The Malaria in Pregnancy (MiP) Library is a regularly updated, comprehensive bibliographic database of published and unpublished literature relating to malaria in pregnancy, including a trial registry of planned and ongoing trials.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 August-September 2023

Article highlights from the update in August-September 2023:

In August 2023, 153 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.

For readers interested in an overview of malaria in pregnancy, Berhe et al. (2023) published a concise review of the problem included in this update. Foetal sex can modify the risks of diseases and has been associated with e.g., maternal asthma, pre-eclampsia and gestational diabetes. Unger et al. (2023) reviewed the relationship between foetal sex and pregnancy-associated malaria; presence of a female foetus was associated with malaria infection at enrolment by light microscopy (risk ratio 1.14, 95% confidence interval [CI] 1.04, 1.24], p = 0.003, 11,729 participants in 11 studies), but not with malaria infection at other time points or diagnostic tests. However, a case control study in Sudan did find an association between placental malaria and female newborns (aOR 2.90, 95% CI 2.08-4.04) (Ahmed et al. 2023).

In a large individual participant data analysis by van Eijk et al (2023), the epidemiology of submicroscopic malaria in pregnancy was reviewed. Submicroscopic infections were more common than microscopic infections and were more likely to present with fever in Africa, but not in Asia and the Americas. In countries with multiple species Plasmodium vivax infections were more likely to be submicroscopic than Plasmodium falciparum infections.The importance of subpatent malaria was underscored in a study in Mozambique, where malaria detected by PCR among women without malaria related complaints was associated with a high stillbirth risk for the infant (Jaén-Sánchez et al. 2023). It should be noted, however, that the caesarean section percentage was high at 96.6% in this study population. Mondeilh et al. (2023) examined the effect of microscopic and submicroscopic infections before uterine Doppler measurement among a cohort of Beninese women followed from preconception to delivery. Microscopic and submicroscopic infections were associated with the presence of a notch, a reduction in uterine artery blood flow (adjusted odds ratio [aOR] 4.5, 95% CI 1.2–16.3 and aOR 3.3, 95% CI 0.9–11.9, respectively), indicating malaria infections in the first half of pregnancy impair placental blood flow. In a secondary analysis from a large multicentre trial (Kenya, Malawi, and Tanzania) with serial prenatal ultrasound measurements to assess foetal weight gain, foetal growth was assessed among women with malaria, with sexually transmitted or reproductive tract infections (STIs/RTIs: Treponema pallidum, Neisseria gonorrhoeae, Trichomonas vaginalis, Chlamydia trachomatis, and bacterial vaginosis) or both (Mtove et al. 2023). Compared to women without infections (n=399), foetal growth reduction was highest when both malaria and STIs/RTIs had been documented (mean difference in Z-score -0.20, 95% CI -0.33 to -0.07, n=353), followed by malaria only (-0.18, -0.31 to -0.04, n=267), and STIs/RTIs only (-0.14, -0.26 to -0.03, n=410), with the largest impact in primigravidae. To assess long term sequelae of malaria, Christensen et al. (2023) tracked and studied skeletal muscle biopsies and aerobic capacity (fitness) of 76 participants in a malaria trial with known placental malaria status at birth (mean age 19.6, standard deviation 0.9 years). They did not identify differences in muscle enzymatic activities or fitness between the groups.

Although severe malaria among pregnant women is less common, it is important that clinicians are aware of disease pattern and prognostic factors. Saito et al. (2023) reviewed 213 cases of severe malaria in pregnancy. The maternal mortality was 12.2%, with coma, hypotension and respiratory failure all associated with mortality, whereas hyperparasitaemia and severe anaemia were not. Risks of foetal loss and small-for-gestational age infants were high, commonly occurring within a week of diagnosis.

For women who just delivered, it may be important to know if it is safe to breastfeed when taking antimalarial or other medication. Ojara et al. (2023) reviewed maternal-to-infant transfer of drugs through breastmilk for malaria, tuberculosis and neglected tropical diseases. They identified nine studies that examined antimalarials, but none of them included sulfadoxine-pyrimethamine, artemisinins, or lumefantrine. They also noted methodological issues for conducting and reporting lactation pharmacokinetic studies.

Malaria prevalence among pregnant women attending for their first antenatal visit has been proposed as a malaria surveillance strategy. Two articles have looked at greater depth into this option. Pujol et al. (2023) compared trends in pregnant women attending ANC with children in the community and at health facilities in Southern Mozambique. P. falciparum rates by PCR in pregnant women mirrored rates in children, independent of gravidity or HIV status, and allowed the detection of malaria hotspots. Munsey et al. (2023) compared parasitaemia prevalence among pregnant women diagnosed at first ANC visit using rapid diagnostic tests (RDTs) with parasitaemia by RDT among children in the community and similarly reported that trends in parasitaemia among ANC attendees were predictive of trends in parasitaemia among children at the community level.

It has proved difficult to optimise IPTp coverage among pregnant women in sub-Saharan Africa. Odwe et al. (2023) examined IPTp coverage in two counties in Kenya; they found a coverage of IPTp3+ of 66%, with the odds of taking IPTp3+ increased among women who had decision-making autonomy (adjusted odds ratio 2.33, 1.81-3.01). Decision making autonomy was measured based on four questions that asked whether the respondent participated in decisions regarding personal earnings, her healthcare, household purchases, and family visits. In a similar study, Sarfo et al. (2023) examined factors associated with IPTp uptake in Ghana, with 61% of women reporting receiving IPTp3+, with level of uptake mainly associated with individual rather than community-level characteristics of pregnant women (the highest association was for number of ANC visits).

The introduction of multiple first-line therapies for malaria can potentially expose more pregnant women to antimalarials with unknown safety in the first trimester. In Kenya, Osoro et al. (2023) examined knowledge of treatment guidelines for malaria in pregnancy in 50 health facilities and 40 drug outlets. Among the 174 providers, they noted that only few (10% from health facilities and 12% from drug outlets had adequate knowledge of malaria treatment in pregnancy, defined as the correct drug and dose for uncomplicated and severe malaria in all trimesters. A qualitative study in Ghana examined health worker’s perspective on malaria case identification and management in pregnancy; the study found that training programs were optional for health workers, with some not having received refresher training since graduation (Adokiya et al. 2023). Cirera et al. (2023) calculated cost-effectiveness of community-based distribution of IPTp-SP (cIPTp) in Nigeria, Madagascar, Democratic Republic of Congo (DRC), and Mozambique. Per 1000 pregnant women, they calculated that net incremental costs of cIPTp when implemented by national health systems and the incremental cost-effectiveness ratio (ICER) was highest in Mozambique and lowest in Nigeria. 

VAR2CSA is the Plasmodium falciparum variant surface antigen that mediates binding of infected erythrocytes to chondroitin sulfate A (CSA) and their sequestration in intervillous spaces of the placenta, leading to placental malaria. As part of vaccine and monoclonal antibody research for malaria in pregnancy, this has antigen been the focus of numerous studies. In a short perspective, Doritchamou et al. (2023) describe the interaction between one such monoclonal antibody and VAR2CSA. Iyamu et al. (2023) reports that VAR2CSA antibodies can also be elicited by P. vivax Duffy binding protein and examines this further in animal models. Lloyd et al. (2023) characterized antibodies to VAR2CSA and found that all 4 measures evaluated (levels above the median, avidity, reduction in binding and phagocytosis) were important and associated with lower placental malaria and parasite densities among Cameroonian women in a low malaria transmission setting.