The Malaria in Pregnancy (MiP) Library is a regularly updated, comprehensive bibliographic database of published and unpublished literature relating to malaria in pregnancy, including a trial registry of planned and ongoing trials.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 May 2015:
In May 2015, over 140 new entries were added to the MiP library. New entries include peer reviewed journal articles, PhD and MSc theses, and reports. Here we highlight a few articles that may be of particular interest:
Important information on the pharmacokinetics of artemisinin derivatives comes from Thailand where a modelling study showed that malaria may increase the absolute oral bioavailability of artesunate by 87%, whereas pregnancy may decrease oral bioavailability by 23% (Kloprogge et al. 2015). The safety of first trimester exposure to artemisinins was assessed in infants of 159 women in Zambia and no difference was detected compared to infants of women with first trimester exposure to SP or quinine (Manyando et al. 2015).
Two studies examined drugs used for intermittent preventive treatment in pregnancy (IPTp) and their effect on bacterial infections. A study in Gabon did not detect an association between Group B Streptococcus colonization in pregnant women and the use of sulfadoxine-pyrimethamine (SP) or mefloquine (Capan Melser 2015 et al.), whereas a trial in Papua New Guinea saw a reduction in carriage of Streptococcus pneumonia and Haemophilus influenza, but not Staphylococcus aureus among participants receiving monthly SP in combination with azithromycin (1000 mg twice a day for 2 days) compared to SP-chloroquine. However, more macrolide-resistant isolates were detected in the SP-azithromycin arm (Unger 2015 et al.).
It is encouraging that several studies on malaria in pregnancy outside of Africa and on the pathology of Plasmodium vivax during pregnancy were published. Mclean et al. published a comprehensive review of the pathology of P. falciparum and P. vivax in pregnancy, with a focus on areas where both species occur. In addition, they reviewed malaria in the immediate postpartum period in an attempt to align epidemiological information with what is known about malaria immunology during pregnancy and postpartum. Brock et al. examined the pathology of P. vivax malaria by ultrasound in the Brazilian Amazon. They detected significant placental thickness changes, but these did not have foetal repercussions at birth, possibly because of the early diagnosis and treatment. However, the risk of P. vivax during pregnancy should not be underestimated is illustrated in a combined study of clinical P. vivax in Brazil and India where pregnancy was associated with severity of disease (Siqueira et al. 2015).
It is still not possible to reliably diagnose placental malaria during pregnancy. Ruizendaal et al. examined host biomarkers which could potentially be used for this purpose. They recommend some candidates for further evaluation during pregnancy (inflammatory markers (TNF-R2, CXCL-13), markers of lipid metabolism (APO-B), angiogenesis (sFlt-1) and hormones (estradiol)) because most previous studies have evaluated markers at the time of delivery.
It is still not possible to reliably diagnose placental malaria during pregnancy. Ruizendaal et al. examined host biomarkers which could potentially be used for this purpose. They recommend some candidates for further evaluation during pregnancy (inflammatory markers (TNF-R2, CXCL-13), markers of lipid metabolism (APO-B), angiogenesis (sFlt-1) and hormones (estradiol)) because most previous studies have evaluated markers at the time of delivery. Two articles of interest are with regards to the economics of malaria in pregnancy. Fernandes et al. modelled the costs of the IPTp strategy with three doses of SP (IPTp-SP3+) compared to two doses.
The delivery of IPTp-SP3+ to 1000 pregnant women averted 113·4 DALYs at an incremental cost of $825·67, producing an incremental cost-effectiveness ratio (ICER) of $7·28 per DALY averted, providing strong evidence to support the current WHO guidelines of monthly IPTp. Sicuri et al. evaluated the economic implications of an alternative drug to SP for use as IPTp. They report that in HIV-negative women, moderate shifts of variables such as malaria incidence, drug cost, and IPTp efficacy increased the ICERs above the cost-effectiveness threshold. In HIV-positive women the intervention remained cost-effective for a substantial (up to 21 times) increase in cost per tablet.
Ever since the introduction of PCR there has been contradicting information on the importance of sub-microscopic infections in malaria during pregnancy, and in this update there are several contributions to this discussion. Cottrell et al. report a clear adverse effect of sub-microscopic infections detected at enrolment on maternal anaemia and infant outcomes in a cohort study in Benin. Sub-microscopic infections were not associated with anaemia among antenatal clinic participants or participants at the time of delivery in cross-sectional surveys in India and were not associated with low birth weight, in contrast to microscopically detected infections (Singh et al. 2015). A cohort study in Papua New Guinea only reports an association between sub-microscopic infections at delivery and low birth weight (Stanisic et al. 2015). Bouyou-Akotet et al. report on an increase of sub-microscopic gametocyte carriage following IPTp-SP implementation observed among pregnant women living in Gabon which contrasts with a previous report from Malawi (Boudova 2014 et al.).
Several articles report on the immunology of malaria in pregnancy, e.g. gravidity and antibodies to VAR2CSA in Senegal (Dechavanne 2015 et al.), the association between VAR2CSA-specific antibodies in pregnant women and pregnancy outcome in Benin (Tuikue Ndam et al. 2015), cytokines and pregnancy outcome in Papua New Guinea (Requena et al. 2015) and the effects of placental malaria on hormones and cytokines in Cameroon (Megnekou et al. 2015).
In this update we included national operational plans for all countries supported by the US President’s Malaria Initiative (PMI) for 2015, providing useful information on the countries’ progress towards the reduction of malaria transmission, and strategies for controlling malaria in pregnant women.