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Open Access Research

Submicroscopic infection of placenta by Plasmodium produces Th1/Th2 cytokine imbalance, inflammation and hypoxia in women from north-west Colombia

Olga M Agudelo1, Beatriz H Aristizabal2, Stephanie K Yanow3, Eliana Arango1, Jaime Carmona-Fonseca1 and Amanda Maestre1*

Author Affiliations

1 Grupo “Salud y Comunidad-César Uribe Piedrahita”, Universidad de Antioquia, Medellin, Colombia

2 Hospital Pablo Tobón Uribe, Laboratorio de Biología Molecular, Medellín, Colombia

3 School of Public Health, University of Alberta; Provincial Laboratory for Public Health, Edmonton, Canada

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Malaria Journal 2014, 13:122  doi:10.1186/1475-2875-13-122

Published: 27 March 2014

Abstract

Background

A large-scale study was set up in order to study the epidemiology, clinical aspects, and immunopathology of gestational and placental malaria in north-west Colombia. In this region, recent reports using a qPCR technique, confirmed frequencies of infection, by Plasmodium falciparum or Plasmodium vivax, up to 45%. Given the high rates of infection observed both in mother and placenta, a first exploratory study was proposed in order to characterize the effect on the inflammation status, tissue damage and hypoxia in Plasmodium spp. infected placentas.

Methods

A descriptive, prospective, cross-sectional design was applied to pregnant women with (PM+) and without (PM-) placental malaria. Messenger RNA expression of Fas, FasL; COX-1, COX-2, HIF, VEGF, and the cytokines IL-2, IL-4, IL-10, IFN-γ and TNF, were measured in peripheral and placental blood using a quantitative PCR. The percentage of apoptotic cells was determined with a TUNEL assay.

Results

In total 50 placentas were studied: 25 were positive for submicroscopic infection and 25 were negative for Plasmodium infection. Expression of IL-4 and IL-10 was observed high in placental tissue of PM+, while IL-2 was high in peripheral blood of the same group. Expression of TNF and IFNγ in peripheral blood of the PM + group was high. Similarly, the apoptotic index and Fas expression were significantly high in PM+. However, FasL expression was observed low in PM + compared to PM-. Inflammation markers (HIF, VEGF) and hypoxia markers (COX-1, COX-2) were high in the PM + group.

Conclusion

During placental malaria expression of some pro-inflammatory cytokines is up-regulated and markers of hypoxia and tissue damage are increased in cases of submicroscopic infection.

Keywords:
Submicroscopic; Placental malaria; Plasmodium; Cytokine; Inflammation; Hypoxia