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The Malaria in Pregnancy (MiP) Library is a regularly updated, comprehensive bibliographic database of published and unpublished literature relating to malaria in pregnancy, including a trial registry of planned and ongoing trials. The MiP library is a product of the Malaria in Pregnancy Consortium and is available free of charge.

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 Article highlights from the update in January 2017

Article highlights from the update in December 2018 - January 2019

In January 2019, 202 new entries were added to the MiP library.New entries include peer reviewed journal articles, PhD and MSc theses, reports, and conference abstracts. Here we highlight new articles that may be of particular interest.

Chloroquine (CQ) has historically been used for malaria prophylaxis and treatment and is still being used as treatment for P. vivax. In Malawi, the use of chloroquine for treatment of malaria was stopped in 1993 because of the high level of drug resistance but a return of susceptibility to chloroquine has been noted since the drug was removed.  An open label trial in Malawi among women in their first and second pregnancies in 2012-2014 compared intermittent preventive treatment (IPTp) with sulfadoxine-pyrimethamine (SP, monthly doses), versus IPTp with CQ (3-day regimen, at least two doses at monthly intervals) versus CQ prophylaxis (300 mg weekly after a start dose of 600 mg) (Divala et al. 2018). No difference was seen in prevalence of placental malaria by histology in unadjusted analyses, but in analyses adjusted for maternal age and other factors, women taking chloroquine as prophylaxis had 34% lower placental infections than those receiving intermittent sulfadoxine-pyrimethamine (RR 0·66, 95% CI 0·46–0·95). No significant differences between arms were noted for clinical malaria, maternal anaemia, and low birth weight. Women in the CQ arms, and particularly in the CQ IPTp arm, reported significant more adverse events. Although not strictly a trial among pregnant women, it is exciting that Mordmuller et al. (2018) report on the first human, randomized, double-blind clinical trial of differentially adjuvanted PAMVAC, a vaccine candidate to prevent pregnancy-associated malaria. Among non-malaria exposed, healthy adult volunteers, PAMVAC was safe and well tolerated at all tested formulations and dosages and induced functional antibodies that persisted for more than six months.

Two new reviews on the safety of antimalarials for pregnant (and lactating) women were published. Saito et al. (2018) conclude that artemisinins are more efficacious and well-tolerated than quinine for the treatment of malaria in pregnancy. Moore et al. (2018) focussed on prevention and stressed the need for alternative drugs or combination therapies to SP for IPTp; however, dose modification of alternative strategies may be needed (e.g. dihydroartemisinin-piperaquine and azithromycin-based combinations).

Although methods of prevention of malaria in pregnancy are available, studies show repeatedly that coverage of insecticide treated nets and IPTp with SP are far from optimal. A study in Liberia reported on the barriers to use such as different beliefs on the cause of malaria, the lack of financial means to access to clinic-based malaria care, the unofficial user fees requested by healthcare workers, and the preference of male partners for traditional medicine (Tarr-Attia et al. 2018).  An update on the uptake and effect of the 2012 policy update on IPTp (recommending monthly dosing, and a minimum of three instead of two doses SP) for the 17 countries involved in the President's Malaria Initiative (PMI) is given by Henry et al. (2018). Although adaptation of the policy was slow, the coverage of IPTp1+, 2+, and 3+ has increased by 19, 16, and 13 percentage points respectively since the revised policy.

Studies in the past on the association between maternal malaria and vertical transmission of HIV have so far given conflicting results.  Sadoh et al. (2018) report no association between congenital malaria and vertical (mother-to-child) transmission of HIV in a Nigerian survey. Highly active retroviral treatment starting before pregnancy was associated with reduction in vertical HIV transmission. A previous trial has demonstrated an unexpected higher risk of vertical HIV transmission when mefloquine (MQ) was used as IPTp; further analyses of pharmacokinetic information revealed that median nevirapine concentrations were significantly lower in the MQ study arm compared with the placebo study arm in maternal and cord plasma, whereas plasma concentrations of zidovudine and lamivudine did not seem to be affected by MQ (Haaland et al. 2018).

Malaria during pregnancy can affect development of immunity to vaccines, e.g. to tetanus vaccination. A study among Colombian pregnant women noted that Plasmodium infection altered the development of the immune response to the TT vaccine (Alvarex-Larotta et al. 2019). In Tanzania Moeller et al. (2018) explored the effect of malaria in the first trimester on the development of the placenta and reported that malaria infection in early pregnancy impedes placental vascular development; these vascular changes were detectable at delivery; indicators of impeded placental development were associated with lower birth weight and reduced gestational length. However, a study in Benin did not detect any direct effect of 1st trimester malaria infections on birth outcomes; the association of early infections with infections later in pregnancy tended to increase the risk of low birthweight. Malaria in the 1st trimester was significantly associated with maternal anaemia in the 3rd trimester in the Benin study (Accrombessi et al. 2018). Natama et al examined cytokines, chemokines and growth factors in cord blood and the association with malaria exposure during pregnancy and malaria risk in infancy in Burkina Faso. They noted that past placental malaria had a profound effect on foetal immune system and that differential alterations of innate immune responses by malaria exposure during pregnancy might drive heterogeneity between individuals to clinical malaria susceptibility during the first year of life. Odorizzi et al. (2018) assessed the frequency, phenotype, and function of cord blood T cells from Ugandan infants born to mothers with and without placental malaria and reported that foetal CD4(+) and CD8(+) T cells from placental malaria-exposed infants exhibited greater in vitro proliferation to malaria antigens. Malaria-specific CD4(+) T cell proliferation correlated with prospective protection from malaria during childhood.

A proteomics study from Colombia examined data from a mouse model of placental malaria and from 5 human placentas with (past infection) and 5 placentas without evidence of malaria exposure during pregnancy, and suggested that apoptosis-related mechanisms are associated with placental malaria (Kawahara et al. 2018).

Results of a pharmacokinetic modelling study predicted that higher piperaquine concentrations may be needed in pregnant women to prevent infections with mutant compared to wild type parasites and that the overall burden of infections with mutant parasites may be lower for dihydroartemisinin-piperaquine (DP) than SP (Wallender et al. 2018). A pharmacokinetic study on artemether-lumefantrine reported that lumefantrine pharmacokinetic target attainment appeared to be reassuring in Rwandese pregnant women (Lohy Das et al. 2018).

A study in Ghana comparing submicroscopic gametocyte levels among different age groups and by pregnancy status reported that children and pregnant women are particularly important as P. falciparum submicroscopic gametocyte reservoirs (Lamptey et al. 2018). In Benin, Jafari-Guemouri et al. (2018) examined the effect of IPTp-SP on gametocyte carriage in infected pregnant women; IPTp-SP treatment contributed to modifications of the parasite populations' structure during pregnancy and this may be a risk factor for increased transmission.