The Malaria in Pregnancy (MiP) Library is a regularly updated, comprehensive bibliographic database of published and unpublished literature relating to malaria in pregnancy, including a trial registry of planned and ongoing trials.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 2016:
In January 2016, 220 new entries were added to the MiP library. New entries include peer reviewed journal articles, PhD and MSc theses, and reports. Relevant abstracts from the 9th European Congress on Tropical Medicine and International Health (Basel, Switzerland) and from the 64th annual meeting of the American Society of Tropical Medicine and Hygiene (Philadelphia, USA) were included as well. Here we highlight a few articles that may be of particular interest:
The results of a multicentre trial comparing intermittent screening using rapid diagnostic malaria tests and treatment of women testing positive with dihydroartemisinin-piperaquine (ISTp-DP) versus intermittent preventive treatment using sulfadoxine-pyrimethamine (IPTp-SP) or intermittent preventive treatment with DP (IPTp-DP) in Kenya were published in the Lancet (Desai et al. 2015). Compared to IPTp-SP, IPTp-DP was associated with an 84% reduction in the incidence of clinical malaria during pregnancy, a 68% reduction in the risk of malaria infection at delivery and a 22% lower risk of anaemia at delivery, whereas ISTp-DP was associated with a higher incidence of malaria in pregnancy. IPTp-DP was also associated with up to 75% lower risk of stillbirths and early infant mortality than with SP.
SP resistance is of concern for the effectiveness of IPTp. An individual patient data analysis of data from 8 sites in 6 countries reported that IPTp-SP use was associated with increases in birth weight and maternal haemoglobin even in areas with high resistance provides reassurance about continued effectiveness, nevertheless assessment of efficacy of alternative drugs or strategies are needed (Desai et al. 2015). Information on the prevalence of molecular markers associated with SP resistance is available from several other articles (e.g. Braun et al. 2015; Tahita et al. 2015), and a systematic review examined if a prevalence threshold for the 581G mutation would be meaningful to guide policy (Chico et al. 2015). IPTp coverage at the national level from 2003-2013 was reviewed by Andrews et al. who noted that coverage of recommended tetanus toxoid exceeded that of IPTp in all but one surveyed country.
From Mozambique, there is a descriptive study of parasitologic, immunologic, and clinical trends among pregnant women participating in two clinical trials of malaria prevention over a 10-year period (2003-2005 versus 2010-2012). Paradoxically, with decreasing prevalence of malaria and malarial antibodies, the adverse effects of malaria infection on haemoglobin and birthweight increased (Mayor et al. 2015). Decreasing malarial antibodies after introduction of IPTp-SP was also reported from Cameroon (Babakhanyan et al.). Multiple studies reported on immunological issues related to vaccine development, e.g. Doritchamou et al.2015, Gangnard et al. 2015, Fried et al. 2015, Nielsen et al.2015, and Thrane et al. 2015.
Both malaria and indoor residual spraying for prevention of malaria can have negative effects on the developing foetus. In a mouse model, offspring exposed to malaria in pregnancy were more likely to have persistent neurocognitive deficits in memory and affective-like behaviour compared to unexposed controls (McDonalds et al. 2015). Intrauterine DDT exposure might have an effect on cognitive development in children measured at the age of 7, and more so in girls (Gaspar et al. 2015).
No differences in pharmacokinetics were detected in a pharmacokinetic study of artemether-lumefantrine comparing 30 pregnant women versus 30 non-pregnant adults (11 males) in Uganda, except for a difference in the terminal elimination half-life of dihydroartemisinin and lumefantrine, which might contribute to shorter post treatment prophylaxis in pregnancy. In Uganda, a pharmacokinetic study of SP in the 2nd and 3rd trimester, compared to non-pregnant women, found higher clearance of both drugs detected during pregnancy (Odongo et al. 2015).
In Kenya, the pharmacokinetics of mefloquine were examined among HIV-infected pregnant women, and the potential interaction with cotrimoxazole. Mefloquine pharmacokinetics did not seem affected compared to reported values, but sulfamethoxazole levels decreased after mefloquine intake, and returned to pre-dose levels in 28 days. However, no clinical consequences were detected (Green et al. 2015).
With regards to policy, a meeting report of the WHO Evidence Review Group on malaria in pregnancy is now available, recommending that for the treatment of clinical uncomplicated malaria episodes in women in the first trimester of pregnancy the guideline should be updated as follows: “Treat pregnant women with uncomplicated P. falciparum malaria with either the first-line ACT for 3 days or quinine and clindamycin for 7 days.” Artemether-lumefantrine (AL) should be the preferred ACT, because most of the available data derive from AL exposure. Data on the safety of artemisinin-combination therapies (ACTs) for treatment in pregnancy are available from two studies; a prospective cohort study in Kenya, which confirmed inadvertent artemisinin exposure during the potential embryo-sensitive period was not associated with increased risk of miscarriage (Dellicour et al. 2015), and a systematic review confirming that ACTs are better than quinine in the second and third trimesters (Burger et al. 2015 ).