Genetic diversity of natural populations of Trypanosoma cruzi in clinical samples from patients with Oral Chagas Disease in Venezuela: follow-up after treatment with trypanocidal drugs

BELLO, ZORAIDA DIAZ; MUÑOZ CALDERON ARTURO; SCHIJMAN, ALEJANDRO G.; ALARCÓN DE NOYA BELKISYOLÉ

Mar del Plata

Congreso; Sociedad Argentina de Parasitologia; 2019

Sociedad Argentina de Parasitologia

Oral transmission ofChagas disease (OChD) is an increasingly important aspect in the epidemiology. Venezuelahas reported the two largest outbreaks described so far, affecting a total of192 people mostly children.. The long-term impact after treatment on thedynamics of infection in natural populations of T. cruzi is still unclear. In this sense, we proposed a genetic characterizationof T. cruzi populations present inperipheral blood in order to differentiate responder or non-responder patientsand predict the response to treatment (Tmt). We performed quantification of theparasitic load by qPCR, genetic typing of T.cruzi populations by multiplex qPCR of nuclear genome markers and RFLP-PCR forthe hypervariable region of T. cruzi kDNAto demonstrate changes in Minicircle signatures (Ms) of the parasite populationspresent in 41 clinical samples from 15 patients. To reflect the geneticdiversity found, Jaccard distances (Jd) values were compared. This clinicalmonitoring confirmed the presence of T.cruzi DNA in 26 post-treatment samples up to 9 years after Tmt. Theseresults reveal 100% therapeutic failure for both outbreaks of OChD, classifyingthese patients as non-responders to Tmt. All samples showed homogeneity at theDTU level, being typified as TcI. The Ms showed a high degreeof polymorphism, with a 73% of total post-Tmt samples with Jd values close to1. Analysing the dynamics of each patient`s population separately, in all post-Tmtsamples the change in Ms variability respect to pre-Tmt sample was notstatistically significant. This variability does not reflect a natural orinduced clonal selection process driven by the etiological Tmt; on thecontrary, it could be associated with the clonal histotropism process evidencedin natural T. cruzi infections. Inconclusion, these strategies of molecular characterization of parasite DNA wereuseful to detect Tmt failure and find out the lack of parasite populationselection with Tmt in these OChD settings.<!-- /* Font Definitions */ @font-face{font-family:"MS Mincho";panose-1:2 2 6 9 4 2 5 8 3 4;mso-font-alt:"ＭＳ 明朝";mso-font-charset:128;mso-generic-font-family:modern;mso-font-format:other;mso-font-pitch:fixed;mso-font-signature:-536870145 1791491579 134217746 0 131231 0;}@font-face{font-family:"Cambria Math";panose-1:2 4 5 3 5 4 6 3 2 4;mso-font-charset:0;mso-generic-font-family:roman;mso-font-pitch:variable;mso-font-signature:3 0 0 0 1 0;}@font-face{font-family:Calibri;panose-1:2 15 5 2 2 2 4 3 2 4;mso-font-charset:0;mso-generic-font-family:swiss;mso-font-pitch:variable;mso-font-signature:-1610611985 1073750139 0 0 159 0;}@font-face{font-family:Cambria;panose-1:2 4 5 3 5 4 6 3 2 4;mso-font-charset:0;mso-generic-font-family:roman;mso-font-pitch:variable;mso-font-signature:-1610611985 1073741899 0 0 159 0;}@font-face{font-family:"\@MS Mincho";panose-1:2 2 6 9 4 2 5 8 3 4;mso-font-charset:128;mso-generic-font-family:modern;mso-font-format:other;mso-font-pitch:fixed;mso-font-signature:-536870145 1791491579 134217746 0 131231 0;} /* Style Definitions */ p.MsoNormal, li.MsoNormal, div.MsoNormal{mso-style-unhide:no;mso-style-qformat:yes;mso-style-parent:"";margin:0cm;margin-bottom:.0001pt;mso-pagination:widow-orphan;font-size:12.0pt;font-family:"Cambria",serif;mso-ascii-font-family:Cambria;mso-ascii-theme-font:minor-latin;mso-fareast-font-family:"MS Mincho";mso-fareast-theme-font:minor-fareast;mso-hansi-font-family:Cambria;mso-hansi-theme-font:minor-latin;mso-bidi-font-family:"Times New Roman";mso-bidi-theme-font:minor-bidi;mso-ansi-language:ES-TRAD;mso-fareast-language:ES;}.MsoChpDefault{mso-style-type:export-only;mso-default-props:yes;font-family:"Cambria",serif;mso-ascii-font-family:Cambria;mso-ascii-theme-font:minor-latin;mso-fareast-font-family:"MS Mincho";mso-fareast-theme-font:minor-fareast;mso-hansi-font-family:Cambria;mso-hansi-theme-font:minor-latin;mso-bidi-font-family:"Times New Roman";mso-bidi-theme-font:minor-bidi;mso-ansi-language:ES-TRAD;mso-fareast-language:ES;}size:595.0pt 842.0pt;margin:70.85pt 3.0cm 70.85pt 3.0cm;mso-header-margin:35.4pt;mso-footer-margin:35.4pt;mso-paper-source:0;}div.WordSection1{page:WordSection1;}