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3. Fabrication and Test of a 400 kW-Class Fully Superconducting Synchronous Motor Using REBCO Tape for an Electric Propulsion System

Author

Miyazaki, H., Iwakuma, M., Emori, Y., Sasa, H., Yoshida, K., Sato, S., Miura, S., Sagara, I., Suzuki, Y., Konno, M., Hirai, H., and Izumi, T.

Abstract

Advanced electric propulsion systems have been developed by utilizing superconducting technologies to reduce carbon dioxide emissions from aircraft. This study presents the progress in the development of a 400 kW-class fully superconducting synchronous motor using REBa2Cu3O7−δ (REBCO) tape. REBCO tapes have high critical current densities; thus, they can generate a strong magnetic field without an iron core, permitting the fabrication of small-sized motors compared with conventional motors that use copper wires and iron cores. The 400 kW-class fully superconducting synchronous motor comprises field and armature coils. The field coil was wound with cos-theta-like racetrack distribution to generate a dipole field without an iron core. The maximum magnetic field is 1.45 T when the operating current is 110 A DC. The armature coil comprises six racetrack-shaped pancakes wound with six-strand parallel conductors. The parallel conductors were transposed inside the windings, resulting in a uniform current distribution in each conductor. The motor utilized carbon fiber-reinforced plastic (CFRP) for the casing instead of stainless steel for weight reduction. Foam insulation was adopted to further reduce the mass, in which an adiabatic material was wrapped around the external part of the CFRP casing. The armature coil was cooled using sub-cooled liquid nitrogen (LN2), with high electrical insulation and a stable liquid phase. In contrast, the field coil was cooled by utilizing helium gas instead of LN2 because sealing the LN2 with a magnetic fluid seal is challenging. The motor was tested in a synchronous generator mode and subsequently rotated by utilizing three bipolar power supplies. The motor successfully rotated at 441 rpm when the field current was 72 A, the armature current was 103 Arms, and the frequency was 7.35 Hz.

Published
2024
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4. Sporozoite immunization: innovative translational science to support the fight against malaria.

Author

Richie, T.L., Church, L.W., Murshedkar, T., Billingsley, P.F., James, E.R., Chen, M.C.C., Abebe, Y., Natasha, K.C., Chakravarty, S., Dolberg, D., Healy, Sara A., Diawara, H., Sissoko, M.S., Sagara, I., Cook, D.M., Epstein, J.E., Mordmüller, B., Kapulu, M., Kreidenweiss, A., Franke-Fayard, B., Agnandji, S.T., López Mikue, M.A., McCall, M.B.B., Steinhardt, L., Oneko, M., Olotu, A., Vaughan, A.M., Kublin, J.G., Murphy, S.C., Jongo, S., Tanner, M., Sirima, S.B., Laurens, M.B., Daubenberger, C., Silva, J.C., Lyke, K.E., Janse, C.J., Roestenberg, M., Sauerwein, R.W., Abdulla, S., Dicko, A., Kappe, S.H., Sim, B.K., Duffy, P.E., Kremsner, P.G., Hoffman, S.L., Richie, T.L., Church, L.W., Murshedkar, T., Billingsley, P.F., James, E.R., Chen, M.C.C., Abebe, Y., Natasha, K.C., Chakravarty, S., Dolberg, D., Healy, Sara A., Diawara, H., Sissoko, M.S., Sagara, I., Cook, D.M., Epstein, J.E., Mordmüller, B., Kapulu, M., Kreidenweiss, A., Franke-Fayard, B., Agnandji, S.T., López Mikue, M.A., McCall, M.B.B., Steinhardt, L., Oneko, M., Olotu, A., Vaughan, A.M., Kublin, J.G., Murphy, S.C., Jongo, S., Tanner, M., Sirima, S.B., Laurens, M.B., Daubenberger, C., Silva, J.C., Lyke, K.E., Janse, C.J., Roestenberg, M., Sauerwein, R.W., Abdulla, S., Dicko, A., Kappe, S.H., Sim, B.K., Duffy, P.E., Kremsner, P.G., and Hoffman, S.L.

Abstract

Contains fulltext : 300223.pdf (Publisher’s version ) (Open Access), INTRODUCTION: Malaria, a devastating febrile illness caused by protozoan parasites, sickened 247,000,000 people in 2021 and killed 619,000, mostly children and pregnant women in sub-Saharan Africa. A highly effective vaccine is urgently needed, especially for Plasmodium falciparum (Pf), the deadliest human malaria parasite. AREAS COVERED: Sporozoites (SPZ), the parasite stage transmitted by Anopheles mosquitoes to humans, are the only vaccine immunogen achieving >90% efficacy against Pf infection. This review describes >30 clinical trials of PfSPZ vaccines in the U.S.A., Europe, Africa, and Asia, based on first-hand knowledge of the trials and PubMed searches of 'sporozoites,' 'malaria,' and 'vaccines.' EXPERT OPINION: First generation (radiation-attenuated) PfSPZ vaccines are safe, well tolerated, 80-100% efficacious against homologous controlled human malaria infection (CHMI) and provide 18-19 months protection without boosting in Africa. Second generation chemo-attenuated PfSPZ are more potent, 100% efficacious against stringent heterologous (variant strain) CHMI, but require a co-administered drug, raising safety concerns. Third generation, late liver stage-arresting, replication competent (LARC), genetically-attenuated PfSPZ are expected to be both safe and highly efficacious. Overall, PfSPZ vaccines meet safety, tolerability, and efficacy requirements for protecting pregnant women and travelers exposed to Pf in Africa, with licensure for these populations possible within 5 years. Protecting children and mass vaccination programs to block transmission and eliminate malaria are long-term objectives.

Published
2023

9. Mathematical modelling of a seasonal use-case for the RTS,S/AS01 malaria vaccine

Author

Thompson, H, Hogan, A, Walker, P, Winskill, P, Zongo, I, Sagara, I, Tinto, H, Ouedraogo, J-B, Dicko, A, Chandramohan, D, Greenwood, B, Cairns, M, Ghani, A, Medical Research Council (MRC), and Imperial College LOndon

Subjects
0605 Microbiology, 1117 Public Health and Health Services
Abstract

Background: A recent clinical trial of seasonal RTS,S/AS01E (RTS,S) vaccination showed that vaccination was non-inferior to seasonal malaria chemoprevention (SMC) in preventing clinical malaria. The combination of these two interventions provided significant additional protection against clinical and severe malaria outcomes. Impact projections of this novel approach to RTS,S vaccination in seasonal transmission settings for longer time frames and across a range of epidemiological settings are needed to inform policy recommendations. Methods: We used a mathematical model of malaria transmission to assess the potential impact of an age-based or seasonally targeted RTS,S vaccination schedule in seasonal transmission settings in both the absence and presence of SMC. Estimates of cases and deaths averted in a population of 100,000 children aged 0-5 years were calculated over a 15-year time horizon for a range of levels of Plasmodium falciparum parasite prevalence in 2–10-year-olds and over two West African seasonality archetypes. Findings: Seasonally targeting RTS,S resulted in greater absolute reductions in malaria cases and deaths compared to an age-based strategy, averting between 32%-100% more clinical cases dependent on seasonality and transmission intensity. We predict that adding seasonally targeted RTS,S to SMC would reduce clinical incidence by up to an additional 36%-56% in children under five compared with SMC alone. Transmission season duration was a key determinant of intervention impact, with the advantage of adding RTS,S to SMC predicted to be smaller with shorter transmission seasons. Interpretation: RTS,S vaccination in seasonal settings could be a valuable additional tool to existing interventions, with seasonal delivery maximising impact relative to an age-based approach. Decisions surrounding deployment strategies of RTS,S in such settings will need to consider the local and regional variations in seasonality, current levels of other interventions and potential achievable RTS,S coverage. Funding: UK Medical Research Council, UK Foreign Commonwealth & Development Office, The Wellcome Trust and The Royal society.

Published
2022

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

Author

Abdulla, 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)

Subjects
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
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18. Abstracts of the Eighth EDCTP Forum, 6-9 November 2016.

Author

Makanga, M, Beattie, P, Breugelmans, G, Nyirenda, T, Bockarie, M, Tanner, M, Volmink, J, Hankins, C, Walzl, G, Chegou, N, Malherbe, S, Hatherill, M, Scriba, TJ, Zak, DE, Barry, CE, Kaufmann, SHE, Noor, A, Strub-Wourgaft, N, Phillips, P, Munguambe, K, Ravinetto, R, Tinto, H, Diro, E, Mahendrahata, Y, Okebe, J, Rijal, S, Garcia, C, Sundar, S, Ndayisaba, G, Sopheak, T, Ngoduc, T, Van Loen, H, Jacobs, J, D'Alessandro, U, Boelaert, M, Buvé, A, Kamalo, P, Manda-Taylor, L, Rennie, S, Mokgatla, B, Bahati, Ijsselmuiden, C, Afolabi, M, Mcgrath, N, Kampmann, B, Imoukhuede, E, Alexander, N, Larson, H, Chandramohan, D, Bojang, K, Kasaro, MP, Muluka, B, Kaunda, K, Morse, J, Westfall, A, Kapata, N, Kruuner, A, Henostroza, G, Reid, S, Alabi, A, Foguim, F, Sankarganesh, J, Bruske, E, Mfoumbi, A, Mevyann, C, Adegnika, A, Lell, B, Kranzer, K, Kremsner, P, Grobusch, M, Sabiiti, W, Ntinginya, N, Kuchaka, D, Azam, K, Kampira, E, Mtafya, B, Bowness, R, Bhatt, N, Davies, G, Kibiki, G, Gillespie, S, Lejon, V, Ilboudo, H, Mumba, D, Camara, M, Kaba, D, Lumbala, C, Fèvre, E, Jamonneau, V, Bucheton, B, Büscher, P, Chisenga, C, Sinkala, E, Chilengi, R, Chitundu, H, Zyambo, Z, Wandeler, G, Vinikoor, M, Emilie, D, Camara, O, Mathurin, K, Guiguigbaza-Kossigan, D, Philippe, B, Regassa, F, Hassane, S, Bienvenu, SM, Fabrice, C, Ouédraogo, E, Kouakou, L, Owusu, M, Mensah, E, Enimil, A, Mutocheluh, M, Ndongo, FA, Tejiokem, MC, Texier, G, Penda, C, Ndiang, S, Ndongo, J-A, Guemkam, G, Sofeu, CL, Afumbom, K, Faye, A, Msellati, P, Warszawski, J, Vos, A, Devillé, W, Barth, R, Klipstein-Grobusch, K, Tempelman, H, Venter, F, Coutinho, R, Grobbee, D, Ssemwanga, D, Lyagoba, F, Magambo, B, Kapaata, A, Kirangwa, J, Nannyonjo, M, Nassolo, F, Nsubuga, R, Yebra, G, Brown, A, Kaleebu, P, Nylén, H, Habtewold, A, Makonnen, E, Yimer, G, Burhenne, J, Diczfalusy, U, Aklillu, E, Steele, D, Walker, R, Simuyandi, M, Beres, L, Bosomprah, S, Ansumana, R, Taitt, C, Lamin, JM, Jacobsen, KH, Mulvaney, SP, Leski, T, Bangura, U, Stenger, D, De Vries, S, Zinsou, FJ, Honkpehedji, J, Dejon, JC, Loembe, MM, Bache, B, Pakker, N, Van Leeuwen, R, Hounkpatin, AB, Yazdanbakhsh, M, Bethony, J, Hotez, P, Diemert, D, Bache, BE, Fernandes, JF, Obiang, RM, Kabwende, AL, Grobusch, MP, Krishna, S, Kremsner, PG, Todagbe, AS, Nambozi, M, Kabuya, J-B, Hachizovu, S, Mwakazanga, D, Kasongo, W, Buyze, J, Mulenga, M, Geertruyden, J-P, Gitaka, J, Chan, C, Kongere, J, Kagaya, W, Kaneko, A, Kabore, N, Barry, N, Kabre, Z, Werme, K, Fofana, A, Compaore, D, Nikiema, F, Some, F, Djimde, A, Zongo, I, Ouedraogo, B, Kone, A, Sagara, I, Björkman, A, Gil, JP, Nchinda, G, Bopda, A, Nji, N, Ambada, G, Ngu, L, Tchadji, J, Sake, C, Magagoum, S, Njambe, GD, Lisom, A, Park, CG, Tait, D, Sibusiso, H, Manda, O, Croucher, K, Van Der Westhuizen, A, Mshanga, I, Levin, J, Nanvubya, A, Kibengo, F, Jaoko, W, Pala, P, Perreau, M, Namuniina, A, Kitandwe, P, Tapia, G, Serwanga, J, Yates, N, Fast, P, Mayer, B, Montefiori, D, Tomaras, G, Robb, M, Lee, C, Wagner, R, Sanders, E, Kilembe, W, Kiwanuka, N, Gilmour, J, Kuipers, H, Vooij, D, Chinyenze, K, Priddy, F, Ding, S, Hanke, T, Pantaleo, G, Ngasala, B, Jovel, I, Malmberg, M, Mmbando, B, Premji, Z, Mårtensson, A, Mwaiswelo, R, Agbor, L, Apinjoh, T, Mwanza, S, Chileshe, J, Joshi, S, Malunga, P, Manyando, C, Laufer, M, Dara, A, Niangaly, A, Sinha, I, Brodin, D, Fofana, B, Dama, S, Dembele, D, Sidibe, B, Diallo, N, Thera, M, Wright, K, Gil, J, Doumbo, O, Baraka, V, Nabasumba, C, Francis, F, Lutumba, P, Mavoko, H, Alifrangis, M, Van Geertruyden, J-P, Sissoko, S, Sangaré, C, Toure, S, Sanogo, K, Diakite, H, Doumbia, D, Haidara, K, Julé, A, Ashurst, H, Merson, L, Olliaro, P, Marsh, V, Lang, T, Guérin, P, Awuondo, K, Njenga, D, Nyakarungu, E, Titus, P, Sutamihardja, A, Lowe, B, Ogutu, B, Billingsley, P, Soulama, I, Kaboré, M, Coulibaly, A, Ouattara, M, Sanon, S, Diarra, A, Bougouma, E, Ouedraogo, A, Sombie, B, Kargougou, D, Ouattara, D, Issa, N, Tiono, A, Sirima, S, Chaponda, M, Dabira, E, Dao, F, Dara, N, Coulibaly, M, Tolo, A, Maiga, H, Ouologuem, N, Niangaly, H, Botchway, F, Wilson, N, Dickinson-Copeland, CM, Adjei, AA, Wilson, M, Stiles, JK, Hamid, MA, Awad-Elgeid, M, Nasr, A, Netongo, P, Kamdem, S, Velavan, T, Lasry, E, Diarra, M, Bamadio, A, Traore, A, Coumare, S, Soma, B, Dicko, Y, Sangare, B, Tembely, A, Traore, D, Haidara, A, Dicko, A, Diawara, E, Beavogui, A, Camara, D, Sylla, M, Yattara, M, Sow, A, Camara, GC, Diallo, S, Mombo-Ngoma, G, Remppis, J, Sievers, M, Manego, RZ, Endamne, L, Hutchinson, D, Held, J, Supan, C, Salazar, CLO, Bonkian, LN, Nahum, A, Sié, A, Abdulla, S, Cantalloube, C, Djeriou, E, Bouyou-Akotet, M, Mordmüller, B, Siribie, M, Sirima, SB, Ouattara, SM, Coulibaly, S, Kabore, JM, Amidou, D, Tekete, M, Traore, O, Haefeli, W, Borrmann, S, Kaboré, N, Kabré, Z, Nikèma, F, Compaoré, D, Somé, F, Djimdé, A, Ouédraogo, J, Chalwe, V, Miller, J, Diakité, H, Greco, B, Spangenberg, T, Kourany-Lefoll, E, Oeuvray, C, Mulry, J, Tyagarajan, K, Magsaam, B, Barnes, K, Hodel, EM, Humphreys, G, Pace, C, Banda, CG, Denti, P, Allen, E, Lalloo, D, Mwapasa, V, Terlouw, A, Mwesigwa, J, Achan, J, Jawara, M, Ditanna, G, Worwui, A, Affara, M, Koukouikila-Koussounda, F, Kombo, M, Vouvoungui, C, Ntoumi, F, Etoka-Beka, MK, Deibert, J, Poulain, P, Kobawila, S, Gueye, NG, Seda, B, Kwambai, T, Jangu, P, Samuels, A, Kuile, FT, Kariuki, S, Barry, A, Bousema, T, Okech, B, Egwang, T, Corran, P, Riley, E, Ezennia, I, Ekwunife, O, Muleba, M, Stevenson, J, Mbata, K, Coetzee, M, Norris, D, Moneke-Anyanwoke, N, Momodou, J, Clarke, E, Scott, S, Tijani, A, Djimde, M, Vaillant, M, Samouda, H, Mensah, V, Roetynck, S, Kanteh, E, Bowyer, G, Ndaw, A, Oko, F, Bliss, C, Jagne, YJ, Cortese, R, Nicosia, A, Roberts, R, D'Alessio, F, Leroy, O, Faye, B, Cisse, B, Gerry, S, Viebig, N, Lawrie, A, Ewer, K, Hill, A, Nebie, I, Tiono, AB, Sanou, G, Konate, AT, Yaro, BJ, Sodiomon, S, Honkpehedji, Y, Agobe, JCD, Zinsou, F, Mengue, J, Richie, T, Hoffman, S, Nouatin, O, Ngoa, UA, Edoa, JR, Homoet, A, Engelhon, JE, Massinga-Louembe, M, Esen, M, Theisen, M, Sim, KL, Luty, AJ, Moutairou, K, Dinko, B, King, E, Targett, G, Sutherland, C, Likhovole, C, Ouma, C, Vulule, J, Musau, S, Khayumbi, J, Okumu, A, Murithi, W, Otu, J, Gehre, F, Zingue, D, Kudzawu, S, Forson, A, Mane, M, Rabna, P, Diarra, B, Kayede, S, Adebiyi, E, Kehinde, A, Onyejepu, N, Onubogu, C, Idigbe, E, Ba, A, Diallo, A, Mboup, S, Disse, K, Kadanga, G, Dagnra, Y, Baldeh, I, Corrah, T, De Jong, B, Antonio, M, Musanabaganwa, C, Musabyimana, JP, Karita, E, Diop, B, Nambajimana, A, Dushimiyimana, V, Karame, P, Russell, J, Ndoli, J, Hategekimana, T, Sendegeya, A, Condo, J, Binagwaho, A, Okonko, I, Okerentugba, P, Opaleye, O, Awujo, E, Frank-Peterside, N, Moyo, S, Kotokwe, K, Mohammed, T, Boleo, C, Mupfumi, L, Chishala, S, Gaseitsiwe, S, Tsalaile, L, Bussmann, H, Makhema, J, Baum, M, Marlink, R, Engelbretch, S, Essex, M, Novitsky, V, Saka, E, Kalipalire, Z, Bhairavabhotla, R, Midiani, D, Sherman, J, Mgode, G, Cox, C, Bwana, D, 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Nambajimana, A, Dushimiyimana, V, Karame, P, Russell, J, Ndoli, J, Hategekimana, T, Sendegeya, A, Condo, J, Binagwaho, A, Okonko, I, Okerentugba, P, Opaleye, O, Awujo, E, Frank-Peterside, N, Moyo, S, Kotokwe, K, Mohammed, T, Boleo, C, Mupfumi, L, Chishala, S, Gaseitsiwe, S, Tsalaile, L, Bussmann, H, Makhema, J, Baum, M, Marlink, R, Engelbretch, S, Essex, M, Novitsky, V, Saka, E, Kalipalire, Z, Bhairavabhotla, R, Midiani, D, Sherman, J, Mgode, G, Cox, C, Bwana, D, Mtui, L, Magesa, D, Kahwa, A, Mfinanga, G, Mulder, C, Borain, N, Petersen, L, Du Plessis, J, Theron, G, Holm-Hansen, C, Tekwu, EM, Sidze, LK, Assam, JPA, Eyangoh, S, Niemann, S, Beng, VP, Frank, M, Atiadeve, S, Hilmann, D, Awoniyi, D, Baumann, R, Kriel, B, Jacobs, R, Kidd, M, Loxton, A, Kaempfer, S, Singh, M, Mwanza, W, Milimo, D, Moyo, M, Kasese, N, Cheeba-Lengwe, M, Munkondya, S, Ayles, H, De Haas, P, Muyoyeta, M, Namuganga, AR, Kizza, HM, Mendy, A, Tientcheu, L, Ayorinde, A, Coker, E, Egere, U, Coussens, A, Naude, C, Chaplin, G, Noursadeghi, M, Martineau, A, Jablonski, N, Wilkinson, R, Ouedraogo, HG, Matteelli, A, Regazzi, M, Tarnagda, G, Villani, P, Sulis, G, Diagbouga, S, Roggi, A, Giorgetti, F, Kouanda, S, Bidias, A, Ndjonka, D, Olemba, C, Souleymanou, A, Mukonzo, J, Kuteesa, R, Ogwal-Okeng, J, Gustafsson, LL, Owen, J, Bassi, P, Gashau, W, Olaf, K, Dodoo, A, Okonkwo, P, Kanki, P, Maruapula, D, Seraise, B, Einkauf, K, Reilly, A, Rowley, C, Musonda, R, Framhein, A, Mpagama, S, Semvua, H, Maboko, L, Hoelscher, M, Heinrich, N, Mulenga, L, Kaayunga, C, Davies, M-A, Egger, M, Musukuma, K, Dambe, R, Usadi, B, Ngari, M, Thitiri, J, Mwalekwa, L, Fegan, G, Berkley, J, Nsagha, D, Munamunungu, V, Bolton, C, Siyunda, A, Shilimi, J, Bucciardini, R, Fragola, V, Abegaz, T, Lucattini, S, Halifom, A, Tadesse, E, Berhe, M, Pugliese, K, De Castro, P, Terlizzi, R, Fucili, L, Di Gregorio, M, Mirra, M, Zegeye, T, Binelli, A, Vella, S, Abraham, L, Godefay, H, Rakotoarivelo, R, Raberahona, M, Randriamampionona, N, Andriamihaja, R, Rasamoelina, T, Cornet, M, De Dieu Randria, MJ, Benet, T, Vanhems, P, Andrianarivelo, MR, Chirwa, U, Michelo, C, Hamoonga, R, Wandiga, S, Oduor, P, Agaya, J, Sharma, A, Cavanaugh, S, Cain, K, Mukisa, J, Mupere, E, Worodria, W, Ngom, JT, Koro, F, Godwe, C, Adande, C, Ateugieu, R, Onana, T, Ngono, A, Kamdem, Y, Ngo-Niobe, S, Etoa, F-X, Kanengoni, M, Ruzario, S, Ndebele, P, Shana, M, Tarumbiswa, F, Musesengwa, R, Gutsire, R, Fisher, K, Thyagarajan, B, Akanbi, O, Binuyo, M, Ssengooba, W, Respeito, D, Mambuque, E, Blanco, S, Mandomando, I, Cobelens, F, Garcia-Basteiro, A, Tamene, A, Topp, S, Mwamba, C, Padian, N, Sikazwe, I, Geng, E, Holmes, C, Sikombe, K, Hantuba, Czaicki, N, Simbeza, S, Somwe, P, Umulisa, M, Ilo, J, Kestelyn, E, Uwineza, M, Agaba, S, Delvaux, T, Wijgert, J, Gethi, D, Odeny, L, Tamandjou, C, Kaindjee-Tjituka, F, Brandt, L, Cotton, M, Nel, E, Preiser, W, Andersson, M, Adepoju, A, Magana, M, Etsetowaghan, A, Chilikwazi, M, Sutcliffe, C, Thuma, P, Sinywimaanzi, K, Matakala, H, Munachoonga, P, Moss, W, Masenza, IS, Geisenberger, O, Agrea, P, Rwegoshora, F, Mahiga, H, Olomi, W, Kroidl, A, Kayode, G, Amoakoh-Coleman, M, Ansah, E, Uthman, O, Fokam, J, Santoro, M-M, Musolo, C, Chimbiri, I, Chikwenga, G, Deula, R, Massari, R, Lungu, A, Perno, C-F, Ndzengue, G, Loveline, N, Lissom, A, Flaurent, T, Sosso, S, Essomba, C, Kpeli, G, Otchere, I, Lamelas, A, Buultjens, A, Bulach, D, Baines, S, Seemann, T, Giulieri, S, Nakobu, Z, Aboagye, S, Owusu-Mireku, E, Danso, E, Hauser, J, Hinic, V, Pluschke, G, Stinear, T, Yeboah-Manu, D, Elshayeb, A, Siddig, ME, Ahmed, AA, Hussien, AE, Kabwe, M, Tembo, J, Chilukutu, L, Chilufya, M, Ngulube, F, Lukwesa, C, Enne, V, Wexner, H, Mwananyanda, L, Hamer, D, Sinyangwe, S, Ahmed, Y, Klein, N, Maeurer, M, Zumla, A, Bates, M, Beyala, L, Etienne, G, Anthony, N, Benjamin, A, Ateudjieu, J, Chibwe, B, Ojok, D, Tarr, CA, Perez, GM, Omeonga, S, Kibungu, F, Meyer, A, Lansana, P, Mayor, A, Onyango, P, Van Loggerenberg, F, Furtado, T, Boggs, L, Segrt, A, Dochez, C, Burnett, R, Mphahlele, MJ, Miiro, G, Mbidde, E, Peshu, N, Kivaya, E, Ngowi, B, Kavishe, R, Maowia, M, Sandstrom, E, Ayuo, E, Mmbaga, B, Leisegang, C, Thorpe, M, Batchilly, E, N'Guessan, J-P, Kanteh, D, Søfteland, S, Sebitloane, M, Vwalika, B, Taylor, M, Galappaththi-Arachchige, H, Holmen, S, Gundersen, SG, Ndhlovu, P, Kjetland, EF, Kombe, F, Toohey, J, Pienaar, E, Kredo, T, Cham, PM, Abubakar, I, Dondeh, BL, Vischer, N, Pfeiffer, C, Burri, C, Musukwa, K, Zürcher, S, Mwandu, T, Bauer, S, Adriko, M, Mwaura, P, Omolloh, K, Jones, C, Malecela, M, Hamidu, BA, Jenner, TE, Asiedu, LJ, Osei-Atweneboana, M, Afeke, I, Addo, P, Newman, M, Durnez, L, Eddyani, M, Ammisah, N, Abas, M, Quartey, M, Ablordey, A, Akinwale, O, Adeneye, A, Ezeugwu, S, Olukosi, Y, Adewale, B, Sulyman, M, Mafe, M, Okwuzu, J, Gyang, P, Nwafor, T, Henry, U, Musa, B, Ujah, I, Agobé, JCD, Grau-Pujol, B, Sacoor, C, Nhabomba, A, Casellas, A, Quintó, L, Subirà, C, Giné, R, Valentín, A, Muñoz, J, Nikiema, M, Ky-Ba, A, Comapore, KAM, Sangare, L, Oluremi, A, Michel, M, Camara, Y, Sanneh, B, Cuamba, I, Gutiérrez, J, Lázaro, C, Mejia, R, Adedeji, A, Folorunsho, S, Demehin, P, Akinsanya, B, Cowley, G, Da Silva, ET, Nabicassa, M, De Barros, PDP, Blif, MM, Bailey, R, Last, A, Mahendradhata, Y, Gotuzzo, E, De Nys, K, Casteels, M, Nona, SK, Lumeka, K, Todagbe, A, Djima, MM, Ukpong, M, Sagay, A, Khamofu, H, Torpey, K, Afiadigwe, E, Anenih, J, Ezechi, O, Nweneka, C, Idoko, J, Muhumuza, S, Katahoire, A, Nuwaha, F, Olsen, A, Okeyo, S, Omollo, R, Kimutai, R, Ochieng, M, Egondi, T, Moonga, C, Chileshe, C, Magwende, G, Anumudu, C, Onile, O, Oladele, V, Adebayo, A, Awobode, H, Oyeyemi, O, Odaibo, A, Kabuye, E, Lutalo, T, Njua-Yafi, C, Nkuo-Akenji, T, Anchang-Kimbi, J, Mugri, R, Chi, H, Tata, R, Njumkeng, C, Dodoo, D, Achidi, E, Fernandes, J, Bache, EB, Matakala, K, Searle, K, Greenman, M, and Rainwater-Lovett, K

Published
2017

19. The effect of dose on the antimalarial efficacy of artemether-lumefantrine: a systematic review and pooled analysis of individual patient data

Author

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

Published
2015

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

Author

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

Abstract

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

Published
2015

21. Paramètres entomologiques et parasitologiques de la transmission du paludisme à Douguia, Tchad.

Author

Diarra, A. Z., Dabo, A. K., Saye, R., Coulibaly, D., Guindo, M. A., Sagara, I., Dolo, G., Doumtabe, D., Kerah, H. C., Namangue, K., Mahamat, T. T., and Doumbo Ogobara, K.

Abstract

Copyright of Médecine et Santé Tropicales is the property of John Libbey Eurotext Ltd. and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Published
2017
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23. Facteurs influençant l'observation de la deuxième et troisième dose pendant la chimioprévention du paludisme saisonnier (CPS) - Une étude quantitative au Burkina Faso, Mali et Niger

Author

Somé, A.F., Zongo, I., Sagara, I., Ibrahim, A., Ahanhanzo, C.D., Agbanouvi-Agassi, E.E., Sayi, D.A., Paré, L., Kabré, Z., Nikiéma, F., Bazié, T., Ouédraogo, S., Sombié, I., Dicko, A., Adehossi, E., Ouédraogo, J.B., and Dabiré, K.R.

Abstract

Malgré les efforts remarquables déployés pour réduire le fardeau du paludisme, la maladie reste une cause majeure de morbidité et de mortalité en Afrique subsaharienne notamment chez les enfants de moins de 5 ans. L'objectif de l’étude est d'identifier les facteurs influençant l'observance de la 2èmeet 3èmedose pendant la chimioprévention du paludisme saisonnier (CPS) au Burkina Faso, au Mali et au Niger.

Published
2023
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24. Pharmacovigilance of Malaria Intermittent Preventive Treatment in Infants Coupled With Routine Immunizations in 6 African Countries

Author

de Sousa, A., primary, Rabarijaona, L. P., additional, Tenkorang, O., additional, Inkoom, E., additional, Ravelomanantena, H. V., additional, Njarasoa, S., additional, Whang, J. N., additional, Ndiaye, J. L., additional, Ndiaye, Y., additional, Ndiaye, M., additional, Sow, D., additional, Akadiri, G., additional, Hassan, J., additional, Dicko, A., additional, Sagara, I., additional, Kubalalika, P., additional, Mathanga, D., additional, Bizuneh, K., additional, Randriasamimanana, J. R., additional, Recht, J., additional, Bjelic, I., additional, and Dodoo, A., additional

Published
2012
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29. Quinine treatment selects the pfnhe-1 ms4760-1 polymorphism in Malian patients with Falciparum malaria.

Author

Kone A, Mu J, Maiga H, Beavogui AH, Yattara O, Sagara I, Tekete MM, Traore OB, Dara A, Dama S, Diallo N, Kodio A, Traoré A, Björkman A, Gil JP, Doumbo OK, Wellems TE, Djimde AA, Kone, Aminatou, and Mu, Jianbing

Subjects
DRUG therapy for malaria, PROTOZOA, DNA, BIOLOGICAL transport, DRUG resistance, GENETIC polymorphisms, MALIANS, QUININE, MALARIA, DOCUMENTATION, RESEARCH funding, ANTIMALARIALS, AMINO acids, GENETIC techniques, PHARMACODYNAMICS
Abstract

Background: The mechanism of Plasmodium falciparum resistance to quinine is not known. In vitro quantitative trait loci mapping suggests involvement of a predicted P. falciparum sodium-hydrogen exchanger (pfnhe-1) on chromosome 13.Methods: We conducted prospective quinine efficacy studies in 2 villages, Kollé and Faladié, Mali. Cases of clinical malaria requiring intravenous therapy were treated with standard doses of quinine and followed for 28 days. Treatment outcomes were classified using modified World Health Organization protocols. Molecular markers of parasite polymorphisms were used to distinguish recrudescent parasites from new infections. The prevalence of pfnhe-1 ms4760-1 among parasites before versus after quinine treatment was determined by direct sequencing.Results: Overall, 163 patients were enrolled and successfully followed. Without molecular correction, the mean adequate clinical and parasitological response (ACPR) was 50.3% (n = 163). After polymerase chain reaction correction to account for new infections, the corrected ACPR was 100%. The prevalence of ms4760-1 increased significantly, from 26.2% (n = 107) before quinine treatment to 46.3% (n = 54) after therapy (P = .01). In a control sulfadoxine-pyrimethamine study, the prevalence of ms4760-1 was similar before and after treatment.Conclusions: This study supports a role for pfnhe-1 in decreased susceptibility of P. falciparum to quinine in the field. [ABSTRACT FROM AUTHOR]

Published
2013
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31. What does a single determination of malaria parasite density mean? A longitudinal survey in Mali.

Author

Delley, Véronique, Bouvier, Paul, Breslow, Norman, Doumbo, Ogobara, Sagara, Issaka, Diakite, Mahamadou, Mauris, Anne, Dolo, Amagana, Rougemont, André, Delley, V, Bouvier, P, Breslow, N, Doumbo, O, Sagara, I, Diakite, M, Mauris, A, Dolo, A, and Rougemont, A

Subjects
MALARIA diagnosis, PARASITIC diseases
Abstract

Temporal variations of blood parasite density were evaluated in a longitudinal study of young, asymptomatic men in a village with endemic malaria in Mali (West Africa). Our main intention was to challenge the value of a single measure of parasite density for the diagnosis of malaria, and to define the level of endemicity in any given area. Parasitaemia and body temperature were recorded three times a day in the wet season (in 39 subjects on 12 days) and in the dry season (in 41 subjects on 13 days). Two thousand nine hundred and fifty seven blood smears (98.5% of the expected number) were examined for malaria parasites. We often found 100-fold or greater variations in parasite density within a 6-hour period during individual follow-up. All infected subjects had frequent negative smears. Although fever was most likely to occur in subjects with a maximum parasite density exceeding 10000 parasites/mm3 (P = 0.009), there was no clear relationship between the timing of these two events. Examples of individual profiles for parasite density and fever are presented. These variations (probably due to a 'sequestration-release' mechanism, which remains to be elucidated) lead us to expect a substantial impact on measurements of endemicity when only a single sample is taken. In this study, the percentage of infected individuals varied between 28.9% and 57.9% during the dry season and between 27.5% and 70.7% during the wet season. The highest rates were observed at midday, and there were significant differences between days. Thus, high parasite density sometimes associated with fever can no longer be considered as the gold standard in the diagnosis of malaria. Other approaches, such as decision-making processes involving clinical, biological and ecological variables must be developed, especially in highly endemic areas where Plasmodium infection is the rule rather than the exception and the possible causes of fever are numerous. [ABSTRACT FROM AUTHOR]

Published
2000
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45. Seasonal Malaria Vaccination with or without Seasonal Malaria Chemoprevention.

Author

Chandramohan, D., Zongo, I., Sagara, I., Cairns, M., Yerbanga, R.-S., Diarra, M., Nikièma, F., Tapily, A., Sompougdou, F., Issiaka, D., Zoungrana, C., Sanogo, K., Haro, A., Kaya, M., Sienou, A.-A., Traore, S., Mahamar, A., Thera, I., Diarra, K., and Dolo, A.

Subjects
*MALARIA prevention, *RESEARCH, *VACCINES, *COMBINATION drug therapy, *FEBRILE seizures, *RESEARCH methodology, *MEDICAL cooperation, *EVALUATION research, *AMODIAQUINE, *MALARIA, *SEASONS, *COMPARATIVE studies, *SULFANILAMIDES, *BLIND experiment, *HOSPITAL care, *RESEARCH funding, *ANTIMALARIALS, *COMBINED modality therapy, *CHEMOPREVENTION
Abstract

Background: Malaria control remains a challenge in many parts of the Sahel and sub-Sahel regions of Africa.Methods: We conducted an individually randomized, controlled trial to assess whether seasonal vaccination with RTS,S/AS01E was noninferior to chemoprevention in preventing uncomplicated malaria and whether the two interventions combined were superior to either one alone in preventing uncomplicated malaria and severe malaria-related outcomes.Results: We randomly assigned 6861 children 5 to 17 months of age to receive sulfadoxine-pyrimethamine and amodiaquine (2287 children [chemoprevention-alone group]), RTS,S/AS01E (2288 children [vaccine-alone group]), or chemoprevention and RTS,S/AS01E (2286 children [combination group]). Of these, 1965, 1988, and 1967 children in the three groups, respectively, received the first dose of the assigned intervention and were followed for 3 years. Febrile seizure developed in 5 children the day after receipt of the vaccine, but the children recovered and had no sequelae. There were 305 events of uncomplicated clinical malaria per 1000 person-years at risk in the chemoprevention-alone group, 278 events per 1000 person-years in the vaccine-alone group, and 113 events per 1000 person-years in the combination group. The hazard ratio for the protective efficacy of RTS,S/AS01E as compared with chemoprevention was 0.92 (95% confidence interval [CI], 0.84 to 1.01), which excluded the prespecified noninferiority margin of 1.20. The protective efficacy of the combination as compared with chemoprevention alone was 62.8% (95% CI, 58.4 to 66.8) against clinical malaria, 70.5% (95% CI, 41.9 to 85.0) against hospital admission with severe malaria according to the World Health Organization definition, and 72.9% (95% CI, 2.9 to 92.4) against death from malaria. The protective efficacy of the combination as compared with the vaccine alone against these outcomes was 59.6% (95% CI, 54.7 to 64.0), 70.6% (95% CI, 42.3 to 85.0), and 75.3% (95% CI, 12.5 to 93.0), respectively.Conclusions: Administration of RTS,S/AS01E was noninferior to chemoprevention in preventing uncomplicated malaria. The combination of these interventions resulted in a substantially lower incidence of uncomplicated malaria, severe malaria, and death from malaria than either intervention alone. (Funded by the Joint Global Health Trials and PATH; ClinicalTrials.gov number, NCT03143218.). [ABSTRACT FROM AUTHOR]

Published
2021
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46. Dispersible formulation of artemether/lumefantrine: specifically developed for infants and young children

Author

Sagara Issaka and Abdulla Salim

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

Abstract Infants and children under five years of age are the most vulnerable to malaria with over 1,700 deaths per day from malaria in this group. However, until recently, there were no WHO-endorsed paediatric anti-malarial formulations available. Artemisinin-based combination therapy is the current standard of care for patients with uncomplicated falciparum malaria in Africa. Artemether/lumefantrine (AL) meets WHO pre-qualification criteria for efficacy, safety and quality. Coartem®, a fixed dose combination of artemether and lumefantrine, has consistently achieved cure rates of >95% in clinical trials. However, AL tablets are inconvenient for caregivers to administer as they need to be crushed and mixed with water or food for infants and young children. Further, in common with other anti-malarials, they have a bitter taste, which may result in children spitting the medicine out and not receiving the full therapeutic dose. There was a clear unmet medical need for a formulation of AL specifically designed for children. Ahead of a call from WHO for child-friendly medicines, Novartis, working in partnership with Medicines for Malaria Venture (MMV), started the development of a new formulation of AL for infants and young children: Coartem® Dispersible. The excellent efficacy, safety and tolerability already demonstrated by AL tablets were confirmed with dispersible AL in a large trial comparing the crushed tablets with dispersible tablets in 899 African children with falciparum malaria. In the evaluable population, 28-day PCR-corrected cure rates of >96% were achieved. Further, its sweet taste means that it is palatable for children, and the dispersible formulation makes it easier for caregivers to administer than bitter crushed tablets. Easing administration may foster compliance, hence improving therapeutic outcomes in infants and young children and helping to preserve the efficacy of ACT.

Published
2009
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47. Gametocyte clearance dynamics following oral artesunate treatment of uncomplicated falciparum malaria in Malian children

Author

Djimde Abdoulaye A., Maiga Amelia W., Ouologuem Dinkorma, Fofana Bakary, Sagara Issaka, Dembele Demba, Toure Sekou, Sanogo Kassim, Dama Souleymane, Sidibe Bakary, and Doumbo Ogobara K.

Subjects
Plasmodium falciparum, Gametocyte clearance, Gametocyte density, Artesunate monotherapy, Infectious and parasitic diseases, RC109-216
Abstract

Artemisinin-based combination therapies decrease Plasmodium gametocyte carriage. However, the role of artesunate in monotherapy in vivo, the mechanisms involved, and the utility of gametocyte carriage as a potential tool for the surveillance of antimalarial resistance are poorly understood. In 2010–2011, we conducted an open-label, prospective efficacy study of artesunate as monotherapy in children 1–10 years of age with uncomplicated falciparum malaria in Bougoula-Hameau, Mali. Standard oral doses of artesunate were administered for 7 days and patients were followed up for 28 days. The data were compared to a similar study conducted in 2002–2004. Of 100 children enrolled in the 2010–2011 study, 92 were analyzed and compared to 217 children enrolled in the 2002–2004 study. The proportion of gametocyte carriers was unchanged at the end of treatment (23% at baseline vs. 24% on day 7, p = 1.0) and did not significantly decline until day 21 of follow-up (23% vs. 6%, p = 0.003). The mean gametocyte density at inclusion remained unchanged at the end of treatment (12 gametocytes/μL vs. 16 gametocytes/μL, p = 0.6). Overall, 46% of the 71 initial non-carriers had gametocytes detected by day 7. Similar results were found in the 2002–2004 study. In both studies, although gametocyte carriage significantly decreased by the end of the 28-day follow-up, artesunate did not clear mature gametocytes during treatment and did not prevent the appearance of new stage V gametocytes as assessed by light microscopy. Baseline gametocyte carriage was significantly higher 6 years after the deployment of artemisinin-based combination therapies in this setting.

Published
2016
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48. Community screening and treatment of asymptomatic carriers of Plasmodium falciparum with artemether-lumefantrine to reduce malaria disease burden: a modelling and simulation analysis

Author

Ubben David, Sagara Issaka, Gaye Oumar, Premji Zulfiqarali, Gbadoé Adama, Makanga Michael, Tiono Alfred B, Kern Steven E, Cousin Marc, Oladiran Fiyinfolu, Sander Oliver, and Ogutu Bernhards

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

Abstract Background Asymptomatic carriers of Plasmodium falciparum serve as a reservoir of parasites for malaria transmission. Identification and treatment of asymptomatic carriers within a region may reduce the parasite reservoir and influence malaria transmission in that area. Methods Using computer simulation, this analysis explored the impact of community screening campaigns (CSC) followed by systematic treatment of P. falciparum asymptomatic carriers (AC) with artemether-lumefantrine (AL) on disease transmission. The model created by Okell et al (originally designed to explore the impact of the introduction of treatment with artemisinin-based combination therapy on malaria endemicity) was modified to represent CSC and treatment of AC with AL, with the addition of malaria vector seasonality. The age grouping, relative distribution of age in a region, and degree of heterogeneity in disease transmission were maintained. The number and frequency of CSC and their relative timing were explored in terms of their effect on malaria incidence. A sensitivity analysis was conducted to determine the factors with the greatest impact on the model predictions. Results The simulation showed that the intervention that had the largest effect was performed in an area with high endemicity (entomological inoculation rate, EIR > 200); however, the rate of infection returned to its normal level in the subsequent year, unless the intervention was repeated. In areas with low disease burden (EIR < 10), the reduction was sustained for over three years after a single intervention. Three CSC scheduled in close succession (monthly intervals) at the start of the dry season had the greatest impact on the success of the intervention. Conclusions Community screening and treatment of asymptomatic carriers with AL may reduce malaria transmission significantly. The initial level of disease intensity has the greatest impact on the potential magnitude and duration of malaria reduction. When combined with other interventions (e.g. long-lasting insecticide-treated nets, rapid diagnostic tests, prompt diagnosis and treatment, and, where appropriate, indoor residual spraying) the effect of this intervention can be sustained for many years, and it could become a tool to accelerate the reduction in transmission intensity to pre-elimination levels. Repeated interventions at least every other year may help to prolong the effect. The use of an effective diagnostic tool and a highly effective ACT, such as AL, is also vital. The modelling supports the evaluation of this approach in a prospective clinical trial to reduce the pool of infective vectors for malaria transmission in an area with marked seasonality.

Published
2011
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49. Increase in EPI vaccines coverage after implementation of intermittent preventive treatment of malaria in infant with Sulfadoxine -pyrimethamine in the district of Kolokani, Mali: Results from a cluster randomized control trial

Author

Salomon Roger, Rogier Christophe, Diallo Alpha T, Sissoko Mahamadou S, Toure Ousmane B, Sagara Issaka, Traore Mariam, Toure Sidy O, Dicko Alassane, de Sousa Alexandra, and Doumbo Ogobara K

Subjects
malaria, intermittent preventive treatment, sulphadoxine-pyrimethamine, expanded program of immunization, Public aspects of medicine, RA1-1270
Abstract

Abstract Background Even though the efficacy of Intermittent Preventive Treatment in infants (IPTi) with Sulfadoxine-Pyrimethamine (SP) against clinical disease and the absence of its interaction with routine vaccines of the Expanded Immunization Programme (EPI) have been established, there are still some concerns regarding the addition of IPTi, which may increase the work burden and disrupt the routine EPI services especially in Africa where the target immunization coverage remains to be met. However IPTi may also increase the adherence of the community to EPI services and improve EPI coverage, once the benefice of strategy is perceived. Methods To assess the impact of IPTi implementation on the coverage of EPI vaccines, 22 health areas of the district of Kolokani were randomized at a 1:1 ratio to either receive IPTi-SP or to serve as a control. The EPI vaccines coverage was assessed using cross-sectional surveys at baseline in November 2006 and after one year of IPTi pilot-implementation in December 2007. Results At baseline, the proportion of children of 9-23 months who were completely vaccinated (defined as children who received BGG, 3 doses of DTP/Polio, measles and yellow fever vaccines) was 36.7% (95% CI 25.3% -48.0%). After one year of implementation of IPTi-SP using routine health services, the proportion of children completely vaccinated rose to 53.8% in the non intervention zone and 69.5% in the IPTi intervention zone (P The proportion of children in the target age groups who received IPTi with each of the 3 vaccinations DTP2, DTP3 and Measles, were 89.2% (95% CI 85.9%-92.0%), 91.0% (95% CI 87.6% -93.7%) and 77.4% (95% CI 70.7%-83.2%) respectively. The corresponding figures in non intervention zone were 2.3% (95% CI 0.9% -4.7%), 2.6% (95% CI 1.0% -5.6%) and 1.7% (95% CI 0.4% - 4.9%). Conclusion This study shows that high coverage of the IPTi can be obtained when the strategy is implemented using routine health services and implementation results in a significant increase in coverage of EPI vaccines in the district of Kolokani, Mali. Trial Registration ClinicalTrials.gov NCT00766662

Published
2011
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50. Anaemia in a phase 2 study of a blood stage falciparum malaria vaccine

Author

Guindo Aldiouma, Guindo Merepen A, Miura Kazutoyo, Dicko Alassane, Sagara Issaka, Fay Michael P, Ellis Ruth D, Sissoko Mahamadou S, Doumbo Ogobara K, and Diallo Dapa

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

Abstract Background A Phase 1-2b study of the blood stage malaria vaccine AMA1-C1/Alhydrogel was conducted in 336 children in Donéguébougou and Bancoumana, Mali. In the Phase 2 portion of the study (n = 300), no impact on parasite density or clinical malaria was seen; however, children who received the study vaccine had a higher frequency of anaemia (defined as haemoglobin < 8.5 g/dL) compared to those who received the comparator vaccine (Hiberix). This effect was one of many tested and was not significant after adjusting for multiple comparisons. Methods To further investigate the possible impact of vaccination on anaemia, additional analyses were conducted including patients from the Phase 1 portion of the study and controlling for baseline haemoglobin, haemoglobin types S or C, alpha-thalassaemia, G6PD deficiency, and age. A multiplicative intensity model was used, which generalizes Cox regression to allow for multiple events. Frailty effects for each subject were used to account for correlation of multiple anaemia events within the same subject. Intensity rates were calculated with reference to calendar time instead of time after randomization in order to account for staggered enrollment and seasonal effects of malaria incidence. Associations of anaemia with anti-AMA1 antibody were further explored using a similar analysis. Results A strong effect of vaccine on the incidence of anaemia (risk ratio [AMA1-C1 to comparator (Hiberix)]= 2.01, 95% confidence interval [1.26,3.20]) was demonstrated even after adjusting for baseline haemoglobin, haemoglobinopathies, and age, and using more sophisticated statistical models. Anti-AMA1 antibody levels were not associated with this effect. Conclusions While these additional analyses show a robust effect of vaccination on anaemia, this is an intensive exploration of secondary results and should, therefore, be interpreted with caution. Possible mechanisms of the apparent adverse effect on haemoglobin of vaccination with AMA1-C1/Alhydrogel and implications for blood stage vaccine development are discussed. The potential impact on malaria-associated anaemia should be closely evaluated in clinical trials of AMA1 and other blood stage vaccines in malaria-exposed populations.

Published
2011
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