Aptamer-Based Detection of Disease Biomarkers in Mouse Models for Chagas Drug Discovery

Araújo, Fernanda Fortes de; Nagarkatti, Rana; Gupta, Charu; Marino, Ana Paula M.P.; Debrabant, Alain

doi:10.1371/journal.pntd.0003451

Cited by 19 publications

(35 citation statements)

References 34 publications

(59 reference statements)

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“…However, levels did not return to those seen in non-infected treated mice, suggesting parasitemia was reduced but parasitological cure was not achieved. These results are in agreement with the detection of parasites in the heart and skeletal muscles by PCR and suggest that the assay can be used to assess treatment efficacy in vivo in murine drug discovery models [76]. However, its ability to predict parasitological cure needs to be confirmed.…”

Section: Aptamerssupporting

confidence: 78%

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Chagas Disease Treatment Efficacy Biomarkers: Myths and Realities

2019

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Chagas disease (CD), caused by Trypanosoma cruzi, affects millions of people worldwide. Although CD R&D has made progress during the last decade, clinicians and general practitioners are still facing the same challenge, i.e., the lack of adequate markers of clinical cure, hindering assessment of new drug efficacy in clinical trials and counseling of patients about treatment outcome. To date, no new markers have been validated as surrogates of seroreversion-the only marker of parasitological cure which is itself considered to be a surrogate of clinical benefit. T. cruzi DNA detected using PCR cannot currently be considered as a surrogate of seroconversion. Much emphasis has been placed on different T. cruzi antigens but no definite proof of correlation between titers, as determined by serology at a given timepoint, and seroreversion has been shown. Thanks to the improvement of analytical methods and the application of new methodologies, the identification of potential new markers is being facilitated, and some of these are progressing. However, there is a long journey from the identification of a potential biomarker to its clinical validation and acceptance by the regulatory authorities that requires a common effort from the entire Chagas community.

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Section: Aptamerssupporting

confidence: 78%

“…Increasing the SELEX rounds and the stringency of the conditions, de Araujo et al found an aptamer (Apt29) with a higher signal for TESA in infected mice and a higher signal-to-noise ratio compared to Apt-L44 [76]. This aptamer was also able to differentiate infected from non-infected mice and predict treatment failure.…”

Section: Aptamersmentioning

confidence: 99%

Chagas Disease Treatment Efficacy Biomarkers: Myths and Realities

2019

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“…New detection tools continue to be developed. For example, nucleic acid aptamers to identify T. cruzi secreted antigens in serum may surpass the sensitivity of PCR [24], and lineage-specific serology has the potential to define historical exposure to different parasite subtypes [25]. …”

Section: Measuring Parasite Loadsmentioning

confidence: 99%

“…Ongoing investigation of a number of other biomarkers may expand the options available to monitor clinical interventions e.g. [24]. …”

Section: Figurementioning

confidence: 99%

Putting Infection Dynamics at the Heart of Chagas Disease

Lewis

Kelly

2016

Trends in Parasitology

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In chronic Trypanosoma cruzi infections, parasite burden is controlled by effective, but non-sterilising immune responses. Infected cells are difficult to detect because they are scarce and focally distributed in multiple sites. However, advances in detection technologies have established a link between parasite persistence and the pathogenesis of Chagas heart disease. Long-term persistence likely involves episodic reinvasion as well as continuous infection, to an extent that varies between tissues. The primary reservoir sites in humans are not definitively known, but analysis of murine models has identified the gastrointestinal tract. Here, we highlight that quantitative, spatial and temporal aspects of T. cruzi infection are central to a fuller understanding of the association between persistence, pathogenesis and immunity, and for optimising treatment.

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“…Además, se han llevado a cabo ensayos ELA (siglas en inglés, enzyme linked aptamer) para buscar en roedores murinos infestados con T. cruzi posibles biomarcadores que sirvan para la monitorización y evaluación de los futuros fármacos antitripanosomiásicos (41) .…”

Section: Nuevos Avances En El Tratamientounclassified

Tripanosomiasis americana, una mirada desde el tratamiento

et al. 2016

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ResumenLa tripanosomiasis americana o enfermedad de Chagas es una infección parasitaria causada por el parásito flagelado Trypanosoma cruzi, cuyo principal vector es un insecto de la clase hemíptera conocido como triatomino. La quimioterapia, adicional a un control oportuno de vectores y rigurosidad en el control de las transfusiones, son los elementos más importantes para el manejo de esta parasitosis. En la actualidad, el mercado farmacéutico solo ofrece nifurtimox y benznidazol como opciones terapéuticas, y a pesar de que se han obtenido resultados satisfactorios con el uso de estos medicamentos en fases agudas de la enfermedad, tripanosomiasis congénita y accidentes de laboratorio, la efectividad en las fases crónicas es notoriamente menor. Además, ambos fármacos generan ciertos efectos adversos que deben ser tenidos en cuenta por el personal de la salud, antes de iniciar el debido manejo de esta enfermedad. El objetivo del presente artículo es revisar el estado actual del tratamiento farmacológico de la tripanosomiasis americana, buscando resumir los nuevos avances terapéuticos y dar a conocer las limitaciones de los mismos debido a sus efectos adversos. Palabras clave. Enfermedad de Chagas; Tripanosomiasis; Terapéutica. Abstract American trypanosomiasis or Chagas disease is a parasitic infection caused by the flagellate parasite Trypanosoma cruzi, whose main vector is an insect of the Hemiptera class, called triatomine. Chemotherapy, in addition to an appropriate vector control and a rigorous control of transfusions, are the most important strategies for the management of this parasitosis. Currently, the pharmaceutical market only offers nifurtimox and benznidazole as treatment options, and although satisfactory results have been obtained with the use of these drugs in either acute stages of the disease, congenital trypanosomiasis and laboratory accidents, its effectiveness in the chronic phases is significantly smaller. In addition, both drugs produce some side effects that must be taken into account by health workers, before starting the proper management of the disease. The aim of this article is to review the current state of the American trypanosomiasis treatment, in order to summarize the new advances in therapeutics and to introduce their limitations due to adverse effects. Keywords. Chagas Disease; Trypanosomiasis; Therapeutics. An INTRODUCCIÓNLa tripanosomiasis americana, también conocida como enfermedad de Chagas, es la infección parasitaria más importante en las Américas, en donde afecta de 8 a 10 millones de personas (1)(2)(3) . Es causada por el parásito flagelado Trypanosoma cruzi, cuyo principal vector es un insecto de la clase hemíptera conocido como triatomino. El parási-to también puede ser adquirido por el consumo de alimentos y bebidas contaminadas, trasplantes de órganos, transfusiones sanguíneas y por vía congénita, siendo estas vías menos frecuentes (1,4) .En el curso natural de la enfermedad es posible diferenciar tres fases clínicas: una fase aguda, usualmente asintomá-tica, que t...

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Aptamer-Based Detection of Disease Biomarkers in Mouse Models for Chagas Drug Discovery

Cited by 19 publications

References 34 publications

Chagas Disease Treatment Efficacy Biomarkers: Myths and Realities

Chagas Disease Treatment Efficacy Biomarkers: Myths and Realities

Putting Infection Dynamics at the Heart of Chagas Disease

Tripanosomiasis americana, una mirada desde el tratamiento

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