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The Malaria in Pregnancy (MiP) Library is a regularly updated, comprehensive bibliographic database of published and unpublished literature relating to malaria in pregnancy, including a trial registry of planned and ongoing trials.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 August 2022

Article highlights from the update in August 2022:

In September 2022, 125 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.

Intermittent preventive treatment

Rubenstein et al. (2022) described the results of a cluster randomized trial evaluating delivery of intermittent preventive treatment (IPTp) with sulfadoxine-pyrimethamine (SP) by community health workers (CHWs) on IPTp and antenatal clinic (ANC) coverage in Malawi. Although the mean number of IPTp doses increased from 2.3 to 2.8 doses, and ANC attendance increased in the intervention arm (ANC4+ from 46.9% to 56.8%), no significant increase was noted in IPTp3+ between the arms before and after the intervention (6.9% difference-in-difference, 95% CI -5.9 to 19.6%). A study in Nigeria evaluated the effect of CHWs training on IPTp3+ in a region where CHWs had been trained to dispense SP and promote ANC visits (Orji et al. 2022). The data was extracted from a Maternity Record Booklet, which contained data on IPTp and referrals by CHWs (N=936). Pregnant women referred for at least one ANC visit by a CHW had 1.60 times greater odds (95% CI 1.08-2.38) to receive the third SP dose than women who were never referred. A large study in a low malaria transmission area at the Kenyan coast (27,786 deliveries) showed lower levels of low birth weight with increasing doses of SP (21.0% among newborns of mothers who received 0 doses, and 9.7% among newborns of mothers who received 5+ doses, p <0.001 (Kamau et al. 2022). A dose-dependent effect was also seen for stillbirths. Frequencies of the mutations 540E and the 581G in dihydropteroate synthase (dhps) genes were >90% and <2%, respectively, at the study site. A meta-ethnographic review described factors affecting use of malaria in pregnancy interventions by pregnant women (Aberese-Ako et al. 2022): Main factors motivating uptake of MiP interventions were: (1) well organized ANC, positive attitudes of health workers and availability of MiP services; (2) Women's knowledge of the effects of malaria in pregnancy, previous experience of accessing responsive ANC; (3) financial resources and encouragement from partners, relatives and friends and (4) favourable weather conditions and nearness to a health facility. Flegg et al. (2022) analysed data from the WWARN SP Molecular Surveyor; the high prevalence of pfdhps540E mutation was restricted to East and Southeast Africa, where several foci where pfdhps581G prevalence exceeded 10% were identified. Using blood samples from pregnant and delivering women in Ghana, Dosoo et al. (2022) examined SP resistance mutations in Ghana; the prevalence of the quintuple mutant was 4.4% (1 /23) and the A581G mutant was not detected. The threat of SP resistance for malaria in pregnancy was reviewed by Sundararaman and John (2022) ; they also presented a framework for the ideal pharmacokinetic and pharmacodynamic properties for future IPTp regimens.

Two immunological reviews describe aspects of the interaction between maternal immunity and placental malaria. Kobia et al (2022) review the foetal-maternal innate conflict during placental malaria, whereas Barateiro et al (2022) reviews a potential protective role of placental autophagy to circumvent inflammation-induced stress in the Plasmodium falciparum infected placenta.

Several studies in this update describe malaria in pregnancy outside of Africa, in regions where Plasmodium vivax can be more common than P. falciparum. Jain et al. (2022) reviewed 16 studies on malaria in pregnancy, which were reported from nine states in India; prevalence was mostly low with some exceptions and ranged from 1.3-35% in studies among asymptomatic women after 2000. Cardona-Arias et al. (2022) described their experiences with gestational and placental malaria in northwestern Colombia from 2009-2020 in two papers, where P. vivax and P.falciparum are both occurring in approximately equal numbers .

Dombrowski et al. (2022) described malaria in pregnancy in Brazil between 2004 and 2018, where P. vivax dominates, and clustering of cases is prevalent in the Amazon region. From the same country is a study by Pincelli et al. (2022) from a birth cohort (N=435) where children were followed for two years; 23 (5.3%) had developed antibodies to P. vivax infections in this period. However, among children with 15 clinical episodes, only 8 developed antibodies. Children born to women who had a P. vivax infection in pregnancy were more likely to develop a clinical P. vivax infection. However, those breastfed for ≥12 months were less likely to become P. vivax seropositive.There were three articles in this update from a long-term project in South Africa which reported on the effect of DDT exposure in pregnancy on children, using concentrations of DDT metabolites in maternal serum and urine obtained peripartum (N=637 pregnancies). They reported that boys with higher prenatal exposure to pyrethroid insecticides were at higher risk of hypospadias (the ectopic opening of the urethra on the penis or scrotum) among 68 boys without phimosis, out of 359 boys examined at one year of age (Bornman et al. 2022). Additionally, they concluded that gestational exposure to pyrethroids may be associated with maternally reported behavioural problems in two-year old children (An et al. 2022) and may reduce adiposity in children at 5 years of age (Kim et al. 2022).

A review by Clark (2022) reviewed the use of artemisinin-based combination therapies (ACTs) in the first trimester and recommends that the results of ACT should be evaluated during different 1- to 2-week periods of the first trimester to exclude week-specific teratogenicity. A case-report from Nigeria reported on a first trimester miscarriage after intravenous quinine treatment for P. falciparum; markers indicative of quinine resistance were identified (Oboh et al. 2022).

Economic studies are not very common for malaria in pregnancy: (Duval et al. 2022) report on household costs related to seeking malaria treatment in pregnancy in Burkina Faso (N=220) and The Gambia (N=263). High malaria treatment costs were incurred in both countries; beyond the medical costs of fees and drugs, costs in terms of transport, food and time were significant drivers.

A Kenyan study evaluated an ultrasensitive rapid malaria diagnostic test (uRDT) and loop-mediated isothermal amplification (LAMP) for the diagnosis of malaria in pregnancy, with photoinduced electron-transfer polymerase chain reaction (PET-PCR) as the reference standard (N=482; Samuels et al. 2022). Sensitivity was 54.7%, 95% CI 46.9% - 62.2% for uRDT, and 68.6%, 95% CI 61.1% - 75.5% for LAMP, and was similar when only febrile women were included. The sensitivity of a conventional RDT was 49.4%; 95% CI 41.7% - 57.1, showing that uRDT only provided moderate improvement in detecting low density infections in pregnant women compared to conventional RDTs.

A secondary analysis from a multi-country trial of prevention of malaria in pregnancy (N=5804) evaluated risk of malaria in adolescents (10-19 years) compared to adult women (Pons-Duran et al. 2022). Adolescents were more likely to present with clinical malaria (incidence risk ratio 1.70, 95% CI 1.20-2.39), and malaria at delivery (peripheral blood; OR 2.28, 95% CI 1.46-3.55; and placental blood: OR 1.97, 95% CI 1.31-2.98); results were similar for HIV infected and uninfected women.

Finally, we would like to bring to your attention the Malaria Chemoprevention Efficacy Study Protocol, published by the World Health Organization (2022), which includes pregnant women as a study group .