Aplicación de las técnicas moleculares en el diagnóstico y seguimiento de pacientes con enfermedad de chagas crónica en un área no endémica.

Abstract

Chagas disease (CD) is the most important parasitic disease in Latin America, where it is endemic. Due to the migratory movements of the last decades, CD has become a global health problem. CD presents a sharp phase characterized by high parasitaemia followed by a chronic phase in which the parasitaemia is low and intermittent._x000D_ For this reason, the polymerase’s chain reaction (PCR) sensitivity in the chronic phase is variable._x000D_ The main objective of this thesis is to evaluate the usefulness of the real-time PCR technique (qPCR) in the diagnosis and monitoring of patients in the chronic phase of CD, followed in two centers of Tropical Medicine in Barcelona._x000D_ The qPCR shows low sensitivity in our cohort and a positive result is not related to the appearance of the visceral involvement characteristic of the chronic phase. Despite this, the results of parasitemia obtained in untreated patients can provide data on the dynamics of the parasite and the different factors that may influence its presence in peripheral blood._x000D_ However, a positive result of qPCR in treated patients is a good surrogate marker of therapeutic failure both in routine clinical practice and to evaluate new treatment patterns in clinical trials._x000D_ In the cohort followed in our center, the failure rate to Benznidazole was very low, which reinforces its effectiveness as trypanocidal. However, the failure of two different treatment regimes with Posaconazole, evaluated in the context of the Chagasazol clinical trial, was close to 90%._x000D_ According to the experience gathered in this thesis, the greatest utility of qPCR in the chronic phase of CD is monitoring the response to trypanocidal treatment. In the_x000D_ absence of new early healing biomarkers, this monitoring should be carried out periodically and over a long period of time._x000D_ The use of external quality control of qPCR results makes them more robust and allows an early evaluation of possible protocol errors.

Date of Award	4 Nov 2019
Original language	Spanish
Supervisor	Tomas Pumarola Suñe (Director), Israel Molina Romero (Director) & Carme Muñoz Batet (Tutor)