Characterization and Follow-Up of Trypanosoma cruzi Natural Populations Refractory to Etiological Chemotherapy in Oral Chagas Disease Patients
| Autor: | Belkisyolé Alarcón de Noya, Zoraida Díaz-Bello, Oscar O. Noya-González, Alejandro G. Schijman, Arturo Muñoz-Calderón |
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| Rok vydání: | 2021 |
| Předmět: |
Microbiology (medical)
Chagas disease Trypanosoma cruzi 030231 tropical medicine Immunology Population Biology Real-Time Polymerase Chain Reaction Microbiology Parasite load Parasite Load Serology purl.org/becyt/ford/1 [https] 03 medical and health sciences Cellular and Infection Microbiology 0302 clinical medicine MINICIRCLE SIGNATURE medicine Humans Chagas Disease 030212 general & internal medicine Genetic variability Seroconversion purl.org/becyt/ford/1.6 [https] education PARASITE LOAD restriction fragment length polymorphism Original Research education.field_of_study RESTRICTION FRAGMENT LENGTH POLYMORPHISM Outbreak TRYPANOSOMA CRUZI genetic diversity DNA Protozoan medicine.disease biology.organism_classification QR1-502 TRYPANOCIDAL CHEMOTHERAPY Oral Chagas disease Infectious Diseases therapeutic failure GENETIC DIVERSITY minicircle signature THERAPEUTIC FAILURE trypanocidal chemotherapy ORAL CHAGAS DISEASE Follow-Up Studies |
| Zdroj: | Frontiers in Cellular and Infection Microbiology, Vol 11 (2021) Frontiers in Cellular and Infection Microbiology CONICET Digital (CONICET) Consejo Nacional de Investigaciones Científicas y Técnicas instacron:CONICET |
| ISSN: | 2235-2988 |
| Popis: | We aimed to characterize the genetic constitution of natural T. cruzi populations involved in an Oral Chagas Disease (OCD) outbreak at a rural school of the community of Chichiriviche de la Costa, Venezuela, which affected patients did not respond to the etiological treatment. Peripheral blood samples and/or hemocultures were obtained from twenty-nine OCD patients at time of diagnosis or along nine years of Post-treatment (Tx) follow-up. The IgG serology, T. cruzi discrete typing units (DTU), satellite DNA-qPCR parasitic loads, and minicircle signatures were determined at Pre-Tx and after Tx. The serological titles and parasitic loads changed after treatment, with a significant decrease of IgG titers (Spearman’s r value= -0.961) and median parasite loads from 2.869 [IQR = 2.113 to 3.720] to 0.105 [IQR = -1.147 to 1.761] log10 par eq. /mL at Pre-Tx and Post-Tx, respectively, suggesting infection evolution from acute to chronic phase, without seroconversion or parasitological eradication, which was indicative of treatment failure. All patients were infected with T. cruzi DTU I populations. At Pre-Tx their median Jaccard genetic distances were 0.775 [IQR = 0.708 to 0.882], decreasing in genetic variability towards the end of follow-up (Mann-Whitney U test p= 0.0031). Interestingly, no Post-Tx minicircle signature was identical to its Pre-Tx counterpart population in a same patient, revealing selection of parasite subpopulations between the primary infection and Post-Tx. The parasitic populations isolated from hemocultures showed a lower number of bands in the minicircle signatures with respect to the signatures obtained directly from the patients’ blood samples, demonstrating a process of parasitic selection and reduction of the population variability that initially infected the patients. Decrease of parasitic loads after treatment as well as Pre- and Post-Tx intra-TcI diversity might be a consequence of both, natural evolution of the acute infection to the chronic phase and persistence of refractory populations due to Tx selection. Fil: Muñoz Calderon, Arturo Alejandro. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Investigaciones en Ingeniería Genética y Biología Molecular "Dr. Héctor N. Torres"; Argentina Fil: Díaz Bello, Zoraida. Universidad Central de Venezuela; Venezuela Fil: Alarcón de Noya, Belkisyolé. Universidad Central de Venezuela; Venezuela Fil: Noya González, Oscar O.. Universidad Central de Venezuela; Venezuela Fil: Schijman, Alejandro Gabriel. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Investigaciones en Ingeniería Genética y Biología Molecular "Dr. Héctor N. Torres"; Argentina |
| Databáze: | OpenAIRE |
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