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
Prof Clara Menendez (IS Global, Spain) and Dr Meghna Desai (CDC, USA)European partners:
Prof Michel Cot (L'Institut de recherche pour le développement (IRD), France), Dr Michael Ramharter (Medical University of Vienna, Austria)Site PIs:
Dr Eusebio Macete (Manhiça Health Research Centre, Mozambique), Dr Achille Massougbodji (Université d'Abomey, Benin), Dr Ghyslain Mombo-Ngoma (Albert Schweitzer Hospital, Gabon), Prof Salim Abdulla (Ifakara Health Research and Development Centre (IHRDC),Tanzania)
The first trial aimed to compare the tolerability and efficacy of mefloquine (MQ) to sulfadoxine-pyrimethamine (SP) as intermittent preventative treatment (IPTp) for prevention of malaria in pregnancy in the context of long-lasting insecticide treated nets (LLIN).
The second trial aimed to determine the safety and efficacy of IPTp with mefloquine among HIV infected pregnant women receiving cotrimoxazole (CTX) prophylaxis.Study design
Trial 1 was an open-label randomised, three-arm trial to compare the safety, tolerability and efficacy of two-dose MQ with two-dose SP as IPTp, and to compare the tolerability of two different MQ administration regimens – with 15 mg/kg MQ given in one dose or split across two days, in the context of LLINs. A total of 4,749 pregnant women were enrolled across sites in Benin, Gabon, Mozambique, and Tanzania.
Trial 2 was a randomised double-blind placebo-controlled trial on the efficacy of three-monthly doses of MQ as IPTp compared with placebo-IPTp in HIV infected pregnant women receiving CTX prophylaxis in the context of LLIN use. A total of 1,071 HIV-infected women from Kenya, Mozambique, and Tanzania were enrolled on the trial.
In both trials, pregnant women were recruited at the first antenatal visit and followed up until one month after delivery.Results and Conclusions
Trial 1: Two IPTp administrations with MQ in the context of LLIN use had a better antimalarial prophylactic efficacy than SP, with a comparable safety profile on pregnancy outcomes. However, the tolerability of MQ was much lower than SP, even when splitting the dose over two days, which limits the potential for replacing SP with MQ for IPTp in endemic regions of Africa.
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 trial however demonstrated that an effective antimalarial added to CTXp and LLINs in HIV-infected pregnant women can improve malaria prevention, as well as maternal health through reduction in hospital admissions. MQ was associated with an increased risk of mother to child transmission of HIV, which warrants further research on the pharmacological interactions between antimalarials and antiretroviral drugsImpact of the 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 (Malaria Policy Advisory Committee Meeting 11-13 September 2013)
Ruperez, M., et al. (2016). "Mortality, Morbidity, and Developmental Outcomes in Infants Born to Women Who Received Either Mefloquine or Sulfadoxine-Pyrimethamine as Intermittent Preventive Treatment of Malaria in Pregnancy: A Cohort Study." PLoS Med 13(2): e1001964.
Green, M., et al. (2016). "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 15: 7.
Gonzalez, R., et al. (2014). "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.
Gonzalez, R., et al. (2014). "Intermittent preventive treatment of malaria in pregnancy with mefloquine in HIV-negative women: a multicentre randomized controlled trial." PLoS Med 11(9): e1001733.
Pell, C., et al. (2014). "The acceptability of intermittent screening and treatment versus intermittent preventive treatment during pregnancy: results from a qualitative study in Northern Ghana." Malar J 13: 432.
Ouedraogo, S., et al. (2013). "Maternal anemia in pregnancy: assessing the effect of routine preventive measures in a malaria-endemic area." Am J Trop Med Hyg 88(2): 292-300.
Basra, A., et al. (2013). "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 56(6): e68-75.
Ouedraogo, S., et al. (2012). "Malaria and gravidity interact to modify maternal haemoglobin concentrations during pregnancy." Malar J 11: 348.
Ouedraogo, S., et al. (2012). "Maternal anemia at first antenatal visit: prevalence and risk factors in a malaria-endemic area in Benin." Am J Trop Med Hyg 87(3): 418-424.
Capan-Melser, M., 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(6): 1898-1902.
Mombo-Ngoma, G., et al. (2015). "Loa loa Infection in Pregnant Women, Gabon." Emerg Infect Dis 21(5): 899a-901.
Sicuri, E., et al. (2015). "Economic evaluation of an alternative drug to sulfadoxine-pyrimethamine as intermittent preventive treatment of malaria in pregnancy." PLoS One 10(4): e0125072.
Moya-Alvarez, V., et al. (2015). "Does Iron Increase the Risk of Malaria in Pregnancy?" Open Forum Infect Dis 2(2): ofv038.
Capan-Melser, M., et al. (2015). "Epidemiology of Human Herpes Virus 8 in Pregnant Women and their Newborns--A cross-sectional delivery survey in Central Gabon." Int J Infect Dis 39: 16-19.
Mayor, A., et al. (2015). "Changing Trends in P. falciparum Burden, Immunity, and Disease in Pregnancy." N Engl J Med 373(17): 1607-1617.
Menendez, C., et al. (2007). "Reducing the burden of malaria in pregnancy by preventive strategies." Lancet Infect Dis 7(2): 126-135.