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Amplification of a Trypanosoma cruzi DNA sequence from inflammatory lesions in human chagasic cardiomyopathy
E M Jones1, D G Colley, S Tostes
1Department of Pathology, Vanderbilt University Medical Center, Nashville, Tennessee.
Insights
Chronic Chagas
Area of Science:
- Infectious Diseases
- Cardiology
- Immunology
Background:
- Chagas' disease cardiomyopathy is a major cause of death, often developing years after infection.
- Detecting Trypanosoma cruzi in heart tissue is challenging, leading to theories of autoimmune causes for chronic damage.
- Previous research has focused on autoimmune mechanisms due to difficulties in organism detection.
Purpose of the Study:
- To investigate the persistence of Trypanosoma cruzi DNA in host tissues of patients with Chagas' disease.
- To determine if Trypanosoma cruzi is present in cardiac lesions associated with chronic Chagas' disease cardiomyopathy.
Main Methods:
- DNA was extracted from formalin-fixed, paraffin-embedded autopsy specimens.
- Polymerase chain reaction (PCR) with T. cruzi-specific primers was used to amplify DNA.
- Samples included heart, gonadal, and adrenal tissues from seronegative, seropositive without CCC, and seropositive with severe CCC patients.
Main Results:
- Trypanosoma cruzi DNA was not consistently detected in seronegative patients or seropositive patients without severe cardiomyopathy.
- In seropositive patients with severe chronic chagasic cardiomyopathy (CCC), T. cruzi DNA was amplified from 18 of 21 cardiac tissue samples adjacent to inflammatory infiltrates.
- T. cruzi DNA was rarely detected in gonadal or adrenal tissues from patients with severe CCC.
Conclusions:
- Trypanosoma cruzi DNA, or part of its genome, is present within the inflammatory lesions of chronic cardiac Chagas' disease.
- These findings support the role of persistent parasitic presence in the pathogenesis of Chagas' disease cardiomyopathy.
- The study demonstrates the utility of PCR in detecting T. cruzi in archival tissue samples.
Abstract:
The major cause of morbidity and mortality in Chagas' disease is a chronic inflammatory cardiomyopathy, which presents ten or more years following initial infection. Demonstration of Trypanosoma cruzi in cardiac tissue by routine microscopy or culture is difficult in these patients, which has suggested that persistent organisms are not required for chronic disease. Consequently, studies have focused on elucidating an autoimmune pathogenesis of chronic injury. To further assess the persistence of T. cruzi in host tissue, DNA extracted from formalin-fixed, paraffin-embedded autopsy specimens from seronegative or seropositive patients was amplified by the polymerase chain reaction using T. cruzi-specific primers. Trypanosoma cruzi DNA sequences were not consistently amplified from four seropositive patients who lacked evidence of fatal chronic chagasic cardiomyopathy (CCC) (0 positive of 12 heart samples, 0 positive of four gonadal samples, and 0 positive of four adrenal samples) or nine seronegative patients (0 positive of 27 heart samples, 0 positive of nine gonadal samples and 0 positive of nine adrenal samples). In seven seropositive patients with severe CCC, cardiac tissue adjacent to inflammatory infiltrates yielded amplified T. cruzi DNA sequences in 18 of 21 heart samples. Parallel testing of gonadal and adrenal tissues from these same patients produced detectable T. cruzi DNA in none of the gonadal tissue samples and one of the seven adrenals. Our studies demonstrate that T. cruzi, or a portion of its genome, is present in the inflammatory lesion of chronic cardiac Chagas' disease.