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51. South-Asian tsunami

Author

Yap, Eric P.H., Koh, Victor W.H., Loh, Jimmy J.P., Ng, Yih Yng, Ooi, Eng Eong, Jimba, Masamine, Wakai, Susumu, Guthmann, Jean-Paul, Sauvageot, Delphine, De Filippi, Loris, Burny, Marie-Eve, Brown, Vincent, Nayar, K.R., Sagar, Alapana D., Zamperetti, Nereo, Bellomo, Rinaldo, Ratuwithana, Charith, and Nitkunan, Arani

Subjects
Doctors Without Borders -- Social aspects, Indian Ocean Earthquake and Tsunami, 2004
Published
2005

52. Baseline data of parasite clearance in patients with falciparum malaria treated with an artemisinin derivative : an individual patient data meta-analysis

Author

WWARN Parasite Clearance Study Group, Abdulla, Salim, Ashley, Elizabeth A, Bassat, Quique, Bethell, Delia, Björkman, Anders, Borrmann, Steffen, D'Alessandro, Umberto, Dahal, Prabin, Day, Nicholas P, Diakite, Mahamadou, Djimde, Abdoulaye A, Dondorp, Arjen M, Duong, Socheat, Edstein, Michael D, Fairhurst, Rick M, Faiz, M Abul, Falade, Catherine, Flegg, Jennifer A, Fogg, Carole, Gonzalez, Raquel, Greenwood, Brian, Guérin, Philippe J, Guthmann, Jean-Paul, Hamed, Kamal, Hien, Tran Tinh, Htut, Ye, Juma, Elizabeth, Lim, Pharath, Mårtensson, Andreas, Mayxay, Mayfong, Mokuolu, Olugbenga A, Moreira, Clarissa, Newton, Paul, Noedl, Harald, Nosten, Francois, Ogutu, Bernhards R, Onyamboko, Marie A, Owusu-Agyei, Seth, Phyo, Aung Pyae, Premji, Zul, Price, Ric N, Pukrittayakamee, Sasithon, Ramharter, Michael, Sagara, Issaka, Se, Youry, Suon, Seila, Stepniewska, Kasia, Ward, Stephen A, White, Nicholas J, and Winstanley, Peter A

Subjects
Male, Artemether/lumefantrine, Social and Clinical Pharmacy, Drug Resistance, Physiology, Parasitemia, Drug resistance, chemistry.chemical_compound, Medicine, Parasite hosting, Artemisinin, Malaria, Falciparum, Child, Diagnosis & treatment, Clinical Trials as Topic, Surveillance, monitoring, evaluation, biology, Public Health, Global Health, Social Medicine and Epidemiology, Middle Aged, Artemisinins, 3. Good health, Infectious Diseases, Blood, Artemisinin resistance, Child, Preschool, Female, medicine.drug, Adult, endocrine system, Adolescent, Plasmodium falciparum, Antimalarials, Young Adult, Health Sciences, parasitic diseases, Animals, Humans, Aged, Parasite clearance, business.industry, Research, Samhällsfarmaci och klinisk farmaci, Infant, medicine.disease, biology.organism_classification, Malaria, Folkhälsovetenskap, global hälsa, socialmedicin och epidemiologi, chemistry, Artesunate, Immunology, Parasitology, business
Abstract

Background Artemisinin resistance in Plasmodium falciparum manifests as slow parasite clearance but this measure is also influenced by host immunity, initial parasite biomass and partner drug efficacy. This study collated data from clinical trials of artemisinin derivatives in falciparum malaria with frequent parasite counts to provide reference parasite clearance estimates stratified by location, treatment and time, to examine host factors affecting parasite clearance, and to assess the relationships between parasite clearance and risk of recrudescence during follow-up. Methods Data from 24 studies, conducted from 1996 to 2013, with frequent parasite counts were pooled. Parasite clearance half-life (PC1/2) was estimated using the WWARN Parasite Clearance Estimator. Random effects regression models accounting for study and site heterogeneity were used to explore factors affecting PC1/2 and risk of recrudescence within areas with reported delayed parasite clearance (western Cambodia, western Thailand after 2000, southern Vietnam, southern Myanmar) and in all other areas where parasite populations are artemisinin sensitive. Results PC1/2 was estimated in 6975 patients, 3288 of whom also had treatment outcomes evaluate d during 28–63 days follow-up, with 93 (2.8 %) PCR-confirmed recrudescences. In areas with artemisinin-sensitive parasites, the median PC1/2 following three-day artesunate treatment (4 mg/kg/day) ranged from 1.8 to 3.0 h and the proportion of patients with PC1/2 >5 h from 0 to 10 %. Artesunate doses of 4 mg/kg/day decreased PC1/2 by 8.1 % (95 % CI 3.2–12.6) compared to 2 mg/kg/day, except in populations with delayed parasite clearance. PC1/2 was longer in children and in patients with fever or anaemia at enrolment. Long PC1/2 (HR = 2.91, 95 % CI 1.95–4.34 for twofold increase, p

Published
2015

53. 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

54. Incidence, severity and treatment outcome of tuberculosis in the era of the COVID-19 pandemic, France, 2018-2023

Author

Guthmann, Jean-Paul, Robert, Jérôme, Viriot, Delphine, and Parent du Chatelet, Isabelle

Abstract

•High quality and complete data are necessary to describe trends of tuberculosis epidemiology and assess how these trends may vary as a consequence of external events such as the COVID-19 pandemic;•Discussing reasons why specific social and medical interventions might have impacted the incidence of TB should help to organise and better manage health system disruptions in case of new crisis onset;•Tuberculosis is still an important public health problem in special groups of the EU population such as immigrants and homeless persons and should deserve significant efforts in order to meet the WHO targets of TB elimination;•Documenting treatment outcome deserves a major attention in countries where this information is largely missing, such as in France.

Published
2024
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55. Réseau de surveillance de la couverture vaccinale et des conditions d’immunisation du personnel des établissements de santé : pourquoi, comment

Author

Floret, Nathalie, primary, Abiteboul, Dominique, additional, Bouvet, Elisabeth, additional, Gehanno, Jean-François, additional, Guthmann, Jean-Paul, additional, Koeck, Jean-Louis, additional, Launay, Odile, additional, Lecieux, Fabienne, additional, L’heriteau, François, additional, Rabaud, Christian, additional, Rolland, Patrick, additional, Touche, Sylvie, additional, and Verdun-Esquer, Catherine, additional

Published
2016
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56. Baseline data of parasite clearance in patients with falciparum malaria treated with an artemisinin derivative : an individual patient data meta-analysis

Author

Abdulla, Salim, Ashley, Elizabeth A., Bassat, Quique, Bethell, Delia, Bjorkman, Anders, Borrmann, Steffen, D'Alessandro, Umberto, Dahal, Prabin, Day, Nicholas P., Diakite, Mahamadou, Djimde, Abdoulaye A., Dondorp, Arjen M., Duong, Socheat, Edstein, Michael D., Fairhurst, Rick M., Faiz, M. Abul, Falade, Catherine, Flegg, Jennifer A., Fogg, Carole, Gonzalez, Raquel, Greenwood, Brian, Guerin, Philippe J., Guthmann, Jean-Paul, Hamed, Kamal, Hien, Tran Tinh, Htut, Ye, Juma, Elizabeth, Lim, Pharath, Mårtensson, Andreas, Mayxay, Mayfong, Mokuolu, Olugbenga A., Moreira, Clarissa, Newton, Paul, Noedl, Harald, Nosten, Francois, Ogutu, Bernhards R., Onyamboko, Marie A., Owusu-Agyei, Seth, Phyo, Aung Pyae, Premji, Zul, Price, Ric N., Pukrittayakamee, Sasithon, Ramharter, Michael, Sagara, Issaka, Se, Youry, Suon, Seila, Stepniewska, Kasia, Ward, Stephen A., White, Nicholas J., Winstanley, Peter A., Abdulla, Salim, Ashley, Elizabeth A., Bassat, Quique, Bethell, Delia, Bjorkman, Anders, Borrmann, Steffen, D'Alessandro, Umberto, Dahal, Prabin, Day, Nicholas P., Diakite, Mahamadou, Djimde, Abdoulaye A., Dondorp, Arjen M., Duong, Socheat, Edstein, Michael D., Fairhurst, Rick M., Faiz, M. Abul, Falade, Catherine, Flegg, Jennifer A., Fogg, Carole, Gonzalez, Raquel, Greenwood, Brian, Guerin, Philippe J., Guthmann, Jean-Paul, Hamed, Kamal, Hien, Tran Tinh, Htut, Ye, Juma, Elizabeth, Lim, Pharath, Mårtensson, Andreas, Mayxay, Mayfong, Mokuolu, Olugbenga A., Moreira, Clarissa, Newton, Paul, Noedl, Harald, Nosten, Francois, Ogutu, Bernhards R., Onyamboko, Marie A., Owusu-Agyei, Seth, Phyo, Aung Pyae, Premji, Zul, Price, Ric N., Pukrittayakamee, Sasithon, Ramharter, Michael, Sagara, Issaka, Se, Youry, Suon, Seila, Stepniewska, Kasia, Ward, Stephen A., White, Nicholas J., and Winstanley, Peter A.

Abstract

Background: Artemisinin resistance in Plasmodium falciparum manifests as slow parasite clearance but this measure is also influenced by host immunity, initial parasite biomass and partner drug efficacy. This study collated data from clinical trials of artemisinin derivatives in falciparum malaria with frequent parasite counts to provide reference parasite clearance estimates stratified by location, treatment and time, to examine host factors affecting parasite clearance, and to assess the relationships between parasite clearance and risk of recrudescence during follow-up. Methods: Data from 24 studies, conducted from 1996 to 2013, with frequent parasite counts were pooled. Parasite clearance half-life (PC1/2) was estimated using the WWARN Parasite Clearance Estimator. Random effects regression models accounting for study and site heterogeneity were used to explore factors affecting PC1/2 and risk of recrudescence within areas with reported delayed parasite clearance (western Cambodia, western Thailand after 2000, southern Vietnam, southern Myanmar) and in all other areas where parasite populations are artemisinin sensitive. Results: PC1/2 was estimated in 6975 patients, 3288 of whom also had treatment outcomes evaluate d during 28-63 days follow-up, with 93 (2.8 %) PCR-confirmed recrudescences. In areas with artemisinin-sensitive parasites, the median PC1/2 following three-day artesunate treatment (4 mg/kg/day) ranged from 1.8 to 3.0 h and the proportion of patients with PC1/2 > 5 h from 0 to 10 %. Artesunate doses of 4 mg/kg/day decreased PC1/2 by 8.1 % (95 % CI 3.2-12.6) compared to 2 mg/kg/day, except in populations with delayed parasite clearance. PC1/2 was longer in children and in patients with fever or anaemia at enrolment. Long PC1/2 (HR = 2.91, 95 % CI 1.95-4.34 for twofold increase, p < 0.001) and high initial parasitaemia (HR = 2.23, 95 % CI 1.44-3.45 for tenfold increase, p < 0.001) were associated independently with an increased risk of recrude

Published
2015
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57. 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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59. Susceptibility of health care students to measles, Paris, France

Author

Loulergue, Pierre, Guthmann, Jean-Paul, Fonteneau, Laure, Armengaud, Jean-Baptiste, Levy-Bruhl, Daniel, and Launay, Odile

Subjects
Students, Measles-mumps-rubella vaccine -- Dosage and administration, Health care industry, Health care industry, Health
Abstract

To the Editor: A measles epidemic is currently occurring in several countries in Europe (1 ,2). Although most cases concern unvaccinated children and young adults, health care professionals (HCPs) are [...]

Published
2011
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61. Évaluation de l'efficacité antipaludéenne en période de changement des combinaisons thérapeutiques à base d'artémisinine : Le rôle de Médecins Sans Frontières

Author

Guthmann, Jean-Paul, Checchi, Francesco, van den Broek, Ingrid, Balkan, Suna, Van Herp, Michel, Comte, Eric, Bernal, Oscar, Kindermans, Jean-Marie, Venis, Sarah, Legros, Dominique, Guerin, Philippe, Institut de Veille Sanitaire (INVS), Department of Infectious and Tropical Diseases, London School of Hygiene and Tropical Medicine (LSHTM), Médecins Sans Frontières Belgique, Médecins Sans Frontières, Centre de Mathématiques Appliquées (CMA), MINES ParisTech - École nationale supérieure des mines de Paris, Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL), LECEMO - Les Cultures de l'Europe Méditérranéenne Occidentale - EA 3979 (LECEMO), and Université Sorbonne Nouvelle - Paris 3

Subjects
ComputingMilieux_MISCELLANEOUS, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology
Abstract

International audience

Published
2008

62. Vaccine Knowledge in Students in Paris, France, and surrounding Regions

Author

Mellon, Guillaume, primary, Rigal, Laurent, additional, Partouche, Henri, additional, Aoun, Olivier, additional, Jaury, Philippe, additional, Joannard, Nathalie, additional, Guthmann, Jean Paul, additional, Cochereau, Delphine, additional, Caumes, Eric, additional, Bricaire, Francois, additional, and Salmon-Céron, Dominique, additional

Published
2014
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63. The relationship between the haemoglobin concentration and the haematocrit in Plasmodium falciparum malaria

Author

Lee, Sue J., Stepniewska, Kasia, Anstey, Nicholas M., Ashley, Elizabeth, Barnes, Karen, Binh, Tran Quang, D`Alessandro, Umberto, Day, Nicholas P. J., Vries, Peter J. de, Dorsey, Grant, Guthmann, Jean-Paul, Mayxay, Mayfong, Newton, Paul N., Nosten, Francois, Olliaro, Piero, Osario, Lyda, Pinoges, Loretxu, Price, Ric N., Rowland, Mark, White, Nicholas J., et al., Lee, Sue J., Stepniewska, Kasia, Anstey, Nicholas M., Ashley, Elizabeth, Barnes, Karen, Binh, Tran Quang, D`Alessandro, Umberto, Day, Nicholas P. J., Vries, Peter J. de, Dorsey, Grant, Guthmann, Jean-Paul, Mayxay, Mayfong, Newton, Paul N., Nosten, Francois, Olliaro, Piero, Osario, Lyda, Pinoges, Loretxu, Price, Ric N., Rowland, Mark, White, Nicholas J., and et al.

Abstract

BackgroundMalaria is a very important cause of anaemia in tropical countries. Anaemia is assessed either by measurement of the haematocrit or the haemoglobin concentration. For comparisons across studies, it is often necessary to derive one measure from the other.MethodsData on patients with slide-confirmed uncomplicated falciparum malaria were pooled from 85 antimalarial drug trials conducted in 25 different countries, to assess the haemoglobin/haematocrit relationship at different time points in malaria. Using a linear random effects model, a conversion equation for haematocrit was derived based on 3,254 measurements from various time points (ranging from day 0 to day 63) from 1,810 patients with simultaneous measurements of both parameters. Haemoglobin was also estimated from haematocrit with the commonly used threefold conversion.ResultsA good fit was obtained using Haematocrit = 5.62 + 2.60 * Haemoglobin. On average, haematocrit/3 levels were slightly higher than haemoglobin measurements with a mean difference (± SD) of -0.69 (± 1.3) for children under the age of 5 (n = 1,440 measurements from 449 patients).ConclusionBased on this large data set, an accurate and robust conversion factor both in acute malaria and in convalescence was obtained. The commonly used threefold conversion is also valid.

Published
2008

67. Incidence of H1N1 2009 Virus Infection through the Analysis of Paired Plasma Specimens among Blood Donors, France

Author

Bone, Angie, primary, Guthmann, Jean-Paul, additional, Assal, Azzedine, additional, Rousset, Dominique, additional, Degeorges, Armelle, additional, Morel, Pascal, additional, Valette, Martine, additional, Enouf, Vincent, additional, Jacquot, Eric, additional, Pelletier, Bertrand, additional, Le Strat, Yann, additional, Pillonel, Josiane, additional, Fonteneau, Laure, additional, van der Werf, Sylvie, additional, Lina, Bruno, additional, Tiberghien, Pierre, additional, and Lévy-Bruhl, Daniel, additional

Published
2012
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72. Efficacy of artesunate-amodiaquine for treating uncomplicated falciparum malaria in sub-Saharan Africa: a multi-centre analysis

Author

Zwang, Julien, primary, Olliaro, Piero, additional, Barennes, Hubert, additional, Bonnet, Maryline, additional, Brasseur, Philippe, additional, Bukirwa, Hasifa, additional, Cohuet, Sandra, additional, D'Alessandro, Umberto, additional, Djimdé, Abdulaye, additional, Karema, Corine, additional, Guthmann, Jean-Paul, additional, Hamour, Sally, additional, Ndiaye, Jean-Louis, additional, Mårtensson, Andreas, additional, Rwagacondo, Claude, additional, Sagara, Issaka, additional, Same-Ekobo, Albert, additional, Sirima, Sodiomon B, additional, van den Broek, Ingrid, additional, Yeka, Adoke, additional, Taylor, Walter RJ, additional, Dorsey, Grant, additional, and Randrianarivelojosia, Milijaona, additional

Published
2009
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73. Varying efficacy of artesunate+amodiaquine and artesunate+sulphadoxine-pyrimethamine for the treatment of uncomplicated falciparum malaria in the Democratic Republic of Congo: a report of two in-vivo studies

Author

Bonnet, Maryline, primary, van den Broek, Ingrid, additional, van Herp, Michel, additional, Urrutia, Pedro Pablo Palma, additional, van Overmeir, Chantal, additional, Kyomuhendo, Juliet, additional, Ndosimao, Célestin Nsibu, additional, Ashley, Elizabeth, additional, and Guthmann, Jean-Paul, additional

Published
2009
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75. Multiple Origins and Regional Dispersal of Resistant dhps in African Plasmodium falciparum Malaria

Author

Pearce, Richard J., primary, Pota, Hirva, additional, Evehe, Marie-Solange B., additional, Bâ, El-Hadj, additional, Mombo-Ngoma, Ghyslain, additional, Malisa, Allen L., additional, Ord, Rosalynn, additional, Inojosa, Walter, additional, Matondo, Alexandre, additional, Diallo, Diadier A., additional, Mbacham, Wilfred, additional, van den Broek, Ingrid V., additional, Swarthout, Todd D., additional, Getachew, Asefaw, additional, Dejene, Seyoum, additional, Grobusch, Martin P., additional, Njie, Fanta, additional, Dunyo, Samuel, additional, Kweku, Margaret, additional, Owusu-Agyei, Seth, additional, Chandramohan, Daniel, additional, Bonnet, Maryline, additional, Guthmann, Jean-Paul, additional, Clarke, Sian, additional, Barnes, Karen I., additional, Streat, Elizabeth, additional, Katokele, Stark T., additional, Uusiku, Petrina, additional, Agboghoroma, Chris O., additional, Elegba, Olufunmilayo Y., additional, Cissé, Badara, additional, A-Elbasit, Ishraga E., additional, Giha, Hayder A., additional, Kachur, S. Patrick, additional, Lynch, Caroline, additional, Rwakimari, John B., additional, Chanda, Pascalina, additional, Hawela, Moonga, additional, Sharp, Brian, additional, Naidoo, Inbarani, additional, and Roper, Cally, additional

Published
2009
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77. Different methodological approaches to the assessment of in vivo efficacy of three artemisinin-based combination antimalarial treatments for the treatment of uncomplicated falciparum malaria in African children

Author

Ashley, Elizabeth A, primary, Pinoges, Loretxu, additional, Turyakira, Eleanor, additional, Dorsey, Grant, additional, Checchi, Francesco, additional, Bukirwa, Hasifa, additional, van den Broek, Ingrid, additional, Zongo, Issaka, additional, Urruta, Pedro Pablo Palma, additional, van Herp, Michel, additional, Balkan, Suna, additional, Taylor, Walter R, additional, Olliaro, Piero, additional, and Guthmann, Jean-Paul, additional

Published
2008
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78. The relationship between the haemoglobin concentration and the haematocrit in Plasmodium falciparum malaria

Author

Lee, Sue J, primary, Stepniewska, Kasia, additional, Anstey, Nicholas, additional, Ashley, Elizabeth, additional, Barnes, Karen, additional, Binh, Tran Quang, additional, D'Alessandro, Umberto, additional, Day, Nicholas PJ, additional, de Vries, Peter J, additional, Dorsey, Grant, additional, Guthmann, Jean-Paul, additional, Mayxay, Mayfong, additional, Newton, Paul, additional, Nosten, Francois, additional, Olliaro, Piero, additional, Osario, Lyda, additional, Pinoges, Loretxu, additional, Price, Ric, additional, Rowland, Mark, additional, Smithuis, Frank, additional, Taylor, Robert, additional, and White, Nicholas J, additional

Published
2008
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83. Relapses ofPlasmodium vivaxInfection Usually Result from Activation of Heterologous Hypnozoites

Author

Imwong, Mallika, primary, Snounou, Georges, additional, Pukrittayakamee, Sasithon, additional, Tanomsing, Naowarat, additional, Kim, Jung Ryong, additional, Nandy, Amitab, additional, Guthmann, Jean‐Paul, additional, Nosten, Francois, additional, Carlton, Jane, additional, Looareesuwan, Sornchai, additional, Nair, Shalini, additional, Sudimack, Daniel, additional, Day, Nicholas P. J., additional, Anderson, Timothy J. C., additional, and White, Nicholas J., additional

Published
2007
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87. Supervised versus unsupervised antimalarial treatment with six-dose artemether-lumefantrine: pharmacokinetic and dosage-related findings from a clinical trial in Uganda

Author

Checchi, Francesco, primary, Piola, Patrice, additional, Fogg, Carole, additional, Bajunirwe, Francis, additional, Biraro, Samuel, additional, Grandesso, Francesco, additional, Ruzagira, Eugene, additional, Babigumira, Joseph, additional, Kigozi, Isaac, additional, Kiguli, James, additional, Kyomuhendo, Juliet, additional, Ferradini, Laurent, additional, Taylor, Walter RJ, additional, and Guthmann, Jean-Paul, additional

Published
2006
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89. HIGH EFFICACY OF TWO ARTEMISININ-BASED COMBINATIONS (ARTESUNATE + AMODIAQUINE AND ARTEMETHER + LUMEFANTRINE) IN CAALA, CENTRAL ANGOLA

Author

GUTHMANN, JEAN-PAUL, primary, FRANCIS, MAX, additional, KYOMUHENDO, JULIET, additional, RIGUTTO, CHRISTINE, additional, KIGULI, JAMES, additional, COHUET, SANDRA, additional, SARAIVA, NILTON, additional, FORTES, FILOMENO, additional, BALKAN, SUNA, additional, NOËL, FRÉDÉRIC, additional, and MULEMBA, MARYLINE, additional

Published
2006
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90. South-Asian tsunami

Author

Guthmann, Jean-Paul, primary, Sauvageot, Delphine, additional, De Filippi, Loris, additional, Burny, Marie-Eve, additional, and Brown, Vincent, additional

Published
2005
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91. In Vivo Assessment of Drug Efficacy against Plasmodium falciparum Malaria: Duration of Follow-Up

Author

Stepniewska, Kasia, primary, Taylor, Walter R.J., additional, Mayxay, Mayfong, additional, Price, Ric, additional, Smithuis, Frank, additional, Guthmann, Jean-Paul, additional, Barnes, Karen, additional, Myint, Hla Yin, additional, Adjuik, Martin, additional, Olliaro, Piero, additional, Pukrittayakamee, Sasithon, additional, Looareesuwan, Sornchai, additional, Hien, Tran Tinh, additional, Farrar, Jeremy, additional, Nosten, François, additional, Day, Nicholas P.J., additional, and White, Nicholas J., additional

Published
2004
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94. Efficacy of chloroquine, sulphadoxine–pyrimethamine and amodiaquine for treatment of uncomplicatedPlasmodium falciparummalaria in Kajo Keji county, Sudan.

Author

Stivanello, Elisa, Cavailler, Philippe, Cassano, Francesco, Omar, Sabah Ahmed, Kariuki, Daniel, Mwangi, Jonathan, Piola, Patrice, and Guthmann, Jean-Paul

Subjects
DRUG efficacy, PHARMACODYNAMICS, CHLOROQUINE, ANTIMALARIALS, ANTIPARASITIC agents, PLASMODIUM falciparum, PHARMACOLOGY
Abstract

To provide advice on the rational use of antimalarial drugs, Médecins Sans Frontières conducted a randomized, an open label efficacy study in Kajo Keji, an area of high transmission of malaria in southern Sudan. The efficacy of chloroquine (CQ), sulphadoxine-pyrimethamine (SP) and amodiaquine (AQ) were measured in a 28-day in vivo study, with results corrected by PCR genotyping. Of 2010 children screened, 115 children aged 6–59 months with uncomplicated Plasmodium falciparum malaria were randomized into each group to receive a supervised course of treatment. Of these, 114, 103 and 111 were analysed in the CQ, SP and AQ groups, respectively. The overall parasitological failure rates at day 28 were 93.9% [95% confidence interval (CI) 87.3–97.3] for CQ, 69.9% (95% CI 60.0–78.3) for SP, and 25.2% (95% CI 17.7–34.5) for AQ. These results provide important missing data on antimalarial drug efficacy in southern Sudan. They indicate that none of the drugs could be used in monotherapy and suggest that even in combination with artemisinin, cure rates might not be efficacious enough. We recommend a combination of artemether and lumefantrine as first-line treatment for uncomplicated P. falciparum malaria cases in Kajo Keji county. [ABSTRACT FROM AUTHOR]

Published
2004
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95. In Vivo Assessment of Drug Efficacy against Plasmodium falciparumMalaria: Duration of Follow-Up

Author

Stepniewska, Kasia, Taylor, Walter R.J., Mayxay, Mayfong, Price, Ric, Smithuis, Frank, Guthmann, Jean-Paul, Barnes, Karen, Myint, Hla Yin, Adjuik, Martin, Olliaro, Piero, Pukrittayakamee, Sasithon, Looareesuwan, Sornchai, Hien, Tran Tinh, Farrar, Jeremy, Nosten, François, Day, Nicholas P.J., and White, Nicholas J.

Abstract

ABSTRACTTo determine the optimum duration of follow-up for the assessment of drug efficacy against Plasmodium falciparummalaria, 96 trial arms from randomized controlled trials (RCTs) with follow-up of 28 days or longer that were conducted between 1990 and 2003 were analyzed. These trials enrolled 13,772 patients, and participating patients comprised 23% of all patients enrolled in RCTs over the past 40 years; 61 (64%) trial arms were conducted in areas where the rate of malaria transmission was low, and 58 (50%) trial arms were supported by parasite genotyping to distinguish true recrudescences from reinfections. The median overall failure rate reported was 10% (range, 0 to 47%). The widely used day 14 assessment had a sensitivity of between 0 and 37% in identifying treatment failures and had no predictive value. Assessment at day 28 had a sensitivity of 66% overall (28 to 100% in individual trials) but could be used to predict the true failure rate if either parasite genotyping was performed (r2= 0.94) or if the entomological inoculation rate was known. In the assessment of drug efficacy against falciparum malaria, 28 days should be the minimum period of follow-up.

Published
2004
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96. Outbreak of Hepatitis E Virus Infection in Darfur, Sudan: Effectiveness of Real-Time Reverse Transcription-PCR Analysis of Dried Blood Spots

Author

Me´rens, Audrey, Gue´rin, Philippe Jean, Guthmann, Jean-Paul, and Nicand, Elisabeth

Abstract

ABSTRACTBiological samples collected in refugee camps during an outbreak of hepatitis E were used to compare the accuracy of hepatitis E virus RNA amplification by real-time reverse transcription-PCR (RT-PCR) for sera and dried blood spots (concordance of 90.6%). Biological profiles (RT-PCR and serology) of asymptomatic individuals were also analyzed.

Published
2009
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97. 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, White, Nicholas J., 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.

Abstract

Parasite clearance data from 18,699 patients with falciparum malaria treated with an artemisinin derivative in areas of low (n = 14,539), moderate (n = 2077), and high (n = 2083) levels of malaria transmission across the world were analyzed to determine the factors that affect clearance rates and identify a simple in vivo screening measure for artemisinin resistance. The main factor affecting parasite clearance time was parasite density on admission. Clearance rates were faster in high-transmission settings and with more effective partner drugs in artemisinin-based combination treatments (ACTs). The result of the malaria blood smear on day 3 (72 h) was a good predictor of subsequent treatment failure and provides a simple screening measure for artemisinin resistance. Artemisinin resistance is highly unlikely if the proportion of patients with parasite densities of <100,000 parasites/µL given the currently recommended 3-day ACT who have a positive smear result on day 3 is <3%; that is, for n patients the observed number with a positive smear result on day 3 does not exceed (n + 60)/24

98. An unusual outbreak of parvovirus B19 infections, France, 2023 to 2024.

Author

d'Humières C, Fouillet A, Verdurme L, Lakoussan SB, Gallien Y, Coignard C, Hervo M, Ebel A, Soares A, Visseaux B, Maire B, Juan PH, Parent du Châtelet I, Guthmann JP, and Durand J

Subjects
Humans, France epidemiology, Adult, Female, Male, Child, Adolescent, Child, Preschool, Middle Aged, Antibodies, Viral blood, Erythema Infectiosum epidemiology, Erythema Infectiosum diagnosis, Young Adult, Infant, Aged, Parvovirus B19, Human isolation & purification, Disease Outbreaks, Parvoviridae Infections epidemiology, Parvoviridae Infections diagnosis, Immunoglobulin M blood
Abstract

From April 2023 to May 2024, an unusual epidemic of parvovirus B19 (B19V) infections occurred in France. The number of B19V IgM-positive serologies was four times higher than in the previous epidemic in 2019. Clinical data from emergency networks corroborated this observation. Morbidity and mortality consequences were observed in children through all data sources. In adults, the increase was only observed in laboratory-confirmed data. Physicians and decisionmakers should be informed in order to better prevent, diagnose and manage at-risk patients.

Published
2024
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99. Tuberculosis incidence in foreign-born people residing in European countries in 2020.

Author

Vasiliu A, Köhler N, Altpeter E, Ægisdóttir TR, Amerali M, de Oñate WA, Bakos Á, D'Amato S, Cirillo DM, van Crevel R, Davidaviciene E, Demuth I, Domínguez J, Duarte R, Günther G, Guthmann JP, Hatzianastasiou S, Holm LH, Herrador Z, Hribar U, Huberty C, Ibraim E, Jackson S, Jensenius M, Josefsdottir KS, Koch A, Korzeniewska-Kosela M, Kuksa L, Kunst H, Lienhardt C, Mahler B, Makek MJ, Muylle I, Normark J, Pace-Asciak A, Petrović G, Pieridou D, Russo G, Rzhepishevska O, Salzer HJF, Marques MS, Schmid D, Solovic I, Sukholytka M, Svetina P, Tyufekchieva M, Vasankari T, Viiklepp P, Villand K, Wallenfels J, Wesolowski S, Mandalakas AM, Martinez L, Zenner D, and Lange C

Subjects
Humans, Incidence, Cross-Sectional Studies, Somalia, Europe epidemiology, Tuberculosis diagnosis, Tuberculosis epidemiology
Abstract

BackgroundEuropean-specific policies for tuberculosis (TB) elimination require identification of key populations that benefit from TB screening.AimWe aimed to identify groups of foreign-born individuals residing in European countries that benefit most from targeted TB prevention screening.MethodsThe Tuberculosis Network European Trials group collected, by cross-sectional survey, numbers of foreign-born TB patients residing in European Union (EU) countries, Iceland, Norway, Switzerland and the United Kingdom (UK) in 2020 from the 10 highest ranked countries of origin in terms of TB cases in each country of residence. Tuberculosis incidence rates (IRs) in countries of residence were compared with countries of origin.ResultsData on 9,116 foreign-born TB patients in 30 countries of residence were collected. Main countries of origin were Eritrea, India, Pakistan, Morocco, Romania and Somalia. Tuberculosis IRs were highest in patients of Eritrean and Somali origin in Greece and Malta (both > 1,000/100,000) and lowest among Ukrainian patients in Poland (3.6/100,000). They were mainly lower in countries of residence than countries of origin. However, IRs among Eritreans and Somalis in Greece and Malta were five times higher than in Eritrea and Somalia. Similarly, IRs among Eritreans in Germany, the Netherlands and the UK were four times higher than in Eritrea.ConclusionsCountry of origin TB IR is an insufficient indicator when targeting foreign-born populations for active case finding or TB prevention policies in the countries covered here. Elimination strategies should be informed by regularly collected country-specific data to address rapidly changing epidemiology and associated risks.

Published
2023
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100. Baseline data of parasite clearance in patients with falciparum malaria treated with an artemisinin derivative: an individual patient data meta-analysis.

Author

Abdulla S, Ashley EA, Bassat Q, Bethell D, Björkman A, Borrmann S, D'Alessandro U, Dahal P, Day NP, Diakite M, Djimde AA, Dondorp AM, Duong S, Edstein MD, Fairhurst RM, Faiz MA, Falade C, Flegg JA, Fogg C, Gonzalez R, Greenwood B, Guérin PJ, Guthmann JP, Hamed K, Hien TT, Htut Y, Juma E, Lim P, Mårtensson A, Mayxay M, Mokuolu OA, Moreira C, Newton P, Noedl H, Nosten F, Ogutu BR, Onyamboko MA, Owusu-Agyei S, Phyo AP, Premji Z, Price RN, Pukrittayakamee S, Ramharter M, Sagara I, Se Y, Suon S, Stepniewska K, Ward SA, White NJ, and Winstanley PA

Subjects
Adolescent, Adult, Aged, Animals, Child, Child, Preschool, Clinical Trials as Topic, Drug Resistance, Female, Humans, Infant, Male, Middle Aged, Plasmodium falciparum drug effects, Young Adult, Antimalarials administration & dosage, Artemisinins administration & dosage, Blood parasitology, Malaria, Falciparum drug therapy, Parasitemia drug therapy, Plasmodium falciparum isolation & purification
Abstract

Background: Artemisinin resistance in Plasmodium falciparum manifests as slow parasite clearance but this measure is also influenced by host immunity, initial parasite biomass and partner drug efficacy. This study collated data from clinical trials of artemisinin derivatives in falciparum malaria with frequent parasite counts to provide reference parasite clearance estimates stratified by location, treatment and time, to examine host factors affecting parasite clearance, and to assess the relationships between parasite clearance and risk of recrudescence during follow-up., Methods: Data from 24 studies, conducted from 1996 to 2013, with frequent parasite counts were pooled. Parasite clearance half-life (PC1/2) was estimated using the WWARN Parasite Clearance Estimator. Random effects regression models accounting for study and site heterogeneity were used to explore factors affecting PC1/2 and risk of recrudescence within areas with reported delayed parasite clearance (western Cambodia, western Thailand after 2000, southern Vietnam, southern Myanmar) and in all other areas where parasite populations are artemisinin sensitive., Results: PC1/2 was estimated in 6975 patients, 3288 of whom also had treatment outcomes evaluate d during 28-63 days follow-up, with 93 (2.8 %) PCR-confirmed recrudescences. In areas with artemisinin-sensitive parasites, the median PC1/2 following three-day artesunate treatment (4 mg/kg/day) ranged from 1.8 to 3.0 h and the proportion of patients with PC1/2 >5 h from 0 to 10 %. Artesunate doses of 4 mg/kg/day decreased PC1/2 by 8.1 % (95 % CI 3.2-12.6) compared to 2 mg/kg/day, except in populations with delayed parasite clearance. PC1/2 was longer in children and in patients with fever or anaemia at enrolment. Long PC1/2 (HR = 2.91, 95 % CI 1.95-4.34 for twofold increase, p < 0.001) and high initial parasitaemia (HR = 2.23, 95 % CI 1.44-3.45 for tenfold increase, p < 0.001) were associated independently with an increased risk of recrudescence. In western Cambodia, the region with the highest prevalence of artemisinin resistance, there was no evidence for increasing PC1/2 since 2007., Conclusions: Several factors affect PC1/2. As substantial heterogeneity in parasite clearance exists between locations, early detection of artemisinin resistance requires reference PC1/2 data. Studies with frequent parasite count measurements to characterize PC1/2 should be encouraged. In western Cambodia, where PC1/2 values are longest, there is no evidence for recent emergence of higher levels of artemisinin resistance.

Published
2015
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