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The Malaria in Pregnancy (MiP) Library is a regularly updated, comprehensive bibliographic database of published and unpublished literature relating to malaria in pregnancy, including a trial registry of planned and ongoing trials.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

Article highlights from the update in August-September 2019

 

In August 2019, 188 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.

This update contains the results of the last trials which were part of the Malaria in Pregnancy Consortium. Intermittent screening and treatment (IST) was compared with passive case detection (PCD) in a cluster randomized trial in India (Jharkand) which enrolled 6,868 women. No significant difference between interventions was detected in placental malaria by histology (primary outcome; 6% in IST and 4% in PCD arm), birthweight, anaemia, gestational age or newborn vital status (Kuepfer et al. 2019). An open-label, three-arm, cluster-randomised, superiority trial comparing intermittent screening and treatment (IST) or intermittent preventive treatment (IPTp) with dihyroartemisinin-piperaquine versus one-time screening and treatment at ANC enrolment (SST) was conducted in 2279 women in Sumba (low malaria transmission site) and Papua (moderate malaria transmission site) in Indonesia (Ahmed et al. 2019). Malaria at delivery (primary outcome, a composite of malaria in any compartment by any laboratory method, including LAMP and histology) was lower in the IPT (11.6%) and IST clusters (11.8%) compared to SST (20.2%). However, malaria at enrolment was lower in the IST arm, making interpretation of the effect of IST challenging. Relative to SST, IPTp was significantly more effective in preventing malaria infections during pregnancy resulting in a reduction of about 41% in the prevalence of malaria infection at delivery, a similar reduction in its incidence during pregnancy, and a 78% reduction in the incidence of clinical malaria during pregnancy. With regards to other outcomes (low birth weight, preterm delivery, maternal haemoglobin < 9 g/dl, foetal loss) there was no clear advantage of one arm over the other.
Other new trials included an open label individually-randomized trial in Papua New Guinea comparing the tolerability and prophylactic efficacy of azithromycin and piperaquine (1 gram AZ, 960 mg PQ per day) over three days versus one day treatment dose of SP for intermittent preventive treatment (IPTp) in 119 participants (Moore et al. 2019). There was no difference in parasitemia by arm at day 42 or at delivery, but newborns in the AZ-PQ arm had a significantly higher birthweight. Women in the AZ-PQ arm had significant more gastro-intestinal side-effects and dizziness. Long term infant follow-up of growth (3-5 year) was reported from a trial in Malawi which compared IPTp with two doses of sulfadoxine-pyrimethamine (SP; control) versus monthly SP or monthly SP plus two doses of AZ (1000 mg once each) against malaria (and other infections) (Hallamaa et al. 2019). IPTp with AZ-SP had a modest, 3-5 year positive impact on child weight, mid-upper arm circumference and head circumference compared to the control group, but not on weight-for-height Z-score. Monthly IPTp with SP had similar results to the AZ-SP group but these were not significant compared to the control group. An open-label trial in Nigeria compared IPTp with SP (three times) versus AZ (500 mg for three days, at monthly intervals, without SP) to prevent malaria among HIV-infected pregnant women (Akinyotu et al. 2019). There was no difference in peripheral malaria at delivery (primary outcome) by arm, nor in other outcomes (placental malaria, low birthweight, maternal anaemia), whereas nausea was higher in the AZ group.

Several studies in this update evaluate coverage of ITNs and IPTp-SP and the factors associated with high uptake or methods to increase uptake. A study in Ghana followed trends in IPTp uptake between 2011-2015 using a local demographic surveillance system (Oppong et al. 2019). Uptake of three or more doses of SP actually decreased over this period, from 40.6% in 2011 to 32.4% in 2015, when stock outs were reported. The intake of three or more SP doses was more common among older women, women with education past primary school, higher frequency of antenatal visits, of higher socio-economic status, and in urban locations, consistent with studies elsewhere. In a report using data from the Ghana national demographic and health survey (DHS 2016), 63% of women were reported to have taken three or more doses of IPTp-SP and showed that uptake was associated with the same factors reported by Oppong et al. (Darteh et al. 2019).

Additionally, uptake of optimal doses of IPTp-SP compared to partial uptake was associated with exposure to media messages on treatment of malaria. In a study in Guinea, (Flueckiger et al. 2019) showed that number of ANC visits and IPTp uptake can be improved using short messaging system alerts on mobile phones of ANC attendees. A study evaluated availability of malaria services and readiness for the provision of these services through ANC in Tanzania using the national Service Provision Assessment (SPA) survey; the authors reported that women who attended a facility with a high readiness score or a facility where directly observed therapy (DOT) was practiced were more likely to receive IPTp (Bajaria et al. 2019). As can be intuited, SP stock outs reduced IPTp coverage. (Theiss-Nyland et al. 2019) used demographic health (DHS) surveys from 25 countries to evaluate how ITN coverage among children <5 years of age can be maintained through routine distribution channels; they reported that an average of 54.0% of children slept under an ITN in countries with an ITN distribution policy via both ANC and EPI, compared to 34.3% and 24.7% in countries with an ITN distribution policy via ANC only, or no facility-based distribution, respectively.

(Mayor et al. 2019) provided an overview on the use of malaria testing at first ANC visit for malaria surveillance and their strengths and limitations. For the ongoing discussion about the safety of iron supplementation in pregnancy in malarious areas, two commentaries from (Verhoef et al. 2019) and (Fowkes et al. 2019) provide contrasting viewpoints.

To evaluate malaria drug therapy in pregnant women, the follow up time of 28-42 days used for non-pregnant persons was generally assumed to be sufficient. (Saito et al. 2019) conducted a secondary analysis of treatment studies in a low malaria transmission area (Thai-Burmese border) to validate this assumption and concluded that only follow up for 63 days detected 95% or more of all recrudescence, except for dihydroartemisinin-piperaquine.

(Teo et al. 2019) examined the effect of malaria prevention strategy (IPTp or IST) on antibody development in Malawi and noted minimal impact of type of prevention on the development and maintenance of malaria immunity. There is quite some debate on the effect of malaria and HIV on the transplacental transfer of antimalarial antibodies; (Ray et al. 2019) report that in a cohort of optimally treated HIV-infected Kenyan women, maternal HIV infection was associated with reduced transplacental transfer of antimalarials antibodies. Several groups use animal models to study malaria in pregnancy and an overview of murine models is provided by (Barateiro et al. 2019), and (Pandya & Penha-Goncalves 2019), and examples of such studies by (Boareto et al. 2019) and (Fontes et al. 2019). The mice study with P. chaubadi from (Morffy Smith et al. 2019) suggests that gut microbiota may have a stronger effect than genetic determinants on malaria severity and pregnancy outcome. Although this technology may be farfetched for practice in humans, (Liu et al. 2019) report on the detection malaria in the placenta in real time using biosensor technologies.

Lastly, a handwritten thesis on malaria in pregnancy was retrieved from 1905 by (Dr Gibson) evaluating whether malaria or quinine cause abortion during the treatment of malarial fever during pregnancy, and the occurrence of malaria during the puerperium (6-week period after childbirth) and its treatment.