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The Malaria in Pregnancy (MiP) Library is a regularly updated, comprehensive bibliographic database of published and unpublished literature relating to malaria in pregnancy, including a trial registry of planned and ongoing trials.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 2017

Article highlights from the update in August 2018

In August 2018, 185 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.

An open label trial in Eastern India examined the safety and efficacy of supervised 3-day combination therapy (artesunate plus sulfadoxine-pyrimethamine versus artesunate plus mefloquine) in malaria infected pregnant women (Anvikar et al. 2018). Malaria infections were detected in 3.5% of screened women. Drug-efficacy of both regimens was high (≥95% in the intention to treat [ITT] analysis and ≥99% in the per protocol analyses). No serious adverse events related to the study drugs were observed; however, women in the arm with mefloquine had more vomiting (6.9% vs 1.6%, respectively).   

A trial in Ghana explored the effect of active involvement of pregnant women in their care, and randomized antenatal clinics into intervention (pregnant women observed malaria and haemoglobin tests being performed and received education on malaria and other tests and health advice) and no intervention (Ampofo et al. 2018). No significant differences were detected in low birth weight or malaria or anaemia during pregnancy or at delivery.

A large trial in Burkina Faso, The Gambia and Benin examined the addition of scheduled malaria screening and treatment by community health workers to intermittent preventive treatment with sulfadoxine-pyrimethamine (IPTp-SP) vs. usual antenatal care only (Cosmic Consortium 2018). No differences were seen in the outcomes for malaria, anaemia, and low birth weight. ANC attendance was significantly higher in the intervention arm in Burkina Faso but not in The Gambia and Benin, and overall, increasing SP doses was protective of adverse pregnancy outcomes.  The receipt of preventive treatment for malaria was a secondary outcome in a stepped-wedge cluster randomized trial in Mozambique to enforce the antenatal care package; the intervention involved four components (kits with medical supplies, a cupboard to store these supplies, a tracking sheet to monitor stocks, and a one-day training session) (Bertran et al. 2018). Preventive treatment for malaria improved from 64% to 94%.

The long term effects of malaria prevention in pregnancy were studied in a trial in Uganda comparing IPTp-SP versus IPTp with dihydroartemisinin-piperaquine (DP), whereby infants were also included in a schedule for DP (every 4 or 8 weeks) (Jagannathan et al. 2018). The results were not straight forward. Children born to mothers who received IPTp with DP every 4 weeks in pregnancy had a significantly higher incidence of malaria and Plasmodium falciparum infection in infancy than the IPTp-SP arm and this increased incidence of malaria was only observed in female infants. Furthermore, female children born to mothers who received IPTp with DP every 4 weeks in pregnancy had significantly lower piperaquine drug levels during infancy compared to male children.

In this update, there were five articles on the safety and effects of insecticides and maternal and infant health. DDT can be used for indoor residual spraying (IRS) to reduce malaria transmission. Three studies were in a birth cohort in South Africa where DDT is used for IRS. Children living in a sprayed area had serum p,p′-DDT/E levels exceeding their mothers' levels during the first two years of life (Verner et al. 2018). However, prenatal exposure to DDT was related to elevated birth size among girls only (Chevrier et al. 2018). In utero IRS insecticide exposure may increase childhood infection rates (Huang et al. 2018), but this was particularly apparent among children from poorer households or whose mothers had low energy intake during pregnancy.

 

 

A case-control study in Finland (where DDT exposure was not through IRS) reported an association with autism, with the odds of autism among offspring significantly increased with maternal p,p:-DDE levels that were in the highest 75th percentile, with adjustment for maternal age, parity, and history of psychiatric disorders (Brown et al. 2018). An in-vitro study suggested that deltamethoprim, an insecticide commonly used in insecticide-treated nets, may interfere with the development of the foetus when the exposure is considerable (Markus et al. 2018).

A study to estimate the long-term impacts of early life (in utero and postnatal) exposure to malaria showed that the eradication of malaria in Taiwan was associated with increased men’s education attainment, and family income (Shih & Lin 2018).

The first trimester of pregnancy is a well-known vulnerable period, but currently ITNs are the only option for malaria prevention. Hounkonnou et al (2018) show that they indeed offer protection, but that the usual indicators of possession and use may not be the best measures to assess their effect.

Pregnancy, HIV and drug combinations affect the pharmacokinetics of drugs. A Nigerian study examined blood levels of efavirenz and lumefantrine in HIV-infected pregnant and non-pregnant women and noted that plasma concentrations for efavirenz were significantly lower in pregnancy, whereas lumefantrine levels were higher among these HIV-infected women (Adegbo et al. 2018). Pooling of pharmacokinetic data for lumefantrine in pregnant (mostly non-HIV-infected) women and using pharmacokinetic models suggested that beyond the first trimester, lengthening the dose regimen (twice daily for 5 days) and, to a lesser extent, intensifying the frequency of dosing (3 times daily for 3 days) would be more efficacious than using higher individual doses in the current standard treatment regimen (Kloprogge et al. 2018).

In a study in Mali, maternal antiparasitic IgG, specifically antibodies to Schizont Egress Antigen-1 (PfSEA-1) measured in cord blood, was associated with reduced risk of severe malaria in infants. A similar protective effect was seen among offspring of female mice vaccinated with the similar antibody against P. berghei, suggesting that vaccination of women can result in a survival advantage of their infants (Kurtis et al. 2018).   

Yaya et al. (2018) report the potentially important role of malaria information received through mass media on utilisation of ITN among women in sub-Saharan Africa. For countries striving to improve IPTp coverage, please note a new toolkit is available in English, French and Portuguese.