La Tuberculosi? no s'havia eradicat? cent anys del bacteri més persistent

Aquest treball pretén donar una visió de l'estat de la lluita contra la tuberculosi fa cent anys a Catalunya, bo i repassant-ne aspectes epidemiològics, de profilaxi i tractament de la malaltia. Igualment s'aprofundeix en les contribucions d'investigadors catalans en l'estudi de l'etiopatogènia: des de la teoria de la mutabilitat del doctor Ferran que porta al disseny de la vacuna antialfa, passant per la matisació que va donar a la teoria Ravetllat-Pla i la comercialització d'una nova teràpia basada en la utilització d'un sèrum específic contra la «forma d'atac» del bacil tuberculós, i a les observacions del doctor Conrad Xalabarder de les formes sense paret ceŀlular. Igualment es posen de manifest els reptes que encara romanen: el desconeixement del mecanisme d'infecció latent o d'inducció de la lesió més característica, la cavitat pulmonar. En aquest sentit es presenten les contribucions del nostre grup basades en la «hipòtesi dinàmica», que defensa la infecció com un procés continu de reinfecció endògena, que preveu la impossibilitat de generar vacunes que l'evitin, i que ha permès el disseny d'una vacuna terapèutica (la RUTI) per reduir el temps de la quimioteràpia.This work pretends to offer a view on the fight against tuberculosis in Catalonia 100 years ago, summarizing aspects on its epidemiology, prophylaxis and treatment. It also explains the contribution of catalonian researchers in the study of its etiopathogenesis: The mutability theory of Dr. Ferran and the design of the anti-alpha vaccine. The refinement of this theory that led to the theory Ravetllat-Pla and the introduction of a new therapy based on the administration of specific serum against the attack form of the bacilli. And the studies of Dr. Conrad Xalabarder on the cell wall deficient forms. Furthermore, it is highlighted the challenges that still remain. The lack of knowledge on the mechanisms that led to latent tuberculosis infection or the induction of the most characteristic lesion: the pulmonary cavity. In this regard the contributions of our group in these fields are summarized. Mainly based in the “dynamic hypothesis”, that considers the infection as a continuous process of endogenous reinfection. This theory supports that the design of vaccines able to avoid it are impossible, and has been the bases for the design of the therapeutic vaccine RUTI, which will allow the reduction of, chemotherapy treatment

Descobreixen per què sols el 10% dels infectats de tuberculosi desenvolupa la malaltia

Un equip d'investigadors de la Unitat de Tuberculosi Experimental (UTE) de la Fundació Institut d'Investigació en Ciències de la Salut Germans Trias i Pujol (IGTP) ha descobert, en col·laboració amb el Centre de Recerca en Sanitat Animal (CReSA), -UAB-IRTA-, el motiu pel qual, més enllà dels tractaments antibiòtics, només el 10% de les persones infectades de tuberculosi desenvolupen la malaltia. La troballa, que es publica en un article científic al número d'abril de la revista PLOS One, demostra per primera vegada la importància del teixit pulmonar en el control de la infecció. Això ha estat possible perquè els experts han traslladat als porcs les investigacions que habitualment feien en ratolins.Descubren por qué sólo el 10% de los infectados de tuberculosis desarrolla la enfermeda

The Progress of Therapeutic Vaccination with Regard to Tuberculosis

Ajudes rebudes: Departament de Salut de la Generalitat de Catalunya; projecte CIBER CRP-T; Plan Nacional I+D+IA major problem with tuberculosis (TB) control is the long duration of drug therapy-both for latent and for active TB. Therapeutic vaccination has been postulated to improve this situation, and to this end there are several candidates already in clinical phases of development. These candidates follow two main designs, namely bacilli-directed therapy based on inactivated -whole or -fragmented bacillus (Mycobacterium w and RUTI) or fusion proteins that integrate non-replicating bacilli -related antigens (H56 vaccine), and host-directed therapy to reduce the tissue destruction. The administration of inactivated Mycobacterium vaccae prevents the "Koch phenomenon" response, and oral administration of heat-killed Mycobacterium manresensis prevents excessive neutrophilic infiltration of the lesions. This review also tries to explain the success of Mycobacterium tuberculosis by reviewing its evolution from infection to disease, and highlights the lack of a definitive understanding of the natural history of TB pathology and the need to improve our knowledge on TB immunology and pathogenesis

A Spotlight on Liquefaction : Evidence from Clinical Settings and Experimental Models in Tuberculosis

Liquefaction is one of the most intriguing aspects of human tuberculosis. It is a major cause of the transition from the infection to active disease (tuberculosis, TB) as well as the transmission of M. tuberculosis to other persons. This paper reviews the natural history of liquefaction in humans from a pathological and radiological point of view and discusses how the experimental models available can be used to address the topic of liquefaction and cavity formation. Different concepts that have been related to liquefaction, from the influence of immune response to mechanical factors, are reviewed. Synchronic necrosis or apoptosis of infected macrophages in a close area, together with an ineffective fibrosis, appears to be clue in this process, in which macrophages, the immune response, and bacillary load interact usually in a particular scenario: the upper lobes of the lung. The summary would be that even if being a stochastic effect, liquefaction would result if the organization of the intragranulomatous necrosis (by means of fibrosis) would be disturbed

Regulatory T Cells in Mycobacterium tuberculosis Infection

Anti-inflammatory regulatory T cells have lately attracted attention as part of the immune response to Mycobacterium tuberculosis infection, where they counterbalance the protective but pro-inflammatory immune response mediated by Th17 cells and especially by the better-known Th1 cells. In chronic infectious diseases there is a delicate balance between pro- and anti-inflammatory responses. While Th1 and Th17 are needed in order to control infection by Mycobacterium tuberculosis, the inflammatory onset can ultimately become detrimental for the host. In this review, we assess current information on the controversy over whether counterbalancing regulatory T cells are promoting pathogen growth or protecting the host

The key role of exudative lesions and their encapsulation: lessons learned from the pathology of human pulmonary tuberculosis

Abstract: A review of the pathology of human pulmonary TB cases at different stages of evolution in the pre-antibiotic era suggests that neutrophils play an instrumental role in the progression toward active TB. This progression is determined by the type of lesion generated. Thus, exudative lesions, in which neutrophils are the major cell type, are both triggered by and induce local high bacillary load, and tend to enlarge and progress toward liquefaction and cavitation. In contrast, proliferative lesions are triggered by low bacillary loads, mainly comprise epithelioid cells and fibroblasts and tend to fibrose, encapsulate and calcify, thus controlling the infection. Infection of the upper lobes is key to the progression toward active TB for two main reasons, namely poor breathing amplitude, which allows local bacillary accumulation, and the high mechanical stress to which the interlobular septae (which enclose secondary lobes) are submitted, which hampers their ability to encapsulate lesions. Overall, progressing factors can be defined as internal (exudative lesion, local bronchogenous dissemination, coalescence of lesions), with lympho-hematological dissemination playing a very limited role, or external (exogenous reinfection). Abrogating factors include control of the bacillary load and the local encapsulation process, as directed by interlobular septae. The age and extent of disease depend on the quality and speed with which lesions liquefy and disseminate bronchially, the volume of the slough, and the amount and distribution of the sloughing debris dispersed

Common mode feedback analysis for EIT systems with distributed current sources

The use of differential voltage measurements is widely used in EIT instruments. Instrumentation amplifiers are always affected by common mode voltages at their input. These voltages may have different origins, being the current sources and multiplexers the ones which contribute the most. However, even considering ideal current sources and multiplexers, some amount of common mode voltage will always be present due to the measurement principle. Errors produced by common mode voltages are very difficult to calibrate because they depend on the object being measured. At low frequencies it is easy to design instrumentation amplifiers with high CMRR values, but common mode voltages are also high, mostly because of unbalances in electrode impedances. At higher frequencies common mode voltages are smaller, but the CMRR of the amplifiers also decreases. Common mode feedback (CMF) to reduce common mode voltages has been largely used in EIT systems. There is a good theoretical understanding of CMF for systems using a single current source and a demultiplexer. However there is a new class of instruments which use distributed current sources. In these systems CMF is actually used to change the inherent unbalance among current sources instead of being applied to the output of the current source. We present a theoretical analysis of this new CMF technique and the results obtained when applying it to our latest EIT systemPostprint (published version

Performance assessment of EIT measurement systems

EIT acquisition systems, when regarded as measuring instruments, can be characterized by their inherent characteristics: reproducibility, repeatability and discrimination. The ultimate limit to all three is noise, whether long-term or short-term noise. In addition, for some applications accuracy can also play a role, although accuracy is not an inherent characteristic and requires a known test object to be defined. Because EIT systems are multichannel instruments and the information of all channels is being combined to produce an image, a procedure to standardize the performance assessment must be set up in order to allow for meaningful comparison of different systems or different settings in the same system. We propose the use of three parameters defined long ago but scarcely used among EIT systems designers: SER (Systematic Error Ratio), NER (Noise Error Ratio) and RER (Reciprocity Error Ratio). We applied these definitions to our latest EIT instruments, TIE5-sys, in a wide frequency range and with different settings in configurable acquisition parameters and provide the interpretation of the results obtained in terms of reproducibility, repeatability and discrimination. We also comment on the tradeoffs that show up when using the usual definition for these figuresPostprint (published version