Latent TB Infection (LTBI) Strategies for Detection and Management Patrick T. Dowling MD,MPH Professor and Chair Dept of Family Medicine David Geffen School of Medicine at UCLA Pri-Med March 29 2014 Pdowling@mednet.ucla.edu Faculty Financial Disclosure Patrick T. Dowling, MD, MPH has no financial relationships to disclose. TB Archetypal Disease of Poverty 17% of the 22 countries that have 80% of all TB have per capital GDP < $760. Poorest have least access to RX. ENEMIES OF HUMANKIND IMDs AIDS 2.6 million deaths/yr TB 1.2 million deaths/yr High income countries with 5% of the burden planning for TB elimination. MALARIA 700K deaths/yr Source: WHO 2012 TB THE FACTS 1/3 of the World is Infected 2 + Billion.. Life lost to TB every 24 seconds; 3900/day 8.6 million new cases 2012 (1.1 M with HIV) - 3 million not reported to PH. Kills 1.2 million per year; 2 nd leading High Risk groups for TB in US Foreign born from high incident countries Elderly Minorities Immuno-compromised Alcohol, Tobacco, substance abuse, mental health + homeless infectious cause. WHO Global TB Report 2013 Eric Pevzner Ph.D Weblinar 1-12-2011 1
TB rates Children < 5 y/o. in US Child / Parent nativity Relative Rate TB US born child and parents 1 FB child and parents 32x US born child; FB parents 6x TB U.S. BORN vs. FOREIGN BORN 2007 U.S. Born Foreign Born TOTAL Hispanic 4.4 19.3 10.5 Black 11.5 9.1 51.3 Asian / PI 5.3 40.6 29.4 White 1.2 6.3 8.0 AI / AN 7.9 -- 8.0 Pang, J Pediatrics 2014 Mar;133(3):e494-504. Source: CDC, March 20048 Healthy Immune System Response to TB bacillus Takes two to ten weeks Halts progression TST Skin test will normally be (+) but may take up to 10 wks after exposure A Patient with Latent TB Infection Has + TST or Blood test; Negative CXR. Has TB bacillus that are alive but inactive. Person not sick or contagious. Not considered a TB case. Potential for active dz. LA County TB Control Program Myth 2 About TB TB Myth: TB testing is the same as TB screening. Fact: Testing for TB is not the same as screening. Infection? Disease TB Screening Risk assessment (series of questions) performed by clinician TB Testing Skin test (TST) or blood test (QFT or T-Spot) Direct Progression vs Reactivation vs dormant What is the Time Frame? If deemed higher risk, test for TB infection is done If positive, then chest x-ray is done 2
TB s Natural History: LATENT TB INFECTION TB may remain latent (dormant) Spectrum of active disease is wide: Pulmonary Pleural Limited Extrapulmonary (e.g., Lymph Node) Disseminated (Miliary) Rapidly fatal Spontaneous involution Moulding T. Pathogenesis, pathophysiology, and immunology: clinical orientations. In Schlossberg D, ed: Tuberculosis and Nontuberculous Mycobacterial Infections, 4th ed.philadelphia,wb Sauders, 1999; pp48-56. 99.5% or 2.1 Billion Asymptomatic. M. tb. persists in lung, cleverly concealed. (Contained, and alive) What is the bug doing? Last year over 8 million progressed to Dz. ENDOGENOUS REACTIVATION ENDOGENOUS REACTIVATION RISKS Clinical Situation Risk Normal 10% Lifetime Person with HIV & TB 7-10% year HIV (+), Newly Infected? (+) PPD Unknown Duration 0-1% Year 5 Years Old Clinical Situation RISKS (Con t) Risk Household/Close Contact 2.5-5.0% 1st Yr Large Residual Bacillary Load 1-4.5% Yr (Abnormal CXR - inadequate treatment) (+) PPD with Chronic Medical Condition RELATIVE RISK FOR SOME SELECT CONDITIONS Relative Risk Silicosis 30 D M 2-4 CRF/Dialysis 10-25 Organ Transplant 20-74 What are the criteria for a (+) TST? > 5 mm is positive in: Persons known or suspected to have HIV Other immunosuppressed (e.g., organ transplant) Close contacts to infectious TB cases Persons with abnormal CXRs c/w TB disease > 10 mm is positive in all others in California Los Angeles County TB Control Program 3
NEGATIVE TST Does Not Exclude Dz False (-) 10-25% Young or Very Old Poor Nutrition Overwhelming TB Viral Infection Immunocompromised WHO SHOULD BE TESTED? Goal is to identify those at risk as they would benefit from Rx. No mass screening; A Decision to Test is A Decision to Treat No Risk, Don t Test! Jasmer, R: NEJM 2002;347:1860 CANDIDATES FOR TESTING Factors to Assess High Risk for TB Risk -Risk Exposure -Risk Infection -Risk Disease Development Example Close household contact Health care workers on TB ward FB persons from high prevalence countries Homeless HIV Recent converter Chronic Med Dz If any of these is Yes TB skin test Parent or child born outside US in highprevalence region Travel to high-incidence country > 1 week Contact with confirmed or suspected TB case NEJM 2002;347:1860-1866 Universal TB Testing for Children in California: What changed in LA? 1985 children entering school for the first time had to be tested. 2011: universal TB screening and risk-based testing in physical exam requirement for children entering 1 st grade. As part of routine health assessment, students should be screened and tested TB only if a risk factor is present. Which Children should be Screened? Only those at High Risk Child or parent is FB Hx of foreign visitors in house Travel to countries with high incidence Exposure to people with active TB,HIV, homeless, institutional IVDU or migrant FW LA County TB Control Program Website www.publichealth.lacounty.gov/tb Flaherrman, V Pediatrics.. July 2007 Amer. A of Ped. Pediatrics. 1996;97:281-84. 4
MEDICATIONS TO TREAT LTBI What s New? INH 300mg/QD x 9 months; not 6! 270 doses Risk of Disease 65 75% New!! INH (900mg) +Rifapentine (900mg) weekly for 12 weeks 12 doses? DOT? MONITORING PATIENTS on INH Baseline LFT s only if: Patients whose initial evaluation suggests a liver disorder. Patients with HIV infection. Pregnant women or those immediate postpartum period. Patients with history of chronic or current liver dx. NEJM 2011 6365:23 pages 2155 MONITORING PATIENTS INH At least monthly, evaluate for: Adherence to prescribed regimen. Signs and symptoms of active TB disease. Signs and symptoms of hepatitis if receiving isoniazid alone. When is the TST (PPD) considered positive? It depends If in 5mm category TST, treat if CXR is ( - ). If in 10mm category, consider Rx based on situation. INH 300 mg/da x 9 months vs INH 900 mg + Rifapentine 900 wkly x 12 wks Pyridoxine 25 mg QD. Monitor LFT s, as needed No yearly CXR needed. HIV Patients with Reconstituted Delayed-Type Hypersensitivity (DTH) Response HIV pts with Neg. TST can convert to + after starting highly active antiretroviral therapy (HAART) if CD4 count increases to about 200 Need to repeat testing for LTBI in HIV patients with previous negative TST result after starting HAART Pregnancy No change in guidelines No evidence that TST has any adverse effects on pregnant mother or fetus Pregnant HCWs should be included in serial skin testing; no contraindications Postponing diagnosis of M. tuberculosis infection during pregnancy is unacceptable 5
WHAT ABOUT BCG? Now possible to distinguish PPD Rxn 2º to true infection vs. BCG Blood test Only 8% of those with BCG at birth were positive 15 years later. Ignore hx of BCG if administered more than one year ago per CDC BOOSTING Some people with LTBI may have negative skin test reaction when tested years after infection. Initial skin test may stimulate (boost) ability to react to tuberculin. Positive reactions to subsequent tests may be misinterpreted as a new infection. Am. J Resp. Crit. 2000;161:S221 http://www.cdc.gov/tb/publications/factsheets/testing/skinte sting.htm 3-17-14 Blood Tests for LTBI IGRA (Interferon Gamma Release Assay) Measures Cellular immune response to TB bacillus Not affected by prior BCG; less likely to cross react with other Mycobacterium Two tests available: Quanti-FERON-TB Gold (QTB- Gold) or T-SPOT TB Assay Use of IGRA s Benefits over TST Requires only one patient visit Assesses responsiveness to M. tuberculosis antigens; No boosting previous responses Interpretation less subjective than for TST Can differentiate between + TST 2/2 exposure or from hx of BCG vaccination Sensitivity >95% less so in HIV patients with low CD4 Cannot distinguish between latent infection or Disease KEY SELECTED REFERENCES Questions? Guidelines for Use Interferon Gamma Assays to detect TBUS 2010 MMWR June 25,2010 Sterling TR, Villarino, M et al. Three months of Rifapentine and INH for LTBI. NEJM 2011;365: 2155-65 Assoc with LTBI in Mexican Amer. Children. Young J and O Connor ME. Pediatrics 2005; 115: 647-653 www.cdc.gov/tb www.cdph.ca.gov/tb/aspn Treatment for Latent TB Infection (LTBI) www.cdc.gov/tb/topic/treatment/default.htm LA County TB Control Program Website www.publichealth.lacounty.gov/tb/ Pamina Bagchi, MPH Policy and Planning, TB Control Program cbagchi@ph.lacounty.gov (213) 744-6194 6