Tuberculosis Education for the Medical Professional

Tuberculosis Education for the Medical Professional North Dakota Diagnosis and Medical Management of Latent TB Infection Dawn Farrell, RN, BSN, PHN Maria Robles, BSN July 10, 2007 Tuberculosis Education for the Medical Professional Diagnosis and Medical Management of Latent TB Infection July 10, 2007 1

Diagnosis and Medical Management of Latent TB Infection: Part 1 Maria Robles, BSN Nurse Educator HeartLand National TB Center Diagnosis OUTLINE Diagnosis of LTBI Identification of those at risk Targeted Testing for LTBI New Methods for diagnosis 2

Latent TB Infection (LTBI) TB Infection without active disease Asymptomatic, patient feels well Usually has a positive TB skin test NOT infectious Needs treatment for LTBI Elimination of TB in the US depends on the accurate diagnosis of LTBI TST (TB skin test) is the most common proven method of identifying infection in persons without active disease. In the United States 10-20 million persons are infected Number of infected people increase by 400,000/ year due to immigration In 2004, 81% of >14,000 TB cases are among racial and ethnic minorities 3

Targeted Skin Testing PURPOSE of screening: Strategy for controlling and preventing TB Identifies and treats persons with active disease Identifies and screens contacts to TB cases Screens populations at HIGH risk for LTBI and active disease Find infected persons who would benefit from LTBI treatment Who should be screened? Should be targeted to persons at higher risk of TB: those with increased rates of infection those with increased risk of progressing to active disease once infected Screening of LOW risk persons should be replaced by targeted testing Screening should be eliminated in the general population 4

Groups at high risk (include in screening) Divided into 2 categories; persons recently infected persons with medical risk factors Risk of infection Contacts of infectious TB cases (active TB) recent exposure ongoing exposure Persons who live or stay in overcrowded, poorly-ventilated environment (shelters, low-cost hotel dwellers) Substance abusers, especially IVDU Recently arrived immigrants (< 5 yrs.) from countries with high TB rates (foreign-born) 5

Risk of infection (cont d) Persons with compromised immune systems (children < 4 years, other immunocompromised) Persons who live or work in institutional settings (nursing homes, correctional facilities) Medically underserved/ low-income groups Health care workers who have contact with High risk persons At Risk of Progression to active disease HIV infected With other medical conditions Previous history of TB disease Fibrotic lesions on CXR (indicative of past TB) Infants and children <5 years old (sentinels of transmission) Malnourished or below recommended weight IV drug users 6

Risk of progression (cont d) With medical conditions Silicosis Diabetes Mellitus Chronic renal failure on dialysis Organ transplant recipients Cancers of head or neck Have had a gastrectomy or jejunoileal bypass Risk of progression (cont d) Recipients of immunosuppressive therapy steroids (prednisone >15 mg/day) Chemotherapy Cyclosporine TNF-a blockers Enbrel, Remicade, Humira For treatment of auto-immune disorders; Crohn s, rheumatoid arthritis 7

Risk of progression (cont d) Recent infection Either as contacts or converters Conversion: 10 mm increase within the last 2 years 4-5% of developing active TB within the first 2 years of being infected Risk can double if contact is < 4 years old 40% in infants younger than 12 months HIV co-infected Progression up to 10% higher per year!! the decision to test is a decision to treat 8

Tuberculin Skin Testing (Mantoux) Common proven method for identifying LTBI Mantoux test is preferred to other types PPD: purified protein derivative Must be read by trained staff Use 0.1 ml of PPD injected intradermally Reading the Tuberculin Skin Test Read reaction 48-72 hours after injection Measure only induration Record reaction in millimeters 9

TST Interpretation ATS/CDC Cut points (1) >5 mm is considered positive in - Recent contacts of infectious TB cases - (known or suspected) - HIV-infected persons - (known or suspected) - Patients receiving immunosuppressed treatments - (include recipients of organ transplants) - TB disease suspect TST Interpretation ATS/CDC Cut points (2) > 10 mm is considered positive in - Recent immigrants from high prevalence countries - IVDU, known to be HIV neg. - Residents and staff of high-risk congregate settings - Medically underserved, low-income populations - Mycobacteriology lab personnel - Children < 4 years of age - Persons with medical conditions that place them at high risk of progression to TB disease 10

TST Interpretation ATS/CDC Cut points (3) > 15mm is considered positive in; - persons (includes children) with no risk factors (If there is no risk. Why did you test?) TST Limitations Sensitivity; ability to correctly identify those who have latent infection (LTBI) Specificity: ability to correctly identify those who do NOT have LTBI 11

Causes False negative reactions Recent TB infei fection Anergy (HIV) Very young age (<6 months old) Other viral, bacterial, fungal infections Live virus vaccinations (MMR, varicella, smallpox) Overwhelming TB disease Incorrect meth thod of administration; incorrect interpretation; tation; improper storage Causes False positive reactions Infection with NTM (non-tuberculosis mycobacteria) Switching tuberculin products (Tubersol to Aplisol) Vaccination with BCG; Used in high prevalent countries Reactions wane 5-10 years after innoculation Large positive +TST reaction usually indicate a M.tb infection Do not alter the interpretation of a TST reaction due to a past BCG vaccination 12

New tests for LTBI QuantiFERON-TB Gold test (QFT) Whole blood interferon release assay Measures immune reaction to M.tb FDA approved Current CDC guidelines; Recommends use in situations where the TST is used ( use in place, NOT in addition to) Limited data on use for children and HIV-infected New Tests (cont d) QuantiFERON-Gold Proteins, are secreted by all M. tuberculosis and M. bovis strain when exposed to the antigens, CFP-10 and ESAT-6 Improved specificity; able to differentiate between TB and NTB, as well as BCG vaccination Studies underway in for use children and HIV infected 13

QuantiFERON-Gold (QFT-G) Advantages Disadvantages Only one patient visit - Few labs offer test - Blood specimen must be Results can be ready processed within 12 24 hours hours after collection No reader bias (need viable white cells) -Cost Not affected by BCG - Limited data on use in No booster children (<17 years) phenomenon or immunocompromised persons QFT vs TST Specific antigens No boosting 1 patient visit Minimal reader bias Obtain results in 1 day - Single antigen - Boosting - 2 patient visits - Reader bias - Results in 2-3 days 14

Before Treatment of LTBI: Exclude Active Tuberculosis Absence of symptoms Negative CXR Negative medical evaluation Order and wait for sputum culture if any question 15

Diagnosis and Medical Management of Latent TB Infection: Part 2 Dawn Farrell, BSN, RN Nurse Consultant HeartLand National TB Center Welcome Hello to the Peace Garden State 16

Guidelines on Diagnosis and Treatment of LTBI ATS/CDC. Treatment of Latent TB April 2000 American Academy of Pediatrics. Targeted Tuberculin Skin Testing and Treatment of LTBI in Children & Adolescents. Pediatrics 2004; 114:No4 October 2004 ATS/CDC/IDSA. Controlling Tuberculosis in the U.S. November 2005 NTCA/CDC. Guidelines for the Investigation of Contacts of Persons with Infectious Tuberculosis. December 2005 CDC. Guidelines for Using the QuantiFERON-TB Gold Test for Detecting Mycobacterium tuberculosis Infection, United States. December 2005 Objective Discuss current recommendations for treatment of LTBI Content: 9 months of INH Alternative regimens Social and cultural issues using real-life case studies 17

Trends in Tuberculosis Incidence United States, 2006 Latent Tuberculosis Infection (LTBI) Infection without disease. Tuberculosis elimination in the U.S. depends on accurate diagnosis of LTBI. Diagnosis of LTBI currently depends on Tuberculin Skin Testing. 18

Rational for Treatment of LTBI Prevent progression of infection to disease Interrupt transmission of disease The next step that must be taken to move toward TB elimination in the US Before Treatment of LTBI: Exclude Active Tuberculosis Absence of symptoms Negative CXR Negative medical evaluation Order and wait for sputum culture if any question 19

Evaluation for Patient at Risk for TB At-risk person Tuberculin Test + Symptom Review Negative Positive Chest X ray Treatment not indicated Normal Candidate for treatment of LTBI Abnormal Evaluate for active TB Candidates for Treatment of LTBI Those at risk of TB who are: TST Positive, CXR normal, asymptomatic Sputum, if done, negative New guidelines - no mention of age as a factor TREATMENT RECOMMENDED for: Positive (5 and 10 mm cut-points) unless contraindication Close Contacts of active case TST Converter (10 mm increase) 20

Goals for Treatment of LTBI To prevent progression of LTBI to active disease Infants and young children exposed to contagious persons To prevent LTBI in persons who may be at high risk for developing TB infection and disease (primary prophylaxis) Immune suppressed persons such as persons with HIV infection Persons at risk for exposure to TB who are to receive treatment with TNF alpha blockers TNF alpha Antagonists Block TNF alpha activity which is required for granuloma formation and control of TB infection Used for rheumatoid arthritis, Crohn s disease, psoriasis and a variety of other immune mediated diseases Remicade (inflixamab) Embril (entanercept) Humira (adalimubab) 21

Warning: Risk Of Infections Infliximab Tuberculosis (frequently disseminated or extrapulmonary at clinical presentation), and other opportunistic infections have been observed in patients receiving Remicade some of these infections have been fatal. Patients should be evaluated for LTBI with a TST. Treatment of LTBI should be initiated prior to therapy with Remicade. SEE WARNING PDR 2004 Good Treatment of Patient at Risk for TB Depends on a Correct Diagnosis Correct diagnosis is critical to proper management. Information must be complete and correct Protocals for patient management Active TB must be excluded 22

Initiating Treatment of LTBI RULE OUT TB DISEASE Get CXR Wait for culture result if specimen is obtained Determine prior history of treatment for LTBI or TB disease Assess risks and benefits of treatment Determine current and previous drug therapy Assess potential compliance issues Treatment of LTBI Treatment can be done with just one drug (INH drug of choice) Number of TB organisms are much less than in TB disease Non-adherence to INH treatment of LTBI rarely causes drug-resistant disease Regimens vary in presence of exposure to drug-resistant cases 23

Treatment of LTBI Treatment regimens: INH x 9 months Alternative: Rifampin 600mg daily x 4 months Possible: INH & Rifampin x 3 to 4 months INH, Rifampin, EMB & PZA x 2 months Has been? Rifampin/PZA x 2 months New? Rifapentine & INH weekly x 12 mo 9 months preferred INH Regimen 6 months less effective, but may be used if unable to complete 9 months May be given daily or intermittently (biw) Must be on DOT for intermittent regimen 24

RIF Regimen When exposure to drug resistant organisms or intolerance to INH, RIF for four months daily may be used Rifabutin may be used instead of RIF for persons with HIV, or other drug-drug interactions LTBI with abnormal CXR CLASS 4 - TB Not Clinically Active Exclude active disease Abnormal but stable CXR findings (>2-3 mo) NODULES/ FIBROTIC LESIONS OF OLD TB PLEURAL THICKENING CALCIFIED GRANULOMA BRONCHIECTASIS Sputum smear and cultures negative Isolated CXR with nodules/fibrotic lesions 4 drug therapy until CXR stable & cultures negative 25

Treatment of Latent TB Infection in Special Situations For children and adolescents (<18 years old): Isoniazid for 9 months For pregnant women: Isoniazid for 9 or 6 months - may defer except for HIVinfected women and those recently infected with M. tb For persons exposed to isoniazid resistant TB: rifampin for 4 months For persons likely infected with multidrug-resistant TB: Pyrazinamide and ethambutol, or pyrazinamide and quinolone for 6-12 months (i.e., at least 2 drugs to which the organism is susceptible) Duration of therapy What is the duration of therapy that provides the maximum degree of protection against developing TB? 26

How Much Isoniazid Is Needed for the Prevention of Tuberculosis? Case rate % Longer durations of therapy corresponded to lower TB rates among those who took 0-9 mo No extra increase in protection among those who took >9 months Community based study, Bethel Alaska 6 12 18 Months of therapy Comstock GW, 1999. Int J Tuberc. Lung Dis 3:847-850 Duration of INH Therapy of LTBI IUAT study of 3, 6 and 12 months Placebo controlled study in patients with fibrotic pulmonary lesions c/w inactive TB Expressed benefits in two ways intention to treat which assesses both efficacy of drug and ability to get patients to take it efficacy in treatment completers-compliers 27

New Tuberculosis Guidelines for INH: A Numbers Game HIV Co-Infection 9 Children Prior TB on CXR (TB-4) All others Managing Medication Toxicities 28

Monitoring in LTBI Treatment Baseline liver function tests (LFTs), alanine aminotransferase (ALT), asparate aminotransferase (AST), and billirubin are not necessary except for patients with the following risk factors: HIV infection History of liver disease Alcoholism Pregnancy or in early postpartum period Clinical Monitoring for LTBI Treatment Monthly assessment for symptoms of liver toxicity and other adverse events such as rash, gastric distress For self-administered treatment (SAT) of LTBI,NEVER dispense more than 30 day supply of medications, due to potential liver toxicity DOT visits for person at high risk of developing TB (close contacts) and children are opportune times to assess for side effects 29

Adverse Drug Events Defined Side effects Side effects Unpleasant, but mild examples reactions Gas No long lasting health Bloating effects Mild nausea Do not usually require Discoloration of body changes in therapy fluids Irritability Difficulty sleeping Photosensitivity Adverse Drug Events Defined Drug toxicity More serious May be life threatening Require changes in dose or discontinuation of drug May require additional therapy and/or hospitalization Drug toxicity, examples: Significant GI upset Hepatotoxicity Dermatologic and hypersensitivity reactions Neurotoxicity CNS toxicity Opthalmic toxicity Ototoxicity Renal toxicity Musculoskeletal adverse effects 30

Risk of Hepatotoxicity in Persons with HBV and HCV Risk of hepatotoxicity not higher in persons with chronic HBV or HCV infection who are treated with INH» McGlynn Am Rev Respir Dis 1986; 134: 666-668» Sadaphal Clin Infect Dis 2001; 33:1687-1691 Completion of Therapy Completion of therapy based on the total number of doses administered, not on the duration alone 31

What s new? Treatment of LTBI For HIV(-), 9 months INH preferred over 6 months For HIV(+), 9 months INH (instead of 12 months) For fibrotic lesions on x-ray, 9 months INH (instead of 12 months) Alternative of RIF 4 months (daily) Changes in the Recommendations Treatment of Latent Tuberculosis Infection For HIV-negative persons, isoniazid for 9 months is preferred over 6 months For HIV-positive persons and those with fibrotic lesions on chest X-ray, isoniazid for 9 months instead of 12 months For HIV-negative and HIV-positive persons, rifampin and pyrazinamide for 2 months For HIV-negative and HIV-positive persons, rifampin for 4 months 32

Treatment of Latent TB Infection Future Directions Efficacy and safety of other intermittent regimens Studies in children and pregnant women Reporting and monitoring of treatment of LTBI in new settings New cost-effectiveness/decision analyses Assessment of new medications and regimens Guidelines on Diagnosis and Treatment of LTBI ATS/CDC. Treatment of Latent TB April 2000 American Academy of Pediatrics. Targeted Tuberculin Skin Testing and Treatment of LTBI in Children & Adolescents. Pediatrics 2004; 114:No4 October 2004 ATS/CDC/IDSA. Controlling Tuberculosis in the U.S. November 2005 NTCA/CDC. Guidelines for the Investigation of Contacts of Persons with Infectious Tuberculosis. December 2005 CDC. Guidelines for Using the QuantiFERON-TB Gold Test for Detecting Mycobacterium tuberculosis Infection, United States. December 2005 33

Rational for Treatment of LTBI Prevent progression of infection to disease Interrupt transmission of disease The next step that must be taken to move toward TB elimination in the US THANK YOU Questions? 34

Thank You Genie Lang Krissie Mayer Paula Winkler Session 3: Diagnosis and Medical Management of TB Disease July 31, 2007 Session 4: TB Contact Investigation August 22, 2007 35

This video conference will be archived to Heartland s website for future viewing. Each participant will receive an email announcement when it is posted at www.heartlandntbc.org No CEUs will be given for viewing on line. 36