anys. Reinfection vs. Reactivation Is this the question?

Transcription

1 Reinfection vs. Reactivation Is this the question?

2 Unitary Concept. Stead Infant and Adult TB is defined as Primary and Post-primary as a conclusion of the mass radiography campaings in Europe after the 2WW.

3 Unitary Concept. Stead Infant and Adult TB is defined as Primary and Post-primary. Premises under the Unitary Concept : Once infected always infected Reinfection is not possible

4 Against the Unitary Concept. Bacilli is constantly cleaned from the lungs. RR to develop active TB in adolescents with recent TST conversion decreases exponentialy. Sutherland 1966 Mtb is constantly drained towards the intestinal tract. The dynamic Hypothesis. Cardona PJ. 2009

5 Against the Unitary Concept. Reinfection is always possible! It depends on the Infection Risk in a community Uys 2015

6 Against the Unitary Concept. Localization in upper ( typical ) or lower lobes ( atypical ) depends on the immunological status of the host. Geng 2005

7 1.- The question is not the endogenous or exogenous origin of the bacilli, but why active TB develops!!!!!

8 Specially taking into account that Mtb infection itself protects in a 90%!!! Heimbeck 1948.

9 And that antigenic repertoire of Mtb is terribly constant! Comas 2010

10 Antigenic repertoire of Mtb is terribly constant! Coscolla 2015

11 Antigenic repertoire of Mtb is terribly constant! ESAT-6 and Ag85 complex! Andersen 1993 Ag85 complex Esat-6

12 ESAT-6 is the major virulence factor: and IT IS IN ALL Mtb STRAINS!!!!! Jo 2013

13 2.- Why M. kansasii, an ESAT-6 producer, do not cause active TB? Or, why ESAT-6 is not enough?

14 Genom Biol Evol. 2015?????

15 Trends Microbiology 2011

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17 Jankute 2017

18 ESAT-6 is the major virulence factor: it allows the Induction of cords in macrophages! Champion 2017

19 Cording favours macrophage extracellular traps, which promote the extracellular growht of the bacilli! Champion 2017

20 Once a clump of M. tuberculosis initiates death of a single macrophage, it may lead to serial killing of other macrophages and a loss of control over the infection. Mahamed 2017

21 Induction of exudative lesions is promoted in upper lobes, because the lower drainage of the alveoli. Cardona PJ. 2017

22 Exudative lesions are the responsible for the induction of active TB. Cardona PJ C B

23 There is a certain percentage of infective droplets that might carry cording bacilli... Wood 2016 Aproximately a 1% of the droplets have cording bacilli

24 ...considering that holds in the upper lobe (20% of the total lung volum) infection with cording bacilli might explain the first phase of active TB induction. The first months after infection. 20% 1% Sutherland 1966

25 Uys 2015 Of course this process can be repeated several times, depending on the risk of infection in the community. 20% 20% 20% 1% 1% 1% 20% 20% 20% 20% 20% 1% 1% 1% 1% 1% 20% 20% 20% 20% 20% 1% 1% 1% 1% 1%

26 How we do explain the wide window for the induction of active TB? Sutherland 1966

27 ... It can be explained by the endogenous reinfection of cording bacilli generated in the lesions. Cording formation in active TB model in C3HeB/FeJ mice Arias et al. unpublished

28 ...endogenous reinfection of cording bacilli would finally generate an exudative lesion... Cardona PJ. In preparation

29 ... in a process that will require a Th17 response to maintain the PMN infiltration in the lesion. IL-4 IFN-g Treg IL-17 IL-4 Th2 Th1 IFN-g IL-17 Th17 Tregs

30 Conclusion: Reinfection vs. Reactivation is this not the question.

31 Endogenous vs. Exogenous Reinfection. This is the question! Wood 2016

32 Coming back to the classics! Disease in humans as a consequence of accumulation of lesions. Pottenger & Canetti Georges Canetti ( ) Francis Pottenger ( )

33 Aknowledgements: to all the students and researchers that have worked and work in our Unit!

34 MERCI!!!! Visiteu-nos a: