Tuberculin Skin Testing Guide

Tuberculosis Infection (latent) and active/suspect cases of tuberculosis are reportable to the Health Unit.

What is Tuberculosis?

Tuberculosis (TB) is an infection with Mycobacterium tuberculosis acquired by inhalation of bacilli-containing droplet nuclei small enough to reach the alveoli. Most individuals’ immune systems are able to eradicate the bacteria, while others replicate it and develop TB infection.

Active TB disease is defined as disease in a person with infection in whom symptoms, signs, and/or radiographic evidence caused by M. tuberculosis complex are apparent; disease may be pulmonary, extrapulmonary, or both.

How is it Transmitted?

Transmission of M. tuberculosis occurs mostly (with very few exceptions) via droplet nuclei which can then be inhaled by those who are exposed. For this reason, only those with active pulmonary and/or laryngeal TB disease are likely to be contagious.

The probability of transmission increases with bacterial burden, amount and severity of cough in the source case, duration of exposure, proximity to source case, crowding and room ventilation, and delays in diagnosis and/or effective treatment.

Symptoms

A chronic cough of at least 2 to 3 weeks' duration that is initially dry but after several weeks to months will become productive.
Fever and night sweats are common but may be absent from the very young and elderly.
Hemoptysis, anorexia, weight loss, chest pain, and other symptoms are general manifestations of advanced disease.

Tuberculosis infection (latent)

The bacteria M. tuberculosis is present in the lungs, but can survive for years in a dormant state. A person with TB infection does not have active disease, is asymptomatic, and is not contagious. TB infection can develop into active disease at any time.

Identification and treatment of TB infection can substantially reduce the risk of development of active TB disease.

Testing

The goal of testing for TB infection is to identify individuals who are at increased risk for the development of active TB disease, and therefore, would benefit from treatment of TB infection.

There are two acceptable tests for identification of TB infection:

Tuberculin skin test (TST)
Interferon Gamma Release Assay (IGRA)

Refer to Chapter 4: Diagnosis of Tuberculosis Infection of the Canadian Tuberculosis Standards, 8th edition (2022) for more information or contact the Communicable Disease Control Program.

Screening and Treatment

Screening for TB infection should be undertaken only when there is a commitment to treatment or monitoring, should the test results be positive.

Treatment for TB infection should be individualized and based on the risk of prior TB exposure and risk of reactivation. Active TB disease must carefully be ruled out prior to starting TB infection treatment.

See international TB rates by country

Tuberculin Skin Testing (TST)

The TST consists of the intradermal injection of a small amount of purified protein derivative (PPD) from M. tuberculosis bacteria.

In a person who has cell-mediated immunity to these tuberculin antigens, a delayed hypersensitivity reaction will occur within 48 to 72 hours. The reaction will cause localized swelling and will manifest as induration of the skin at the injection site.

The use of TSTs or IGRAs for the diagnosis of active TB disease in adults is not recommended.

Two-Step TST

A two-step TST is useful for the initial skin testing of adults who are going to be retested periodically (e.g., healthcare workers), due to an elevated risk of exposure.

These persons should undergo a two-step TST prior to any exposure to account for the booster effect. This is because the initial TST may elicit an immune response in persons with remote TB infection or prior Bacille Calmette-Guerin (BCG) vaccination.

This "booster" immune response results in a greater response if a second TST is administered anytime from a week to more than a year later.

The two-step protocol needs to be performed and documented ONCE. Any subsequent TST should be a one-step, regardless of how long it has been since the last TST.

A second test should be performed 1 to 4 weeks after the first test using the same materials and techniques to administer and read the TST.

The Health Unit offers TSTs to specific populations:

post secondary students who need a TST to be admitted to or continue with a program
people under the age of 65 entering a Long Term Care Home
medically necessary TSTs covered under OHIP for contact tracing, refugees and homeless/ underhoused
clients who have proof from a doctor who need the testing as part of a medical assessment or treatment plan

Contact the Vaccine Preventable Diseases (VPD) program at 705-474-1400 or 1-800-563-2808 ext. 5252 or email at vpd@healthunit.ca.

Contraindications

Do NOT give a TST to someone who has:

Severe blistering TST reactions in the past
Extensive burns or eczema present over TST testing sites
A current major viral infection (e.g., measles, mumps, varicella)
Documented active TB disease or a well-documented history of adequate treatment for TB infection or disease in the past
Received live virus immunization with the past 4 weeks

Vaccination with live viruses may interfere with TST reactions. For persons scheduled to receive a TST, testing should be done as follows:

Either on the same day as vaccination with live-virus vaccine
Or at least 1 month after the administration of the live-virus vaccine

For more information see TST fact sheet

Note: If the opportunity to perform TST might be missed, TST should not be delayed for live virus vaccines. TST may be administered before or on the same day as the live-virus immunizations, but at a different site.

Who can receive a TST

A TST CAN be given to those who:

Are pregnant or breastfeeding
Have a history of receiving a BCG vaccine
Have a previously positive TST
Are taking low doses of systemic corticosteroids (<15mg prednisone or equivalent daily)
Have a common cold
Have had an immunization the same day (TST should be administered at a different site)
Were immunized within the previous 4 weeks with vaccines other than live virus vaccines

Steps to Conducting a TST:

Step 1: Administering
Locate and Clean Use inner aspect of forearm, 10 cm (4 inches) below elbow, preferably on the non-dominant arm. If neither forearm is suitable, use the outside of the forearm or the upper arm Avoid areas with abrasions, swelling, visible veins, lesions, rash, eczema, burns, or tattoos Clean area with alcohol swab and let air dry Do not use EMLA® or other local anesthetic cream on area being tested Prepare 5 tuberculin units of Tubersol® PPD-Standard is recommended in Canada Check expiry date and ensure vials are labelled with dates when opened Use a 0.6 to 1.3 cm (1/4 -1/2 inch), 26 or 27 gauge needle with a disposable plastic tuberculin syringe Draw up solution just prior to injecting it. Do not preload syringes. Withdraw a little more than 0.1 mL of tuberculin solution from vial under aseptic conditions Expel one drop and ensure that 0.1 mL remains in syringe PPD should be stored between 2 to 8 degree Celcius and the syringe should be placed under a towel to maintain darkness prior to injecting; except when doses are actually being withdrawn from the vial Inject Hold skin taut. Position the bevel of the needle facing up. Insert needle intradermally at a 5 to 15 degree angle to the skin, without aspirating. The tip of the needle will be visible just below the surface of the skin. Insert the needle until the entire bevel is covered. Inject 5 tuberculin units (0.1mL) of Tubersol® PPD-Standard, slowly. A 6 to 10 mm wheal (discrete, pale elevation of the skin) should appear. The size of the wheal is not completely reliable, but if a lot of liquid runs out and there is no wheal, then repeat the injection on the opposite forearm or 5 cm away from the initial injection site on the same forearm. A drop of blood is normal. Do not massage area. Teach Client • Do not cover with bandage • Do not scratch site • Perform all normal activities, including showering and bathing, but do not scrub area • Wheal often disappears within 15 minutes Client must return 48 to 72 hours after administration for reading by a trained healthcare professional. Document: • Date and time of injection • Tuberculin dose, manufacturer, lot number, and expiry date • Site of injection • Person administering the TST Monitor Monitor client for 15 minutes post-injection in case of allergic reaction. Although very rare, be prepared to manage anaphylaxis.
Step 2: Reading
A healthcare professional trained to read TSTs should read the test within 48 to 72 hours after administration. If the TST cannot be read within 48 to 72 hours after administration, it should be repeated at a location far enough from the previous test that the reactions do not overlap. No minimum wait time is required before repeat testing. Inspect Support the forearm on a firm surface and flex slightly at the elbow. Look for induration (a hard, dense, raised formation). Note that induration is not always visible. Palpate Use fingertips to check if induration is present. Mark To mark the border of the induration, move the tip of a pen at a 45 degree angle laterally toward the site of the injection The tip will stop at the edge of the induration if it is present Repeat this on the opposite side of the induration Measure Use a caliper (TB ruler) to measure the distance between the pen marks at the widest transverse diameter (at a right angle to the long axis of the forearm) Measure induration in millimetres (mm). Record no induration "0 mm". Avoid words such as "positive", "negative", "reactive", or "non-reactive" If the measurement falls between demarcations on the ruler, record the lower measurement. Do not round off the diameter of the induration to the nearest 5 mm Do NOT measure erythema (redness). Redness does not indicate TB infection and is not a contraindication to future TSTs Document Date induration is read Measurement of the induration, if any, in millimetres (mm) Record any adverse reactions (e.g., blistering) Name of the individual reading the test
Step 3: Interpreting TST Results
False-positive reactions: Some persons may react to the TST even though they are not infected with M. tuberculosis. The causes of these false-positive reactions may include, but are not limited to: Previous TB vaccination with the BCG vaccine (IGRA blood tests are preferred over TST for those that have had a previous BCG vaccination) Infection with non-tuberculous mycobacteria Incorrect measurement or interpretation of reaction Incorrect antigen used False-negative reactions: Some individuals that are infected with M. tuberculosis may not react to the TST. Reasons for this false-negative reaction may include, but are not limited to: Anergy (absence of the normal immune response to a particular antigen) Recent TB infection (within the past 8 to 10 weeks) Very young age (younger than 6 months) A weakened immune system due to a Human Immunodeficiency Virus (HIV) infection Active TB disease, or if they have recently been infected by a person with active TB disease (it takes 3 to 8 weeks after exposure for a TST to become positive) Recent live-virus measles or smallpox vaccination Incorrect method of administering Incorrect measuring or interpretation of TST reaction Interpretation of a positive or negative TST Interpreting a TST result primarily depends on the clinical context. There are multiple dimensions to consider when faced with a positive or negative TST to help decide whether someone is at risk of developing TB disease. These include the pretest probability that the person is truly infected, the individual risk of TB disease, and the ability of the test to identify persons at risk of disease. Refer to Chapter 4: Diagnosis of Tuberculosis Infection of Canadian Tuberculosis Standards, 8th edition for more information. The online TST/IGRA Interpreter interactive algorithm incorporates all three dimensions discussed above and is highly recommended when deciding on TB infection treatment. TB infection and active/suspect cases of TB are reportable to the CDC Program.
Step 4: Managing a Positive TST
Management of a positive TST should occur in two distinct steps: Decide that a TST is positive: Determine if the TST is positive by reviewing the dimensions from Step 3 and the criteria in Table 1 below Investigate further to rule out a false positive If a TST is considered positive, the individual should be referred for medical evaluation 2. Medical Evaluation Assess signs and symptoms suggestive of possible active TB disease, assess patient risk factors, and order chest radiography In the presence of symptoms or abnormal chest x-ray, collect 3 sputum samples at least 1 hour apart for acid-fast bacilli (AFB) smear and culture Testing for active TB disease is indicated when someone has signs and symptoms of TB, and when an individual is considered to be high-risk Diagnosis of TB infection is made if a person has a positive TST result, and a medical evaluation does not indicate TB disease. The decision about treatment for TB infection is based on a person's chances of developing TB disease, by considering their risk factors. TB infection and active/suspect cases of TB are reportable to the CDC program.

Step 1: Administering

Locate and Clean

Use inner aspect of forearm, 10 cm (4 inches) below elbow, preferably on the non-dominant arm. If neither forearm is suitable, use the outside of the forearm or the upper arm
Avoid areas with abrasions, swelling, visible veins, lesions, rash, eczema, burns, or tattoos
Clean area with alcohol swab and let air dry
Do not use EMLA® or other local anesthetic cream on area being tested

Prepare

5 tuberculin units of Tubersol® PPD-Standard is recommended in Canada
Check expiry date and ensure vials are labelled with dates when opened
Use a 0.6 to 1.3 cm (1/4 -1/2 inch), 26 or 27 gauge needle with a disposable plastic tuberculin syringe
Draw up solution just prior to injecting it. Do not preload syringes.
Withdraw a little more than 0.1 mL of tuberculin solution from vial under aseptic conditions
Expel one drop and ensure that 0.1 mL remains in syringe
PPD should be stored between 2 to 8 degree Celcius and the syringe should be placed under a towel to maintain darkness prior to injecting; except when doses are actually being withdrawn from the vial

Inject

Hold skin taut. Position the bevel of the needle facing up. Insert needle intradermally at a 5 to 15 degree angle to the skin, without aspirating. The tip of the needle will be visible just below the surface of the skin. Insert the needle until the entire bevel is covered.
Inject 5 tuberculin units (0.1mL) of Tubersol® PPD-Standard, slowly.
A 6 to 10 mm wheal (discrete, pale elevation of the skin) should appear.
The size of the wheal is not completely reliable, but if a lot of liquid runs out and there is no wheal, then repeat the injection on the opposite forearm or 5 cm away from the initial injection site on the same forearm.
A drop of blood is normal. Do not massage area.

Teach Client

• Do not cover with bandage

• Do not scratch site

• Perform all normal activities, including showering and bathing, but do not scrub area

• Wheal often disappears within 15 minutes

Client must return 48 to 72 hours after administration for reading by a trained healthcare professional.

Document:

• Date and time of injection

• Tuberculin dose, manufacturer, lot number, and expiry date

• Site of injection

• Person administering the TST

Monitor

Monitor client for 15 minutes post-injection in case of allergic reaction. Although very rare, be prepared to manage anaphylaxis.

Step 2: Reading

A healthcare professional trained to read TSTs should read the test within 48 to 72 hours after administration.
If the TST cannot be read within 48 to 72 hours after administration, it should be repeated at a location far enough from the previous test that the reactions do not overlap. No minimum wait time is required before repeat testing.

Inspect

Support the forearm on a firm surface and flex slightly at the elbow.
Look for induration (a hard, dense, raised formation). Note that induration is not always visible.

Palpate

Use fingertips to check if induration is present.

Mark

To mark the border of the induration, move the tip of a pen at a 45 degree angle laterally toward the site of the injection
The tip will stop at the edge of the induration if it is present
Repeat this on the opposite side of the induration

Measure

Use a caliper (TB ruler) to measure the distance between the pen marks at the widest transverse diameter (at a right angle to the long axis of the forearm)
Measure induration in millimetres (mm). Record no induration "0 mm". Avoid words such as "positive", "negative", "reactive", or "non-reactive"
If the measurement falls between demarcations on the ruler, record the lower measurement. Do not round off the diameter of the induration to the nearest 5 mm
Do NOT measure erythema (redness). Redness does not indicate TB infection and is not a contraindication to future TSTs

Document

Date induration is read
Measurement of the induration, if any, in millimetres (mm)
Record any adverse reactions (e.g., blistering)
Name of the individual reading the test

Step 3: Interpreting TST Results

False-positive reactions:

Some persons may react to the TST even though they are not infected with M. tuberculosis. The causes of these false-positive reactions may include, but are not limited to:

Previous TB vaccination with the BCG vaccine (IGRA blood tests are preferred over TST for those that have had a previous BCG vaccination)
Infection with non-tuberculous mycobacteria
Incorrect measurement or interpretation of reaction
Incorrect antigen used

False-negative reactions:

Some individuals that are infected with M. tuberculosis may not react to the TST. Reasons for this false-negative reaction may include, but are not limited to:

Anergy (absence of the normal immune response to a particular antigen)
Recent TB infection (within the past 8 to 10 weeks)
Very young age (younger than 6 months)
A weakened immune system due to a Human Immunodeficiency Virus (HIV) infection
Active TB disease, or if they have recently been infected by a person with active TB disease (it takes 3 to 8 weeks after exposure for a TST to become positive)
Recent live-virus measles or smallpox vaccination
Incorrect method of administering
Incorrect measuring or interpretation of TST reaction

Interpretation of a positive or negative TST

Interpreting a TST result primarily depends on the clinical context. There are multiple dimensions to consider when faced with a positive or negative TST to help decide whether someone is at risk of developing TB disease. These include the pretest probability that the person is truly infected, the individual risk of TB disease, and the ability of the test to identify persons at risk of disease. Refer to Chapter 4: Diagnosis of Tuberculosis Infection of Canadian Tuberculosis Standards, 8th edition for more information.

The online TST/IGRA Interpreter interactive algorithm incorporates all three dimensions discussed above and is highly recommended when deciding on TB infection treatment.

TB infection and active/suspect cases of TB are reportable to the CDC Program.

Step 4: Managing a Positive TST

Management of a positive TST should occur in two distinct steps:

Decide that a TST is positive:

- Determine if the TST is positive by reviewing the dimensions from Step 3 and the criteria in Table 1 below
- Investigate further to rule out a false positive
- If a TST is considered positive, the individual should be referred for medical evaluation

2. Medical Evaluation

- Assess signs and symptoms suggestive of possible active TB disease, assess patient risk factors, and order chest radiography
- In the presence of symptoms or abnormal chest x-ray, collect 3 sputum samples at least 1 hour apart for acid-fast bacilli (AFB) smear and culture
- Testing for active TB disease is indicated when someone has signs and symptoms of TB, and when an individual is considered to be high-risk
- Diagnosis of TB infection is made if a person has a positive TST result, and a medical evaluation does not indicate TB disease. The decision about treatment for TB infection is based on a person's chances of developing TB disease, by considering their risk factors.

TB infection and active/suspect cases of TB are reportable to the CDC program.

Size of Induration

Table 1: Interpretation of TST Results
TST Result	Situation in which a reaction is considered positive:
	These groups are more at risk of developing TB infection and/or active TB disease.
>5 mm	People living with HIV A recent contact of a person with active TB disease People with chest x-ray findings suggestive of previous TB disease People with organ transplants Other immunosuppressed people (e.g., patients on prolonged therapy with corticosteroids equivalent to/greater than 15mg per day of prednisone or those taking Tumor Necrosis Factor antagonists [TNF-antagonists])
>10 mm	People born in countries where TB disease is common (including Mexico, the Philippines, Vietnam, India, China, Haiti, and Guatemala, or other countries with high rates of TB) People who abuse drugs People who live or work in high-risk congregate settings (e.g., nursing homes, homeless shelters, or correctional facilities) People with certain medical conditions that place them at high risk for TB (e.g., silicosis, diabetes mellitus, severe kidney disease, certain types of cancer, and certain intestinal conditions) People with low body weight (<90% of ideal), children younger than 5 years of age, and infants, children, and adolescents exposed to adults in high-risk categories
>15 mm	People with no known risk factors for TB

NOTE: A negative TST or IGRA is expected in up to 30% of children with TB and should not be used to exclude diagnosis. Consider consultation with an infectious disease specialist if there are concerns regarding TB in this population.

Summary of recommended treatment regimens for TB infection (latent)
Regimen	Duration	Dose	Frequency	Common Side Effects
First-line regimens Rifapentine and Isoniazid (3HP)	3 months (12 doses)	Isoniazid: 15mg/kg Maximum: 900mg Rifapentine: 10-14.0 kg: 300mg 14.1-25.0 kg: 450mg 25.1-32.0 kg: 600 mg 32.1-49.9 kg: 750 mg ≥50.0 kg: 900mg Maximum: 900mg	Once weekly	Flu-like reactions, drug interactions
Rifampin (4R)	4 months (120 doses)	10mg/kg Maximum: 600 mg	Daily	Rash, drug interactions
Second-line regimen Isoniazid (9H)	9 months (270 doses)	5mg/kg Maximum: 300mg	Daily	Hepatoxicity, peripheral neuropathy
Alternative regimens Isoniazid (6H)	6 months (180 doses)	5mg/kg Maximum: 300mg	Daily	Hepatoxicity, peripheral neuropathy
Intermittent Isoniazid for 9 months	9 months (78 doses)	15 mg/kg Maximum: 900mg	Twice weekly	Hepatoxicity, peripheral neuropathy
Isoniazid and Rifampin (3HR)	3 months (90 doses)	Isoniazid: 5mg/kg Maximum: 300mg Rifampin: 10mg/kg Maximum: 600mg	Daily	Hepatoxicity, peripheral neuropathy, drug interactions

Resources

Canadian Sources

American Sources

International Sources

References

Communicable Disease Control Program

705-474-1400 or 1-800-563-2808 ext. 5229

cdc@healthunit.ca

Vaccine Preventable Diseases Program

705-474-1400 or 1-800-563-2808 ext. 5252
vpd@healthunit.ca