New Drugs for IPTp

Project Coordinator(s):   

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)

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Objective

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 drugs

Impact 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)