2016 1 2
960 150 120 48 HIV 40 19 3 2035 (SDGs) WHOTB 2020 2025 2030 2035 TB 2015 TB 2015 TB 35% 75% 90% 95% 20% 50% 80% 90% 0% 0% 0% 0% 4
Projected acceleration of TB incidence decline to target levels 2%/ 2025 10% 17% -5%/ 5 2015 6
2035 B 7 2005-2014 18,000 17,000 16,000 72.5 16,472 67.4 15,378 63.2 62.0 57.8 57.2 70 60 ( 1 \ 10 ) 15,000 14,000 14,480 14,265 54.5 53.0 49.4 48.4 50 13,336 13,237 13,000 12,634 12,338 40 12,000 11,528 11,326 11,000 2005 2006 2007 2008 2009 2010 2011 2012 2013 2014 30 8
9 Effect from Nationwide 9M INH in Children in Taiwan MOHW103-CDC-C-315-000302 Tx <5Y 5-12Y 13-17Y status 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
Tx status Effect from Nationwide 9M INH in Taiwan <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 13-29Y RR: 0.10 (0.03 ~ 0.22) 90% protection 30Y RR: 0.27 (0.08 ~ 0.64) 73% protection 11 Period: 2010-2012 Contacts born before 1986: 5,145 Contacts of highly infectious index: 3,810 Complete 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) 12
1. identify Priority group IGRA vs. TST LTBI CLINICAL APPROACH OF LTBI DIAGNOSIS AND TREATMENT 13 IGRA Tuberculosis ESAT-6 CFP-10 TB7.7 Environmental ESAT-6 CFP-10 TB7.7 Complex Strains 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 - - - IGRABCGNTM5 5IGRA 14
Negative and Positive Predictive Value of a Whole-Blood IFN- Release Assay for Developing Active TB 954 close contacts 198 QFT-positive 756 QFT-negative 142 QFT-positive/ TST-positive 5 QFT-positive TST-negative 51 QFT-positive (49 TST-positive) 413 TST positive 343 TST negative Not treated Not treated Chemoprophylaxis RIF and/or INH Not treated Not treated 17 developed active TB Diel R. AJRCCM 2011;183:88-95. 2 developed active TB No active TB No active TB No active TB Mean follow-up >3.5 yr 15 Correlation between TST and QFT TST 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
Results of TST and IGRA 70 60 50 48.9 TST(+) QFT(+) Double(+) % 40 30 20 31.4 14.1 14.1 18.8 34.1 27.3 10 0 <13 13-26 27-34 35-44 45-54 55-64 >=65 (278) (1142) (681) (547) (485) (293) (209) Contact Age 17 LTBI 2015.10.053,975TST+IGRA 15-61% 18
N = 3,975 up to 2015/10/5 1986.1.1 518 527 19 2008.4.1 2016.3.1 LTBI 1986.1.1 LTBI TST IGRA TST IGRA 5TST IGRALTBI3 20
* TBNil 22
2. exclude Active TB 23 3. identify Supervised / Short-course preventive therapy 12270 3HP 9H 24
Efficacy of INH Preventive Therapy (IPT) Directly Observed Preventive Therapy (DOPT) ATS. AJRCCM 2000;161:S221-47. 25 201631 201641 (3HP) once weekly x 3 months = only 12 doses 900mg Isoniazid (INH) + 900mg Rifapentine (RPT) 26
2008.4.1 2016.3.1 LTBI 1986.1.1 LTBI TST IGRA TST IGRA 9H 9H3HP - (500) 5TST IGRALTBI3 27 DOPT 28
4. monitor Side effects 29 Risk of INHinduced hepatitis 4175 3263 700 3227 USPHS 13838 cases 1971/07 ~ 1972/11 2473 Kopanoff DE, et al. Am Rev Respir Dis 1978;117:991-1001.
MOHW104-CDC-C-315-000203 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%) <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 (%) Hepatitis 102 (0.86) 13 (0.11) 125 (1.32) 25 (0.26) 100 (3.48) 42 (1.46) 54 (5.03) 27 (2.52) 72 (6.16) 29 (2.48) 66 (6.50) 28 (2.76) 32 (6.93) 20 (4.33) 11 (4.35) 3 (1.19) Admission 3 3 0 3 3 2 2 0 0 3 (1.42) 0 (0.00) 31 MOHW103-CDC-C-315-000302 50% HEPATITIS HEPATITIS SEVERE SKIN RASH SKIN RASH SEVERE 45% 43.3% 40% 37.9% 37.1% 35% 33.3% 30% 25% 24.8% 20% 15% 19.3% 15.5% 14.3% 18.6% 10% 5% 5.5% 10.0% 10.7% 9.6% 3.6% 7.1% 2.0% 0% All age <13 13-29 >=30 32 32
Follow-up Liver Function Tests 40 35 3HP 9H * * * 30 25 20 15 10 5 0 AST (U/L) ALT (U/L) Total bilirubin (mg/dl) AST (U/L) ALT (U/L) * * * Total bilirubin (mg/dl) AST (U/L) ALT (U/L) Total bilirubin (mg/dl) AST (U/L) ALT (U/L) Total bilirubin (mg/dl) - MOHW104-CDC-C-114-123201 yes no >=35 <35 HBsAg, anti-hcv Ab HIV ELISA/Combo Ag+Ab * 34
TB ICD-10 Z201 R76.1 CXR LTBI 35 IGRALTBI * E4003C 100 E4004C IGRA() 300 E4005C 100 11 5IGRA 36
Z201 R76.1 E4003C E4004C IGRA () E4005C TB 37 Latent TB Infection - PASS 1. identify Priority group 2. exclude Active TB 3. provide Supervised / Short-course preventive therapy 4. monitor Side effect 38