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PLoS One. 2016 Jul 21;11(7):e0158420. doi: 10.1371/journal.pone.0158420. eCollection 2016.

Erythropoietin Levels Increase during Cerebral Malaria and Correlate with Heme, Interleukin-10 and Tumor Necrosis Factor-Alpha in India.

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Centre for Infection and Immunity of Lille, INSERM U1019, CNRS UMR 8204, Université Lille Nord de France, Institut Pasteur de Lille, Lille 59019, France.
CEA, DSV/iMETI, Immunology of viral infections and autoimmune diseases research unit, UMR1184, IDMIT infrastructure, Fontenay-aux-Roses, France.
Lyon 1 University, CarMeN Laboratory, INSERM U-1060, INRA USC-1235, 69921, Oullins, France; Banque de Tissus et de Cellules des Hospices Civils de Lyon, Hôpital Edouard Herriot, Lyon, France.
Institute of Life Sciences, Bhubaneswar, Odisha, India.
Department of Biological Sciences, Tata Institute of Fundamental Research, Mumbai, Maharashtra 400005, India.
SCB Medical College, Cuttack, Odisha 753007, India.


Cerebral malaria (CM) caused by Plasmodium falciparum parasites often leads to the death of infected patients or to persisting neurological sequelae despite anti-parasitic treatments. Erythropoietin (EPO) was recently suggested as a potential adjunctive treatment for CM. However diverging results were obtained in patients from Sub-Saharan countries infected with P. falciparum. In this study, we measured EPO levels in the plasma of well-defined groups of P. falciparum-infected patients, from the state of Odisha in India, with mild malaria (MM), CM, or severe non-CM (NCM). EPO levels were then correlated with biological parameters, including parasite biomass, heme, tumor necrosis factor (TNF)-α, interleukin (IL)-10, interferon gamma-induced protein (IP)-10, and monocyte chemoattractant protein (MCP)-1 plasma concentrations by Spearman's rank and multiple correlation analyses. We found a significant increase in EPO levels with malaria severity degree, and more specifically during fatal CM. In addition, EPO levels were also found correlated positively with heme, TNF-α, IL-10, IP-10 and MCP-1 during CM. We also found a significant multivariate correlation between EPO, TNF-α, IL-10, IP-10 MCP-1 and heme, suggesting an association of EPO with a network of immune factors in CM patients. The contradictory levels of circulating EPO reported in CM patients in India when compared to Africa highlights the need for the optimization of adjunctive treatments according to the targeted population.

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