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)


Objective:

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.

Results

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.

Publications

Green M, Otieno K, Katana A, Slutsker L, Kariuki S, Ouma P, González R, Menendez C, ter Kuile FO, Desai M.  Pharmacokinetics of Mefloquine and Its Effect on Sulfamethoxazole and Trimethoprim Steady-state Blood Levels in Intermittent Preventive Treatment (IPTp) of Pregnant HIV-infected Women in Kenya. Malar J. 2016 Jan 5;15(1):7. doi: 10.1186/s12936.

Capan-Melser et al.  Epidemiology of Human Herpes Virus 8 in Pregnant Women and their Newborns--A cross-sectional delivery survey in Central Gabon. (2015). Int J Infect Dis. 39:16-9. doi: 10.1016/j.ijid.2015.08.004. Epub 2015 Aug 10. 

Capan-Melser M, Mombo Ngoma G, Akerey-Diop D, Basra A, et al. (2015) Evaluation of intermittent preventive treatment of malaria against group B Streptococcus colonization in pregnant women: a nested analysis of a randomized controlled clinical trial of sulfadoxine/pyrimethamine versus mefloquine. J Antimicrob Chemother. 70: 1898-1902. 

Mombo-Ngoma G, Mackanga JR, Basra A, Capan M, Manego RZ, et al. Loa loa Infection in Pregnant Women, Gabon. Emerg Infect Dis 21: 899a-901. 

Moya-Alvarez V, et al.  Does iron increase the risk of malaria in pregnancy? (2015). Open Forum Infectious Diseases. Mar 20;2(2):ofv038. doi: 10.1093/ofid/ofv038. eCollection 2015.

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. 

Basra, A., Mombo-Ngoma,G., Melser,C., M., Diop, D., A., Würbel, H., Mackanga, J.,R., Fürstenau, M., Zoleko, R., M., Adegnika, A., A., Gonzalez, R., Menendez, C., Kremsner, P., G., Ramharter, M. Efficacy of Mefloquine Intermittent Preventive Treatment in Pregnancy Against Schistosoma haematobium Infection in Gabon: A Nested Randomized Controlled Assessor-Blinded Clinical Trial, Clin. Infect. Dis., 2012, 

Oue´draogo,S., Bodeau-Livinec, F., Briand, V., Huynh, B., T., Koura, G., K., Accrombessi, M., M., K., Fievet, N., Massougbodji, A., Deloron, P., Cot, M.  Malaria and gravidity interact to modify maternal haemoglobin concentrations during pregnancy, Malaria Journal, 2012, 11:348

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