Preface

Carlos Ribeiro Justiniano das Chagas (1878–1934) was a notorious Brazilian scientist, active in public health in his country. In 1909, Chagas discovered American trypanosomiasis, also called Chagas disease, an illness caused by the protozoan *Trypanosoma cruzi*. His discovery involved the description of the pathogen, the insect vector, different natural reservoirs, some mechanisms of pathogenesis, and clinical manifestations. Chagas was laureated with awards worldwide, and even today, it is considered a great injustice that he was not awarded the Nobel Prize for his discovery.

More than a century after its discovery, Chagas disease is still somewhat of a mystery. It is one of the seventeen Neglected Tropical Diseases, as determined by the World Health Organization (WHO). It affects more than 1 billion people worldwide and is endemic in 149 countries. The WHO estimates about 8 million people are infected with this protozoan, leading to 10,000 deaths per year due to complications from the disease. Since the 1990s, Chagas disease has emerged as a public health problem even in non-endemic countries, especially because of blood-related transmission (transfusion, organ transplantation, or congenital). The globalization of disease clearly demonstrates the migration of infected people from poor endemic areas in Latin America to well-developed countries in Europe and North America, among other continents. Classically, the main transmission route depends on the direct contact of humans or animals with the feces of blood-sucking triatomine insects. Infection via the oral route, in countries such as Brazil, is responsible for outbreaks of acute cases via the ingestion of food contaminated with feces or urine of infected triatomines. Serious programs must be designed to monitor the ecoepidemiology of the disease.

The progression of Chagas disease is divided into two clinical stages: acute and chronic. In the immediate stage of infection, despite the high number of trypomastigotes detected in the bloodstream, the majority of patients present with mild symptoms or nonspecific febrile illness. After a few months, the host immune system controls the dissemination of the infection, leading to undetectable parasitemia, at least by morphological methods, which characterizes the beginning of the indeterminate chronic phase. This phase is asymptomatic, usually with normal electrocardiographic and radiologic parameters. After three or four decades, one third of infected individuals progress to a symptomatic chronic phase, showing cardiac and digestive manifestations and, more rarely, polyneuropathy. The main clinical complication of the chronic stage is cardiomyopathy, determined by focal and diffuse inflammation with progressive fibrosis and electrical alterations, arrhythmia, heart failure, and secondary embolisms. The digestive form of Chagas disease involves chronic inflammation and destruction of parasympathetic neurons, culminating in the progressive enlargement of the esophagus or colon (occurring in approximately 15% of chronic patients). Molecular mechanisms related to the triggering of the progression to the symptomatic chronic stage represent the most crucial challenges in Chagas disease pathogenesis.

Reinforcing the challenges imposed by *T. cruzi* infection, up to now, the clinical treatment is still based on two nitrocompounds: benznidazole and nifurtimox, which were empirically developed in the 1970s. Both derivatives lead to a parasitological cure in almost all congenital cases (95%) and are very effective in adult acute infections (60%–80%). However, the efficacy of these drugs is drastically reduced with the progression of the chronic phase. Factors such as parasite strain and geographical area are also associated with the limited effect of these drugs, and together with their undesirable side effects, justify the continuous search for alternative treatments.

This book discusses different aspects of Chagas disease.

**Rubem Menna-Barreto** Cell Biology Lab, Oswaldo Cruz Institute, FIOCRUZ, Rio de Janeiro, Brazil
