Malaria variant ups risk of low birth weight, small for gestational age
Infection with different malaria strains results in differential adverse pregnancy and birth weight outcomes in malaria-endemic African populations, a new study has shown. Specifically, parasites that carry 3D7-like variant of the VAR2CSA Plasmodium falciparum protein cause poorer birth outcomes.
“This is the first study investigating effects of specific genetic variants of var2csa on clinical outcomes. We employed an integrative approach, using molecular epidemiology, next-generation sequencing and population genetics,” said researchers.
“The results from our study provide strong support for the development of polyvalent VAR2CSA-based vaccines against pregnancy-associated malaria,” they added.
The study included P. falciparum-infected placental samples from 101 pregnant women, of which 56 were from Malawi (mean maternal age 20.5±4.6 years) and 45 were from Benin (mean maternal age 24±6.3 years). Maternal age (p=0.013) and gestational age at delivery (p<0.001) were significantly higher in the Benin cohort. [Sci Rep 2017;7:7768]
The placental samples were then subjected to amplicon deep-sequencing and subsequent clustering to determine the sequence diversity of the ID1-DBL2X region of the VAR2CSA. This resulted in five distinct clades, two of which, the FCR-3- and 3D7-like variants, were common to both Malawi and Benin cohorts.
“Our study shows that the ID1-DBL2x epitope in the N-terminus region is highly diverse among P. falciparum-infected pregnant women in Malawi and Benin. There were 152 variants found among 101 women, and they clustered phylogenetically into five distinct clades,” the researchers reported.
In the Malawi cohort, mothers infected with the 3D7-like and FCR-3-like variant had median infant birth weight of 2,450 and 2,800 g, respectively. By comparison, those in the Benin cohort had median infant birth weight of 2,710 and 2,720 g, respectively.
Regression models of pooled data showed that mothers infected with the 3D7-like clade birthed infants with lower birth weight (difference, -267.99 g; 95 percent CI, -466.43 to -69.55) after adjusting for parity and country.
Moreover, this trend persisted when data were analysed by country. Infant birth weight was significantly lower in 3D7-like variant-infected mothers from Malawi (adjusted difference, -330.97 g; -628.44 to -33.49) and Benin (adjusted difference, -147.88 g; -530.06 to 234).
The unadjusted prevalence of low birth weight (LBW) was higher in 3D7-like variant-infected women from Malawi (47.6 vs 4.6 percent) and Benin (25 vs 15.4 percent) than in those infected with the FCR-3-like variant. The odds of LBW were also higher in those infected with the 3D7-like variant (odds ratio [OR], 5.41; 0.99 to 29.52).
Similarly, the unadjusted prevalence of small-for-gestational-age (SGA) was higher in Malawi (28.1 vs 9.1 percent) and Benin (50 vs 23.1 percent) women infected with the 3D7-like variant than in those with the FCR-3-like variant (OR, 3.65; 1.01 to 13.38).
“[V]ariants from the 3D7-like clade were associated with adverse birth outcomes including newborns with lower birth weight,” noted researchers.
“Taken together, the intrinsic diversity of this VAR2CSA region along with the association of a specific P. falciparum genotype with more severe clinical consequences suggest that an effective VAR2CSA-based vaccine aimed to prevent placental malaria and its sequelae will require multivalent activity,” they added.