Latent Tuberculosis Infections Controversies in Diagnosis and Management Update 2016

Transcription

1 Latent Tuberculosis Infections Controversies in Diagnosis and Management Update 2016 Randy Culpepper, MD, MPH Deputy Heath Officer/Medical Director Frederick County Health Department March 16, 2016

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3 No conflicts Conflicts and Disclosures Any opinions expressed in this talk are mine and should not be construed as official views of the Frederick County Health Department or the Maryland Department of Health and Hygiene 3

4 Learning Objectives At the end of this presentation, attendees will be able to: Describe epidemiology of TB Describe risk factors for and tests to diagnose active Tuberculosis disease, and 4

5 Epidemiology TB diagnostics Overview TST (Tuberculin Skin Test) IGRA (Interferon γ Release Assay) Quantiferon Gold T Spot TB NAATs INH-RPT 12 week LTBI treatment Summary 5

6 Epidemiology

7 TB terminology Bacteria: Mycobacterium tuberculosis Transmission: respiratory aerosols from a contagious person with active TB disease Latent TB infection (LTBI) Can be present for many years Should be treated to prevent active TB disease Active TB disease Can infect almost any part of the body Symptomatic MDR TB Resistant to both isoniazid (INH) and Rifampin (RIF) 7

8 TB Progression 8

9 TB s Global Impact TB Prevalence 1/3 of world s population infected with TB (2.4 billion people) 11 million infections in the US (~4% of the population) TB now leading cause of death from infectious diseases worldwide (> HIV/AIDS deaths) 9.6 million new cases of active TB in million TB-related deaths from active TB in 2014 Over 1/3 of TB cases and ~ 2/3 of drug-resistant cases are found in the BRICS countries (Brazil, Russia, India, China and South Africa) In 2012, ~530,000 children became ill and 74,000 HIV negative children died of TB. TB case rates (incidence) Markedly decreasing overall but still incredibly rampant Foreign-born persons ~13 times higher than among US-born persons MDR TB: ~ 500K cases worldwide (in US decreased slightly from (1.3%, 91 cases) 9

10 Maryland TB Incidence (176) New Cases and Rates per 100,000 Pop Nationality Foreign-born: 134 (76%) US born: 42 (24%) Race/Ethnicity Hispanic: 39 (22%) White: 13 (7.5%) Black: 71 (41%) Asian: 50 (29%) Sex: Male = female Age of onset (years) 0-14: 7 (4%) 15-34: 56 (32%) 35-64: 78 (44%) 65+: 35 (20%) 10

11 Role of the primary clinician FIND and TREAT latent TB Conduct targeted screening for latent TB Your local health dept. may offer Tx services FIND Active TB Identify suspect TB cases /conduct initial eval. Order appropriate testing and arrange longitudinal follow-up Refer or consult with Health Department if starting treatment 11

12 Latent TB Infection (LTBI) Bacteria first go to lungs Immune system kicks in Some bacteria may or may not survive (LTBI) Positive test (TST, IGRA) Normal chest X-ray NOT infectious No symptoms Sputum smears & cultures are negative NOT a case of TB 12

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14 Extrapulmonary TB TB can affect any part of the body 75-90% pulmonary TB 10-25% extrapulmonary TB Especially common in children and HIV (+) people Lymph nodes (inguinal, axillary, mesenteric, mediastinal, and intra-mammary) Pleura (pleural effusion) Bone and joint (spine [Potts Disease), weight-bearing joints, extraspinal tuberculous osteomyelitis) CNS (TB meningitis) Other places Abdomen - liver, spleen, intestines GU - kidneys, bladder and urinary tract Miliary tuberculosis Tuberculous pericarditis TB associated with tumor necrosis factor-3 (TNF-α) inhibitors Classic CXR: Cavity in the right upper lobe 14

15 TB Diagnostics

16 TB Diagnostics: What to order? TB skin tests (TSTs) Interferon λ Release Assays (IGRAs QFT and T-Spot-TB) Acid Fast Bacteria (AFB) smear (sputum, respiratory aspirate, bronchial wash, bronchoalveolar lavage (BAL), body fluids, CSF, tissue, urine, lymph node) Nucleic Acid Amplification test (NAAT) DNA probes (cultures only) for M. tuberculosis complex, M. avium intracellulare complex, M. gordonae and M. kansasii Mycobacterial culture (sputum, blood, tissues, abscess) Nucleic acid amplification tests (NAATs) (sputum, other tissue) Pearls: All TB suspects should be HIV tested and assessed for immunosuppression Diagnostic tests are only one aspect of diagnosing TB disease; consider context and patient history 16

17 BCG Vaccine and TST BCG most commonly used vaccine worldwide Most endemic countries with >98% coverage Efficacy in adults 0-80% Some efficacy in preventing pediatric disease TST response to BCG likely wanes ~ in a few years Can t tell if positive TST is from BCG or from LTBI Doesn t WORK well to prevent active TB! Ignore BCG status for LTBI evaluation (sort of) 17

18 TST Advantages & Disadvantages Advantages Inexpensive Can be used in young children Disadvantages (+) inter-reader variability Subjective interpretation Sensitivity: 60-90% in active TB Specificity: 60-95% in pts without TB TST positivity is based on risk factors Requires two visits Different PPD different results Cross-reactivity with non- tuberculous mycobacteria (and BCG) Booster phenomenon 18

19 QFT Advantages and Disadvantages Advantages: Avoids false-positive influence of BCG vaccine Minimal cross-reactivity with most non-tb mycobacteria, unlike TSTs Single visit - no follow-up patient visit required unlike with a TST More objective results No booster phenomenon Disadvantages: More expensive; mixed studies re: cost-effectiveness of TST vs QFT Specimen handling Test results erratic in persons with reduced immune response. Reproducibility with serial testing?? Limited data for use in: Children <5 y/o Immunocompromised 19

20 TST and IGRAs Do NOT measure presence of bacteria in the body Do NOT distinguish latent infection from active disease Should NOT be used as the first test to assess for active TB A negative TST/IGRA does NOT rule out active TB Assess immunologic reaction to mycobacterial antigens Once positive, likely always positive for life 20

21 Nucleic Acid Amplification Tests (NAAT) Amplify nucleic acid segments specific for M. tuberculosis Rapid results in hours Multiple tests available: Gen-probe MTD, Xpert MTB/RIF Do not differentiate between live and dead bacteria Should NOT be used to follow patients on treatment Often will stay positive long after cultures are negative CDC recommends at least one respiratory sample be sent for NAAT testing (in addition to smear microscopy/culture) DHMH uses Xpert MTB/RIF (GeneXpert): FDA approved and also provides Rif resistance Smear (+): Sensitivity = 98.7% and Specificity = 97.8% Smear (-): Sensitivity = 62.2% and Specificity = 98.9% 21

22 Xpert MTB/RIF Assay Nucleic acid amplification test (NAAT) Simultaneously detects Mtb complex (MTBC) and resistance to rifampin (RIF) in less than 2 hours (cultures ~ 2 to 6 weeks) Can quickly identify possible multidrug-resistant TB (MDR TB) RIF resistance is a predictor of MDR TB because resistance to RIF, in most instances, co-exists with resistance to INH Avoid unnecessary Tx and isolation Must be interpreted along with clinical, radiographic, and other lab findings Does not replace the need for smear with microscopy for acid-fast bacilli, culture for mycobacteria, and growth-based drug susceptibility testing, in addition to genotyping for early discovery of outbreaks. 22

23 LTBI Treatment

24 LTBI Treatment Alternative INH plus Rifapentine x 12 weekly DOT doses 3HP-DOT equal alternative to 9H or 4R for TLTBI Significantly higher completion rate (> 80%) Lower reactivation rate among 22 TB cases Used in otherwise healthy persons who are: 12 years of age and older Have factors predictive of progressing to TB disease Recent contact of infectious TB disease Have a positive TST or IGRA Optional for HIV-infected persons who are otherwise healthy and not taking antiretrovirals Not recommended HIV-infected persons taking antiretroviral medicines Pregnant women Women expecting to become pregnant during Tx Persons who have LTBI with strains presumed to be resistant to isoniazid or rifapentine. Consider for others if advantageous, such as completion within a limited timeframe 24

25 Summary

26 Summary 1/3 of world s population infected with TB (~ 2.4 billion people) TB tops HIV as leading cause of infectious disease deaths worldwide Foreign-born persons ~13 times higher TB case rates than US-born persons Active TB can infect almost any part of the body % extrapulmonary TB Test all TB suspects for HIV test and evaluate for immunosuppression LTBI can be present for many years LTBI should be treated to prevent active TB Short course DOT is probably the best treatment option for LTBI 26

27 Summary No gold standard for TB testing Once a TST or IGRA is positive, likely positive for life TST s and IGRAs do NOT measure presence of bacteria in the body TSTs and IGRAs have significant drawbacks TST, as imperfect as it is, remains a good choice Ignore BCG status for LTBI testing (sort of) IGRAs are continuing to evolve TST s and IGRAs do NOT distinguish latent infection from active disease AFB smears and NAATs do NOT distinguish between live and dead bacteria Sensitivity and specificity when tested in high prevalence settings does not translate to low prevalence settings QFT - A low positive result of 0.35 IU/mL or a high positive result of 10.0 IU/mL does not reflect the actual infectious burden of the patient NAATs: Send at least one respiratory sample for NAAT testing (in addition to smear microscopy and culture) 27

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