The utility of anti-trypomastigote lytic antibodies for determining cure of Trypanosoma cruzi infections in treated patients: an overview and perspectives

Krettli, Antoniana U.

doi:10.1590/s0074-02762009000900020

Cited by 35 publications

(34 citation statements)

References 38 publications

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“…Several factors contribute to enduring positive results from conventional serological tests for patients that are parasitologically cured, including mechanisms of autoimmunity in Chagas' disease, the long-term presence of antibodies due to parasitic antigens present in dendritic or cardiac cells, anti-idiotypic antibodies, anti-laminine antibodies, and anti-epitopes of sugar residues in T. cruzi membranes and others (23).…”

Section: Discussionmentioning

confidence: 99%

“…In addition, other authors interpret accelerated decay of conventional serological titers as indicative of a cure if present with decreasing titers in nonconventional serological tests and persistently negative parasitological tests (15,22). A third interpretation is that patients with negative results from parasitological methods and nonconventional serology (LMCo or FC-ALTA) are cured, even in the presence of positive results of conventional serology, because the detected antibodies with nonconventional tests are distinct from lytic and anti-live trypomastigote antibodies and are consequently not related to active infection (15,23).…”

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confidence: 99%

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Posttherapeutic Cure Criteria in Chagas' Disease: Conventional Serology followed by Supplementary Serological, Parasitological, and Molecular Tests

Machado-de-Assis¹,

Silva²,

L.³

et al. 2012

Clin. Vaccine Immunol.

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ABSTRACTWe performed a critical study of conventional serology, followed by supplementary serological, parasitological, and molecular tests, to assess the response to etiologic treatment of Chagas' disease. A group of 94 Chagas' disease patients treated with benznidazole at least 10 years earlier were evaluated from the laboratory and clinical points of view. When conventional serology (enzyme-linked immunosorbent assay [ELISA], indirect immunofluorescence [IIF], and indirect hemagglutination [IHA]) and classic criteria (consistent results with any two of the three tests) or more rigorous criteria (consistent results from the three tests) were used, 10.6% and 8.5% of patients were considered treated and cured (TC) by classic and rigorous criteria, respectively. Patients were then evaluated using supplementary (recombinant ELISA andTrypanosoma cruziexcreted-secreted antigen blotting [TESA-blot]), parasitological (hemoculture), and molecular (PCR) tests. The results of recombinant ELISA were similar to those with the rigorous criterion (three consistent test results). The TESA-blot group showed a higher percentage (21.3%) of negative results than the groups defined by either cure criterion. Hemoculture and PCR gave negative results for all treated and cured (TC) patients, regardless of the criterion used. Recombinant ELISA and TESA-blot tests showed negative results for 70% and 87.5% of the patients categorized as TC by the classic and three-test criteria, respectively. For patients with discordant conventional serology, the supplementary serological and molecular tests were the decisive factor in determining therapeutic failure. Clinical evaluation showed that 62.5% of TC patients presented with the indeterminate form of the disease. Additionally, treated patients with negative TESA-blot results should be reevaluated later with all methodologies used here to verify whether TESA-blot is a reliable way to determine early parasitological cure of Chagas' disease.

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Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

Posttherapeutic Cure Criteria in Chagas' Disease: Conventional Serology followed by Supplementary Serological, Parasitological, and Molecular Tests

Machado-de-Assis¹,

Silva²,

L.³

et al. 2012

Clin. Vaccine Immunol.

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“…A specific antitrypomastigote antibody can be detected by complement-mediated lysis in the course of an active infection (157,215,276). The parasite surface antigen targeted by the lytic antibody is a 160-kDa glycoprotein (157,215).…”

Section: Acquired Immunitymentioning

confidence: 99%

Pathogenesis of Chagas' Disease: Parasite Persistence and Autoimmunity

et al. 2011

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SUMMARY Acute Trypanosoma cruzi infections can be asymptomatic, but chronically infected individuals can die of Chagas' disease. The transfer of the parasite mitochondrial kinetoplast DNA (kDNA) minicircle to the genome of chagasic patients can explain the pathogenesis of the disease; in cases of Chagas' disease with evident cardiomyopathy, the kDNA minicircles integrate mainly into retrotransposons at several chromosomes, but the minicircles are also detected in coding regions of genes that regulate cell growth, differentiation, and immune responses. An accurate evaluation of the role played by the genotype alterations in the autoimmune rejection of self-tissues in Chagas' disease is achieved with the cross-kingdom chicken model system, which is refractory to T. cruzi infections. The inoculation of T. cruzi into embryonated eggs prior to incubation generates parasite-free chicks, which retain the kDNA minicircle sequence mainly in the macrochromosome coding genes. Crossbreeding transfers the kDNA mutations to the chicken progeny. The kDNA-mutated chickens develop severe cardiomyopathy in adult life and die of heart failure. The phenotyping of the lesions revealed that cytotoxic CD45, CD8 + γδ, and CD8α + T lymphocytes carry out the rejection of the chicken heart. These results suggest that the inflammatory cardiomyopathy of Chagas' disease is a genetically driven autoimmune disease.

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“…Many serological techniques have been evaluated as possible cure markers 1,13,14,15 . Furthermore, there has been an increase in the use of molecular methods for detecting T. cruzi in blood samples of treated patients 4,7,19,20 .…”

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Evaluation of the ELISA-F29 test as an early marker of therapeutic efficacy in adults with chronic Chagas disease

Fabbro

Velázquez

Bizai

et al. 2013

Rev. Inst. Med. trop. S. Paulo

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SUMMARYThis work compared the time at which negative seroconversion was detected by conventional serology (CS) and by the ELISA-F29 test on a cohort of chronic chagasic patients treated with nifurtimox or benznidazole. A retrospective study was performed using preserved serum from 66 asymptomatic chagasic adults under clinical supervision, and bi-annual serological examinations over a mean follow-up of 23 years. Twenty nine patients received trypanocide treatment and 37 remained untreated. The ELISA-F29 test used a recombinant antigen which was obtained by expressing the Trypanosoma cruzi flagellar calcium-binding protein gene in Escherichia coli. Among the untreated patients, 36 maintained CS titers. One patient showed a doubtful serology in some check-ups. ELISA-F29 showed constant reactivity in 35 out of 37 patients and was negative for the patient with fluctuating CS. The treated patients were divided into three groups according to the CS titers: in 13 they became negative; in 12 they decreased and in four they remained unchanged. ELISA-F29 was negative for the first two groups. The time at which negativization was detected was significantly lower for the ELISA-F29 test than for CS, 14.5 ± 5.7 and 22 ± 4.9 years respectively. Negative seroconversion was observed in treated patients only. The results obtained confirm that the ELISA-F29 test is useful as an early indicator of negative seroconversion in treated chronic patients.

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The utility of anti-trypomastigote lytic antibodies for determining cure of Trypanosoma cruzi infections in treated patients: an overview and perspectives

Abstract: In previous work, we proposed

Cited by 35 publications

References 38 publications

Posttherapeutic Cure Criteria in Chagas' Disease: Conventional Serology followed by Supplementary Serological, Parasitological, and Molecular Tests

Posttherapeutic Cure Criteria in Chagas' Disease: Conventional Serology followed by Supplementary Serological, Parasitological, and Molecular Tests

Pathogenesis of Chagas' Disease: Parasite Persistence and Autoimmunity

Evaluation of the ELISA-F29 test as an early marker of therapeutic efficacy in adults with chronic Chagas disease

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