The Malaria in Pregnancy (MiP) Library is a regularly updated, comprehensive bibliographic database of published and unpublished literature relating to malaria in pregnancy, including a trial registry of planned and ongoing trials.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 December 2023-January 2024

Article highlights from the update in December 2023-January 2024

In January 2024, 224 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.

Two placebo-controlled trials explored safety and efficacy of adding intermittent preventive treatment with dihydroartemisinin-piperaquine to CTX-prophylaxis for malaria prevention among HIV-infected pregnant women.  In Gabon and Mozambique, 666 were randomized. Peripheral parasitaemia at delivery was detected in one of 294 women in the intervention group and none of 308 women in the control group. The incidence of clinical malaria was one episode in the intervention group vs six in the control group (relative risk [RR] 0·12, 95% CI 0·03–0·52, p=0·045), and the composite outcome of overall malaria infection (any diagnostic test during pregnancy or delivery) was lower in the intervention group than in the control group (14 [5%] of 311 women vs 31 [10%] of 320 women; RR 0·48, 95% CI 0·27–0·84, p=0·010; Gonzalez et al. 2024). In Kenya and Malawi, 904 women were randomized; the cumulative risk of any malaria infection during pregnancy or delivery was 31 [7%] of 443 women in the co-trimoxazole plus dihydroartemisinin–piperaquine group and 70 [15%] of 452 women in the co-trimoxazole plus placebo group (risk ratio 0·45, 95% CI 0·30–0·67; p=0·0001). The incidence of any malaria infection during pregnancy or delivery was 25·4 per 100 person-years in the co-trimoxazole plus dihydroartemisinin–piperaquine group versus 77·3 per 100 person-years in the co-trimoxazole plus placebo group (incidence rate ratio 0·32, 95% CI 0·22–0·47, p<0·0001) (Barsosio et al. 2024). In both studies, no differences were noted in birth outcomes or adverse events.

Unger et al. (2023) reviewed the effect and control malaria in pregnancy and lactating women in the Asia-Pacific region using 106 articles published from 2011-2023. Plasmodium falciparum and vivax co-exist in this region, and antimalarial resistance is a challenge, despite decreasing malaria transmission levels. A more systematic approach to prevention is needed. Kojom Foko et al. (2023) evaluated malaria in pregnancy in India in the last 50 years, and examined signs, symptoms, severity, co-morbidities and regions of focus.

Less is known about malaria in South America: Cardona-Arias et al. (2023) conducted a critical ethnographic study on malaria in pregnancy in Colombia and noted a lack of knowledge among pregnant women. Structural problems noted by health workers included limitations of public health programmes and scarcity of resources. Guida Marascia et al. (2023) reviewed imported malaria in pregnancy in Europe for the last 25 years, with favourable outcomes in 35 of 57 cases identified (61%: term pregnancies with normal birthweight infants). The importance to consider malaria in non-endemic countries is illustrated by a case report of P. falciparum malaria in a pregnant woman 11 years after immigration from sub-Saharan Africa to the USA (Drummond et al 2023).

The effect of a P. falciparum infection on the intestinal barrier of a pregnant woman was studied by Wright et al. (2023). They noted increased concentrations of gut-leak markers among women <24 weeks gestational age with malaria indicative of intestinal barrier dysfunction; this was linked to an increased risk of preterm birth.

Several studies have described the beneficial effect of sulfadoxine-pyrimethamine (SP) when used as intermittent preventive treatment in pregnancy on infant weight, without a reduction in malaria. Kim et al. (2024) explored the potential effect of SP on the bowels using a human organ on a chip model, whereby the adult female intestine is replicated with patient organoid-derived duodenal epithelial cells interfaced with human intestinal endothelial cells. They report that SP treatment can reverse multiple intestinal absorptive abnormalities observed in malnourished female Intestine Chips, as validated by transcriptomic and proteomic analyses. SP also reduced the production of inflammatory cytokines and suppressed the recruitment of human peripheral mononuclear cells in nutrient deficient chips.

There is good news for anyone with concerns about development/growth of drug resistance to SP when used as IPTp. A large implementation study of community IPTp for pregnant women did not identify an increase in drug resistance markers in the four countries where the study was implemented (Democratic Republic of the Congo, Madagascar, Mozambique, and Nigeria) when comparing before and 3 years after the implementation of community IPTp, with overall low prevalence of the sextuple mutant (0-2% in over 2400 samples at baseline and endline; Figueroa-Romero et al. 2023). In Southern Rwanda however, where IPTp with SP is not used, the sextuple mutant was identified in 28% of 148 samples of pregnant women (2016-2018; Alruwaili et al. 2023), for which no clear explanation was presented except that resistance markers may be highly focal.  Mayor et al. published guidance on sampling for malaria molecular surveillance (Mayor et al. 2023).

Health workers are often confused about the treatment of malaria in pregnancy; in a qualitative study, Osoro et al. (2023) report on the lack of training and unfamiliarity of health workers with national malaria treatment guidelines for malaria in pregnancy. At the time of the study, quinine was still recommended in the first trimester, yet quinine was often lacking in facilities and providers preferred using artemether-lumefantrine. The good news is that artemether-lumefantrine is now recommended for all uncomplicated malaria in pregnancy, including in the first trimester (Castro et al. 2023).  Additionally, Ashton et al. (2023) and Wolf et al. (2023) report on the positive effect of outreach training and supportive supervision on competency of health workers to deal with malaria in pregnancy.

More sensitive malaria tests can reduce impact of malaria in pregnancy; Kabalu Tshiongo et al. (2023) compared diagnostic performance of regular and ultrasensitive rapid diagnostic tests (RDT and uRDT, respectively) with microscopy and polymerase chain reaction tests (PCR). RDTs performed better than microscopy; although uRDTs performed better than regular RDTs, the difference was not significant (249 samples at screening).  An immunological study correlated different types of maternal and cord blood antibody levels with clinical infant malaria in Burkina Faso and noted that some antibodies to certain erythrocytic antigens were independent predictors of protection from clinical malaria whereas high levels of IgG and antibodies against VAR2CSA were associated with an increased risk of infant clinical malaria (Natama et al. 2023).