Abstract

Chagas’ disease (CD), caused by the hemoflagellate protozoan, Trypanosoma cruzi, is endemic in most countries of Latin America. Heart failure (HF) is often a late manifestation of chronic CD, and is associated with high morbidity and mortality. Inflammatory processes mediated by cytokines play a key role in the pathogenesis and progression of CD. Keeping in view the inflammatory nature of CD, this study investigated the possible role of 21 different inflammatory cytokines as biomarkers for prediction and prognosis of CD. The plasma concentration of these cytokines was measured in a group of patients with CD (n = 94), and then compared with those measured in patients with dilated cardiomyopathy (DCM) from idiopathic causes (n = 48), and with control subjects (n = 25). Monovariately, plasma levels of cytokines such as stem cell growth factor beta (SCGF beta), hepatocyte growth factor (HGF), monokine induced by interferon gamma (CXCL9), and macrophage inhibitory factor (MIF) were significantly increased in CD patients with advanced HF compared to control group. None of the cytokines could demonstrate any prognostic potency in CD patients, and only MIF and stromal derived factor-1 alpha (CXCL12) showed significance in predicting mortality and necessity for heart transplant in DCM patients. However, multivariate analysis prognosticated a large proportion of CD and DCM patients. In CD patients, HGF and Interleukin-12p40 (IL-12p40) together separated 81.9% of 3-year survivors from the deceased, while in DCM patients, CXCL12, stem cell factor (SCF), and CXCL9 together discriminated 77.1% of survivors from the deceased. The significant increase in plasma concentrations of cytokines such as HGF and CXCL9 in CD patients, and the ability of these cytokines to prognosticate a large proportion of CD and DCM patients multivariately, encourages further studies to clarify the diagnostic and prognostic potential of cytokines in such patients.

Highlights

  • Chagas’ disease (CD) is a parasitic disease that is endemic throughout most of Central and South America

  • Inflammatory biomarkers can play a vital role in early diagnosis, as inflammation mediated by cytokines plays an important role in pathogenesis and progression of CD

  • This study investigated the possible role of 21 different inflammatory cytokines as biomarkers for discrimination and risk stratification of CD and idiopathic dilated cardiomyopathy (DCM)

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Summary

Introduction

Chagas’ disease (CD) ( known as American trypanosomiasis) is a parasitic disease that is endemic throughout most of Central and South America. It is caused by the hemoflagellate protozoan, Trypanosoma cruzi (T. cruzi), which is transmitted to humans and other mammals mostly by an insect vector, the blood sucking bugs of the subfamily Triatominae (family Reduviidae) [1]. The cardiac form is the most frequent and serious manifestation of chronic CD It develops in 20–30% of individuals and usually leads to abnormalities of the conduction system, arrhythmias, apical aneurysms, thromboembolism, heart failure (HF), and sudden death [9]

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