Mycobacterial Infections: What the Primary Provider Should Know about Tuberculosis

Transcription

1 Mycobacterial Infections: What the Primary Provider Should Know about Tuberculosis Henry F. Chambers, M.D Professor of Medicine, UCSF Topics for Discussion Epidemiology Diagnosis of active TB Screening for latent TB infection 1

2 Global Impact of TB World population 7,135,000,000 Number infected with TB: 2,4000,000 New reported cases of active TB: 2013: 9,000,000 (126 per 100,000) 2012: 8,600,000 (121 per 100,000) 2011: 9,400,000 (140 per 100,000) US rate 2013: 3.0 per 100,000 New MDR cases (9% XDR): 315,000 >50% in China, India, Russia 1,300,000 deaths #2 cause of death worldwide from infectious disease WHO TB Case Rates,* United States, 2012 D.C. < 3.2 (2012 national average) > 3.2 *Cases per 100,000. CDC 2

3 TB Case Rates,* United States, ,582 cases for ~350,000 Primary Care MDs D.C. < 3.0 (2013 national average) > 3.0 *Cases per 100,000. CDC 20,000 Number of TB Cases in U.S.-born vs. Foreign-born Persons, United States, ,000 No. of Cases 10,000 5, U.S.-born Foreign-born CDC 3

4 TB Case Rates in U.S.-born vs. Foreign-born Persons, United States, Cases per 100, U.S. Overall U.S. -born Foreign-born CDC TB Case Rates by Age Group and Race/Ethnicity, United States, 2013 Cases per 100, Hispanic or Latino American Indian or Alaska Native Asian Black or African American 10 Native Hawaiian or Other Pacific Islander 0 Under White CDC 4

5 TB Case Rates by Age Group and Sex, United States, Cases per 100, Under Male Female CDC Active Tuberculosis Pulmonary tuberculosis: 85% of all cases The infectious form of the disease Clinical suspicion based on Signs, symptoms, setting Chest x-ray 5

6 Sites of TB Infection 120 Percent Extrapulmonary Pulmonary Other Bone/jt Miliary GU Pleural Lymphatic 0 All cases Expul Case Presentation 63 y/o inmate transferred from jail for r/o TB No fever, cough, weight loss 12 mm + PPD, HIV negative Prior work-up 2/2001: AFB smear/culture neg x3 4/2005: AFB smear/culture neg x3 8/2005: AFB smear/culture neg x3 3/2010: AFB smear/culture neg x1 9/2010: AFB smear/culture neg x4 6

7 CXR: LUL nodular infiltrate, slight volume loss, maybe slightly worse since prior film Sputum Examination Routine culture and Gram stain Oral flora AFB smear Induced sputum x2 and BAL x1: no AFB 7

8 What is your estimate of the likelihood of active TB in this case? 1. 75% or higher % % % 5. < 5% Sputum Examination Routine culture and Gram stain Oral flora AFB smear Induced sputum x2 and BAL x1: no AFB Gen-Probe E-MTD test: negative 8

9 What is your revised estimate of the likelihood of active TB in this case? 1. 75% or higher % % % 5. < 5% Diagnosis of TB 9

10 Organism Burden in TB Cavitary TB Pulmonary infiltrate Lymphadenopathy cfu/g cfu/g cfu/g Detection Thresholds of Tests for TB Diagnosis Positive smear Positive NAA test Positive culture cfu/ml cfu/ml 10 1 cfu/ml 10

11 MTB Rapid Diagnostics Test Manufacturer Target FDA Approval E-MTD: Enhanced Amplified Mycobacterium tuberculosis Test Gen-Probe Ribosomal RNA Respiratory specimens, smear + and - Amplicor Mycobacterium tuberculosis Test Roche Ribosomal RNA Respiratory specimens, smear + only Xpert MTB/RIF Cepheid rpob gene Respiratory specimens, smear + and - Performance of Diagnostic Tests for Pulmonary TB Sensitivity Specificity AFB smear 60% 99% NAA test 85% 99% Culture 90% 99% PPD (or QTF) 60% 10% 11

12 Xpert MTB/RIF Test Performance Sensitivity Specificity Smear pos. TB 95-98% Smear neg. TB 60-72% 99% Rifampin R 98-99% % NEJM 361:1005, 2010; Am J Crit Care Med 184:132, 2011 Performance of NAAT for Diagnosis of Pulmonary TB Pre-test probability PPV NPV 90% 100% 43% 75% 98% 69% 50% 96% 87% 25% 91% 95% 5% 57% 99% 12

13 Clinical Course Patient was discharged back to jail Treatment for tuberculosis withheld pending results of work-up 16 days after discharge, one sputum culture and the BAL specimen were reported positive for MTB! Principles of Therapy Start 4 drugs (RIPE) for suspected active TB Never use a single drug for treating active TB: resistance can emerge (1 mutant in 10 4 to 10 6 ) Never add a single drug to a failing regimen Consult and expert and/or local health department Francis Curry National TB Center:

14 Screening for Latent TB Infection (LTBI) Case Presentation LV is a 58 y/o female from Ukraine referred for treatment of hypertension and diabetes She is otherwise well She gives a history of BCG vaccination as a teen 14

15 What is the best course of action? 1. The patient should be screened for LTBI with a tuberculin test 2. The patient should not be screened for LTBI because she is not a candidate for INH prophylaxis due to her age 3. The patient should not be screened because with prior BCG vaccination the tuberculin test will be false positive 4. The patient should be screened for LTBI by chest x-ray LTBI: Goals of Screening Identify active cases Identify infected persons likely to benefit from treatment of latent TB infection (LTBI) Surveillance 15

16 Who Should Be Screened? Persons with increased risk of TB infection Persons with increased risk of progression Not the general population Increased Risk of Infection Close contacts of an active TB case About 30% are infected Foreign-born persons from high TB prevalence areas Asia, Mexico, Middle East, Central and South America, Africa, Eastern Europe Medically underserved, low-income, racial and ethnic minorities Others: HCW, residents of congregate living settings, untreated/inadequately treat prior TB (includes CXR consistent with TB) 16

17 Increased Risk of Progression Children < 5 years old Recent infection (contacts and converters) HIV+ Prior TB Various medical conditions: Diabetes, hematologic/reticuloendotheial diseases, intestinal or gastric bypass, renal dialysis Malabsorption syndromes, malnutrition, silicosis, alcoholism, smokers Immunosuppression, anti-tnf agents > 15 mg prednisone QD for > 3 wks Risk of Progression Risk Factor Increase in risk (+TST) AIDS/Advanced HIV 9.9 Anti-TNFα agent 7.9 Old TB, untreated 5.2 Diabetes 3.1 Smoker 2.7 Underweight

18 Flowchart: Evaluation and Treatment of LTBI TB Risk? Yes No STOP Tuberculin Test + symptom review Negative Positive Treatment not indicated Normal Chest x-ray Abnormal Candidate for Rx of LTBI R/o active TB Diagnosis of LTBI TB Skin Test (TST) Blood test for Interferon γ Release Assay (IGRA) 18

19 Reading the TST Measure reaction in 48 to 72 hours Measure induration, not erythema Record reaction in millimeters, not as negative or positive Positive reactions can be read for up to 7 days Negative reactions can be read accurately for only 72 hours TST Positivity 5 mm + PPD HIV, immunocompromised (e.g., >15 mg prednisone, TNFα antagonists, organ transplant), TB contacts, abnl CXR 10 mm + PPD Those at increased risk of infection: IVDU, health care workers, foreign born, children < 4 yo, high-risk medical conditions 15 mm +PPD Persons not at risk (why did you do the test?) 19

20 TST Conversion Signifies new infection Can takes up to 8 weeks to become positive > 10 mm increase within 2-year period Conversions may represent boosted reactions in some individuals Booster phenomenon detected by 2-step testing with second test 1-3 weeks after 1 st test Tuberculin Skin Test Should NOT be performed on someone with a documented history of a positive test Should be applied, read, and interpreted by a trained health professional RULE OUT active TB before treating for LTBI CXR for all Sputum AFB smear and culture if abnormal 20

21 Interferon Gamma Release Assays (IGRA) Indirect test for M. tuberculosis infection using whole blood Tests for generation of interferon gamma by cell-mediated immunity (not antibody) MMWR 59(RR-5), June 25, 2010 FDA Approved IGRAs Quantiferon-TB Gold In-tube (QFT-GIT) (Cellestis) ELISA: Uses ESAT-6, CFP-10 and TB7.7 (RD4) as antigens affixed to inside of tube T-Spot-TB (Oxford Immunotec) Count of interferon-γ positive cells: Uses ESAT-6 and CFP-10 21

22 QFT Procedure QFT Interpretation 22

23 IGRAs: Species Specificity of ESAT-6 and CFP-10 Mycobacterial species ESAT-6 CFP-10 M. tuberculosis + + M. africanum + + M. bovis + + BCG strains - - M. avium-intracellulare - - M. abscessus - - M. smegmatis - - M. kansasii + + M. marinum + + M. szulgai + + IGRA Advantages Requires a single patient visit to draw a blood sample Results within 24 hours No boosting Is not subject to reader bias that can occur with TST Is not affected by prior BCG 23

24 Performance of IGRA vs TST Performance characteristics TST IGRA Sensitivity 75-91% 80-95% Specificity 80-90% % Correlates with exposure No Maybe Results change with Rx?? Usually yes When Should You Use IGRA? Can be used in all circumstances in which the TST is currently used, including contact investigations evaluation of recent immigrants who have had BCG vaccination TB screening of health care workers others undergoing serial evaluation for TB Preferred in BCG vaccinated patient or for a single encounter Caution when testing certain populations (i.e., children < 5 years old, immunocompromised) because of limited data in use IGRAs 24

25 QFT-GIT Screening of HCWs Manufacturer's IFN-γ cutoff 0.35 IU/ml may be too low for low prevalence settings, inflating positivity and conversion rates, and a higher cut-off may be more appropriate Am J Respir Crit Care Med 188:1005, 2013 Guidelines for Treatment of LTBI Decision to test is decision to treat No 35 year-old cut-off Baseline lab monitoring not routinely indicated 25

26 Regimens for Treatment of LTBI Drug Duration Dose & Interval Minimum Doses INH* 9 mo 300 mg daily mg twice weekly (DOT) INH 6 mo 300 mg daily 180 INH + Rifapentine 900 mg twice weekly (DOT) 3 mo 900 mg mg once weekly (DOT) Rifampin 4 mo 600 mg daily *Preferred regimen What is the best course of action? 1. The patient should be offered a tuberculin test to screen for LTBI 2. The patient should not be screened for LTBI because she is not a candidate for INH prophylaxis due to her age 3. The patient should not be screened with tuberculin test because with prior BCG vaccination the test will be false positive 4. The patient should be screened for LTBI by chest x-ray 26

27 Thanks! 27