In January 2023, 231 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.

Malaria burden

Two studies provide global estimates of the number of pregnancies at risk of malaria and changing risk patterns over the past decennia. They estimate that 121.9 million (Reddy et al. 2022) and 120.4 million pregnancies (Gore-Langton et al. 2022) occurred in malaria transmission areas. Between 2000 and 2020, the number of malaria exposed pregnancies decreased in all regions except Africa.

Bangirana et al. (2022) report on the effect of malaria prevention in pregnancy on neurodevelopment and behavioural outcomes in children followed at 12, 24 and 36 months in Uganda. Mothers participated in a trial evaluating the effect of IPTp with SP, IPTp with dihydroarteminin-piperaquine (DP) every 3 months or monthly DP, and their children were assigned to DP 3-monthly or monthly DP from 2-24 months of age independent of trial arm of the mother. Malaria in pregnancy was associated with worse cognitive, behavioural, and executive function scores in affected children, but more effective malaria chemoprevention measures did not result in better outcomes. A Malawian birth cohort study followed children at 6,12 and 24 months of age to assess the effect of maternal malaria on neurocognitive development; they found an association between preterm birth, low birthweight, and higher maternal education with delay in neurocognitive development but not malaria in pregnancy (Buchwald et al. 2022). Using 19 demographic and health surveys in sub-Saharan Africa since 2014, Godha et al. (2022) evaluated the effect of IPTp-SP and iron and folic acid supplementation on infant growth and neonatal mortality. IPTp was significantly associated with reduced stunting, increased height for-age Z scores, and reduced neonatal mortality, whereas iron and folic acid supplementation was not associated with these outcomes.

A cohort of 358 women in Mali followed from preconception to delivery gave insight into the prevalence of adverse pregnancy outcomes (Gaoussou et al. 2022). Miscarriage occurred among 12%, and 65% of these were in the first trimester. Among the remaining pregnancies, 2.9% ended in a stillbirth. IPTp was associated with a reduction in stillbirths and neonatal deaths. Mtove et al. (2022) showed that it matters which reference is used to define small-for-gestational age (SGA), and that using the reference Intergrowth-21 may result in an underestimate of the relationship between malaria and SGA compared to a more local reference (STOPPAM).

Coinfection of malaria (during pregnancy or at delivery) and HIV at delivery was recorded in Mozambique in a cohort of 819 women; co-infection was noted in 17 (2.1%), HIV infection alone among 86 (10.5%), and malaria among 84 (10.3%). Early neonatal death in the infant was more common with co-infection (aOR 11.6, 95% CI 1.33-101.24; Jaen-Sanchez et al. 2022). The pooled malaria prevalence among HIV-positive pregnant women in Africa was 32.3% (95% CI 26.3–38.6) in a systematic review of 32 studies in malaria among HIV-positive persons by Mirzohreh et al. (2022).

Dombrowski et al. (2023) genetically evaluated P. vivax strains in 177 pregnant women followed during pregnancy with confirmed absence of P. falciparum infections. There was a high genetic diversity and 62% of infections were polyclonal, which could be the result of relapses and/or reinfection. Carrion-Nessi et al. (2022) reported a case-series of five pregnant women in Venezuela who were hospitalized with COVID-19 and P. vivax with two fatal maternal outcomes and three fatal foetal outcomes.

Treatment studies

Artemisinin-based treatment (ABT) has long been deemed unsafe in the first trimester. A review using individual patient data from 12 cohorts compared pregnancy outcomes in 737 pregnancies with confirmed first trimester exposure to ABT and 1076 pregnancies with exposures to non-ABTs. Adverse pregnancy outcomes occurred in 42 (5·7%) of 736 ABT-exposed pregnancies compared with 96 (8·9%) of 1074 non-ABT-exposed pregnancies in the first trimester (adjusted hazard ratio 0·71, 95% CI 0·49–1·03). The risk of adverse pregnancy outcomes was lower with artemether–lumefantrine than with oral quinine in the first trimester of pregnancy (25 [4·8%] of 524 vs 84 [9·2%] of 915; aHR 0·58, 0·36–0·92) (Saito et al. 2022). Based on these results, WHO consequently changed its malaria treatment guidelines in November 2022 to recommend: “Treatment in the first trimester of pregnancy (2022): Treat pregnant women with uncomplicated P. falciparum malaria with artemether-lumefantrine during the first trimester.” (WHO November 2022 WHO guidelines for malaria).

Prevention

As part of a quasi-experimental study to evaluate intermittent preventive treatment (IPTp) with sulfadoxine-pyrimethamine (SP) delivered by community health workers (CHWs) in four countries (Madagascar, Mozambique, the Democratic Republic of Congo and Nigeria; 2018-2021), a qualitive study was conducted to identify key factors that could influence c-IPTp acceptability. Factors that were important in all four countries included alignment of the strategy with existing social norms surrounding pregnancy and maternal health-seeking practices, the active involvement of influential and trusted actors in implementation activities, existing and sustained trust in CHWs, the influence of husbands and other relatives in pregnant women’s care-seeking decision-making, the working conditions of CHWs, pregnant women’s perceptions of SP for IPTp and persistent barriers to facility-based antenatal care access (Alonso et al. 2022). Mohammed et al. (2022) used a mixed study design to assess health workers’ compliance with IPTp-SP in Ghana; they noted that lower-level health facilities recorded the least compliance levels. Factors contributing to higher compliance included higher job satisfaction, having received in-service training, having supervision, availability of job aids and longer health workers experience.

Ampofo et al. (2022) used the Ghana’s District Health information Management System to track control of malaria in pregnancy and pregnancy outcomes (2012-2021). Although the system showed an increase in ANC visits, IPTp, iron and folic acid doses and ITN distribution, and a decrease in malaria prevalence, this was not accompanied by a reduction in maternal anaemia and low birth weight, necessitating investigation into possible reasons. A cross-sectional study in Cameroon showed that 1+ doses of SP were associated with a reduced risk of submicroscopic malaria in pregnancy (OR 0.12, 95% CI 0.01–0.98; Apinjoh et al. 2022). Akpa et al. (2022) reported a large difference in adequate (3+ doses) IPTp uptake between urban (83%) and rural (61%) areas in Nigeria. In Cameroon, Cohen et al. (2023) examined the mutations of Plasmodium falciparum dihydropteroate synthetase (dhps) gene in Central and West Africa; the mutations I431V, A437G, A581G and A613S, and the combination of mutations I431V, S436A, A437G, A581G and A613S were more common among pregnant women who had received SP, but K540E was not.

In seven African countries, ITN distribution through ANC and immunization programs were studied for 2021 (Miller et al. 2022); the ITN issuing rate from the ANC ranged from 13% to 93% (median 64%) and authors stress the importance of optimizing the channel for distribution of ITNs.

Immunology

Matambisso et al. (2022) followed malaria prevalence among first ANC attendees in three regions with different malaria transmission levels in Mozambique over 3 years. The proportion of detectable infections declined over time at all sites, whereby in the high transmission area among secundigravidae the parasite density increased, and antibody levels decreased. Kassa et al. (2022) examined antibodies to malaria in Brazil among women with P. falciparum, P. falciparum and P. vivax, or no infection and noted that infection with either malaria species was associated with higher seropositivity rate for antibodies against P. vivax proteins. Kayatani et al. (2022) examined transplacental transfer of antibodies to P. falciparum between 24^th weeks of gestation and term in Cameroonian cord samples and noted that premature babies in Africa are likely to have reduced antibody levels to some but not all antigens. Mosavati et al. (2022) examined glucose transport in placental malaria in a “placenta-on-a-chip” model and noted that chondroitin sulfate A-binding erythrocytes infected with P. falciparum added resistance to the simulated placental barrier for glucose perfusion and decreased the glucose transfer across this barrier.

Pharmacokinetics

Banda et al. (2022) examined the pharmacokinetics of dihydroartemisinin-piperaquine (DHA-PQ) in the presence of efavirenz-based and dolutegravir-based antiretroviral therapy (ART) among HIV-infected pregnant women. Their findings suggest that the efficacy of DHA-PQ will be retained in the presence of ART.