The Malaria in Pregnancy (MiP) Library is a regularly updated, comprehensive bibliographic database of published and unpublished literature relating to malaria in pregnancy, including a trial registry of planned and ongoing trials.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 2016:
In May 2016, 144 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:
Results of two trials important for policies for malaria in pregnancy were published in the New England Journal of Medicine. Four artemisinin-combinations were compared for the treatment of malaria in pregnancy in a large (3428 participants) multicentre multi-country (Burkina Faso, Ghana, Malawi and Zambia) study (The PregAct Study Group). The PCR adjusted cure rates in the per protocol analysis were 94.8% in the artemether–lumefantrine group, 98.5% in the amodiaquine–artesunate group, 99.2% in the dihydroartemisinin–piperaquine group, and 96.8% in the mefloquine–artesunate group. The unadjusted cure rates, used as a measure of the post-treatment prophylactic effect, were significantly lower in the artemether–lumefantrine group (52.5%) than in groups that received amodiaquine–artesunate (82.3%), dihydroartemisinin–piperaquine (86.9%), or mefloquine–artesunate (73.8%). There were no significant differences between treatment groups in serious adverse events or birth outcomes, but drug related adverse events were more common in the mefloquine-artesunate arm (50.6%) and the amodiaquine-artesunate arm (48.5%), compared to the dihydroartemisinin-arm (20.6%) and the artemether-lumefantrine arm (11.5%). A trial in Uganda involving 300 HIV-negative women compared three doses dihydroartemisinin-piperaquine (DP) during pregnancy versus a monthly dose of DP or intermittent preventive treatment using sulfadoxine-pyrimethamine (IPTp-SP) for the prevention of malaria (Kakuru et al. 2015). Compared to IPTp with SP, three doses of DP showed a protective efficacy of 32% (95% CI 3-52%) for placental malaria by histology whereas the protective efficacy for monthly doses was 46% (95% CI -21%-63%). For a composite endpoint of adverse birth outcomes (abortion, stillbirth, low birth weight, prematurity, or congenital anomaly), compared to IPTp with SP, the protective efficacy of the monthly DP arm was 51%, 95% CI -4-77%, P=0.05, but no difference was seen for the three-dose DP arm (P=0.64). The incidence of clinical malaria during pregnancy was reduced from 40.5% in the IPTp-SP arm to 16.6% in the three-dose DP arm and 0% in the monthly DP arm.
It is estimated that each year four million pregnancies are at risk of malaria in Latin America, and their importance as a reservoir for malaria transmission was reviewed by Yanow et al. Malaria infection during pregnancy can be asymptomatic, and most infections fail to be detected by routine diagnostics. In addition, P. vivax can have dormant liver stages which cannot be treated during pregnancy. Costs of malaria in pregnancy can be considerable in the Latin American setting, as reported in the amazon region in Brazil by Botto-Menezes et al. A study of non-falciparum infections detected by PCR in pregnancy in West Africa (Burkina Faso, The Gambia, Ghana and Mali) by Williams et al. showed a low prevalence (1.4%) overall, with the highest prevalence in Mali (3.8%); the majority (71.4%) presented as mixed infections with P. falciparum. P. malariae infections were 48.6% and four P. vivax infections were detected in Mali. No difference in birth outcomes were seen when comparing outcome among women with non-falciparum infections to non-infected women.
Pregnancies followed by ultrasound in Benin by Briand et al. showed that malaria in both early and late pregnancy was associated with a reduction in foetal growth velocity, either immediately or with delay after the infection, whereas DeBeaudrap et al. showed in Uganda that infant growth is also affected, with growth restriction highest if maternal malaria was 12 weeks prior to delivery. Although the Uganda study noted an association between maternal and infant malaria, this association was not seen for placental malaria among infants whose mothers participated in a malaria prevention trial in Ghana (Awine et al.). Lybbert et al. provide a potential mechanism for the effect of placental malaria on foetal growth, while Charnaud et al. and Dechavanne et al. studied the effect of maternal malaria on the transfer of antibodies. Charnaud et al. noted that maternal P. vivax IgG acquisition was not associated with recent exposure unlike P. falciparum IgG, in an area of low transmission in Thailand. Placental malaria was not associated with a high level of soluble HLA-G among infants in Benin (D’Almeida et al.)
A large observational study from Thailand spanning 19 years by Moore et al. reports on first trimester malaria, malaria treatment and miscarriage, and shows a significant increased risk of miscarriage after the first P. falciparum (hazard ratio 1.61, 95% CI 1.32-1.97) or recurrent P. falciparum (HR 3.24, 95% CI 2.24-4.68) or recurrent symptomatic P. vivax infection (HR 2.44, 95% CI 1.01-5.88). Compared to quinine, artemisinin treatment in the first trimester was not associated with an increased risk of miscarriage or major congenital malformations. Among infants whose mothers participated in a trial comparing IPTp with SP or Mefloquine, no differences were seen in malaria, anaemia, or clinical illness by study arm when followed in their first year (Ruperez et al.). However, there were some differences in psychomotor development milestones in the mefloquine group at 9 months of age which may deserve further attention.
This update includes studies on health seeking behaviour among pregnant women in the face of perceived costs (Klein et al.), malaria knowledge (Mbonye et al.), and adherence to antimalarial therapy (Jaiteh et al.). Studies by Theiss-Nyland et al. reviewed and evaluated the use of antenatal clinics for the routine supply of LLINs (article 2).
Some studies in this update raise serious concerns about provider practices in the treatment and prevention of malaria in pregnancy. For example, treatments and practices of prevention of malaria in pregnancy in private health facilities in Uganda, and health facilities and drug outlets in Kenya, were generally inadequate (Mbonye et al., Riley et al., Dellicour et al.) and the main brand of SP in Ghana used for IPTp was found to be of substandard quality, which will have contributed to poor effectiveness of IPTp found in the Central Region of Ghana locally (Yeboah et al.)
Pharmacokinetics of antimalarials in pregnancy are reviewed by Burger et al., in addition to information on azithromycin and piperaquine from a study in Papua New Guinea (Moore et al.). A new diagnostic malaria test using urine is presented by Yunga et al., but it is not yet clear how the results relate to placental malaria. Menegon et al. present the genetic characteristics of P. vivax strains obtained from pregnant women in four countries (Brazil, Colombia, India and Papua New Guinea), and Patel et al. report on sickle cell trait and placental malaria in Malawi.