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The Malaria in Pregnancy (MiP) Library is a regularly updated, comprehensive bibliographic database of published and unpublished literature relating to malaria in pregnancy, including a trial registry of planned and ongoing trials.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 January 2020

Article highlights from the update in August-September 2021:

 

In September 2021, 133 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 Saito et al. (2021) compared malaria treatment efficacy of Plasmodium falciparum and P. vivax with dihydroartemisinin-piperaquine (DP, artesunate-mefloquine (AM) and extended artemether-lumefantrine (AL+, 4 days). The trial was stopped prematurely because successful malaria elimination reduced falciparum infections to a rare occasion. Among the 511 of the 1005 planned women who were enrolled, the majority had recurrent malaria, mainly P. vivax relapses. DP and ASMQ provided longer recurrence-free intervals. Recrudescence was almost exclusively among P. falciparum with Pfkelch13 mutations. Side effects were more common with AM. Malaria prevention among HIV-infected women is important; a trial in the Central African Republic explored if cotrimoxazole (CTX, one daily tablet) was more effective than three treatments of sulfadoxine-pyrimethamine (SP) (Manirakiza et al. 2021). Because of political unrest and insecurity, only 193 of the 300 planned women could be enrolled and 112 had a primary outcome. Placental malaria (combining microscopy and PCR) by treatment arm was 8.5% and 15.1% in CTX and SP arm, respectively (p=0.28).

Reviews and meta-analyses Heng et al. (2021) used a novel method to estimate the effect of decreasing malaria burden on low birth weight from Demographic and Health Surveys from 2000-2015 supplemented with malaria indicators from the malaria atlas project. Using a process of double matching and imputation of missing low birth weight data, they estimate that a decline in malaria prevalence of 20% (from 40% to 20%) in children 2-10 years of age would result in a decrease in low birth weight of 1.48 percentage points (95% CI -3.70 to 0.74); for primigravidae this might be 3.73% (-9.11 to 1.64). Cardona-Arias & Carmona-Fonseca (2021) reviewed prevalence of malaria in pregnancy in Colombia; infections by P. vivax were dominant over P. falciparum when tested by microscopy but the PCR test gave similar proportions. Hawadak et al. (2021) reviewed P. malaria and P. ovale globally, and noted that in Africa, P. malariae was equally distributed among adults (2.13%), children (2.90%) and pregnant women (2.77%) (p = 0.862), whereas P. ovale spp. was more prevalent in pregnant women (2.90%) than in children ≤ 15 years (0.97%) and in patients > 15 years old (0.39%) (p = 0.021).

Epidemiology In this update there are several articles on the effect of malaria in pregnancy on the infant. A total of 192 infants whose mothers were participating in a trial (IPTp-DP vs. IPTp-SP) in Malawi were followed from birth to 24 months; the authors did not find evidence that IPTp regimen or placental malaria exposure influenced risk of malaria during infancy in this population (Andronescu et al. 2021). Garrison et al. (2021) described short and long term follow up of the effects of malaria in pregnancy on neurocognitive development in the infant using data from a trial among 493 pregnant women. Impaired gross motor scores and lower non-verbal scores in the infant were associated with malaria in pregnancy. An observational study in Ghana assessed neurological functioning within 48 hours of birth among 211 term neonates; only in the reflexes-subdomain did malaria-exposed neonates score suboptimally compared to unexposed neonates (Lawford et al. 2021). Pincelli et al. (2021) describe the malaria experience of a birth cohort in Brazil with P. vivax as the dominant species; children seemed protected in the first year but became as vulnerable to P. vivax as their mothers after 12 months of age. Antenatal malaria was a risk factor for malaria in the infant, after adjusting for local transmission intensity. Repeated child vivax episodes were associated with anaemia. Simon et al. (2021) assessed the occurrence of maternal cells in cord blood in a Ugandan study; this was associated with early maternal parasitaemia, but not with first parasitaemic episode of the infant. Honkpehedji et al. (2021) studied the effect of the presence of multiple parasites (e.g., plasmodium, helminthic infections, Schistosoma) in the mother on birth weight in the infant in Gabon and noted an increasing trend in the risk of low birth weight with the number of types of parasites that the mother was carrying (e.g., two parasites adjusted OR [aOR] 2.63, 95% CI 1.51-4.62, 3+ parasites aOR 5.08, 95% CI 2.5-10.38).

Immunology Multiple studies gave new insights in immunology of malaria in pregnancy in Papua New Guinea. Aitken et al. (2021) used machine learning techniques to select antibody features that were associated with protection from placental malaria. In a study by McLean et al. (2021) IgG levels against VAR2CSA domains were associated with higher birthweights and less malaria if women had P. falciparum at enrolment in mid-pregnancy; however, this was not the case for women without P. falciparum at enrolment. In the same population, Opi et al. (2021) noted that a higher magnitude of complement fixing antibodies was prospectively associated with reduced odds of placental infection. In the sulfadoxine-pyrimethamine (SP) trial arm of a study in Uganda, Singoei et al. (2021) described placental changes in the chorioamniotic membrane with malaria infection in 116 Kenyan women, half without placental infection. Wang et al. (2021) examined the structure of placental VAR2CSA when viewing up close using cryo-electron microscopy.

Malaria prevention An entomological study was combined with confirmation of sleeping behaviour the previous night of pregnant women in southern Benin; the authors noted that more than 90% of malaria vectors bites and Plasmodium falciparum transmission occurred between 10 p.m. and 6 a.m., a period at which over 80% of pregnant women were under bed net in the study area (Djenontin et al. 2021). In Nigeria, a study among 500 pregnant women showed that 65.8% were willing to use indoor residual spraying in their house (Oladoyinbo et al. 2021). Hansen et al. (2021) confirmed that recall data about IPTp was comparable to the coverage rates indicated by the antenatal clinic cards. Two qualitative studies investigated acceptability of screening and treatment using rapid diagnostic tests; Hoyt et al. (2021) found in a Kenyan study using focus group discussions among pregnant women and in-depth interviews among health workers that intermittent screening and treatment with dihydroartemisinin–piperaquine (DP) was an acceptable alternative to IPTp with SP and that both treatment and prevention could be delivered in ANC despite some concerns about increased workloads for ANC nurses. Kitojo et al. (2021) found in Tanzania that a single screen with an RDT at the antenatal booking visit and treatment according to national policy if positive was acceptable to pregnant women and health workers, but nurses were frustrated they were not allowed to prescribe antimalarials to immediately treat women if needed.

Chloroquine and hydroxychloroquine Probably because of its potential use to treat COVID-19, there is a striking number of studies which have looked at chloroquine and hydroxychloroquine use early in pregnancy and risk of adverse birth outcomes in the infant. Huybrechts et al. (2021) looked at an American cohort where 60% of women used 400 mg hydroxychloroquine daily. Overall, 54.8 per 1000 infants exposed to hydroxychloroquine in the first trimester were born with a major congenital malformation versus 35.3 per 1000 unexposed infants, corresponding to an unadjusted relative risk of 1.51 (95% confidence interval, 1.27-1.81). Andersson et al. (2021) evaluated a Danish cohort with and without chloroquine or hydroxychloroquine exposure; the prevalence OR for birth defects was 0.94, 95% CI 0.59-1.52, and no association was seen with a preterm or small-for-gestational-age birth. In a Canadian cohort, the aOR of congenital malformations after first trimester exposure was 1.01, 95% CI 0.67-1.52 and no association with prematurity was detected (Berard et al. 2021). If one would conduct a meta-analysis for birth defects after first trimester chloroquine/hydroxychloroquine exposure using results from these three studies, the pooled estimate would be 1.19, 95% CI 0.79-1.58, I2 68.7% (unpublished, conducted by AMvE).