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1. Temporal distribution of Plasmodium falciparum recrudescence following artemisinin-based combination therapy: an individual participant data meta-analysis

Author

Dahal, P, Simpson, JA, Abdulla, S, Achan, J, Adam, I, Agarwal, A, Allan, R, Anvikar, AR, Ashley, EA, Bassat, Q, Borrmann, S, Bousema, T, Bukirwa, H, Carrara, V, Corsi, M, D'Alessandro, U, Davis, TME, Deloron, P, Desai, M, Dimbu, PR, Djalle, D, Djimde, A, Dorsey, G, Drakeley, CJ, Duparc, S, Edstein, MD, Espie, E, Abul, F, Falade, C, Fanello, C, Faucher, J-F, Faye, B, Fortes, FDJ, Gadalla, NB, Gaye, O, Gil, JP, Gilayeneh, J, Greenwood, B, Grivoyannis, A, Hien, TT, Hwang, J, Janssens, B, Juma, E, Kamugisha, E, Karema, C, Karunajeewa, HA, Kiechel, JR, Kironde, F, Kofoed, P-E, Kremsner, PG, Lee, SJ, Marsh, K, Martensson, A, Mayxay, M, Menan, H, Mens, P, Mutabingwa, TK, Ndiaye, J-L, Ngasala, BE, Noedl, H, Nosten, F, Offianan, AT, Ogutu, BR, Olliaro, PL, Ouedraogo, JB, Piola, P, Plowe, C, Plucinski, MM, Pratt, OJ, Premji, Z, Ramharter, M, Rogier, C, Vitare, P, Rombo, L, Rosenthal, PJ, Sibley, C, Sirima, S, Smithuis, F, Staedke, SG, Sutanto, I, Talisuna, AO, Tarning, J, Taylor, WRJ, Temu, E, Thriemer, K, Thuy-Nhien, N, Udhayakumar, V, Ursing, JD, van Herp, M, van Lenthe, M, van Vugt, M, William, Y, Winnips, C, Zaloumis, S, Zongo, I, White, NJ, Guerin, PJ, Stepniewska, K, Price, RN, Arinaitwe, E, Dahal, P, Simpson, JA, Abdulla, S, Achan, J, Adam, I, Agarwal, A, Allan, R, Anvikar, AR, Ashley, EA, Bassat, Q, Borrmann, S, Bousema, T, Bukirwa, H, Carrara, V, Corsi, M, D'Alessandro, U, Davis, TME, Deloron, P, Desai, M, Dimbu, PR, Djalle, D, Djimde, A, Dorsey, G, Drakeley, CJ, Duparc, S, Edstein, MD, Espie, E, Abul, F, Falade, C, Fanello, C, Faucher, J-F, Faye, B, Fortes, FDJ, Gadalla, NB, Gaye, O, Gil, JP, Gilayeneh, J, Greenwood, B, Grivoyannis, A, Hien, TT, Hwang, J, Janssens, B, Juma, E, Kamugisha, E, Karema, C, Karunajeewa, HA, Kiechel, JR, Kironde, F, Kofoed, P-E, Kremsner, PG, Lee, SJ, Marsh, K, Martensson, A, Mayxay, M, Menan, H, Mens, P, Mutabingwa, TK, Ndiaye, J-L, Ngasala, BE, Noedl, H, Nosten, F, Offianan, AT, Ogutu, BR, Olliaro, PL, Ouedraogo, JB, Piola, P, Plowe, C, Plucinski, MM, Pratt, OJ, Premji, Z, Ramharter, M, Rogier, C, Vitare, P, Rombo, L, Rosenthal, PJ, Sibley, C, Sirima, S, Smithuis, F, Staedke, SG, Sutanto, I, Talisuna, AO, Tarning, J, Taylor, WRJ, Temu, E, Thriemer, K, Thuy-Nhien, N, Udhayakumar, V, Ursing, JD, van Herp, M, van Lenthe, M, van Vugt, M, William, Y, Winnips, C, Zaloumis, S, Zongo, I, White, NJ, Guerin, PJ, Stepniewska, K, Price, RN, and Arinaitwe, E

Abstract

BACKGROUND: The duration of trial follow-up affects the ability to detect recrudescent infections following anti-malarial treatment. The aim of this study was to explore the proportions of recrudescent parasitaemia as ascribed by genotyping captured at various follow-up time-points in treatment efficacy trials for uncomplicated Plasmodium falciparum malaria. METHODS: Individual patient data from 83 anti-malarial efficacy studies collated in the WorldWide Antimalarial Resistance Network (WWARN) repository with at least 28 days follow-up were available. The temporal and cumulative distributions of recrudescence were characterized using a Cox regression model with shared frailty on study-sites. Fractional polynomials were used to capture non-linear instantaneous hazard. The area under the density curve (AUC) of the constructed distribution was used to estimate the optimal follow-up period for capturing a P. falciparum malaria recrudescence. Simulation studies were conducted based on the constructed distributions to quantify the absolute overestimation in efficacy due to sub-optimal follow-up. RESULTS: Overall, 3703 recurrent infections were detected in 60 studies conducted in Africa (15,512 children aged < 5 years) and 23 studies conducted in Asia and South America (5272 patients of all ages). Using molecular genotyping, 519 (14.0%) recurrences were ascribed as recrudescent infections. A 28 day artemether-lumefantrine (AL) efficacy trial would not have detected 58% [95% confidence interval (CI) 47-74%] of recrudescences in African children and 32% [95% CI 15-45%] in patients of all ages in Asia/South America. The corresponding estimate following a 42 day dihydroartemisinin-piperaquine (DP) efficacy trial in Africa was 47% [95% CI 19-90%] in children under 5 years old treated with > 48 mg/kg total piperaquine (PIP) dose and 9% [95% CI 0-22%] in those treated with ≤ 48 mg/kg PIP dose. In absolute terms, the simulation study found that trials limited to 28 days follow-up

Published
2022

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

Author

Mansoor, R, Commons, RJ, Douglas, NM, Abuaku, B, Achan, J, Adam, I, Adjei, GO, Adjuik, M, Alemayehu, BH, Allan, R, Allen, EN, Anvikar, AR, Arinaitwe, E, Ashley, EA, Ashurst, H, Asih, PBS, Bakyaita, N, Barennes, H, Barnes, K, Basco, L, Bassat, Q, Baudin, E, Bell, DJ, Bethell, D, Bjorkman, A, Boulton, C, Bousema, T, Brasseur, P, Bukirwa, H, Burrow, R, Carrara, V, Cot, M, D'Alessandro, U, Das, D, Das, S, Davis, TME, Desai, M, Djimde, AA, Dondorp, AM, Dorsey, G, Drakeley, CJ, Duparc, S, Espie, E, Etard, J-F, Falade, C, Faucher, JF, Filler, S, Fogg, C, Fukuda, M, Gaye, O, Genton, B, Rahim, AG, Gilayeneh, J, Gonzalez, R, Grais, RF, Grandesso, F, Greenwood, B, Grivoyannis, A, Hatz, C, Hodel, EM, Humphreys, GS, Hwang, J, Ishengoma, D, Juma, E, Kachur, SP, Kager, PA, Kamugisha, E, Kamya, MR, Karema, C, Kayentao, K, Kazienga, A, Kiechel, J-R, Kofoed, P-E, Koram, K, Kremsner, PG, Lalloo, DG, Laman, M, Lee, SJ, Lell, B, Maiga, AW, Martensson, A, Mayxay, M, Mbacham, W, McGready, R, Menan, H, Menard, D, Mockenhaupt, F, Moore, BR, Muller, O, Nahum, A, Ndiaye, J-L, Newton, PN, Ngasala, BE, Nikiema, F, Nji, AM, Noedl, H, Nosten, F, Ogutu, BR, Ojurongbe, O, Osorio, L, Ouedraogo, J-B, Owusu-Agyei, S, Pareek, A, Penali, LK, Piola, P, Plucinski, M, Premji, Z, Ramharter, M, Richmond, CL, Rombo, L, Rosenthal, PJ, Salman, S, Same-Ekobo, A, Sibley, C, Sirima, SB, Smithuis, FM, Some, FA, Staedke, SG, Starzengruber, P, Strub-Wourgaft, N, Sutanto, I, Swarthout, TD, Syafruddin, D, Talisuna, AO, Taylor, WR, Temu, EA, Thwing, J, Tinto, H, Tjitra, E, Toure, OA, Tran, TH, Ursing, J, Valea, I, Valentini, G, van Vugt, M, von Seidlein, L, Ward, SA, Were, V, White, NJ, Woodrow, CJ, Yavo, W, Yeka, A, Zongo, I, Simpson, JA, Guerin, PJ, Stepniewska, K, Price, RN, Roper, C, Mansoor, R, Commons, RJ, Douglas, NM, Abuaku, B, Achan, J, Adam, I, Adjei, GO, Adjuik, M, Alemayehu, BH, Allan, R, Allen, EN, Anvikar, AR, Arinaitwe, E, Ashley, EA, Ashurst, H, Asih, PBS, Bakyaita, N, Barennes, H, Barnes, K, Basco, L, Bassat, Q, Baudin, E, Bell, DJ, Bethell, D, Bjorkman, A, Boulton, C, Bousema, T, Brasseur, P, Bukirwa, H, Burrow, R, Carrara, V, Cot, M, D'Alessandro, U, Das, D, Das, S, Davis, TME, Desai, M, Djimde, AA, Dondorp, AM, Dorsey, G, Drakeley, CJ, Duparc, S, Espie, E, Etard, J-F, Falade, C, Faucher, JF, Filler, S, Fogg, C, Fukuda, M, Gaye, O, Genton, B, Rahim, AG, Gilayeneh, J, Gonzalez, R, Grais, RF, Grandesso, F, Greenwood, B, Grivoyannis, A, Hatz, C, Hodel, EM, Humphreys, GS, Hwang, J, Ishengoma, D, Juma, E, Kachur, SP, Kager, PA, Kamugisha, E, Kamya, MR, Karema, C, Kayentao, K, Kazienga, A, Kiechel, J-R, Kofoed, P-E, Koram, K, Kremsner, PG, Lalloo, DG, Laman, M, Lee, SJ, Lell, B, Maiga, AW, Martensson, A, Mayxay, M, Mbacham, W, McGready, R, Menan, H, Menard, D, Mockenhaupt, F, Moore, BR, Muller, O, Nahum, A, Ndiaye, J-L, Newton, PN, Ngasala, BE, Nikiema, F, Nji, AM, Noedl, H, Nosten, F, Ogutu, BR, Ojurongbe, O, Osorio, L, Ouedraogo, J-B, Owusu-Agyei, S, Pareek, A, Penali, LK, Piola, P, Plucinski, M, Premji, Z, Ramharter, M, Richmond, CL, Rombo, L, Rosenthal, PJ, Salman, S, Same-Ekobo, A, Sibley, C, Sirima, SB, Smithuis, FM, Some, FA, Staedke, SG, Starzengruber, P, Strub-Wourgaft, N, Sutanto, I, Swarthout, TD, Syafruddin, D, Talisuna, AO, Taylor, WR, Temu, EA, Thwing, J, Tinto, H, Tjitra, E, Toure, OA, Tran, TH, Ursing, J, Valea, I, Valentini, G, van Vugt, M, von Seidlein, L, Ward, SA, Were, V, White, NJ, Woodrow, CJ, Yavo, W, Yeka, A, Zongo, I, Simpson, JA, Guerin, PJ, Stepniewska, K, Price, RN, and Roper, C

Abstract

BACKGROUND: Plasmodium falciparum malaria is associated with anaemia-related morbidity, attributable to host, parasite and drug factors. We quantified the haematological response following treatment of uncomplicated P. falciparum malaria to identify the factors associated with malarial anaemia. METHODS: Individual patient data from eligible antimalarial efficacy studies of uncomplicated P. falciparum malaria, available through the WorldWide Antimalarial Resistance Network data repository prior to August 2015, were pooled using standardised methodology. The haematological response over time was quantified using a multivariable linear mixed effects model with nonlinear terms for time, and the model was then used to estimate the mean haemoglobin at day of nadir and day 7. Multivariable logistic regression quantified risk factors for moderately severe anaemia (haemoglobin < 7 g/dL) at day 0, day 3 and day 7 as well as a fractional fall ≥ 25% at day 3 and day 7. RESULTS: A total of 70,226 patients, recruited into 200 studies between 1991 and 2013, were included in the analysis: 50,859 (72.4%) enrolled in Africa, 18,451 (26.3%) in Asia and 916 (1.3%) in South America. The median haemoglobin concentration at presentation was 9.9 g/dL (range 5.0-19.7 g/dL) in Africa, 11.6 g/dL (range 5.0-20.0 g/dL) in Asia and 12.3 g/dL (range 6.9-17.9 g/dL) in South America. Moderately severe anaemia (Hb < 7g/dl) was present in 8.4% (4284/50,859) of patients from Africa, 3.3% (606/18,451) from Asia and 0.1% (1/916) from South America. The nadir haemoglobin occurred on day 2 post treatment with a mean fall from baseline of 0.57 g/dL in Africa and 1.13 g/dL in Asia. Independent risk factors for moderately severe anaemia on day 7, in both Africa and Asia, included moderately severe anaemia at baseline (adjusted odds ratio (AOR) = 16.10 and AOR = 23.00, respectively), young age (age < 1 compared to ≥ 12 years AOR = 12.81 and AOR = 6.79, respectively), high parasitaemia (AOR = 1.78 and AOR = 1.

Published
2022

8. 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, San Maurice Ouattara, 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, 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, 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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

10. Comparison of chlorproguanil-dapsone with sulfadoxine-pyrimethamine for the treatment of uncomplicated falciparum malaria in young African children: double-blind randomised controlled trial

Author

Alloueche, A., Bailey, W., Barton, S., Bwika, J., Chimpeni, P., Falade, C.O., Fehintola, F.A., Horton, J., Jaffar, S., Kanyok, T., Kremsner, P.G., Kublin, J.G., Lang, T., Missinou, M.A., Mkandala, C., Oduola, A.M.J., Premji, Z., Robertson, L., Sowunmi, S., Ward, S.A., and Winstanley, P.A.

Subjects
Dapsone -- Health aspects, Dapsone -- Research, Malaria -- Care and treatment, Malaria -- Health aspects, Antimalarials -- Health aspects, Antimalarials -- Research
Published
2004

11. 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

12. 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

13. Current clinical efficacy of chloroquine for the treatment of Plasmodium falciparum infections in urban Dar es Salaam, United Republic of Tanzania

Author

Premji, Z., Makwaya, C., and Minjas, J.N.

Subjects
Malaria -- Drug therapy, Chloroquine -- Evaluation, Tanzania -- Health aspects
Abstract

Reported is the use of a 14-day WHO protocol, which takes into account the clinical, parasitological and haematological responses to antimalarial drugs, to determine the efficacy of chloroquine in the treatment of uncomplicated malaria in young children (n = 200) in urban Dar es Salaam. Chloroquine failure was found in 43% of the children. Of these, 12.5% were considered to be early treatment failures and were given a single dose of sulfadoxine-pyrimethamine. Fever subsided in all children treated with sulfadoxine-pyrimethamine and there were no parasitological failures. In addition, children treated with sulfadoxine-pyrimethamine because of early treatment failure with chloroquine had better haematological recovery than the chloroquine-sensitive group. It is concluded that chloroquine can no longer be considered an effective therapy for P. falciparum malaria in young children in Dar es Salaam., Voir page 743 le resume en francais. En la pagina 744 figura un resumen en espanol. Introduction Since the emergence of chloroquine-resistant falciparum malaria in the United Republic of Tanzania [...]

Published
1999

15. A shortened verbal autopsy instrument for use in routine mortality surveillance systems

Author

Serina, P, Riley, I, Stewart, A, Flaxman, AD, Lozano, R, Mooney, MD, Luning, R, Hernandez, B, Black, R, Ahuja, R, Alam, N, Alam, SS, Ali, SM, Atkinson, C, Baqui, AH, Chowdhury, HR, Dandona, L, Dandona, R, Dantzer, E, Darmstadt, GL, Das, V, Dhingra, U, Dutta, A, Fawzi, W, Freeman, M, Gamage, S, Gomez, S, Hensman, D, James, SL, Joshi, R, Kalter, HD, Kumar, A, Kumar, V, Lucero, M, Mehta, S, Neal, B, Ohno, SL, Phillips, D, Pierce, K, Prasad, R, Praveen, D, Premji, Z, Ramirez-Villalobos, D, Rampatige, R, Remolador, H, Romero, M, Said, M, Sanvictores, D, Sazawal, S, Streatfield, PK, Tallo, V, Vadhatpour, A, Wijesekara, N, Murray, CJL, Lopez, AD, Serina, P, Riley, I, Stewart, A, Flaxman, AD, Lozano, R, Mooney, MD, Luning, R, Hernandez, B, Black, R, Ahuja, R, Alam, N, Alam, SS, Ali, SM, Atkinson, C, Baqui, AH, Chowdhury, HR, Dandona, L, Dandona, R, Dantzer, E, Darmstadt, GL, Das, V, Dhingra, U, Dutta, A, Fawzi, W, Freeman, M, Gamage, S, Gomez, S, Hensman, D, James, SL, Joshi, R, Kalter, HD, Kumar, A, Kumar, V, Lucero, M, Mehta, S, Neal, B, Ohno, SL, Phillips, D, Pierce, K, Prasad, R, Praveen, D, Premji, Z, Ramirez-Villalobos, D, Rampatige, R, Remolador, H, Romero, M, Said, M, Sanvictores, D, Sazawal, S, Streatfield, PK, Tallo, V, Vadhatpour, A, Wijesekara, N, Murray, CJL, and Lopez, AD

Abstract

BACKGROUND: Verbal autopsy (VA) is recognized as the only feasible alternative to comprehensive medical certification of deaths in settings with no or unreliable vital registration systems. However, a barrier to its use by national registration systems has been the amount of time and cost needed for data collection. Therefore, a short VA instrument (VAI) is needed. In this paper we describe a shortened version of the VAI developed for the Population Health Metrics Research Consortium (PHMRC) Gold Standard Verbal Autopsy Validation Study using a systematic approach. METHODS: We used data from the PHMRC validation study. Using the Tariff 2.0 method, we first established a rank order of individual questions in the PHMRC VAI according to their importance in predicting causes of death. Second, we reduced the size of the instrument by dropping questions in reverse order of their importance. We assessed the predictive performance of the instrument as questions were removed at the individual level by calculating chance-corrected concordance and at the population level with cause-specific mortality fraction (CSMF) accuracy. Finally, the optimum size of the shortened instrument was determined using a first derivative analysis of the decline in performance as the size of the VA instrument decreased for adults, children, and neonates. RESULTS: The full PHMRC VAI had 183, 127, and 149 questions for adult, child, and neonatal deaths, respectively. The shortened instrument developed had 109, 69, and 67 questions, respectively, representing a decrease in the total number of questions of 40-55%. The shortened instrument, with text, showed non-significant declines in CSMF accuracy from the full instrument with text of 0.4%, 0.0%, and 0.6% for the adult, child, and neonatal modules, respectively. CONCLUSIONS: We developed a shortened VAI using a systematic approach, and assessed its performance when administered using hand-held electronic tablets and analyzed using Tariff 2.0. The len

Published
2015

16. 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

17. Improving performance of the Tariff Method for assigning causes of death to verbal autopsies

Author

Serina, P, Riley, I, Stewart, A, James, SL, Flaxman, AD, Lozano, R, Hernandez, B, Mooney, MD, Luning, R, Black, R, Ahuja, R, Alam, N, Alam, SS, Ali, SM, Atkinson, C, Baqui, AH, Chowdhury, HR, Dandona, L, Dandona, R, Dantzer, E, Darmstadt, GL, Das, V, Dhingra, U, Dutta, A, Fawzi, W, Freeman, M, Gomez, S, Gouda, HN, Joshi, R, Kalter, HD, Kumar, A, Kumar, V, Lucero, M, Maraga, S, Mehta, S, Neal, B, Ohno, SL, Phillips, D, Pierce, K, Prasad, R, Praveen, D, Premji, Z, Ramirez-Villalobos, D, Rarau, P, Remolador, H, Romero, M, Said, M, Sanvictores, D, Sazawal, S, Streatfield, PK, Tallo, V, Vadhatpour, A, Vano, M, Murray, CJL, Lopez, AD, Serina, P, Riley, I, Stewart, A, James, SL, Flaxman, AD, Lozano, R, Hernandez, B, Mooney, MD, Luning, R, Black, R, Ahuja, R, Alam, N, Alam, SS, Ali, SM, Atkinson, C, Baqui, AH, Chowdhury, HR, Dandona, L, Dandona, R, Dantzer, E, Darmstadt, GL, Das, V, Dhingra, U, Dutta, A, Fawzi, W, Freeman, M, Gomez, S, Gouda, HN, Joshi, R, Kalter, HD, Kumar, A, Kumar, V, Lucero, M, Maraga, S, Mehta, S, Neal, B, Ohno, SL, Phillips, D, Pierce, K, Prasad, R, Praveen, D, Premji, Z, Ramirez-Villalobos, D, Rarau, P, Remolador, H, Romero, M, Said, M, Sanvictores, D, Sazawal, S, Streatfield, PK, Tallo, V, Vadhatpour, A, Vano, M, Murray, CJL, and Lopez, AD

Abstract

BACKGROUND: Reliable data on the distribution of causes of death (COD) in a population are fundamental to good public health practice. In the absence of comprehensive medical certification of deaths, the only feasible way to collect essential mortality data is verbal autopsy (VA). The Tariff Method was developed by the Population Health Metrics Research Consortium (PHMRC) to ascertain COD from VA information. Given its potential for improving information about COD, there is interest in refining the method. We describe the further development of the Tariff Method. METHODS: This study uses data from the PHMRC and the National Health and Medical Research Council (NHMRC) of Australia studies. Gold standard clinical diagnostic criteria for hospital deaths were specified for a target cause list. VAs were collected from families using the PHMRC verbal autopsy instrument including health care experience (HCE). The original Tariff Method (Tariff 1.0) was trained using the validated PHMRC database for which VAs had been collected for deaths with hospital records fulfilling the gold standard criteria (validated VAs). In this study, the performance of Tariff 1.0 was tested using VAs from household surveys (community VAs) collected for the PHMRC and NHMRC studies. We then corrected the model to account for the previous observed biases of the model, and Tariff 2.0 was developed. The performance of Tariff 2.0 was measured at individual and population levels using the validated PHMRC database. RESULTS: For median chance-corrected concordance (CCC) and mean cause-specific mortality fraction (CSMF) accuracy, and for each of three modules with and without HCE, Tariff 2.0 performs significantly better than the Tariff 1.0, especially in children and neonates. Improvement in CSMF accuracy with HCE was 2.5%, 7.4%, and 14.9% for adults, children, and neonates, respectively, and for median CCC with HCE it was 6.0%, 13.5%, and 21.2%, respectively. Similar levels of improvement are seen in an

Published
2015

20. Understanding Caretakers' Dilemma in Deciding Whether or Not to Adhere with Referral Advice after Pre-Referral Treatment with Rectal Artesunate

Author

Simba, D. O., Kakoko, D. C., Warsame, M., Premji, Z., Gomes, M. F., Tomson, G., and Johansson, E.

Abstract

Background: Malaria kills. A single rectal dose of artesunate before referral can reduce mortality and prevent permanent disability. However, the success of this intervention depends on caretakers' adherence to referral advice for follow-up care. This paper explores the dilemma facing caretakers when they are in the process of deciding whether or not to transit their child to a health facility after pre-referral treatment with rectal artesunate. Methods: Four focus group discussions were held in each of three purposively selected villages in Mtwara rural district of Tanzania. Data were analysed manually using latent qualitative content analysis. Results: The theme "Caretakers dilemma in deciding whether or not to adhere with referral advice after pre-referral treatment with rectal artesunate" depicts the challenge they face. Caretakers' understanding of the rationale for going to hospital after treatment - when and why they should adhere - influenced adherence. Caretakers, whose children did not improve, usually adhered to referral advice. If a child had noticeably improved with pre-referral treatment however, caretakers weighed whether they should proceed to the facility, balancing the child's improved condition against other competing priorities, difficulties in reaching the health facilities, and the perceived quality of care at the health facility. Some misinterpretation were found regarding the urgency and rationale for adherence among some caretakers of children who improved which were attributed to be possibly due to their prior understanding. Conclusion: Some caretakers did not adhere when their children improved and some who adhered did so without understanding why they should proceed to the facility. Successful implementation of the rectal artesunate strategy depends upon effective communication regarding referral to clinic.

Published
2010

21. Using verbal autopsy to measure causes of death: the comparative performance of existing methods

Author

Murray, CJL, Lozano, R, Flaxman, AD, Serina, P, Phillips, D, Stewart, A, James, SL, Vahdatpour, A, Atkinson, C, Freeman, MK, Ohno, SL, Black, R, Ali, SM, Baqui, AH, Dandona, L, Dantzer, E, Darmstadt, GL, Das, V, Dhingra, U, Dutta, A, Fawzi, W, Gomez, S, Hernandez, B, Joshi, R, Kalter, HD, Kumar, A, Kumar, V, Lucero, M, Mehta, S, Neal, B, Praveen, D, Premji, Z, Ramirez-Villalobos, D, Remolador, H, Riley, I, Romero, M, Said, M, Sanvictores, D, Sazawal, S, Tallo, V, Lopez, AD, Murray, CJL, Lozano, R, Flaxman, AD, Serina, P, Phillips, D, Stewart, A, James, SL, Vahdatpour, A, Atkinson, C, Freeman, MK, Ohno, SL, Black, R, Ali, SM, Baqui, AH, Dandona, L, Dantzer, E, Darmstadt, GL, Das, V, Dhingra, U, Dutta, A, Fawzi, W, Gomez, S, Hernandez, B, Joshi, R, Kalter, HD, Kumar, A, Kumar, V, Lucero, M, Mehta, S, Neal, B, Praveen, D, Premji, Z, Ramirez-Villalobos, D, Remolador, H, Riley, I, Romero, M, Said, M, Sanvictores, D, Sazawal, S, Tallo, V, and Lopez, AD

Abstract

BACKGROUND: Monitoring progress with disease and injury reduction in many populations will require widespread use of verbal autopsy (VA). Multiple methods have been developed for assigning cause of death from a VA but their application is restricted by uncertainty about their reliability. METHODS: We investigated the validity of five automated VA methods for assigning cause of death: InterVA-4, Random Forest (RF), Simplified Symptom Pattern (SSP), Tariff method (Tariff), and King-Lu (KL), in addition to physician review of VA forms (PCVA), based on 12,535 cases from diverse populations for which the true cause of death had been reliably established. For adults, children, neonates and stillbirths, performance was assessed separately for individuals using sensitivity, specificity, Kappa, and chance-corrected concordance (CCC) and for populations using cause specific mortality fraction (CSMF) accuracy, with and without additional diagnostic information from prior contact with health services. A total of 500 train-test splits were used to ensure that results are robust to variation in the underlying cause of death distribution. RESULTS: Three automated diagnostic methods, Tariff, SSP, and RF, but not InterVA-4, performed better than physician review in all age groups, study sites, and for the majority of causes of death studied. For adults, CSMF accuracy ranged from 0.764 to 0.770, compared with 0.680 for PCVA and 0.625 for InterVA; CCC varied from 49.2% to 54.1%, compared with 42.2% for PCVA, and 23.8% for InterVA. For children, CSMF accuracy was 0.783 for Tariff, 0.678 for PCVA, and 0.520 for InterVA; CCC was 52.5% for Tariff, 44.5% for PCVA, and 30.3% for InterVA. For neonates, CSMF accuracy was 0.817 for Tariff, 0.719 for PCVA, and 0.629 for InterVA; CCC varied from 47.3% to 50.3% for the three automated methods, 29.3% for PCVA, and 19.4% for InterVA. The method with the highest sensitivity for a specific cause varied by cause. CONCLUSIONS: Physician review of verba

Published
2014

22. Chlorproguanil - Dapsone - Artesunate versus artemether - Lumefantrine: A randomized, double-blind phase III trial in African children and adolescents with uncomplicated Plasmodium falciparum malaria

Author

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.

Subjects
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

23. Factors Influencing Adherence to Referral Advice Following Pre-Referral Treatment with Artesunate Suppositories in Children in Rural Tanzania

Author

Simba, D. O., Warsame, M., Kimbute, O., Kakoko, D., Petzold, M., Tomson, G., Premji, Z., and Gomes, M.

Abstract

OBJECTIVE WHO recommends artemisinin suppository formulations as pre-referral treatment for children who are unable to take oral medication and cannot rapidly reach a facility for parenteral treatment. We investigated factors influencing caretakers' adherence to referral advice following pre-referral treatment of their children with rectal artesunate suppositories. METHODS The study was nested within an intervention study that involved pre-referral treatment of all children who came to a community dispenser for treatment because they were unable to take oral medications because of repeated vomiting, lethargy, convulsions or altered consciousness. All patients who did not comply with referral advice were stratified by actions taken post-referral: taking their children to a drug shop, a traditional healer, or not seeking further treatment, and added to a random selection of patients who complied with referral advice. Caretakers of the children were interviewed about their socioeconomic status (SES), knowledge about malaria, referral advice given and actions they took following pre-referral treatment. Interview data for 587 caretakers were matched with symptoms of the children, the time of treatment, arrival at a health facility or other actions taken post-pre-referral treatment. RESULTS The majority (93.5%) of caretakers reported being given referral advice by the community drug dispenser. The odds of adherence with this advice were three times greater for children with altered consciousness and/or convulsions than for children with other symptoms [odds ratio (OR) 3.47, 95% confidence interval (CI) 2.32-5.17, P < 0.001]. When questioned, caretakers who remembered when (OR 2.19, 95% CI 1.48-3.23, P < 0.001) and why (OR 1.77, 95% CI 1.07-2.95, P = 0.026) they were advised to proceed to health facility - were more likely to follow referral advice. Cost did not influence adherence except within a catchment area of facilities that charged for services. In these areas, costs deterred adherence by four to five times for those who had previously paid for laboratory services (OR = 0.25, 95% CI: 0.09-0.67, P = 0.006) or consultation (OR 0.20, 95% CI: 0.06-0.61, P = 0.005) compared with those who had not. CONCLUSION When given referral advice, caretakers of patients with life-threatening symptoms adhere to referral advice more readily than other caretakers. Health service charges deter adherence.

Published
2009

24. Dhfr and dhps mutations in Plasmodium falciparum isolates in Mlandizi, Kibaha

Author

Kidima, W, Nkwengulila, G, Premji, Z, Malisa, A, and Mshinda, H

Subjects
Plasmodium falciparum, sulfadoxine-pyrimethamine, dhfr, dhps, Tanzania
Abstract

Sulfadoxine-pyrimethamine (SP), the current first line antimalarial drug in Tanzania, is compromised by evolution and spread of mutations in the parasite's dhfr and dhps genes. In the present study we established the baseline frequencies of Plasmodium falciparum dihydrofolate reductase (pfdhfr) and dihydropteroate synthase (pfdhps) mutant genotypes and their potential for predicting the in vivo efficacy of SP in Mlandizi, Tanzania. The efficacy of SP treatment was by following 116 children with uncomplicated falciparum malaria for 14 days after treatment. Infected blood samples were collected on filter paper at days 0, 3, 7 and 14. Parasite genomic DNA was extracted and point mutations at positions 51, 59, 108 and 164 of the dhfr gene and at 581, 540 and 437 of the dhps gene were analysed by nested Polymerase Chain Reaction/ Restriction Fragment Length Polymorphism. Out of 116 children enrolled, 98 (86%) of eligible children demonstrated an adequate clinical response by day 14. There were 7.3 % early and 6.7% late therapeutic failures. At day 0, only 8.0% (4/50) the parasites showed no mutation at the dhfr locus; for dhps this was 73%. Triple mutant dhfr alleles (Ile 51, Arg 59, Asn 108) occurred in 47%, double mutant dhps (Gly 437, Glu 540) alleles in 7.9%. No mutation was detected at codon 164 of the dhfr gene. The presence of triple dhfr mutant alleles was related to clinical failure, but did not show significant association (Fisher exact test, P=0.166, OR 2.15 0.776.20). The higher rates of mutation on the dhfr do not spell a bright future for SP treatment in Tanzania. It is rational to think of an alternative first line antimalarial drug, while retaining SP for malaria intermittent treatment in regnancy. Keywords: Plasmodium falciparum, sulfadoxine-pyrimethamine, dhfr, dhps, TanzaniaTanzania Health Research Bulletin Vol. 8 (2) 2006: pp. 50-55

Published
2007

25. Population Health Metrics Research Consortium gold standard verbal autopsy validation study: design, implementation, and development of analysis datasets

Author

Murray, CJL, Lopez, AD, Black, R, Ahuja, R, Ali, SM, Baqui, A, Dandona, L, Dantzer, E, Das, V, Dhingra, U, Dutta, A, Fawzi, W, Flaxman, AD, Gomez, S, Hernandez, B, Joshi, R, Kalter, H, Kumar, A, Kumar, V, Lozano, R, Lucero, M, Mehta, S, Neal, B, Ohno, SL, Prasad, R, Praveen, D, Premji, Z, Ramirez-Villalobos, D, Remolador, H, Riley, I, Romero, M, Said, M, Sanvictores, D, Sazawal, S, Tallo, V, Murray, CJL, Lopez, AD, Black, R, Ahuja, R, Ali, SM, Baqui, A, Dandona, L, Dantzer, E, Das, V, Dhingra, U, Dutta, A, Fawzi, W, Flaxman, AD, Gomez, S, Hernandez, B, Joshi, R, Kalter, H, Kumar, A, Kumar, V, Lozano, R, Lucero, M, Mehta, S, Neal, B, Ohno, SL, Prasad, R, Praveen, D, Premji, Z, Ramirez-Villalobos, D, Remolador, H, Riley, I, Romero, M, Said, M, Sanvictores, D, Sazawal, S, and Tallo, V

Abstract

BACKGROUND: Verbal autopsy methods are critically important for evaluating the leading causes of death in populations without adequate vital registration systems. With a myriad of analytical and data collection approaches, it is essential to create a high quality validation dataset from different populations to evaluate comparative method performance and make recommendations for future verbal autopsy implementation. This study was undertaken to compile a set of strictly defined gold standard deaths for which verbal autopsies were collected to validate the accuracy of different methods of verbal autopsy cause of death assignment. METHODS: Data collection was implemented in six sites in four countries: Andhra Pradesh, India; Bohol, Philippines; Dar es Salaam, Tanzania; Mexico City, Mexico; Pemba Island, Tanzania; and Uttar Pradesh, India. The Population Health Metrics Research Consortium (PHMRC) developed stringent diagnostic criteria including laboratory, pathology, and medical imaging findings to identify gold standard deaths in health facilities as well as an enhanced verbal autopsy instrument based on World Health Organization (WHO) standards. A cause list was constructed based on the WHO Global Burden of Disease estimates of the leading causes of death, potential to identify unique signs and symptoms, and the likely existence of sufficient medical technology to ascertain gold standard cases. Blinded verbal autopsies were collected on all gold standard deaths. RESULTS: Over 12,000 verbal autopsies on deaths with gold standard diagnoses were collected (7,836 adults, 2,075 children, 1,629 neonates, and 1,002 stillbirths). Difficulties in finding sufficient cases to meet gold standard criteria as well as problems with misclassification for certain causes meant that the target list of causes for analysis was reduced to 34 for adults, 21 for children, and 10 for neonates, excluding stillbirths. To ensure strict independence for the validation of methods and assessment

Published
2011

26. Causes, Magnitude and Management of Burns in Under-Fives in District Hospitals in Dar Es Salaam, Tanzania.

Author

Justin-Temu, M., Rimoy, G., Premji, Z., Matemu, G., Justin-Temu, M., Rimoy, G., Premji, Z., and Matemu, G.

Abstract

Objectives: To determine the causes, magnitude and management of burns in children under five years of age who were admitted in the district hospitals of Dar es Salaam City, Tanzania. Methods: In this study, a total of 204 under fives were enrolled. Questionnaires were used to elicit if the parent/caretaker had the knowledge of the cause of the burns, what was done immediately after burn injury, first aid given immediately after burn, source of the knowledge of first aid and when the child was taken to the hospital. Also the questionnaire was cited with data on the management of burns in the hospitals through observation and checking the treatment files. Results: Forty nine percent were males while 50.5% were females. Most of the children (54.9%) were aged between 1-2 years. 78.4 % had scalds while 21.6 % had flame burns. No children w ere found to have burns caused by chemicals or electricity. Most of the burns (97.5%) occurred accidentally, although some (2.5%) were intentional. 68.6 % of these burn injuries occurred in the kitchen. Immediately after burn 87.3% of the children had first aid applied on their wounds while 12.7% didn’t apply anything. Of the agents used, honey was the most used (32.8%) followed by cold water (16.7%). The source of knowledge on these agents was from relatives and friends (72.5%), schools (7%), media (6%) and medical personnel (14%). The study further revealed that analgesics, intravenous fluids, antiseptics and antibiotics were the drugs used for treatment of burns in the hospital and that there was no specialized unit for burns in the hospitals. Conclusions: Causes of childhood burns are largely preventable requiring active social/medical education and public enlighten campaigns on the various methods of prevention. The government to see to it that hospitals have specialized units for managing burn cases and also the socio-economic status of its people be improved.

Published
2008

27. Dhfr and dhps mutations in Plasmodium falciparum isolates in Mlandizi, Kibaha, Tanzania: association with clinical outcome

Author

Kidima, W., Nkwengulila, G., Premji, Z., Malisa, A., Mshinda, H., Kidima, W., Nkwengulila, G., Premji, Z., Malisa, A., and Mshinda, H.

Abstract

Sulfadoxine-pyrimethamine (SP), the current first line antimalarial drug in Tanzania, is compromised by evolution and spread of mutations in the parasite's dhfr and dhps genes. In the present study we established the baseline frequencies of Plasmodium falciparum dihydrofolate reductase (pfdhfr) and dihydropteroate synthase (pfdhps) mutant genotypes and their potential for predicting the in vivo efficacy of SP in Mlandizi, Tanzania. The efficacy of SP treatment was by following 116 children with uncomplicated falciparum malaria for 14 days after treatment. Infected blood samples were collected on filter paper at days 0, 3, 7 and 14. Parasite genomic DNA was extracted and point mutations at positions 51, 59, 108 and 164 of the dhfr gene and at 581, 540 and 437 of the dhps gene were analysed by nested Polymerase Chain Reaction/ Restriction Fragment Length Polymorphism. Out of 116 children enrolled, 98 (86%) of eligible children demonstrated an adequate clinical response by day 14. There were 7.3 % early and 6.7% late therapeutic failures. At day 0, only 8.0% (4/50) the parasites showed no mutation at the dhfr locus; for dhps this was 73%. Triple mutant dhfr alleles (Ile 51, Arg 59, Asn 108) occurred in 47%, double mutant dhps (Gly 437, Glu 540) alleles in 7.9%. No mutation was detected at codon 164 of the dhfr gene. The presence of triple dhfr mutant alleles was related to clinical failure, but did not show significant association (Fisher exact test, P=0.166, OR 2.15 0.776.20). The higher rates of mutation on the dhfr do not spell a bright future for SP treatment in Tanzania. It is rational to think of an alternative first line antimalarial drug, while retaining SP for malaria intermittent treatment in pregnancy.

Published
2007

28. Efficacy and Effectiveness of Artemether-Lumefantrine after Initial and Repeated Treatment in Children < 5 Years of Age with Acute Uncomplicated Plasmodium falciparum Malaria in Rural Tanzania: A Randomized Trial

Author

Ngasala, B. E., primary, Malmberg, M., additional, Carlsson, A. M., additional, Ferreira, P. E., additional, Petzold, M. G., additional, Blessborn, D., additional, Bergqvist, Y., additional, Gil, J. P., additional, Premji, Z., additional, Bjorkman, A., additional, and Martensson, A., additional

Published
2011
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42. Influence of consecutive-day blood sampling on polymerase chain reaction-adjusted parasitological cure rates in an antimalarial-drug trial conducted in Tanzania.

Author

Martensson A, Ngasala B, Ursing J, Veiga MI, Wiklund L, Membi C, Montgomery SM, Premji Z, Färnert A, and Björkman A

Abstract

We assessed the influence that consecutive-day blood sampling, compared with single-day blood sampling, had on polymerase chain reaction (PCR)-adjusted parasitological cure after stepwise genotyping of merozoite surface proteins 2 (msp2) and 1 (msp1) in 106 children in Tanzania who had uncomplicated falciparum malaria treated with either sulfadoxine-pyrimethamine or artemether-lumefantrine; 78 of these children developed recurrent parasitemia during the 42-day follow-up period. Initial msp2 genotyping identified 27 and 33 recrudescences by use of single- and consecutive-day sampling, respectively; in subsequent msp1 genotyping, 17 and 21 of these episodes, respectively, were still classified as recrudescences; these results indicate a similar sensitivity of the standard single-day PCR protocol--that is, 82% (27/33) and 81% (17/21), in both genotyping steps. Interpretation of PCR-adjusted results will significantly depend on methodology. Copyright © 2007 Infectious Diseases Society of America [ABSTRACT FROM AUTHOR]

Published
2007
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44. An analysis of anemia and child mortality.

Author

Brabin, B J, Premji, Z, and Verhoeff, F

Subjects
*ANEMIA treatment, *IRON deficiency anemia treatment, *AGE distribution, *ANEMIA, *BLOOD transfusion, *DEMOGRAPHY, *IRON deficiency anemia, *LONGITUDINAL method, *MALARIA, *SURVIVAL analysis (Biometry), *CROSS-sectional method, *CASE-control method, *DISEASE complications, DEVELOPING countries
Abstract

The relationship of anemia as a risk factor for child mortality was analyzed by using cross-sectional, longitudinal and case-control studies, and randomized trials. Five methods of estimation were adopted: 1) the proportion of child deaths attributable to anemia; 2) the proportion of anemic children who die in hospital studies; 3) the population-attributable risk of child mortality due to anemia; 4) survival analyses of mortality in anemic children; and 5) cause-specific anemia-related child mortality. Most of the data available were hospital based. For children aged 0-5 y the percentage of deaths due to anemia was comparable for reports from highly malarious areas in Africa (Sierra Leone 11.2%, Zaire 12.2%, Kenya 14.3%). Ten values available for hemoglobin values <50 g/L showed a variation in case fatality from 2 to 29.3%. The data suggested little if any dose-response relating increasing hemoglobin level (whether by mean value or selected cut-off values) with decreasing mortality. Although mortality was increased in anemic children with hemoglobin <50 g/L, the evidence for increased risk with less severe anemia was inconclusive. The wide variation for mortality with hemoglobin <50 g/L is related to methodological variation and places severe limits on causal inference; in view of this, it is premature to generate projections on population-attributable risk. A preliminary survival analysis of an infant cohort from Malawi indicated that if the hemoglobin decreases by 10 g/L at age 6 mo, the risk of dying becomes 1.72 times higher. Evidence from a number of studies suggests that mortality due to malarial severe anemia is greater than that due to iron-deficiency anemia. Data are scarce on anemia and child mortality from non-malarious regions. Primary prevention of iron-deficiency anemia and malaria in young children could have substantive effects on reducing child mortality from severe anemia in children living in malarious areas. [ABSTRACT FROM AUTHOR]

Published
2001
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47. The pervasive triad of food security, gender inequity and women's health: Exploratory research from sub-Saharan Africa

Author

Adnan Hyder, Maman, S., Nyoni, J. E., Khasiani, S. A., Teoh, N., Premji, Z., and Sohani, S.

Abstract

Objectives: This study was designed to explore the interactions between food securing activities, health and gender equity from the perspective of rural east African women. The specific objectives were to document the critical interaction among these three issues—food security, gender inequity, women's health within the context of sub-Saharan Africa; to describe the nature of this triad from the perspective of women farmers in Africa; and to propose a framework for linking available interventions to the vicious nature of this triad. Setting: In-depth interviews and focus group discussions were conducted with rural women farmers in Kwale District, Kenya and Bagamoyo District, Tanzania. Methods: A total of 12 in-depth interviews and 4 focus group discussions have been included in this analysis. Transcribed text from interviews and focus group discussions were coded and thematic conceptual matrices were developed to compare dimensions of common themes across interviews and settings. A thematic analysis was then performed and a framework developed to understand the nature of the triad and explore the potential for interventions within the interactions. Findings: The vicious cycle of increasing work, lack of time, and lack of independent decision making for women who are responsible for food production and health of their families, has health and social consequences. Food securing activities have negative health consequences for women, which are further augmented by issues of gender inequity. Conclusion: The African development community must respond by thinking of creative solutions and appropriate interventions for the empowerment of women farmers in the region to ensure their health. African Health Sciences Vol. 5 (4) 2005: pp. 328-334

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