based Combination Therapy (ACT) Africa Baseline Study Group, Dahal, Prabin, d'Alessandro, Umberto, Dorsey, Grant, Guerin, Philippe J, Nsanzabana, Christian, Price, Ric N, Sibley, Carol H, Stepniewska, Kasia, and Talisuna, Ambrose O

Subjects
WWARN Artemisinin based Combination Therapy (ACT) Africa Baseline Study Group, Humans, Plasmodium falciparum, Malaria, Falciparum, Artemisinins, Quinolines, Amodiaquine, Drug Combinations, Antimalarials, Drug Therapy, Combination, Prospective Studies, Middle Aged, Infant, Africa, Africa South of the Sahara, Male, Vector-Borne Diseases, Clinical Research, Prevention, Rare Diseases, Infectious Diseases, Clinical Trials and Supportive Activities, Malaria, 2.2 Factors relating to the physical environment, Infection, General & Internal Medicine, Medical and Health Sciences
Abstract

BackgroundArtemisinin-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).MethodsA 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.ResultsIn 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 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).ConclusionsThe 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.

Published
2015

23. 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, 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

Subjects
WorldWide Antimalarial Resistance Network (WWARN) AS-AQ Study Group, Humans, Malaria, Falciparum, Recurrence, Artemisinins, Amodiaquine, Drug Combinations, Antimalarials, Treatment Outcome, Risk Factors, Dose-Response Relationship, Drug, Middle Aged, Africa, Female, Male, Malaria, Plasmodium falciparum, Drug resistance, Artesunate, Dosing, Efficacy, Falciparum, Dose-Response Relationship, Drug, Medical and Health Sciences, General & Internal Medicine
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

Published
2015

27. The effect of chloroquine dose and primaquine on Plasmodium vivax recurrence: a WorldWide Antimalarial Resistance Network systematic review and individual patient pooled meta-analysis

Author

Commons, Robert J, Simpson, Julie A, Thriemer, Kamala, Humphreys, Georgina S, Abreha, Tesfay, Alemu, Sisay G, Añez, Arletta, Anstey, Nicholas M, Awab, Ghulam R, Baird, J Kevin, Barber, Bridget E, Borghini-Fuhrer, Isabelle, Chu, Cindy S, D'Alessandro, Umberto, Dahal, Prabin, Daher, André, de Vries, Peter J, Erhart, Annette, Gomes, Margarete S M, Gonzalez-Ceron, Lilia, Grigg, Matthew J, Heidari, Aliehsan, Hwang, Jimee, Kager, Piet A, Ketema, Tsige, Khan, Wasif A, Lacerda, Marcus V G, Leslie, Toby, Ley, Benedikt, Lidia, Kartini, Monteiro, Wuelton M, Nosten, Francois, Pereira, Dhelio B, Phan, Giao T, Phyo, Aung P, Rowland, Mark, Saravu, Kavitha, Sibley, Carol H, Siqueira, André M, Stepniewska, Kasia, Sutanto, Inge, Taylor, Walter R J, Thwaites, Guy, Tran, Binh Q, Tran, Hien T, Valecha, Neena, Vieira, José Luiz F, Wangchuk, Sonam, William, Timothy, Woodrow, Charles J, Zuluaga-Idarraga, Lina, Guerin, Philippe J, White, Nicholas J, and Price, Ric N

Published
2018
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28. Global estimation of anti-malarial drug effectiveness for the treatment of uncomplicated Plasmodium falciparum malaria 1991–2019

Author

Rathmes, Giulia, Rumisha, Susan F., Lucas, Tim C. D., Twohig, Katherine A., Python, Andre, Nguyen, Michele, Nandi, Anita K., Keddie, Suzanne H., Collins, Emma L., Rozier, Jennifer A., Gibson, Harry S., Chestnutt, Elisabeth G., Battle, Katherine E., Humphreys, Georgina S., Amratia, Punam, Arambepola, Rohan, Bertozzi-Villa, Amelia, Hancock, Penelope, Millar, Justin J., Symons, Tasmin L., Bhatt, Samir, Cameron, Ewan, Guerin, Philippe J., Gething, Peter W., and Weiss, Daniel J.

Published
2020
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30. The duration of chemoprophylaxis against malaria after treatment with artesunate-amodiaquine and artemether-lumefantrine and the effects of pfmdr1 86Y and pfcrt 76T: a meta-analysis of individual patient data

Author

Bretscher, Michael T., Dahal, Prabin, Griffin, Jamie, Stepniewska, Kasia, Bassat, Quique, Baudin, Elisabeth, D’Alessandro, Umberto, Djimde, Abdoulaye A., Dorsey, Grant, Espié, Emmanuelle, Fofana, Bakary, González, Raquel, Juma, Elizabeth, Karema, Corine, Lasry, Estrella, Lell, Bertrand, Lima, Nines, Menéndez, Clara, Mombo-Ngoma, Ghyslain, Moreira, Clarissa, Nikiema, Frederic, Ouédraogo, Jean B., Staedke, Sarah G., Tinto, Halidou, Valea, Innocent, Yeka, Adoke, Ghani, Azra C., Guerin, Philippe J., and Okell, Lucy C.

Published
2020
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32. 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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35. The haematological consequences of Plasmodium vivax malaria after chloroquine treatment with and without primaquine: a WorldWide Antimalarial Resistance Network systematic review and individual patient data meta-analysis

Author

Commons, Robert J., Simpson, Julie A., Thriemer, Kamala, Chu, Cindy S., Douglas, Nicholas M., Abreha, Tesfay, Alemu, Sisay G., Añez, Arletta, Anstey, Nicholas M., Aseffa, Abraham, Assefa, Ashenafi, Awab, Ghulam R., Baird, J. Kevin, Barber, Bridget E., Borghini-Fuhrer, Isabelle, D’Alessandro, Umberto, Dahal, Prabin, Daher, André, de Vries, Peter J., Erhart, Annette, Gomes, Margarete S. M., Grigg, Matthew J., Hwang, Jimee, Kager, Piet A., Ketema, Tsige, Khan, Wasif A., Lacerda, Marcus V. G., Leslie, Toby, Ley, Benedikt, Lidia, Kartini, Monteiro, Wuelton M., Pereira, Dhelio B., Phan, Giao T., Phyo, Aung P., Rowland, Mark, Saravu, Kavitha, Sibley, Carol H., Siqueira, André M., Stepniewska, Kasia, Taylor, Walter R. J., Thwaites, Guy, Tran, Binh Q., Hien, Tran T., Vieira, José Luiz F., Wangchuk, Sonam, Watson, James, William, Timothy, Woodrow, Charles J., Nosten, Francois, Guerin, Philippe J., White, Nicholas J., and Price, Ric N.

Published
2019
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37. Microbiology Investigation Criteria for Reporting Objectively (MICRO): a framework for the reporting and interpretation of clinical microbiology data

Author

Turner, Paul, Fox-Lewis, Andrew, Shrestha, Poojan, Dance, David A. B., Wangrangsimakul, Tri, Cusack, Tomas-Paul, Ling, Clare L., Hopkins, Jill, Roberts, Tamalee, Limmathurotsakul, Direk, Cooper, Ben S., Dunachie, Susanna, Moore, Catrin E., Dolecek, Christiane, van Doorn, H. Rogier, Guerin, Philippe J., Day, Nicholas P. J., and Ashley, Elizabeth A.

Published
2019
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38. Correction: A systematic review and an individual patient data meta-analysis of ivermectin use in children weighing less than fifteen kilograms: Is it time to reconsider the current contraindication?

Author

Jittamala, Podjanee, primary, Monteiro, Wuelton, additional, Smit, Menno R., additional, Pedrique, Belen, additional, Specht, Sabine, additional, Chaccour, Carlos J., additional, Dard, Céline, additional, Giudice, Pascal Del, additional, Khieu, Virak, additional, Maruani, Annabel, additional, Failoc-Rojas, Virgilio E., additional, Sáez-de-Ocariz, Marimar, additional, Soriano-Arandes, Antoni, additional, Piquero-Casals, Jaime, additional, Faisant, Anne, additional, Brenier-Pinchart, Marie-Pierre, additional, Wimmersberger, David, additional, Coulibaly, Jean T., additional, Keiser, Jennifer, additional, Boralevi, Franck, additional, Sokana, Oliver, additional, Marks, Michael, additional, Engelman, Daniel, additional, Romani, Lucia, additional, Steer, Andrew C., additional, von Seidlein, Lorenz, additional, White, Nicholas J., additional, Harriss, Eli, additional, Stepniewska, Kasia, additional, Humphreys, Georgina S., additional, Kennon, Kalynn, additional, Guerin, Philippe J., additional, and Kobylinski, Kevin C., additional

Published
2023
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40. Erratum:Correction: A systematic review and an individual patient data meta-analysis of ivermectin use in children weighing less than fifteen kilograms: Is it time to reconsider the current contraindication? (PLoS neglected tropical diseases (2021) 15 3 (e0009144))

Author

Jittamala, Podjanee, Monteiro, Wuelton, Smit, Menno R., Pedrique, Belen, Specht, Sabine, Chaccour, Carlos J., Dard, C. line, Giudice, Pascal Del, Khieu, Virak, Maruani, Annabel, Failoc-Rojas, Virgilio E., Sáez-de-Ocariz, Marimar, Soriano-Arandes, Antoni, Piquero-Casals, Jaime, Faisant, Anne, Brenier-Pinchart, Marie-Pierre, Wimmersberger, David, Coulibaly, Jean T., Keiser, Jennifer, Boralevi, Franck, Sokana, Oliver, Marks, Michael, Engelman, Daniel, Romani, Lucia, Steer, Andrew C., von Seidlein, Lorenz, White, Nicholas J., Harriss, Eli, Stepniewska, Kasia, Humphreys, Georgina S., Kennon, Kalynn, Guerin, Philippe J., and Kobylinski, Kevin C.

Abstract

[This corrects the article DOI: 10.1371/journal.pntd.0009144.].

Published
2023

41. Erratum: Correction: A systematic review and an individual patient data meta-analysis of ivermectin use in children weighing less than fifteen kilograms: Is it time to reconsider the current contraindication? (PLoS neglected tropical diseases (2021) 15 3 (e0009144))

Author

Jittamala, Podjanee, Monteiro, Wuelton, Smit, Menno R., Pedrique, Belen, Specht, Sabine, Chaccour, Carlos J., Dard, C. line, Giudice, Pascal Del, Khieu, Virak, Maruani, Annabel, Failoc-Rojas, Virgilio E., Sáez-de-Ocariz, Marimar, Soriano-Arandes, Antoni, Piquero-Casals, Jaime, Faisant, Anne, Brenier-Pinchart, Marie-Pierre, Wimmersberger, David, Coulibaly, Jean T., Keiser, Jennifer, Boralevi, Franck, Sokana, Oliver, Marks, Michael, Engelman, Daniel, Romani, Lucia, Steer, Andrew C., von Seidlein, Lorenz, White, Nicholas J., Harriss, Eli, Stepniewska, Kasia, Humphreys, Georgina S., Kennon, Kalynn, Guerin, Philippe J., Kobylinski, Kevin C., General Paediatrics, APH - Global Health, and Pediatrics

Abstract

[This corrects the article DOI: 10.1371/journal.pntd.0009144.].

Published
2023

42. 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 BS, 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 ME, 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, Martensson, 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, Resistance, WorldWide Antimalarial, WorldWide Antimalarial Resistance Network Falciparum Haematology Study Group, Vecteurs - Infections tropicales et méditerranéennes (VITROME), Institut de Recherche pour le Développement (IRD)-Aix Marseille Université (AMU)-Institut de Recherche Biomédicale des Armées [Brétigny-sur-Orge] (IRBA), Epidémiologie des Maladies Chroniques en zone tropicale (EpiMaCT), CHU Limoges-Institut d'Epidémiologie Neurologique et de Neurologie Tropicale-Institut National de la Santé et de la Recherche Médicale (INSERM)-OmégaHealth (ΩHealth), Université de Limoges (UNILIM)-Université de Limoges (UNILIM), Group, WorldWide Antimalarial Resistance Network Falciparum Haematology Study, Mansoor, R, Ashley, EA, Ashurst, H, Burrow, R, Carrara, VI, Das, D, Dondorp, AM, Humphreys, GS, Lee, SJ, Mayxay, M, McGready, R, Newton, PN, Nosten, F, Richmond, CL, Sibley, C, Smithuis, FM, Taylor, WR, Tran, TH, von Seidlein, L, White, NJ, Woodrow, CJ, Guerin, PJ, Stepniewska, K, Price, RN, AII - Infectious diseases, Intensive Care Medicine, Infectious diseases, APH - Global Health, and APH - Quality of Care

Subjects
Infectious Medicine, Plasmodium falciparum, wh_120, Infektionsmedicin, Severe anaemia, Parasitemia, wa_530, Antimalarials, Non-artemisinin-based therapy, [SDV.MHEP.CSC]Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system, [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases, parasitic diseases, qv_256, Humans, [SDV.MP.PAR]Life Sciences [q-bio]/Microbiology and Parasitology/Parasitology, Malaria, Falciparum, Child, [SDV.MHEP.ME]Life Sciences [q-bio]/Human health and pathology/Emerging diseases, Pooled analysis of individual patient data, Anemia, Public Health, Global Health, Social Medicine and Epidemiology, General Medicine, Artemisinin-based therapy, [SDV.MP.BAC]Life Sciences [q-bio]/Microbiology and Parasitology/Bacteriology, Malaria, wc_750, Folkhälsovetenskap, global hälsa, socialmedicin och epidemiologi, lnfectious Diseases and Global Health Radboud Institute for Health Sciences [Radboudumc 4], [SDV.MP.VIR]Life Sciences [q-bio]/Microbiology and Parasitology/Virology, Haemoglobin
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 = 1.78 and AOR = 1.58, respectively) and delayed parasite clearance (AOR = 2.44 and AOR = 2.59, respectively). In Asia, patients treated with an artemisinin-based regimen were at significantly greater risk of moderately severe anaemia on day 7 compared to those treated with a non-artemisinin-based regimen (AOR = 2.06 [95%CI 1.39–3.05], p < 0.001). Conclusions In patients with uncomplicated P. falciparum malaria, the nadir haemoglobin occurs 2 days after starting treatment. Although artemisinin-based treatments increase the rate of parasite clearance, in Asia they are associated with a greater risk of anaemia during recovery.

Published
2022

44. The risk of Plasmodium vivax parasitaemia after P. falciparum malaria: An individual patient data meta-analysis from the WorldWide Antimalarial Resistance Network

Author

Hossain, Mohammad S., Commons, Robert J., Douglas, Nicholas M., Thriemer, Kamala, Alemayehu, Bereket H., Amaratunga, Chanaki, Anvikar, Anupkumar R., Ashley, Elizabeth A., Asih, Puji B. S., Carrara, Verena I., Lon, Chanthap, D'Alessandro, Umberto, Davis, Timothy M. E., Dondorp, Arjen M., Edstein, Michael D., Fairhurst, Rick M., Ferreira, Marcelo U., Hwang, Jimee, Janssens, Bart, Karunajeewa, Harin, Kiechel, Jean R., Ladeia-Andrade, Simone, Laman, Moses, Mayxay, Mayfong, McGready, Rose, Moore, Brioni R., Mueller, Ivo, Newton, Paul N., Thuy-Nhien, Nguyen T., Noedl, Harald, Nosten, Francois, Phyo, Aung P., Poespoprodjo, Jeanne R., Saunders, David L., Smithuis, Frank, Spring, Michele D., Stepniewska, Kasia, Suon, Seila, Suputtamongkol, Yupin, Syafruddin, Din, Tran, Hien T., Valecha, Neena, Van Herp, Michel, Van Vugt, Michele, White, Nicholas J., Guerin, Philippe J., Simpson, Julie A., and Price, Ric N.

Subjects
Malaria -- Drug therapy -- Complications and side effects, Protozoan diseases -- Risk factors, Biological sciences
Abstract

Background There is a high risk of Plasmodium vivax parasitaemia following treatment of falciparum malaria. Our study aimed to quantify this risk and the associated determinants using an individual patient data meta-analysis in order to identify populations in which a policy of universal radical cure, combining artemisinin-based combination therapy (ACT) with a hypnozoitocidal antimalarial drug, would be beneficial. Methods and findings A systematic review of Medline, Embase, Web of Science, and the Cochrane Database of Systematic Reviews identified efficacy studies of uncomplicated falciparum malaria treated with ACT that were undertaken in regions coendemic for P. vivax between 1 January 1960 and 5 January 2018. Data from eligible studies were pooled using standardised methodology. The risk of P. vivax parasitaemia at days 42 and 63 and associated risk factors were investigated by multivariable Cox regression analyses. Study quality was assessed using a tool developed by the Joanna Briggs Institute. The study was registered in the International Prospective Register of Systematic Reviews (PROSPERO: CRD42018097400). In total, 42 studies enrolling 15,341 patients were included in the analysis, including 30 randomised controlled trials and 12 cohort studies. Overall, 14,146 (92.2%) patients had P. falciparum monoinfection and 1,195 (7.8%) mixed infection with P. falciparum and P. vivax. The median age was 17.0 years (interquartile range [IQR] = 9.0-29.0 years; range = 0-80 years), with 1,584 (10.3%) patients younger than 5 years. 2,711 (17.7%) patients were treated with artemether-lumefantrine (AL, 13 studies), 651 (4.2%) with artesunate-amodiaquine (AA, 6 studies), 7,340 (47.8%) with artesunate-mefloquine (AM, 25 studies), and 4,639 (30.2%) with dihydroartemisinin-piperaquine (DP, 16 studies). 14,537 patients (94.8%) were enrolled from the Asia-Pacific region, 684 (4.5%) from the Americas, and 120 (0.8%) from Africa. At day 42, the cumulative risk of vivax parasitaemia following treatment of P. falciparum was 31.1% (95% CI 28.9-33.4) after AL, 14.1% (95% CI 10.8-18.3) after AA, 7.4% (95% CI 6.7-8.1) after AM, and 4.5% (95% CI 3.9-5.3) after DP. By day 63, the risks had risen to 39.9% (95% CI 36.6-43.3), 42.4% (95% CI 34.7-51.2), 22.8% (95% CI 21.2-24.4), and 12.8% (95% CI 11.4-14.5), respectively. In multivariable analyses, the highest rate of P. vivax parasitaemia over 42 days of follow-up was in patients residing in areas of short relapse periodicity (adjusted hazard ratio [AHR] = 6.2, 95% CI 2.0-19.5; p = 0.002); patients treated with AL (AHR = 6.2, 95% CI 4.6-8.5; p < 0.001), AA (AHR = 2.3, 95% CI 1.4-3.7; p = 0.001), or AM (AHR = 1.4, 95% CI 1.0-1.9; p = 0.028) compared with DP; and patients who did not clear their initial parasitaemia within 2 days (AHR = 1.8, 95% CI 1.4-2.3; p < 0.001). The analysis was limited by heterogeneity between study populations and lack of data from very low transmission settings. Study quality was high. Conclusions In this meta-analysis, we found a high risk of P. vivax parasitaemia after treatment of P. falciparum malaria that varied significantly between studies. These P. vivax infections are likely attributable to relapses that could be prevented with radical cure including a hypnozoitocidal agent; however, the benefits of such a novel strategy will vary considerably between geographical areas., Author(s): Mohammad S. Hossain 1,2,3,4, Robert J. Commons 1,2,5, Nicholas M. Douglas 2,3, Kamala Thriemer 2, Bereket H. Alemayehu 6, Chanaki Amaratunga 7, Anupkumar R. Anvikar 8, Elizabeth A. Ashley [...]

Published
2020
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45. Spatiotemporal spread of Plasmodium falciparum mutations for resistance to sulfadoxine-pyrimethamine across Africa, 1990–2020

Author

Flegg, Jennifer A., primary, Humphreys, Georgina S., additional, Montanez, Brenda, additional, Strickland, Taryn, additional, Jacome-Meza, Zaira J., additional, Barnes, Karen I., additional, Raman, Jaishree, additional, Guerin, Philippe J., additional, Hopkins Sibley, Carol, additional, and Dahlström Otienoburu, Sabina, additional

Published
2022
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46. Cooperation in Countering Artemisinin Resistance in Africa: Learning from COVID-19

Author

Rosenthal, Philip J., primary, Björkman, Anders, additional, Dhorda, Mehul, additional, Djimde, Abdoulaye, additional, Dondorp, Arjen M., additional, Gaye, Oumar, additional, Guerin, Philippe J., additional, Juma, Elizabeth, additional, Kwiatkowski, Dominic P., additional, Merson, Laura, additional, Ntoumi, Francine, additional, Price, Ric N., additional, Raman, Jaishree, additional, Roos, David S., additional, ter Kuile, Feiko, additional, Tinto, Halidou, additional, Tomko, Sheena S., additional, White, Nicholas J., additional, and Barnes, Karen I., additional

Published
2022
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47. Temporal distribution of Plasmodium falciparum recrudescence following artemisinin-based combination therapy: an individual participant data meta-analysis

Author

Dahal, Prabin, Simpson, Julie Anne, Abdulla, Salim, Achan, Jane, Adam, Ishag, Agarwal, Aarti, Allan, Richard, Anvikar, Anupkumar R., Ashley, Elizabeth A., Bassat, Quique, Borrmann, Steffen, Bousema, Teun, Bukirwa, Hasifa, Carrara, Verena, I, Corsi, Marco, D'Alessandro, Umberto, Davis, Timothy M. E., Deloron, Philippe, Desai, Meghna, Dimbu, Pedro Rafael, Djalle, Djibrine, Djimde, Abdoulaye, Dorsey, Grant, Drakeley, Chris J., Duparc, Stephan, Edstein, Michael D., Espie, Emmanuelle, Faiz, Abul, Falade, Catherine, Fanello, Caterina, Faucher, Jean-Francois, Faye, Babacar, Fortes, Filomeno de Jesus, Gadalla, Nahla B., Gaye, Oumar, Gil, J. Pedro, Gilayeneh, Julius, Greenwood, Brian, Grivoyannis, Anastasia, Hien, Tran Tinh, Hwang, Jimee, Janssens, Bart, Juma, Elizabeth, Kamugisha, Erasmus, Karema, Corine, Karunajeewa, Harin A., Kiechel, Jean R., Kironde, Fred, Kofoed, Poul-Erik, Kremsner, Peter G., Lee, Sue J., Marsh, Kevin, Mårtensson, Andreas, Mayxay, Mayfong, Menan, Herve, Mens, Petra, Mutabingwa, Theonest K., Ndiaye, Jean-Louis, Ngasala, Billy, Noedl, Harald, Nosten, Francois, Offianan, Andre Toure, Ogutu, Bernhards R., Olliaro, Piero L., Ouedraogo, Jean Bosco, Piola, Patrice, Plowe, Christopher, V, Plucinski, Mateusz M., Pratt, Oliver James, Premji, Zulfikarali, Ramharter, Michael, Rogier, Christophe, Vitare, Primum, Rombo, Lars, Rosenthal, Philip J., Sibley, Carol, Sirima, Sodiomon, Smithuis, Frank, Staedke, Sarah G., Sutanto, Inge, Talisuna, Ambrose Otau, Tarning, Joel, Taylor, Walter R. J., Temu, Emmanuel, Thriemer, Kamala, Thuy-Nhien, Nguyen, Udhayakumar, Venkatachalam, Ursing, Johan D., van Herp, Michel, van Lenthe, Marit, van Vugt, Michele, William, Yavo, Winnips, Cornelis, Zaloumis, Sophie, Zongo, Issaka, White, Nick J., Guerin, Philippe J., Stepniewska, Kasia, Price, Ric N., Arinaitwe, Emmanuel, and Group, WorldWide Antimalarial Resistance Network Methodology Study

Subjects
Infectious Medicine, Efficacy, Follow-up, Recrudescence, Artemether, Lumefantrine Drug Combination, Plasmodium falciparum, Infektionsmedicin, Distribution, Artemisinins, Malaria, Antimalarials, lnfectious Diseases and Global Health Radboud Institute for Health Sciences [Radboudumc 4], Infectious Diseases, Recurrence, Child, Preschool, Humans, Parasitology, Artemether, Child
Abstract

Background The duration of trial follow-up affects the ability to detect recrudescent infections following anti-malarial treatment. The aim of this study was to explore the proportions of recrudescent parasitaemia as ascribed by genotyping captured at various follow-up time-points in treatment efficacy trials for uncomplicated Plasmodium falciparum malaria. Methods Individual patient data from 83 anti-malarial efficacy studies collated in the WorldWide Antimalarial Resistance Network (WWARN) repository with at least 28 days follow-up were available. The temporal and cumulative distributions of recrudescence were characterized using a Cox regression model with shared frailty on study-sites. Fractional polynomials were used to capture non-linear instantaneous hazard. The area under the density curve (AUC) of the constructed distribution was used to estimate the optimal follow-up period for capturing a P. falciparum malaria recrudescence. Simulation studies were conducted based on the constructed distributions to quantify the absolute overestimation in efficacy due to sub-optimal follow-up. Results Overall, 3703 recurrent infections were detected in 60 studies conducted in Africa (15,512 children aged 48 mg/kg total piperaquine (PIP) dose and 9% [95% CI 0–22%] in those treated with ≤ 48 mg/kg PIP dose. In absolute terms, the simulation study found that trials limited to 28 days follow-up following AL underestimated the risk of recrudescence by a median of 2.8 percentage points compared to day 63 estimates and those limited to 42 days following DP underestimated the risk of recrudescence by a median of 2.0 percentage points compared to day 42 estimates. The analysis was limited by few clinical trials following patients for longer than 42 days (9 out of 83 trials) and the imprecision of PCR genotyping which overcalls recrudescence in areas of higher transmission biasing the later distribution. Conclusions Restricting follow-up of clinical efficacy trials to day 28 for AL and day 42 for DP will miss a proportion of late recrudescent treatment failures but will have a modest impact in derived efficacy. The results highlight that as genotyping methods improve consideration should be given for trials with longer duration of follow-up to detect early indications of emerging drug resistance.

Published
2022

48. The efficacy of dihydroartemisinin-piperaquine and artemether-lumefantrine with and without primaquine on Plasmodium vivax recurrence: A systematic review and individual patient data meta-analysis

Author

Commons, Robert J., Simpson, Julie A., Thriemer, Kamala, Abreha, Tesfay, Adam, Ishag, Anstey, Nicholas M., Assefa, Ashenafi, Awab, Ghulam R., Baird, J. Kevin, Barber, Bridget E., Chu, Cindy S., Dahal, Prabin, Daher, André, Davis, Timothy M. E., Dondorp, Arjen M., Grigg, Matthew J., Humphreys, Georgina S., Hwang, Jimee, Karunajeewa, Harin, Laman, Moses, Lidia, Kartini, Moore, Brioni R., Mueller, Ivo, Nosten, Francois, Pasaribu, Ayodhia P., Pereira, Dhelio B., Phyo, Aung P., Poespoprodjo, Jeanne R., Sibley, Carol H., Stepniewska, Kasia, Sutanto, Inge, Thwaites, Guy, Hien, Tran T., White, Nicholas J., William, Timothy, Woodrow, Charles J., Guerin, Philippe J., and Price, Ric N.

Subjects
EPUB (Standard), Artemisinin -- Analysis, Primaquine -- Analysis, Medical research -- Analysis, Malaria -- Analysis, Recurrence (Disease), Prophylaxis, Retirement benefits, Hemoglobins, Antimalarials, Biological sciences, World Health Organization
Abstract

Background Artemisinin-based combination therapy (ACT) is recommended for uncomplicated Plasmodium vivax malaria in areas of emerging chloroquine resistance. We undertook a systematic review and individual patient data meta-analysis to compare the efficacies of dihydroartemisinin-piperaquine (DP) and artemether-lumefantrine (AL) with or without primaquine (PQ) on the risk of recurrent P. vivax. Methods and findings Clinical efficacy studies of uncomplicated P. vivax treated with DP or AL and published between January 1, 2000, and January 31, 2018, were identified by conducting a systematic review registered with the International Prospective Register of Systematic Reviews (PROSPERO): CRD42016053310. Investigators of eligible studies were invited to contribute individual patient data that were pooled using standardised methodology. The effect of mg/kg dose of piperaquine/lumefantrine, ACT administered, and PQ on the rate of P. vivax recurrence between days 7 and 42 after starting treatment were investigated by Cox regression analyses according to an a priori analysis plan. Secondary outcomes were the risk of recurrence assessed on days 28 and 63. Nineteen studies enrolling 2,017 patients were included in the analysis. The risk of recurrent P. vivax at day 42 was significantly higher in the 384 patients treated with AL alone (44.0%, 95% confidence interval [CI] 38.7-49.8) compared with the 812 patients treated with DP alone (9.3%, 95% CI 7.1-12.2): adjusted hazard ratio (AHR) 12.63 (95% CI 6.40-24.92), p < 0.001. The rates of recurrence assessed at days 42 and 63 were associated inversely with the dose of piperaquine: AHRs (95% CI) for every 5-mg/kg increase 0.63 (0.48-0.84), p = 0.0013 and 0.83 (0.73-0.94), p = 0.0033, respectively. The dose of lumefantrine was not significantly associated with the rate of recurrence (1.07 for every 5-mg/kg increase, 95% CI 0.99-1.16, p = 0.0869). In a post hoc analysis, in patients with symptomatic recurrence after AL, the mean haemoglobin increased 0.13 g/dL (95% CI 0.01-0.26) for every 5 days that recurrence was delayed, p = 0.0407. Coadministration of PQ reduced substantially the rate of recurrence assessed at day 42 after AL (AHR = 0.20, 95% CI 0.10-0.41, p < 0.001) and at day 63 after DP (AHR = 0.08, 95% CI 0.01-0.70, p = 0.0233). Results were limited by follow-up of patients to 63 days or less and nonrandomised treatment groups. Conclusions In this study, we observed the risk of P. vivax recurrence at day 42 to be significantly lower following treatment with DP compared with AL, reflecting the longer period of post-treatment prophylaxis; this risk was reduced substantially by coadministration with PQ. We found that delaying P. vivax recurrence was associated with a small but significant improvement in haemoglobin. These results highlight the benefits of PQ radical cure and also the provision of blood-stage antimalarial agents with prolonged post-treatment prophylaxis., Author(s): Robert J. Commons 1,2,*, Julie A. Simpson 3, Kamala Thriemer 1, Tesfay Abreha 4, Ishag Adam 5, Nicholas M. Anstey 1, Ashenafi Assefa 6, Ghulam R. Awab 7,8, J. [...]

Published
2019
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