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Will Personalized Medicine be the clue to eradicate TB?. Pere-Joan Cardona

Will Personalized Medicine be the clue to eradicate TB?. Pere-Joan Cardona. CONFER È NCIA DE L ’ EUROPAN PARLIAMENTARY TECHNOLOGY. Mycobacterium tuberculosis is still the major killer of the humankind. 130.2 million - 7 %- (12%). 1583.4 million - 85 %- (38%). 142.3 million - 7,7 %-

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Will Personalized Medicine be the clue to eradicate TB?. Pere-Joan Cardona

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  1. Will Personalized Medicine be the clue to eradicate TB?. Pere-Joan Cardona CONFERÈNCIA DE L’EUROPAN PARLIAMENTARY TECHNOLOGY

  2. Mycobacterium tuberculosis is still the major killer of the humankind 130.2 million -7%- (12%) 1583.4 million -85%- (38%) 142.3 million -7,7%- (18%) Prevalence of LTBI Currey et al 2007 PER YEAR! 2 million deaths 10 million new TB cases 100 million new LTBI cases

  3. Incidence of TB is still very high: about 10 milion/year

  4. Very much related to HIV prevalence

  5. Being resistance a growing issue.

  6. Being resistance a growing issue. Proportion MDR among new TB (2010) WHO REPORT 2011

  7. Being resistance a growing issue.

  8. … and not that far from Europe…

  9. … and not that far from Europe… 13 33 27 89 55

  10. The evolution of TB in Barcelona 1986-2010 cases/100,000 inhab. Lower incidence Less IDU among prison inmates. HIV-infection treated with HAART Increase in immigration TB Program founded High incidence HIV-IDU association Prison inmates Annual decline 10% 7,1/100000

  11. …Very much related to poverty…

  12. …Very much related to poverty…

  13. …Very much related to poverty…

  14. WHY D O T S ??? BASES of TB Treatment Spontaneous mutation rate Bactericidal activity 108 100 Rifampicin 100 105 Isoniazid 103 Pyrazinamide 5-10 3-4 106 Ethambutol

  15. 1st Rule: the need to avoid resistance

  16. 2nd Rule: to treat all the different bacilli populations

  17. The “SHORT-TERM” CHEMOTHERAPY Replicating bacilli Non-replicating bacilli 9 HRZM 8 7 6 5 Log Bacillary load (in logs) 4 HR 3 Sputum culture negative 2 1 0 4 6 1 5 2 3 Time (in months) H= isoniazid; R= rifampicin; Z=pyrazinamide; M=ethambutol

  18. The “SHORT-TERM” CHEMOTHERAPY can be even worse… Replicating bacilli Non-replicating bacilli 9 AEMO 8 7 6 5 Log Bacillary load (in logs) 4 3 2 EMO 1 0 21 17 19 15 11 13 7 1 5 9 3 Time (in months) A= aminoglycoside; E= ethionamide; M=ethambutol; O=ofloxacine

  19. Nobody is perfect but Rifampicin and isoniazid…

  20. Is “D O T S” enough?

  21. Is “D O T S” enough?

  22. Is “D O T S” enough?

  23. Is “D O T S” enough?

  24. Natural history of TB “Only” a 10% with LTBI will develop an active TB Post primary TB Primary TB Log (bacilli/lung) Active TB LTBI Time (years)

  25. The M. tuberculosis cycle II I VI Vb III V IV IVb Cardona et al. 2011

  26. CT No of lesions New lesions Old lesions weeks PRESENCE OF NEW LESIONS ARE CONTROLLED THROUGH TIME TOWARDS A LOW RATE Gil et al. 2010

  27. Risk of having active TB is higher soon after the infection… Acute Phase Chronic Phase B Chance to develop TB Chance to develop TB

  28. pO2 ! %? Active disease in adults tends to focus in the upper lobes. This is because a high oxygen pressure and a lower capillary net that favors a delayed immune response.

  29. Towards Active TB 0,5 mm 20 mm Marzo et al. Submitted

  30. Progression Towards Active TB 0,5 mm Ø, d21 Marzo et al. Submitted

  31. 1 mm Ø, d28 Marzo et al. Submitted

  32. 2 mm Ø, d30 Marzo et al. Submitted

  33. 8 mm Ø, d33 Marzo et al. Submitted

  34. … requiring a host’s hyper-reactivity from the beginning… The M. tuberculosis cycle: last sketch? Cardona PJ. 2012

  35. The discovery of the host’s hyperreactivity will be the clue to identify the 5% of susceptible population… The M. tuberculosis cycle: last sketch? Cardona PJ. 2012

  36. The discovery of the host’s hyperreactivity will be the clue to identify the 5% of susceptible population… Tobin et al 2010

  37. The discovery of the host’s hyperreactivity will be the clue to identify the 5% of susceptible population… Tobin et al 2010

  38. Berry et al 2010

  39. THANK YOU !!!

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