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Ó 2012 by the author
Evidence provided by recent metanalyses on treatment: what is
new?
GB Migliori
WHO Collaborating Centre for TB and Lung Diseases, Fondazione S. Maugeri, Tradate Italy
3
Aims
To describe and discuss:• Existing guidelines and definitions• Epidemiology of MDR-TB in Europe and globally
derived from surveillance and M&E (Monitoring and Evaluation)
• The new information on MDR-TB diagnosis• The new information on MDR-TB treatment deriving
from recent meta-analyses• The principles of MDR-TB control, with prevention and
public health aspects
4
Aims
To describe and discuss:• Existing guidelines and definitions• Epidemiology of MDR-TB in Europe and globally
derived from surveillance and M&E (Monitoring and Evaluation)
• The new information on MDR-TB diagnosis• The new information on MDR-TB treatment deriving
from recent meta-analyses• The principles of MDR-TB control, with prevention and
public health aspects
5
2000
6
7
Guidelines for the programmatic management of drug-resistant tuberculosis (1)
1 Background information on DR-TB2 Framework for effective control of DR-TB3 Political commitment and coordination 4 Definitions: case registration, bacteriology and treatment
outcomes5 Case-finding strategies 6 Laboratory aspects 7 Treatment strategies for MDR-TB and XDR-TB 8 Mono- and poly-resistant strains9 Treatment of DR-TB in special conditions and situations10 DR-TB and HIV infection 11 Initial evaluation, monitoring of treatment and management of
adverse effects
8
Guidelines for the programmatic management of drug-resistant tuberculosis (2)
12 Treatment delivery and community-based DR-TB support 13 Management of patients with MDR-TB treatment failure14 Management of contacts of MDR-TB patients15 Drug resistance and infection control 16 Human resources: training and staffing17 Management of second-line antituberculosis drugs 18 Category IV recording and reporting system19 Managing DR-TN through patient-centered careANNEX 1 Drug information sheetsANNEX 2 Weight-based dosing of drugs for adultsANNEX 3 Suggestions for further readingANNEX 4 Legislation, human rights, and patient’s right in TB
care prevention and control ANNEX 5 Use of experimental drugs outside of clinical trials ANNEX 5 Methodology
9
Causes of DR
10
Causes of MDR
Patient mismanagement
11
DOTS MDR-TBFUNDING: Government Commitment (10$/ case)
> moneyUp to 20,000 $/ case
DIAGNOSIS: SS microscopy, QA and safety measures
+C, DST, SRL, QA, infection control
TREATMENT: SCC,DOT, 6-8 months, no hospitalization
24 months, mandatory DOT & hospitalization in reference facilities
TB drugs only, no AE relevant toxicity, need special drugs + expertise
TREATMENT MONITORING: SS, standard outcome definitions
C, DST, special outcome definitons
12
Definitions• Mono-R• Poly-R• MDR• XDR
• SS+, C+• Cure, failure• Treatment monitoring
DefinitionsMDR-TB = Strains resistant to at least INH and RIF (most important 1st-line drugs)XDR-TB = MDR TB strains with additional resistance to any fluoroquinolone and any of the 3 injectable second-line drugs (amikacin, kanamycin, capreomycin)TDR, XXDR = Resistance to all drugs (not standardised defin)
MDR TB XDR TBTB with any drug resistance
TDR/XXDR TB
14
1st-line oral
• INH• RIF• PZA• EMB• (Rfb)
Injectables
• SM• KM• AMK• CM
Fluoroquinolones
• Cipro• Oflox• Levo• Moxi• (Gati
)
Oral bacteriostatic 2nd line
Unclear efficacy• ETA/PTA• PASA• CYS
Not routinely recommended, efficacy unknown, e.g., amoxacillin/clavulanic acid, clarithromycin, clofazamine, linezolid, inmipenem/cilastatin, high dose isonizid
XDR= HR + 1 FQ + 1 Injectable (KM or AMK or CM)
15
Aims
To describe and discuss:• Existing guidelines and definitions• Epidemiology of MDR-TB in Europe and globally
derived from surveillance and M&E (Monitoring and Evaluation)
• The new information on MDR-TB diagnosis• The new information on MDR-TB treatment deriving
from recent meta-analyses• The principles of MDR-TB control, with prevention and
public health aspects
Notified cases of MDR-TB
Cases of MDR-TB
0–99100–9991000–9999≥10 000NA
Estimated absolute numbers of reported cases with MDR-TB*
Notified cases of MDR-TB
Cases of MDR-TB
0–99100–9991000–9999≥10 000NA
*among reported pulmonary TB patients
<100100–9991000–9999>10,000
Distribution of MDR-TB among new TB cases, 1994-2010.
17
0-<3
3-<6
6-<12
12-<18
>18
No data available
Subnational data only
Distribution of MDR-TB among previously treated TB cases, 1994-2010.
18
0-<6
6-<12
12-<30
30-<50
>50
No data available
Subnational data only
13 top settings with highest % of MDR-TB among new cases, 2001-2010
16.5
19.2
19.3
19.4
20.0
22.3
23.8
27.3
28.3
15.4
14.8
16.0
16.1
0 5 10 15 20 25 30
Tashkent, Uzbekistan (2005)
Estonia (2008)
Donetsk Oblast, Ukraine (2006)
Mary El Republic, Russian Federation (2008)
Dushanbe city and Rudaki district, Tajikistan (2009)
Belgorod Oblast, Russian Federation (2008)
Kaliningrad Oblast, Russian Federation (2008)
Republic of Moldova (2006)
Ivanovo Oblast, Russian Federation (2008)
Baku city, Azerbaijan (2007)
Arkhangelsk Oblast, Russian Federation (2008)
Pskov Oblast, Russian Federation (2008)
Murmansk Oblast, Russian Federation (2008)
35.3Minsk, Belarus (2010) Preliminary results ERJ 2012
Notifications of MDR-TB increasingBUT only ~ 1 in 6 (16%) of estimated cases of MDR-TB among reported TB patients diagnosed and treated in 2010
Notified cases of MDR-TB
0
10
20
30
40
50
60
2005 2006 2007 2008 2009 2010
Num
ber o
f pat
ient
s (th
ousa
nds)
19,000
53,000
Global Plan target ~270,000 in 2015
0
50
100
150
200
250
300
SE Asia
W. Pac
ific
EuropeAfri
caEMR
Americas
World
Not on treatmentTreated
MDR-TB cases treated and estimated numbers not treated for MDR-TB, among notified TB patients, 2010
290,000
Proportion of TB patients tested for MDR-TB remains low
51%
19%
6%3% 2%
6%
0.3%0%
10%
20%
30%
40%
50%
60%
% o
f pat
ient
s
Global plan target for 2015 = 100%
Previously treated
30%
5%
1% 0.2%2%0.4% 0.1%
0%
5%
10%
15%
20%
25%
30%
35%
40%
Europe
Americas
SE Asia
W Pacific EMR
Africa
WORLD
% o
f pat
ient
s
New cases
Global plan target for 2015 = 20%
22
Trend of MDR-TB among new cases, Estonia, Latvia and…Tomsk Oblast, RF
% MDR among new
0.00
0.05
0.10
0.15
0.20
0.25
0.30
0.35
1997 1999 2001 2003 2005
p=0.6213Estonia
0102030405060708090
100
1997 1999 2001 2003 2005 2007
Latvia0.00
0.05
0.10
0.15
0.20
0.25
0.30
0.35
1997 1999 2001 2003 2005
p=0.3260
TB notification rate
0
10
20
30
40
50
60
70
1997 1999 2001 2003 2005 2007
0
20
40
60
80
100
120
1998 2000 2002 2004 20060.00
0.05
0.10
0.15
0.20
0.25
0.30
0.35
1997 1999 2001 2003 2005
p=0.0055Tomsk oblast, RF
Countries that had reported at least one XDR-TB case by Oct 2011
Argentina Burkina Faso Estonia Japan Namibia Republic of Korea The Former Yugoslav Republic of MacedoniaArmenia Bhutan France Kazakhstan Nepal Republic of Moldova TogoAustralia Cambodia Georgia Kenya Netherlands Romania TunisiaAustria Canada Germany Kyrgyzstan Niger Russian Federation TurkeyAzerbaijan Chile Greece Latvia Norway Slovenia UkraineBangladesh China India Lesotho Pakistan South Africa United Arab EmiratesBelarus Colombia Indonesia Lithuania Peru Spain United KingdomBelgium Czech Republic Iran (Islamic Rep. of) Mexico Philippines Swaziland United Republic of TanzaniaBenin Dominican Republic Ireland Mongolia Poland Sweden United States of AmericaBotswana Ecuador Israel Mozambique Portugal Tajikistan UzbekistanBrazil Egypt Italy Myanmar Qatar Thailand Viet Nam
24
Aims
To describe and discuss:• Existing guidelines and definitions• Epidemiology of MDR-TB in Europe and globally
derived from surveillance and M&E (Monitoring and Evaluation)
• The new information on MDR-TB diagnosis• The new information on MDR-TB treatment deriving
from recent meta-analyses• The principles of MDR-TB control, with prevention and
public health aspects
Culture and DST laboratories to diagnose MDR-TB, 2010
Laboratories per5M population
≥1<1NA
20/36 HBCs* have insufficient capacity to diagnose MDR-TB
*HBC= high-burden countryCountries = Afghanistan, Armenia, Azerbaijan, Bangladesh, Belarus, Brazil, Bulgaria, Cambodia, China, DR Congo, Estonia, Ethiopia, Georgia, India, Indonesia, Kazakhstan, Kenya, Kyrgyzstan, Latvia, Lithuania, Mozambique, Myanmar, Nigeria, Pakistan, Philippines, Republic of Moldova, Russian Federation, South Africa, Tajikistan, Tanzania, Thailand, Uganda, Ukraine, Uzbekistan, Viet Nam, Zimbabwe
Culture and DST laboratories to diagnose MDR-TB, 2010
Laboratories per5M population
≥1<1NA
≥1<1
Culture and DST laboratories per 5M, 2010
The “magic” Gene Xpert
27
The message
Any person at high risk of MDR-TB should
• undergo rapid testing
• to start an appropriate treatment immediately
• while an additional sputum specimen
undergoes conventional culture and DST
28
Aims
To describe and discuss:• Existing guidelines and definitions• Epidemiology of MDR-TB in Europe and globally
derived from surveillance and M&E (Monitoring and Evaluation)
• The new information on MDR-TB diagnosis• The new information on MDR-TB treatment deriving
from recent meta-analyses• The principles of MDR-TB control, with prevention and
public health aspects
29
The challenge of MDR
30
Expensive and toxic drugs are necessary
31
1st-line oral
• INH• RIF• PZA• EMB• (Rfb)
Injectables
• SM• KM• AMK• CM
Fluoroquinolones
• Cipro• Oflox• Levo• Moxi• (Gati
)
Oral bacteriostatic 2nd line
Unclear efficacy• ETA/PTA• PASA• CYS
Not routinely recommended, efficacy unknown, e.g., amoxacillin/clavulanic acid, clarithromycin, clofazamine, linezolid, inmipenem/cilastatin, high dose isonizid
Group 1
Group 2
Group 3
Group 4
Group 5
Grouping drugs
32
How to design a MDR-TB regimen
33
Metanalysis of 9,153 cases from 32 Countries
• Treatment success vs. to failure/relapse, was associated with use of:
• later generation quinolones, ofloxacin, ethionamide or prothionamide
• use of 4 or more likely effective drugs in the initial intensive phase, and 3 or more likely effective drugs in the continuation phase.
• Maximum odds of success: initial intensive phase of 7.1-8.5 months and total treatment duration of 18.6-21.5 months
35
Changes to the recommendations on regimen composition between the 2008 and 2011 updates of WHO MDR-TB guidelines
2008 emergency update 2011 updateInclude at least four anti-TB drugs with either certain, or almost certain, effectiveness during the intensive phase of Tx
Include at least 4 2nd -line anti-TB drugs likely to be effective as well as Z during the intensive phase of Tx
Consider adding more drugs in patients with extensive disease or uncertain effectiveness
No evidence found to support the use of > 4 2nd-line anti-TB drugs in patients with extensive disease. Increasing the number of 2nd -line drugs in a regimen is permissible if the effectiveness of some of the drugs is uncertain.
The regimen should include Z and/or E one FQ, one parenteral agent and 2nd -line oral bacteriostatic anti-TB drugs (no preference of oral bacteriostatic 2nd -line anti-TB drug was made).
The regimen should include Z a FQ, a parenteral agent, ethionamide (or prothionamide), and cycloserine, or else PAS if cycloserine cannot be used.
E may be considered effective and included in the regimen if DST shows susceptibility
E may be used but is not included among the drugs making up the standard regimen.
Tx with Group 5 drugs is recommended only if additional drugs are needed to bring the total to 4
Group 5 drugs may be used but are not included among the drugs making up the standard regimen
Intensive phase min 6 months (min 4 months after C conversion) for a total duration of min 18 months after C conversion
Intensive phase min 8 months for a total duration>=20 months
Treatment monitoring
• Treatment failure was detected best with monthly culture in MDR-TB cases.
• Thus the available evidence does not support replacing monthly culture (or quarterly culture) with monthly smear
37
38
39
40
Consilium for MDR-TB case and programme management
41
42
XDR-TB
MDR-TB, resistant to all FLD
MDR-TB, suscep to at least one FLD
Eur Respir J 2007
4,853 C+, 361 MDR, 64 XDR
TDR-TB (MDR+FQ+ Gr IV)
43
Pooled Success = 0.54 (0.48 to 0.60) Inconsistency (I-square) = 97.4%
AuthorN°
SuccessN°
Treated
Avendano 64 72Burgos 30 45Chan 134 194Chiang 72 125Cox 54 77DeRiemer 5 47Escudero 14 18Geerligs 40 43Granich/Banerjee 74 100Holts 1073 2174Kim(Shim) 432 1288Kim(Yim) 118 182Kwon 85 129Leimane/Riekstina 679 945Lockman 128 218Masjedi 16 27Migliori 17 83Mitnick 417 654Munsiff/Li 127 671Narita 39 66ORiordan 19 28Palmero 70 112Park 60 131Perez-Guzman 15 33Quy 79 157Schaaf 20 36Shin 353 535Shiraishi 54 61Tupasi 97 159Uffredi 23 41Van Deun 440 603Yew 84 99
Treatment Success vs Fail and Relapse and Death and Default
44
XDR TB(n=405)
MDR-TB +FQr
(n = 426)
MDR-TB +INJr
(n=1130)
MDR-TB, suscept- to FQ &
Inj(n=4763)
Total
Pooled Outcomes(From study level meta-analysis)
Success 40% (27, 53) 48% (36, 60) 56% (45, 66) 64% (57, 72) 62% (54,69)
Failed/Relapse 22% (15, 28) 18% (14, 21) 12% (9, 15) 4% (2, 6) 7% (4, 9)
Died 15% (8, 23) 11% (3, 19) 8% (3, 14) 8% (5, 11) 9% (5, 12)
Defaulted 16% (8, 24) 12% (1,23) 16% (7, 24) 18% (12,24) 17% (11, 22)
Treatment outcomes by MDR-TB patient group
45
Association between clinical characteristics and treatment success vs. failure/relapse/death in the different MDR-TB
sub-groups
CharacteristicsOdds of success vs
failure/relapse/death N aOR (95%CI)
Male sex (vs female)* 4653 1.0 (0.9, 1.1)Older age (per 10 years older)* 6724 0.8 (0.8, 0.9)HIV positive (vs HIV neg.)* 615 0.3 (0.2, 0.4)Extensive disease (vs not)* 4792 0.5 (0.4, 0.6)Prior TB treatment*
None 1275 1.0 (Reference)FLD only 4410 0.6 (0.5, 0.8)FLD and SLD 618 0.2 0.15, 0.3)
MDR sub-groups: †Not resistant to a FQN nor a 2nd line injectable 4763 1.0 (Reference)Resistant to a second-line injectable, but not a FQN 1130 0.6 (0.5, 0.7)Resistant to a fluoroquinolone, but not a 2nd line injectable 426 0.3 (0.2, 0.40Resistant to both a fluoroquinolone and at least one 2nd line injectable (XDR) 405 0.2 0.2, 0.3)
Pulmonary resection surgery performed (vs not) † 373 1.5 (0.9, 2.6)Experienced a serious adverse event (vs not) † 1511 1.0 (0.8, 1.2)
46
INTENSPHASEN° drugs
XDR MDR–TB+FQr MDR–TB+INJr MDR-TB, susceptible to FQ & Inj
N aOR (95%CI) N aOR
(95%CI)
N aOR (95%CI) N aOR (95%CI)
0 - 2 24
1.0 (reference)
10
1.0 (reference)
29 1.0 (referenc
e) 45 1.0(referenc
e)
3 47 3227 1.7 (0.5, 5.2)
62 1.1(0.5, 2.3)
4 46 1.9 (0.8, 4.3) 49 1.6
(0.7, 3.8)
83 1.3
(0.5, 3.1) 165
1.9(1.0, 3.7)
5 36 1.8 (0.5, 6.6) 35 1.4
(0.3, 6.4)
137 1.2
(0.4, 3.4) 296
1.7
(0.8, 3.8)
6+ 20 4.9(1.4, 16.6) 27 1.1
(0.4, 2.9)
120 1.3
(0.5, 3.3) 380
1.0
(0.5, 1.8)
CONTPHASEN° drugs
XDR MDR–TB+FQr MDR–TB+INJr MDR, susceptible to FQ & Inj
N aOR (95%CI) N aOR
(95%CI)
N aOR (95%CI) N aOR (95%CI)
0 - 2 27 1.0 (ref) 35 1.0 (ref) 46 1.0 (ref) 77 1.0 (ref)
3 32 3.3
(1.3, 8.5)
27 2.5
(0.8, 7.4)
33 12.2 (3.4, 44)
133 5.9
(3.1, 11.0)
4 28 6.1
(1.4, 26.3)
27 3.1
(0.5, 21.1)
101 3.7 (1.7, 8.2)
239 6.0
(2.8, 13.1)
5+ 17 2.3
(0.7, 7.6)
20 2.3
(0.7, 7.2)
100 3.1 (1.7, 6.0)
233 4.7(2.7, 8.1)
47
Age/sex
Country of birth
prev TX >
30 days
Drug received during previous
TX periods
Drug resistance at XDR diagnosis
HospitAdmis (days)
SS conv
(days)
C conv (days)
Outcome
TX dur (mo
43/F IT 3 SRHEZ;FQ,Eth,AK,PAS,C,K,Cyc,Rb,Clof,Dap,Cl,Th
SRHEZ;FQ,Eth,AK,PAS,C,K,Cyc,Rb,Clof
422 No No Died 94
49/F IT 3 SRHEZ;FQ,Eth,AK,PAS,C,K,Cyc,Rb,Clof, Dap,Cl,Th
SRHEZ;FQ,Eth,AK,PAS,C,K,Cyc,Rb,Clof,Dap,Cl,Th
625 No No Died 60
First tuberculosis cases in Italy resistant to all tested drugs GB Migliori ([email protected]), G De Iaco, G Besozzi, R Centis, DM Cirillo WHO Collaborating Centre for TB and Lung Diseases, Fondazione S. Maugeri,
Care and Research Institute, Tradate
Eurosurveillance 2007
48
49
Treatment outcomeXDR-alone XDR+2sli XDR+sliG4 XDR+sliG4EZ
n = 301 n = 68 n = 48 n =42
Cured 1.0 (reference) 0.4 (0.2, 0.8) 0.6 (0.2, 1.6) 0.5 (0.2, 1.7)
Failed 1.0 (reference) 2.1 (1.0, 4.5) 1.8 (0.7, 4.7) 1.9 (0.7, 5.3)
Died 1.0 (reference) 1.6 (0.6, 4.4) 1.7 (0.6, 4.9) 1.8 (0.6, 5.3)
Failed or Died 1.0 (reference) 2.6 (1.2, 4.4) 2.6 (1.1, 6.7) 2.8 (1.0, 7.9)
Defaulted 1.0 (reference) 1.0 (0.3, 2.6) 0.5 (0.2, 1.8) 0.5 (0.1, 2.0)
Treatment outcome XDR alone XDR+2sli XDR+sliG4† XDR+sliG4EZ
n = 301 n = 68 n = 48 n =42
Cured 43 (27, 58) 30 (17, 43) 34 (-, -) 19 (0, 48)*
Failed 20 (15, 25) 29 (8, 50) 33 (-, -) 26 (14, 38)
Died 13 (6, 20) 18 (7, 29) 30 (18, 41)* 35 (21, 50)*
Failed or died 35 (26, 45) 54 (40, 69)* 48 (-, -) 49 (37, 61)
Defaulted 15 (5, 24) 15 (3, 27) 18 (-, -) 19 (6, 32)
50
51
52
53
Building a regimen for XDR-TB
54
55
56
Adverse events0 0.2 0.4 0.6 0.8 1
Alffenaar JWC et al. [46] 0.00 (0.00 - 0.37)Anger HA/Condos R et al. [34] 1.00 (0.78 - 1.00)De Lorenzo S et al. [35] 0.67 (0.09 - 0.99)FortunJ et al. [22] 1.00 (0.29 - 1.00)Koh WJ et al. [45] 0.82 (0.48 - 0.98)Migliori GB et al. [8] 1.00 (0.03 - 1.00)Park IN et al. [44] 0.71 (0.29 - 0.96)Schecter GF et al. [30] 0.22 (0.07 - 0.44)Singla R et al. [31] 0.71 (0.42 - 0.92)Udwadia ZF et al. [32] 1.00 (0.29 - 1.00)Villar M et al. [33] 0.22 (0.03 - 0.60)Von der Lippe B et al. [43] 0.80 (0.44 - 0.97)
Proportion of adverse events (95% CI)
Pooled Proportion = 0.59 (0.49 to 0.68)Chi-square = 61.94; df = 11 (p = 0.0000)Inconsistency (I2) = 82.2 %
Linezolid interruption due to adverse events 0 0.2 0.4 0.6 0.8 1
Alffenaar JWC et al. [46] 0.00 (0.00 - 0.37)Anger HA/Condos R et al. [34] 0.87 (0.60 - 0.98)FortunJ et al. [22] 1.00 (0.29 - 1.00)Koh WJ et al. [45] 0.82 (0.48 - 0.98)Migliori GB et al. [8] 1.00 (0.03 - 1.00)Park IN et al. [44] 0.40 (0.05 - 0.85)Schecter GF et al. [30] 1.00 (0.03 - 1.00)Singla R et al. [31] 1.00 (0.69 - 1.00)Udwadia ZF et al. [32] 0.54 (0.25 - 0.81)Villar M et al. [33] 1.00 (0.03 - 1.00)Von der Lippe B et al. [43] 0.70 (0.35 - 0.93)
Proportion of linezolid interruption due to adverse events (95% CI)
Pooled Proportion = 0.69 (0.58 to 0.79)Chi-square = 37.19; df = 10 (p = 0.0001)Inconsistency (I2) = 73.1 %
AE in Linezolid- containing regimens. Sotgiu et al, ERJ 2012
Meropenem (De Lorenzo S, Alffenar JW et al- ERJ 2012 in press)
57
Variables
Cases: 37
Controlls: 61
Total
Cases
Meropenem/clavulanate -
containing anti-TB regimen
-Italian cohort
Controls
Meropenem/clavulanate -
sparing anti-TB regimen
-Dutch cohort
p-value
Sputum smear conversion at 30 days of treatment, n (%) 16/50 (32.0) 7/32 (21.9) 9/18 (50.0) 0.04
Sputum smear conversion at 60 days of treatment, n (%)
27/48 (56.3) 20/32 (62.5) 7/16 (43.8) 0.22
Sputum smear conversion at 90 days of treatment, n (%)
37/48 (77.1) 28/32 (87.5) 9/16 (56.3) 0.02
Culture conversion at 30 days of treatment, n (%) 24/66 (36.4) 12/37 (32.4) 12/29 (41.4) 0.45
Culture conversion at 60 days of treatment, n (%) 37/62 (59.7) 24/37 (64.9) 13/25 (52.0) 0.31
Culture conversion at 90 days of treatment, n (%) 46/61 (75.4) 31/37 (83.8) 15/24 (62.5) 0.06
Median (IQR) period from start of anti-TB therapy to sputum smear conversion, days
51 (28.0-75.0)52.5 (38.5-65.0) 46.0 (6.0-157.0) 0.85
Median (IQR) period from start of anti-TB therapy to culture conversion, days
42 (16.5-82.0)42.0 (28.0-65.0) 46.0 (13.0-96.0) 0.96
58
Aims
To describe and discuss:• Existing guidelines and definitions• The epidemiology of TB and MDR-TB in Europe and
globally derived from surveillance and M&E (Monitoring and Evaluation)
• The new information on MDR-TB diagnosis• The new information on MDR-TB treatment• The principles of MDR-TB control, with prevention and
public health aspects
TB patients with inappropriate regimen have a 27-fold higher risk of developing MDR-TB
59
Multidrug resistance after inappropriate tuberculosis treatment: A meta-analysisMarieke J. van der Werf, Miranda W. Langenda, Emma Huitric, Davide Manissero
ERJ 2012 in press
60
Global Policy: MDR-TB and XDR-TB
1. Strengthen basic TB control, to prevent M/XDR-TB
2. Scale-up programmatic management and care of MDR-TB and XDR-TB
3. Strengthen laboratory services for adequate and timely diagnosis of MDR-TB and XDR-TB
4. Ensure availability of quality drugs and their rational use
5. Expand MDR-TB and XDR-TB surveillance 6. Introduce infection control, especially in high HIV
prevalence settings7. Mobilize urgently resources domestically and
internationally8. Promote research and development into new
diagnostics, drugs and vaccines
61
Global Policy: MDR-TB and XDR-TB
1. Strengthen basic TB control, to prevent M/XDR-TB2. Scale-up programmatic management and care of
MDR-TB and XDR-TB 3. Strengthen laboratory services for
adequate and timely diagnosis of MDR-TB and XDR-TB
4. Ensure availability of quality drugs and their rational use
5. Expand MDR-TB and XDR-TB surveillance 6. Introduce infection control, especially in high HIV
prevalence settings7. Mobilize urgently resources domestically and
internationally8. Promote research and development into new
diagnostics, drugs and vaccines
62
Global Policy: MDR-TB and XDR-TB
1. Strengthen basic TB control, to prevent M/XDR-TB2. Scale-up programmatic management and care of
MDR-TB and XDR-TB 3. Strengthen laboratory services for adequate and
timely diagnosis of MDR-TB and XDR-TB4. Ensure availability of quality drugs and
their rational use5. Expand MDR-TB and XDR-TB surveillance 6. Introduce infection control, especially in high HIV
prevalence settings7. Mobilize urgently resources domestically and
internationally8. Promote research and development into new
diagnostics, drugs and vaccines
63
Global Policy: MDR-TB and XDR-TB
1. Strengthen basic TB control, to prevent M/XDR-TB2. Scale-up programmatic management and care of
MDR-TB and XDR-TB 3. Strengthen laboratory services for adequate and
timely diagnosis of MDR-TB and XDR-TB4. Ensure availability of quality drugs and their
rational use5. Expand MDR-TB and XDR-TB surveillance 6. Introduce infection control, especially in
high HIV prevalence settings7. Mobilize urgently resources domestically
and internationally8. Promote research and development into new
diagnostics, drugs and vaccines
64
Global Policy: MDR-TB and XDR-TB
1. Strengthen basic TB control, to prevent M/XDR-TB2. Scale-up programmatic management and care of
MDR-TB and XDR-TB 3. Strengthen laboratory services for adequate and
timely diagnosis of MDR-TB and XDR-TB4. Ensure availability of quality drugs and their rational
use5. Expand MDR-TB and XDR-TB surveillance 6. Introduce infection control, especially in high HIV
prevalence settings7. Mobilize urgently resources domestically and
internationally
8. Promote research and development into new diagnostics, drugs and vaccines
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1966, the last anti-TB drug was discovered
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Bedaquiline
Delamanid
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Carlo Forlanini,first notes on Pneumothorax
January 7th, 1907
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Interventions over time: old weapons might be useful again to manage XDR
First sanatorium Germany, 1857 First Dispensary,
Scotland, 1897
Koch, Mtb,1882
Drugs, 1945-1962
MMR,1950-1980
Fox:Ambulatory treatment, 1968
Styblo model, 1978
DOTS, 1991
sanatoria Outbreak Management,
Risk Group Managementscreening
BCG vaccination
drug therapy
Socio-economic improvement
Pneumotorax, Italy, 1907
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Pneumothorax
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“Nobody wants me around..”
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XDR and TB control: which future ?