The Malaria in Pregnancy (MiP) Library is a regularly updated, comprehensive bibliographic database of published and unpublished literature relating to malaria in pregnancy, including a trial registry of planned and ongoing trials.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 May 2018

In May 2018, 155 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 interest.

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).

A trial reported by Gies et al. (2018) in Burkina Faso explores the impact of iron supplementation on malaria and anaemia among adolescent and adult pregnant and non-pregnant women in a malarious environment. In this double blind randomized controlled non-inferior trial, non-pregnant nulliparae were assigned to weekly supplementation (60 mg iron and 2.8 mg folic acid) (n=980) or 2.8 mg folic acid (n=979) and followed until first antenatal visit (ANC1), or 18 months if remaining non-pregnant. There was no difference at first antenatal visit (n=315) or after 18 months (n=916) in parasitaemia or anaemia or plasma iron biomarkers. In this location, parasitemia was high among pregnant and non-pregnant women (54.3% and 41.0%, respectively by microscopy). As a unique occurrence, there were two additional studies in this review (all in West Africa) reporting on malaria among cohorts of women followed from pre-conception into pregnancy. Among 387 women followed from pre-conception into pregnancy in Benin, malaria prevalence before conception was 6.3%, in the 1st month 16.7%, 2nd month 9.2% and 3rd month 11.2% (microscopy); the risk of malaria infection decreased throughout the first trimester in multigravidae (aOR: 0.61; 95% CI, 0.38–0.96), but not in primigravidae,  and women infected with malaria before pregnancy remained significantly more likely to be infected with malaria during the first trimester (Accrombessi et al. 2018).   Tuikue-Ndam et al. (2018) followed a cohort of 275 nulligravidae in Benin, and 68 women became pregnant. Before pregnancy, P. falciparum prevalence rates were 15% by microscopy and 66% by PCR. Microscopic infection rates increased to 29% until intermittent preventive treatment with sulphadoxine-pyrimethamine (IPTp-SP) administration in the 4 month of pregnancy, and their density increased by 20-fold. Conversely, submicroscopic infections decreased. Following IPT administration, malaria infections decreased, but increased again late in pregnancy. They also noted that there was an increased risk of infection in women who were infected before pregnancy, and this was not related to season of occurrence. The persistence of infections was proven using genotyping; Ofori et al. corroborated on this using immunological studies

There has been conflicting information on the effect of malaria during pregnancy or in the placenta on infant malaria, and this update is no exception. Bouaziz et al (2018) followed a cohort of 500 infants born to mothers with known placental malaria status for 18 months with weekly visits in Benin. Placental malaria was not associated with an overall susceptibility to malaria but only with the delay of occurrence of the first malaria attack; children who experienced 1 malaria attack were more likely to develop subsequent attacks, independent of placental malaria. Tassi et al (2018) reports in a smaller study (n=72, up to 12 months postpartum) that only low placental parasitemia (compared to high) was associated with increased susceptibility to malaria during infancy. Results of a trial in Burkina Faso where IPTp was supplemented with community screening and treatment in one arm vs. routine IPTp-SP in the other followed infants in the first year as well and reported that the first arm may provide additional protection against both malaria and non-malarial fevers in infants, and suggest that malaria control interventions during pregnancy could have long-term benefits in infants (Natama et al. 2018). They noted an interaction with season of birth. Hallamaa et al. (2018) described the additional benefits of azithromycin added to IPTp during pregnancy from a trial in Malawi on child development (0-60 months) with significantly higher child length, decreased stunting, higher developmental scores, and lower post-neonatal mortality in the azithromycin-SP arm.  



Gonzalez et al. published a Cochrane review on mefloquine for preventing malaria in HIV-infected and uninfected pregnant women including 6 trials. Mefloquine was more efficacious than SP in HIV-uninfected women or daily cotrimoxazole prophylaxis in HIV-infected pregnant women for prevention of malaria infection and was associated with lower risk of maternal anaemia, and no adverse effects on pregnancy outcomes (such as stillbirths and abortions), but with no effects on low birth weight and prematurity. However, the high proportion of mefloquine-related adverse events constitutes an important barrier to its effectiveness for malaria preventive treatment in pregnant women. For people who would like an update on progress for malaria in pregnancy in the last 10 years, there is a series of articles in the Lancet Infectious Diseases reviewing exactly that; the articles cover prevention (Desai et al. 2018), treatment (d’Allessandro et al. 2018) and burden/pathology and costs (Rogerson et al. 2018). Using pooled datasets from studies on malaria in pregnancy and nutrition, Cates et al. examined population intervention effects of several interventions on low birth weight (full ITN coverage, maternal malnutrition prevention, increasing IPT doses) and concluded that administering 3 or more doses of IPT-SP would have the largest impact on LBW prevalence.

In this update, there are multiple articles on the development of immunity to placental malaria (e.g. Fried et al. (2018); Rodrigues-Duarte et al. (2018), and the pathology of placental malaria (e.g. Fastman et al. (2018); Dobano et al. (2018). McDonald et al. (2018) corroborated findings from epidemiological studies in Malawi where malaria in pregnancy was associated with l-arginine concentrations, and confirmed this in animal studies whereby l-arginine supplementation in dams improved birth outcomes compared with controls. Singh et al. reported on the presence of cytokines among women infected with P. vivax in India Singh et al. (2018), and Gavina et al. on antibody development and submicroscopic malaria in Colombia, an area with mixed malaria species (P. falciparum and P. vivax 2018. Gavina et al did not see an association between malaria infection and birth weight, whereas in a study in Brazil even a single vivax malaria episode was associated with a significant reduction in birth weight and length and maternal hemoglobin (Pincelli et al. 2018).

With regards to treatment of malaria in pregnancy, CDC updated their malaria policy to reflect the WHO recommendation to include artemether-lumefantrine as a treatment option for uncomplicated malaria during the second and third trimesters of pregnancy and during the first trimester of pregnancy when other treatment options are unavailable (Ballard et al. 2018). Zhang et al. report on a promising method of drug delivery to the placenta using trophoblast-targeted nanoparticles (mice model 2018). Using data from a trial on dihydroartemisinin-piperaquine (DHA-PQ) in HIV-infected pregnant women, Savic et al used modelling to see whether piperaquine dosing levels could be improved to reduce adverse birth outcomse and concluded that studies of alternative dosing strategies leading to PQ levels above a target concentration should be explored (Savic et al. 2018). Tan et al. (2018) identified 10 women with (accidental) atovaquone-proguanil exposure in the first trimester and all pregnancies resulted in term births with no birth defects.  

Lastly, two studies reported on DDT and pregnancy. Coker et al. (2018) report on DDT exposure during pregnancy and child development in the first two years in a prospective cohort in South Africa and noted an interaction with child gender whereby maternal serum DDT concentration was consistently and positively associated with body composition and body weight in young girls and maternal urinary pyrethroid metabolite concentrations were negatively associated with body weight and body composition in young boys. In the same cohort, Murray et al. (2018) examined the relationship between exposure to DDT and hypertensive disorders during pregnancy (HDP) and noticed significant associations with HDP self-report and DDT concentrations; however, compared to medical reports the results were mixed.