In May 2023, 173 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.

Trials

This update has a relatively high number of results from trials or quasi-experimental studies. An individually randomized, double blind, partly placebo-controlled trial in Kenya, Tanzania and Malawi (N=4680 women) compared monthly intermittent preventive treatment in pregnancy with dihydroartemisinin-piperaquine (IPTp-DP) and IPTp-DP with a single treatment course of azithromycin (AZ, 1000 mg per day for two days) with IPTp with sulphadoxine-pyrimethamine (IPTp-SP) (Madanitsa et al. 2023). No differences were seen in incidence of serious adverse events by treatment arm. The primary outcome, a composite of adverse pregnancy outcomes (small for gestational age, low birth weight or preterm combined), was significantly more common in both IPTp-DP arms compared to IPTp-SP (27.9% in IPTp-DP, 27.6% in IPTp-DP+AZ and 23.3% in IPTp-SP), despite malaria outcomes being more frequent in the IPTp-SP arm (e.g., any placental histology 11.4%, 15.4% and 17.6% in IPTp-DP, IPTp-DP+AZ and IPTp-SP arms, respectively). Lingani et al. (2023 ) conducted an open label randomized controlled trial (N=992 women) in Burkina Faso comparing IPTp-SP with IPTp-SP and two additional doses of AZ (1 gram daily for two doses, once in second and in third trimester). No significant differences were seen in low birth weight (primary outcome 8.7% in AZ arm vs. 9.4% in control arm), preterm births or number of serious adverse events, or uncomplicated malaria (1.4% vs. 1.8%, respectively).  A secondary analysis compared malaria outcomes and foetal growth in a trial evaluating the effect of monthly IPTp-SP, IPTp-SP combined with two AZ treatments vs. IPTp-SP twice only in Malawi (N=1320, Hallamaa et al. 2023 ). They noted that AZ did not provide much additional antimalarial effect compared to monthly IPTp-SP and had no effect on foetal growth.

A cluster randomized controlled trial in Rwanda by Uwimana et al. (2023 ) examined the effect of intermittent screening (independent of symptoms) and treatment of malaria in pregnancy (ISTp) at all scheduled ANC visits compared to screening of suspected clinical malaria in the control arm (treatment with quinine or artemether-lumefantrine according to national guidelines); all women received an insecticide treated net. Compared to the control group (n=811), ISTp (n=975) did not result in a reduction in placental malaria (adjusted relative risk [aRR] 0.94, 95% CI 0.59-1.50), or anaemia (aRR 1.08, 0.57-2.04) or low birth weight (aRR 1.59, 1.02-2.49), or an increase in mean birthweight (3054 vs. 3096 grams, p=0.395).  Baseline malaria prevalence was about 10% in ISTp arm, and 3.7% (febrile women tested only) in the control arm; about 43% of houses of all participants had received IRS within 6 months of enrolment. An individually randomized double blind trial in Nigeria by Okoro et al. (2023) compared IPTp-DP and IPTp-SP (N=250). Of the 206 participants with outcomes available, 84 had received 3+ doses of DP or SP (40.8%). No significant differences were seen for placental malaria by histology (primary outcome: 62.5% in IPTp-DP vs. 51.1% in IPTp-SP arm), low birth weight (9.8% and 16.1% respectively) or other outcomes.

Despite the benefits of IPTp-SP, increasing the coverage of 3+ doses of IPTp-SP has proved challenging. In this update there are several studies which have evaluated alternative strategies to increase IPTp coverage. A large quasi-experimental study in 4 countries (Democratic Republic of Congo [DRC], Madagascar, Mozambique and Nigeria, N=18215 women) explored the use of community health workers (CHWs) to distribute SP to pregnant women in the community (Gonzalez et al. 2023). Surveys were conducted among women who had delivered in the past 6 months before and after the implementation of provision of SP by CHWs in addition to IPTp through routine antenatal clinic visits The coverage of at least 3 doses of SP (IPTp3+) increased in 3 of the four countries (comparing baseline to endline: DRC 22.5% to 65.2%; Madagascar 17.7% to 74.9%, Nigeria 12.7% to 62.7%, Mozambique 51.8% to 58.6%), whereas antenatal (ANC) attendance was not significantly affected (ANC 4 or more visits: DRC 42.3% to 49.3%; Madagascar 51.2% to 66.2%, Nigeria 70.5% to 68.4%; Mozambique 49.8% to 37.2%).

Kayentao et al. (2023) examined weekly home visits by CHWs to encourage ANC visits compared to a control arm in a cluster randomized study (N=5112); ANC4+ and IPTp3+ increased (39.8% vs. 31.8%, and 57.3% vs. 53.9% in control arm). However, there were interventions in both control and intervention arm: these interventions included improvements of the community health sites, training of CHWs, upgrading of primary care clinic teams and infrastructure, and abolishing fees for antenatal care. Compared to baseline and combining both arms, ANC4+, IPTp3+ and institutional deliveries at endline increased from 15.6% to 35.9%, 19.4% to 55.6% and 43.5% to 58.1% respectively. A cluster randomized trial in Cote d’Ivoire (N=767; Kone et al. 2023 ) compared the effect of a personal information session at home and home delivery of haematinics/SP (by a nurse) vs. a personal information session at home on IPTp and haematinics (once, by a nurse at a clinic, no drug delivery) vs. a control arm on the coverage of haematinics and IPTp, and postpartum malaria and anaemia (within 2 weeks of delivery).  Results in home drug delivery, home information and control arm, respectively, were: ANC4+ 48.6%, 37.3% and 34.5%, IPTp3+ 95.4%, 64.0% and 60.9%, postpartum anaemia (<11 g/dl) 35.9%, 40.9% and 42.0% and postpartum malaria 0.8%, 4.5% and 4.8% (except for anaemia all significantly different).

An open-label individually randomized trial (N=862) by Pasricha et al. (2023) in Malawi, evaluating different regimens for iron supplementation (ferric carboxymaltose once intravenous or 60 mg elemental iron twice daily for 90 days) among pregnant women with a haemoglobin < 10 g/dl did not see a difference in anaemia at 36 weeks, maternal malaria, or infant birthweight. Women in both arms were fully protected by IPTp. A trial in The Gambia and Burkina Faso (N = 11983) evaluating the effect of a single dose of azithromycin at delivery on maternal and infant outcomes did not find a difference in neonatal sepsis (2.0% vs. 1.9%), infant mortality (1.0% vs. 0.5%) or maternal malaria (0-28 days postpartum; 0.2% in both arms) between azithromycin and placebo arm, although mastitis and puerperal fever were significantly less common in the azithromycin group than in the placebo group (mastitis 0.3% vs. 0.5%, Roca et al. 2023).  

Other studies

Anabire et al. (2023) show the rapid decline of parasitemia among 17 Ghanese RDT-positive women post-delivery; genotyping showed a selective reduction of the gene encoding VAR2CSA in infected erythrocytes. Hong et al. (2023) examined the interaction between malaria treatment with DP and efavirenz-based antiretroviral therapy among HIV-infected pregnant women in Uganda and noted that the impact of pregnancy and efavirenz-based treatment on the exposure and, in turn, the efficacy of piperaquine for malaria prevention may not be as important as previously thought.

Ding et al. (2023) reviewed highly sensitive rapid diagnostic tests (HS-RDTs) for the detection of P. falciparum in pregnancy (13 studies) and noted that the HS-RDT had a slightly higher analytical sensitivity to detect malaria infections in pregnancy than the co-RDT used in a study but that this mostly translated to only fractional and not statistically significant improvement in clinical performance by gravidity, trimester, geography or transmission intensity.

A cost-analysis of malaria in pregnancy by Cirera et al. (2023 conducted in the study of Gonzalez et al. reported above) provided the direct and indirect costs associated with malaria prevention and treatment in pregnancy. Societal costs for these four countries were estimated to range from 30 to 46 US dollar per pregnancy.