TY - JOUR
T1 - Severity of chagasic cardiomyopathy is associated with response to a novel rapid diagnostic test for trypanosoma cruzi TcII/V/VI
AU - Bhattacharyya, Tapan
AU - Messenger, Louisa A.
AU - Bern, Caryn
AU - Mertens, Pascal
AU - Gilleman, Quentin
AU - Zeippen, Nicolas
AU - Bremer Hinckel, Bruno C.
AU - Murphy, Niamh
AU - Gilman, Robert H.
AU - Miles, Michael A.
N1 - Funding Information:
Financial support. This work was supported by the National Institutes of Health (grant R01-AI087776, 5R01AI107028, D43TW006581). T. B. and M. A. M. have received support from the European Commission Framework Programme Project, Comparative Epidemiology of Genetic Lineages of Trypanosoma cruzi, ChagasEpiNet (contract 223034). B. C. B. was supported by European Commission Marie Sklodowska-Curie grant (agreement N642609).
Publisher Copyright:
© The Author(s) 2018.
PY - 2018/8/1
Y1 - 2018/8/1
N2 - Background. Trypanosoma cruzi causes Chagas disease in the Americas. The outcome of infection ranges from lifelong asymptomatic status to severe disease. Relationship between T. cruzi lineage (TcI-TcVI) infection history and prognosis is not understood. We previously described peptide-based lineage-specific enzyme-linked immunosorbent assay (ELISA) with trypomastigote small surface antigen (TSSA). Methods. A novel rapid diagnostic test (RDT; Chagas Sero K-SeT) that incorporates a peptide that corresponds to the TSSA II/V/VI common epitope was developed and validated by comparison with ELISA. Patients from Bolivia and Peru, including individuals with varying cardiac pathology, and matched mothers and neonates, were then tested using Chagas Sero K-SeT. Results. Chagas Sero K-SeT and ELISA results, with a Bolivian subset of cardiac patients, mothers, and neonates, were in accord. In adult chronic infections (n = 121), comparison of severity class A (no evidence of Chagas cardiomyopathy) with class B (electrocardiogram suggestive of Chagas cardiomyopathy) and class C/D (decreased left ventricular ejection fraction; moderate/severe Chagas cardiomyopathy) revealed a statistically significant increase in Chagas Sero K-SeT reactivity with increasing severity (χ2 for trend, 7.39; P =.007). In Peru, Chagas Sero K-SeT detected the sporadic TcII/V/VI infections. Conclusions. We developed a low cost RDT that can replace ELISA for identification of TSSA II/V/VI immunoglobulin G. Most importantly, we show that response to this RDT is associated with severity of Chagas cardiomyopathy and thus may have prognostic value. Repeated challenge with T. cruzi infection may both exacerbate disease progression and boost the immune response to the TSSApep-II/V/VI epitope.
AB - Background. Trypanosoma cruzi causes Chagas disease in the Americas. The outcome of infection ranges from lifelong asymptomatic status to severe disease. Relationship between T. cruzi lineage (TcI-TcVI) infection history and prognosis is not understood. We previously described peptide-based lineage-specific enzyme-linked immunosorbent assay (ELISA) with trypomastigote small surface antigen (TSSA). Methods. A novel rapid diagnostic test (RDT; Chagas Sero K-SeT) that incorporates a peptide that corresponds to the TSSA II/V/VI common epitope was developed and validated by comparison with ELISA. Patients from Bolivia and Peru, including individuals with varying cardiac pathology, and matched mothers and neonates, were then tested using Chagas Sero K-SeT. Results. Chagas Sero K-SeT and ELISA results, with a Bolivian subset of cardiac patients, mothers, and neonates, were in accord. In adult chronic infections (n = 121), comparison of severity class A (no evidence of Chagas cardiomyopathy) with class B (electrocardiogram suggestive of Chagas cardiomyopathy) and class C/D (decreased left ventricular ejection fraction; moderate/severe Chagas cardiomyopathy) revealed a statistically significant increase in Chagas Sero K-SeT reactivity with increasing severity (χ2 for trend, 7.39; P =.007). In Peru, Chagas Sero K-SeT detected the sporadic TcII/V/VI infections. Conclusions. We developed a low cost RDT that can replace ELISA for identification of TSSA II/V/VI immunoglobulin G. Most importantly, we show that response to this RDT is associated with severity of Chagas cardiomyopathy and thus may have prognostic value. Repeated challenge with T. cruzi infection may both exacerbate disease progression and boost the immune response to the TSSApep-II/V/VI epitope.
KW - Cardiomyopathy
KW - Chagas disease
KW - Prognosis
KW - Rapid diagnostic test
KW - Trypanosoma cruzi
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U2 - 10.1093/cid/ciy121
DO - 10.1093/cid/ciy121
M3 - Article
C2 - 29438471
AN - SCOPUS:85055057714
SN - 1058-4838
VL - 67
SP - 519
EP - 524
JO - Clinical Infectious Diseases
JF - Clinical Infectious Diseases
IS - 4
ER -