Mefloquine for preventing malaria in pregnant women

Abstract

BackgroundThe World Health Organization recommends intermittent preventive treatment in pregnancy (IPTp) with sulfadoxine-pyrimethamine for malaria for all women who live in moderate to high malaria transmission areas in Africa. However, parasite resistance to sulfadoxine-pyrimethamine has been increasing steadily in some areas of the region. Moreover, HIV-infected women on cotrimoxazole prophylaxis cannot receive sulfadoxine-pyrimethamine because of potential drug interactions. Thus, there is an urgent need to identify alternative drugs for prevention of malaria in pregnancy. One such candidate is mefloquine.ObjectivesTo assess the effects of mefloquine for preventing malaria in pregnant women, specifically, to evaluate:the efficacy, safety, and tolerability of mefloquine for preventing malaria in pregnant women; andthe impact of HIV status, gravidity, and use of insecticide-treated nets on the effects of mefloquine.Search methodsWe searched the Cochrane Infectious Diseases Group Specialized Register, the Cochrane Central Register of Controlled Trials (CENTRAL) in the Cochrane Library, MEDLINE, Embase, Latin American Caribbean Health Sciences Literature (LILACS), the Malaria in Pregnancy Library, and two trial registers up to 31 January 2018. In addition, we checked references and contacted study authors to identify additional studies, unpublished data, confidential reports, and raw data from published trials.Selection criteriaRandomized and quasi-randomized controlled trials comparing mefloquine IPT or mefloquine prophylaxis against placebo, no treatment, or an alternative drug regimen.Data collection and analysisTwo review authors independently screened all records identified by the search strategy, applied inclusion criteria, assessed risk of bias, and extracted data. We contacted trial authors to ask for additional information when required. Dichotomous outcomes were compared using risk ratios (RRs), count outcomes as incidence rate ratios (IRRs), and continuous outcomes using mean differences (MDs). We have presented all measures of effect with 95% confidence intervals (CIs). We assessed the certainty of evidence using the GRADE approach for the following main outcomes of analysis: maternal peripheral parasitaemia at delivery, clinical malaria episodes during pregnancy, placental malaria, maternal anaemia at delivery, low birth weight, spontaneous abortions and stillbirths, dizziness, and vomiting.Main resultsSix trials conducted between 1987 and 2013 from Thailand (1), Benin (3), Gabon (1), Tanzania (1), Mozambique (2), and Kenya (1) that included 8192 pregnant women met our inclusion criteria.Two trials (with 6350 HIV-uninfected pregnant women) compared two IPTp doses of mefloquine with two IPTp doses of sulfadoxine-pyrimethamine. Two other trials involving 1363 HIV-infected women compared three IPTp doses of mefloquine plus cotrimoxazole with cotrimoxazole. One trial in 140 HIV-infected women compared three doses of IPTp-mefloquine with cotrimoxazole. Finally, one trial enrolling 339 of unknown HIV statu...

Markers of sulfadoxine–pyrimethamine resistance in Eastern Democratic Republic of Congo; implications for malaria chemoprevention

“…However, with resistance markers well above the threshold of 50% (for K540E) this cannot be supported. Although WHO still recommends IPTp with SP in areas with high level of resistance to SP, based on studies in Tanzania and Malawi [32], the current findings of high prevalence of SP resistance among the target population suggest that the efficacy of IPTp in this setting should continue to be monitored [33] and alternative drugs such as dihydroartemisinin-piperaquine, mefloquine or doxycycline may be worth considering [34][35][36].…”

“…In the Democratic Republic of Congo (DRC) cases of malaria are rising, and the death toll is increasing [1]. In 2017 in DRC there was an estimated number of 25 million (15.7-36.8) cases of malaria and an estimated 46,800 (36,300) deaths. The majority of malaria cases in DRC are caused by Plasmodium falciparum, although Plasmodium ovale [2], Plasmodium malariae, and Plasmodium vivax are present among symptomatic cases [3].…”

In vitro hepatic metabolism of mefloquine using microsomes from cats, dogs and the common brush-tailed possum (Trichosurus vulpecula)

“…The antimalarial drug mefloquine is currently used for both prevention (as a monotherapy) and treatment (either alone, or in combination with artesunate) of chloroquine-resistant Plasmodium falciparum malaria in humans [6][7][8]. It was found to substantially reduce the viral load of FIPV and feline calicivirus (FCV) at low concentrations in infected Crandell Rees feline kidney cells without cytotoxic effects [9,10].…”

Severe acute respiratory syndrome coronavirus-2 and the deduction effect of angiotensin-converting enzyme 2 in pregnancy

“…However, a large-scale study demonstrated the safety of chloroquine in pregnancy. 62 – 64 Pregnant women with SARS-CoV-2 infection are considered relatively high risk. The management strategy is shown below.…”