Embed Size (px)
Citation preview
Will Personalized Medicine be the clue to eradicate TB?.Pere-Joan CardonaCONFERÈNCIA DE L’EUROPAN PARLIAMENTARY TECHNOLOGY
Mycobacterium tuberculosis is still the major killer of the humankind
PER YEAR! 2 million deaths10 million new TB cases
100 million new LTBI cases
Prevalence of LTBI Currey et al
2007
142.3 million -7,77,7%-(18%)
130.2 million -77%-(12%) 1583.4 million -
8585%-(38%)
Incidence of TB is still very high: about 10 milion/year
Very much related to HIV prevalence
Being resistance a growing issue.
Being resistance a growing issue.
0-<3
3-<6
6-<12
12-<18
>18
No data available
Subnational data only
Proportion MDR among new TB (2010)Proportion MDR among new TB (2010)
WHO REPORT 2011WHO REPORT 2011
Being resistance a growing issue.
… and not that far from Europe…
… and not that far from Europe…
1313
27273333
5555 89 89
4339
3735
3230
2630
2831
2624
27
6768
6058
46
36
27
48
55566061
0
10
20
30
40
50
60
70
80
observed objective
The evolution of TB in Barcelona The evolution of TB in Barcelona 1986-20101986-2010
cases/100,000 inhab.cases/100,000 inhab.
TBTBProgram Program
foundedfounded
High incidenceHigh incidenceHIV-IDU associationHIV-IDU association
Prison inmatesPrison inmates
Lower incidence Lower incidence Less IDU among prison inmates.Less IDU among prison inmates.
HIV-infection treated with HAART HIV-infection treated with HAART
Increase in immigrationIncrease in immigration
7,1/1000007,1/100000
Annual decline 10%Annual decline 10%
…Very much related to poverty…
…Very much related to poverty…
…Very much related to poverty…
WHY D O T S ???BASES of TB Treatment
Rifampicin
Isoniazid
PyrazinamideEthambutol
Spontaneous mutation rate
Bactericidal activity
108
105
103
106
1001005-103-4
1st Rule: the need to avoid resistance
2nd Rule: to treat all the different bacilli populations
The “SHORT-TERM” CHEMOTHERAPY
Sputum culture negative
1
2
3
4
5
6
7
8
9
01 2 3 4 5 6
Log
Bacilla
ry load
(in
log
s)
Time (in months)
HRZM
HR
Replicating bacilli
Non-replicating bacilli
H= isoniazid; R= rifampicin; Z=pyrazinamide; M=ethambutol
The “SHORT-TERM” CHEMOTHERAPY can be even worse…
11
22
33
44
55
66
77
88
99
0011 33 55 77 99 1111 1313 1515 1717 1919 2121
AEMO
EMO
Replicating bacilli
Non-replicating bacilli
A= aminoglycoside; E= ethionamide; M=ethambutol; O=ofloxacine
Log
Bacilla
ry load
(in
log
s)
Time (in months)
Nobody is perfect but Rifampicin and isoniazid…
Is “D O T S” enough?
Is “D O T S” enough?
Is “D O T S” enough?
Is “D O T S” enough?
Natural history of TB“Only” a 10% with LTBI will develop an
active TB
Primary TB Post primary TB
Time (years)
Lo
g (
bac
illi/l
un
g)
Active TB
LTBI
The M. tuberculosis cycle
Cardona et al. 2011
IVb
I II
IV
V
VIVb III
PRESENCE OF NEW LESIONS ARE CONTROLLED THROUGH TIME TOWARDS A LOW RATE
CT
New lesions
Old lesions
weeks
No
of
les
ion
s
Gil et al. 2010
Risk of having active TB is higher soon after the infection…
BB
Acute Phase Chronic Phase
Chance to develop TB Chance to develop TB
pOpO2 2 !!%% ??
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.
0,5 mm
20 mmMarzo et al. Submitted
Towards Active TB
0,5 mm Ø, d21Marzo et al. Submitted
Progression Towards Active
TB
1 mm Ø, d28Marzo et al. Submitted
2 mm Ø, d30Marzo et al. Submitted
8 mm Ø, d338 mm Ø, d33
Marzo et al. Submitted
The M. tuberculosis cycle: last sketch?Cardona PJ. 2012
… requiring a host’s hyper-reactivity from the beginning…
The M. tuberculosis cycle: last sketch?Cardona PJ. 2012
The discovery of the host’s hyperreactivity will be the clue to identify the 5% of susceptible
population…
The discovery of the host’s hyperreactivity will be the clue to identify the 5% of susceptible
population…
Tobin et al 2010
The discovery of the host’s hyperreactivity will be the clue to identify the 5% of susceptible
population…
Tobin et al 2010
Berry et al 2010
THANK YOU !!!THANK YOU !!!
