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The Malaria in Pregnancy (MiP) Library is a regularly updated, comprehensive bibliographic database of published and unpublished literature relating to malaria in pregnancy, including a trial registry of planned and ongoing trials.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 December 2019-January 2020:

 

In January 2020, 201 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.

Pregnancy can alter the way a drug is metabolized in the body and in this way can alter treatment outcome. (Mutagonda et al. 2019) examined lumefantrine concentration on day 7 post treatment when given for malaria (in combination with artemether) among 205 pregnant and 72 non-pregnant women in Tanzania. Compared to non-pregnant women, mean day 7 lumefantrine concentrations were lower among pregnant women; patients with lower day 7 lumefantrine concentration had a high risk of treatment failure. (Onyamboko et al. 2019) evaluated in an open label randomized controlled trial the efficacy and pharmacokinetics of 3 days versus 5 days of artemether-lumefantrine for the treatment of uncomplicated falciparum malaria in 48 pregnant and 48 non-pregnant women in Kinshasa, Democratic Republic of Congo. Compared to non-pregnant women, parasite clearance half-lives were longer, but both groups and regimens achieved 100% cure rates. Compared to non-pregnant women, exposures to artemether and dihydroartemisinin were lower in pregnant women, but no difference detected for lumefantrine. Exposure to lumefantrine improved with an extended regimen. The extended regimen was well tolerated and safe and babies followed for one year showed normal development.

Three studies explored the potential of using pregnant women as a sentinel population, whereby two studies appear to have used similar data sources in Tanzania (Kitojo et al. 2019; Brunner et al. 2019): screening data at the first antenatal visit compared with malaria prevalence in children aged 6-59 months from national surveys (DHS, and malaria indicator survey). (Kitojo et al. 2019) noted that routine antenatal care-based screening can be used to assess heterogeneity in transmission at finer resolution than population-based surveys but concluded that declines in prevalence at antenatal care might lag behind those among children. (Brunner et al. 2019) compared ANC data with results from national surveys in children 6-59 months, school surveys and the Malaria Atlas Project 2015 and concluded that although ANC data can be used to assess trends, it cannot be used to predict the prevalence in other population subgroups, concluding that complementary surveys are needed. Fonseca et al. (2019) evaluated the usefulness of VAR2CSA serology to assess malaria burden in pregnant women using samples from Mozambique, Benin, Kenya, Gabon, Tanzania, and Spain. They selected antibodies with a short half-life which indicate recent exposure in pregnant women and showed that, in areas with well-attended maternal healthcare services, this pregnancy specific serologic test may serve as a useful sentinel surveillance tool for flagging changes in malaria burden and progress in malaria elimination efforts (http://dx.doi.org/10.3201/eid2510.181177).

There were a considerable number of studies with information on the uptake of intermittent preventive treatment with sulfadoxine-pyrimethamine for the prevention of malaria in pregnancy in Africa. (Mchwampaka et al. 2019) reported a coverage of 48.4% of ≥3 doses of SP in Tanzania among 556 postpartum women, associated with higher level of education, early first ANC visit, and ≥4 antenatal visits. Health workers reported that stock-outs were still a challenge. In Ghana, 64.5% of 935 women had received ≥3 doses of SP at delivery; the receipt of ≥3 doses and sulfadoxine blood levels measured at delivery were associated with an increase in birthweight (Quakyi et al. 2019). (Roman et al. 2019) conducted a review on factors affecting of uptake of IPTp including 42 studies and 20 programme reviews and noted that many of previously signalled problems still exist (discordant national malaria control and reproductive health policies, medication stock-outs, weak and unstandardized quality improvement programmes, weak recording and reporting practices) but can be addressed at the country level to improve IPTp coverage.

(Elphinstone et al. 2019) examined malaria as a risk factor for preterm delivery in a secondary analysis of a randomized trial of malaria prevention in Malawi (1628 participants) and noted that infections early in pregnancy increased the risk of preterm delivery and was associated with altered kinetics of inflammatory and metabolic mediators over the course of pregnancy. A pregnancy cohort in Benin, starting from preconception through to delivery (273 women), noted the highest incidence of microscopic and submicroscopic malaria in the first trimester, with young age and pre-pregnancy submicroscopic malaria as risk factors for malaria infection in pregnancy (Hounkonnou et al. 2019). A trial in Burkina Faso, which collected information among nulligravidae (972) and among participants who consecutively became primigravidae (314), compared indicators of iron deficiency among pregnant and non-pregnant participants, either or not with malaria, and noted that among primigravidae, early pregnancy haemoglobin was not a good indicator of need of iron supplementation; body iron actually increased in early gestation and was higher among primigravidae with malaria, whereas haemoglobin decreased (Diallo et al. 2019). They previously reported on an increased risk of preterm delivery among primigravidae receiving iron supplemented in early pregnancy in the same study (Brabin et al. 2019). The same group proposed a dual hit model, whereby following long-term iron supplementation, dual inflammatory pathways that mediate hepcidin expression and culminate in progesterone withdrawal may account for the reduction in gestational age observed in first pregnancies in this area of high malaria exposure (Brabin et al. 2019).

In this update, there are several articles on the effects of malaria in pregnancy and comorbidities on the infant. A cohort study in western Kenya (1066 participants) examined HIV, malaria and cytomegalovirus (CMV) in pregnancy; maternal prevalence was 19.7%, 19.4% (malaria at enrolment or follow up) and 93.1% (maternal CMV IgG status), respectively. Congenital CMV infection was 3.6% overall, and was associated with HIV infection, whereas the role of malaria was unclear (Otieno et al. 2019). A cross-sectional study at delivery in Malawi (454 mother-infant pairs) examined the effect of HIV and placental malaria on transplacental transfer of influenza antibodies (Ho et al. 2019); maternal HIV infection influenced maternal antibody response to influenza A virus infection, and thereby antibody levels in newborns, but did not affect transplacental antibody transfer. Placental malaria had an inconsistent effect on maternal and infant seropositivity. Lastly, a pregnancy cohort study from preconception to 3 months postpartum in Benin (158 mother-infant pairs) examined the effect of malaria and schistosomiasis in early pregnancy on the infant (Agbota et al. 2019). Malaria, particularly in the first trimester, was significantly associated with a higher risk of infant’s febrile infection, whereas pre-pregnancy malaria and schistosomiasis were associated with lower infant haemoglobin.

Currently, two trials are underway evaluating potential placental malaria vaccines based on VAR2CSA. (Gangnard et al. 2019) showed the existence of cross-species inhibitory epitopes in VAR2CSA between chimpanzee parasite Plasmodium reichenowi and Plasmodium falciparum. (Mitran et al. 2019) describe the molecular mechanism underlying cross-species immunity whereby antibodies to the Plasmodium vivax invasion protein, PvDBP, cross-react with P. falciparum VAR2CSA. For people who would like to know more about malaria in pregnancy pathology and immunology, there is a review by (Feeney et al. 2019) on immunology, and by (Ngai et al. 2019) on potential mechanisms for pathology.

Finally, it is reassuring to know that in a systematic literature review to assess the risk of ocular anomalies in children in utero exposed to chloroquine or quinine in pregnancy among 331 infants who had ophthalmologic examination, a low-to-non-existent risk of visual abnormalities in offspring was detected (Gaffar et al.).