Estudio de la tuberculosis pulmonar mediante tomografía computarizada multidetector en un modelo experimental de minipig

Abstract

Nowadays, tuberculosis is still an important Public Health problem at worldwide level. According to the last WHO report, on 2015, there were 10.5 million of new cases, and up to 1.8 million people died from tuberculosis. In Catalonia, there are 1200 new cases each year, most of them diagnosed in Barcelona city. At prophylactical level, there is only one available vaccine, the BCG, with a variable effectivity according to populations, and not protecting adults from pulmonary forms. Lots of resources have been devoted to the development of new vaccine candidates, systematically tested in experimental animal models. In the context of an european project, the Experimental Tuberculosis Unit of the Germans Trias i Pujol Foundation evaluated the efficacy of 3 vaccine candidates in a experimental model of tuberculosis using minipigs, comparing them to the unvaccinated control group. _x000D_ The hypothesis of the present thesis work was that the evaluation by multidetector TC is useful to describe the course of tuberculosis in a minipig experimental model, and to evaluate the effect of new vaccine candidates on this course. Up to 3 objectives were set up: _x000D_ 1) To define an adequate technical protocol to study post-necropsia the lung and tracheo-bronchial tree of the minipig;_x000D_ 2) To determine the radiologic characteristics by multidetector TC of tuberculous lesions in a minipig experimental model; and _x000D_ 3) To evaluate by multidetector TC the effect of new vaccine candidates in the course of tuberculosis infection in a minipig experimental model. _x000D_ With this aim, the broncho-pulmonary pieces of 24 minipigs were used, all collected within the Experimental Tuberculosis Unit’s project, and analyzed by multidetector TC. Once the technical characteristics adjusted, and with the help of the MOSIMBIO group of the Politecnic University of Catalunya (in catalan, UPC), the images were analyzed. From each minipig, the following data of the tuberculous lesions were recorded: number of lesions, localization, size, Houndsfield Units, distance between lesions. In a secondary phase, a correlation between the radiologic semiology of the images obtained and the histopathological study of the samples was done. _x000D_ No statistically significant differences were observed between specimens in terms of morphology and anatomy. In all but one minipig unilateral lug affectation was found, and we attribute the differences encountered to the initial infection and not to the different experimental groups. The majority (96.2%) of tuberculous lesions were localized in caudal lobes. The 5% of the detected lesions were grouped in clusters of minimum 2 lesions. No statistically significant differences were found between the experimental groups according to the distribution in sagital, antero-posterior or craneo-caudal spacial planes. A 20-25% of the lesions were in contact with the pleura, with no statistically significant differences encountered between the experimental groups. The number of lesions detected in the unvaccinated control group was lower than in vaccinated groups, and had smaller sizes. However, the vaccinated animals showed a higher percentage of calcification in their lesions, measured as Houndsfield Units of more than 120 (25% of total lesions from the control group vs 66% of those from the vaccinated groups). On the correlation with the histopathology, the Multidetector TC detected more lesions than the histopathology analysis, but was less sensitive in classifying them. _x000D_ As conclusion, this thesis work confirms the usefulness of the MultiDetector TC as an useful diagnostic tool to evaluate new therapeutical and prophylactical strategies in experimental animal models of tuberculosis or in humans.

Date of Award	18 Jan 2017
Original language	Undefined/Unknown
Awarding Institution	Germans Trias i Pujol University Hospital
Supervisor	Jordi Tor Aguilera (Tutor), Ricardo Perez Andres (Director) & Cristina Vilaplana Massaguer (Director)