Polyclonal antibodies for the detection of Trypanosoma cruzi circulating antigens

Machaca, Edith Málaga; Romero-Ramirez, Alessandra; Gilman, Robert H.; Astupiña-Figueroa, Sofía; Angulo, Noelia; Florentini, Alejandro; Lovon-Luque, Cinthya J.; Gonza, Remo A.; Carpio-Sanz, Ada del; Cabello, Inés; Camargo, Rosina; Recuenco, Fernando; Barrueta-Soria, Liliam A.; Verástegui, Manuela; Calderón, Maritza; Mayta, Holger

doi:10.1371/journal.pntd.0006069

Cited by 9 publications

(9 citation statements)

References 43 publications

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“…These assays detect the residual levels of circulating antigens in blood based on antigen expression and secretion levels, and the half-life of the antigen resulting from typical biological processes such as, degradation, clearance in urine, and sequestration in immune complex or complexed with other globular proteins found in blood. Recently, ELISA using polyclonal antibodies raised against TESA and a trypomastigote lysate were used to detect antigens in plasma and serum samples obtained from patients with CD 18 . Combined with recent advances in single molecule detection using digital ELISA such as the Simoa technology, it is now possible to improve the sensitivity of antigen detection assays by 2-3 orders of magnitude over conventional ELISAs 45,46 .…”

Section: Discussionmentioning

confidence: 99%

“…To overcome the drawbacks of current diagnostic assays in establishing treatment efficacy, we and others have shown that it was possible to detect parasite antigens in blood of infected mice and human and discussed the use of these antigen for diagnostic applications and in pre-clinical drug development 18 – 21 . We reported previously the development of Enzyme Linked Aptamer (ELA) assays to detect T. cruzi excreted secreted antigens (TESA) 21 .…”

Section: Introductionmentioning

confidence: 99%

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A novel Trypanosoma cruzi secreted antigen as a potential biomarker of Chagas disease

Nagarkatti

Acosta

Acharyya

et al. 2020

Sci Rep

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Chagas drug discovery has been hampered by a lack of validated assays to establish treatment efficacy in pre-clinical animal models and in patients infected with T. cruzi. Reduced levels of parasite secreted antigens in the blood of infected hosts could be used to demonstrate treatment efficacy. A published proteomic study of parasite secreted antigens identified the hypothetical protein Tc_5171 as a secreted antigen. In this report, we developed Tc_5171 specific antibodies and showed that the native protein was expressed by the three life cycle stages of the parasite. Anti-peptide antibodies were able to detect the parasite antigen in blood of infected mice during the acute and the chronic phase of infection. Benznidazole treatment of infected mice significantly reduced their blood antigen levels. Of clinical significance, patients diagnosed with Chagas disease, either asymptomatic or with cardiac clinical symptoms had significantly higher Tc_5171 antigen levels compared to endemic controls. Pair-wise analysis, before and after Benznidazole treatment, of patients with asymptomatic Chagas disease showed a significant reduction in antigen levels post treatment. Taken together, our results indicate that Tc_5171 could be used as a novel biomarker of Chagas disease for diagnosis and to assess treatment efficacy.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

A novel Trypanosoma cruzi secreted antigen as a potential biomarker of Chagas disease

Nagarkatti

Acosta

Acharyya

et al. 2020

Sci Rep

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“…To develop a diagnostic test based on a capture ELISA system, a panel of polyclonal antibodies was produced against membrane antigens or trypomastigote excreted/secreted antigens. The test performed on urine from patients positive for ELISA capture against sera demonstrated a 100% positivity [197]. Antigens are present in urine at low concentrations and are susceptible to degradation after collection.…”

Section: Urinementioning

confidence: 99%

Noninvasive Biological Samples to Detect and Diagnose Infections due to Trypanosomatidae Parasites: A Systematic Review and Meta-Analysis

Sereno

Akhoundi

Sayehmri

et al. 2020

IJMS

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Unicellular eukaryotes of the Trypanosomatidae family include human and animal pathogens that belong to the Trypanosoma and Leishmania genera. Diagnosis of the diseases they cause requires the sampling of body fluids (e.g., blood, lymph, peritoneal fluid, cerebrospinal fluid) or organ biopsies (e.g., bone marrow, spleen), which are mostly obtained through invasive methods. Body fluids or appendages can be alternatives to these invasive biopsies but appropriateness remains poorly studied. To further address this question, we perform a systematic review on clues evidencing the presence of parasites, genetic material, antibodies, and antigens in body secretions, appendages, or the organs or proximal tissues that produce these materials. Paper selection was based on searches in PubMed, Web of Science, WorldWideScience, SciELO, Embase, and Google. The information of each selected article (n = 333) was classified into different sections and data were extracted from 77 papers. The presence of Trypanosomatidae parasites has been tracked in most of organs or proximal tissues that produce body secretions or appendages, in naturally or experimentally infected hosts. The meta-analysis highlights the paucity of studies on human African trypanosomiasis and an absence on animal trypanosomiasis. Among the collected data high heterogeneity in terms of the I 2 statistic (100%) is recorded. A high positivity is recorded for antibody and genetic material detection in urine of patients and dogs suffering leishmaniasis, and of antigens for leishmaniasis and Chagas disease. Data on conjunctival swabs can be analyzed with molecular methods solely for dogs suffering canine visceral leishmaniasis. Saliva and hair/bristles showed a pretty good positivity that support their potential to be used for leishmaniasis diagnosis. In conclusion, our study pinpoints significant gaps that need to be filled in order to properly address the interest of body secretion and hair or bristles for the diagnosis of infections caused by Leishmania and by other Trypanosomatidae parasites.

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“…These data confirm the persistence of inconclusive results, which, in this study, occurred in both new and returning donors, including those with up to 29 repeatedly non-reactive donations. The search for confirmatory tests, such as the trypomastigote excreted-secreted antigen (TESA)-blot 7 , 8 , 9 , radioimmunoprecipitation assay 10 , 11 and/or application of latent class analysis 12 , that can be routinely used in blood banks to define the exact profile of blood donors with 100% certainty has been the subject of several studies.…”

Section: Introductionmentioning

confidence: 99%

Chagas disease: Performance analysis of immunodiagnostic tests anti-Trypanosoma cruzi in blood donors with inconclusive screening results

Ferreira-Silva

Pereira

Rodrigues-Júnior

et al. 2021

Hematology, Transfusion and Cell Therapy

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Background The screening of Trypanosoma cruzi -infected blood donors using two serological techniques frequently leads to conflicting results. This fact prompted us to evaluate the diagnostic performance of four “in-house” immunodiagnostic tests and two commercially available enzyme-linked immunosorbent assays (ELISAs). Material and Methods One hundred and seventy-nine blood donors, whose screening for Chagas disease was doubtful, underwent three in-house ELISAs, one in-house immunoblotting test (TESA-blot), and two commercial ELISAs (bioMérieux and Wiener) in an attempt to define the presence or absence of infection. Simultaneously, 29 donors with previous positive results from three conventional serological tests and 30 donors with constant negative results were evaluated. Results The ELISA-Wiener showed the highest rate in sensitivity (98.92%) and the ELISA-bioMérieux, the highest specificity (99.45%), followed by the TESA-blot, which showed superior performance, with lower false-negative (2.18%) and false-positive (1.12%) rates. In series, the combination composed of the TESA-blot and ELISA-bioMérieux showed slightly superior performance, with trifunctional protein deficiency (TFP) = 0.01%. Conclusion Our study confirms the high sensitivity and specificity of commercial kits. To confirm the presence or absence of T. cruzi infection, the combination of TESA-blot and ELISA-bioMérieux may be suggested as the best alternative. Individually, the TESA-blot performed the closest to the gold standard; however, it is not commercially available.

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Polyclonal antibodies for the detection of Trypanosoma cruzi circulating antigens

Cited by 9 publications

References 43 publications

A novel Trypanosoma cruzi secreted antigen as a potential biomarker of Chagas disease

A novel Trypanosoma cruzi secreted antigen as a potential biomarker of Chagas disease

Noninvasive Biological Samples to Detect and Diagnose Infections due to Trypanosomatidae Parasites: A Systematic Review and Meta-Analysis

Chagas disease: Performance analysis of immunodiagnostic tests anti-Trypanosoma cruzi in blood donors with inconclusive screening results

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