Working Together To Stop TB

Physician’s Guide to Tuberculosis

Think TB For more information about TB, contact York Region Community and Health Services The Regional Municipality of York, 17250 Yonge Street, Newmarket, ON L3Y 6Z1 905-830-4444 or 1-877-464-9675, Ext. 6000 TTY 1-866-252-9933 Fax: 905-895-5450 or visit www.york.ca/TB

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Tuberculosis (TB) is PREVENTABLE, TREATABLE, AND CURABLE York Region Community and Health Services continue to see new TB cases. This resource is a tool to assist you in assessing suspect cases and implementing next steps. For more detailed information about the treatment and management of TB disease and infection, please refer to The Canadian Tuberculosis Standards (CTS), 6th Edition 2007. Roles and Responsibilities Treating physician • Diagnose and supervise treatment • Notify York Region Community and Health Services and provide information about client promptly (suspects and confirmed cases) • Instruct client to take prescription to York Region’s designated pharmacies for free TB medication • Prescribe and supervise chemoprophylaxis

York Region Community and Health Services, TB Program • Ensure early identification and treatment of TB disease • Provide Directly Observed Therapy (DOT) for TB cases • Evaluate and follow-up close contacts of TB cases • Screen populations at high risk for TB • Provide publicly funded TB medication (disease and infection) • Follow-up with new entrants to Canada diagnosed with inactive TB • Provide health teaching to clients, families, health care providers

Targeted testing for TB is done to identify persons at high risk for TB who would benefit from treatment for latent TB infection (LTBI). Skin tests can diagnose TB infection in persons at increased risk for progression

to active disease. The skin test is not reliable for diagnosis of active disease. For more information on indications, method and frequency of testing, please see the Canadian TB Standards (CTS), 6th Edition 2007, p. 55.

Indications for TB Skin Testing

WHO SHOULD BE TESTED? • Close contacts of cases with TB disease • Persons with a history of active TB disease or chest x-ray evidence of past TB disease who have not received adequate treatment • Foreign-born persons from areas where TB is endemic, especially immigrants who have arrived in the last 2 years • Foreign-born persons, including immigrant children and adolescents < 20 years of age, and refugees between 20 and 50 years of age, from countries with a high incidence of TB, should be tested as soon as they arrive in Canada • Those who come from aboriginal communities with high rates of LTBI or TB disease • Persons with HIV infection, cancer, diabetes, renal disease, silicosis, substance abuse, the malnourished (< 90 % ideal body weight, BMI ≤ 20), organ transplantation clients, and those who are immunosuppressed • Persons taking glucocorticoids, tumour necrosis factor (TNF) alpha-inhibitors, or any other medications that may lower the immune response

WHO SHOULD BE TESTED? ... continued • The under-housed or homeless • Those referred for immigration medical surveillance • Staff/volunteers of long term care, correctional and child care facilities • Those at risk of occupational exposure to TB, especially health care workers • Individuals who stay for prolonged periods in TB endemic countries, especially if they are in settings which would put them at risk of TB exposure (i.e., refugee camps, hospitals, missions) should be tested before leaving Canada (baseline) then on return. NOTE: Pregnancy or history of BCG vaccine is not a contraindication to having a TB skin test.

WHO SHOULD NOT BE TESTED? • Persons with TB disease or a well documented history of adequate treatment for TB infection or disease in the past • Persons who have a documented positive skin test • Anyone who has had a Tuberculin test in the past that severely blistered • Anyone with extensive burns or eczema present over testing sites • Those with a viral infection in the past month, e.g., measles, mumps, rubella, varicella or yellow fever • Anyone who has had a live vaccine immunization in the past 4 weeks, e.g., MMR, Varivax NOTE: A single skin test may elicit a modest immune response. A repeat skin test any time from one week to one year later will elicit a much greater response if an individual was infected a long time ago.

WHEN IS A TWO STEP SKIN TEST NECESSARY? Two step Tuberculin skin testing is necessary for persons who: • Will subsequently be tested at regular intervals (i.e. health care workers, child care workers, correctional service workers) • Are travelling to TB endemic countries for prolonged periods of time • Had a negative first skin test. Complete a second skin test 1 to 4 weeks later (up to 1 year). Each skin test should be read by a trained health care professional and recorded in mm (not +ve or -ve) at 48 to 72 hours after planting.

If the TB skin test (TST) is requested by public health and a completed form/report is needed, then both the test and the completion of the form/report cannot be billed to the client. Only the appropriate OHIP fees can be claimed (e.g., A001 for the visit/assessment and G372 for the injection). If a TST is requested by a client as evidence of immunization status*, for admission or continuation in a day care or pre-school program or a school, community college, university or other educational institution or program as evidence of immunization status (for example), then the TST is insured by OHIP. However the completion and transmission of a form/report is uninsured and cannot be billed to OHIP. *The only way to assess ‘immunization status’ is to perform a TST. If a TST is requested solely for employment purposes (e.g., a hospital), then the test and the completion of the form is uninsured and can be billed to the patient or third party.

Serum provided by the government is not to be used for uninsured TB testing. When uninsured TB testing is performed, the serum should be either: I. Acquired by the physician and sold to the client at a direct cost (with reasonable mark-up to account for any indirect costs e.g., storage, administration, etc.) OR II. Acquired by the client from the pharmacy via prescription, provided by the physician. Ontario Medical Association (OMA) January 2011 Physician’s Guide to Third Party and Other Uninsured Services p. 17.

Charging for TB Skin Tests

Proper interpretation of the TB skin test should include size of the reaction (induration), predictive value of the test (considering causes of false-negative, false-positive reactions), and risk of progression to active disease. Tuberculin Reaction Size

Situation in which reaction is considered positive

(mm of induration)

0 to 4 mm

• HIV infection with immune suppression and the expected likelihood of TB infection is high (e.g., client is from a population with a high prevalence of TB infection, is a close contact of an active contagious case or has an abnormal x-ray)

5 to 9 mm

• HIV infection • Close contact of active contagious case • Children suspected of having tuberculosis disease • Abnormal chest x-ray with fibronodular disease • Other immune suppression: TNF-alpha inhibitors, chemotherapy, metabolic disturbances

≥ 10 mm

All others CTS p. 63

NOTE: Results must be reported in mm duration (not positive, negative). Any person with a POSITIVE skin test should have a complete tuberculosis assessment which includes: • A history and physical examination • A chest x-ray AP and lateral • In the presence of symptoms or chest x-ray findings consistent with pulmonary TB, collect 3 sputum specimens for AFB and MTB culture. Specimens can be collected 8 to 24 hours apart (or longer if necessary). At least one specimen should be collected in the early morning upon awakening. Causes of false negative reactions: • Persons with active TB disease or another severe illness • Poor injection technique or when solution is improperly stored • Person has been immunized with a live vaccine in the past 4 weeks (i.e., measles, mumps, rubella, varicella, yellow fever) • Immune suppression (HIV, cancer, diabetes, chronic renal failure, severe protein deficiency, on systemic corticosteroids, TNF- alpha inhibitors or burns) • Severe malnutrition • Major viral infections in the past 4 weeks (i.e. mononucleosis, mumps, measles) • Infants < 6 months of age, or persons of advanced age Causes of false positive reactions: • Infection with non-tuberculosis mycobacterium (i.e., environmental mycobacterium) • Prior BCG vaccination. Refer to The Canadian Tuberculosis Standards (6th Ed.) (2007), p. 63 to 64. Additional resource available at McGill University’s website, http://www.tstin3d.com

Interpreting TB Skin Tests

Recommendations for treatment of latent TB infection (LTBI) Drug Isoniazid (INH)

Interval and duration

Oral Dosage

Criteria for completion

Comments

Daily for 9 months

Adult: 5 Minimum 270 mg/kg/day doses within Max. 300 12 months mg/day

• R ecommended treatment regimen • P rovides optimal protection in preventing progression against active disease For children, consult with Sick Kids Hospital ID Clinic or a Pediatrician

Daily for 6 months

Adult: 5 mg/kg/day Max. 300 mg/day

Provides 69% protection to active disease

Vitamin Daily with B6 INH (Pyridoxine)

25 mg /day

Rifampin (RMP)

Adult: 10 mg/kg/ day Max: 600 mg/day

Daily for 4 months

Minimum 180 doses within 9 months

Indicated in HIV infection, poor nutrition, alcoholism, pregnancy, diabetes, uremia, neonatal period and neuropathy Minimum 120 doses within 6 months

Table adapted from Toronto Public Health LTBI Quick Reference

Alternate regimen for persons: • Who cannot tolerate INH • Who are contacts of persons with INH resistance • When INH for 9 months or months is not an option

Consider treatment of LTBI according to the Canadian Tuberculosis Standards. Approximately 10% of persons infected with TB will go on to develop active TB disease: • 5% within 2 years of infection and • 5% for the remainder of their life “If LTBI treatment is refused by client or is contraindicated yet in whom the risk of TB disease is high, counsel client regarding signs and symptoms of TB and follow-up with a chest x-ray at 6, 12 and 24 months. This is the period of highest risk.” (CTS p. 136) A POSITIVE skin test can indicate either INFECTION OR DISEASE. All positive skin tests are required to be reported to York Region Community and Health Services. Infection: • A positive skin test • Normal chest x-ray or abnormal chest x-ray but active disease has been ruled out • Negative smear with negative culture • Asymptomatic

Management of Positive Skin Tests

BCG Information BCG Bacille Calmette-Guerin (BCG) is a live, attenuated vaccine for TB. It was first used in 1921 and continues to be used today in European and TB endemic countries. It was discontinued in Canada as a routine vaccination in the early 1970’s. In Canada, the vaccine is currently given to select groups of people who still have high rates of TB, such as newborns and infants living on some First Nation reserves and in Inuit communities. Can a person who received BCG in the past have a TB skin test? Yes. TB skin testing is recommended and can be given to people who have received BCG vaccination in the past.

BCG vaccination should be considered the likely cause of a positive TB skin test if: • BCG vaccine was given after 12 months of age and the person is either Canadian-born nonAboriginal or an immigrant/visitor from a low TB incidence country. BCG vaccination can be ignored as a cause of a positive TB skin test if: • BCG vaccination was given in infancy, and the person tested is now aged 10 years or older • There is a high probability of TB infection: - Close contacts of an infectious TB case - Aboriginal Canadians from a high-risk community - Immigrants/visitors from a country with high TB incidence. • There is high risk of progression from TB infection to disease (CTS, p. 64)

FIGURE 2.3

Estimated TB incidence rates, 2010

RUSSIAN FEDERATION

CHINA

INDIA PAKISTAN AFGHANISTAN NIGERIA BRAZIL

DR CONGO

ETHIOPIA UGANDA KENYA UR TANZANIA

ZIMBABWE SOUTH AFRICA

MYANMAR THAILAND INDONESIA

Estimated new TB cases (all forms) per 100 000 population 0–24

MOZAMBIQUE

25–49 50–99 100–299 ≥300 No estimate

FIGURE 2.4

Estimated H IV prevalence in new TB cases, 2010

BANGLADESH VIET NAM CAMBODIA PHILIPPINES

Risk Factors for the Development of Active TB among Persons infected with Mycobacterium tuberculosis (CTS p. 65) High Risk • Acquired immunodeficiency syndrome (AIDS) • Human immunodeficiency virus (HIV) infection • Transplantation (related to immunosuppressant therapy) • Silicosis • Chronic renal failure requiring hemodialysis • Carcinoma • Recent TB infection (≤ 2 years) • Abnormal chest x-ray – fibronodular disease Increased Risk • Treatment with glucocorticoids • Tumor necrosis factor (TNF) -alpha inhibitors • Diabetes mellitus (all types) • Underweight (< 90% ideal body weight; for most persons this is a body mass index ≤ 20%) • Young age when infected (0 to 4 years) • Cigarette smoker (1 pack/day) • Abnormal chest x-ray – granuloma Low Risk • Infected person • No known risk factor • Normal chest x-ray (low risk reactor)

Risk factors for the Development of Active TB

York Region Community and Health Services should be notified if a client has: • A positive culture of mycobacterium tuberculosis complex from sputum, body fluid or tissues OR • Without bacterial evidence but with clinical signs or symptoms, radiological or pathological evidence, of active pulmonary or non-pulmonary with a positive TB skin test and/or AFB smears from sputum or other body fluids or tissues. Assess for common signs and symptoms: Signs: • Not always obvious • Abnormal chest radiography It is important to watch for signs of non-pulmonary disease such as lymphadenopathy, pleural effusion, abdominal or bone and joint involvement as these are often found concomitantly, especially in persons with HIV. Symptoms: • Cough of at least 3 weeks duration that initially is dry but in 2 to 3 months will become productive • Fever • Night sweats • Anorexia

• Unexplained weight loss • Fatigue • Chest pain • Chills • Hemoptysis

Management of TB Disease

If pulmonary TB is suspected and/or confirmed: • Initiate airborne precautions for suspect or confirmed case • Order chest x-ray, if not previously done • Collect sputum for TB (AFB, culture) • Order HIV testing • Prescribe and supervise medical treatment • Referral to Infectious Disease Specialist or Respirologist is recommended. The Tuberculosis Diagnostic and Treatment Services for Uninsured Persons (TB-UP) Program is available to assist suspect or confirmed cases of TB who have no OHIP coverage, providing payment for outpatient medical and testing services. York Region Community and Health Services can help access this program.

Daily dose adults and [children] mg/kg**

Usual adult daily dose mg**

Twice weekly dose mg**

Common adverse reactions*

INH (Isoniazid)

5 [10-15]

300

900

RMP (Rifampin)

10 [10-20]

600

600

Asymptomatic elevation of aminotransferases, hepatitis, paresthesias. Hepatitis, flu-like illness, orange discoloration of body fluids, drug interactions

PZA (Pyrazinamide)

18-26 [15-30]

1000-2000

2000-4000

Hepatitis, elevated uric acid levels, arthralgia

EMB (Ethambutol)

18-26 [15-20]

800-1600

2000-4000

Retrobulbar neuritis

Drug

(CTS p. 123)

* All drugs may cause rash, nausea, or fever. ** American Thoracic Society recommendations based on lean body mass.

Doses and Common Adverse Reactions to Anti-TB Drugs

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All TB drugs are publicly funded. York Region has 3 designated pharmacies which dispense tuberculosis medication, free of charge. Health+Pharmacy York Central Hospital 10 Trench Street, Richmond Hill Phone: 905-883-7500 Fax: 905-883-7502

Dales Pharmacy Markham Stouffville Hospital 377 Church Street, Markham Phone: 905-471-1234 Fax: 905-471-3732

Centric Health Pharmacy Southlake Regional Health Centre 101- 581 Davis Drive, Newmarket Phone: 905-830-5988 Fax: 905-830-5984

Tuberculosis Clinics serving the Greater Toronto Area St. Michael’s Hospital Respiratory Clinic 416-813-8097 Phone: Fax: 416-813-6675

West Park Healthcare Centre TB Clinic 416-243-3600 Phone: Fax: 416-243-8947

Toronto Western Hospital TB Clinic Phone: 416-603-5853 Fax: 416-603-5987

The Hospital for Sick Children TB Clinic Phone: 416-813-8327 Fax: 416-813-5032 For more information, visit www.york.ca/tb

www.tstin3d.com (Interpreting TB skin tests) http://www.phac-aspc.gc.ca/tbpc-latb/itir-eng.php (list of countries that are considered to have a high TB burden)

How to order TB Medications and Resources

Individuals newly arrived in Canada may have been referred for medical surveillance for tuberculosis by Citizenship and Immigration Canada because of a previous history of TB or an abnormal chest radiograph suggestive of inactive TB. Following their arrival in Canada, these persons are required to report to the local Public Health authorities who will direct them to a health care provider to: • Confirm if the client has latent tuberculosis infection (LTBI) • Ensure no active TB currently exists • Determine the appropriate course of medical care, which may include treatment of LTBI Follow-up of new entrants to Canada for active TB disease and infection • history of active TB not previously treated • history of adequate treatment of active TB • abnormal CXR suggestive of inactive TB • recent contact with infectious TB

 Rule out active TB • history • physical • CXR • smear/cultures as appropriate



Active TB



• consult with a TB expert • consider possibility of drug resistance • treat according to Canadian TB Standards

 Latent TB Infection

  • once treatment is completed, counsel regarding signs & symptoms of TB and discontinue follow-up







• consider treatment of LTBI according to CanadianTB Standards • if suspect drug resistance, consult with a TB expert

• if treatment for LTBI refused/ not tolerated, counsel re signs & symptoms of TB; follow-up for 2 years with CXR at 6-12 month intervals Symptoms suggestive of TB should immediately be evaluated to rule out active TB Adapted from Heywood et al CMA J 2003; 168 (12) p. 1564

Immigration Medical Surveillance Requirements

Acknowledgements References Heywood, et al, “Guidelines for the investigation and follow-up of individuals under medical surveillance for tuberculosis after arriving in Canada : a summary”, in Canadian Medical Association Journal, 2003; 168 (12) p. 1563-5. Ministry of Health and Long-Term Care, Tuberculosis Protocol, September 2006. Ministry of Health and Long-Term Care, Tuberculosis and Control Guidance Document, 2011. Ontario Medical Association, January 2011, Physician’s Guide to Third Party and Other Uninsured Services, p. 17 Pottie, K., et al. “Evidence-based clinical guidelines for immigrants and refugees.” Canadian Medical Journal, 183 (12), p. E852-E857 Toronto Public Health, “Assessment and Treatment of Latent Tuberculosis Infection in Adults.” Quick Reference Sheet. Tuberculosis Prevention and Control, Public Health Agency of Canada and the Canadian Lung Association/Canadian Thoracic Society. (6th ed.). (2007). Canadian Tuberculosis Standards. Ottawa, ON: Minister of Health.

Working Together To Stop TB

Physician’s Guide to Tuberculosis

Think TB For more information about TB, contact York Region Community and Health Services The Regional Municipality of York, 17250 Yonge Street, Newmarket, ON L3Y 6Z1 905-830-4444 or 1-877-464-9675, Ext. 76000 TTY 1-866-252-9933 Fax: 905-895-5450 or visit www.york.ca/tb

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