Tuberculosis

by Matthew Magyar MDCM FRCPC and Vincent Deslandes PhD, MDCM, FRCPC
August 25, 2023

What is tuberculosis?

Tuberculosis is a common disease caused by bacteria belonging to the Mycobacteria Tuberculosis Complex (MTBC) group.  Bacteria in this group that are known to cause disease in humans are M. tuberculosis, M. africanum, and M. bovis. While the incidence of tuberculosis has declined in many countries over the last century, it is still an important public health concern and the leading cause of death from infectious diseases worldwide. Health authorities estimate that approximately one-quarter of the world’s population will become infected with MTBC at some point in their life.

How is tuberculosis spread? 

Tuberculosis is typically spread when a person who has the disease in their lungs cough or sneeze. This results in tiny respiratory particles called aerosols floating in the air for some time.  Uninfected individuals may breathe the bacteria into their lungs. Once inside the body, the bacteria are either removed by the immune system or remain in the lungs as a persistent infection.

The rate of tuberculosis is higher in large cities or other places where people live or work in close contact with each other. Laboratory workers who work with these pathogens, and health care workers caring for infected patients, may also contract the disease if the appropriate precautions are not taken.

Latent vs. active tuberculosis

Most people who become infected with MBTC will not show any symptoms because their immune system has successfully managed the disease. This is called latent tuberculosis. A person with latent tuberculosis is very unlikely to spread the disease to other people because bacteria are not leaving their body when they cough or sneeze. However, a person with latent tuberculosis may start to develop symptoms. At this point, the disease is called active tuberculosis.

Risk factors for developing active tuberculosis include:

• Infection at a young age
• Infection within the last 18 months
• Immunosuppression
• Malnutrition
• Higher intensity and duration of exposure to someone spreading the disease

What are the symptoms of active tuberculosis?

People with active tuberculosis may show a wide range of symptoms that may mimic other common conditions, leading to delayed diagnosis and treatment.

Symptoms of active tuberculosis include:

• Persistent cough
• Difficulty breathing
• Fever
• Weight loss
• Poor appetite
• Decreased energy
• Sweating at night
• Swollen lymph nodes

How do doctors test for tuberculosis?

Testing is usually performed on people suspected of having active tuberculosis. Most people with respiratory symptoms are asked to provide a sputum sample, which is fluid from inside the lungs produced after a big cough. However, other body fluids or tissue samples may also be used. For example, a small sample of lymph node tissue is commonly removed in a procedure called a biopsy to test for MBTC. Unlike other types of bacteria, MTBC can take several weeks to grow in the laboratory. As a result, it often takes several weeks to let people know their test results.

Tests performed to look for active disease

Acid-fast staining

This test uses a special dye, which makes the bacteria look red when examined under the microscope. The test is called “acid-fast” because unlike other types of bacteria, the bacteria that cause tuberculosis look red even after being exposed to acid. The test usually takes 24-72 hours to perform.

A report that says, “acid-fast bacilli seen”, or “AFB seen”, means that bacteria were seen when your sample was examined under the microscope. This is considered a positive result. However, this test is not specific for MBTC and other types of bacteria may also produce a positive result. For this reason, your doctor will need to interpret this result in combination with other information about you, including your symptoms and possible exposure to tuberculosis in the past.

Because the bacteria that cause tuberculosis are slow-growing, most samples contain very few bacteria. For this reason, a negative result does not exclude the possibility that a person has tuberculosis, and doctors are advised to consider performing additional tests for people at high risk for the disease.

Mycobacterial culture

This test involves growing bacteria from a sputum, body fluid, or tissue sample in a laboratory dish. It is considered the gold standard method of detecting MTBC and for the diagnosis of active tuberculosis. The bacteria that cause tuberculosis grow very slowly and it may take several weeks to complete the test. If bacteria grow in the dish, additional tests will be performed to confirm that they are part of the MTBC. A positive result in combination with appropriate symptoms is diagnostic of tuberculosis. A negative result is usually only reported after 4-6 weeks of incubation.

In Canada, when MTBC is identified, physicians and the microbiology laboratory staff have a duty to notify local public health agencies.

Polymerase chain reaction (PCR)

This test has recently been introduced to help diagnose tuberculosis earlier in the course of the disease. PCR works by looking for genetic material (DNA) found only in the bacteria that cause tuberculosis. This test is faster than acid-fast staining and culture, and it may be performed directly on the sample taken from a person. As with the acid-fast test described above, a negative test does not completely exclude the possibility that the person has tuberculosis, and doctors are advised to consider performing additional tests for people at high risk for the disease.

Tests may also be performed to look for latent tuberculosis in individuals that may have been exposed to tuberculosis in the past. Unlike the tests for active tuberculosis that look for bacteria in the body, the tests for latent tuberculosis examine the immune system to see if it has a “memory” of the disease.

Tests performed to look for latent disease

Tuberculin skin test (TST)

This test is performed by placing a small, non-infectious sample of MTBC bacteria under the skin. After 48-72 hours, a health professional will assess the area for firmness and measure its size. If the reaction is determined to be positive, this would typically indicate past exposure to tuberculosis. A person who was previously treated for tuberculosis, or who received the BCG vaccination as a child, may also test positive.

Interferon-Gamma Release Assay (IGRA)

This test is performed using a blood sample. It works by looking at how the immune cells in the blood respond when exposed to parts of the MTBC bacteria. If a person has been previously exposed to the bacteria, the immune cells will produce chemicals designed to fight the infection. This is considered a positive result. There are, however, rare situations in which a person who has not been exposed to MTBC bacteria will produce a positive result. This needs to be discussed with your doctor.

References

1. Fitzgerald DW, Sterling TR, Haas DW. Mycobacterium tuberculosis. In: Mandell, Douglas, and Bennett’s Principles and Practice of Infectious Diseases. 2020.
2. Forbes BA, Hall GS, Miller MB, Novak SM, Rowlinson MC, Salfinger M, et al. Practice guidelines for clinical microbiology laboratories: Mycobacteria. In: Clin Microbiol Rev. 2018.