LTBI: Who to Test & When to Treat

Transcription

1 LTBI: Who to Test & When to Treat TB Intensive May 10 th, 2016 David Horne, MD, MPH Harborview Medical Center University of Washington

2 DISCLOSURES I have no disclosures or conflicts of interest to report

3 LTBI Treatment Outline LTBI Guidelines: Who to Test Additional Risk Factors for TB Progression Estimating Individual TB Risk When to Treat: Risks vs. Benefits

4 Variability in TB Outcomes 80% of U.S. TB cases due to reactivation: PREVENTABLE ~90% will not progress to TB Small NEJM 2001

5 Targeted Testing & LTBI Fundamental Principles: As a low incidence country, targeted testing and treatment of LTBI is essential component of the strategic plan for TB elimination in the US Focus on high risk individuals Goal: Reduce reservoir of latent TB A Decision to Test is a Decision to Treat.

6 Baseline TB Progression Risk Horsburgh NEJM 2004

7 LTBI: Screening & Treatment Balance

8 LTBI: Screening & Treatment Balance 80% of U.S. TB cases due to reactivation LTBI treatment is effective Minority of individuals with positive LTBI test progress to TB Adverse effects of Tx Poor completion rates Cost/Resources

9 LTBI Testing Guideline Recommendations

10 Who to Screen? Targeted Testing Screening should be targeted to those at higher risk of TB who would benefit from treatment NOT the general population Target populations with: Increased rates of recent TB infection Increased risk of progression to active TB

11 Target: Risk of Recent Infection Recent infection (contacts and converters): 4-5% risk of developing active disease within the first 1-2 years Risk may double if <4 years old 40% progression to disease in infants younger than twelve months old CDC definition of Converter : >10 mm increase in PPD within 2 year period

12 Target: Risk of Recent Infection Close contacts of infectious TB cases Recent immigrants (< 5 years) TB endemic countries Residents/employees of high-risk congregate settings Healthcare, Correctional, Long-term care facilities Medically underserved (consider local demographics) Homeless Migrant workers Low-cost hotel dwellers or crowded living conditions Street drug users Racial and ethnic minorities Children of parents with these TB risk factors

13 US LTBI Prevalence: Subgroups Horsburgh, NEJM 2011

14 Target: Risk of Progression HIV Individual with abnormal CXR compatible with past TB Infants and young children < 5 yrs. age ( Sentinels of transmission ) Specific medical conditions Diabetes, Immunosuppression, Renal failure, Lymphoma/Leukemia, Head and neck CA, Silicosis, Alcoholism, Gastrectomy/Jejunoileal bypass, Malnutrition

15 Target: Risk of Progression HIV infection Screen as early as possible (anergy increases as HIV disease advances) Screen every 6-12 months (depends on lifestyle and environmental TB risks) Exceptionally high rate of reactivation (7-10% per year) Rapid development to active disease once newly infection

16 Target: Risk of Progression TB4: Individuals with abnormal CXR compatible with past (untreated) TB Risk of active disease is 10x that of a person with a normal x-ray and no other risk factors Higher underlying bacillary load *PPD and sputum part of screening in spite of stability of chest x-ray and history of treatment, must rule out active TB disease with cultures before starting LTBI treatment

17 Target: Risk of Progression Risk Factor Relative Risk (95% CI) Advanced untreated HIV 9.9 (8.7-11) Close Contacts 6.1 ( ) CXR c/w prior healed TB 5.2 ( ) Prednisone >15mg/day 2.8 ( ) Chronic Renal Failure 2.4 ( ) TNF alpha inhibitor 2.0 ( ) Poorly controlled diabetes 1.7 ( ) Weight <10% below normal 1.6 ( ) Smoking 1.5 ( ) Horsburgh NEJM 2011

18 TST Cut-offs Reflect Risk Interpretation of TST Results 5mm HIV close contact of infectious case fibrotic changes on CXR consistent with old TB severely immunosuppressed (e.g. organ transplant, TNFα blockade) 10mm Recent immigrants (<5 yrs) from high prevalence countries Residents/employees of high-risk congregate settings TB lab personnel Medical conditions: silicosis, DM, chronic renal insufficiency. leukemia/lymphoma, head/neck/lung cancer, weight loss of >10% of ideal body weight, gastrectomy/jejunoileal bypass IVDA Children < 4 years of age (screened if there are risk factors) 15mm (no need to screen) - all others 2000 ATS/CDC Guidelines

19 IGRA Screening & Low LTBI Risk IGRA responses may change over time 2400 U.S. HCW, serial TST, QFT, T-SPOT (Dorman AJRCCM 2014) Conversions occurred: TST 0.9% QFT 6.1% T-SPOT 8.3%

20 Guideline Recommendations Presumed Recent Infection with M. tuberculosis Close contacts Recent immigrants (< 5 years) from high TB regions Known converters Children < 5 years Homeless, IVDU, institutional setting exposures Increased Risk for Progression HIV infection CXR suggestive of old TB (fibrotic) Co-morbidities, e.g. DM, silicosis, dialysis, cancer Medically immunosuppressed ATS Guidelines, 2000 Don t Test Low Risk Individuals

21 LTBI Risk: Beyond the Guidelines

22 Lifetime TB Risk: Age Matters Horsburgh NEJM 2004 Horsburgh, NEJM

23 Risk for TB Progression: Effect of Age on Co-factors Horsburgh NEJM 2004

24 TB among Foreign Born Foreign-born persons: ~60% of U.S. TB cases are foreign-born Emphasis on newcomers to the U.S. (<5 years), However, elevated TB rates may persist for longer High and intermediate incidence countries (Asia and Pacific Islands, Africa, Central and South America, Eastern Europe, Middle East)

25 Unlike U.S. Born, TB Cases among Foreign Born have not declined U.S. TB cases 64% are foreign born (2013)

26 TB Rates Remain Elevated in Foreign Born Years after Immigration Cain JAMA 2008

27 Long-term Reactivation Risk Differs by Region of Origin Cain AJRCCM 2007

28 Seattle-King County Experience PHSKC Annual Report on TB, 2010

29 Linas, AJRCCM 2011 Seattle-King County Experience

30 Predicting Risk of TB Progression

31 Predicting Risk of TB Progression: tstin3d.com

32 TST in 3D Caveats May overestimate individual risk of TB progression Assumes baseline annual risk of TB = 0.1% in healthy persons If patient is recent close contact, then risk of TB is 5% for the first 2 years and 0.1% thereafter Horsburgh differences Same baseline risk, lower risks following new conversion by age group Lower risks for progression in co-existing conditions May overestimate INH DILI risk No risk estimates for other LTBI treatment regimens

33 IGRA: Screening in Low Risk In low risk patients with IGRA results near the cutpoint, conversions and reversions are common Unlike TST, no additional criteria for conversion Bottom line: the value of IGRA (TB ag nil) should be evaluated by clinician

34 TST & IGRA Agreement US Born Foreign Born Take advantage of poor test agreement in patients at high risk of TB progression if latently infected (e.g. HIV-positive, TNF-alpha blocker therapy) Dual testing: if TST negative then perform IGRA and treat for any positive tst Ghassemieh AJRCCM 2016

35 When to Treat: Risks vs. Benefits

36 What if Minimum TB Risk Level for Offering Treatment? At what level of risk for TB progression should you recommend LTBI Treatment? No guideline recommendations Some experts use cut-offs of 3% risk or 5% risk Based on USPHS study estimated risk of age-related INH toxicity (50 64 = 2.3%, >65 years = 4.6 percent) Remember: Seattle study, 0.28% of >65 years LTBI treatments other than 9H are lower risk for hepatotoxicity

37 Dobler, ERJ 2015 A Decision Aid for LTBI Treatment

38 Shared Decision Making Firm cut-off will not be appropriate for all situations Individual costs involve more than DILI Discuss with patient using available tools Patients need to be motivated to actually complete treatment Completion rates < 50% in many series

39 Summary Beyond Recommended Screening remember the impact of age, HIV, abnormal CXR, and TB incidence in country of origin Screening in Low Risk Individuals Don t Do Individual Risk Estimation TST in 3D Dual Testing Sometimes useful Treatment is a shared decision