Tuberculosis in Primary Care April 22, 2015 ADVANCES IN INFECTIOUS - PDF document

4/22/15 Tuberculosis in Primary Care April 22, 2015 ADVANCES IN INFECTIOUS DISEASES Julie Higashi, MD, PhD TB Controller, San Francisco DPH Assistant Clinical Professor of Medicine UCSF, Curry International Tuberculosis Center 1 Disclosure Slide n I have nothing to disclose 2 1

4/22/15 Objectives: List the main risks for TB infection and 1. progression to active disease Describe advantages and disadvantages of 2. TST and IGRAs in LTBI diagnosis Discuss regimen options for LTBI treatment 3. Describe the follow-up, monitoring, and 4. treatment completion for LTBI therapy 3 We ¡are ¡not ¡making ¡progress ¡toward ¡TB ¡ elimina4on ¡ San ¡Francisco ¡ CA U.S. 2010 ¡Goal 50 Rate ¡per ¡100,000 40 30 20 10 0 1990 1994 1998 2002 2006 2010 2014 Figure ¡1. ¡TB ¡Case ¡Rates ¡by ¡Year ¡1990-­‑2014 2

4/22/15 TB elimination model What is the most significant barrier to testing/treating LTBI in your practice? Lack of time • Unclear guidelines/lack • TB knowledge Access to diagnostic • testing (IGRAs) Lack of consistent • documentation to track testing/treatment 3

4/22/15 Flowchart: Evaluation to Treatment of LTBI At-risk person TB test + symptom review Negative Positive Chest x-ray Normal Abnormal Candidate for Treatment Evaluate for Rx of latent TB not indicated active TB Assess TB Risks First http://www.ctca.org/fileLibrary/file_703.pdf 8 4

4/22/15 Targeted Testing Persons at high risk for developing TB disease fall into 2 categories: 1. Recently infected 2. Clinical conditions that increase risk of progressing from LTBI to TB disease 9 Recent Infection n TST or IGRA converters (within past 2 yrs) q Skin test conversion is an increase of ≥ 10 mm within a 2-year period q 4-5% risk developing active disease within first 1-2 years. Risk doubles in children < 4 years old q 40% progression to disease in infants < 12 months n Close contacts to person with infectious TB n Residents and employees of high-risk congregate settings ( e.g., correctional facilities, homeless shelters, healthcare facilities) 10 5

4/22/15 Risk Factors for Progression n HIV infection – greatest risk n Radiographic evidence of old, untreated tuberculosis (> 2 cm 2 ) n Immunosuppression q Organ transplant, prednisone >15mg/d for more than 1 month, TNF- α inhibitors Horsburgh NEJM 2004, Horsburgh NEJM 2011 11 Risk Factors for Progression (2) n Diabetes ~2X n Smoking ~4X n Chronic renal failure n Silicosis n Leukemia/lymphoma n Head/neck cancer n Malnutrition, weight loss >10% of ideal weight, gastric bypass surgery Horsburgh NEJM 2004, Horsburgh NEJM 2011 Sterling NEJM 2011 12 6

4/22/15 Which of the following groups should be assessed annually for new TB exposure risk? 1. Homeless person in San Francisco 2. Person born in Mexico 3. US born elderly person (> 70 year old) 4. San Francisco resident with HIV infection 0% 0% 0% 0% 5. All of the above 1 2 3 4 13 Which of the following groups should be tested annually for TB? 1. Homeless person in San Francisco 2. Person born in Mexico 3. US born elderly person (> 70 year old) 4. San Francisco resident with HIV infection 0% 0% 0% 0% 5. All of the above 1 2 3 4 14 7

4/22/15 What should be the frequency of re-testing for the following groups? 1. Homeless person in San Francisco 2. Person born in Mexico 3. US born elderly person (> 70 year old) 4. San Francisco resident with HIV infection 15 What should be the frequency of re-testing for the following groups? Assess risk annually – test if new risk 1. Homeless person in San Francisco (Annual) 2. Person born in Mexico (Known Contact or Travel) 3. US born elderly person (> 70 year old) (Known Contact or Travel) 4. San Francisco resident with HIV infection (Annual) 16 8

4/22/15 Case 1 - 25 yr old female Radiology reading: Fibrotic opacity in the right upper lobe with pleural thickening consistent with scarring from old TB 17 Case 1 - 25 yr old female (2) Asymptomatic n TST = 16mm n 3 months post-partum n No other PMHx, HIV (-) n Sputum AFB smear (-) x 3 n Would you start her on LTBI treatment? 1. Yes 2. No (ARS on next slide) 18 9

4/22/15 Case 1 - 25 yr old female (2) (ARS) Would you start her on LTBI treatment? Yes 1. No 2. 0% 0% 0% ¡ ¡Yes ¡ ¡No 19 Case 1 - 25 yr old female (3) All 3 sputa grew MTB! Two months into treatment … 20 10

4/22/15 Flowchart: Evaluation to Treatment of LTBI At-risk person TB test + symptom review Negative Positive Chest x-ray Normal Abnormal Candidate for Treatment Evaluate for Rx of latent TB not indicated active TB How do you place a Tuberculin Skin Test (TST)? Performing a TST n Inject 0.1 ml of 5 TU PPD intradermally on volar surface of lower arm using a 27-gauge needle n Produce a wheal 6 to 10 mm in diameter 11

4/22/15 How do you read the TST? n Measure reaction in 48 to 72 hours n Measure induration, not erythema n Record reaction in millimeters, not “negative” or “positive” n Ensure a trained health care professional measures and interprets the TST 23 TST for LTBI Diagnosis Criteria for a Positive Reaction ≥ 5 mm ≥ 10 mm ≥ 15 mm HIV infection Recent immigrants No risk* Contact to High-risk medical active TB case conditions Abnormal CXR Injection drug users Immunosuppression Children < 4 years Healthcare Workers Residents of jails/nursing homes, hospitals *These persons should not be screened in the absence of an indication 24 12

4/22/15 What if the patient comes back late? If the patient returns after 72 hours q Read the test q If the reaction is large enough to be considered positive, record the result and proceed with the evaluation (ie CXR) q If there is a small reaction or no reaction, the test should be repeated 25 What about BCG Vaccination? • BCG protects children from developing severe forms of TB but does not protect from infection • Prior BCG is not a contraindication for a TST • The TST is considered reliable for diagnosing LTBI if the BCG was given > 1 year prior • Reactions due to BCG wane over time so the CDC recommends interpreting (+) tests the same as persons without BCG 26 13

4/22/15 The BCG World Atlas http://www.bcgatlas.org/ 27 TST: Sensitivity for Active TB Diel, Chest April 2010 137(4): 952 28 28 14

4/22/15 Advantages of the TST n Cheap n Relatively easy to perform n Extensive experience and clinical data correlating a (+) TST with the risk of progressing to active TB 29 29 Limitations of the TST n Subjective interpretation n Difficult to maintain proficiency n Requires 2 visits n Affected by prior BCG vaccination and NTM infection n Only moderately sensitive for active TB n Despite > 100 yrs of use, still no standard place for recording results in the medical record 30 30 15

4/22/15 Case 2 - 20 y/o student n Born in India, in US for 4 years n Required to get TB testing for college enrollment n TST = 11 mm CXR = normal “ It ’ s due to my BCG ” n Asks for a “ blood test for TB ” n Quantiferon-Gold in Tube (QFT-G in Tube) n Result = positive IFN-g release from TB agonist - Nil = 1.15 IU/ml Reference cut-off for positive result ≥ 0.35 IU/ml 31 31 What is the Quantiferon-Gold in Tube? “Interferon-gamma Release Assays” n Blood tests for detecting TB infection n Uses ESAT-6 and CFP-10 as antigens, which are more specific for M. tuberculosis complex n Require only 1 visit to get a result n Less subject to reader bias and error Lancet 2000;356:1099-104 32 16

4/22/15 QuantiFERON-Gold in tube 33 T-SPOT. TB 34 17

4/22/15 Species Specificity of ESAT-6 and CFP-10 Tuberculosis Antigens Environmental Antigens complex strains ESAT CFP ESAT CFP M abcessus - - M tuberculosis + + M avium - - M africanum + + M branderi - - M bovis M celatum - - + + M chelonae - - BCG substrain M fortuitum - - gothenburg - - M gordonii - - moreau - - M intracellulare - - M kansasii + + tice - - M malmoense - - tokyo - - M marinum + + danish - - M oenavense - - M scrofulaceum glaxo - - - - montreal - - M smegmatis - - M szulgai + + pasteur - - M terrae - - M vaccae - - M xenopi - - 35 IGRAs are preferred for: 1. BCG vaccinated 2. Groups with historically low return rates for TST readings MMWR June 25,2010 Vol 59: RR-5 36 36 18

4/22/15 Case 2 - 20 y/o student (2) n Born in India n Required to get TB testing for college enrollment n TST = 11 mm CXR = normal “It’s due to my BCG” n QFT positive (TB-nil = 1.15 IU/ml) “It’s boosting from the TST” n Repeat QFT negative (TB-nil = 0.34 IU/ml) “Finally we agree” 37 Online TB Risk Calculator http://www.tstin3d.com/ 38 19