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1. 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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2. 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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3. Making data map-worthy—enhancing routine malaria data to support surveillance and mapping of Plasmodium falciparum anti-malarial resistance in a pre-elimination sub-Saharan African setting: a molecular and spatiotemporal epidemiology study

Author

Kagoro, Frank M., Allen, Elizabeth, Mabuza, Aaron, Workman, Lesley, Magagula, Ray, Kok, Gerdalize, Davies, Craig, Malatje, Gillian, Guérin, Philippe J., Dhorda, Mehul, Maude, Richard J., Raman, Jaishree, and Barnes, Karen I.

Published
2022
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4. 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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5. 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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6. A pharmacokinetic randomised interventional study to optimise dihydroartemisinin-piperaquine dosing for malaria preventive treatment in Malawian infants: A protocol for the OPTIMAL study

Author

Banda, Clifford G, primary, Kantonya, Mphatso S, additional, Munharo, Steven, additional, Chirwa, Marumbo E, additional, Kapulula, Mayamiko D, additional, Chavula, Hellen D, additional, Chiyana, Aubrey, additional, Katunga-Phiri, Vincent, additional, Patel, Diksha, additional, Katangwe, Vusumuzi, additional, Allen, Elizabeth, additional, ter Kuile, Feiko, additional, Mwapasa, Victor, additional, Terlouw, Dianne J, additional, Tarning, Joel, additional, and Barnes, Karen I, additional

Published
2024
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7. 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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8. Academic Promotions at a South African University: Questions of Bias, Politics and Transformation

Author

Sadiq, Hassan, Barnes, Karen I., Price, Max, Gumedze, Freedom, and Morrell, Robert G.

Abstract

The system of academic promotion provides a mechanism for the achievements of staff to be recognised. However, it can be a mechanism that creates or reflects inequalities, with certain groups rising to the top more readily than others. In many universities, especially in the global North, white men are preponderant in senior academic ranks. This leads to concerns about sexism and racism operating within processes of promotion. There is a global sensitivity that academic hierarchies should be demographically representative. In this study, we examine the data on eleven years of promotions at the University of Cape Town (UCT), a highly ranked, research-led university in South Africa. Its historical roots lie in a colonial past, and despite substantial increases in the number of black scholars, its academic staff complement is still majority white, driving the intensification of its transformation efforts. A quantitative analysis using time to promotion as a proxy for fairness was used to examine patterns of promotion at the university. Although international staff, those in more junior positions, with higher qualifications and in certain faculties enjoyed quicker promotion time, no association was found between time to promotion and gender. There were some differences in time to promotion associated with self-declared ethnicity (taken as synonymous with race), but these associations were not consistent. Although our findings provide some quantitative evidence of UCT's success at creating a fair system of academic advancement, broader demographic transformation remains a priority. However, this cannot be addressed in isolation from the wider higher education enterprise.

Published
2019
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9. 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

11. Correction to: Pharmacokinetic profile of amodiaquine and its active metabolite desethylamodiaquine in Ghanaian patients with uncomplicated falciparum malaria

Author

Anyorigiya, Thomas A., Castel, Sandra, Mauf, Katya, Atuguba, Frank, Ogutu, Bernhards, Oduro, Abraham, Dosoo, David, Asante, Kwaku-Poku, Owusu-Agyei, Seth, Dodoo, Alexander, Hodgson, Abraham, Binka, Fred, Workman, Lesley J., Allen, Elizabeth N., Denti, Paolo, Wiesner, Lubbe, and Barnes, Karen I.

Published
2021
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12. A legacy of progress in clinical pharmacology and social justice; remembering Peter Ian Folb

Author

Barnes, Karen I., Olliaro, Piero, and Gomes, Melba F.

Subjects
Homeopathy -- Materia medica and therapeutics, Pharmacology -- Laws, regulations and rules -- Social aspects, Therapeutics -- Social aspects -- Laws, regulations and rules, Malaria -- Social aspects -- Laws, regulations and rules, Government regulation, Health
Abstract

There are few effective and safe therapeutics for diseases that disproportionally affect impoverished populations, such as malaria and other neglected tropical diseases. But even these few therapeutics would not have [...]

Published
2023
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16. Erratum for Banda et al., “Impact of Dolutegravir-Based Antiretroviral Therapy on Piperaquine Exposure following Dihydroartemisinin-Piperaquine Intermittent Preventive Treatment of Malaria in Pregnant Women Living with HIV”

Author

Banda, Clifford G., primary, Nkosi, Dumisile, additional, Allen, Elizabeth, additional, Workman, Lesley, additional, Madanitsa, Mwayiwawo, additional, Chirwa, Marumbo, additional, Kapulula, Mayamiko, additional, Muyaya, Sharon, additional, Munharo, Steven, additional, Tarning, Joel, additional, Phiri, Kamija S., additional, Mwapasa, Victor, additional, ter Kuile, Feiko O., additional, Maartens, Gary, additional, and Barnes, Karen I., additional

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

Author

Mansoor, Rashid, Commons, Robert J, Douglas, Nicholas M, Abuaku, Benjamin, Achan, Jane, Adam, Ishag, Adjei, George O, Adjuik, Martin, Alemayehu, Bereket H, Allan, Richard, Allen, Elizabeth N, Anvikar, Anupkumar R, Arinaitwe, Emmanuel, Ashley, Elizabeth A, Ashurst, Hazel, Asih, Puji 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
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19. Impact of Dolutegravir-Based Antiretroviral Therapy on Piperaquine Exposure following Dihydroartemisinin-Piperaquine Intermittent Preventive Treatment of Malaria in Pregnant Women Living with HIV

Author

Banda, Clifford G., primary, Nkosi, Dumisile, additional, Allen, Elizabeth, additional, Workman, Lesley, additional, Madanitsa, Mwayiwawo, additional, Chirwa, Marumbo, additional, Kapulula, Mayamiko, additional, Muyaya, Sharon, additional, Munharo, Steven, additional, Tarning, Joel, additional, Phiri, Kamija S., additional, Mwapasa, Victor, additional, ter Kuile, Feiko O., additional, Maartens, Gary, additional, and Barnes, Karen I., additional

Published
2022
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20. Safety, Tolerability, and Parasite Clearance Kinetics in Controlled Human Malaria Infection after Direct Venous Inoculation of Plasmodium falciparum Sporozoites: A Model for Evaluating New Blood-Stage Antimalarial Drugs

Author

Chughlay, M. Farouk, primary, Chalon, Stephan, additional, El Gaaloul, Myriam, additional, Gobeau, Nathalie, additional, Möhrle, Jörg J., additional, Berghmans, Pieter-Jan, additional, Van Leuven, Katrin, additional, Marx, Michael W., additional, Rosanas-Urgell, Anna, additional, Flynn, Julia, additional, Escoffier, Emilie, additional, Izquierdo-Juncàs, Daniel, additional, Jansen, Bastiaan, additional, Mitov, Venelin, additional, Kümmel, Anne, additional, Van Geertruyden, Jean-Pierre, additional, and Barnes, Karen I., additional

Published
2022
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23. 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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24. 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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25. Additional file 2 of 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

Abstract

Additional file 2: List L1. List of included studies. Table S1. Summary of characteristics of included studies.

Published
2022
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26. Additional file 3 of 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

Abstract

Additional file 3: Table S2. Baseline characteristics of patients in the analysis of haematological response. Table S3. Association between haemoglobin change and baseline value. Table S4. Bi-variable analysis of factors associated with drop in haemoglobin on Day 7. Table S5. Bi-variable analysis of factors associated with anaemia on Day 7. Table S6. Univariable analysis of recovery from anaemia. Table S7. Haemoglobin measurements in patients with severe anaemia at any time. Table S8. Baseline characteristics of patients included in the analysis of adverse events. Table S9. Listing of Serious Adverse Events reported in any study. Table S10. Baseline characteristics of patients included in the analysis of haemoglobinuria. Table S11. Univariable analysis for haemoglobinuria. Table S12. Multivariable model of change in haemoglobin on Day 7 in sub-Saharan Africa. Fig. S1. Map of study sites. Fig. S2. Haemoglobin in G6PD deficient patients not included in the Day 7 analysis. Fig. S3. Relationship between haemoglobin at baseline and Day 7 as absolute change. Fig. S4. Relationship between haemoglobin at baseline and Day 7 as fractional change Fig. S5. Relationship between baseline parasitaemia and haematological endpoints. Fig. S6. Dose response relationship for haematological endpoints. Fig. S7. Time to recovery by day when anaemia was first recorded. Fig. S8. Meta-analysis of odds of haemoglobinuria after PQ administration. Fig. S9. Distribution of parasitaemia (observed) used in the simulation study. Figure S10- Predicted risk of severe anaemia (Hb

Published
2022
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27. Additional file 4 of 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

Abstract

Additional file 4: Table S13. Risk of bias assessment. Table S14. Individual participant data not available. Fig. S12. Sensitivity analysis for the main haematological results.

Published
2022
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28. Additional file 1 of Making data map-worthy—enhancing routine malaria data to support surveillance and mapping of Plasmodium falciparum anti-malarial resistance in a pre-elimination sub-Saharan African setting: a molecular and spatiotemporal epidemiology study

Author

Kagoro, Frank M., Allen, Elizabeth, Mabuza, Aaron, Workman, Lesley, Magagula, Ray, Kok, Gerdalize, Davies, Craig, Malatje, Gillian, Guérin, Philippe J., Dhorda, Mehul, Maude, Richard J., Raman, Jaishree, and Barnes, Karen I.

Abstract

Additional file 1: Figure S1. Data flow and linkage for notified malaria cases and case investigation reports on drug adherence and response. Figure S2. GPS coordinates’ coverage trend over the two-year study period (2018–2020). Figure S3. Accuracy trend of malaria case residential coordinates collected over the two-year study period (2018–2020). Figure S4. Percentage of mRDTs barcoded over the two-year study period (2018–2020). Figure S5. Barcode accuracy trend over the two-year study period (2018–2020). Figure S6. Linkage of the patients’ and antimalarial resistance data over the two-year study period (2018–2020). Figure S7. Three different types of shapefiles evaluated for the study area. Tool S1. GPS tools for training malaria case investigators. Tool S1A. Training guide for trainers. Tool S1B. Standard operating procedures for eTrex 10 GPS device (adapted from Health Geolab Collaborative, 2018).

Published
2022
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29. In Vivo Parasitological Measures of Artemisinin Susceptibility

Author

Stepniewska, Kasia, Ashley, Elizabeth, Lee, Sue J., Anstey, Nicholas, Barnes, Karen I., Binh, Tran Quang, D'Alessandro, Umberto, Day, Nicholas P. J., de Vries, Peter J., Dorsey, Grant, Guthmann, Jean-Paul, Mayxay, Mayfong, Newton, Paul N., Olliaro, Piero, Osorio, Lyda, Price, Ric N., Rowland, Mark, Smithuis, Frank, Taylor, Walter R. J., Nosten, François, and White, Nicholas J.

Published
2010

31. Effect of dihydroartemisinin/piperaquine for malaria intermittent preventive treatment on dolutegravir exposure in pregnant women living with HIV

Author

Banda, Clifford G., primary, Nkosi, Dumisile, additional, Allen, Elizabeth, additional, Workman, Lesley, additional, Madanitsa, Mwayiwawo, additional, Chirwa, Marumbo, additional, Kapulula, Mayamiko, additional, Muyaya, Sharon, additional, Munharo, Steven, additional, Wiesner, Lubbe, additional, Phiri, Kamija S., additional, Mwapasa, Victor, additional, Ter Kuile, Feiko O., additional, Maartens, Gary, additional, and Barnes, Karen I., additional

Published
2022
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33. Making Data Map Worthy - Enhancing Routine Malaria Data to Support Surveillance and Mapping of Plasmodium Falciparum Antimalarial Resistance in a Pre-Elimination Sub-Saharan African Setting: A Molecular and Spatiotemporal Epidemiology Study

Author

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

Published
2022
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34. Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of Coadministered Ruxolitinib and Artemether-Lumefantrine in Healthy Adults

Author

Chughlay, M. Farouk, primary, Barnes, Karen I., additional, El Gaaloul, Myriam, additional, Abla, Nada, additional, Möhrle, Jörg J., additional, Griffin, Paul, additional, van Giersbergen, Paul, additional, Reuter, Stephanie E., additional, Schultz, Hayley B., additional, Kress, Anita, additional, Tapley, Peter, additional, Webster, Rebecca A., additional, Wells, Timothy, additional, McCarthy, James S., additional, Barber, Bridget E., additional, Marquart, Louise, additional, Boyle, Michelle J., additional, Engwerda, Christian R., additional, and Chalon, Stephan, additional

Published
2022
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36. Artemether-lumefantrine dosing for malaria treatment in young children and pregnant women: A pharmacokinetic-pharmacodynamic meta-analysis

Author

Kloprogge, Frank, Workman, Lesley, Borrmann, Steffen, Tékété, Mamadou, Lefèvre, Gilbert, Hamed, Kamal, Piola, Patrice, Ursing, Johan, Kofoed, Poul Erik, Mårtensson, Andreas, Ngasala, Billy, Björkman, Anders, Ashton, Michael, Friberg Hietala, Sofia, Aweeka, Francesca, Parikh, Sunil, Mwai, Leah, Davis, Timothy M. E., Karunajeewa, Harin, Salman, Sam, Checchi, Francesco, Fogg, Carole, Newton, Paul N., Mayxay, Mayfong, Deloron, Philippe, Faucher, Jean François, Nosten, François, Ashley, Elizabeth A., McGready, Rose, van Vugt, Michele, Proux, Stephane, Price, Ric N., Karbwang, Juntra, Ezzet, Farkad, Bakshi, Rajesh, Stepniewska, Kasia, White, Nicholas J., Guerin, Philippe J., Barnes, Karen I., and Tarning, Joel

Subjects
Lumefantrine -- Patient outcomes, Malaria -- Development and progression -- Care and treatment, Pregnant women -- Health aspects, Artemether -- Patient outcomes, Biological sciences
Abstract

Background The fixed dose combination of artemether-lumefantrine (AL) is the most widely used treatment for uncomplicated Plasmodium falciparum malaria. Relatively lower cure rates and lumefantrine levels have been reported in young children and in pregnant women during their second and third trimester. The aim of this study was to investigate the pharmacokinetic and pharmacodynamic properties of lumefantrine and the pharmacokinetic properties of its metabolite, desbutyl-lumefantrine, in order to inform optimal dosing regimens in all patient populations. Methods and findings A search in PubMed, Embase, ClinicalTrials.gov, Google Scholar, conference proceedings, and the WorldWide Antimalarial Resistance Network (WWARN) pharmacology database identified 31 relevant clinical studies published between 1 January 1990 and 31 December 2012, with 4,546 patients in whom lumefantrine concentrations were measured. Under the auspices of WWARN, relevant individual concentration-time data, clinical covariates, and outcome data from 4,122 patients were made available and pooled for the meta-analysis. The developed lumefantrine population pharmacokinetic model was used for dose optimisation through in silico simulations. Venous plasma lumefantrine concentrations 7 days after starting standard AL treatment were 24.2% and 13.4% lower in children weighing Conclusions Our findings suggest that revised AL dosing regimens for young children and pregnant women would improve drug exposure but would require longer or more complex schedules. These dosing regimens should be evaluated in prospective clinical studies to determine whether they would improve cure rates, demonstrate adequate safety, and thereby prolong the useful therapeutic life of this valuable antimalarial treatment., Author(s): Frank Kloprogge 1,2,3, Lesley Workman 4,5, Steffen Borrmann 6,7, Mamadou Tékété 7,8, Gilbert Lefèvre 9, Kamal Hamed 10, Patrice Piola 11, Johan Ursing 12,13,14, Poul Erik Kofoed 14,15, Andreas [...]

Published
2018
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37. Additional file 1 of Pharmacokinetic profile of amodiaquine and its active metabolite desethylamodiaquine in Ghanaian patients with uncomplicated falciparum malaria

Author

Anyorigiya, Thomas A., Castel, Sandra, Mauff, Katya, Atuguba, Frank, Bernhards Ogutu, Oduro, Abraham, Dosoo, David, Kwaku-Poku Asante, Owusu-Agyei, Seth, Dodoo, Alexander, Hodgson, Abraham, Binka, Fred, Workman, Lesley J., Allen, Elizabeth N., Denti, Paolo, Wiesner, Lubbe, and Barnes, Karen I.

Abstract

Additional file 1. Liquid chromatography tandem mass spectrometry assay methods.

Published
2021
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38. Additional file 2 of Pharmacokinetic profile of amodiaquine and its active metabolite desethylamodiaquine in Ghanaian patients with uncomplicated falciparum malaria

Author

Anyorigiya, Thomas A., Castel, Sandra, Mauff, Katya, Atuguba, Frank, Bernhards Ogutu, Oduro, Abraham, Dosoo, David, Kwaku-Poku Asante, Owusu-Agyei, Seth, Dodoo, Alexander, Hodgson, Abraham, Binka, Fred, Workman, Lesley J., Allen, Elizabeth N., Denti, Paolo, Wiesner, Lubbe, and Barnes, Karen I.

Subjects
parasitic diseases
Abstract

Additional file 2. Pharmacokinetic parameters (median, IQR) of amodiaquine and desethylamodiaquine following artesunate-amodiaquine fixed-dose combination treatment of Ghanaian patients with uncomplicated P. falciparum malaria, by study site and age category.

Published
2021
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43. Population Pharmacokinetic Properties of Piperaquine in Falciparum Malaria: An Individual Participant Data Meta-Analysis

Author

Hoglund, Richard M., Workman, Lesley, Edstein, Michael D., Thanh, Nguyen Xuan, Quang, Nguyen Ngoc, Zongo, Issaka, Ouedraogo, Jean Bosco, Borrmann, Steffen, Mwai, Leah, Nsanzabana, Christian, Price, Ric N., Dahal, Prabin, Sambol, Nancy C., Parikh, Sunil, Nosten, Francois, Ashley, Elizabeth A., Phyo, Aung Pyae, Lwin, Khin Maung, McGready, Rose, Day, Nicholas P. J., Guerin, Philippe J., White, Nicholas J., Barnes, Karen I., and Tarning, Joel

Subjects
Antimalarials -- Dosage and administration, Pharmacokinetics -- Models, Biological sciences
Abstract

Background Artemisinin-based combination therapies (ACTs) are the mainstay of the current treatment of uncomplicated Plasmodium falciparum malaria, but ACT resistance is spreading across Southeast Asia. Dihydroartemisinin-piperaquine is one of the five ACTs currently recommended by the World Health Organization. Previous studies suggest that young children ( Methods and Findings Published pharmacokinetic studies on piperaquine were identified through a systematic literature review of articles published between 1 January 1960 and 15 February 2013. Individual plasma piperaquine concentration-time data from 11 clinical studies (8,776 samples from 728 individuals) in adults and children with uncomplicated malaria and healthy volunteers were collated and standardised by the WorldWide Antimalarial Resistance Network. Data were pooled and analysed using nonlinear mixed-effects modelling. Piperaquine pharmacokinetics were described successfully by a three-compartment disposition model with flexible absorption. Body weight influenced clearance and volume parameters significantly, resulting in lower piperaquine exposures in small children ( Conclusions The derived population pharmacokinetic model was used to develop a revised dose regimen of dihydroartemisinin-piperaquine that is expected to provide equivalent piperaquine exposures safely in all patients, including in small children with malaria. Use of this dose regimen is expected to prolong the useful therapeutic life of dihydroartemisinin-piperaquine by increasing cure rates and thereby slowing resistance development. This work was part of the evidence that informed the World Health Organization technical guidelines development group in the development of the recently published treatment guidelines (2015)., Author(s): Richard M. Hoglund 1,2,3, Lesley Workman 1,4, Michael D. Edstein 5, Nguyen Xuan Thanh 6, Nguyen Ngoc Quang 7, Issaka Zongo 8,9, Jean Bosco Ouedraogo 8, Steffen Borrmann 10,11, [...]

Published
2017
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45. Efficacy of single dose primaquine with artemisinin combination therapy on P. falciparum gametocytes and transmission : A WWARN individual patient meta-analysis.

Author

Stepniewska, Kasia, Humphreys, Georgina S, Gonçalves, Bronner P, Craig, Elaine, Gosling, Roly, Guerin, Philippe J, Price, Ric N, Barnes, Karen I, Raman, Jaishree, Smit, Menno R, D'Alessandro, Umberto, Stone, Will J R, Bjorkman, Anders, Samuels, Aaron M, Arroyo-Arroyo, Maria I, Bastiaens, Guido J H, Brown, Joelle M, Dicko, Alassane, El-Sayed, Badria B, Elzaki, Salah-Eldin G, Eziefula, Alice C, Kariuki, Simon, Kwambai, Titus K, Maestre, Amanda E, Mårtensson, Andreas, Mosha, Dominic, Mwaiswelo, Richard O, Ngasala, Billy E, Okebe, Joseph, Roh, Michelle E, Sawa, Patrick, Tiono, Alfred B, Chen, Ingrid, Drakeley, Chris J, Bousema, Teun, Stepniewska, Kasia, Humphreys, Georgina S, Gonçalves, Bronner P, Craig, Elaine, Gosling, Roly, Guerin, Philippe J, Price, Ric N, Barnes, Karen I, Raman, Jaishree, Smit, Menno R, D'Alessandro, Umberto, Stone, Will J R, Bjorkman, Anders, Samuels, Aaron M, Arroyo-Arroyo, Maria I, Bastiaens, Guido J H, Brown, Joelle M, Dicko, Alassane, El-Sayed, Badria B, Elzaki, Salah-Eldin G, Eziefula, Alice C, Kariuki, Simon, Kwambai, Titus K, Maestre, Amanda E, Mårtensson, Andreas, Mosha, Dominic, Mwaiswelo, Richard O, Ngasala, Billy E, Okebe, Joseph, Roh, Michelle E, Sawa, Patrick, Tiono, Alfred B, Chen, Ingrid, Drakeley, Chris J, and Bousema, Teun

Abstract

BACKGROUND: Since the World Health Organization recommended single low-dose (0.25mg/kg) primaquine (PQ) in combination with artemisinin-based combination therapies (ACTs) in areas of low transmission or artemisinin-resistant P. falciparum, several single-site studies have been conducted to assess its efficacy. METHODS: An individual patient meta-analysis to assess the gametocytocidal and transmission-blocking efficacy of PQ used in combination with different ACTs was conducted. Random effects logistic regression was used to quantify PQ effect on (i) gametocyte carriage in the first two weeks post-treatment; (ii) the probability of infecting at least one mosquito or of a mosquito becoming infected. RESULTS: In 2,574 participants from fourteen studies, PQ reduced PCR-determined gametocyte carriage on days 7 and 14, most apparently in patients presenting with gametocytaemia on day 0 (Odds Ratio (OR)=0.22; 95%CI 0.17-0.28 and OR=0.12; 95%CI 0.08-0.16, respectively). The rate of decline in gametocyte carriage was faster when PQ was combined with artemether-lumefantrine (AL) compared to dihydroartemisinin-piperaquine (DP) (p=0.010 for day 7). Addition of 0.25mg/kg PQ was associated with near complete prevention of transmission to mosquitoes. CONCLUSION: Primaquine's transmission-blocking effects are achieved with 0.25 mg/kg PQ. Gametocyte persistence and infectivity are lower when PQ is combined with AL compared to DP.

Published
2020
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46. An Individual Participant Data Population Pharmacokinetic Meta-Analysis of Drug-drug Interactions between Lumefantrine and Commonly-used Antiretroviral Treatment

Author

Francis, Jose, Barnes, Karen I., Workman, Lesley, Kredo, Tamara, Vestergaard, Lasse S., Hoglund, Richard M, Byakika-Kibwika, Pauline, Lamorde, Mohammed, Walimbwa, Stephen I, Chijioke-Nwauche, Ifeyinwa, Sutherland, Colin J., Merry, Concepta, Scarsi, Kimberley K, Nyagonde, Nyagonde, Lemnge, Martha M., Khoo, Saye H, Bygbjerg, Ib C, Parikh, Sunil, Aweeka, Francesca T, Tarning, Joel, Denti, Paolo, Francis, Jose, Barnes, Karen I., Workman, Lesley, Kredo, Tamara, Vestergaard, Lasse S., Hoglund, Richard M, Byakika-Kibwika, Pauline, Lamorde, Mohammed, Walimbwa, Stephen I, Chijioke-Nwauche, Ifeyinwa, Sutherland, Colin J., Merry, Concepta, Scarsi, Kimberley K, Nyagonde, Nyagonde, Lemnge, Martha M., Khoo, Saye H, Bygbjerg, Ib C, Parikh, Sunil, Aweeka, Francesca T, Tarning, Joel, and Denti, Paolo

Abstract

Treating malaria in HIV co-infected individuals should consider potential drug-drug interactions. Artemether-lumefantrine is the most widely recommended treatment for uncomplicated malaria globally. Lumefantrine is metabolized by CYP3A4, an enzyme that commonly-used antiretrovirals often induce or inhibit. A population pharmacokinetic meta-analysis was conducted using individual participant data from ten studies, with 6,100 lumefantrine concentrations from 793 non-pregnant adult participants (41% HIV-malaria co-infected, 36% malaria-infected, 20% HIV-infected, and 3% healthy volunteers). Lumefantrine exposure increased 3.4-fold with co-administration of lopinavir/ritonavir-based antiretroviral therapy (ART), while it decreased by 47% with efavirenz-based ART and by 59% in the patients with rifampicin-based anti-tuberculosis treatment. Nevirapine- or dolutegravir-based ART and malaria- or HIV-infection were not associated with significant effects. Monte Carlo simulations showed that those on concomitant efavirenz or rifampicin have 49% and 80% probability of day-7 concentrations <200 ng/mL respectively, a threshold associated with an increased risk of treatment failure. The risk of achieving sub-therapeutic concentrations increases with larger body weight. An extended 5-day and 6-day artemether-lumefantrine regimen is predicted to overcome these drug-drug interactions with efavirenz and rifampicin respectively.

Published
2020

48. Population pharmacokinetics of artesunate and dihydroartemisinin following intra-rectal dosing of artesunate in malaria patients

Author

Simpson, Julie A., Agbenyega, Tsiri, Barnes, Karen I., Di Perri, Gianni, Folb, Peter, Homes, Melba, Krishna, Sanjeev, Krudsood, Srivicha, Looareesuwan, Sornchai, Mansor, Sharif, McIlleron, Helen, Miller, Raymond, Molyneux, Malcolm, Mwenechanya, James, Navaratnam, Visweswaran, Nosten, Francois, Olliaro, Piero, Pang, Lorrin, Ribeiro, Isabela, Tembo, Madalitso, van Vugt, Michele, Ward, Steve, Weerasuriya, Kris, Win, Kyaw, and White, Nicholas J.

Subjects
Antimalarials -- Usage, Malaria -- Care and treatment, Pharmacokinetics -- Analysis
Abstract

ABSTRACT Background Intra-rectal artesunate has been developed as a potentially life-saving treatment of severe malaria in rural village settings where administration of parenteral antimalarial drugs is not possible. We studied [...]

Published
2006

49. The World Bank: false financial and statistical accounts and medical malpractice in malaria treatment

Author

Attaran, Amir, Barnes, Karen I., Bate, Roger, Binka, Fred, d'Alessandro, Umberto, Fanello, Caterina I., Garrett, Laurie, Mutabingwa, Theonest K., Roberts, Donald, Sibley, Carol Hopkins, Talisuna, Ambrose, Van geertruyden, Jean-Pierre, and Watkins, William M.

Subjects
World Bank Group. World Bank -- Management, World Bank Group. World Bank -- Finance, Malaria -- Care and treatment, Malaria -- Standards, Malaria -- Public opinion, Medical personnel -- Malpractice, Company business management, Company financing
Published
2006

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