New Drugs for IPTp
Evaluation of alternative antimalarial drugs to sulfadoxine-pyrimethamine for intermittent preventive treatment in pregnancy (IPTp) in the context of insecticide treated nets
Project Coordinator(s): Clara Menendez (Spain) and Meghna Desai (USA)European partners:
Michel Cot (France), Michael Ramharter (Austria), Gabriela Schreyer (Austria)Site PIs:
Eusebio Macete (Mozambique), Achille Massougbodji (Benin), Ghyslain Mombo-Ngoma (Gabon), Salim Abdulla (Tanzania), Meghna Desai (Kenya)
The first trial compared the safety, tolerability and efficacy of mefloquine to sulfadoxine-pyrimethamine as IPTp for the prevention for malaria in pregnancy in the context of ITNs. This study involved 4749 pregnant women in research centres in Mozambique, Benin, Tanzania and Gabon.
The second trial looked to determine safety and efficacy of IPTp with mefloquine among HIV infected pregnant women receiving cotrimoxazole (CTX) prophylaxis and involved 1071 women in Kenya, Tanzania and Mozambique.
The allocation of funds in this project represented a unique opportunity not only for research activities through clinical trials but the overall project objectives facilitated excellent capacity building and networking activities among all institutions involved.
Trial 1: Two IPTp administrations with MQ in the context if ITN use had a better antimalarial prophylactic efficacy than SP, with a comparable safety profile on pregnancy outcomes. However, the tolerability of MQ was worse than SP which limits the potential for IPTp with MQ.
Trial 2: While there was a reduction in maternal parasitaemia and placental infection with IPTp with MQ, there was no difference in prevalence of adverse pregnancy outcomes and drug tolerability was poorer with MQ. The frequency of perinatal mother to child transmission of HIV was increased in the women who received MQ in exploratory analysis, and requires further research.
The results were presented and discussed by WHO Expert Review Group in 2013 and 2015 and WHO experts concluded that MQ at a dose of 15mg/kg could not be recommended for IPTp because of low tolerability.
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Sicuri, E, Fernandes, S, Macete, E, Gonzalez, R, Mombo-Ngoma, G, Massougbodgi, A, Abdulla, S, Kuwawenaruwa, A, Katana, A, Desai, M, Cot, M, Ramharter, M, Kremsner, P, Menendez, C. Economic evaluation of an alternative drug to sulfadoxine-pyrimethamine as intermittent preventive treatment of malaria in pregnancy. PLoS ONE 10(4): e0125072 http://dx.doi.org/ 10.1371/journal.pone.0125072
González, R., Desai, M., Macete, E., Ouma, P., Kakolwa, M. A., Abdulla, S., Aponte, J. J., Bulo, H., Kabanywanyi, A. M., Katana, A., Maculuve, S., Mayor, A., Nhacolo, A., Otieno, K., Pahlavan, G., Rupérez, M., Sevene, E., Slutsker, L., Vala, A., Williamsom, J., Menéndez, C. Intermittent Preventive Treatment of Malaria in Pregnancy with Mefloquine in HIV-Infected Women Receiving Cotrimoxazole Prophylaxis: A Multicenter Randomized Placebo-Controlled Trial. PLoS Med 11(9):e1001735.
González, R., Mombo-Ngoma, G., Ouédraogo, S., Kakolwa, M. A., Abdulla, S., Accrombessi, M., Aponte, J. J., Akerey-Diop, D., Basra, A., Briand, V., Capan, M., Cot, M., Kabanywanyi, A. M., Kleine, C., Kremsner, P. G., Macete, E., Mackanga, J. R., Massougbodgi, A., Mayor, A., Nhacolo, A., Pahlavan G., Ramharter, M., Rupérez, M., Sevene, E., Vala, A., Zoleko-Manego, R., Menéndez, C. Intermittent Preventive Treatment of Malaria in Pregnancy with Mefloquine in HIV-Negative Women: A Multicentre Randomized Controlled Trial. PLoS Med 11(9):e1001733.
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Oué'draogo, S., K. Koura, G., K., Bodeau-Livinec, F., Manfred M. K. Accrombessi, M., M., K., Massougbodji, A., Cot, M. Maternal Anemia in Pregnancy: Assessing the Effect of Routine Preventive Measures in a Malaria-Endemic Area, Am.J. Trop. Med. Hyg, 2013, 88(2), pp. 292-300, 95