TB in Corrections Phoenix, Arizona

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1 TB in Corrections Phoenix, Arizona March 24, 2011 Treatment of Latent TB Infection Renuka Khurana MD, MPH March 24, 2011 Renuka Khurana, MD, MPH has the following disclosures to make: No conflict of interests No relevant financial relationships with No relevant financial relationships with any commercial companies pertaining to this educational activity 1

2 Renuka Khurana MD, MPH Medical Director Clinical services Maricopa County Department of Public Health Financial Disclosures None 2

3 Discuss current CDC/ATS treatment Guidelines for latent TB infection Describe recommendations for follow up and monitoring of patients with latent TB infection Background and Targeted Testing Evaluation Treatment Summary 3

4 As tuberculosis (TB) disease rates in the United States (U.S.) decrease, finding and treating persons at high risk for latent TB infection (LTBI) has become a priority. LTBI Targeted Testing and Treatment of LTBI High Risk Groups Progression Months-Years New Infection Transmission Days-Weeks Active TB Disease Case Finding and Treatment of Active Disease 4

5 LTBI is the presence of M.tuberculosis organisms (tubercle bacilli) without symptoms or radiographic evidence of active TB disease Focus program activities and provider practices on groups at the highest risk for TB Benefits Focuses and detects persons with LTBI who will benefit from treatment Reduces the waste of resources and prevent inappropriate treatment De-emphasizes testing of persons who are not high risk for TB 5

6 Patient A history 29-year-old African- American female History of diabetes 35 weeks pregnant TST = 20 mm of induration No symptoms of TB disease CXR, CBC, LFTs normal No known contact with TB patient Patient B history 47-year-old Hispanic male Moved to U.S. from Bolivia i 4 years ago Known contact of infectious TB case TST = 5 mm of induration 3 months later TST = 23 mm of induration No symptoms of TB disease Normal CXR, CBC, AST, and bilirubin What are the What are the patients risk factors for TB disease or infection? 6

7 Screening Goals: Not the general population Strategic Component of TB Control o Determine Risk By identifying persons at high risk of developing TB disease Populations with increased risk of infection Recent M TB infection Persons/groups (if infected, with clinical conditions) in whom risk of progression from LTBI to TB disease is increased Know the TB status of your at risk patients. Who is considered at risk? Foreign born patients from TB endemic countries, where prior TB exposure is almost certain (Recent arrival within 5years) What countries are considered TB endemic? All of Asia except Japan All of Central and South America All of Africa All of Eastern Europe Russia (Practically the whole world) 7

8 Individuals at risk for exposure to or infection with TB Recent Infection or Close contacts of Active TB cases (within the last 2 years) Fibrotic changes on CXR c/w prior TB Previous TB with inadequate (or undocumented) treatment Healthcare workers who serve high risk clients Children <5 years old Residents & employees of congregate settings Medically underserved/low-income groups: Homeless Migrant workers Street drug users Children with parents who have risk factors Medical Conditions HIV Infection Renal dialysis Diabetes mellitus Silicosis Cancer of the head and neck\hematologic and reticuloendothelial diseases Intestinal bypass or gastrectomy Chronic malabsorption syndromes Low body weight/malnutrition Immunocompromised (>15 mg prednisone once a day for1month or more) Organ Transplant/ TNF-inhibitor treatment 8

9 Healthcare workers Close contacts to infectious TB cases Frequent travelers to abroad If baseline TST is negative, consider retesting your patients that have extended travel to high risk areas. Do symptom review upon return and possibly retesting ti 8-10 week after return. CASE A CASE B Persons with diabetes Patient t is a contact t of an mellitus are 2 to 4 infectious TB case Recent immigrant to the times more likely to U.S. from a country with a develop TB disease high prevalence of TB than those without Rates of TB approach diabetes those of their countries of origin for 5 years after Risk may be higher in insulin-dependent diabetics and those with poorly controlled diabetes arrival in the U.S. These increased rates most likely result from recent M. tuberculosis infection in their native country 9

10 Background and Targeted Testing Evaluation Treatment Summary 4-5% risk within the first 1-2 years 5% lifetime risk after first 2 years 10

11 Mantoux tuberculin skin test (TST) OR Interferon-gamma release assays (IGRAs): QuantiFERON -TB Gold test (QFT-G) QuantiFERON -TB Gold In-Tube (QFT-GIT) T-SPOT TB Limited specificity and sensitivity False positive Nontuberculous mycobacteria & BCG Need for return visit Variable Interpretation 11

12 Mantoux tuberculin skin test (TST) OR Interferon-gamma release assays (IGRAs): QuantiFERON -TB Gold test (QFT-G) QuantiFERON -TB Gold In-Tube (QFT-GIT) T-SPOT TB 12

13 Measures Interferon gamma released by peripheral blood cells when stimulated by MTB specific antigens ESAT-6--- Early Secreted Antigen Target 6 CFP-10---Culture Filtrate Protein 10 TB7.7(p4)---QuantiFERON -TB Gold In-Tube only QuantiFERON -TB Gold test (QFT-G) FDA approved December 2004 QuantiFERON -TB Gold In-Tube (QFT-GIT)FDA approved October 2007 T-SPOT TB Approved July2008 No cross reactivity with BCG with most Non-tubercular Mycobacteria except M.kansasii, M.szulgai and M marinum Cross reacts with M.bovis, microti and africanum Uses control antigens NIL (negative) control Mitogen phytohemagglutinin h ti i antigen (positive) control Does not differentiate between LTBI and Active TB Disease 13

14 Sensitivity Specifity TST 65%-74% 46-87% QFT-G IT 70%-89% 99% T-spot 89%-96% 97% T-spot more sensitive i in children<2years, immune-compromised and malnourished clients T-spot is more labor intensive Result Positive Negative Indeterminate Report/Interpretation M. tuberculosis infection likely M. tuberculosis infection unlikely, but cannot be excluded especially if: 1. Patient has TB signs and symptoms 2. Patient has a high risk for developing TB disease once infected with M. tuberculosis Test did not provide useful information about the likelihood of M. tuberculosis infection. Options are to repeat test, administer a TST, or do no additional testing 28 14

15 Single visit Higher specificity than TST (BCG, NTM) Less variability (application and interpretation) Positive and Negative controls No Boosting (except QFT-G IT with TST) Cost Effective (in some populations HCW, FB, Contacts) Decreased CXR Decreased investigationi i Decreased LTBI evaluation and treatment Decreased personnel cost Decreased personnel time away Natural History of conversion and reversion is unknown Uncertain of response to treatment---if IGRA increase, decrease or demonstrate no change Uncertain predictive value for disease progression in IGRA positive Test selection QFT-G vs T-spot Specific IGRA for certain populations children and immunocomprimsed Indeterminate results--what to do 15

16 Latent TB Infection TST or IGRA s positive Negative chest radiograph No symptoms or physical findings suggestive of TB disease Pulmonary TB Disease TST or IGRA s usually positive Chest radiograph may be abnormal Symptoms may include one or more of the following: fever, cough, night sweats, weight loss, fatigue, hemoptysis, decreased appetite Respiratory specimens may be smear or culture positive Background and Targeted Testing Evaluation Treatment Summary 16

17 DECISION TO EVALUATE IS A DECISION TO TREAT Anyone who has been diagnosed with latent TB infection is a candidate for treatment, if they also fulfill the following criteria: Willing and able to complete a full course of therapy Available to be monitored during the full course of treatment No medical contraindications e.g. active liver disease (Note: careful assessment to rule out the possibility of active TB disease is always necessary before treatment for LTBI is started.) 17

18 Before initiating treatment for LTBI Rule out TB disease (i.e., wait for culture result if specimen obtained) Determine prior history of treatment for LTBI or TB disease Assess risks and benefits of treatment Determine current and previous drug therapy 35 Clinical or Epidemiologic risk factor for Tuberculosis LTBI MANAGEMENT overall approach No Yes Adapted from Jasmer et al. NEJM 2002;347: No tuberculin skin test TST or IGRA s Negative Positive High-risk exposure within 3 months CXR/clinical evaluation No Yes No Symptoms Normal CXR TB Symptoms (eg. fever, cough, weight loss) or Abnormal CXR Treatment of LTBI not indicated Evaluate for treatment of LTBI Evaluate for Active TB 18

19 Patient A history 29-year-old African- American female History of diabetes 35 weeks pregnant TST = 20 mm of induration No symptoms of TB disease CXR, CBC, LFTs normal No known contact with TB patient Patient B history 47-year-old Hispanic male Moved to U.S. from Bolivia i 4 years ago Known contact of infectious TB case TST = 5 mm of induration 3 months later TST = 23 mm of induration No symptoms of TB disease Normal CXR, CBC, AST, and bilirubin What is the management of case A and B? 19

20 CASE A Pregnancy has minimal influence on the pathogenesis of TB or the likelihood of LTBI progressing to disease Pregnant women should be targeted for TB testing only if they have specific risk factors for LTBI or progression to disease Some experts prefer to delay treatment until after the early postpartum period, unless the person has recent TB infection or HIV infection CASE B Should be treated for LTBI if TST reactions 10 mm of induration As a contact of an active TB case, 5 mm of induration is considered positive This patient should have been treated for LTBI immediately after the first TST No 35 year old cutoff in age since 2000 CDC now encourages treatment of LTBI in all age groups Use clinical judgment in treating older patients 9 months of INH is preferred over 6 months Baseline laboratory monitoring not routinely indicated unless risk factors for hepatoxicity Completion of therapy is based on the total number of doses administered, not on duration alone. *CDC/ATS Guidelines: Morbidity and Mortality Weekly Report (MMWR), Targeted Tuberculin Testing and Treatment of Latent Tuberculosis Infection. June 9,

21 Lower TB rates among those who took 9 months No significant decrease in rates among those who took >9 months Comstock Int J Tuberc Lung Dis 1999, 3(10):847- Drug Dose Frequency Duration Isoniazid (INH) 300 mg Daily 9 months A minimum of 270 doses A minimum of 270 doses must be administered within 12 months 21

22 Drug Dose Frequency Duration Other Isoniazid 900 mg Isoniazid 300 mg Twice weekly 9 months Daily 6 months DOT Dosages to complete 76 within 12 months 180 within 9 months 52 within 9 months Isoniazid id 900 Twice 6 DOT 52 ithi mg weekly months Rifampin 600 mg Daily (never twice weekly) 4 months 120 within 6 months Rifampin plus pyrazinamide x 2 months This regimen has been associated with increased risk of severe hepatic injury and death Source: Update: Adverse Event Data and Revised American Thoracic Society/CDC Recommendations Against the Use of Rifampin and Pyrazinamide for Treatment of Latent Tuberculosis Infection---United States, 2003 ; MMWR, August 8, 2003 / 52(31);

23 Intermittent dosing: always DOT Use Rifabutin in HIV infected patients on protease inhibitors For persons intolerant of INH, use RIF for 4 months TB Screening/rule out active disease required prior to initiating TNF inhibitors Class V pulmonary TB evaluation and treatment Initiate treatment with INH, RIF, EMB and PZA for culture negative TB Reassess in 2 months If no change in radiograph findings or stable and patient felt to have LTBI---discontinue medications and LTBI treatment considered complete 23

24 Contacts of INH Resistant Cases RIF for 4 months in adults RIF for 6 months in children and immunocompromised Contact to MDR case Consult TB specialist Treatment regimen 2 drugs to which MTB is susceptible Duration is 6-12 months based on other risk factors Extend or re-start treatment if interruptions were frequent or prolonged enough to preclude completion When treatment has been interrupted for more than 2 months, patient should be examined to rule out TB disease Recommend and arrange for DOT as needed 24

25 Baseline and monthly laboratory testing (ALT, AST & Bili) not needed Evaluate patients monthly for Adherence and compliance to treatment Symptoms of hepatitis (fatigue, weight loss, nausea, vomiting, jaundice) Brief physical exam for hepatitis Instruct patient to report signs or symptoms of adverse drug reactions Rash Anorexia, nausea, vomiting, or abdominal pain in right upper quadrant Fatigue or weakness Dark urine Persistent numbness in hands or feet 50 25

26 Monthly visits should include a brief physical exam and a review of Rationale for treatment Adherence with therapy Symptoms of adverse drug reactions Plans to continue treatment 51 Incidence of hepatitis in persons taking INH is lower than previously thought (0.1 to 0.15%) Hepatitis risk increases with age Uncommon in persons < 20 years old Nearly 2% in persons 50 to 64 years old Risk increased with underlying liver disease or heavy alcohol consumption 52 26

27 N=13,838 Age (Yr) Hepatitis cases/1000 < > Kopanoff et al ARRD 1976;117:991 N=11,141 Age (Yr) Hepatitis cases/ Nolan CL et al JAMA1999;281:1014 Frequent (~5%): Liver Enzyme Elevations Infrequent (~0.1% to 0.15%): Hepatitis Baseline liver function tests (e.g., AST, ALT, and bilirubin) are not necessary except for patients with the following risk factors: HIV infection History of liver disease Alcoholism Pregnancy or in early postpartum period Patients on Chemotherapy 54 27

28 Repeat laboratory monitoring if patient has Abnormal baseline results Current or recent pregnancy High risk for adverse reactions Symptoms of adverse reaction Liver enlargement or tenderness during examination 55 Asymptomatic elevation of hepatic enzymes seen in 10%-20% of people p taking INH Levels usually return to normal after completion of treatment Some experts recommend withholding INH if transaminase level exceeds 3 times the upper limit of normal if patient has symptoms of hepatotoxicity, and 5 times the upper limit of normal if patient is asymptomatic 7 7MMWR June 9, 2000; 49(No. RR-6): 39 28

29 Yes, they can receive treatment for LTBI Baseline liver function tests and at 1 month If the tests are normal at 1 month, no further testing is necessary unless symptoms develop If the tests are elevated at 1 month, continue monthly testing as long as levels are abnormal If any one of the liver function tests exceeds 3-5 times the upper limit of normal at any time, strongly consider stopping therapy 29

30 Background and Targeted Testing Evaluation Treatment Summary For every patient Assess clinical and epidemiological TB risk factors If risk is present, perform TST or IGRA s If TST or IGRA s positive, or patient is symptomatic rule out active TB disease Caution TST or IGRA s can be falsely negative If active TB disease is ruled out, initiate iti t treatment for LTBI If treatment is initiated, ensure completion 30

31 CDC s Morbidity and Mortality Weekly Report Updated Guidelines for Using Interferon Gamma Release Assays to Detect Mycobacterium tuberculosis Infection United States, 2010 MMWR 2010; 59 (RR-5); 1-25 Targeted Tuberculin Testing and Treatment of Latent Tuberculosis Infection MMWR 2000; 49 (No. RR-6) American Thoracic Society Arizona Department of Health Heartland National TB Center for Midwestern Region 31