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

Will personalised medicine be the key to eradicating TB?

Cada any dos milions de persones moren de tuberculosi. Gairebé un terç de la població mundial està infectada, i un 10 % d'aquest grup desenvoluparà la malaltia. Els dos objectius principals del tractament de la tuberculosi són la prevenció de la resistència i el tractament de totes les poblacions de bacils. Però l'aparició de soques de tuberculosi multiresistent i tuberculosi extremament resistent s'està convertint en un problema cada vegada més preocupant, i, perquè els tractaments s'han de perllongar, en una enorme càrrega per als sistemes sanitaris. Des d'aquesta perspectiva, la medicina personalitzada pot millorar el tractament dels pacients amb tuberculosi. Mitjançant l'ús de proves genètiques que detecten polimorfismes específics podem identificar els pacients que responen més bé als fàrmacs disponibles, i considerar teràpies alternatives per als que no hi responen tan bé. La investigació continuada en biomarcadors donarà suport a la medicina personalitzada en el tractament de malalties infeccioses, especialment de la tuberculosi, una malaltia per la qual els tractaments disponibles actualment tenen moltes limitacions.Every year, 2 million people die from tuberculosis. Nearly one third of the world’s population is already infected, and 10 % of this group will go on to develop TB. The two basic goals of TB treatment are the avoidance of resistance and the treatment of all bacilli populations. But the appearance of multiple drug resistant TB (MDR-TB) and extensively drug resistant TB (XDR-TB) strains is becoming an increasingly troublesome issue, and because treatments have to be prolonged, and enormous burden for health systems. From this perspective, personalised medicine can improve the treatment of patients with TB. By using genetic testing to detect specific polymorphisms and identify patients that best respond to the available drugs, and to consider therapeutic alternatives for those who are not. Further research for biomarkers will support personalised medicine in the treatment of infectious diseases, especially TB, where we are already confronted with the many limitations of the currently available treatments

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

Publication analysis of the contact lens field: What are the current topics of interest?

Preprin

Multiple Consecutive Infections Might Explain the Lack of Protection by BCG

Although contacts between tuberculosis patients may result in multiple consecutive infections (MCI), no experimental animal models consider this fact when used in basic studies. Moreover, the current TB vaccine (BCG) has demonstrated a limited protection in humans. In this study we evaluate the effect of tuberculosis MCI by way of a simple mathematical analysis using data from the low dose aerosol murine experimental model. The results show that a higher number of, or shorter intervals between, multiple consecutive infections reduce the protective effect of BCG. This is due to both the increase in bacillary load at the stationary level of the infection, and the protective immune response induced by the infection itself. This factor must therefore be taken into account when designing new prophylactic strategies as candidate vaccines for the replacement of BCG