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The Malaria in Pregnancy (MiP) Library is a regularly updated, comprehensive bibliographic database of published and unpublished literature relating to malaria in pregnancy, including a trial registry of planned and ongoing trials.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 September and December 2017

In January 2018, 208 new entries were added to the MiP library.New entries include peer reviewed journal articles, PhD and MSc theses, reports, and conference abstracts. We report here articles that may be of particular interest from the last two updates (September and December 2017) owing to a technical glitch during the September update (198 new entries).

A large multicentre study reported on the burden and impact of Plasmodium vivax in pregnancy, and detected a significant number of submicroscopic infections in four countries, and an association between clinical vivax malaria during pregnancy and maternal anaemia comparable to clinical P. falciparum. Asymptomatic vivax malaria was not associated with maternal anaemia (Bardaji et al. 2017). Similarly, an African multicentre study evaluated the effect of P. falciparum in 4 countries among HIV-negative and HIV-positive women, and concluded that the lowest levels of resistance (defined by the proportion of submicroscopic infections and the levels of anti-parasite antibodies quantified by Luminex) were accompanied by the largest adverse impact of P. falciparum infections (Ndam et al. 2017).

Two trials evaluated drugs for malaria treatment in pregnant women. Nambozi et al. (2017) compared artemether-lumefantrine, mefloquine-artesunate and dihydroartemisinin-piperaquine (DHS-PPQ) for P. falciparum in Zambia. DHS-PPQ had the lowest PCR-adjusted treatment failure, but overall, all three drugs performed well. A trial in Ghana compared DHS-PPQ with artesunate-amodiaquine (ASAQ); DHA-PPQ was non-inferior to ASAQ (Osarfo et al. 2017). A systematic review of the efficacy of artemisinin-based and quinine based malaria treatment in pregnant women is available, discussing both methodological issues (“Efficacy studies in pregnancy are not only limited in number but use varied methodological assessments”(Saito et al. 2017) and safety reporting (“Incomplete reporting and varied methodological assessment of pregnancy outcomes in anti-malarial drug efficacy studies limits comparison across studies” (Saito et al. 2017). The use of artemisinins in the first trimester has been so far only deemed acceptable in emergency situations whereby the benefits to the mother outweigh the potential embryo-toxic risk to the infant. However, a new large systematic review by Dellicour et al. (2017) reported on adverse outcomes of first trimester use of artemisinin derivatives versus quinine or no antimalarial treatment. Compared to quinine, artemisinin treatment in the first trimester was not associated with an increased risk of miscarriage, stillbirth, or congenital anomalies.

There was plenty of new information on the epidemiology of malaria in pregnancy. Moore et al. (2017) described the influence of number and timing of malaria episodes on prematurity and small-for-gestational age among cohorts of pregnant women followed in a low transmission are at the Thai-Burmese border (N=50,060). Malaria was highest early in the first trimester; the number of malaria episodes was associated with small-for-gestational age, and malaria in or after the 2nd trimester was associated with preterm birth. Additionally, they described the risk of stillbirth and neonatal death in the same cohorts (Moore et al. 2017); symptomatic falciparum and vivax malaria (but not asymptomatic malaria) increased the hazard of antepartum stillbirth. Vivax and falciparum malaria during pregnancy were associated with neonatal deaths. In a conclusive study, the same group reported a systematic review on malaria and stillbirths, including 59 studies, 141,415 women and 3387 stillbirths (Moore et al. 2017); P falciparum and P vivax malaria in pregnancy both increased the stillbirth risk whereby the association between P falciparum malaria in pregnancy and stillbirth was two times greater in areas of low-to-intermediate endemicity than in areas of high endemicity . They estimated that 20% of the stillbirths in sub-Saharan Africa could be attributed to falciparum malaria. The high malaria risk in the first trimester was also highlighted in West Africa by a study by Berry et al. (2017)Schmiegelow et al. (2017) followed pregnancies in the first trimester and with no other malaria infections using ultrasound and showed an adverse effect of first trimester malaria infection on foetal growth, pregnancy duration and birth weight.

 

endemicity . They estimated that 20% of the stillbirths in sub-Saharan Africa could be attributed to falciparum malaria. The high malaria risk in the first trimester was also highlighted in West Africa by a study by Berry et al. (2017)Schmiegelow et al. (2017) followed pregnancies in the first trimester and with no other malaria infections using ultrasound and showed an adverse effect of first trimester malaria infection on foetal growth, pregnancy duration and birth weight.

A large meta-analysis using individual patient data examined the relationship between malaria, malnutrition and birth weight (Cates et al. 2017) using pooled data from 14,633 pregnancies from 13 studies. They concluded that pregnant women with malnutrition and malaria infection are at increased risk of LBW compared to women with only one risk factor or none, but malaria and malnutrition did not act synergistically.

HIV-infected pregnant women are at increased risk of malaria compared to HIV-uninfected pregnant women; they are recommended to receive daily trimethoprim-sulphamethoxazole (CTX) prophylaxis but this may not always happen in reality. Stoner et al. (2017) showed that three doses of SP was associated with a reduction of low birth weight among HIV-positive women not using CTX, and that women taking antiretroviral therapy benefited as well. Roh et al. (2017) evaluated the effect of indoor residual spraying with insecticide (IRS); IRS was associated with reductions in malaria and preterm birth among pregnant women with HIV receiving bed nets, daily CTX, and combination antiretroviral therapy. Choi et al. (2017) presented a cost-effectiveness analyses of malaria prophylaxis among HIV-infected pregnant women and concluded that in malarious regions of sub-Saharan Africa, daily CTX for HIV-infected pregnant women regardless of CD4 cell count is cost-effective compared with 3-dose IPTp-SP as long as more than 82% of women adhere to daily dosing.

In the past, pregnant women were often excluded from pharmacokinetic studies although pharmacokinetics of drugs may be different compared to non-pregnant adults because of the physiological changes during pregnancy, or comorbidity of other diseases (HIV) or the concomitant use of other medication (e.g. antiretroviral therapy). Fortunately, this is changing and in this update De Kock et al. (2017) reported on a large multi-country study of the pharmacokinetics of sulphadoxine-pyrimethamine and Salman et al. supplemented the study of De Kock (2017) with data obtained from Papua New Guinea. In a separate article, Salman et al. provided information on the pharmacokinetics of chloroquine (Salman et al. 2017). Wallender et al. (2017) used population-pharmacokinetic models to come to an optimal DHA-PPQ strategy for HIV-infected women receiving efavirenz-based antiretroviral therapy, because previous studies showed that in this group piperaquine exposure was markedly reduced.

There were several articles which related to the effect of maternal malaria on the materno-foetal antibody transfer (McLean et al. 2017, McKittrick et al. 2017). Although there are numerous other interesting articles with regards to the immunology, epidemiology, and pathophysiology of malaria in pregnancy and health service delivery for malaria in pregnancy, we lastly mention Natama et al. (2017). In the past many authors have expressed concern about the risk of congenital malaria, but Natama et al. (2017) report no evidence of a significant clinical impact of congenital malaria detected by PCR on infant’s health from birth to 59 days.