2016

1

2

3

960 150 120HIV

40

48

19

2035

4

(SDGs) WHO TB

2020 2025 2030 2035TB

201535% 75% 90% 95%

TB2015

20% 50% 80% 90%TB 0% 0% 0% 0%

Projected acceleration of TB incidence decline to target levels

2025

10%

-5%/

2%/

17%

5

6

2015

B2035

7

2005-2014

16,472

15,378

14,48014,265

13,336 13,237

12,63412,338

11,52811,326

72.5

67.4

63.2 62.0

57.8 57.2

54.5 53.0

49.4 48.4

30

40

50

60

70

11,000

12,000

13,000

14,000

15,000

16,000

17,000

18,000

2005 2006 2007 2008 2009 2010 2011 2012 2013 2014

(

1\

10

)

8

9

Effect from Nationwide 9M INH in Children in TaiwanMOHW103-CDC-C-315-000302

Txstatus

<5Y 5-12Y 13-17Y

No. TB No. Incidence No. TB No. Incidence No. TB No. Incidence

Ever 2550 1 35 6703 8 75 2395 5 125

Never 804 5 600 1812 17 332 1257 14 1118

RR: 0.06 (<0.01 ~ 0.34)94% protection

RR: 0.22 (0.06 ~ 0.74)78% protection

RR: 0.11 (0.02 ~ 0.34)89% protection

10

11

Txstatus

<13Y 13-29Y ≥30Y

No. TB Incidence No. TB Incidence No. TB Incidence

Ever 29169 7 63 14067 8 123 13597 15 113

Never 8307 17 420 10939 45 1130 25146 59 404

Effect from Nationwide 9M INH in Taiwan

≥30YRR: 0.27 (0.08 ~ 0.64)

73% protection

13-29YRR: 0.10 (0.03 ~

0.22)90% protection

12

Period: 2010-2012Contacts born before 1986: 5,145Contacts of highly infectious index: 3,810Complete TST: 2,217 (58.2%)Complete QFT: 2,259 (59.3%)TST/QFT both available: 2,202 (57.8%)

HR: 50.9 (5.88 - 439)

LTBICLINICAL APPROACH OF LTBI DIAGNOSIS AND TREATMENT

IGRA vs. TST

13

1. identify Priority group

Tuberculosis Complex

ESAT-6 CFP-10 TB7.7 Environmental Strains

ESAT-6 CFP-10 TB7.7

M tuberculosis + + + M abcessus - - -M africanum + + + M avium - - -M bovis + + + M branderi - - -

M celatum - - -BCG substrain M chelonae - - -

gothenburg - - - M fortuitum - - -moreau - - - M gordonii - - -tice - - - M intracellulare - - -tokyo - - - M kansasii + + -danish - - - M malmoense - - -glaxo - - - M marinum + + -montreal - - - M oenavense - - -pasteur - - - M scrofulaceum - - -

M smegmatis - - -M szulgai + + -M terrae - - -M vaccae - - -M xenopi - - -

IGRA

IGRA BCG NTM 55 IGRA

14

954 close contacts

142 QFT-positive/TST-positive

Chemoprophylaxis RIF and/or INH

No active TB

51 QFT-positive(49 TST-positive)

Mean follow-up >3.5 yr

Not treated

17 developed active TB

343 TST negative

5 QFT-positiveTST-negative

Not treated

2 developed active TB

413 TST positive

Not treated Not treated

No active TB No active TB

198 QFT-positive 756 QFT-negative

Diel R. AJRCCM 2011;183:88-95. 15

Negative and Positive Predictive Value of a Whole-Blood IFN-� Release Assay for Developing Active TB

Correlation between TST and QFTTST induration (mm) No. QFT-positive

10 – 14 55 4 (7.2%)

15 – 19 30 6 (20.0%)

20 – 24 7 2 (28.6%)

25 – 29 0

30 – 34 1 1 (100%)

-MOHW104-CDC-C-114-123201

0 34

MOHW

48.9

31.4

14.1 14.118.8

34.1

27.3

0

10

20

30

40

50

60

70

<13 13-26 27-34 35-44 45-54 55-64 >=65

%

Contact Age

TST(+) QFT(+) Double(+)

Results of TST and IGRA

17

(681) (547) (485) (293) (209)(278) (1142)

18

• 15-61%

• 2015.10.05 3,975 TST+IGRA

LTBI

19

• N = 3,975 up to 2015/10/5

1986.1.1

518

527

2008.4.1 2016.3.1

LTBI 1986.1.1

LTBI TST IGRA

TST IGRA

5 TSTIGRA LTBI 3

20

�••

�

��

≥ ≥

≥

* TB Nil

22

23

2. exclude Active TB

24

3. identify Supervised / Short-course preventive therapy

12 2703HP 9H

25

Efficacy of INH Preventive Therapy (IPT)

ATS. AJRCCM 2000;161:S221-47.

Directly Observed Preventive Therapy (DOPT)

2016 3 1

2016 4 1(3HP)

26

once weekly x 3 months = only 12 doses900mg Isoniazid (INH) +900mg Rifapentine (RPT)

2008.4.1 2016.3.1

LTBI 1986.1.1

LTBI TST IGRA

TST IGRA

9H 9H 3HP

- ( 500 )

5 TSTIGRA LTBI 3

27

DOPT

28

29

4. monitor Side effects

2473

3227

4175

3263

700Risk of INH-

induced hepatitis

Kopanoff DE, et al. Am Rev Respir Dis 1978;117:991-1001.

• USPHS• 13838 cases• 1971/07 ~ 1972/11

31

2008 2009 2010 2011 2012 2013 2014

Case No. 1402 2628 3902 4948 5906 5485 4082

Interruption 515 944 1376 1829 1509 1196 857

Due to AE (%) 16(1.1%)

27(1.0%)

57(1.5%)

117(2.4%)

153(2.6%)

106(1.9%)

85(2.1%)

MOHW104-CDC-C-315-000203

<10 10-19 20-29 30-39 40-49 50-59 60-69 70-79 ≥80

Case No. 11809 9486 2874 1073 1169 1015 462 253 212

Follow (p-m) 79713 72140 22839 7524 8291 7274 3312 1774 1516

AE (%) 102(0.86)

125(1.32)

100(3.48)

54(5.03)

72(6.16)

66(6.50)

32(6.93)

11(4.35)

3(1.42)

Hepatitis 13(0.11)

25(0.26)

42(1.46)

27(2.52)

29(2.48)

28(2.76)

20(4.33)

3(1.19)

0(0.00)

Admission 3 3 0 3 3 2 2 0 0

32

32

19.3%

10.0%

18.6%

24.8%

33.3%

10.7%

37.1%

43.3%

15.5%

37.9%

9.6%

7.1%5.5%

14.3%

3.6%2.0%

0%

5%

10%

15%

20%

25%

30%

35%

40%

45%

50%

All age <13 13-29 >=30

HEPATITIS HEPATITIS SEVERE SKIN RASH SKIN RASH SEVERE

MOHW103-CDC-C-315-000302

Follow-up Liver Function Tests

0

5

10

15

20

25

30

35

40

AST(U/L)

ALT(U/L)

Totalbilirubin(mg/dL)

AST(U/L)

ALT(U/L)

Totalbilirubin(mg/dL)

AST(U/L)

ALT(U/L)

Totalbilirubin(mg/dL)

AST(U/L)

ALT(U/L)

Totalbilirubin(mg/dL)

3HP 9H*

* *

* * *

-

MOHW104-CDC-C-114-123201

34

yes no

•

••

>=35

HBsAg, anti-HCV AbHIV ELISA/Combo Ag+Ab

<35

*

���

TB

• ICD-10– Z201–

R76.1

•CXR

• LTBI

35

•IGRA LTBI

•

•

36

*

E4003C 100

E4004C IGRA ( ) 300

E4005C 100

• 1 1• 5 IGRA

– Z201R76.1

–E4003CE4004C IGRA ( )E4005C

– TB –

37

38

Latent TB Infection - PASS

1. identify Priority group

2. exclude Active TB

3. provide Supervised / Short-course preventive therapy

4. monitor Side effect