Review Article The role of parasite persistence in pathogenesis of Chagas heart disease F. R. S. GUTIERREZ, 1 P. M. M. GUEDES, 1 R. T. GAZZINELLI 2 & J. S. SILVA 1 1 Department of Biochemistry and Immunology, Ribeir¼o Preto School of Medicine, Universityof S¼o Paulo, S¼o Paulo, Brazil, 2 Depart- ment of Parasitology, Institute of Biological Sciences, Federal Universityof Minas Gerais, Belo Horizonte, Brazil SUMMARY Chagas disease (CD) is caused by the infection with the protozoan haemoflagellate Trypanosoma cruzi. This disease is still a great menace to public health, and is largely neglected as it affects mostly the poorest populations of Latin America. Nonetheless, there are neither effective diag- nostic markers nor therapeutic options to accurately detect and efficiently cure this chronic infection. In spite of the great advances in the knowledge of the biology of natural transmission, as well as the immunobiology of the host–par- asite interaction, the understanding of the pathogenesis of CD remains largely elusive. In the recent decades, a contro- versy in the research community has developed about the rel- evance of parasite persistence or autoimmune phenomena in the development of chronic cardiac pathology. One of the most notable aspects of chronic CD is the progressive deteri- oration of cardiac function, derived mostly from structural derangement, as a consequence of the intense inflammatory process. Here we review the evidence supporting the multi- factorial nature of Chagas heart disease comprising patho- gen persistence and altered host immunoregulatory mechanisms. Keywords cytokines, immune response, myocarditis, parasite persistence, Trypanosoma cruzi INTRODUCTION Trypanosoma cruzi is an intracellular protozoan which causes Chagas disease (CD). Endemic to several regions in Latin America, this disease persists as the major infectious heart disease in the world (1,2). It is estimated that around 75 million people live in risk areas (3) and 13 million peo- ple are currently infected in Central and South America. The global incidence of the disease is considered to be 300 000 new cases per year. Natural transmission of the disease occurs through fae- ces of the vector (a haematophagous bug belonging to the subfamily Triatominae, family Reduviidae), deposited near a skin lesion or mucosa (80–90%), via organ transplanta- tion or blood transfusion (5–20%) or congenital transmis- sion (0Æ5–8%) (4). Majority of infections occur during early childhood, and around 30% infected people develop chronic cardiac involvement, usually after decades of asymptomatic infection (5). The interaction between human beings and vectors is favoured by several factors. For example, human invasion of the natural habitat where Triatominae insects are ende- mic, deforestation and even climatic phenomena can con- tribute to domestic adaptation of novel species of transmitter haematophages (6,7). The South Cone Initiative against CD, carried out as an attempt to control the transmission of the disease by erad- icating the insects from residential settings, has had an impact on the natural transmission of the disease. As a result, it is estimated that the local annual incidence has fallen from 800 000 new cases in the 1980s to 200 000 today, and in some of these countries the disease was declared to be ‘controlled’ (8,9). The maintenance of this trend depends on continued surveillance and interventions where necessary. However, Correspondence: Dr Jo¼o S. Silva, Department of Biochemistry and Immunology, Ribeir¼o Preto School of Medicine, USP. Av. Bandeirantes, 3900 Ribeir¼o Preto (SP), Brazil 14049-900 (e-mail: jsdsilva@fmrp.usp.br). Disclosures: The authors received an honorarium from the Publisher for preparation of this article. Received: 26 December 2008 Accepted for publication: 17 February 2009 Parasite Immunology, 2009, 31, 673–685 DOI: 10.1111/j.1365-3024.2009.01108.x Ó 2009 Blackwell Publishing Ltd 673