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The Malaria in Pregnancy (MiP) Library is a regularly updated, comprehensive bibliographic database of published and unpublished literature relating to malaria in pregnancy, including a trial registry of planned and ongoing trials.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 2020

Article highlights from the update in August-September 2020:

 

In September 2020, 168 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.

Covid-19. Covid-19 is now an endemic infection and not likely to disappear without a vaccine. Several articles and reports discus the implications of Covid-19 for malaria control and strongly suggest that malaria prevention and control should continue to avoid malaria epidemics (e.g. Rogerson et al. 2020; Amimo et al. 2020). Practical guidelines on safety measures are provided by TIPTOP (2020) on intermittent preventive treatment (IPTp) delivery by community workers, and by WHO 2020 on malaria prevention in general (tailoring malaria interventions in the COVID-19 response).

Trials. A Ugandan trial which compared IPTp with sulfadoxine-pyrimethamine (SP) versus IPTp with dihydroartemisinin-piperaquine (DP) among pregnant women reported malaria results among their infants followed for one year. The incidence of malaria and complicated malaria was lower in infants in the DP arm (p=0.11 and p=0.02, respectively); there was effect modification by infant gender with a stronger malaria protective effect among male infants of mothers in the DP-arm, especially after the first 3 months of life, whereas no difference was noted by treatment arm among female infants (Kakuru et al. 2020). A cluster randomized trial in Burkina Faso evaluated the effect of IPTp delivery by community health workers compared to ANC only (Gutman et al. 2020; Brieger et al. 2020). At baseline, women received a median of 2.1 doses; by endline, women received a median of 1.8 doses in the control group and 2.8 doses in the intervention group (p < 0.0001). There was a non-statistically significant increase in the proportion of women attending four ANC visits in the intervention compared to control group, suggesting that in this setting IPTp delivered by community health workers did not reduce antenatal visits. A mediation analysis of data from trials in Kenya and Uganda tried to disentangle the effect of SP on birthweight that cannot be attributed to malaria prevention, by comparing with results from IPTp with DP (Roh et al. 2020). SP conferred a greater non-malarial effect than DP (mean difference 87 g, 95% CI 43 to 131), whereas DP conferred a slightly greater antimalarial effect than SP (8 g, –9 to 26), although more frequent dosing of DP increased the antimalarial effect (31 g, 3 to 60).

Systematic Reviews. An individual patient data analysis examined efficacy of different treatments of malaria episodes among pregnant women (Saito et al. 2020 Lancet Infectious Diseases) and managed to include 92% of patients identified in the literature search. Compared to artemether-lumefantrine, PCR-corrected treatment failure was significantly higher in quinine-treated patients (n=244, adjusted hazard ratio 6.11, 95% CI 2,.57-14.54) and significantly lower in artesunate combined with either amodiaquine or mefloquine, or dihydroartemisinin-piperaquine. Risk of gametocyte carriage was also higher on day 7 after quinine-based therapy than artemisinin-based treatments (adjusted Odds Ratio 7.38, 95% CI 2.29-23.82). The authors note that the lower efficacy of artemether-lumefantrine compared with other artemisinin-combination therapies (ACTs) might require dose optimisation. The same group also assessed pregnancy outcomes and risk of placental malaria following treatment with these various therapies (Saito et al. 2020 BMC Medicine). The overall pooled proportion of stillbirth was 1.1% (84/4361), preterm birth 10.0% (619/4131), small-for-gestational age 32.3% (1007/3707), and placental malaria 80.1% (2543/3035), and there were no significant differences of considered outcomes by ACT. Higher parasitaemia before treatment was associated with a higher risk of small-for-gestational age and deposition of malaria pigment in the placenta. These studies were initiated by the WWARN-platform (WorldWide Antimalarial Resistance Network). Note that there is a WorldWide Antimalarial Resistance Network Clinical Trials Publication Library (Takata et al. 2020), which is a live, open-access database of Plasmodium treatment efficacy trials for the wider malaria community. There is an ongoing debate about the use of artemisinins for treatment of malaria in the first trimester. The potential embryotoxic effect of artemisinin derivatives seen among mammals as reviewed by Gonzalez et al. (2020) and D’Alessandro et al. (2020) cannot be completely excluded among humans although human first trimester experiences are so far assuring (Dellicour et al. 2017; D’Alessandro et al. 2020). Quinine is currently recommended for the first trimester, but, as Saito et al (2020), and Gutman et al. (2020) pointed out, adherence to quinine can be poor because of side-effects and affect drug efficacy. In this update there is a systematic review on prevalence of congenital malaria (Bilal et al. 2020) and clinical congenital malaria (Danwang et al. 2020). The overall prevalence of congenital malaria was 6.9% (95 % CI: 4.8–7.9 %) (562/8148) in 24 studies; the overall crude prevalence of clinical congenital malaria was 4.0% (95% CI 2.0–6.8; 17 studies).


Other (non-systematic) reviews. For people who want to know about the progress of malaria vaccines, there is a review by Duffy et al. (2020), whereas Moore & Davis (2020) compiled information on pharmacokinetics of antimalarials currently used in pregnancy and note that pregnant women continue to receive treatment regimens optimized for non-pregnant adults. However, in-silico models may identify alternative dosing regimens that may work better for pregnant women.

Prevention. So far, screening strategies using RDTs at regular intervals in ANC have not shown clear benefits over IPTp with SP. Walker et al. (2020) used modelling to assess if there is a role for malaria screening in ANC alone or as part of IPTp and confirms that monthly ISTp with standard or ultrasensitive RDTs is not superior to monthly IPTp. However, adding screening at the first ANC visit to IPTp as part of a hybrid strategy may be beneficial in areas with high SP resistance, and can also be used in the first trimester when SP is contraindicated. Amoakoh-Colemen et al. (2020) evaluated the effect of IPTp among obstetric referrals in Ghana; a significant protective effect of ≥3 doses of SP was seen on newborn complications, low birthweight and preterm delivery. For maternal complications a protective effect was seen in univariate but not in multivariate analysis.

Epidemiology. A cohort study in Benin noted that among 63 women with malaria infections detected before conception and in the first trimester, 29 (46%) were similar based on both msp-2 and glurp genotyping (Jafari-Guemouri et al. 2020). The same cohort study examined submicroscopic and microscopic malaria throughout pregnancy; The incidence rate of submicroscopic P. falciparum infections during pregnancy was 12.7 per 100 person-months (95% CI 10.8–14.9), compared to 6.7 per 100 person-months (95% CI 5.5–8.1) for microscopic infections. The prevalences were highest in the first trimester, and risk factors included young age and submicroscopic infections acquired before pregnancy (Hounkounnou et al. 2020).

Treatment and drug resistance. A study in Colombia (Castro-Cavadia et al. 2020, Spanish language) assessed chloroquine efficacy among 47 pregnant women; there were 2 cases of drug resistance within 28 days. Among the 34 women followed until day 120, 13 cases had a recurrence or relapse; the authors estimate that the recurrence or relapse rate is between 29-53%. Primaquine is contra-indicated in pregnant women: a Brazilian study estimated that 23% of pregnant women infected with P. vivax have one ore more vivax recurrences over the next 12 weeks, and 86% can be attributable to relapses or later recrudescence instead of new infections. Weekly chemoprophylaxis with chloroquine after the first vivax episode may reduce this by 20-65% (Corder et al. 2020).

Immunology. A study in Yaoundé, a relatively low-malaria transmission area in Cameroon observed that following 10 years of IPTp-SP implementation, few women had antibodies to VAR2CSA (Djontu et al. 2020). Dobano et al. (2020) examined cytokine responses among P. vivax infection during pregnancy and at delivery; CCL11 was the only biomarker to show a negative association with P. vivax infection and its concentration at recruitment was positively associated with haemoglobin levels at delivery.

Diagnosis of malaria. A study in Colombia evaluated five tests for P. falciparum (microscopy, conventional rapid diagnostic tests (RDT), highly sensitive RDT (hsRDT), LAMP and nested polymerase chain reaction-PCR) among pregnant women. Compared to PCR, sensitivity of the hsRDT (64%) was slightly better than microscopy and RDT (59 and 54% respectively), whereas LAMP had the highest sensitivity (90%) (Vasquez et al. 2020). Prevalence by PCR was 4.5% with half of infections subpatent. A similar study was conducted in a cohort in Benin, using a common RDT, hsRDT, microscopy, and a quantitative PCR (Briand et al. 2020). Compared to PCR, RDT and hsRDT had a sensitivity of 44 and 61%; sensitivity differed by trimester and was higher in the peripheral blood at delivery. Prevalence by PCR was 18%, and about 40% of infections were subpatent. Tadesse et al. (2020) evaluated LAMP as part of an IST strategy (screening for malaria in three ANC visits by either routine tests of RDT or microscopy vs. LAMP) in Ethiopia. Among 435 samples, RDT and microscopy had a sensitivity of 67% and 56% compared to LAMP. Of the 9 infections detected by LAMP in the IST cohort of 149 women, 33% were subpatent.