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The Malaria in Pregnancy (MiP) Library is a regularly updated, comprehensive bibliographic database of published and unpublished literature relating to malaria in pregnancy, including a trial registry of planned and ongoing trials.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 2020

Article highlights from the update in May 2021:

 

In May 2021, 145 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.

Trials. A trial in Thailand assessed the effect of malaria treatment with dihydroartemisinin-piperaquine (DP) or artesunate-mefloquine (ASMQ) or an extended regimen of artemether-lumefantrine on corrected and uncorrected QT interval in ECGs. ECGs were conducted before 277 treatments, 4 to 6 h following the last treatment dose, and on day 7 (Saito et al. 2021). None of the treatments exceeded conventional thresholds in pregnant women for an increased risk of torsade de pointes. In coastal Tanzania, 956 RDT-negative women negative for malaria with a rapid test, were randomized to monthly intermittent preventive treatment (IPTp) with DP or sulfadoxine-pyrimethamine (SP) in an area with 90% of the quintuple SP resistance haplotype (Mlugu et al. 2021). IPTp with DP resulted in a lower detection of malaria in pregnancy or at delivery compared to SP, and a lower risk of low birth weight (4.6% versus 9.6%) and a lower but not significant difference in a composite birth outcome (low birth weight, preterm delivery, spontaneous abortion, stillbirth and foetal anaemia: 23.8% versus 17.9%, p=0.06).

Reviews. In this update there is a wealth of information on the immunology of malaria in pregnancy, including vaccine development. As part of the research topic “Immunity to parasitic infections in pregnancy”, the journal “Frontiers in Immunology” published 11 articles, of which 9 were about malaria in pregnancy, with 4 reviews among them. Tomlinson et al. (2021 ) summarized the VAR2CSA-mediated host defense evasion mechanisms employed by the parasite during placental malaria to ensure its survival. Chua et al. (2021) provided an overview of malaria in pregnancy and the different pathological pathways leading to malaria in pregnancy-associated low birthweight and discuss current prevention and management strategies. Gamain et al. (2021) discussed recent advances in placental malaria vaccine development, with a focus on the recent clinical data. Lastly, Callaway et al. (2021) summarized information on adaptive B and T cell responses to perinatal pathogens in utero, and discussed how this could be used to develop malaria vaccines.

Immunology. Vanda et al. (2021) studied antibodies and antibody avidity, a marker for maturation of the response, to VAR2CSA among 695 women with known placental malaria status; a more mature antibody response was associated with an increase in birthweight among urban women in Cameroon. Factors associated with foetal anaemia (610 mother-infant pairs) were evaluated in a cross-sectional Tanzanian study in a high malaria transmission area. Foetal anaemia was present in 46.2% of the neonates but was not related to placental malaria. However, among offspring of iron-deficient women, the odds of foetal anaemia increased with foetal alpha+-thalassemia, as well as certain patterns of cord blood cytokines: increased cord IL-6, decreased TNF-RI, and decreased sTfR (Kabyemela et al. 2021). Alonso et al. (Frontiers in Immunology 2021 and Journal of Infection 2021) described the placental transfer of antibodies against 14 pathogens and vaccine antigens among 341 mother-infant pairs with known maternal HIV-status. Maternal antibody levels were the main determinant of cord antibody levels. Maternal HIV infection reduced the placental transfer and cord levels of IgG and IgG1 principally, but also IgG2 to half of the antigens tested. P. falciparum exposure and prematurity were negatively associated with cord antibody levels and placental transfer, but this was antigen-subclass dependent. Among a pregnancy cohort in Benin, Tornyigah et al. (2021) evaluated anti-VAR2CSA IgG subclass responses to the PAMVAC candidate vaccine antigen; cytophilic IgG1 and IgG3 responses were the most frequent. Elevated levels of VAR2CSA-specific total IgG and cytophilic IgG3 during pregnancy were consistently associated with higher birth weights, whilst high levels of IgG4 were associated with a reduced risk of placental infections. Damelang et al. (2021) studied the capacity of IgG antibodies from samples of 77 pregnant women, with placental malaria or non-placental malaria, to induce NK cell activation in response to placental malaria-associated antigens DBL2 and DBL3, and concluded that although anti-inflammatory glycans and antibody-dependent natural-killer cell activation were detected in pregnant women with malaria, a definitive role for these antibody features in protecting against placental malaria remains to be proven.


Epidemiology. In a large pregnancy cohort (1850 women) in Mali, the effect of malaria on pregnancy outcome was studied; malaria infection was associated with stillbirth and preterm delivery in primigravidae, and early neonatal death in multigravidae (Mahamar et al. 2021). In cross-sectional studies in 2013/2014 and 2017, Rouamba et al. (2021) showed that asymptomatic malaria but not anaemia in pregnancy decreased over time. Kwizera et al. (2021) followed pregnancies with simple (n=361) or severe malaria (n=85) in Rwanda; severe malaria and adverse perinatal outcomes were more common later in pregnancy. Stillbirths occurred in 6.1% of women. A significant difference in perinatal outcomes between simple and severe malaria was seen: 64% of women with simple malaria had a normal term delivery as compared to 30.6% with severe malaria (p<0.0001). Harrington et al. (2021) studied the relationship between hypertensive disorders of pregnancy and malaria in the dataset of pregnancies followed at the Thai Burmese border between 1986 and 2016. Falciparum malaria was associated with gestational hypertension amongst multigravidae (adjusted odds ratio (AOR) 2.59, 95% CI 1.59–4.23); among primigravidae, it was associated with the combined outcome of pre-eclampsia/eclampsia (AOR 2.61, 95% CI 1.01–6.79). There was no association between vivax malaria and hypertensive disorders in pregnancy (AOR 0.78, 95% CI 0.51-1.18). To study the effect of P. vivax in pregnancy, Dombrowski et al. (2021) followed a pregnancy cohort between 2013 and 2015 in the Brazilian Amazon; the presence of plasma IgG against the P. vivax MSP119 protein was used as a marker of exposure and women with previous P. vivax infections were excluded. P. vivax infections during the first trimester of pregnancy were associated with adverse gestational outcomes such as premature birth (AOR 8.12, 95%CI 2.69–24.54) and reduced head circumference (AOR 3.58, 95%CI 1.29–9.97). Histopathology analysis showed marked differences between placentas from P. vivax-infected and non-infected pregnant women.

Please note that WHO has published ‘living’ guidelines for malaria which is a compilation of existing WHO recommendations on malaria.