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Cytokine signatures of Plasmodium vivax infection during pregnancy and delivery outcomes
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Plasmodium vivax malaria is a neglected disease,
particularly during pregnancy. Severe vivax malaria is
associated with inflammatory responses but in pregnancy immune
alterations make it uncertain as to what cytokine signatures
predominate, and how the type and quantity of blood immune
mediators influence delivery outcomes. We measured the plasma
concentrations of a set of thirty-one biomarkers, comprising
cytokines, chemokines and growth factors, in 987 plasma samples
from a cohort of 572 pregnant women from five malaria-endemic
tropical countries and related these concentrations to delivery
outcomes (birth weight and hemoglobin levels) and malaria
infection. Samples were collected at recruitment (first
antenatal visit) and at delivery (periphery, cord and placenta).
At recruitment, we found that P. vivax-infected pregnant women
had higher plasma concentrations of proinflammatory (IL-6,
IL-1\xCE\xB2, CCL4, CCL2, CXCL10) and TH1-related cytokines
(mainly IL-12) than uninfected women. This biomarker signature
was essentially lost at delivery and was not associated with
birth weight nor hemoglobin levels. Antiinflammatory cytokines
(IL-10) were positively associated with infection and poor
delivery outcomes. CCL11 was the only biomarker to show a
negative association with P. vivax infection and its
concentration at recruitment was positively associated with
hemoglobin levels at delivery. Birth weight was negatively
associated with peripheral IL-4 levels at delivery. Our
multi-biomarker multicenter study is the first comprehensive one
to characterize the immunological signature of P. vivax
infection in pregnancy thus far. In conclusion, data show that
while TH1 and pro-inflammatory responses are dominant during P.
vivax infection in pregnancy, antiinflammatory cytokines may
compensate excessive inflammation avoiding poor delivery
outcomes, and skewness toward a TH2 response may trigger worse
delivery outcomes. CCL11, a chemokine largely neglected in the
field of malaria, emerges as an important marker of exposure or
mediator in this condition.
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DOBAÑO, Carlota, et al. Cytokine signatures of Plasmodium vivax infection during pregnancy and delivery outcomes. PLoS Neglected Tropical Diseases. 2020. Vol. 14, num. 5, pags. e0008155. ISSN 1935-2735. [consulted: 23 of August of 2026]. Available at: https://hdl.handle.net/2445/173927