결핵노출접촉자감염관리 서울아산병원감염내과 김성한

TB incidence (2012) TB incidence South Korea 108 China 73 Taiwan 68 Portucal 26 Japan 19 Spain 14 US 3.6 * unit- per 100,000 population Adapted from WHO

Adapted from WHO

Emerg Infect Dis 2015;21:1913-20

Reasons for not-declining TB High prevalence of LTBI in elderly population Increasing population with DM High smoking rate Inadequate patient management Immigrants from high-burden countries Emerg Infect Dis 2015;21:1913-20

Exposure to contacts 1. Intensity 2. Duration No infection (50%) Infection (25-50%) CMI No disease (90%) Disease (10%) Early progressive (5%) Late recrudescent (5%) Primary progressive TB Postprimary TB Reactivation TB

Factors for the TB transmission The characteristics of the index patient smear positivity, cavity, cough The characteristics of the contact children < 5 years immunocompromised The feature of exposure time spent with the index patient degree and duration of proximity characteristics of the place

1574 culture-positive TB in SF DNA fingerprints for 1359 (86%) Of 71 clusters of matching fingerprints, 28 (39%) had a smear-negative TB 183 secondary cases in these 71 clusters, of whom 32 (17% [95% CI 16-32%]) were attributed to infection by smear-negative

551 (98%) of 561 patients with smearpositive TB 123 (73%) of 171 patients with smearnegative TB

Smear-negative TB 결론 Smear-negative TB 의경우전파가덜되기는하지만전체결핵전파의최소 20% 를차지한다 격리필요 Smear-negative TB 의 3/4 은 Xpert TB/RIF 검사로 detection 할수있다 적극적인검사필요

5 세미만 Int J Tuberc Lung Dis 1997;1:38-43 South Africa > 98% BCG vccination Of 155 children under 5 years of age in contact with 80 index cases 14% infected, 34% diseased, 52% not infected Of 154 household members over 5 years 21% diseased

HIV 100 배이식 50 배투석 20 배 최근접촉 15 배 Old TB lesion 10 배 스테로이드 5 배 TNF blocker 3 배 DM 2-3 배 담배 2-3 배

Contact investigations Infectious period AFB (+): 3 months before airborne precaution or persistent AFB (-) AFB (-): 1 month before airborne precaution Exposure intensity Infectiousness of index case Presence or absence of risk procedure Proximity: a shared airspace Overlap with infectious period Duration of exposure: 4 hours, 8 hours, 100 hours? Presence or absence of PPE

Household vs casual contact Household contact Those who lived in the same house as the index patient Casual contact Those who did not live in the same house as the index patient; these were mostly family, workplace and school contacts Eur Respir J 2013;41:758-60

Size of exposure site Small- < 20 m 2 (car, bedroom, living room or office) Large- 20 m 2 (restaurant) Eur Respir J 2013;41:758-60

Exposure sites With ventilation- with windows Without ventilation- without windows Eur Respir J 2013;41:758-60

Importance of household contact Eur Respir J 2013;41:758-60

Brazil, close contact definition changed > 100 hours in total before 2005 Active TB 2% (16/810) LTBI 62% (496/794) > 4 hours a week since 2005 according to TB Trial Consortium Active TB 2.7% (35/1310) LTBI 69% (877/1275) NN to screen (contact/new case) 50 37 NN to contact trace (index case/new case) 16 10

Contact tracing 결론 Household contact 은감염이잘되지만, casual contact 은감염이덜된다 5 세미만및면역저하환자는감염이잘된다 Duration of exposure 등은 recall bias 등으로부정확할가능성이높다 주당 4 시간을많이사용 감염이발생한상황 (household, prison, aerosol procedure) 이더좋은지표이다

Priorities for contact investigation Case characteristics Susceptibility and vulnerability of contacts (contact risk factors) Circumstances of the exposures (exposure environment) MMWR 2015;54:RR-15

Case characteristics High-priority cases Pulmonary, laryngeal, or pleural TB with AFB (+) and/or cavity Medium-priority cases Pulmonary, laryngeal or pleural TB with AFB (-) and/or non-cavity Low-priority cases Extrapulmonary TB MMWR 2015;54:RR-15

Contact risk factors HIV Household contacts Contacts in congregated settings < 5 years old Certain medical procedure Certain medical risk factors (DM, silicosis, gastrectomy ) * medium-priority: 5-14 years old MMWR 2015;54:RR-15

Exposure environment High-priority contacts > 8 hours in a small poorly ventilated space > 16 hours in a small well ventilated space > 24 hours in a classroom size space > 100 hours in a large open space Medium-priority contacts > 4 hours in a small poorly ventilated space > 8 hours in a small well ventilated space > 12 hours in a classroom size space > 50 hours in a large open space MMWR 2015;54:RR-15

High-priority contacts > 8 hours in a small poorly ventilated space > 16 hours in a small well ventilated space > 24 hours in a classroom size space > 100 hours in a large open space Medium-priority contacts > 4 hours in a small poorly ventilated space > 8 hours in a small well ventilated space > 12 hours in a classroom size space > 50 hours in a large open space MMWR 2015;54:RR-15

MMWR 2015;54:RR-15

High- and medium-priority contacts MMWR 2015;54:RR-15

Previous TST (+) MMWR 2015;54:RR-15

활동성결핵및잠복결핵진단 전통적인방법 - 결핵피부반응검사 새로운방법 (2000 년대중반이후 )- TB IGRA

Gene difference between M. TB and NTM M. bovis (BCG strain) Most NTM RD1 RD2.RD16 M. tuberculosis ESAT-6 CFP-10 Potent T-cell antigens

Lalvani A, et al. Curr Opinion Infect Dis 2007;20:264-71

TTT (targeted tuberculin test) > 5 mm > 10 mm > 15 mm HIV Other conditions All others Recent contacts CXR c/w old TB Conferring inc. risk From an edemic area IDU Employees of high risk TB lab personnel 2000 ATS guideline

18~20 years observational study after TST (n=82,269) Induration size of TST No. of cases Average annual rate Age (years) Age (years) 1-6 7-12 13-18 total 1-6 7-12 13-18 total 16 mm 79 70 73 160 238 123 149 160 11-15 mm 22 21 16 98 186 89 65 98 6-10 mm 11 14 13 46 59 40 44 45 Comstock GW, et al. Am J Epidemiol 1974:99:131-8

Landmark longitudinal study Diel R, et al. AJRCCM 2008;177:1164-70 - 601 recent contact persons with active TB for 2 years F/U 6 TB development Diel R, et al. AJRCCM 2011;183:88-95 - 1033 recent contact persons with active TB for 4 years F/U 19 TB development - QFT (+) without INH tx 13% (19/158) TB - TST ( 5 mm) without INH tx 3% (17/555) TB - TST ( 10 mm) without INH tx 5% (10/207) TB

Landmark HCW study Dorman, et al. AJRCCM 2014;189:77-87 - 2,563 HCW in US - TST, QFT, T-SPOT baseline and every 6 months for 18 months - (+) 5% by TST, 0.9% conversion - (+) 5% by QFT, 6% conversion - (+) 6% by T-SPOT, 8% conversion - About ¾ of converter became negative when retested 6 months later false-positive d/t short- and long-term variability

김성한등 Am J Transplant 2011;11:1927-35

이유미, 김성한등 J Infect 2014;69:165-73

김성한등 J Antimicrob Chemother 2015;70:1567-72

IGRA in LTBI Recent contact (recommended) - Recent infection (intimate contact) Health care workers (not recommended) - Recent infection (intimate contact) vs insignificant infection (casual contact) Immunocompromised patients (?) - Remote infection reactivation

Recent HCW study King, et al. AJRCCM 2015;192:367-73 - 42,155 T-SPOT from 16,076 HCW in US - Mean conversion rate 0.8% (0.0%-2.5%) - Mean reversion rate 17.6% - T-SPOT as reliable as TST in serial testing

증례 1 장 O 록 M/71 세 - 2015년 12월 18일 KT - 2016년 2월 8일기침을주소로응급실내원 - 홍O인전공의가 5분가량문진과청진 * ER 홍O인전공의 : AFB (-) and non-cavitary CXR? IGRA? TST?

MMWR 2015;54:RR-15

High- and medium-priority contacts

증례 1 장 O 록 M/71 세 - 2015년 12월 18일 KT - 2016년 2월 8일기침을주소로응급실내원 - 홍O인전공의가 5분가량문진과청진 * ER 홍O인전공의 : AFB (-) and non-cavitary 증상있으면 CT 촬영해야함 CXR TST (not done) TST 8 weeks later (IGRA 8 weeks later?)

증례 2 김 O 균 M/47 세 - 2013 년 7 월 KT - 당시 IGRA (+) INH 9 months - 2016 년 3 월초같이사는어머니가 AFB (+) and non-cavitary TB 진단 - CXR normal - 2016 년 4 월 IGRA (+) retreatment?

Previous TST (+)