Malaria Infection Is Common and Associated With Perinatal Mortality and Preterm Delivery Despite Widespread Use of Chemoprevention in Mali: An Observational Study 2010 to 2014.

BACKGROUND: In malaria-endemic areas, pregnant women and especially first-time mothers are more susceptible to Plasmodium falciparum. Malaria diagnosis is often missed during pregnancy, because many women with placental malaria remain asymptomatic or have submicroscopic parasitemia, masking the association between malaria and pregnancy outcomes. Severe maternal anemia and low birthweight deliveries are well-established sequelae, but few studies have confirmed the relationship between malaria infection and severe outcomes like perinatal mortality in high transmission zones. METHODS: Pregnant women of any gestational age enrolled at antenatal clinic into a longitudinal cohort study in Ouelessebougou, Mali, an area of high seasonal malaria transmission. Follow-up visits included scheduled and unscheduled visits throughout pregnancy. Blood smear microscopy and polymerase chain reaction (PCR) analysis were employed to detect both microscopic and submicroscopic infections, respectively. Intermittent preventative treatment in pregnancy with sulfadoxine-pyrimethamine (IPTp-SP) was documented and prompt treatment regardless of symptoms given upon malaria diagnosis. RESULTS: Of the 1850 women followed through delivery, 72.6% of women received 2 or more IPTp-SP doses, 67.2% of women experienced at least 1 infection between enrollment up to and including delivery. Malaria infection increased the risks of stillbirth (adjusted hazard ratio [aHR] 3.87, 95% confidence interval [CI]: 1.18-12.71) and preterm delivery (aHR 2.41, 95% CI: 1.35-4.29) in primigravidae, and early neonatal death (death within 7 days) in secundigravidae and multigravidae (aHR 6.30, 95% CI: 1.41-28.15). CONCLUSIONS: Malaria treatment after diagnosis, alongside IPTp-SP, is insufficient to prevent malaria-related stillbirth, early neonatal death and preterm delivery (PTD). Although IPTp-SP was beneficial in Mali during the study period, new tools are needed to improve pregnancy outcomes. CLINICAL TRIALS REGISTRATION: NCT01168271.

Adverse pregnancy outcomes among women presenting at antenatal clinics in Ouélessébougou, Mali.

BACKGROUND: In sub-Saharan Africa, malaria continues to scourge the population and is the primary cause of morbidity and mortality in young children and pregnant women. As current preventative measures such as intermittent preventive treatment and use of insecticide-treated nets provide incomplete protection, several malaria vaccines are currently under development, including one to specifically prevent pregnancy malaria. Prior to conducting vaccine trials, it is important to obtain background information on poor pregnancy outcomes in the target population to establish a baseline. METHODS: Pregnant women presenting at community health care centers for antenatal care were recruited to the study. Gestational age was determined by ultrasound examination following recruitment. Antenatal care and pregnancy outcome information were collected during a visit 4-8 weeks post-delivery. RESULTS: One thousand eight hundred fifty women completed the study, and analysis included 1814 women after excluding multiple gestations (n = 26) and missing/incomplete data (n = 10). The percentage (95% CI) of adverse pregnancy outcomes is as follows: miscarriage, 0.28% (0.04-0.52); stillbirth, 1.93% (1.30-2.56); early neonatal death, 1.65% (1.03-2.24); late neonatal death, 0.39%, (0.10-0.68); and preterm delivery (PTD), 4.74% (3.76-5.73). The percentages of early and late neonatal deaths and PTD were significantly higher (p < 0.01) in primigravid compared to multigravid women. In primigravidae, 3.1, 1.1 and 7.1% of pregnancies resulted in early neonatal death, late neonatal death and PTD, respectively, while these outcomes in multigravidae were 1.0, 0.1 and 2.7%, respectively. Major malformations were identified in 4 newborns. CONCLUSIONS: Low gravidity and young age predict perinatal death and PTD. The information collected here can be used as a baseline for adverse pregnancy outcomes in future vaccine trials in pregnant women.

Antibody levels to recombinant VAR2CSA domains vary with Plasmodium falciparum parasitaemia, gestational age, and gravidity, but do not predict pregnancy outcomes.

BACKGROUND: Maternal malaria is a tropical scourge associated with poor pregnancy outcomes. Women become resistant to Plasmodium falciparum pregnancy malaria as they acquire antibodies to the variant surface antigen VAR2CSA, a leading vaccine candidate. Because malaria infection may increase VAR2CSA antibody levels and thereby confound analyses of immune protection, gravidity-dependent changes in antibody levels during and after infection, and the effect of VAR2CSA antibodies on pregnancy outcomes were evaluated. METHODS: Pregnant women enrolled in a longitudinal cohort study of mother-infant pairs in Ouelessebougou, Mali provided plasma samples at enrollment, gestational week 30-32, and delivery. Antibody levels to VAR2CSA domains were measured using a multiplex bead-based assay. RESULTS: Antibody levels to VAR2CSA were higher in multigravidae than primigravidae. Malaria infection was associated with increased antibody levels to VAR2CSA domains. In primigravidae but not in secundigravidae or multigravidae, antibodies levels sharply declined after an infection. A relationship between any VAR2CSA antibody specificity and protection from adverse pregnancy outcomes was not detected. CONCLUSIONS: During malaria infection, primigravidae acquire short-lived antibodies. The lack of an association between VAR2CSA domain antibody reactivity and improved pregnancy outcomes suggests that the recombinant proteins may not present native epitopes targeted by protective antibodies.