The MiPPAD study aimed to evaluate the safety, tolerability and efficacy of mefloquine (MQ) as an alternative to SP used for Intermittent Preventive Treatment in pregnancy (IPTp) in combination with Long Lasting Insecticide Treated Nets (LLITNs). It also involved HIV-infected pregnant women to provide a better understanding of the interactions between antimalarial treatment and HIV.
The first trial compared the currently recommended IPTp regime with two different formulations of MQ in 4,749 HIV-negative pregnant women. The main outcome of this trial was the frequency of children born with low birth weight.
The second trial compared three doses of MQ with a placebo in 1,017 HIV-positive pregnant women who also received cotrimoxazole. It compared the rates of women with malaria parasites in their blood or placenta at delivery. The trials also measured adverse pregnancy outcomes, such as miscarriage or stillbirth, as well as other indicators of maternal health during pregnancy and drug tolerability.
Both trials reported that MQ reduced malaria infections and improved overall health in pregnant women, compared to either SP (first trial) or placebo (second trial). However, results of the first trial indicated that neither of the two MQ regimens was better than SP at preventing low birth weight. In addition, tolerability for MQ was poorer than for SP, with more participants in the MQ groups reporting nausea and dizziness.
The second trial showed no difference in adverse pregnancy outcomes or in low birth weight between the two groups. It also showed poorer tolerability in the MQ group than the placebo group. Moreover, the second trial found that women in the MQ group had higher HIV viral loads at delivery than women in the placebo group, and were more likely to transmit HIV to their child around the time of birth. This result was based on an unplanned exploratory analysis and needs further investigation before drawing definitive conclusions as to whether MQ interferes with HIV suppression.
Based on these findings, the study concluded that MQ cannot be recommended as an alternative to SP in HIV-negative pregnant women nor for malaria prevention during pregnancy in HIV-positive women.
The trials were conducted in Benin (Allada, Sékou and Attogon), Gabon (Fougamou and Lambaréné), Kenya (Kisumu), Mozambique (Manhiça and Maragra), and in Tanzania (Makole and Chambwino). The study has also strengthened capacity development at institutional and individual levels for antimalarial research in all participating sites.