A Study Details for the First Time the Signature of Immune Mediators Associated with ‘Plasmodium vivax’ Infection during Pregnancy

A detailed analysis of the immune profile of pregnant women infected by Plasmodium vivax indicates that the inflammation caused by the infection is compensated by an anti-inflammatory response, thereby avoiding adverse outcomes for the baby. The study led by ISGlobal, an institution supported by “la Caixa”, also identifies the CCL11/eotaxin protein as a possible marker of parasite exposure.

P. vivax is the most widely distributed malaria parasite outside sub-Saharan Africa and, although to a lesser degree than P. falciparum, it represents a threat to pregnant women and their babies. P. vivax infection is associated with an inflammatory response, particularly in severe cases. However, it is not clear whether this also occurs in pregnant women, given that their immune system undergoes changes in order to protect the foetus.

To address this question, an international team led by ISGlobal researcher Carlota Dobaño, measured 31 molecules (cytokines, chemokines and growth factors) in blood samples from 572 pregnant women, infected or not with P. vivax. The work was performed under the PregVax project, whose goal was to measure the burden and health impact of malaria vivax in pregnant women from five endemic countries (Brazil, Colombia, Guatemala, India, Papua Nueva Guinea).

The results, obtained from samples taken at different timepoints during pregnancy and delivery, reveal that infected pregnant women had higher levels of inflammatory and T_H1-type cytokines than non-infected women. These differences were no longer observed upon delivery and did not affect the mother’s or infant’s health. The researchers also observed an increase in anti-inflammatory cytokines (particularly IL-10). “We think that the anti-inflammatory cytokines could compensate the excessive inflammation caused by the parasite, thereby avoiding adverse delivery outcomes” says Pilar Requena, senior author of the study. In contrast, babies born to women with high levels of IL-4 (a T_H2-type cytokine) had a lower weight upon birth, suggesting the importance of generating a controlled T_H1-type response.

Of the 31 markers analysed, the only one negatively associated with infection was CCL11, a chemokine the research team had already found to be decreased in malaria-exposed individuals. “This suggests that CCL11, a molecule poorly studied in the context of malaria, could be used as a marker of parasite infection or exposure,” says Dobaño.

Reference

Dobaño C, Bardají A, Arévalo-Herrera M, et al. Cytokine signatures of Plasmodium vivax infection during pregnancy and delivery outcomes. 2020. PLoS Negl Trop Dis. 2020 May 4;14(5):e0008155. doi: 10.1371/journal.pntd.0008155