Thank you for viewing this presentation. We would like to remind you that this material is the property of the author. It is provided to you by the ERS

Thank you for viewing this presentation.

We would like to remind you that this material is the property of the author.

It is provided to you by the ERS for your personal use only, as submitted by the

author.

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






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-TB

FUNDING: 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

Definitions

MDR-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






Notified cases of MDR-TB

Cases of MDR-TB

0–99

100–999

1000–9999

≥10 000

NA

Estimated absolute numbers of reported cases with MDR-TB*


Cases of MDR-TB

0–99

100–999

1000–9999

≥10 000

NA*among reported pulmonary TB patients

<100100–999

1000–9999>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


0

10

20

30

40

50

60

2005 2006 2007 2008 2009 2010

Nu

mb

er

of

pa

tie

nts

(th

ou

sa

nd

s)

19,000

53,000

Global Plan target ~270,000 in 2015

0

50

100

150

200

250

300

SE Asi

a

W. P

acifi

c

Europe

Africa

EMR

Americ

as

World

Not on treatment

Treated

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 p

ati

en

ts

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

Americ

as

SE Asi

a

W P

acific

EMR

Africa

WORLD

% o

f p

atie

nts

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

0

10

20

30

40

50

60

70

80

90

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






Culture and DST laboratories to diagnose MDR-TB, 2010

Laboratories per5M population

≥1

<1

NA

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

<1

NA

≥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






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

INTENSPHASE

N° 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)

CONTPHASE

N° 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



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


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


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






62



MDR-TB and XDR-TB 3. Strengthen laboratory services for adequate and

timely diagnosis of MDR-TB and XDR-TB






63




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 settings

7. Mobilize urgently resources domestically and internationally

8. Promote research and development into new diagnostics, drugs and vaccines

64




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


internationally

8. Promote research and development into new diagnostics, drugs and vaccines

65

1966, the last anti-TB drug was discovered

66

Bedaquiline

Delamanid

67

Carlo Forlanini,first notes on Pneumothorax

January 7th, 1907

68

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 Management

screening

BCG vaccination

drug therapy

Socio-economic improvement

Pneumotorax, Italy, 1907

69

71

Pneumothorax

72

“Nobody wants me around..”

73

74

XDR and TB control: which future ?

Documents

Thank you for viewing this presentation. We would like to remind you that this material is the property of the author. It is provided to you by the ERS