144 results on '"Duparc S"'
Search Results
2. Quantifying primaquine effectiveness and improving adherence: a round table discussion of the APMEN Vivax Working Group
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Thriemer, K, Bobogare, A, Ley, B, Gudo, CS, Alam, MS, Anstey, NM, Ashley, E, Baird, JK, Gryseels, C, Jambert, E, Lacerda, M, Laihad, F, Marfurt, J, Pasaribu, AP, Poespoprodjo, JR, Sutanto, I, Taylor, WR, van den Boogaard, C, Battle, KE, Dysoley, L, Ghimire, P, Hawley, B, Hwang, J, Khan, WA, Mudin, RNB, Sumiwi, ME, Ahmed, R, Aktaruzzaman, MM, Awasthi, KR, Bardaji, A, Bell, D, Boaz, L, Burdam, FH, Chandramohan, D, Cheng, Q, Chindawongsa, K, Culpepper, J, Das, S, Deray, R, Desai, M, Domingo, G, Duoquan, W, Duparc, S, Floranita, R, Gerth-Guyette, E, Howes, RE, Hugo, C, Jagoe, G, Sariwati, E, Jhora, ST, Jinwei, W, Karunajeewa, H, Kenangalem, E, Lal, BK, Landuwulang, C, Le Perru, E, Lee, S-E, Makita, LS, McCarthy, J, Mekuria, A, Mishra, N, Naket, E, Nambanya, S, Nausien, J, Duc, TN, Thi, TN, Noviyanti, R, Pfeffer, D, Qi, G, Rahmalia, A, Rogerson, S, Samad, I, Sattabongkot, J, Satyagraha, A, Shanks, D, Sharma, SN, Sibley, CH, Sungkar, A, Syafruddin, D, Talukdar, A, Tarning, J, Kuile, F, Thapa, S, Theodora, M, Huy, TT, Waramin, E, Waramori, G, Woyessa, A, Wongsrichanalai, C, Xa, NX, Yeom, JS, Hermawan, L, Devine, A, Nowak, S, Jaya, I, Supargiyono, S, Grietens, KP, and Price, RN
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lcsh:Arctic medicine. Tropical medicine ,Efficacy ,Radical cure ,lcsh:RC955-962 ,Effectiveness ,Primaquine ,Meeting Report ,wc_750 ,lcsh:Infectious and parasitic diseases ,qv_258 ,Adherence ,qx_135 ,Vivax malaria ,APMEN ,lcsh:RC109-216 ,Plasmodium vivax - Abstract
The goal to eliminate malaria from the Asia-Pacific by 2030 will require the safe and widespread delivery of effective radical cure of malaria. In October 2017, the Asia Pacific Malaria Elimination Network Vivax Working Group met to discuss the impediments to primaquine (PQ) radical cure, how these can be overcome and the methodological difficulties in assessing clinical effectiveness of radical cure. The salient discussions of this meeting which involved 110 representatives from 18 partner countries and 21 institutional partner organizations are reported. Context specific strategies to improve adherence are needed to increase understanding and awareness of PQ within affected communities; these must include education and health promotion programs. Lessons learned from other disease programs highlight that a package of approaches has the greatest potential to change patient and prescriber habits, however optimizing the components of this approach and quantifying their effectiveness is challenging. In a trial setting, the reactivity of participants results in patients altering their behaviour and creates inherent bias. Although bias can be reduced by integrating data collection into the routine health care and surveillance systems, this comes at a cost of decreasing the detection of clinical outcomes. Measuring adherence and the factors that relate to it, also requires an in-depth understanding of the context and the underlying sociocultural logic that supports it. Reaching the elimination goal will require innovative approaches to improve radical cure for vivax malaria, as well as the methods to evaluate its effectiveness.
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- 2018
3. Comprehensive case management of malaria: Operational research informing policy
- Author
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Anvikar, AnupkuamarR, primary, Pradhan, MM, additional, Daumerie, PGrewal, additional, Pradhan, S, additional, Dutta, A, additional, Shah, NK, additional, Joshi, PL, additional, Banerji, J, additional, Duparc, S, additional, Mendis, K, additional, Murugasampillay, S, additional, and Valecha, N, additional
- Published
- 2019
- Full Text
- View/download PDF
4. Challenges for achieving safe and effective radical cure of P. vivax – a round table discussion of the APMEN Vivax Working Group
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Thriemer, K, Ley, B, Bobogare, A, Dysoley, L, Alam, M, Pasaribu, A, Sattabongkot, J, Jambert, E, Domingo, G, Commons, R, Auburn, S, Marfurt, J, Devine, A, Akturazzaman, M, Sohel, N, Namgay, R, Drukpa, T, Sharma, S, Sarawati, E, Samad, I, Theodora, M, Nambanya, S, Ounekham, S, Mudin, R, Da Thakur, G, Makita, L, Deray, R, Lee, S, Boaz, L, Danansuriya, M, Mudiyanselage, S, Chinanonwait, N, Kitchakarn, S, Nausien, J, Naket, E, Duc, T, Manh, H, Hong, Y, Cheng, Q, Richards, J, Kusriastuti, R, Satyagraha, A, Noviyanti, R, Ding, X, Khan, W, Swe, C, Guoding, Z, Qi, G, Kaneko, A, Miotto, O, Nguitragool, W, Roobsoong, W, Battle, K, Howes, R, Roca-Feltrer, A, Duparc, S, Bhowmick, I, Kenangalem, E, Bibit, J, Berry, A, Sintasath, D, Abeyasinghe, R, Sibley, C, McCarthy, J, von Seidlein, L, Baird, K, and Price, R
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parasitic diseases - Abstract
The delivery of safe and effective radical cure for Plasmodium vivax is one of the greatest challenges for achieving malaria elimination from the Asia-Pacific by 2030. During the annual meeting of the Asia Pacific Malaria Elimination Network (APMEN) Vivax Working Group in October 2016, a round table discussion was held to discuss the programmatic issues hindering the widespread use of primaquine (PQ) radical cure. Participants included 73 representatives from 16 partner countries and 33 institutional partners and other research institutes. In this review the key discussion points are presented and grouped into five themes: (i) current barriers for glucose-6-phosphate deficiency (G6PD) testing prior to PQ radical cure, (ii) necessary properties of G6PD tests for wide scale deployment, (iii) the promotion of G6PD testing, (iv) improving adherence to PQ regimens and (v) the challenges for future tafenoquine (TQ) roll out. Robust point of care (PoC) G6PD tests are needed, which are suitable and cost-effective for clinical settings with limited infrastructure. An affordable and competitive test price is needed, accompanied by sustainable funding for the product with appropriate training of healthcare staff, and robust quality control and assurance processes. In the absence of quantitative PoC G6PD tests, G6PD status can be gauged with qualitative diagnostics, however none of the available tests is currently sensitive enough to guide TQ treatment. TQ introduction will require overcoming additional challenges including the management of severely and intermediately G6PD deficient individuals. Robust strategies are needed to ensure that effective treatment practices can be deployed widely, and these should highlight the caveats as well as the benefits of radical cure for both the patients and the community. Widespread access to quality controlled G6PD testing will be critical.
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- 2017
5. LA SERVITUDE POUR DETTES
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Finley, I. and Duparc, S.
- Published
- 1965
6. 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
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Abdulla, S, Adam, I, Adjei, G, Adjuik, M, Alemayehu, B, Allan, R, Arinaitwe, E, Ashley, E, Ba, MS, Barennes, H, Barnes, K, Bassat, Q, Baudin, E, Berens-Riha, N, Bjoerkman, A, Bompart, F, Bonnet, M, Borrmann, S, Bousema, T, Brasseur, P, Bukirwa, H, Checchi, F, Dahal, P, D'Alessandro, U, Desai, M, Dicko, A, Djimde, A, Dorsey, G, Doumbo, O, Drakeley, C, Duparc, S, Eshetu, T, Espie, E, Etard, J, Faiz, A, Falade, C, Fanello, C, Faucher, J, Faye, B, Faye, O, Filler, S, Flegg, J, Fofana, B, Fogg, C, Gadalla, N, Gaye, O, Genton, B, Gething, P, Gil, J, Gonzalez, R, Grandesso, F, Greenhouse, B, Greenwood, B, Grivoyannis, A, Guerin, P, Guthmann, J, Hamed, K, Hamour, S, Hay, S, Hodel, E, Humphreys, G, Hwang, J, Ibrahim, M, Jima, D, Jones, J, Jullien, V, Juma, E, Kachur, P, Kager, P, Kamugisha, E, Kamya, MR, Karema, C, Kayentao, K, Kiechel, J, Kironde, F, Kofoed, P, Kremsner, P, Krishna, S, Lameyre, V, Lell, B, Lima, A, Makanga, M, Malik, E, Marsh, K, Martensson, A, Massougbodji, A, Menan, H, Menard, D, Menendez, C, Mens, P, Meremikwu, M, Moreira, C, Nabasumba, C, Nambozi, M, Ndiaye, J, Ngasala, B, Nikiema, F, Nsanzabana, C, Ntoumi, F, Oguike, M, Ogutu, B, Olliaro, P, Omar, SA, Ouedraogo, J, Owusu-Agyei, S, Penali, L, Pene, M, Peshu, J, Piola, P, Plowe, C, Premji, Z, Price, R, Randrianarivelojosia, M, Rombo, L, Roper, C, Rosenthal, P, Sagara, I, Same-Ekobo, A, Sawa, P, Schallig, H, Schramm, B, Seck, A, Shekalaghe, SA, Sibley, C, Sinou, V, Sirima, S, Som, F, Sow, D, Staedke, S, Stepniewska, K, Sutherland, C, Swarthout, T, Sylla, K, Talisuna, A, Taylor, W, Temu, E, Thwing, J, Tine, R, Tinto, H, Tommasini, S, Toure, O, Ursing, J, Vaillant, M, Valentini, G, Van den Broek, I, Van Vugt, M, Ward, SA, Winstanley, P, Yavo, W, Yeka, A, Zolia, Y, Zongo, I, Based, W, Unité de Recherche sur le Paludisme [Antananarivo, Madagascar], Institut Pasteur de Madagascar, and Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP)
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Male ,Infektionsmedicin ,Antimalarial ,MESH: Africa ,law.invention ,Amodiaquine/therapeutic use ,chemistry.chemical_compound ,0302 clinical medicine ,Randomized controlled trial ,[SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases ,law ,030212 general & internal medicine ,Artemether ,Prospective Studies ,Malaria, Falciparum ,Prospective cohort study ,MESH: Plasmodium falciparum ,Medicine(all) ,MESH: Middle Aged ,MESH: Malaria, Falciparum ,Malaria, Falciparum/drug therapy ,General Medicine ,Middle Aged ,MESH: Infant ,Artemisinins ,3. Good health ,Drug Combinations ,Meta-analysis ,parasite ,Quinolines ,Drug Therapy, Combination ,Artemisinin based Combination Therapy (ACT) ,MESH: Quinolines ,medicine.drug ,Falciparum ,Infectious Medicine ,medicine.medical_specialty ,030231 tropical medicine ,Plasmodium falciparum ,ARTEMISININ-RESISTANT MALARIA PLASMODIUM-FALCIPARUM PARASITE CLEARANCE ARTEMETHER-LUMEFANTRINE COMBINATION THERAPY IN-VIVO EFFICACY ARTESUNATE CHILDREN PHARMACOKINETICS ,Quinolines/administration & dosage ,African patients ,03 medical and health sciences ,Antimalarials ,Internal medicine ,MESH: Artemisinins ,parasitic diseases ,Artemisinin combination therapy ,medicine ,Humans ,MESH: Africa South of the Sahara ,Falciparum malaria ,Risk factor ,MESH: Amodiaquine ,Africa South of the Sahara ,Parasite clearance ,MESH: Drug Combinations ,MESH: Humans ,business.industry ,Amodiaquine ,Infant ,Odds ratio ,MESH: Antimalarials ,MESH: Male ,MESH: Prospective Studies ,Surgery ,Malaria ,Clinical trial ,Artemisinins/administration & dosage ,MESH: Drug Therapy, Combination ,chemistry ,Artesunate ,Africa ,Commentary ,Antimalarials/administration & dosage ,business - Abstract
WWARN Artemisinin based Combination Therapy (ACT) Africa Baseline Study Group; International audience; 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
7. 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
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Abdulla, S., Adam, I., Adjei, G. O., Adjuik, M. A., Alemayehu, B., Allan, R., Arinaitwe, E., Ashley, E. A., Ba, M. S., Barennes, H., Barnes, K. I., Bassat, Q., Baudin, E., Berens-Riha, N., Bjorkman, A., Bompart, F., Bonnet, M., Borrmann, S., Bousema, T., Brasseur, Philippe, Bukirwa, H., Checchi, F., Dahal, P., D'Alessandro, U., Desai, M., Dicko, A., Djimde, A. A., Dorsey, G., Doumbo, O. K., Drakeley, C. J., Duparc, S., Eshetu, T., Espie, E., and Etard, Jean-François
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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 degrees 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
8. The effect of dose on the antimalarial efficacy of artemether-lumefantrine: a systematic review and pooled analysis of individual patient data
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Anstey, NM, Price, RN, Davis, TME, Karunajeewa, HA, Mueller, I, D'Alessandro, U, Massougbodji, A, Nikiema, F, Ouedraogo, JB, Tinto, H, Zongo, I, Same-Ekobo, A, Kone, M, Menan, H, Toure, AO, Yavo, W, Kofoed, PE, Alemayehu, BH, Jima, D, Baudin, E, Espie, E, Nabasumba, C, Pinoges, L, Schramm, B, Cot, M, Deloron, P, Faucher, JF, Guthmann, JP, Lell, B, Borrmann, S, Adjei, GO, Ursing, J, Tjitra, E, Marsh, K, Peshu, J, Juma, E, Ogutu, BR, Omar, SA, Sawa, P, Talisuna, AO, Khanthavong, M, Mayxay, M, Newton, PN, Piola, P, Djimde, AA, Doumbo, OK, Fofana, B, Sagara, I, Bassat, Q, Gonzalez, R, Menendez, C, Smithuis, F, Bousema, T, Kager, PA, Mens, PF, Schallig, HDFH, van Den Broek, I, van Vugt, M, Ibrahim, ML, Falade, CO, Meremikwu, M, Gil, JP, Karema, C, Ba, MS, Faye, B, Faye, O, Gaye, O, Ndiaye, JL, Pene, M, Sow, D, Sylla, K, Tine, RCK, Penali, LK, Barnes, KI, Workman, LJ, Lima, A, Adam, I, Gadalla, NB, Malik, EFM, Bjorkman, A, Martensson, A, Ngasala, BE, Rombo, L, Aliu, P, Duparc, S, Filler, S, Genton, B, Hodel, EM, Olliaro, P, Abdulla, S, Kamugisha, E, Premji, Z, Shekalaghe, SA, Ashley, EA, Carrara, VI, McGready, R, Nosten, F, Faiz, AM, Lee, SJ, White, NJ, Dondorp, AM, Smith, JJ, Tarning, J, Achan, J, Bukirwa, H, Yeka, A, Arinaitwe, E, Staedke, SG, Kamya, MR, Kironde, F, Drakeley, CJ, Oguike, M, Sutherland, CJ, Checchi, F, Dahal, P, Flegg, JA, Guerin, PJ, Moreira, C, Nsanzabana, C, Sibley, CH, Stepniewska, K, Gething, PW, Hay, SI, Greenwood, B, Ward, SA, Winstanley, PA, Dorsey, G, Greenhouse, B, Rosenthal, PJ, Grivoyannis, A, Hamed, K, Hwang, J, Kachur, PS, and Nambozi, M
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- 2015
9. Comprehensive case management of malaria: Operational research informing policy.
- Author
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Pradhan, M. M., Anvikar, Anupkuamar R., Daumerie, P. Grewal, Pradhan, S., Dutta, A., Shah, N. K., Joshi, P. L., Banerji, J., Duparc, S., Mendis, K., Murugasampillay, S., and Valecha, N.
- Published
- 2019
- Full Text
- View/download PDF
10. An Open-Label, Randomised Study of Dihydroartemisinin-Piperaquine Versus Artesunate-Mefloquine for Falciparum Malaria in Asia
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Valecha N, Ap, Phyo, Mayxay M, Pn, Newton, Krudsood S, Keomany S, Khanthavong M, Pongvongsa T, Ruangveerayuth R, Uthaisil C, Ubben D, Duparc S, Bacchieri A, Corsi M, Bhk, Rao, Pc, Bhattacharya, Dubhashi N, Sk, Ghosh, Dev V, Kumar A, and Pukrittayakamee S
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Multidisciplinary ,Science ,lcsh:R ,Medicine ,Correction ,lcsh:Medicine ,lcsh:Q ,lcsh:Science - Published
- 2010
11. Chlorproguanil - Dapsone - Artesunate versus artemether - Lumefantrine: A randomized, double-blind phase III trial in African children and adolescents with uncomplicated Plasmodium falciparum malaria
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Premji, Z., Umeh, R. E., Owusu-Agyei, S., Esamai, F., Ezedinachi, E. U., Oguche, S., Borrmann, S., Sowunmi, A., Duparc, S., Kirby, P. L., Pamba, A., Kellam, L., Guiguemdé, R., Greenwood, B., Ward, Stephen, and Winstanley, P. A.
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wc_770 ,wc_20 ,qx_20 ,qv_4 ,qx_135 ,parasitic diseases ,qv_38 ,ws_460 ,wb_330 ,wc_750 ,ws_430 - Abstract
Background\ud \ud Chlorproguanil-dapsone-artesunate (CDA) was developed as an affordable, simple, fixed-dose artemisinin-based combination therapy for use in Africa. This trial was a randomized parallel-group, double-blind, double-dummy study to compare CDA and artemether-lumefantrine (AL) efficacy in uncomplicated Plasmodium falciparum malaria and further define the CDA safety profile, particularly its hematological safety in glucose-6-phosphate dehydrogenase (G6PD) -deficient patients. \ud \ud Methods and Findings\ud \ud The trial was conducted at medical centers at 11 sites in five African countries between June 2006 and August 2007. 1372 patients (≥1 to
- Published
- 2009
12. Essai comparatif de l'artéméther et de la quinine dans le paludisme grave à Plasmodium falciparum de l'adulte et du grand enfant au Cameroun
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Fargier, J.J., Louis, F.J., Duparc, S., Hounsinou, C., Ringwald, Pascal, and Danis, M.
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TRAITEMENT MEDICAL ,ARTEMETHER ,ENFANT D'AGE SCOLAIRE ,ETUDE COMPARATIVE ,MEDICAMENT ,TOLERANCE ,PALUDISME ,EFFICACITE ,ADULTE ,QUININE - Abstract
Une étude comparative de l'arthéméther et de la quinine dans le traitement du paludisme grave à #Plasmodium falciparum$ de l'adulte et du grand enfant a été conduite au Cameroun de juin 1993 à juin 1994. Les patients du groupe artéméther ont reçu par voie intramusculaire 3,2 mg/kg d'artéméther le premier jour puis 1,6 mg/kg les quatre jours suivants. Ceux du groupe quinine ont reçu par voie intraveineuse 16 mg/kg de quinine base les 4 premières heures puis 8 mg/kg toutes les 8 heures pendant 3 jours. Sur 95 patients enrôlés, 84 dossiers (40 artéméther et 44 quinine) ont été validés. Dans ces deux groupes comparables sur tous les paramètres lors de l'inclusion, les auteurs ont montré que l'artéméther apparaît supérieur à la quinine sur les paramètres clairance totale de la parasitémie, clairance parasitaire à 90 p. 100 et clairance thermique et qu'il est comparable à la quinine sur les paramètres clairance parasitaire à 50 p. 100 et temps de normalisation de la conscience. Ces résultats associés à un mode d'administration simple, la voie intramusculaire, font de l'artéméther un antipaludique d'excellence pour le traitement du paludisme grave et du neuropaludisme dans des régions peu médicalisées. (Résumé d'auteur)
- Published
- 1999
13. A Simplified Intravenous Artesunate Regimen for Severe Malaria-Reply
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Kremsner, P. G., primary, Taylor, T., additional, Issifou, S., additional, Kombila, M., additional, Chimalizeni, Y., additional, Kawaza, K., additional, Bouyou Akotet, M. K., additional, Duscha, M., additional, Mordmuller, B., additional, Kosters, K., additional, Humberg, A., additional, Scott Miller, R., additional, Weina, P., additional, Duparc, S., additional, Mohrle, J., additional, Kun, J. F. J., additional, Planche, T., additional, Teja-Isavadharm, P., additional, Simpson, J. A., additional, Kohler, C., additional, and Krishna, S., additional
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- 2012
- Full Text
- View/download PDF
14. Modeling and simulation to evaluate pyronaridine exposure in pediatric malaria patients
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Fleckenstein, L., primary, Methaneethorn, J., additional, Duparc, S., additional, Borghini-Fuhrer, I., additional, Shin, C.-S., additional, and Jung, D., additional
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- 2012
- Full Text
- View/download PDF
15. Le royaume latin de Jérusalem P. U. F. Jean Richard
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Duparc, S.
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- 1957
16. The mind of the Middle Ages. An historical survey A.D. 200-1500 Frédéric B. Artz
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Duparc, S.
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- 1957
17. Etude sur le Songe du vieil Pèlerin de Philippe de Mézières (1327-1405) Dora M. Bell
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Duparc, S.
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- 1957
18. Histoire du commerce de Marseille, t. I, 1949, t. II, t. III
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Duparc, S.
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- 1957
19. ANCIEN DROIT
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Ourliac, P., Kalifa, Simon, Le Bras, Gabriel, Duparc, S., and Sicard
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- 1958
20. La Moralité professionnelle des origines à nos jours François Prévet
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Duparc, S.
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- 1958
21. Histoire de saint Dominique H. M. Vicaire
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Duparc, S.
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- 1959
22. Ancien Droit
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Vandenbossche, A., Duparc, S., and Lepointe, G.
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- 1959
23. ANCIEN DROIT
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Vandenbossche, A., Duparc, S., and Berlia, G.
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- 1960
24. HISTOIRE GÉNÉRALE DU DROIT ET DES INSTITUTIONS
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Cardascia, G., Duparc, S., Vandenbossche, A., and Le Moal, F.
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- 1971
25. Le Christianisme dans l'Empire romain Michel Meslin
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Duparc, S.
- Published
- 1971
26. Jogtörténeti tanulmânyok (= Etudes d'histoire du droit), vol. II, (= Editions Juridiques et Economiques). (en hongrois, avec des résumés en russe et en allemand, en anglais et en français)
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Duparc, S.
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- 1969
27. Matricule de l'Université de Louvain t. V, 19 févr. 1616- févr. 1651 A. Schillings
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Duparc, S.
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- 1969
28. Glucose-6-phosphate dehydrogenase deficiency and antimalarial drug development
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Beutler, E., Duparc, S., Doumbo, O., Ghosh, K., Lacerda, M. V. G., Lapierre, D., Looareesuwan, S., Premji, Z., Vulliamy, T., and Christopher Whitty
29. Pyronaridine-artesunate granules versus artemether-lumefantrine crushed tablets in children with Plasmodium falciparum malaria: a randomized controlled trial
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Kayentao Kassoum, Doumbo Ogobara K, Pénali Louis K, Offianan André T, Bhatt Kirana M, Kimani Joshua, Tshefu Antoinette K, Kokolomami Jack HT, Ramharter Michael, de Salazar Pablo Martinez, Tiono Alfred B, Ouédraogo Alphonse, Bustos Maria Dorina G, Quicho Frederick, Borghini-Fuhrer Isabelle, Duparc Stephan, Shin Chang-Sik, and Fleckenstein Lawrence
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Pyronaridine-artesunate ,Artemether-lumefantrine ,Malaria ,Plasmodium falciparum ,Pediatric ,Arctic medicine. Tropical medicine ,RC955-962 ,Infectious and parasitic diseases ,RC109-216 - Abstract
Abstract Background Children are most vulnerable to malaria. A pyronaridine-artesunate pediatric granule formulation is being developed for the treatment of uncomplicated Plasmodium falciparum malaria. Methods This phase III, multi-center, comparative, open-label, parallel-group, controlled clinical trial included patients aged ≤12 years, bodyweight ≥5 to P. falciparum malaria. Patients were randomized (2:1) to pyronaridine-artesunate granules (60/20 mg) once daily or artemether-lumefantrine crushed tablets (20/120 mg) twice daily, both dosed by bodyweight, orally (liquid suspension) for three days. Results Of 535 patients randomized, 355 received pyronaridine-artesunate and 180 received artemether-lumefantrine. Day-28 adequate clinical and parasitological response (ACPR), corrected for re-infection using polymerase chain reaction (PCR) genotyping (per-protocol population) was 97.1% (329/339; 95% CI 94.6, 98.6) for pyronaridine-artesunate; 98.8% (165/167; 95% CI 95.7, 99.9) for artemether-lumefantrine. The primary endpoint was achieved: pyronaridine-artesunate PCR-corrected day-28 ACPR was statistically significantly >90% (P 3 times the upper limit of normal (ULN) and peak total bilirubin >2xULN (i.e. within the Hy’s law definition). Conclusions The pyronaridine-artesunate pediatric granule formulation was efficacious and was non-inferior to artemether-lumefantrine. The adverse event profile was similar for the two comparators. Pyronaridine-artesunate should be considered for inclusion in paediatric malaria treatment programmes. Trial registration ClinicalTrials.gov: identifier NCT00541385
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- 2012
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30. The global pipeline of new medicines for the control and elimination of malaria
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Anthony Melinda P, Burrows Jeremy N, Duparc Stephan, JMoehrle Joerg, and Wells Timothy NC
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Drugs ,Resistance ,Combinations ,ACT ,Endoperoxide ,Spiroindolone ,Relapse ,Transmission ,Arctic medicine. Tropical medicine ,RC955-962 ,Infectious and parasitic diseases ,RC109-216 - Abstract
Abstract Over the past decade, there has been a transformation in the portfolio of medicines to combat malaria. New fixed-dose artemisinin combination therapy is available, with four different types having received approval from Stringent Regulatory Authorities or the World Health Organization (WHO). However, there is still scope for improvement. The Malaria Eradication Research agenda identified several gaps in the current portfolio. Simpler regimens, such as a single-dose cure are needed, compared with the current three-day treatment. In addition, new medicines that prevent transmission and also relapse are needed, but with better safety profiles than current medicines. There is also a big opportunity for new medicines to prevent reinfection and to provide chemoprotection. This study reviews the global portfolio of new medicines in development against malaria, as of the summer of 2012. Cell-based phenotypic screening, and ‘fast followers’ of clinically validated classes, mean that there are now many new classes of molecules starting in clinical development, especially for the blood stages of malaria. There remain significant gaps for medicines blocking transmission, preventing relapse, and long-duration molecules for chemoprotection. The nascent pipeline of new medicines is significantly stronger than five years ago. However, there are still risks ahead in clinical development and sustainable funding of clinical studies is vital if this early promise is going to be delivered.
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- 2012
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31. Review of pyronaridine anti-malarial properties and product characteristics
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Croft Simon L, Duparc Stephan, Arbe-Barnes Sarah J, Craft J, Shin Chang-Sik, Fleckenstein Lawrence, Borghini-Fuhrer Isabelle, and Rim Han-Jong
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Pyronaridine ,Plasmodium falciparum ,Plasmodium vivax ,Review ,Artemisinin containing compound ,Anti-malarial therapy ,Arctic medicine. Tropical medicine ,RC955-962 ,Infectious and parasitic diseases ,RC109-216 - Abstract
Abstract Pyronaridine was synthesized in 1970 at the Institute of Chinese Parasitic Disease and has been used in China for over 30 years for the treatment of malaria. Pyronaridine has high potency against Plasmodium falciparum, including chloroquine-resistant strains. Studies in various animal models have shown pyronaridine to be effective against strains resistant to other anti-malarials, including chloroquine. Resistance to pyronaridine appears to emerge slowly and is further retarded when pyronaridine is used in combination with other anti-malarials, in particular, artesunate. Pyronaridine toxicity is generally less than that of chloroquine, though evidence of embryotoxicity in rodents suggests use with caution in pregnancy. Clinical pharmacokinetic data for pyronaridine indicates an elimination T1/2 of 13.2 and 9.6 days, respectively, in adults and children with acute uncomplicated falciparum and vivax malaria in artemisinin-combination therapy. Clinical data for mono or combined pyronaridine therapy show excellent anti-malarial effects against P. falciparum and studies of combination therapy also show promise against Plasmodium vivax. Pyronaridine has been developed as a fixed dose combination therapy, in a 3:1 ratio, with artesunate for the treatment of acute uncomplicated P. falciparum malaria and blood stage P. vivax malaria with the name of Pyramax® and has received Positive Opinion by European Medicines Agency under the Article 58 procedure.
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- 2012
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32. Review of the clinical pharmacokinetics of artesunate and its active metabolite dihydroartemisinin following intravenous, intramuscular, oral or rectal administration
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Shin Chang-Sik, Jung Donald, Borghini-Fuhrer Isabelle, Duparc Stephan, Morris Carrie A, and Fleckenstein Lawrence
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Arctic medicine. Tropical medicine ,RC955-962 ,Infectious and parasitic diseases ,RC109-216 - Abstract
Abstract Artesunate (AS) is a clinically versatile artemisinin derivative utilized for the treatment of mild to severe malaria infection. Given the therapeutic significance of AS and the necessity of appropriate AS dosing, substantial research has been performed investigating the pharmacokinetics of AS and its active metabolite dihydroartemisinin (DHA). In this article, a comprehensive review is presented of AS clinical pharmacokinetics following administration of AS by the intravenous (IV), intramuscular (IM), oral or rectal routes. Intravenous AS is associated with high initial AS concentrations which subsequently decline rapidly, with typical AS half-life estimates of less than 15 minutes. AS clearance and volume estimates average 2 - 3 L/kg/hr and 0.1 - 0.3 L/kg, respectively. DHA concentrations peak within 25 minutes post-dose, and DHA is eliminated with a half-life of 30 - 60 minutes. DHA clearance and volume average between 0.5 - 1.5 L/kg/hr and 0.5 - 1.0 L/kg, respectively. Compared to IV administration, IM administration produces lower peaks, longer half-life values, and higher volumes of distribution for AS, as well as delayed peaks for DHA; other parameters are generally similar due to the high bioavailability, assessed by exposure to DHA, associated with IM AS administration (> 86%). Similarly high bioavailability of DHA (> 80%) is associated with oral administration. Following oral AS, peak AS concentrations (Cmax) are achieved within one hour, and AS is eliminated with a half-life of 20 - 45 minutes. DHA Cmax values are observed within two hours post-dose; DHA half-life values average 0.5 - 1.5 hours. AUC values reported for AS are often substantially lower than those reported for DHA following oral AS administration. Rectal AS administration yields pharmacokinetic results similar to those obtained from oral administration, with the exceptions of delayed AS Cmax and longer AS half-life. Drug interaction studies conducted with oral AS suggest that AS does not appreciably alter the pharmacokinetics of atovaquone/proguanil, chlorproguanil/dapsone, or sulphadoxine/pyrimethamine, and mefloquine and pyronaridine do not alter the pharmacokinetics of DHA. Finally, there is evidence suggesting that the pharmacokinetics of AS and/or DHA following AS administration may be altered by pregnancy and by acute malaria infection, but further investigation would be required to define those alterations precisely.
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- 2011
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33. Frequency of glucose-6-phosphate dehydrogenase deficiency in malaria patients from six African countries enrolled in two randomized anti-malarial clinical trials
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Duparc Stephan, Pamba Allan, Carter Nick, and Waitumbi John N
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Arctic medicine. Tropical medicine ,RC955-962 ,Infectious and parasitic diseases ,RC109-216 - Abstract
Abstract Background Glucose-6-phosphate dehydrogenase (G6PD) deficiency is common in populations living in malaria endemic areas. G6PD genotype and phenotype were determined for malaria patients enrolled in the chlorproguanil-dapsone-artesunate (CDA) phase III clinical trial programme. Methods Study participants, aged > 1 year, with microscopically confirmed uncomplicated Plasmodium falciparum malaria, and haemoglobin ≥ 70 g/L or haematocrit ≥ 25%, were recruited into two clinical trials conducted in six African countries (Burkina Faso, Ghana, Kenya, Nigeria, Tanzania, Mali). G6PD genotype of the three most common African forms, G6PD*B, G6PD*A (A376G), and G6PD*A- (G202A, A542T, G680T and T968C), were determined and used for frequency estimation. G6PD phenotype was assessed qualitatively using the NADPH fluorescence test. Exploratory analyses investigated the effect of G6PD status on baseline haemoglobin concentration, temperature, asexual parasitaemia and anti-malarial efficacy after treatment with CDA 2/2.5/4 mg/kg or chlorproguanil-dapsone 2/2.5 mg/kg (both given once daily for three days) or six-dose artemether-lumefantrine. Results Of 2264 malaria patients enrolled, 2045 had G6PD genotype available and comprised the primary analysis population (1018 males, 1027 females). G6PD deficiency prevalence was 9.0% (184/2045; 7.2% [N = 147] male hemizygous plus 1.8% [N = 37] female homozygous), 13.3% (273/2045) of patients were heterozygous females, 77.7% (1588/2045) were G6PD normal. All deficient G6PD*A- genotypes were A376G/G202A. G6PD phenotype was available for 64.5% (1319/2045) of patients: 10.2% (134/1319) were G6PD deficient, 9.6% (127/1319) intermediate, and 80.2% (1058/1319) normal. Phenotype test specificity in detecting hemizygous males was 70.7% (70/99) and 48.0% (12/25) for homozygous females. Logistic regression found no significant effect of G6PD genotype on adjusted mean baseline haemoglobin (p = 0.154), adjusted mean baseline temperature (p = 0.9617), or adjusted log mean baseline parasitaemia (p = 0.365). There was no effect of G6PD genotype (p = 0.490) or phenotype (p = 0.391) on the rate of malaria recrudescence, or reinfection (p = 0.134 and p = 0.354, respectively). Conclusions G6PD deficiency is common in African patients with malaria and until a reliable and simple G6PD test is available, the use of 8-aminoquinolines will remain problematic. G6PD status did not impact baseline haemoglobin, parasitaemia or temperature or the outcomes of anti-malarial therapy. Trial registration Clinicaltrials.gov: NCT00344006 and NCT00371735.
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- 2011
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34. Tafenoquine versus Primaquine to Prevent Relapse of Plasmodium vivax Malaria.
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Llanos-Cuentas, A., Lacerda, M. V. G., Hien, T. T., Vélez, I. D., Namaik-larp, C., Chu, C. S., Villegas, M. F., Val, F., Monteiro, W. M., Brito, M. A. M., Costa, M. R. F., Chuquiyauri, R., Casapía, M., Nguyen, C. H., Aruachan, S., Papwijitsil, R., Nosten, F. H., Bancone, G., Angus, B., and Duparc, S.
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DRUG therapy for malaria , *CHLOROQUINE , *ANTIMALARIALS , *COMBINATION drug therapy , *COMPARATIVE studies , *HEMOGLOBINS , *LONGITUDINAL method , *MALARIA , *RESEARCH methodology , *MEDICAL cooperation , *INBORN errors of metabolism , *OXIDOREDUCTASES , *PRIMAQUINE , *PROGNOSIS , *PROTOZOA , *QUINOLINE , *RESEARCH , *EVALUATION research , *RANDOMIZED controlled trials , *BLIND experiment , *KAPLAN-Meier estimator , *PARASITEMIA , *DISEASE complications , *THERAPEUTICS ,DISEASE relapse prevention - Abstract
Background: Tafenoquine, a single-dose therapy for Plasmodium vivax malaria, has been associated with relapse prevention through the clearance of P. vivax parasitemia and hypnozoites, termed "radical cure."Methods: We performed a phase 3, prospective, double-blind, double-dummy, randomized, controlled trial to compare tafenoquine with primaquine in terms of safety and efficacy. The trial was conducted at seven hospitals or clinics in Peru, Brazil, Colombia, Vietnam, and Thailand and involved patients with normal glucose-6-phosphate dehydrogenase (G6PD) enzyme activity and female patients with moderate G6PD enzyme deficiency; all patients had confirmed P. vivax parasitemia. The patients were randomly assigned, in a 2:1 ratio, to receive a single 300-mg dose of tafenoquine or 15 mg of primaquine once daily for 14 days (administered under supervision); all patients received a 3-day course of chloroquine and were followed for 180 days. The primary safety outcome was a protocol-defined decrease in the hemoglobin level (>3.0 g per deciliter or ≥30% from baseline or to a level of <6.0 g per deciliter). Freedom from recurrence of P. vivax parasitemia at 6 months was the primary efficacy outcome in a planned patient-level meta-analysis of the current trial and another phase 3 trial of tafenoquine and primaquine (per-protocol populations), and an odds ratio for recurrence of 1.45 (tafenoquine vs. primaquine) was used as a noninferiority margin.Results: A protocol-defined decrease in the hemoglobin level occurred in 4 of 166 patients (2.4%; 95% confidence interval [CI], 0.9 to 6.0) in the tafenoquine group and in 1 of 85 patients (1.2%; 95% CI, 0.2 to 6.4) in the primaquine group, for a between-group difference of 1.2 percentage points (95% CI, -4.2 to 5.0). In the patient-level meta-analysis, the percentage of patients who were free from recurrence at 6 months was 67.0% (95% CI, 61.0 to 72.3) among the 426 patients in the tafenoquine group and 72.8% (95% CI, 65.6 to 78.8) among the 214 patients in the primaquine group. The efficacy of tafenoquine was not shown to be noninferior to that of primaquine (odds ratio for recurrence, 1.81; 95% CI, 0.82 to 3.96).Conclusions: Among patients with normal G6PD enzyme activity, the decline in hemoglobin level with tafenoquine did not differ significantly from that with primaquine. Tafenoquine showed efficacy for the radical cure of P. vivax malaria, although tafenoquine was not shown to be noninferior to primaquine. (Funded by GlaxoSmithKline and Medicines for Malaria Venture; GATHER ClinicalTrials.gov number, NCT02216123 .). [ABSTRACT FROM AUTHOR]- Published
- 2019
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35. Pyronaridine-artesunate versus mefloquine plus artesunate for malaria.
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Rueangweerayut R, Phyo AP, Uthaisin C, Poravuth Y, Binh TQ, Tinto H, Pénali LK, Valecha N, Tien NT, Abdulla S, Borghini-Fuhrer I, Duparc S, Shin CS, Fleckenstein L, Pyronaridine-Artesunate Study Team, Rueangweerayut, Ronnatrai, Phyo, Aung Pyae, Uthaisin, Chirapong, Poravuth, Yi, and Binh, Tran Quang
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Background: Pyronaridine-artesunate is an artemisinin-based combination therapy under evaluation for the treatment of Plasmodium falciparum and P. vivax malaria.Methods: We conducted a phase 3, open-label, multicenter, noninferiority trial that included 1271 patients between 3 and 60 years of age from Asia (81.3%) or Africa (18.7%) with microscopically confirmed, uncomplicated P. falciparum malaria. Patients underwent randomization for treatment with a fixed-dose combination of 180 mg of pyronaridine and 60 mg of artesunate or with 250 mg of mefloquine plus 100 mg of artesunate. Doses were calculated according to body weight and administered once daily for 3 days.Results: Pyronaridine-artesunate was noninferior to mefloquine plus artesunate for the primary outcome: adequate clinical and parasitologic response in the per-protocol population on day 28, corrected for reinfection with the use of polymerase-chain-reaction (PCR) genotyping. For this outcome, efficacy in the group receiving pyronaridine-artesunate was 99.2% (743 of 749 patients; 95% confidence interval [CI], 98.3 to 99.7) and that in the group receiving mefloquine plus artesunate was 97.8% (360 of 368 patients; 95% CI, 95.8 to 99.1), with a treatment difference of 1.4 percentage points (95% CI, 0.0 to 3.5; P=0.05). In the intention-to-treat population, efficacy on day 42 in the group receiving pyronaridine-artesunate was 83.1% (705 of 848 patients; 95% CI, 80.4 to 85.6) and that in the group receiving mefloquine plus artesunate was 83.9% (355 of 423 patients; 95% CI, 80.1 to 87.3). In Cambodia, where there were 211 study patients, the median parasite clearance time was prolonged for both treatments: 64 hours versus 16.0 to 38.9 hours in other countries (P<0.001, on the basis of Kaplan-Meier estimates). Kaplan-Meier estimates of the recrudescence rate in the intention-to-treat population in Cambodia until day 42 were higher with pyronaridine-artesunate than with mefloquine plus artesunate (10.2% [95% CI, 5.4 to 18.6] vs. 0%; P=0.04 as calculated with the log-rank test), but similar for the other countries combined (4.7% [95% CI, 3.3 to 6.7] and 2.8% [95% CI, 1.5 to 5.3], respectively; P=0.24). Elevated levels of aminotransferases were observed in those receiving pyronaridine-artesunate. Two patients receiving mefloquine plus artesunate had seizures.Conclusions: Fixed-dose pyronaridine-artesunate was efficacious in the treatment of uncomplicated P. falciparum malaria. In Cambodia, extended parasite clearance times were suggestive of in vivo resistance to artemisinin. (Funded by Shin Poong Pharmaceutical Company and the Medicines for Malaria Venture; ClinicalTrials.gov number, NCT00403260.). [ABSTRACT FROM AUTHOR]- Published
- 2012
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36. Efficacy and safety of a fixed-dose oral combination of pyronaridine-artesunate compared with artemether-lumefantrine in children and adults with uncomplicated Plasmodium falciparum malaria: a randomised non-inferiority trial.
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Tshefu AK, Gaye O, Kayentao K, Thompson R, Bhatt KM, Sesay SS, Bustos DG, Tjitra E, Bedu-Addo G, Borghini-Fuhrer I, Duparc S, Shin CS, Fleckenstein L, Pyronaridine-artesunate Study Team, Tshefu, Antoinette K, Gaye, Oumar, Kayentao, Kassoum, Thompson, Ricardo, Bhatt, Kirana M, and Sesay, Sanie S S
- Abstract
Background: There is a need for new artemisinin-based combination therapies that are convenient, effective, and safe. We compared the efficacy and safety of pyronaridine-artesunate with that of artemether-lumefantrine for treatment of uncomplicated P falciparum malaria.Methods: This phase 3, parallel-group, double-blind, randomised, non-inferiority trial was undertaken in seven sites in Africa and three sites in southeast Asia. In a double-dummy design, patients aged 3-60 years with uncomplicated P falciparum malaria were randomly assigned in a 2:1 ratio to receive pyronaridine-artesunate once a day or artemether-lumefantrine twice a day, orally for 3 days, plus respective placebo. Randomisation was done by computer-generated randomisation sequence in blocks of nine by study centre. Intervention tablets contained 180 mg pyronaridine and 60 mg artesunate; control tablets contained 20 mg artemether and 120 mg lumefantrine. Both treatments were given according to bodyweight. The primary efficacy outcome was PCR-corrected adequate clinical and parasitological response (ACPR) rate at day 28 in the per-protocol population. Non-inferiority was shown if the lower limit of the two-sided 95% CI for the difference between groups was greater than -5%. This study is registered with ClinicalTrials.gov, number NCT00422084.Findings: 1272 patients were randomly assigned to treatment (pyronaridine-artesunate, n=849; artemether-lumefantrine, n=423). The per-protocol population consisted of 784 patients in the pyronaridine-artesunate group and 386 patients in the artemether-lumefantrine group. PCR-corrected ACPR rate at day 28 was 99.5% (780 patients; 95% CI 98.7-99.9) in the pyronaridine-artesunate group and 99.2% (383 patients; 95% CI 97.7-99.8) in the artemether-lumefantrine group (treatment difference 0.3%, 95% CI -0.7 to 1.8; p=0.578). There were 509 (60.0%) adverse events in 849 patients assigned to pyronaridine-artesunate and 241 (57.0%) in 423 patients assigned to artemether-lumefantrine. The most frequent drug-related adverse event was eosinophilia (pyronaridine-artesunate, 53 events [6.2%]; artemether-lumefantrine 24 events [5.7%]). 21 (2.5%) patients in the pyronaridine-artesunate group and seven (1.7%) in the artemether-lumefantrine group discontinued study drugs or were withdrawn from the study. Mild and transient increases in alanine aminotransferase and aspartate aminotransferase concentrations were seen in the pyronaridine-artesunate group but not in the artemether-lumefantrine group.Interpretation: Efficacy of pyronaridine-artesunate was non-inferior to that of artemether-lumefantrine for treatment of uncomplicated falciparum malaria. Pyronaridine-artesunate should be considered for inclusion in malaria treatment programmes.Funding: Shin Poong Pharmaceutical and the Medicines for Malaria Venture. [ABSTRACT FROM AUTHOR]- Published
- 2010
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37. Defining the next generation of severe malaria treatment: a target product profile.
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Achan J, Barry A, Leroy D, Kamara G, Duparc S, Kaszubska W, Gandhi P, Buffet B, Tshilab P, Ogutu B, Taylor T, Krishna S, Richardson N, Ramachandruni H, and Rietveld H
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- Humans, Artemisinins therapeutic use, Drug Resistance, Antimalarials therapeutic use, Malaria drug therapy
- Abstract
Background: Severe malaria is a life-threatening infection, particularly affecting children under the age of 5 years in Africa. Current treatment with parenteral artemisinin derivatives is highly efficacious. However, artemisinin partial resistance is widespread in Southeast Asia, resulting in delayed parasite clearance after therapy, and has emerged independently in South America, Oceania, and Africa. Hence, new treatments for severe malaria are needed, and it is prudent to define their characteristics now. This manuscript focuses on the target product profile (TPP) for new treatments for severe malaria. It also highlights preparedness when considering ways of protecting the utility of artemisinin-based therapies., Target Product Profile: Severe malaria treatments must be highly potent, with rapid onset of antiparasitic activity to clear the infection as quickly as possible to prevent complications. They should also have a low potential for drug resistance selection, given the high parasite burden in patients with severe malaria. Combination therapies are needed to deter resistance selection and dissemination. Partner drugs which are approved for uncomplicated malaria treatment would provide the most rapid development pathway for combinations, though new candidate molecules should be considered. Artemisinin combination approaches to severe malaria would extend the lifespan of current therapy, but ideally, completely novel, non-artemisinin-based combination therapies for severe malaria should be developed. These should be advanced to at least phase 2 clinical trials, enabling rapid progression to patient use should current treatment fail clinically. New drug combinations for severe malaria should be available as injectable formulations for rapid and effective treatment, or as rectal formulations for pre-referral intervention in resource-limited settings., Conclusion: Defining the TPP is a key step to align responses across the community to proactively address the potential for clinical failure of artesunate in severe malaria. In the shorter term, artemisinin-based combination therapies should be developed using approved or novel drugs. In the longer term, novel combination treatments should be pursued. Thus, this TPP aims to direct efforts to preserve the efficacy of existing treatments while improving care and outcomes for individuals affected by this life-threatening disease., (© 2024. The Author(s).)
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- 2024
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38. Operational effectiveness of tafenoquine and primaquine for the prevention of Plasmodium vivax recurrence in Brazil: a retrospective observational study.
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Brito M, Rufatto R, Brito-Sousa JD, Murta F, Sampaio V, Balieiro P, Baía-Silva D, Castro V, Alves B, Alencar A, Duparc S, Grewal Daumerie P, Borghini-Fuhrer I, Jambert E, Peterka C, Edilson Lima F Jr, Carvalho Maia L, Lucena Cruz C, Maciele B, Vasconcelos M, Machado M, Augusto Figueira E, Alcirley Balieiro A, Batista Pereira D, and Lacerda M
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- Humans, Retrospective Studies, Female, Male, Adult, Brazil epidemiology, Adolescent, Child, Young Adult, Middle Aged, Child, Preschool, Infant, Secondary Prevention methods, Chloroquine therapeutic use, Chloroquine administration & dosage, Recurrence, Treatment Outcome, Aged, Malaria, Vivax drug therapy, Malaria, Vivax prevention & control, Primaquine therapeutic use, Primaquine administration & dosage, Antimalarials therapeutic use, Antimalarials administration & dosage, Aminoquinolines therapeutic use, Aminoquinolines administration & dosage, Plasmodium vivax drug effects
- Abstract
Background: Prevention of Plasmodium vivax malaria recurrence is essential for malaria elimination in Brazil. We evaluated the real-world effectiveness of an updated treatment algorithm for P vivax radical cure in the Brazilian Amazon., Methods: In this non-interventional observational study, we used retrospective data from the implementation of a P vivax treatment algorithm at 43 health facilities in Manaus and Porto Velho, Brazil. The treatment algorithm consisted of chloroquine (25 mg/kg over 3 days) and point-of-care quantitative glucose-6-phosphate dehydrogenase (G6PD) testing followed by single-dose tafenoquine 300 mg (G6PD normal, aged ≥16 years, not pregnant and not breastfeeding), 7-day primaquine 0·5 mg/kg per day (G6PD intermediate or normal, aged ≥6 months, not pregnant, and not breastfeeding or breastfeeding for >1 month), or primaquine 0·75 mg/kg per week for 8 weeks (G6PD deficient, aged ≥6 months, not pregnant, and not breastfeeding or breastfeeding for >1 month). P vivax recurrences were identified from probabilistic linkage of routine patient records from the Brazilian malaria epidemiological surveillance system. Recurrence-free effectiveness at day 90 and day 180 was estimated using Kaplan-Meier analysis and hazard ratios (HRs) by multivariate analysis. This clinical trial is registered with ClinicalTrials.gov, NCT05096702, and is completed., Findings: Records from Sept 9, 2021, to Aug 31, 2022, included 5554 patients with P vivax malaria. In all treated patients of any age and any G6PD status, recurrence-free effectiveness at day 180 was 75·8% (95% CI 74·0-77·6) with tafenoquine, 73·4% (71·9-75·0) with 7-day primaquine, and 82·1% (77·7-86·8) with weekly primaquine. In patients aged at least 16 years who were G6PD normal, recurrence-free effectiveness until day 90 was 88·6% (95% CI 87·2-89·9) in those who were treated with tafenoquine (n=2134) and 83·5% (79·8-87·4) in those treated with 7-day primaquine (n=370); after adjustment for confounding factors, the HR for recurrence following tafenoquine versus 7-day primaquine was 0·65 (95% CI 0·49-0·86; p=0·0031), with similar outcomes between the two treatments at day 180 (log-rank p=0·82). Over 180 days, median time to recurrence in patients aged at least 16 years who were G6PD normal was 92 days (IQR 76-120) in those treated with tafenoquine and 68 days (52-94) in those treated with 7-day primaquine., Interpretation: In this real-world setting, single-dose tafenoquine was more effective at preventing P vivax recurrence in patients aged at least 16 years who were G6PD normal compared with 7-day primaquine at day 90, while overall efficacy at 180 days was similar. The public health benefits of the P vivax radical cure treatment algorithm incorporating G6PD quantitative testing and tafenoquine support its implementation in Brazil and potentially across South America., Funding: Brazilian Ministry of Health, Municipal and State Health Secretariats; Fiocruz; Medicines for Malaria Venture; Bill & Melinda Gates Foundation; Newcrest Mining; and the UK Government., Translation: For the Portuguese translation of the abstract see Supplementary Materials section., Competing Interests: Declaration of interests SD, PGD, IB-F, and EJ are employees of Medicines for Malaria Venture. DBP declares grants from Butantan, PATH, and Janssen, payment for lectures or presentations from GSK, and support for attending meetings and travel from Janssen. All other authors declare no competing interests., (Copyright © 2024 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license. Published by Elsevier Ltd.. All rights reserved.)
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- 2024
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39. Optimal balance of benefit versus risk for tafenoquine in the treatment of Plasmodium vivax malaria.
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Sharma R, Sharma H, Jones S, Borghini-Fuhrer I, Domingo GJ, Gibson RA, Rolfe K, Tan L, Fiţa IG, Chen C, Bird P, Pingle A, and Duparc S
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- Humans, Primaquine administration & dosage, Primaquine therapeutic use, Primaquine adverse effects, Risk Assessment, Treatment Outcome, Drug Therapy, Combination, Plasmodium vivax drug effects, Chloroquine therapeutic use, Chloroquine adverse effects, Chloroquine administration & dosage, Malaria, Vivax drug therapy, Aminoquinolines administration & dosage, Aminoquinolines adverse effects, Aminoquinolines therapeutic use, Antimalarials therapeutic use, Antimalarials administration & dosage, Antimalarials adverse effects
- Abstract
A single 300 mg dose of tafenoquine (an 8-aminoquinoline), in combination with a standard 3-day course of chloroquine, is approved in several countries for the radical cure (prevention of relapse) of Plasmodium vivax malaria in patients aged ≥ 16 years. Despite this, questions have arisen on the optimal dose of tafenoquine. Before the availability of tafenoquine, a 3-day course of chloroquine in combination with the 8-aminoquinoline primaquine was the only effective radical cure for vivax malaria. The World Health Organization (WHO)-recommended standard regimen is 14 days of primaquine 0.25 mg/kg/day or 7 days of primaquine 0.5 mg/kg/day in most regions, or 14 days of primaquine 0.5 mg/kg/day in East Asia and Oceania, however the long treatment courses of 7 or 14 days may result in poor adherence and, therefore, low treatment efficacy. A single dose of tafenoquine 300 mg in combination with a 3-day course of chloroquine is an important advancement for the radical cure of vivax malaria in patients without glucose-6-phosphate dehydrogenase (G6PD) deficiency, as the use of a single-dose treatment will improve adherence. Selection of a single 300 mg dose of tafenoquine for the radical cure of P. vivax malaria was based on collective efficacy and safety data from 33 studies involving more than 4000 trial participants who received tafenoquine, including over 800 subjects who received the 300 mg single dose. The safety profile of single-dose tafenoquine 300 mg is similar to that of standard-dosage primaquine 0.25 mg/kg/day for 14 days. Both primaquine and tafenoquine can cause acute haemolytic anaemia in individuals with G6PD deficiency; severe haemolysis can lead to anaemia, kidney damage, and, in some cases, death. Therefore, relapse prevention using an 8-aminoquinoline must be balanced with the need to avoid clinical haemolysis associated with G6PD deficiency. To minimize this risk, the WHO recommends G6PD testing for all individuals before the administration of curative doses of 8-aminoquinolines. In this article, the authors review key efficacy and safety data from the pivotal trials of tafenoquine and argue that the currently approved dose represents a favourable benefit-risk profile., (© 2024. The Author(s).)
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- 2024
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40. Operational feasibility of Plasmodium vivax radical cure with tafenoquine or primaquine following point-of-care, quantitative glucose-6-phosphate dehydrogenase testing in the Brazilian Amazon: a real-life retrospective analysis.
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Brito M, Rufatto R, Murta F, Sampaio V, Balieiro P, Baía-Silva D, Castro V, Alves B, Alencar A, Duparc S, Grewal Daumerie P, Borghini-Fuhrer I, Jambert E, Peterka C, Edilson Lima F Jr, Carvalho Maia L, Lucena Cruz C, Maciele B, Vasconcelos M, Machado M, Augusto Figueira E, Alcirley Balieiro A, Menezes A, Ataídes R, Batista Pereira D, and Lacerda M
- Subjects
- Female, Humans, Pregnancy, Brazil, Feasibility Studies, Glucosephosphate Dehydrogenase analysis, Plasmodium vivax, Point-of-Care Systems, Primaquine therapeutic use, Retrospective Studies, Aminoquinolines, Antimalarials therapeutic use, Malaria, Vivax drug therapy
- Abstract
Background: To achieve malaria elimination, Brazil must implement Plasmodium vivax radical cure. We aimed to investigate the operational feasibility of point-of-care, quantitative, glucose-6-phosphate dehydrogenase (G6PD) testing followed by chloroquine plus tafenoquine or primaquine., Methods: This non-interventional, observational study was done at 43 health facilities in Manaus (Amazonas State) and Porto Velho (Rondônia State), Brazil, implementing a new P vivax treatment algorithm incorporating point-of-care quantitative G6PD testing to identify G6PD status and single-dose tafenoquine (G6PD normal, aged ≥16 years, and not pregnant or breastfeeding) or primaquine (intermediate or normal G6PD, aged ≥6 months, not pregnant, or breastfeeding >1 month). Following training of health-care providers, we collated routine patient records from the malaria epidemiological surveillance system (SIVEP-Malaria) retrospectively for all consenting patients aged at least 6 months with parasitologically confirmed P vivax malaria mono-infection or P vivax plus P falciparum mixed infection, presenting between Sept 9, 2021, and Aug 31, 2022. The primary endpoint was the proportion of patients aged at least 16 years with P vivax mono-infection treated or not treated appropriately with tafenoquine in accordance with their G6PD status. The trial is registered with ClinicalTrials.gov, NCT05096702, and is completed., Findings: Of 6075 patients enrolled, 6026 (99·2%) had P vivax mono-infection, 2685 (44·6%) of whom were administered tafenoquine. G6PD status was identified in 2685 (100%) of 2685 patients treated with tafenoquine. The proportion of patients aged at least 16 years with P vivax mono-infection who were treated or not treated appropriately with tafenoquine in accordance with their G6PD status was 99·7% (95% CI 99·4-99·8; 4664/4680)., Interpretation: Quantitative G6PD testing before tafenoquine administration was operationally feasible, with high adherence to the treatment algorithm, supporting deployment throughout the Brazilian health system., Funding: Brazilian Ministry of Health, Municipal and State Health Secretariats; Fiocruz; Medicines for Malaria Venture; Bill & Melinda Gates Foundation; Newcrest Mining; and the UK Government., Translation: For the Portuguese translation of the abstract see Supplementary Materials section., Competing Interests: Declaration of interests SD, PGD, IB-F, and EJ are employed by Medicines for Malaria Venture. All other authors declare no competing interests., (Copyright © 2024 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license. Published by Elsevier Ltd.. All rights reserved.)
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- 2024
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41. Safety and efficacy of pyronaridine-artesunate paediatric granules in the treatment of uncomplicated malaria in children: insights from randomized clinical trials and a real-world study.
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Ramharter M, Djimde AA, Borghini-Fuhrer I, Miller R, Shin J, Aspinall A, Richardson N, Wibberg M, Fleckenstein L, Arbe-Barnes S, and Duparc S
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- Child, Humans, Artemether, Lumefantrine Drug Combination therapeutic use, Artemether therapeutic use, Randomized Controlled Trials as Topic, Drug Combinations, Treatment Outcome, Vomiting chemically induced, Vomiting drug therapy, Ethanolamines therapeutic use, Antimalarials adverse effects, Artemisinins adverse effects, Malaria, Falciparum drug therapy, Malaria drug therapy, Artesunate, Naphthyridines
- Abstract
Background: Children are particularly at risk of malaria. This analysis consolidates the clinical data for pyronaridine-artesunate (PA) paediatric granules in children from three randomized clinical trials and a real-world study (CANTAM)., Methods: An integrated safety analysis of individual patient data from three randomized clinical trials included patients with microscopically-confirmed Plasmodium falciparum, body weight ≥ 5 kg to < 20 kg, who received at least one dose of study drug (paediatric safety population). PA was administered once daily for 3 days; two trials included the comparator artemether-lumefantrine (AL). PCR-adjusted day 28 adequate clinical and parasitological response (ACPR) was evaluated. Real-world PA granules safety and effectiveness was also considered., Results: In the integrated safety analysis, 63.9% (95% CI 60.2, 67.4; 426/667) of patients had adverse events following PA and 62.0% (95% CI 56.9, 66.9; 222/358) with AL. Vomiting was more common with PA (7.8% [95% CI 6.0, 10.1; 52/667]) than AL (3.4% [95% CI 1.9, 5.8; 12/358]), relative risk 2.3 (95% CI 1.3, 4.3; P = 0.004), occurring mainly following the first PA dose (6.7%, 45/667), without affecting re-dosing or adherence. Prolonged QT interval occurred less frequently with PA (3.1% [95% CI 2.1, 4.8; 21/667]) than AL (8.1% [95% CI 5.7, 11.4; 29/358]), relative risk 0.39 (95% CI 0.22, 0.67; P = 0.0007). In CANTAM, adverse events were reported for 17.7% (95% CI 16.3, 19.2; 460/2599) of patients, most commonly vomiting (5.4% [95% CI 4.6, 6.4; 141/2599]), mainly following the first dose, (4.5% [117/2599]), with all patients successfully re-dosed, and pyrexia (5.4% [95% CI 4.6, 6.3; 140/2599]). In the two comparative clinical trials, Day 28 ACPR in the per-protocol population for PA was 97.1% (95% CI 94.6, 98.6; 329/339) and 100% (95% CI 99.3, 100; 514/514) versus 98.8% (95% CI 95.7, 99.9; 165/167) and 98.4% (95% CI 95.5, 99.7; 188/191) for AL, respectively. In CANTAM, PA clinical effectiveness was 98.0% (95% CI 97.3, 98.5; 2273/2320)., Conclusions: Anti-malarial treatment with PA paediatric granules administered once daily for 3 days was well tolerated in children and displayed good clinical efficacy in clinical trials, with effectiveness confirmed in a real-world study. Trial registration Clinicaltrials.gov: SP-C-003-05: identifier NCT00331136; SP-C-007-07: identifier NCT0541385; SP-C-021-15: identifier NCT03201770. Pan African Clinical Trials Registry: SP-C-013-11: identifier PACTR201105000286876., (© 2024. The Author(s).)
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- 2024
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42. Community health workers in clinical research at the example of a phase IIIb/ IV antimalarial drug trial conducted in five African countries.
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Groger M, Lutete GT, Assi SB, Bigoga JD, Ntamabyaliro NY, Arbe-Barnes S, Shin J, Adegnika AA, Ntoumi F, Kremsner PG, Ramharter M, Duparc S, Borghini-Fuhrer I, and Mombo-Ngoma G
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- Child, Humans, Africa, Community Health Workers, Antimalarials therapeutic use, Malaria drug therapy, Malaria prevention & control, Malaria epidemiology
- Abstract
Global health, particularly in underserved settings can benefit immensely from well-trained community health workers (CHWs) supporting primary healthcare interventions. They can reduce morbidity and mortality of infectious diseases like malaria. Disease control programs can particularly benefit from a tight link between CHWs and communities and several studies have shown the benefit of the participation of non-facility-based CHWs in malaria control program activities for reducing malaria-related mortality in children. Because CHWs are often part of and trusted by served communities, they can also be an important resource to address challenges faced by their communities. Where post-marketing surveillance systems are underserved, they can relay important information about suspected safety signals and factors affecting therapeutic effectiveness in their communities. The CANTAM-Pyramax® trial was a phase IIIb/ IV cohort event monitoring study conducted at six centers in five African countries. To assess real-world effectiveness and safety of the anti-malarial pyronaridine-artesunate in 8560 malaria episodes, follow-up was not primarily conducted by medical staff but by specifically trained CHWs. This perspective paper discusses how the participation of a CHW workforce can be of benefit for effectiveness trials in limited-resource settings, using the example of the CANTAM-Pyramax trial., Competing Interests: Declarations of competing interest IBF and SD are full-time employees at Medicines for Malaria Venture, JS is a full-time employee at Shin-Poong Pharmaceutical and SAB is a consultant paid by Shin-Poong Pharmaceutical. The other authors declare no conflict of interest., (Copyright © 2023 The Authors. Published by Elsevier Ltd.. All rights reserved.)
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- 2023
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43. Tafenoquine co-administered with dihydroartemisinin-piperaquine for the radical cure of Plasmodium vivax malaria (INSPECTOR): a randomised, placebo-controlled, efficacy and safety study.
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Sutanto I, Soebandrio A, Ekawati LL, Chand K, Noviyanti R, Satyagraha AW, Subekti D, Santy YW, Crenna-Darusallam C, Instiaty I, Budiman W, Prasetya CB, Lardo S, Elyazar I, Duparc S, Cedar E, Rolfe K, Fernando D, Berni A, Jones S, Kleim JP, Fletcher K, Sharma H, Martin A, Taylor M, Goyal N, Green JA, Tan LK, and Baird JK
- Subjects
- Humans, Primaquine therapeutic use, Drug Therapy, Combination, Chloroquine therapeutic use, Plasmodium vivax, Malaria, Vivax drug therapy, Malaria, Vivax prevention & control, Antimalarials, Quinolines therapeutic use, Artemisinins adverse effects, Malaria drug therapy
- Abstract
Background: Tafenoquine, co-administered with chloroquine, is approved for the radical cure (prevention of relapse) of Plasmodium vivax malaria. In areas of chloroquine resistance, artemisinin-based combination therapies are used to treat malaria. This study aimed to evaluate tafenoquine plus the artemisinin-based combination therapy dihydroartemisinin-piperaquine for the radical cure of P vivax malaria., Methods: In this double-blind, double-dummy, parallel group study, glucose-6-phosphate dehydrogenase-normal Indonesian soldiers with microscopically confirmed P vivax malaria were randomly assigned by means of a computer-generated randomisation schedule (1:1:1) to dihydroartemisinin-piperaquine alone, dihydroartemisinin-piperaquine plus a masked single 300-mg dose of tafenoquine, or dihydroartemisinin-piperaquine plus 14 days of primaquine (15 mg). The primary endpoint was 6-month relapse-free efficacy following tafenoquine plus dihydroartemisinin-piperaquine versus dihydroartemisinin-piperaquine alone in all randomly assigned patients who received at least one dose of masked treatment and had microscopically confirmed P vivax at baseline (microbiological intention-to-treat population). Safety was a secondary outcome and the safety population comprised all patients who received at least one dose of masked medication. This study is registered with ClinicalTrials.gov, NCT02802501 and is completed., Findings: Between April 8, 2018, and Feb 4, 2019, of 164 patients screened for eligibility, 150 were randomly assigned (50 per treatment group). 6-month Kaplan-Meier relapse-free efficacy (microbiological intention to treat) was 11% (95% CI 4-22) in patients treated with dihydroartemisinin-piperaquine alone versus 21% (11-34) in patients treated with tafenoquine plus dihydroartemisinin-piperaquine (hazard ratio 0·44; 95% CI [0·29-0·69]) and 52% (37-65) in the primaquine plus dihydroartemisinin-piperaquine group. Adverse events over the first 28 days were reported in 27 (54%) of 50 patients treated with dihydroartemisinin-piperaquine alone, 29 (58%) of 50 patients treated with tafenoquine plus dihydroartemisinin-piperaquine, and 22 (44%) of 50 patients treated with primaquine plus dihydroartemisinin-piperaquine. Serious adverse events were reported in one (2%) of 50, two (4%) of 50, and two (4%) of 50 of patients, respectively., Interpretation: Although tafenoquine plus dihydroartemisinin-piperaquine was statistically superior to dihydroartemisinin-piperaquine alone for the radical cure of P vivax malaria, the benefit was not clinically meaningful. This contrasts with previous studies in which tafenoquine plus chloroquine was clinically superior to chloroquine alone for radical cure of P vivax malaria., Funding: ExxonMobil, Bill & Melinda Gates Foundation, Newcrest Mining, UK Government all through Medicines for Malaria Venture; and GSK., Translation: For the Indonesian translation of the abstract see Supplementary Materials section., Competing Interests: Declaration of interests IS reports grants or contracts from Menzies School of Health Research, Darwin and the National Health and Medical Research Council, and funding from Medicines for Malaria Venture (MMV) and GSK. AS, KC, RN, DS, YWS, II, WB, CBP, and SL report that they or their institutions received funding from MMV to do the study and editorial support from GSK for this publication. LLE and AWS report institutional funding from Menzies School of Health Research, MMV, and GSK. CC-D reports institutional funding from MMV, GSK, and the Chan Zuckerberg Initiative. IE reports institutional funding from MMV, GSK, WHO, SPARK (University of Melbourne), and honoraria from the Indonesian Ministry of Health. SD is an employee of MMV; his institution received funding from ExxonMobil, the Bill & Melinda Gates Foundation (grant number INV-007155/19-BMGF-006), Newcrest Mining, and the UK Government to fund the INSPECTOR study. EC is a former independent contractor at GSK and holds shares in the company. EC developed the first draft of the manuscript and provided editorial services as an independent medical writer funded by GSK. KR, DF, AB, SJ, KF, HS, AM, MT, and LKT are employees of GSK and hold shares in the company. J-PK, NG, and JAG are former employees of GSK and hold shares in GSK. JKB reports institutional research funding from MMV, GSK, the Wellcome Trust, the Gates Foundation, FIND, Sanaria, UKAid, University of Oxford, US Centers for Disease Control and Prevention, and the Chinese Center for Disease Control; travel and speaking fees from the Belgian Society of Tropical Medicine, the International Conference of Tropical Medicine and Malariology, and Singapore Malaria Group Conference; and participation on the US National Health Institute Data Safety Monitoring Board., (Copyright © 2023 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license. Published by Elsevier Ltd.. All rights reserved.)
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- 2023
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44. A pharmacometrics approach to assess the feasibility of capillary microsampling to replace venous sampling in clinical studies: Tafenoquine case study.
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Bachhav SS, Taylor M, Martin A, Green JA, Duparc S, Rolfe K, Sharma H, Tan LK, and Goyal N
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- Humans, Child, Feasibility Studies, Aminoquinolines pharmacokinetics, Biological Availability, Antimalarials pharmacokinetics
- Abstract
Aim: Microsampling has the advantage of smaller blood sampling volume and suitability in vulnerable populations compared to venous sampling in clinical pharmacokinetics studies. Current regulatory guidance requires correlative studies to enable microsampling as a technique. A post hoc population pharmacokinetic (POPPK) approach was utilized to investigate blood capillary microsampling as an alternative to venous sampling., Methods: Pharmacokinetic data from microsampling and venous sampling techniques during a paediatric study evaluating tafenoquine, a single-dose antimalarial for P. vivax, were used. Separate POPPK models were developed and validated based on goodness of fit and visual predictive checks, with pharmacokinetic data obtained via each sampling technique., Results: Each POPPK model adequately described tafenoquine pharmacokinetics using a two-compartment model with body weight based on allometric scaling of clearance and volume of distribution. Tafenoquine pharmacokinetic parameter estimates including clearance (3.4 vs 3.7 L/h) were comparable across models with slightly higher interindividual variability (38.3% vs 27%) in capillary microsampling-based data. A bioavailability/bioequivalence comparison demonstrated that the point estimate (90% CI) of capillary microsample versus venous sample model-based individual post hoc estimates for area under the concentration-time curve from time zero to infinity (AUC
0-inf ) (100.7%, 98.0-103.5%) and Cmax (79.7%, 76.9-82.5%) met the 80-125% and 70-143% criteria, respectively. Overall, both POPPK models led to the same dose regimen recommendations across weight bins based on achieving target AUC., Conclusions: This analysis demonstrated that a POPPK approach can be employed to assess the performance of alternative pharmacokinetic sampling techniques. This approach provides a robust solution in scenarios where variability in pharmacokinetic data collected via venous sampling and microsampling may not result in a strong linear relationship. The findings also established that microsampling techniques may replace conventional venous sampling methods., (© 2022 Medicines for Malaria Venture and GlaxoSmithKline Biologicals. British Journal of Clinical Pharmacology published by John Wiley & Sons Ltd on behalf of British Pharmacological Society.)- Published
- 2023
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45. Randomized, open-label, phase 2a study to evaluate the contribution of artefenomel to the clinical and parasiticidal activity of artefenomel plus ferroquine in African patients with uncomplicated Plasmodium falciparum malaria.
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Gansane A, Lingani M, Yeka A, Nahum A, Bouyou-Akotet M, Mombo-Ngoma G, Kaguthi G, Barceló C, Laurijssens B, Cantalloube C, Macintyre F, Djeriou E, Jessel A, Bejuit R, Demarest H, Marrast AC, Debe S, Tinto H, Kibuuka A, Nahum D, Mawili-Mboumba DP, Zoleko-Manego R, Mugenya I, Olewe F, Duparc S, and Ogutu B
- Subjects
- Humans, Plasmodium falciparum, Aminoquinolines therapeutic use, Treatment Outcome, Drug Combinations, Antimalarials pharmacology, Malaria, Falciparum drug therapy, Malaria, Falciparum parasitology
- Abstract
Background: The contribution of artefenomel to the clinical and parasiticidal activity of ferroquine and artefenomel in combination in uncomplicated Plasmodium falciparum malaria was investigated., Methods: This Phase 2a, randomized, open-label, parallel-group study was conducted from 11th September 2018 to 6th November 2019 across seven centres in Benin, Burkina Faso, Gabon, Kenya, and Uganda. Patients aged ≥ 14-69 years with microscopically confirmed infection (≥ 3000 to ≤ 50,000 parasites/µL blood) were randomized 1:1:1:1 to 400 mg ferroquine, or 400 mg ferroquine plus artefenomel 300, 600, or 1000 mg, administered as a single oral dose. The primary efficacy analysis was a logistic regression evaluating the contribution of artefenomel exposure to Day 28 PCR-adjusted adequate clinical and parasitological response (ACPR). Safety was also evaluated., Results: The randomized population included 140 patients. For the primary analysis in the pharmacokinetic/pharmacodynamic efficacy population (N = 121), the contribution of artefenomel AUC
0-∞ to Day 28 PCR-adjusted ACPR was not demonstrated when accounting for ferroquine AUC0-d28 , baseline parasitaemia, and other model covariates: odds ratio 1.1 (95% CI 0.98, 1.2; P = 0.245). In the per-protocol population, Day 28 PCR-adjusted ACPR was 80.8% (21/26; 95% CI 60.6, 93.4) with ferroquine alone and 90.3% (28/31; 95% CI 74.2, 98.0), 90.9% (30/33; 95% CI 75.7, 98.1) and 87.1% (27/31; 95% CI 70.2, 96.4) with 300, 600, and 1000 mg artefenomel, respectively. Median time to parasite clearance (Kaplan-Meier) was 56.1 h with ferroquine, more rapid with artefenomel, but similar for all doses (30.0 h). There were no deaths. Adverse events (AEs) of any cause occurred in 51.4% (18/35) of patients with ferroquine 400 mg alone, and 58.3% (21/36), 66.7% (24/36), and 72.7% (24/33) with 300, 600, and 1000 mg artefenomel, respectively. All AEs were of mild-to-moderate severity, and consistent with the known profiles of the compounds. Vomiting was the most reported AE. There were no cases of QTcF prolongation ≥ 500 ms or > 60 ms from baseline., Conclusion: The contribution of artefenomel exposure to the clinical and parasitological activity of ferroquine/artefenomel could not be demonstrated in this study. Parasite clearance was faster with ferroquine/artefenomel versus ferroquine alone. All treatments were well tolerated., Trial Registration: ClinicalTrials.gov, NCT03660839 (7 September, 2018)., (© 2023. The Author(s).)- Published
- 2023
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46. Plasmodium vivax in Children: Hidden Burden and Conspicuous Challenges, a Narrative Review.
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Drysdale M, Tan L, Martin A, Fuhrer IB, Duparc S, and Sharma H
- Abstract
There has been progress towards decreasing malaria prevalence globally; however, Plasmodium vivax has been less responsive to elimination efforts compared with Plasmodium falciparum. P. vivax malaria remains a serious public health concern in regions where it is the dominant species (South and South-East Asia, the Eastern Mediterranean region, and South America) and is increasingly recognized for its contribution to overall morbidity and mortality worldwide. The incidence of P. vivax decreases with increasing age owing to rapidly acquired clinical immunity and there is a disproportionate burden of P. vivax in infants and children, who remain highly vulnerable to severe disease, recurrence, and anemia with associated developmental impacts. Diagnosis is sometimes difficult owing to the sensitivity of diagnostic tests to detect low levels of parasitemia. Additionally, the propensity of P. vivax to relapse following reactivation of dormant hypnozoites in the liver contributes to disease recurrence in infants and children, and potentiates morbidity and transmission. The 8-aminoquinolines, primaquine and tafenoquine, provide radical cure (relapse prevention). However, the risk of hemolysis in patients with glucose-6-phosphate dehydrogenase (G6PD) deficiency necessitates testing prior to administration of 8-aminoquinolines, which has limited their uptake. Additional challenges include lack of availability of pediatric dose formulations and problems with adherence to primaquine owing to the length of treatment recommended. A paucity of data and studies specific to pediatric P. vivax malaria impacts the ability to deliver targeted interventions. It is imperative that P. vivax in infants and children be the focus of future research, control initiatives, and anti-malarial drug development., (© 2022. The Author(s).)
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- 2023
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47. Efficacy, Safety, Tolerability, and Pharmacokinetics of MMV390048 in Acute Uncomplicated Malaria.
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Mohammed R, Asres MS, Gudina EK, Adissu W, Johnstone H, Marrast AC, Donini C, Duparc S, and Yilma D
- Subjects
- Adult, Humans, Male, Plasmodium falciparum, Antimalarials adverse effects, Malaria drug therapy, Malaria, Falciparum drug therapy, Malaria, Falciparum parasitology, Malaria, Vivax drug therapy, Malaria, Vivax parasitology
- Abstract
An open label, phase IIa study conducted in Ethiopia evaluated the efficacy, safety, tolerability, and pharmacokinetics of a single 120-mg dose of the phosphatidylinositol 4-kinase inhibitor MMV390048 in Plasmodium vivax malaria. The study was not completed for operational reasons and emerging teratotoxicity data. For the eight adult male patients enrolled, adequate clinical and parasitological response at day 14 (primary endpoint) was 100% (8/8). Asexual parasites and gametocytes were cleared in all patients by 66 and 78 hours postdose, respectively. There were two recurrent P. vivax infections (days 20 and 28) and a new Plasmodium falciparum infection (day 22). MMV390048 exposure in P. vivax patients was lower than previously observed for healthy volunteers. Mild adverse events, mainly headache and gastrointestinal symptoms, were reported by eight patients. Single-dose MMV390048 (120 mg) rapidly cleared asexual parasites and gametocytes in patients with P. vivax malaria and was well tolerated.
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- 2022
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48. Safety and efficacy of four drug regimens versus standard-of-care for the treatment of symptomatic outpatients with COVID-19: A randomised, open-label, multi-arm, phase 2 clinical trial.
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Chandiwana N, Kruger C, Johnstone H, Chughlay MF, Ju C, Kim B, Dineka Y, Arbe-Barnes S, Miller R, Owen A, Hill A, Windgassen D, Abla N, Marrast AC, Duparc S, and Francois Venter WD
- Subjects
- Humans, Adult, SARS-CoV-2, Outpatients, Thiazoles, Treatment Outcome, COVID-19
- Abstract
Background: This exploratory study investigated four repurposed anti-infective drug regimens in outpatients with COVID-19., Methods: This phase 2, single centre, randomised, open-label, clinical trial was conducted in South Africa between 3rd September 2020 and 23rd August 2021. Symptomatic outpatients aged 18-65 years, with RT-PCR confirmed SARS-CoV-2 infection were computer randomised (1:1:1:1:1) to standard-of-care (SOC) with paracetamol, or SOC plus artesunate-amodiaquine (ASAQ), pyronaridine-artesunate (PA), favipiravir plus nitazoxanide (FPV + NTZ), or sofosbuvir-daclatasvir (SOF-DCV). The primary endpoint was the incidence of viral clearance, i.e., the proportion of patients with a negative SARS-CoV-2 RT-PCR on day 7, compared to SOC using a log-binomial model in the modified intention-to-treat (mITT) population., Findings: The mITT population included 186 patients: mean age (SD) 34.9 (10.3) years, body weight 78.2 (17.1) kg. Day 7 SARS-CoV-2 clearance rates (n/N; risk ratio [95% CI]) were: SOC 34.2% (13/38), ASAQ 38.5% (15/39; 0.80 [0.44, 1.47]), PA 30.3% (10/33; 0.69 [0.37, 1.29]), FPV + NTZ 27.0% (10/37; 0.60 [0.31, 1.18]) and SOF-DCV 23.5% (8/34; 0.47 [0.22, 1.00]). Three lower respiratory tract infections occurred (PA 6.1% [2/33]; SOF-DCV 2.9% [1/34]); two required hospitalisation (PA, SOF-DCV). There were no deaths. Adverse events occurred in 55.3% (105/190) of patients, including one serious adverse event (pancytopenia; FPV + NTZ)., Interpretation: There was no statistical difference in viral clearance for any regimen compared to SOC. All treatments were well tolerated., Funding: Medicines for Malaria Venture, with funding from the UK Foreign, Commonwealth and Development Office, within the Covid-19 Therapeutics Accelerator in partnership with Wellcome, the Bill and Melinda Gates Foundation, and Mastercard., Competing Interests: Declaration of interests NC declares grants and non-financial support from Shin Poong Pharm. Co. Ltd. during the conduct of the study and grants and non-financial support from ViiV Healthcare and Gilead Sciences, grants, personal fees and non-financial support from Johnson & Johnson, personal fees from Cipla and Frontiers Biotech outside the submitted work. NA, ACM, and SD are employees of Medicines for Malaria Venture. MFC is a former employee of Medicines for Malaria Venture. HJ is a consultant for Medicines for Malaria Venture and was a consultant medical monitor for this study. CJ and BK are employees of Shin Poong Pharm. Co. Ltd. CJ has a patent pharmaceutical composition for COVID-19 treatment pending. SA-B and RM are employees of Artemida Pharma which received funding from Shin Poong Pharm. Co. Ltd. RM consulted for Shin Poong Pharm. Co Ltd. and is the Shin Poong Pharm. Co. Ltd. qualified person for pharmacovigilance, responsible for providing interpretation of the safety data of this study and other studies involving pyronaridine-artesunate. SA-B consulted for Shin Poong Pharm. Co. Ltd. during the study for the operational aspects and in particular all activities related to the Data Monitoring Committee. AO is a director of Tandem Nano Ltd., co-inventor of patents relating to drug delivery, and has received grants and consultancy from AstraZeneca and Janssen, and grants and personal fees from Merck, ViiV healthcare, and Gilead outside of the submitted work. AH received a research grant from the funders for advice on statistical design and analysis during the conduct of the study. DW is an employee of DATAMAP. WDFV reports grants from Unitaid during the conduct of the study; grants from the Bill and Melinda Gates Foundation, the South African Medical Research Council, USAID, National Institutes of Health, FIND, Children's Investment Fund Foundation, personal fees from Virology Education, grants, personal fees and non-financial support from ViiV Healthcare, personal fees and non-financial support from Gilead Healthcare, grants, personal fees and non-financial support from MSD, grants, personal fees and non-financial support from Johnson & Johnson, and personal fees from Mylan/Viatris, Adcock-Ingram, Aspen, Abbott, Roche, and Sanofi outside the submitted work. CK and YD declare no competing interests., (Copyright © 2022 The Authors. Published by Elsevier B.V. All rights reserved.)
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- 2022
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49. Effectiveness of pyronaridine-artesunate against Plasmodium malariae, Plasmodium ovale spp, and mixed-Plasmodium infections: a post-hoc analysis of the CANTAM-Pyramax trial.
- Author
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Groger M, Tona Lutete G, Mombo-Ngoma G, Ntamabyaliro NY, Kahunu Mesia G, Muena Mujobu TB, Dimessa Mbadinga LB, Zoleko Manego R, Egger-Adam D, Borghini-Fuhrer I, Shin J, Miller R, Arbe-Barnes S, Duparc S, and Ramharter M
- Subjects
- Artesunate, Drug Combinations, Humans, Naphthyridines, Plasmodium malariae, Malaria drug therapy, Plasmodium ovale genetics
- Abstract
Background: High-quality evidence for the therapeutic efficacy and effectiveness of antimalarials for infections caused by Plasmodium malariae, Plasmodium ovale spp, and mixed-Plasmodium infections is scarce. In this study, we aimed to analyse the efficacy of pyronaridine-artesunate for the treatment of non-falciparum and mixed-species Plasmodium infections from a large phase 3b/4 clinical trial in central Africa., Methods: This post-hoc analysis was done in a random subset of samples from two sites (in the Democratic Republic of the Congo and in Gabon) of the CANTAM-Pyramax trial assessing pyronaridine-artesunate therapy. We randomly selected paired dried blood spot samples from day 0 and day 28 (or unforeseen visit) and analysed them by quantitative PCR for mixed Plasmodium infections or non-falciparum mono-infections. Day 28 (or unforeseen visit) samples positive for non-falciparum malaria were re-assessed by microscopy to identify microscopic versus submicroscopic infections. Analyses were done on two sample sets: a per-protocol set and an intention-to-treat set., Findings: Among 1502 randomly selected samples, 192 (12·8%) showed mixed-Plasmodium infections or non-falciparum mono-infections. We did not detect P vivax in the samples. For both the per-protocol and intention-to-treat sets, the overall day 28 cure rates for P malariae, P ovale curtisi, and P ovale wallikeri were 96·3% or higher (95% CIs from 81·0-99·9 to 95·7-100). Cure rates were consistently high in P malariae (99·2%, 95·7-100) and P ovale spp (97·9%, 88·7-99·9, for P ovale curtisi and 96·3%, 81·0-99·9, for P ovale wallikeri) infections., Interpretation: This post-hoc analysis provides important evidence supporting the high efficacy of pyronaridine-artesunate against mono-infections with P malariae, P ovale curtisi, or P ovale wallikeri and mixed-Plasmodium infections in a real-world setting., Funding: Medicines for Malaria Venture., Competing Interests: Declaration of interests IB-F and SD are full-time employees of Medicines for Malaria Venture (MMV). JS is a full-time employee of Shin-Poong Pharmaceutical. RM and SA-B are consultants paid by Shin-Poong Pharmaceutical. All other authors declare no competing interests., (Copyright © 2022 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license. Published by Elsevier Ltd.. All rights reserved.)
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- 2022
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50. Impact of the malaria comprehensive case management programme in Odisha, India.
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Pradhan MM, Pradhan S, Dutta A, Shah NK, Valecha N, Joshi PL, Pradhan K, Grewal Daumerie P, Banerji J, Duparc S, Mendis K, Sharma SK, Murugasampillay S, and Anvikar AR
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- Data Collection, Humans, Incidence, India epidemiology, Interrupted Time Series Analysis, Case Management, Malaria diagnosis, Malaria epidemiology, Malaria prevention & control
- Abstract
Background: The Comprehensive Case Management Project (CCMP), was a collaborative implementation research initiative to strengthen malaria early detection and complete treatment in Odisha State, India., Methods: A two-arm quasi-experimental design was deployed across four districts in Odisha, representing a range of malaria endemicity: Bolangir (low), Dhenkanal (moderate), Angul (high), and Kandhamal (hyper). In each district, a control block received routine malaria control measures, whereas a CCMP block received a range of interventions to intensify surveillance, diagnosis, and case management. Impact was evaluated by difference-in-difference (DID) analysis and interrupted time-series (ITS) analysis of monthly blood examination rate (MBER) and monthly parasite index (MPI) over three phases: phase 1 pre-CCMP (2009-2012) phase 2 CCMP intervention (2013-2015), and phase 3 post-CCMP (2016-2017)., Results: During CCMP implementation, adjusting for control blocks, DID and ITS analysis indicated a 25% increase in MBER and a 96% increase in MPI, followed by a -47% decline in MPI post-CCMP, though MBER was maintained. Level changes in MPI between phases 1 and 2 were most marked in Dhenkanal and Angul with increases of 976% and 287%, respectively, but declines in Bolangir (-57%) and Kandhamal (-22%). Between phase 2 and phase 3, despite the MBER remaining relatively constant, substantial decreases in MPI were observed in Dhenkanal (-78%), and Angul (-59%), with a more modest decline in Bolangir (-13%), and an increase in Kandhamal (14%)., Conclusions: Overall, CCMP improved malaria early detection and treatment through the enhancement of the existing network of malaria services which positively impacted case incidence in three districts. In Kandhamal, which is hyperendemic, the impact was not evident. However, in Dhenkanal and Angul, areas of moderate-to-high malaria endemicity, CCMP interventions precipitated a dramatic increase in case detection and a subsequent decline in malaria incidence, particularly in previously difficult-to-reach communities., Competing Interests: The authors have declared that no competing interests exist.
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- 2022
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