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157 results on '"Schramm, Birgit"'

1. 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. 'We give them threatening advice...': expectations of adherence to antiretroviral therapy and their consequences among adolescents living with HIV in rural Malawi

Author

Burns, Rose, Magalasi, Denview, Blasco, Philippe, Szumilin, Elisabeth, Pasquier, Estelle, Schramm, Birgit, and Wringe, Alison

Subjects
HIV patients -- Social aspects, Highly active antiretroviral therapy -- Social aspects, Youth -- Social aspects, Patient compliance -- Social aspects, HIV -- Social aspects, Caregivers -- Social aspects, Health
Abstract

Introduction: Many adolescents living with HIV in sub-Saharan Africa struggle to achieve optimal adherence to antiretrovira therapy (ART), but few studies have investigated how their treatment-taking decisions are influenced by their social interactions with providers, caregivers and community leaders. This study aims to explore the narratives that define expectations of adherence to ART among adolescents living with HIV in a rural Malawian setting. Methods: Overall, 45 in-depth interviews were conducted in 2016 with adolescents living with HIV, caregivers, health workers and community leaders, and four group sessions using participatory tools were undertaken with adolescents. Interviews and group sessions were audio-recorded, transcribed and translated into English. Data were coded inductively and analysed thematically Results: Adolescents were given strict behavioural codes around optimal treatment adherence, which were often enforced through encouragement, persuasian and threats. In HIV clinics, some staff supported adolescents with broader concerns relating to living with HIV, but other measures to address sub-optimal adherence in HIV clinics were perceived by patients as punitive, including pill-counts and increased frequency of clinic visits. Community leaders felt responsible for young peoples' health, sometimes attempting to influence their treatment-taking by threatening to withdraw services, or to publically 'out' those deemed to be non-adherent. At home, discussions with adolescents about HIV were often limited to dose reminders, and some caretakers resorted to physical punishment to ensure adherence. While some adolescents complied with strictly-enforced adherence rules, others demonstrated resistance by hiding missed doses, secretly throwing away drugs, or openly refusing to take them. Conclusions: The potential of young people to adhere to their ART may be undermined by restrictive messages and punitive approaches to enforce and control their engagement with treatment at home, in the clinic and in the wider community. Interventions should focus on creating safe spaces for adolescents to speak frankly about the adherence challenges that they face and support for caregivers including home-based interventions. Keywords: adherence; adolescents living with HIV; antiretroviral therapy; Malawi; qualitative, 1 | INTRODUCTION Adolescents are the face of a burgeoning HIV epidemic in sub-Saharan Africa, with an estimated 1.6 million 10- to 19-year olds living with HIV by 2018 [1]. [...]

Published
2020
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4. 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

5. MDR M. tuberculosis outbreak clone in Eswatini missed by Xpert has elevated bedaquiline resistance dated to the pre-treatment era

Author

Beckert, Patrick, Sanchez-Padilla, Elisabeth, Merker, Matthias, Dreyer, Viola, Kohl, Thomas A., Utpatel, Christian, Köser, Claudio U., Barilar, Ivan, Ismail, Nazir, Omar, Shaheed Vally, Klopper, Marisa, Warren, Robin M., Hoffmann, Harald, Maphalala, Gugu, Ardizzoni, Elisa, de Jong, Bouke C., Kerschberger, Bernhard, Schramm, Birgit, Andres, Sönke, Kranzer, Katharina, Maurer, Florian P., Bonnet, Maryline, and Niemann, Stefan

Published
2020
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7. 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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9. Point-of-care viral load monitoring: outcomes from a decentralized HIV programme in Malawi

Author

Nicholas, Sarala, Poulet, Elisabeth, Wolters, Liselotte, Wapling, Johanna, Rakesh, Ankur, Amoros, Isabel, Szumilin, Elisabeth, Gueguen, Monique, and Schramm, Birgit

Subjects
Viremia -- Measurement, Patient monitoring -- Methods, HIV infection -- Patient outcomes -- Care and treatment, Health
Abstract

: Introduction: Routinely monitoring the HIV viral load (VL) of people living with HIV (PLHIV) on anti‐retroviral therapy (ART) facilitates intensive adherence counselling and faster ART regimen switch when treatment failure is indicated. Yet standard VL‐testing in centralized laboratories can be time‐intensive and logistically difficult in low‐resource settings. This paper evaluates the outcomes of the first four years of routine VL‐monitoring using Point‐of‐Care technology, implemented by Médecins Sans Frontières (MSF) in rural clinics in Malawi. Methods: We conducted a retrospective cohort analysis of patients eligible for routine VL‐ testing between 2013 and 2017 in four decentralized ART‐clinics and the district hospital in Chiradzulu, Malawi. We assessed VL‐testing coverage and the treatment failure cascade (from suspected failure (first VL>1000 copies/mL) to VL suppression post regimen switch). We used descriptive statistics and multivariate logistic regression to assess factors associated with suspected failure. Results and Discussion: Among 21,400 eligible patients, VL‐testing coverage was 85% and VL suppression was found in 89% of those tested. In the decentralized clinics, 88% of test results were reviewed on the same day as blood collection, whereas in the district hospital the median turnaround‐time for results was 85 days. Among first‐line ART patients with suspected failure (N = 1544), 30% suppressed (VL Conclusions: Viral load testing at the point‐of‐care in Chiradzulu, Malawi achieved high coverage and good drug regimen switch rates among those identified as treatment failures. In decentralized clinics, same‐day test results and shorter time‐to‐switch illustrated the game‐changing potential of POC‐based VL‐testing. Nevertheless, gaps were identified along all steps of the failure cascade. Regular staff training, continuous monitoring and creating demand are essential to the success of routine VL‐testing., Introduction Viral load (VL) testing is the gold standard approach for monitoring treatment effectiveness in HIV‐positive patients on anti‐retroviral therapy (ART). VL suppression can be a performance indicator for ART [...]

Published
2019
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10. Correction: Potential value of urine lateral-flow lipoarabinomannan (LAM) test for diagnosing tuberculosis among severely acute malnourished children

Author

Schramm, Birgit, primary, Nganaboy, Rodrigue C., additional, Uwiragiye, Piex, additional, Mukeba, Didier, additional, Abdoubara, Aboubacar, additional, Abdou, Illa, additional, Nshimiymana, Jean-Claude, additional, Sounna, Seyni, additional, Hiffler, Laurent, additional, Flevaud, Laurence, additional, and Huerga, Helena, additional

Published
2021
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11. Potential value of urine lateral-flow lipoarabinomannan (LAM) test for diagnosing tuberculosis among severely acute malnourished children

Author

Schramm, Birgit, primary, Nganaboy, Rodrigue C., additional, Uwiragiye, Piex, additional, Mukeba, Didier, additional, Abdoubara, Aboubacar, additional, Abdou, Illa, additional, Nshimiymana, Jean-Claude, additional, Sounna, Seyni, additional, Hiffler, Laurent, additional, Flevaud, Laurence, additional, and Huerga, Helena, additional

Published
2021
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12. High Prevalence of NRTI and NNRTI Drug Resistance Among ART-Experienced, Hospitalized Inpatients.

Author

Bossard, Claire, Schramm, Birgit, Wanjala, Stephen, Jain, Lakshmi, Mucinya, Gisèle, Opollo, Valarie, Wiesner, Lubbe, van Cutsem, Gilles, Poulet, Elisabeth, Szumilin, Elisabeth, Ellman, Tom, and Maman, David

Abstract

Supplemental Digital Content is Available in the Text. Background: Patients hospitalized with advanced HIV have a high mortality risk. We assessed viremia and drug resistance among differentiated care services and explored whether expediting the switching of failing treatments may be justified. Setting: Hospitals in the Democratic Republic of (DRC) Congo (HIV hospital) and Kenya (general hospital including HIV care). Methods: Viral load (VL) testing and drug resistance (DR) genotyping were conducted for HIV inpatients ≥15 years, on first-line antiretroviral therapy (ART) for ≥6 months, and CD4 ≤350 cells/µL. Dual-class DR was defined as low-, intermediate-, or high-level DR to at least 1 nucleoside reverse transcriptase inhibitor and 1 non-nucleoside reverse transcriptase inhibitor. ART regimens were considered ineffective if dual-class DR was detected at viral failure (VL ≥1000 copies/mL). Results: Among 305 inpatients, 36.7% (Kenya) and 71.2% (DRC) had VL ≥1000 copies/mL, of which 72.9% and 73.7% had dual-class DR. Among viral failures on tenofovir disoproxil fumarate (TDF)-based regimens, 56.1% had TDF-DR and 29.8% zidovudine (AZT)-DR; on AZT regimens, 71.4% had AZT-DR and 61.9% TDF-DR, respectively. Treatment interruptions (≥48 hours during past 6 months) were reported by 41.7% (Kenya) and 56.7% (DRC). Approximately 56.2% (Kenya) and 47.4% (DRC) on TDF regimens had tenofovir diphosphate concentrations <1250 fmol/punch (suboptimal adherence). Among viral failures with CD4 <100 cells/µL, 76.0% (Kenya) and 84.6% (DRC) were on ineffective regimens. Conclusions: Many hospitalized, ART-experienced patients with advanced HIV were on an ineffective first-line regimen. Addressing ART failure promptly should be integrated into advanced disease care packages for this group. Switching to effective second-line medications should be considered after a single high VL on non-nucleoside reverse transcriptase inhibitor–based first-line if CD4 ≤350 cells/µL or, when VL is unavailable, among patients with CD4 ≤100 cells/µL. [ABSTRACT FROM AUTHOR]

Published
2022
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14. Additional file 2 of MDR M. tuberculosis outbreak clone in Eswatini missed by Xpert has elevated bedaquiline resistance dated to the pre-treatment era

Author

Beckert, Patrick, Sanchez-Padilla, Elisabeth, Merker, Matthias, Dreyer, Viola, Kohl, Thomas A., Utpatel, Christian, Köser, Claudio U., Barilar, Ivan, Ismail, Nazir, Shaheed Vally Omar, Klopper, Marisa, Warren, Robin M., Hoffmann, Harald, Gugu Maphalala, Ardizzoni, Elisa, Jong, Bouke C. De, Kerschberger, Bernhard, Schramm, Birgit, Andres, Sönke, Kranzer, Katharina, Maurer, Florian P., Bonnet, Maryline, and Niemann, Stefan

Abstract

Additional file 2. Supplemental methods and description of resistance mutations.

Published
2020
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15. Additional file 3 of MDR M. tuberculosis outbreak clone in Eswatini missed by Xpert has elevated bedaquiline resistance dated to the pre-treatment era

Author

Beckert, Patrick, Sanchez-Padilla, Elisabeth, Merker, Matthias, Dreyer, Viola, Kohl, Thomas A., Utpatel, Christian, Köser, Claudio U., Barilar, Ivan, Ismail, Nazir, Shaheed Vally Omar, Klopper, Marisa, Warren, Robin M., Hoffmann, Harald, Gugu Maphalala, Ardizzoni, Elisa, Jong, Bouke C. De, Kerschberger, Bernhard, Schramm, Birgit, Andres, Sönke, Kranzer, Katharina, Maurer, Florian P., Bonnet, Maryline, and Niemann, Stefan

Abstract

Additional file 3: Fig. S1. Phylogenetic diversity and drug susceptibility of the 412 M. tuberculosis complex isolates from Eswatini. Fig. S2. Lineage distribution across Eswatini. Fig. S3. Isolates selected for further whole-genome sequencing analysis.

Published
2020
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16. Implementation and operational feasibility of SAMBA I HIV‐1 semi‐quantitative viral load testing at the point‐of‐care in rural settings in Malawi and Uganda

Author

Gueguen, Monique, primary, Nicholas, Sarala, additional, Poulet, Elisabeth, additional, Schramm, Birgit, additional, Szumilin, Elisabeth, additional, Wolters, Liselotte, additional, Wapling, Johanna, additional, Ajule, Ephrahim, additional, Rakesh, Ankur, additional, Mwenda, Reuben, additional, Kiyaga, Charles, additional, and Balkan, Suna, additional

Published
2020
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22. Competing risk events in antimalarial drug trials in uncomplicated Plasmodium falciparum malaria : a WorldWide Antimalarial Resistance Network individual participant data meta-analysis

Author

Dahal, Prabin, Simpson, Julie Anne, Abdulla, Salim, Achan, Jane, Adam, Ishag, Agarwal, Aarti, Allan, Richard, Anvikar, Anupkumar R., Arinaitwe, Emmanuel, Ashley, Elizabeth A., Awab, Ghulam Rahim, Bassat, Quique, Bjorkman, Anders, Bompart, Francois, Borrmann, Steffen, Bousema, Teun, Broek, Ingrid, Bukirwa, Hasifa, Carrara, Verena I., Corsi, Marco, Cot, Michel, D'Alessandro, Umberto, Davis, Timothy M. E., de Wit, Marit, Deloron, Philippe, Desai, Meghna, Dimbu, Pedro Rafael, Djalle, Djibrine, Djimde, Abdoulaye, Dorsey, Grant, Doumbo, Ogobara K., 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, Greenwood, Brian, Grivoyannis, Anastasia, Hamed, Kamal, Hien, Tran Tinh, Hughes, David, Humphreys, Georgina, Hwang, Jimee, Ibrahim, Maman Laminou, Janssens, Bart, Jullien, Vincent, Juma, Elizabeth, Kamugisha, Erasmus, Karema, Corine, Karunajeewa, Harin A., Kiechel, Jean R., Kironde, Fred, Kofoed, Poul-Erik, Kremsner, Peter G., Lameyre, Valerie, Lee, Sue J., Marsh, Kevin, Mårtensson, Andreas, Mayxay, Mayfong, Menan, Herve, Mens, Petra, Mutabingwa, Theonest K., Ndiaye, Jean-Louis, Ngasala, Billy E., Noedl, Harald, Nosten, Francois, Offianan, Andre Toure, Oguike, Mary, Ogutu, Bernhards R., Olliaro, Piero, Ouedraogo, Jean Bosco, Piola, Patrice, Plowe, Christopher V., Plucinski, Mateusz M., Pratt, Oliver James, Premji, Zulfikarali, Ramharter, Michael, Rogier, Christophe, Rombo, Lars, Rosenthal, Philip J., Sawa, Patrick, Schramm, Birgit, Sibley, Carol, Sinou, Veronique, Sirima, Sodiomon, Smithuis, Frank, Staedke, Sarah G., Sutanto, Inge, Talisuna, Ambrose Otau, Tarning, Joel, Taylor, Walter R. J., Temu, Emmanuel, Thriemer, Kamala L., Thuy, Nhien Nguyen, Udhayakumar, Venkatachalam, Ursing, Johan, van Herp, Michel, van Vugt, Michele, Whitty, Christopher, William, Yavo, Winnips, Cornelis, Zongo, Issaka, Guerin, Philippe, Price, Ric N., Stepniewska, Kasia, Dahal, Prabin, Simpson, Julie Anne, Abdulla, Salim, Achan, Jane, Adam, Ishag, Agarwal, Aarti, Allan, Richard, Anvikar, Anupkumar R., Arinaitwe, Emmanuel, Ashley, Elizabeth A., Awab, Ghulam Rahim, Bassat, Quique, Bjorkman, Anders, Bompart, Francois, Borrmann, Steffen, Bousema, Teun, Broek, Ingrid, Bukirwa, Hasifa, Carrara, Verena I., Corsi, Marco, Cot, Michel, D'Alessandro, Umberto, Davis, Timothy M. E., de Wit, Marit, Deloron, Philippe, Desai, Meghna, Dimbu, Pedro Rafael, Djalle, Djibrine, Djimde, Abdoulaye, Dorsey, Grant, Doumbo, Ogobara K., 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, Greenwood, Brian, Grivoyannis, Anastasia, Hamed, Kamal, Hien, Tran Tinh, Hughes, David, Humphreys, Georgina, Hwang, Jimee, Ibrahim, Maman Laminou, Janssens, Bart, Jullien, Vincent, Juma, Elizabeth, Kamugisha, Erasmus, Karema, Corine, Karunajeewa, Harin A., Kiechel, Jean R., Kironde, Fred, Kofoed, Poul-Erik, Kremsner, Peter G., Lameyre, Valerie, Lee, Sue J., Marsh, Kevin, Mårtensson, Andreas, Mayxay, Mayfong, Menan, Herve, Mens, Petra, Mutabingwa, Theonest K., Ndiaye, Jean-Louis, Ngasala, Billy E., Noedl, Harald, Nosten, Francois, Offianan, Andre Toure, Oguike, Mary, Ogutu, Bernhards R., Olliaro, Piero, Ouedraogo, Jean Bosco, Piola, Patrice, Plowe, Christopher V., Plucinski, Mateusz M., Pratt, Oliver James, Premji, Zulfikarali, Ramharter, Michael, Rogier, Christophe, Rombo, Lars, Rosenthal, Philip J., Sawa, Patrick, Schramm, Birgit, Sibley, Carol, Sinou, Veronique, Sirima, Sodiomon, Smithuis, Frank, Staedke, Sarah G., Sutanto, Inge, Talisuna, Ambrose Otau, Tarning, Joel, Taylor, Walter R. J., Temu, Emmanuel, Thriemer, Kamala L., Thuy, Nhien Nguyen, Udhayakumar, Venkatachalam, Ursing, Johan, van Herp, Michel, van Vugt, Michele, Whitty, Christopher, William, Yavo, Winnips, Cornelis, Zongo, Issaka, Guerin, Philippe, Price, Ric N., and Stepniewska, Kasia

Abstract

Background: Therapeutic efficacy studies in uncomplicated Plasmodium falciparum malaria are confounded by new infections, which constitute competing risk events since they can potentially preclude/pre-empt the detection of subsequent recrudescence of persistent, sub-microscopic primary infections. Methods: Antimalarial studies typically report the risk of recrudescence derived using the Kaplan-Meier (K-M) method, which considers new infections acquired during the follow-up period as censored. Cumulative Incidence Function (CIF) provides an alternative approach for handling new infections, which accounts for them as a competing risk event. The complement of the estimate derived using the K-M method (1 minus K-M), and the CIF were used to derive the risk of recrudescence at the end of the follow-up period using data from studies collated in the WorldWide Antimalarial Resistance Network data repository. Absolute differences in the failure estimates derived using these two methods were quantified. In comparative studies, the equality of two K-M curves was assessed using the log-rank test, and the equality of CIFs using Gray's k-sample test (both at 5% level of significance). Two different regression modelling strategies for recrudescence were considered: cause-specific Cox model and Fine and Gray's sub-distributional hazard model. Results: Data were available from 92 studies (233 treatment arms, 31,379 patients) conducted between 1996 and 2014. At the end of follow-up, the median absolute overestimation in the estimated risk of cumulative recrudescence by using 1 minus K-M approach was 0.04% (interquartile range (IQR): 0.00-0.27%, Range: 0.00-3.60%). The overestimation was correlated positively with the proportion of patients with recrudescence [Pearson's correlation coefficient (rho): 0.38, 95% Confidence Interval (CI) 0.30-0.46] or new infection [rho: 0.43; 95% CI 0.35-0.54]. In three study arms, the point estimates of failure were greater than 10% (the WHO threshold

Published
2019
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23. Population Pharmacokinetics of the Antimalarial Amodiaquine: a Pooled Analysis To Optimize Dosing

Author

Ali, Ali Mohamed, Penny, Melissa, Smith, Thomas, Workman, Lesley, Sasi, Philip, Adjei, George O, Aweeka, Francesca, Kiechel, Jean-René, Jullien, Vincent, Rijken, Marcus, Mcgready, Rose, Mwesigwa, Julia, Kristensen, Kim, Stepniewska, Kasia, Tarning, Joel, Barnes, Karen, Denti, Paolo, Massougbodji, Achille, Gansané, Adama, Adeothy, Adicat, Aubouy, Agnès, Ouedraogo, Alphonse, Annerberg, Anna, Bruneel, Arnaud, Phyo, Aung Pyae, Win, Aye Kyi, Benakis, A., Goka, Bamenla, Gourmel, Bernard, Ogutu, Bernhards, Schramm, Birgit, McGee, Bryan, Morgan, Caroline, Obonyo, Charles, Mazinda, Charles, Parzy, D., Ashley, Elizabeth, Baudin, Elisabeth, Juma, Elizabeth, Comte, Eric, Ouedraogo, Esperance, Nosten, François, Sugnaux, F., Cottrell, Gilles, Dorsey, Grant, Carn, Gwenaelle, Kossou, Hortense, Amedome, Hyacinthe, Kalyango, Joan, Faucher, Jean-François, Jones, Joel, Simpson, Julie, Doritchamou, Justin, Kurtzhals, J., Pinoges, Loretxu, Hoegberg, Lotte, BERTAUX, L., Malaika, L. Tshilolo Muepu, Bergstrand, Martin, Alifrangis, Michael, Branger, Michel, Cot, Michel, Cammas, Mireille, Kamya, Moses, Day, Nicholas, White, Nicholas, Taudon, N., Rodrigues, Onike, Chotsiri, Palang, Valeh, Parastou, Houzé, Pascal, Deloron, Philippe, Guérin, Philippe, Rosenthal, Philip, Hsi, Poe, German, Polina, Singhasivanon, Pratap, Smith, Richard, Lwango, R., Sirima, Sodiomon, Parikh, Sunil, Alegre, S. Sese, Clark, Tamara, Sundaygar, Timothy, Drysdale, Troy, Taylor, Walter, Sinou, V., Zolia, Yah, Swiss Tropical and Public Health Institute [Basel], University of Basel (Unibas), Ifakara Health Institute, University of Cape Town, Muhimbili University of Health and Allied Sciences, University of Ghana, University of California, Drugs for Neglected Diseases Initiative, Service de Pharmacologie, Hôpital Européen George Pompidou, Université Paris Descartes, Paris, France, Hôpital Européen Georges Pompidou [APHP] (HEGP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO), Mahidol University [Bangkok], University of Oxford [Oxford], London School of Hygiene & Tropical Medicine [Fajara, The Gambia], University of Antwerp (UA), Development DMPK-PKPD, Novo Nordisk, Copenhagen, Denmark, Univ Copenhagen, Fac Hlth & Med Sci, Novo Nordisk Fdn, Dis Syst Biol,Ctr Prot Res, Copenhagen, Denmark, and Partenaires INRAE-Partenaires INRAE

Subjects
pediatrics, dose optimization, malaria, [SDV.SP]Life Sciences [q-bio]/Pharmaceutical sciences, NONMEM
Abstract

International audience; Amodiaquine plus artesunate is the recommended antimalarial treatment in many countries where malaria is endemic. However, pediatric doses are largely based on a linear extrapolation from adult doses. We pooled data from previously published studies on the pharmacokinetics of amodiaquine, to optimize the dose across all age groups. Adults and children with uncomplicated malaria received daily weight-based doses of amodiaquine or artesunate-amodiaquine over 3 days. Plasma concentration-time profiles for both the parent drug and the metabolite were characterized using nonlinear mixed-effects modeling. Amodiaquine pharmacokinetics were adequately described by a two-compartment disposition model, with first-order elimination leading to the formation of desethylamodiaquine, which was best described by a three-compartment disposition model. Body size and age were the main covariates affecting amodiaquine clearance. After adjusting for the effect of weight, clearance rates for amodiaquine and desethylamodiaquine reached 50% of adult maturation at 2.8 months (95% confidence interval [CI], 1.5 to 3.7 months) and 3.9 months (95% CI, 2.6 to 5.3 months) after birth, assuming that the baby was born at term. Bioavailability was 22.4% (95% CI, 15.6 to 31.9%) lower at the start of treatment than during convalescence, which suggests a malaria disease effect. Neither the drug formulation nor the hemoglobin concentration had an effect on any pharmacokinetic parameters. Results from simulations showed that current manufacturer dosing recommendations resulted in low desethylamodiaquine exposure in patients weighing 8 kg, 15 to 17 kg, 33 to 35 kg, and >62 kg compared to that in a typical 50-kg patient. We propose possible optimized dosing regimens to achieve similar drug exposures among all age groups, which require further validation.

Published
2018

24. Single low-dose primaquine for blocking transmission of Plasmodium falciparum malaria – a proposed model-derived age-based regimen for sub-Saharan Africa

Author

Taylor, W Robert, Naw, Htee Khu, Maitland, Kathryn, Williams, Thomas N, Kapulu, Melissa, D’Alessandro, Umberto, Berkley, James A, Bejon, Philip, Okebe, Joseph, Achan, Jane, Amambua, Alfred Ngwa, Affara, Muna, Nwakanma, Davis, van Geertruyden, Jean-Pierre, Mavoko, Muhindo, Lutumba, Pascal, Matangila, Junior, Brasseur, Philipe, Piola, Patrice, Randremanana, Rindra, Lasry, Estrella, Fanello, Caterina, Onyamboko, Marie, Schramm, Birgit, Yah, Zolia, Jones, Joel, Fairhurst, Rick M, Diakite, Mahamadou, Malenga, Grace, Molyneux, Malcolm, Rwagacondo, Claude, Obonyo, Charles, Department of Medicine, and Faculty of Health Sciences

Subjects
Adult, Aged, 80 and over, Adolescent, Dose-Response Relationship, Drug, Plasmodium falciparum, Age Factors, Infant, Primaquine, Malaria, Antimalarials, Glucosephosphate Dehydrogenase Deficiency, Clinical Protocols, Age-based dosing, Child, Preschool, Humans, Female, Transmission blocking, Malaria, Falciparum, Child, Africa South of the Sahara, Aged
Abstract

BACKGROUND: In 2012, the World Health Organization recommended blocking the transmission of Plasmodium falciparum with single low-dose primaquine (SLDPQ, target dose 0.25 mg base/kg body weight), without testing for glucose-6-phosphate dehydrogenase deficiency (G6PDd), when treating patients with uncomplicated falciparum malaria. We sought to develop an age-based SLDPQ regimen that would be suitable for sub-Saharan Africa. METHODS: Using data on the anti-infectivity efficacy and tolerability of primaquine (PQ), the epidemiology of anaemia, and the risks of PQ-induced acute haemolytic anaemia (AHA) and clinically significant anaemia (CSA), we prospectively defined therapeutic-dose ranges of 0.15-0.4 mg PQ base/kg for children aged 1-5 years and 0.15-0.5 mg PQ base/kg for individuals aged ≥6 years (therapeutic indices 2.7 and 3.3, respectively). We chose 1.25 mg PQ base for infants aged 6-11 months because they have the highest rate of baseline anaemia and the highest risks of AHA and CSA. We modelled an anthropometric database of 661,979 African individuals aged ≥6 months (549,127 healthy individuals, 28,466 malaria patients and 84,386 individuals with other infections/illnesses) by the Box-Cox transformation power exponential and tested PQ doses of 1-15 mg base, selecting dosing groups based on calculated mg/kg PQ doses. RESULTS: From the Box-Cox transformation power exponential model, five age categories were selected: (i) 6-11 months (n = 39,886, 6.03%), (ii) 1-5 years (n = 261,036, 45.46%), (iii) 6-9 years (n = 20,770, 3.14%), (iv) 10-14 years (n = 12,155, 1.84%) and (v) ≥15 years (n = 328,132, 49.57%) to receive 1.25, 2.5, 5, 7.5 and 15 mg PQ base for corresponding median (1st and 99th centiles) mg/kg PQ base of: (i) 0.16 (0.12-0.25), (ii) 0.21 (0.13-0.37), (iii) 0.25 (0.16-0.38), (iv) 0.26 (0.15-0.38) and (v) 0.27 (0.17-0.40). The proportions of individuals predicted to receive optimal therapeutic PQ doses were: 73.2 (29,180/39,886), 93.7 (244,537/261,036), 99.6 (20,690/20,770), 99.4 (12,086/12,155) and 99.8% (327,620/328,132), respectively. CONCLUSIONS: We plan to test the safety of this age-based dosing regimen in a large randomised placebo-controlled trial (ISRCTN11594437) of uncomplicated falciparum malaria in G6PDd African children aged 0.5 - 11 years. If the regimen is safe and demonstrates adequate pharmacokinetics, it should be used to support malaria elimination.

Published
2018
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25. ‘I saw it as a second chance’: A qualitative exploration of experiences of treatment failure and regimen change among people living with HIV on second- and third-line antiretroviral therapy in Kenya, Malawi and Mozambique

Author

Burns, Rose, primary, Borges, Joana, additional, Blasco, Philippe, additional, Vandenbulcke, Alexandra, additional, Mukui, Irene, additional, Magalasi, Denview, additional, Molfino, Lucas, additional, Manuel, Rolanda, additional, Schramm, Birgit, additional, and Wringe, Alison, additional

Published
2019
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26. Heterogeneous decrease in malaria prevalence in children over a six-year period in south-western Uganda

Author

Grandesso Francesco, Turyakira Eleanor, Nabasumba Carolyn, De Beaudrap Pierre, Schramm Birgit, Boum Yap, and Etard Jean-François

Subjects
Arctic medicine. Tropical medicine, RC955-962, Infectious and parasitic diseases, RC109-216
Abstract

Abstract Background Malaria is a major public health problem, especially for children. However, recent reports suggest a decline in the malaria burden. The aim of this study was to assess the change in the prevalence of malaria infection among children below five years of age between 2004 and 2010 in a mesoendemic area of Uganda and to analyse the risk factors of malaria infection. Methods Two cross-sectional surveys were conducted in 2004 and in 2010 at the end of the rainy and dry seasons to measure the prevalence of P. falciparum infection among children less than five years of age. Rapid diagnostic tests and blood smears were used to diagnose malaria infection. In 2010, sampling was stratified by urban and rural areas. In each selected household, knowledge of malaria and bed nets, and bed net ownership and use, were assessed. Results In 2004 and 2010, respectively, a total of 527 and 2,320 (999 in the urban area and 1,321 in rural areas) children less than five years old were enrolled. Prevalence of malaria infection declined from 43% (95% CI: 34-52) in 2004, to 23% (95% CI: 17-30) in rural areas in 2010 and 3% (95% CI: 2-5) in the urban area in 2010. From the rainy to dry season in 2010, prevalence decreased from 23% to 10% (95% CI: 6-14) in rural areas (P = 0.001) and remained stable from 3% to 4% (95% CI: 1-7) in the urban area (P = 0.9). The proportion of households reporting ownership and use of at least one bed net increased from 22.9% in 2004 to 64.7% in the urban area and 44.5% in rural areas in 2010 (P < 0.001). In 2010, the risk of malaria infection was consistently associated with child age and household wealth. In rural areas, malaria infection was also associated with geographic factors. Conclusions This study reports a significant drop in the prevalence of malaria infection among children below five years of age, paralleled by an uptake in bed-net use. However, prevalence remains unacceptably high in rural areas and is strongly associated with poverty.

Published
2011
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27. Implementation and operational feasibility of SAMBA I HIV‐1 semi‐quantitative viral load testing at the point‐of‐care in rural settings in Malawi and Uganda.

Author

Gueguen, Monique, Nicholas, Sarala, Poulet, Elisabeth, Schramm, Birgit, Szumilin, Elisabeth, Wolters, Liselotte, Wapling, Johanna, Ajule, Ephrahim, Rakesh, Ankur, Mwenda, Reuben, Kiyaga, Charles, and Balkan, Suna

Subjects
VIRAL load, HIV, POINT-of-care testing, RURAL health, MEDICAL personnel
Abstract

Copyright of Tropical Medicine & International Health is the property of Wiley-Blackwell and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Published
2021
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28. Single low-dose primaquine for blocking transmission of Plasmodium falciparum malaria – a proposed model-derived age-based regimen for sub-Saharan Africa

Author

Taylor, W. Robert, primary, Naw, Htee Khu, additional, Maitland, Kathryn, additional, Williams, Thomas N., additional, Kapulu, Melissa, additional, D’Alessandro, Umberto, additional, Berkley, James A., additional, Bejon, Philip, additional, Okebe, Joseph, additional, Achan, Jane, additional, Amambua, Alfred Ngwa, additional, Affara, Muna, additional, Nwakanma, Davis, additional, van Geertruyden, Jean-Pierre, additional, Mavoko, Muhindo, additional, Lutumba, Pascal, additional, Matangila, Junior, additional, Brasseur, Philipe, additional, Piola, Patrice, additional, Randremanana, Rindra, additional, Lasry, Estrella, additional, Fanello, Caterina, additional, Onyamboko, Marie, additional, Schramm, Birgit, additional, Yah, Zolia, additional, Jones, Joel, additional, Fairhurst, Rick M., additional, Diakite, Mahamadou, additional, Malenga, Grace, additional, Molyneux, Malcolm, additional, Rwagacondo, Claude, additional, Obonyo, Charles, additional, Gadisa, Endalamaw, additional, Aseffa, Abraham, additional, Loolpapit, Mores, additional, Henry, Marie-Claire, additional, Dorsey, Grant, additional, John, Chandy, additional, Sirima, Sodiomon B., additional, Barnes, Karen I., additional, Kremsner, Peter, additional, Day, Nicholas P., additional, White, Nicholas J., additional, and Mukaka, Mavuto, additional

Published
2018
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30. Clinical determinants of early parasitological response to ACTs in African patients with uncomplicated falciparum malaria: a literature review and meta-analysis of individual patient data

Author

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

Subjects
parasitic diseases
Abstract

BACKGROUND: Artemisinin-resistant Plasmodium falciparum has emerged in the Greater Mekong sub-region and poses a major global public health threat. Slow parasite clearance is a key clinical manifestation of reduced susceptibility to artemisinin. This study was designed to establish the baseline values for clearance in patients from Sub-Saharan African countries with uncomplicated malaria treated with artemisinin-based combination therapies (ACTs). METHODS: A literature review in PubMed was conducted in March 2013 to identify all prospective clinical trials (uncontrolled trials, controlled trials and randomized controlled trials), including ACTs conducted in Sub-Saharan Africa, between 1960 and 2012. Individual patient data from these studies were shared with the WorldWide Antimalarial Resistance Network (WWARN) and pooled using an a priori statistical analytical plan. Factors affecting early parasitological response were investigated using logistic regression with study sites fitted as a random effect. The risk of bias in included studies was evaluated based on study design, methodology and missing data. RESULTS: In total, 29,493 patients from 84 clinical trials were included in the analysis, treated with artemether-lumefantrine (n = 13,664), artesunate-amodiaquine (n = 11,337) and dihydroartemisinin-piperaquine (n = 4,492). The overall parasite clearance rate was rapid. The parasite positivity rate (PPR) decreased from 59.7 % (95 % CI: 54.5-64.9) on day 1 to 6.7 % (95 % CI: 4.8-8.7) on day 2 and 0.9 % (95 % CI: 0.5-1.2) on day 3. The 95th percentile of observed day 3 PPR was 5.3 %. Independent risk factors predictive of day 3 positivity were: high baseline parasitaemia (adjusted odds ratio (AOR) = 1.16 (95 % CI: 1.08-1.25); per 2-fold increase in parasite density, P 37.5 °C) (AOR = 1.50 (95 % CI: 1.06-2.13), P = 0.022); severe anaemia (AOR = 2.04 (95 % CI: 1.21-3.44), P = 0.008); areas of low/moderate transmission setting (AOR = 2.71 (95 % CI: 1.38-5.36), P = 0.004); and treatment with the loose formulation of artesunate-amodiaquine (AOR = 2.27 (95 % CI: 1.14-4.51), P = 0.020, compared to dihydroartemisinin-piperaquine). CONCLUSIONS: The three ACTs assessed in this analysis continue to achieve rapid early parasitological clearance across the sites assessed in Sub-Saharan Africa. A threshold of 5 % day 3 parasite positivity from a minimum sample size of 50 patients provides a more sensitive benchmark in Sub-Saharan Africa compared to the current recommended threshold of 10 % to trigger further investigation of artemisinin susceptibility.

Published
2015

31. Selection of Plasmodium falciparum pfcrt and pfmdr1 polymorphisms after treatment with artesunate–amodiaquine fixed dose combination or artemether–lumefantrine in Liberia

Author

Otienoburu, Sabina Dahlström, primary, Maïga-Ascofaré, Oumou, additional, Schramm, Birgit, additional, Jullien, Vincent, additional, Jones, Joel J., additional, Zolia, Yah M., additional, Houzé, Pascal, additional, Ashley, Elizabeth A., additional, Kiechel, Jean-René, additional, Guérin, Philippe J., additional, Le Bras, Jacques, additional, and Houzé, Sandrine, additional

Published
2016
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32. The effect of dosing strategies on the therapeutic efficacy of artesunate-amodiaquine for uncomplicated malaria : a meta-analysis of individual patient data

Author

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

Abstract

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

Published
2015
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34. Polymorphisms in Plasmodium falciparum chloroquine resistance transporter and multidrug resistance 1 genes : parasite risk factors that affect treatment outcomes for P. falciparum malaria after artemether-lumefantrine and artesunate-amodiaquine.

Author

Venkatesan, Meera, Gadalla, Nahla B, Stepniewska, Kasia, Dahal, Prabin, Nsanzabana, Christian, Moriera, Clarissa, Price, Ric N, Mårtensson, Andreas, Rosenthal, Philip J, Dorsey, Grant, Sutherland, Colin J, Guérin, Philippe, Davis, Timothy M E, Ménard, Didier, Adam, Ishag, Ademowo, George, Arze, Cesar, Baliraine, Frederick N, Berens-Riha, Nicole, Björkman, Anders, Borrmann, Steffen, Checchi, Francesco, Desai, Meghna, Dhorda, Mehul, Djimdé, Abdoulaye A, El-Sayed, Badria B, Eshetu, Teferi, Eyase, Frederick, Falade, Catherine, Faucher, Jean-François, Fröberg, Gabrielle, Grivoyannis, Anastasia, Hamour, Sally, Houzé, Sandrine, Johnson, Jacob, Kamugisha, Erasmus, Kariuki, Simon, Kiechel, Jean-René, Kironde, Fred, Kofoed, Poul-Erik, LeBras, Jacques, Malmberg, Maja, Mwai, Leah, Ngasala, Billy, Nosten, Francois, Nsobya, Samuel L, Nzila, Alexis, Oguike, Mary, Otienoburu, Sabina Dahlström, Ogutu, Bernhards, Ouédraogo, Jean-Bosco, Piola, Patrice, Rombo, Lars, Schramm, Birgit, Somé, A Fabrice, Thwing, Julie, Ursing, Johan, Wong, Rina P M, Zeynudin, Ahmed, Zongo, Issaka, Plowe, Christopher V, Sibley, Carol Hopkins, Venkatesan, Meera, Gadalla, Nahla B, Stepniewska, Kasia, Dahal, Prabin, Nsanzabana, Christian, Moriera, Clarissa, Price, Ric N, Mårtensson, Andreas, Rosenthal, Philip J, Dorsey, Grant, Sutherland, Colin J, Guérin, Philippe, Davis, Timothy M E, Ménard, Didier, Adam, Ishag, Ademowo, George, Arze, Cesar, Baliraine, Frederick N, Berens-Riha, Nicole, Björkman, Anders, Borrmann, Steffen, Checchi, Francesco, Desai, Meghna, Dhorda, Mehul, Djimdé, Abdoulaye A, El-Sayed, Badria B, Eshetu, Teferi, Eyase, Frederick, Falade, Catherine, Faucher, Jean-François, Fröberg, Gabrielle, Grivoyannis, Anastasia, Hamour, Sally, Houzé, Sandrine, Johnson, Jacob, Kamugisha, Erasmus, Kariuki, Simon, Kiechel, Jean-René, Kironde, Fred, Kofoed, Poul-Erik, LeBras, Jacques, Malmberg, Maja, Mwai, Leah, Ngasala, Billy, Nosten, Francois, Nsobya, Samuel L, Nzila, Alexis, Oguike, Mary, Otienoburu, Sabina Dahlström, Ogutu, Bernhards, Ouédraogo, Jean-Bosco, Piola, Patrice, Rombo, Lars, Schramm, Birgit, Somé, A Fabrice, Thwing, Julie, Ursing, Johan, Wong, Rina P M, Zeynudin, Ahmed, Zongo, Issaka, Plowe, Christopher V, and Sibley, Carol Hopkins

Abstract

Adequate clinical and parasitologic cure by artemisinin combination therapies relies on the artemisinin component and the partner drug. Polymorphisms in the Plasmodium falciparum chloroquine resistance transporter (pfcrt) and P. falciparum multidrug resistance 1 (pfmdr1) genes are associated with decreased sensitivity to amodiaquine and lumefantrine, but effects of these polymorphisms on therapeutic responses to artesunate-amodiaquine (ASAQ) and artemether-lumefantrine (AL) have not been clearly defined. Individual patient data from 31 clinical trials were harmonized and pooled by using standardized methods from the WorldWide Antimalarial Resistance Network. Data for more than 7,000 patients were analyzed to assess relationships between parasite polymorphisms in pfcrt and pfmdr1 and clinically relevant outcomes after treatment with AL or ASAQ. Presence of the pfmdr1 gene N86 (adjusted hazards ratio = 4.74, 95% confidence interval = 2.29 - 9.78, P < 0.001) and increased pfmdr1 copy number (adjusted hazards ratio = 6.52, 95% confidence interval = 2.36-17.97, P < 0.001 : were significant independent risk factors for recrudescence in patients treated with AL. AL and ASAQ exerted opposing selective effects on single-nucleotide polymorphisms in pfcrt and pfmdr1. Monitoring selection and responding to emerging signs of drug resistance are critical tools for preserving efficacy of artemisinin combination therapies; determination of the prevalence of at least pfcrt K76T and pfmdr1 N86Y should now be routine.

Published
2014
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35. Efficacy of artesunate-amodiaquine and artemether-lumefantrine fixed-dose combinations for the treatment of uncomplicated Plasmodium falciparum malaria among children aged six to 59 months in Nimba County, Liberia: an open-label randomized non-inferiority trial

Author

Schramm, Birgit, primary, Valeh, Parastou, additional, Baudin, Elisabeth, additional, Mazinda, Charles S, additional, Smith, Richard, additional, Pinoges, Loretxu, additional, Dhorda, Mehul, additional, Boum, Yap, additional, Sundaygar, Timothy, additional, Zolia, Yah M, additional, Jones, Joel J, additional, Comte, Eric, additional, Houzé, Pascal, additional, Jullien, Vincent, additional, Carn, Gwenaelle, additional, Kiechel, Jean-René, additional, Ashley, Elizabeth A, additional, and Guérin, Philippe J, additional

Published
2013
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36. Tolerability and safety of artesunate-amodiaquine and artemether-lumefantrine fixed dose combinations for the treatment of uncomplicated Plasmodium falciparum malaria: two open-label, randomized trials in Nimba County, Liberia

Author

Schramm, Birgit, primary, Valeh, Parastou, additional, Baudin, Elisabeth, additional, Mazinda, Charles S, additional, Smith, Richard, additional, Pinoges, Loretxu, additional, Sundaygar, Timothy, additional, Zolia, Yah M, additional, Jones, Joel J, additional, Comte, Eric, additional, Bruneel, Arnaud, additional, Branger, Michel, additional, Jullien, Vincent, additional, Carn, Gwenaelle, additional, Kiechel, Jean-René, additional, Ashley, Elizabeth A, additional, and Guérin, Philippe J, additional

Published
2013
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47. Meeting Report: EMBO Workshop‘Cell Biology of Virus Infection’, September 25–29, 2004, EMBL, Heidelberg, Germany.

Author

Sodeik, Beate, Schramm, Birgit, Suomalainen, Maarit, and Locker, Jacomine Krijnse

Subjects
*BIOLOGICAL interfaces, *SEMINARS, *LIFE sciences, *MEDICAL radiography, *TOMOGRAPHY, *GENETICS
Abstract

This article focuses on EMBO Workshop "Cell Biology of Virus Infection," held in September 25-29, 2004, EMBL, Heidelberg, Germany. The sessions covered virus entry, intracellular transport, cell tropism, signalling, nuclear events, assembly at cellular membranes and the analysis of viral structures using electron tomography. Before viruses can replicate, amplify their genome and assemble new particles, they must gain access to the host cytosol. Chlamydia uptake also involves a rearrangement of the actin cytoskeleton at the entry site that is controlled by the small GTPase Rac-1, and for some strains also by Cdc42.

Published
2005
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48. Field Evaluation of a Simple Fluorescence Method for Detection of Viable Mycobacterium tuberculosisin Sputum Specimens during Treatment Follow-Up

Author

Schramm, Birgit, Hewison, Cathy, Bonte, Laurence, Jones, Warren, Camélique, Olivier, Ruangweerayut, Ronnatrai, Swaddiwudhipong, Witaya, and Bonnet, Maryline

Abstract

ABSTRACTSimple tuberculosis (TB) treatment monitoring tools are needed. We assessed the performance of fluorescein-diacetate (FDA) smear microscopy for detection of viable Mycobacterium tuberculosisin sputum specimens (n= 288) of TB cases under treatment compared to culture (17.4% culture positivity). FDA sensitivity was moderate (83.7% [95% confidence interval {CI}, 70.3 to 92.6]), and specificity was low (66.1% [59.5 to 72.2]). The good negative predictive value (94.8% [90.1 to 97.8]) and negative likelihood ratio (0.2) suggest using this method to rule out treatment failure in settings without access to culture.

Published
2012
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49. Additional file 2: Table S1. of Single low-dose primaquine for blocking transmission of Plasmodium falciparum malaria â a proposed model-derived age-based regimen for sub-Saharan Africa

Author

W. Taylor, Htee Naw, Maitland, Kathryn, Williams, Thomas, Kapulu, Melissa, D’Alessandro, Umberto, Berkley, James, Bejon, Philip, Okebe, Joseph, Achan, Jane, Amambua, Alfred, Affara, Muna, Nwakanma, Davis, Geertruyden, Jean-Pierre Van, Muhindo Mavoko, Lutumba, Pascal, Junior Matangila, Philipe Brasseur, Piola, Patrice, Rindra Randremanana, Lasry, Estrella, Fanello, Caterina, Onyamboko, Marie, Schramm, Birgit, Zolia Yah, Jones, Joel, Fairhurst, Rick, Mahamadou Diakite, Malenga, Grace, Molyneux, Malcolm, Rwagacondo, Claude, Obonyo, Charles, Endalamaw Gadisa, Aseffa, Abraham, Mores Loolpapit, Marie-Claire Henry, Dorsey, Grant, Chandy John, Sodiomon Sirima, Barnes, Karen, Kremsner, Peter, Day, Nicholas, White, Nicholas, and Mavuto Mukaka

Subjects
3. Good health
Abstract

Data type by country. (DOCX 14 kb)

50. Gametocyte carriage in uncomplicated Plasmodium falciparum malaria following treatment with artemisinin combination therapy: a systematic review and meta-analysis of individual patient data

Author

Abdulla, Salim, Achan, Jane, Adam, Ishag, Alemayehu, Bereket H, Allan, Richard, Allen, Elizabeth N, Ankivar, Anupkumar R, Arinaitwe, Emmanuel, Ashley, Elizabeth A, Asih, Puji Budi Setia, Awab, Ghulam Rahib, Barnes, Karen I, Bassat, Quique, Baudin, Elisabeth, Björkman, Anders, Bompart, Francois, Bonnet, Maryline, Borrmann, Steffen, Bousema, Teun, Carrara, Verena I, Cenci, Fabio, Checchi, Francesco, Cot, Michel, Dahal, Prabin, D'Alessandro, Umberto, Deloron, Phillippe, Djimdé, Abdoulaye, Dondorp, Arjen, Dorsey, Grant, Doumbo, Ogobara K, Drakeley, Chris J, Duparc, Stephan, Espie, Emmanuelle, Faiz, Abul, Falade, Catherine O, Fanello, Caterina, Faucher, Jean-François, Faye, Babacar, Filler, Scott, Fofana, Bakary, Fogg, Carole, Gansane, Adama, Gaye, Oumar, Genton, Blaise, Gething, Peter W, Gonzalez, Raquel, Grandesso, Francesco, Greenwood, Brian, Grivoyannis, Anastasia, Guerin, Philippe J, Hamed, Kamal, Hatz, Cristoph, Hay, Simon I, Hodel, Eva Maria, Humphreys, Georgina S, Hwang, Jimee, Janssens, Bart, Juma, Elizabeth, Kachur, S Patrick, Kager, Piet, Kamya, Moses R, Kapulu, Melissa, Karema, Corine, Kayentao, Kassoum, Kiechel, Jean R, Kofoed, Poul-Erik, Lameyre, Valerie, Lee, Sue J, Lell, Bertrand, Lima, Nines, Marsh, Kevin, Mårtensson, Andreas, Massougbodji, Achille, Mayxay, Mayfong, McGready, Rose, Menan, Hervé, Menendez, Clara, Mens, Petra, Meremikwu, Martin, Mockenhaupt, Frank P, Moreira, Clarissa, Nabasumba, Carolyn, Nambozi, Michael, Ndiaye, Jean-Louis, Newton, Paul N, Ngasala, Billy E, Nosten, Francois, Nsanzabana, Christian, Offianan, Andre Toure, Oguike, Mary, Ogutu, Bernards R, Olliaro, Piero, Omar, Sabah A, Osorio, Lyda, Owusu-Agyei, Seth, Penali, Louis K, Pene, Mbaye, Peshu, Judy, Premji, Zul, Price, Ric N, Ramharter, Michael, Rombo, Lars, Roper, Cally, Rosenthal, Philip J, Sagara, Issaka, Sawa, Patrick, Schallig, Henk D F H, Schramm, Birgit, Shekalaghe, Seif A, Sibley, Carol H, Sirima, Sodiomon, Smithuis, Frank, Sow, Doudou, Staedke, Sarah G, Stepniewska, Kasia, Sutanto, Inge, Sutherland, Colin J, Swarthout, Todd D, Syafruddin, Din, Sylla, Khadime, Talisuna, Ambrose O, Taylor, Walter R, Tema, Emmanuel A, Ter Kuile, Feiko, Tinto, Halidou, Tjitra, Emiliana, Ursing, Johan, Valecha, Neena, van den Broek, Ingrid, van Herp, Michel, van Vugt, Michele, Ward, Stephen A, White, Nicholas J, Winstanley, Peter A, Woodrow, Charles J, Yeka, Adoke, Zwang, Julien, and WWARN Gametocyte Study Group

Subjects
Male, 0301 basic medicine, gametocytes, Plasmodium falciparum/drug effects, Artemisinins/therapeutic use, Amodiaquine/therapeutic use, chemistry.chemical_compound, 0302 clinical medicine, Recurrence, Malaria, Falciparum, Artemisinin, GeneralLiterature_REFERENCE(e.g.,dictionaries,encyclopedias,glossaries), Medicine(all), Microscopy, biology, Mefloquine, Malaria, Falciparum/drug therapy, Hazard ratio, General Medicine, Middle Aged, Artemisinins, 3. Good health, Drug Combinations, Child, Preschool, Drug Therapy, Combination, Research Article, medicine.drug, medicine.medical_specialty, plasmodium falciparum, Plasmodium falciparum, 030231 tropical medicine, Gametocyte, malaria, Malària, Amodiaquine, Host-Parasite Interactions, Antimalarials, 03 medical and health sciences, Internal medicine, parasitic diseases, medicine, Humans, Proportional Hazards Models, Resistència als medicaments, drug resistance, business.industry, medicine.disease, biology.organism_classification, Malaria, Logistic Models, lnfectious Diseases and Global Health Radboud Institute for Health Sciences [Radboudumc 4], 030104 developmental biology, chemistry, Host-Parasite Interactions/drug effects, Artesunate, Drug resistance, Antimalarials/therapeutic use, Immunology, business
Abstract

BACKGROUND: Gametocytes are responsible for transmission of malaria from human to mosquito. Artemisinin combination therapy (ACT) reduces post-treatment gametocyte carriage, dependent upon host, parasite and pharmacodynamic factors. The gametocytocidal properties of antimalarial drugs are important for malaria elimination efforts. An individual patient clinical data meta-analysis was undertaken to identify the determinants of gametocyte carriage and the comparative effects of four ACTs: artemether-lumefantrine (AL), artesunate/amodiaquine (AS-AQ), artesunate/mefloquine (AS-MQ), and dihydroartemisinin-piperaquine (DP). METHODS: Factors associated with gametocytaemia prior to, and following, ACT treatment were identified in multivariable logistic or Cox regression analysis with random effects. All relevant studies were identified through a systematic review of PubMed. Risk of bias was evaluated based on study design, methodology, and missing data. RESULTS: The systematic review identified 169 published and 9 unpublished studies, 126 of which were shared with the WorldWide Antimalarial Resistance Network (WWARN) and 121 trials including 48,840 patients were included in the analysis. Prevalence of gametocytaemia by microscopy at enrolment was 12.1 % (5887/48,589), and increased with decreasing age, decreasing asexual parasite density and decreasing haemoglobin concentration, and was higher in patients without fever at presentation. After ACT treatment, gametocytaemia appeared in 1.9 % (95 % CI, 1.7-2.1) of patients. The appearance of gametocytaemia was lowest after AS-MQ and AL and significantly higher after DP (adjusted hazard ratio (AHR), 2.03; 95 % CI, 1.24-3.12; P = 0.005 compared to AL) and AS-AQ fixed dose combination (FDC) (AHR, 4.01; 95 % CI, 2.40-6.72; P < 0.001 compared to AL). Among individuals who had gametocytaemia before treatment, gametocytaemia clearance was significantly faster with AS-MQ (AHR, 1.26; 95 % CI, 1.00-1.60; P = 0.054) and slower with DP (AHR, 0.74; 95 % CI, 0.63-0.88; P = 0.001) compared to AL. Both recrudescent (adjusted odds ratio (AOR), 9.05; 95 % CI, 3.74-21.90; P < 0.001) and new (AOR, 3.03; 95 % CI, 1.66-5.54; P < 0.001) infections with asexual-stage parasites were strongly associated with development of gametocytaemia after day 7. CONCLUSIONS: AS-MQ and AL are more effective than DP and AS-AQ FDC in preventing gametocytaemia shortly after treatment, suggesting that the non-artemisinin partner drug or the timing of artemisinin dosing are important determinants of post-treatment gametocyte dynamics.

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