Indeterminate form of Chagas disease: historical, conceptual, clinical, and prognostic aspects

Abstract

Chagas disease (CD) remains a serious endemic disease in Latin America and a major public health problem. Because of globalization, the disease has spread to non-endemic areas in the northern hemisphere. In the chronic phase of the disease, most patients present with the indeterminate form (IF), characterized by positive serology for Trypanosoma cruzi, absence of clinical findings, and normal findings in electrocardiogram (ECG). IF was not recognized as a clinical entity until decades after the discovery of the disease, and only in the 1940-50s, it was categorized as a form of CD, and its conceptual definition was ratified in the 1980s. Children, adolescents, and young adults with the IF benefit from etiological treatment and tend to have less progression to heart disease in the long term than the untreated ones. IF patients have an essentially benign clinical condition, and their prognosis can be compared to that of healthy individuals with normal ECG findings. Currently, because of aging, patients with the IF have comorbidities that require attention in health services.

Longitudinal Speckle Tracking Strain Abnormalities in Chagas Disease: A Systematic Review and Meta-Analysis

“…Nevertheless, recent studies have revealed that myocardial involvement in CD is not restricted to patients with CCM, as patients in the IF of the disease have also exhibited pathological findings such as myocyte degeneration and ongoing fibrosis [ 51 , 52 ]. The IF of CD is defined as the presence of a positive anti- T. cruzi serology (based on two different assays) along with the absence of symptoms or physical signs of disease, a normal electrocardiogram, and normal chest and gastrointestinal radiographic studies [ 1 , 9 , 53 ]. However, these criteria were defined almost 40 years ago, relying on relatively simple measures and heart and myocardial function assessments.…”

“…More recently, the concept of “indeterminate form” has been widely debated, as several studies have reported anatomical and functional myocardial derangements in patients with this form of CD [ 54 ]. The reported functional alterations include anomalies in left ventricle contractility, atrioventricular conduction disorders, alterations in the systolic function of the right ventricle, and even LV segmental wall motion abnormalities [ 9 , 22 , 55 ].…”

“…The acute phase of this disease often goes underrecognized, as it is rarely severe; afterward, the chronic stage of the disease develops, in which the parasite persists in specific host tissues [ 6 , 7 , 8 ]. This period is called the indeterminate form (IF) of CD, which is characterized by the latency of the disease, and approximately 80% of the patients remain in this stage without exhibiting signs or symptoms of organ involvement [ 9 ]. From the IF, around 10% to 20% of patients will develop the cardiac form of the disease, named chronic Chagas cardiomyopathy (CCM) [ 10 ].…”

Indeterminate Form of Chagas Disease: Some Immunological Insights

“…We read with interest the article by Hasslocher-Moreno and colleagues about the indeterminate form of Chagas Disease (CD) 1 .…”

“…More importantly, from a pathophysiological point of view, it remains unclear why some patients, after the acute phase of CD, manifest cardiac or gastrointestinal symptoms (or even a combination of them), while the majority remain in the indeterminate form, with a life expectancy similar to that of uninfected participants 2,3 . Factors related to Trypanosoma cruzi infection in areas with sustained vector transmission, male sex, parasite load, genetic aspects of the host, nutritional status, comorbidities, and the social context and quality of life of patients with CD are involved 1 . In addition, we believe that an imbalance between some cell actors in the host's immune system and the parasite is also involved.…”