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The Malaria in Pregnancy (MiP) Library is a regularly updated, comprehensive bibliographic database of published and unpublished literature relating to malaria in pregnancy, including a trial registry of planned and ongoing trials.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 April-May 2019

In May 2019, 211 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.

In the search for alternatives for sulphadoxine-pyrimethamine (SP) for intermittent preventive treatment (IPTp) when facing SP resistance, treatment courses of dihydroartemisinin-piperaquine (DHP) have been tried, either as IPTp or for intermittent screening and treatment. Though promising results were seen with DHP for IPTp in earlier studies in Kenya and Uganda, further studies were needed. Kajubi et al. (2019) report on a subsequent larger trial comparing monthly IPTp with SP versus monthly treatment courses of DHP (over 3 days). The results show significant reductions in the DHP arm compared to monthly SP for all malaria measurements (malaria during pregnancy or at delivery) but did not see a reduction in birth outcome in the DHP arm (a composite of low birth weight, preterm birth or small for gestational age). Quinoline antimalarials such as piperaquine have long been associated with QTc prolongation, only visible in electrocardiograms; severe prolongation can cause arrhythmias. In this study with repeated exposure to DHP, QTc interval prolongation was seen in 9 women in the DHP arm but did not lead to clinical illness. Less anaemia was seen among primigravidae in the DHP arm. Evidence for an antibiotic effect in antimalarials used for intermittent preventive treatment were available from a secondary analysis by Unger et al. (2019) of a trial comparing one treatment dose of SP-chloroquine with SP-azithromycin (three treatment doses). The authors concluded that SP- azithromycin may protect against adverse pregnancy outcomes by reducing inflammation and preventing its deleterious consequences, including dysregulation of placental angiogenesis, in women with and without malarial infection.

The resilience of SP was shown in a review by van Eijk et al. (2009) to determine the potential effect of SP resistance on IPTp. They matched studies with data on SP doses and birth outcome with levels of SP resistance markers (Ala437Gly, Lys540Glu, and Ala581Gly substitutions in the dhps gene) by time and location. The protective effect of SP on low birth weight declined in areas with increasing prevalence of the Lys540Glu mutation; however, even in areas with a very high level of this mutation (>90%) and <10% Ala581Gly, a beneficial effect of SP was still seen. The Lys540Glu and Ala581Gly mutations were mainly present in East and South Africa, so not yet a concern for West and Central Africa.

In this update, there were several articles on malaria and iron in pregnant women. There has been concern that iron supplementation in pregnant women in malarious areas may increase risk of malaria. Tang & Krebs (2019) provide an overview and note that in clinical trials, iron supplementation did not increase the risk of malaria in pregnancy; however, treatment of malaria infections should be considered before or together with iron supplementation. One reason for the conflicting results may be in the measurement of iron-deficiency, which measures serum ferritin, a biomarker which is increased in the presence of inflammation and malaria. Mwangi et al. (2019) used different analytical methods to adjust for ferritin concentration for inflammation and malaria among pregnant women and found that the application of linear regression methods to adjust for circulating ferritin concentration for inflammation and malaria leads to markedly decreased point estimates for ferritin concentration and increased estimates for the prevalence of iron deficiency in pregnancy.

There are two additional publications from a trial in Burkina Faso which explored pre-pregnancy iron supplementation and pregnancy outcome in primigravidae. The primary publication by Gies et al. (2018) noted that weekly iron and folic acid supplementation for up to 18 months did not significantly affect the prevalence of Plasmodium falciparum, iron deficiency or anaemia compared to folic acid alone, in either pregnant or non-pregnant women. However, Brabin et al. (2019) noted that primigravidae receiving weekly iron supplementation up to the first ANC visit had a significantly higher prevalence of preterm delivery; preterm birth incidence during the rainy season was ~ 50% in the iron arm and < 20% in controls (P = 0.001).

For an overview of the immunology and pathology of placental malaria, Seitz et al. (2019) provide an article describing the molecular processes in P. falciparum infection in pregnancy which may be involved in the development of intrauterine growth retardation (IUGR), and Lawford et al. (2019) provide an overview of the potential impact of placental malaria on infant neurodevelopment. Degarage et al. (2019) present a meta-analysis of the effect of ABO blood group on asymptomatic, uncomplicated and placental P. falciparum infection and conclude that ABO blood group may not affect susceptibility to asymptomatic and/or uncomplicated P. falciparum infection. However, the odds of active placental P. falciparum infection were lower in primigravidae with non-O blood groups compared to O-blood groups (3 studies).

Andrejko et al. (2019) explored the safety of atovaquone-proguanil (AP) for the prevention and treatment of malaria in pregnancy and noted that among 16 identified studies, outcomes following AP exposure (miscarriage, stillbirth, early neonatal death and congenital anomalies) were comparable to expected rates in similar populations. Nambozi et al. (2019) evaluated congenital malformations, perinatal, neonatal and infant mortality after treatment of malaria in the second and third trimester with artemisinin based combination therapy (artemether-lumefantrine, amodiaquine-artesunate, mefloquine-artesunate, and dihydroartemisinin-piperaquine) as part of a trial, and noted no differences between arms.

Chene et al. (2019) report on the production process for a malaria in pregnancy vaccine, an important step in the vaccine development. Doritchamou et al. (2019) note that there may be geographic bias in circulating strains identified in placental malaria which may impact antibody functions and are important for the development of placental malaria vaccines. Chauvet et al. (2019) noted that it is important to assess erythrocyte disorders such as sickle cell trait when studying the immunological responses to P. falciparum in pregnant women. Yeo et al. (2019) show the complexity of the effect of infections during pregnancy such as malaria, HIV and cytomegalovirus on prenatal fetal immune priming. McDonald et al. (2019) show that co-trimoxazole may not provide enough protection against malaria and the adverse effects in HIV-infected pregnant women.   

Integration of malaria services for pregnant women into existing ANC service delivery is important. Young et al. (2019) report on a qualitative study on the integration of point-of-care (POC) testing for malaria, anaemia, syphilis and HIV in western Kenya. Odjija et al. (2019) provide a quantitative analysis of survey data to assesses the capacity of the Tanzanian health system to provide integrated malaria, tuberculosis and HIV services. Katoba et al. (2019) provide a review on the availability of POC testing designed for diagnosing HIV, syphilis, and malaria in pregnancy to improve maternal and child health in low- and middle-income countries.