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Tuberculin Under Your Skin

The Tuberculin skin test was created 80 years ago and is still used today to screen for tuberculosis. What is the history behind this test, and what happens under our skin when tuberculin is injected?

Throughout its lifetime, tuberculosis (or TB) has gone by . The ancient Greeks called it 鈥減hthisis鈥. In the 1700s, it was 鈥渢he white plague鈥. And in the 1800s, it was 鈥渃onsumption鈥 鈥 perhaps because of how the rapid weight loss caused by TB seems to consume the patient. Tuberculosis is not just of historical interest; it is still with us today and is a . The disease is the 13th leading cause of death and the second leading infectious killer (first place currently goes to COVID-19). While most TB cases are overseas, TB still exists . The incidence rate in the general population is 5 per 100,000, and much higher in Inuit people at 135 per 100,000.

An essential step for preventing the spread of TB is screening for it. In Canada, most people who work in hospitals, hospices, or other high-risk areas are tested for TB regularly using a tuberculin skin test (TST).

What can you expect when getting a ? The healthcare practitioner will inject tuberculin, an extract of the bacterium that causes tuberculosis, below your skin with a special needle. If you aren鈥檛 squeamish and decide to watch the injection, you鈥檒l see a small circle of skin bubble up 鈥 called a wheal 鈥 as the practitioner injects fluid into your arm (don鈥檛 worry, this is temporary). The practitioner will circle the wheal with a pen, and when you return within 48 to 72 hours, will look within the penned circle to find any signs of reaction. The result of the test depends on the amount of swelling (or hopefully lack of swelling). If there is no swelling, the TST is negative, indicating you likely were never infected by TB bacteria. If there is swelling, the TST is positive, indicating you have been infected. You鈥檒l need to do more tests, such as a chest x-ray and physical exam, to determine if you have active TB disease or a latent TB infection.

This widely used test wasn鈥檛 exactly intentionally created. Instead, it was stumbled upon in one physician鈥檚 quest to find a cure for TB.

Bacteria for the History Books

In the 1800s, no one knew what caused TB. Some believed it was hereditary; others thought it was caused by excessive dancing. A few even speculated it was not a disease but the . German physician was the first to discover the bacteria that we now know cause TB. His meticulous work on anthrax bacteria was the perfect preparation for Koch to capture, isolate and cultivate Mycobacterium tuberculosis. Mycobacterium tuberculosis is a that is part of the larger Mycobacterium family, which includes the bacteria that causes leprosy, called . Koch鈥檚 groundbreaking discovery showed that TB is an infectious disease caused by microscopic bacteria (not vampire attacks). Always the hardworking scientist, Koch wanted to go a step further and discover a cure for TB.

Koch created the first formulation of tuberculin by heating and filtering a culture of Mycobacterium tuberculosis. Despite Koch鈥檚 initial hopes, the scientific community found that tuberculin had no value as a cure for TB. But the newly created substance showed promise as a diagnostic tool for the disease. In 1908, showed that an intradermal injection of tuberculin was the best method to detect the disease (hence why the TST is sometimes called the Mantoux test). In the 1930s, discovered a way to isolate and standardize the potency of tuberculin solutions, creating the Purified Protein Derivative (PPD) Tuberculin that is still used today!

Our T-Cells Signal for Trouble

How does the TST tell us who has TB, and why does swelling indicate a positive result? The answer lies in specialized cells that are part of our . The purpose of our immune system is to protect us from intruding pathogens such as bacteria (like Mycobacterium tuberculosis) or viruses (like COVID-19). One component of our immune system is the adaptive immune system. As the name suggests, this system creates defences specifically adapted to each new bacterium or virus we encounter. The adaptive immune system creates and 鈥榯rains鈥 specialized , sometimes called T-cells, to recognize the bacteria or virus and remember it for life. In the case of TB, if you鈥檝e been exposed to Mycobacterium tuberculosis, your body will have already created and trained those T-cells. When during the test, your T-cells think it is Mycobacterium tuberculosis and will initiate an immune response, leading to swelling at the injection site. People who haven鈥檛 been exposed to Mycobacterium tuberculosis will not have those specially trained T-cells, so injecting PPD tuberculin won鈥檛 elicit any reaction.

PPD tuberculin is good at showing those exposed to TB but is not effective at preventing TB disease. Finding a widely effective TB vaccine has proven to be one of the most significant challenges for modern medicine. The is commonly used for young children in countries with high rates of TB but has low efficacy in the general population. In June 2023, a received funding to start large clinical trials, with hopes that this will be the first widely effective vaccine.


@MayaMcKeown

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