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Got TB? An update on Latent Tuberculosis Infection (LTBI) for Family Practice Nurses from the new release of the Canadian TB Standards 7th edition. Shelley Walkerley, NP-PHC, PhD Stonegate Community Health Centre Clare Burnell, RN, BScN Tuberculosis Prevention and Control, Toronto Public Health Acknowledgements to Elizabeth Rea, MD, MSc, FRCPC, Associate Medical Officer of Health, Tuberculosis Prevention and Control, Toronto Public Health May 2, 2014 TB Around the World 1/3 of the world’s population is infected with the TB bacteria 8.6 million people were diagnosed with active TB disease in 2012 1.3 million people died from TB disease in 2012 TB occurs in every part of the world. Source: WHO TB in Canada ≈1500 Active TB Cases occur in Canada annually ≈ 600 Active TB Cases occur in Ontario annually ≈ 300 Active TB Cases occur in Toronto Annually What is TB? • Bacteria (Mycobacterium Tuberculosis) • Usually affects lungs • Can be TB disease or TB infection TB Body Locations Transmission • Airborne • Active TB disease in lungs throat coughs / sneezes • Requires close, frequent, prolonged exposure • Not highly contagious! NOT transmitted by TB Infection vs TB Disease TB Infection (Latent) + TB Skin Test Not Infectious No Symptoms Bacteria = Dormant Normal Chest X-ray TB Disease (Active) +/- TB Skin Test Infectious (possibly) Symptomatic (possibly) Bacteria = Multiplying Abnormal Chest X-ray Why do a TST? Why do we screen for TB at all? • not universal – focus on high risk of exposure/progression • Younger: LTBI and preventive treatment • Older: active TB disease - early detection and treatment • Contact follow-up (individual + determining scope of transmission) Goal determines the test: •in active TB 25% are TST negative– TST is not for ruling out active disease! •If patient is a candidate for LTBI treatment…then do a TST Decision to test = decision to treat • Approximately 10% of persons infected with TB will go on to develop active TB disease: • 5% within 2 years of infection • 5% over the remaining life. • Treatment of LTBI reduces the individual’s risk for developing active disease by up to 90% Who Should be Tested? High risk of having had TB exposure: •Contacts of infectious TB. •People who were born in or visited TB-endemic countries; especially <20 years old and immigrants who have arrived within the last 2 years. •All refugees >20 years old or <50 years old from countries with a high incidence of TB, ASAP on arrival in Canada and all adult immigrants with risk factors. •Persons from Aboriginal communities with high rates of TB *Nunavut. •People with x-ray evidence of old, healed TB disease and no history of treatment. Who else should be tested? Occupational/congregate setting risks: •Health care workers (risk of occupational exposure to TB, risk of transmission to patients). •Staff and residents in communal care: LTC, corrections, shelters, etc. Medical high risk if exposed: •People with increased risk of progression to active TB. Risk Factors for Developing Active TB in Persons With LTBI High Risk – screen at any age •AIDS •HIV infection •Chronic Renal Failure/Hemodialysis •Transplantation •Silicosis •Carcinoma of the head/neck •Recent TB infection (up to 2 years) •Abnormal CXR: fibronodular disease) Increased Risk – screen up to 65 yrs •Treatment with chemotherapeutic agents or glucocorticoids equivalent to prednisone (≥ 15mg/day) •Treatment with TNF inhibitors •Diabetes Mellitus •< 5 years of age at time of infection •Cigarette smoking (1+ ppd) •Heavy alcohol consumption (3+ drinks/day) •Abnormal chest x-ray (granuloma) •Underweight (≤ 90% ideal weight, generally BMI ≤ 20) Low Risk - screen up to 50 yrs •No known medical risk factor •Normal chest x-ray Screening Case • 25 year-old woman • Born in Philippines, emigrated to Canada 3 years ago • Type 2 diabetes, on oral medication • Enrolling in nursing; TB screening required for school Reasons to test: • TB endemic country – high risk of TB exposure • Diabetes – moderate risk of progression • Health care worker Contraindications for TST Already positive – no need to repeat: •Documented positive TST in the past •Tuberculin reactions that have severely blistered in the past •Documented active TB in the past •Clear past history of treatment for TB infection or disease High likelihood of false negative: •live-virus vaccinations in the past month (MMR, Varicella, or Yellow Fever) or major viral infections. NOT Contraindications for TST • BCG vaccination in the past • Common cold • Immunized with any vaccine on the same day as TST • Recent vaccination with non-live virus vaccine • Pregnancy or breastfeeding. • History of positive TST that is not documented • Taking low dose corticosteroids (≤ 15 mg/day) TST Technique • 0.1 ml of PPD • Inject intradermally on volar (inner) aspect of forearm • small wheal (6-10 mm) will disappear in 10-15 minutes. Reading TST • Read at 48-72 hours • Self-reading strongly discouraged • Induration, not redness! • Calipers ideal • Measure across forearm • Record in mm • “no reaction” = 0mm Interpretation of the TST Based on all of the following: •Size of the reaction (induration) •Predictive value of the test (considering potential causes of false-negative, false-positive reactions). •Risk of progression to active TB disease. On-line TST interpreter available at the McGill University website: http://www.tstin3d.com TST Reaction (mm induration) Situation in which reaction considered positive 0-4 mm In general this is considered negative. For contacts under 4 years – window prophylaxis pending definitive TST at 8 weeks post exposure 5-9 mm • • • • ≥ 10 mm All others Close contact of active contagious case Abnormal chest x-ray with fibronodular disease Immune suppression HIV infection Causes of False-Negative TST • Active TB! • Poor injection technique • Conversion window period: TB exposure <8 weeks ago • Age < 6 months? • Anergy (severe illness, dialysis, very elderly, cancer tx, • • • • etc) Immunization within the past 4 weeks with live virus vaccine (MMR, Varicella, Yellow Fever) Major viral illness in the past 4 weeks (measles, mumps, mononucleosis) Immune suppression Severe malnutrition Causes of False Positive TST •Infection with non-tuberculous mycobacteria (generally <15 mm) •Prior BCG vaccination BCG Smallpox BCG: it matters how old at vaccination BCG Vaccination Relationship to TST Results Received in infancy Unlikely to cause a TB reaction of ≥ 10 mm after ≥ 10 years of age Received at 1-5 years of age 10-15% will have a positive TST up to 25 years later. Received at 6 years of age or older 40% chance of having a persistent positive TST later in life www.bcgatlas.org Ignore Prior History of BCG when: Risk of real TB exposure is high: •Close contacts of a person with infectious TB disease •Populations with high prevalence of TB infection, eg • Immigrants from TB-endemic areas • Persons from Aboriginal communities with high rates of TB •Chest x-ray consistent with old healed active TB disease And/or risk of progression to active TB is high: •Immunocompromised, including • HIV infection • Renal Failure • Diabetes Mellitus TST interpretation – a case • Canadian born 18 year old, no travel, no TB exposure hx • TST required for volunteering • No TB signs or symptoms • 10mm • CXR normal • Very low risk – likely “false positive” TST interpretation – another case • 37 year man old born in India • BCG • Household contact of brother with pulmonary TB • Well, no medical co-morbidities • TST = 17 mm Ignore BCG and interpret as “positive” because • contact of infectious case • Lived in TB - endemic country, high risk real TB exposure • BCG at birth minimal impact on TST as adult Two-Step TST • Distinguishes a booster effect (due to prior infection) from a conversion due to recent infection • Should be performed only for people who will be getting serial TSTs (health care workers; corrections workers, etc) • If the first test is negative, do a second test 1-4 weeks later • Each TST should be read and recorded at 48-72 hours after planting Management of a Positive TST • First rule out active TB disease • History and physical examination • Chest x-ray - anterior and posterior (AP) and lateral views • If symptoms or chest x-ray findings consistent with pulmonary TB, get 2 -3 sputum samples to send for Acid Fast Bacillus (AFB) smear and culture. • Report all positive tests to the local public health department Evaluation: 1.Clinical Picture Symptoms of TB: • New or worsening cough of at least 2 weeks duration. • Cough is initially dry and may become productive after several weeks. • Fever and night sweats (may be absent in the very young and elderly) • Hemoptysis, anorexia, weight loss and chest pain in more advanced cases. • Lymph node TB is the most common extra-pulmonary site •Most people with TB have normal physical examinations. Evaluation: 2. Interpretation of CXR • PA and lateral views • Chest x-rays should always be interpreted in the context of history, clinical and laboratory findings. Evaluation: 3. bacteriological testing Sputum Collection: •Collect 3 specimens at least 1 hours apart; early a.m. may be easiest, collect over several days if necessary •Collect 5-10 cc of sputum per specimen •Ideally send to Ontario Public Health Lab Other sites if necessary: request TB smear/culture specifically! •Biopsy (eg of enlarged lymph node) •Pleural fluid/pleural biopsy (for pleural effusion) •CSF (if TB meningitis suspected) Contacts: Young Children and HIV+ • Contacts age <5 or HIV+ should ideally be assessed by a specialist. • Babies and toddlers: CXR best quality via hospital radiology dept • Window prophylaxis is strongly recommended pending TST at 8-10 weeks post-exposure - initiate as soon as active disease is ruled out. • Educate parents and older children regarding symptoms of adverse reactions and signs of hepatotoxicity. Decision to Start LTBI Treatment Should be based on: 1.Interpretation of TST in context of patient’s history: • Size of induration in millimetres • Predictive value of the test • Risk of progression to active disease 2. Medical Contraindications • Patients under 65 years old with no comorbidities have low rates of hepatotoxicity 3. Likelihood of adherence to full length of LTBI treatment • Patient ability and commitment • Provider ability to continue monthly follow-up 4. Discussion of risks and benefits with patient 5. Active TB has been ruled out Decision to treat – general approach • In general, high / moderate risk of reactivation <65 should be treated • >65, benefits will likely only outweigh potential harms of treatment if at high risk of reactivation and no comorbidities • In patients <65 who are at slightly increased risk or low risk, decision should be primarily the patient’s Treatment – a case study • 54 year-old man • First Nations Canadian, originally from northern Manitoba • Mother had pulmonary TB when he was 2 yrs old • Current smoker, 1 pack per day, 20 pack year history • Diabetic, on oral meds • Feeling well, no TB signs or symptoms • Chest x-ray: ‘Fibronodular densities in both upper lobes, right greater than left.’ • Had BCG as baby • TST = 23mm Recommendations for TLTBI * medication is free from local PHD Name Interval and Duration Oral Dosage Criteria for Completion Comments Isoniazid (INH) Daily for 9 months Adult: 5mg/kg/day to a max of 300mg daily 9 months (270 doses). Completing 9 months within a 12 month period is acceptable without having to restart treatment. • Recommended treatment regime • Provides optimal protection in preventing progression. • Consult specialist for children, especially < age 5. Vitamin B6 (Pyridoxine) Daily with INH 25 mg Usually prescribed. Effectiveness of INH Consultation or Referral to a TB specialist is recommended for persons who are: Assuming sensitivity to INH and ≥ 80% compliance: •INH, when taken for 12 months is 93% effective in preventing progression to active disease. •However, INH, when taken for 9 months is 90%; thus recommended duration. •INH, when taken for 6 months is 69% effective. • • • • HIV positive Contacts of multidrug-resistant TB Children Pregnant women at high risk for TB disease • Abnormal chest x-ray Treatment – case study #2 • High risk for TB exposure, moderate risk for reactivation • Active TB ruled out – 3 sputums smear/culture neg • LTBI treatment recommended and accepted • INH 9 months • Smoking cessation • What monitoring does he need? • Does he need repeat LFTs during treatment? INH: Adverse Reactions and Monitoring Adverse Reactions Monitoring Comments • • • • • • • • • • • Hepatitis risk and age: ↑ Liver enzymes Hepatitis Peripheral neuropathy CNS GI Hematological Hypersensitivity Drug Interactions (see CPS) Baseline AST/ALT Monthly clinical monitoring Monthly AST/ALT for patients with: • Liver disease • Age ≥ 35 • Alcohol abuse • Prior INH hepatitis • Pregnant or within 3 months postpartum. Age <20 20-34 35-49 50-64 ≥ 65 Risk 0.1-0.2% 0.3% 0.5% 1.0-3.0% 2.0-5.0% •Hepatitis risk increases with daily alcohol intake or viral hepatitis •INH hepatitis is almost always reversible •INH given alone to people with active TB disease can lead to INHresistant TB. Second line alternative for treatment of LTBI Name Interval and Duration Oral Dosage Criteria for Completion Comments Isoniazid and Rifampin (INH/RMP) Daily for 3-4 months Adult: NA Consider collecting sputum and pending for culture results prior to initiation to avoid inducing drug resistance. INH 5mg/kg/day to a max 300mg daily RMP 10mg/kg/day to a max 600mg daily Effectiveness of INH/RMP Consultation or Referral to a TB specialist is recommended for persons who are: • Published efficacy of 3 months of INH/RMP is 64% • Efficacy and safety is similar to 6-9 months of INH alone Use this regime in consultation with a specialist. Rifampin : Adverse Reactions and Monitoring Adverse Reactions Monitoring • • • • • • • • • CNS Dermatological Hypersensitivity Hepatitis GI Hematological Renal Drug Interactions (see CPS) • Comments Baseline bilirubin, serum • creatinine, CBC, platelets and liver • enzymes Repeat measurements if: • • Baseline are abnormal • Patient has symptoms of an adverse reaction. • Colours body fluids reddish-orange May permanently discolour contact lenses By accelerating estrogen metabolism, Rifampin may interfere with effectiveness of birth control pills; alternative contraception should be advised. Contraindicated in severe chronic liver disease. LTBI treatment refused, contraindicated or stopped early… • Counsel about the symptoms of active TB and advise to return for medical assessment if those symptoms arise. • Flag the chart – if symptoms compatible with TB occur in the future, get specimens for TB smear and culture • Routine CXR or follow-up is not recommended. Interferon Gamma Release Assays (IRGAs) • Two types of IGRAs are approved by Health Canada for use: QuantiFERON-TB Gold In-Tube (QFT) and TSPOT. • Currently these tests are not covered by OHIP. • QFT testing is available on a limited basis through Gamma-Dynacare Medical Laboratories. Role of Public Health Reportable • Health Promotion & Protection Act (HPPA) • Both TB infection and disease are reportable to Public Health Contact Follow-up • Active case investigation (source, transmission) • Contact identification and follow-up Drug Ordering • Provision of LTBI medications to Health Care Providers • Supply TB Clinics & Pharmacies Education & Consultation • Client education (new LTBI diagnosed) • HCP consultation Websites www.publichealth.gc.ca www.cdc.gov/tb/ www.who.org www.on.lung.ca www.bcgatlas.org www.phac-aspc.gc.ca www.tstin3d.com www.respiratoryguidelines.ca/tb-standards-2013 Credit Slid