Tuberculin purified protein derivative, commonly called PPD, is a solution of proteins extracted from the bacterium that causes tuberculosis. It is the active ingredient in the tuberculin skin test (also known as the Mantoux test), one of the most widely used screening tools for TB infection worldwide. PPD itself does not contain live bacteria and cannot cause tuberculosis. Its sole purpose is to provoke an immune reaction in people whose bodies have previously encountered TB bacteria.
How PPD Is Made
PPD is manufactured by growing a human strain of Mycobacterium tuberculosis in specialized liquid culture media under tightly controlled conditions. As the bacteria grow, they release proteins into the surrounding liquid. That liquid is then filtered to remove the bacteria, and the protein fraction is isolated and purified. The result is a sterile, clear solution that contains only inactivated protein fragments, not whole or live organisms.
The standard dose used for skin testing is 5 tuberculin units (TU) delivered in a tiny 0.1 milliliter injection. That 5 TU dose traces back to a single master batch prepared by researcher Florence Seibert in 1939, known as lot 49608. It was later renamed PPD-S (“S” for standard), and in 1952 the World Health Organization adopted it as the international reference. By definition, 5 TU equals the skin-test activity contained in 0.0001 milligrams of PPD-S. Every commercial PPD product sold in the United States is still calibrated against that original standard using bioassays in both guinea pigs and human volunteers.
What Happens in Your Body After Injection
PPD is injected just beneath the surface of the skin on the inner forearm. If your immune system has previously fought off TB bacteria, or even been exposed without developing active disease, it has memory T-cells that recognize TB proteins. When those T-cells encounter the injected PPD, they trigger a delayed-type hypersensitivity reaction: they rush to the injection site, release signaling molecules, and recruit other immune cells. This process causes the skin to swell into a firm, raised bump called induration.
The reaction is called “delayed” because it doesn’t happen immediately. It typically peaks between 48 and 72 hours after the injection, which is why you need to return to a healthcare provider within that window to have the result measured. The provider measures only the raised, hardened area, not any surrounding redness, using a ruler in millimeters.
How Results Are Interpreted
A PPD result is not simply positive or negative. The size of induration that counts as “positive” depends on your personal risk factors, because the test needs to balance catching real infections against avoiding false alarms.
- 5 millimeters or more is considered positive for people at highest risk: those with HIV, organ transplant recipients, people on immunosuppressive therapy, and anyone who has been in close contact with a person with active TB.
- 10 millimeters or more is positive for people with moderate risk factors, including recent immigrants from countries where TB is common, healthcare workers, and people with certain medical conditions like diabetes or kidney disease.
- 15 millimeters or more is positive for people with no known risk factors for TB.
These thresholds exist because a small reaction in a low-risk person is more likely to be meaningless, while the same small reaction in someone with HIV could signal a real and dangerous infection.
Why the Test Can Be Wrong
PPD testing has well-known limitations in both directions. False positives occur most commonly in people who received the BCG vaccine, a tuberculosis vaccine given routinely in many countries outside the United States. BCG contains a related mycobacterium, and the immune memory it creates can cross-react with PPD proteins, producing a bump even though the person was never infected with TB. A 55-year follow-up study confirmed that BCG vaccination causes false-positive skin test results through this cross-reactivity, sometimes decades after vaccination.
False negatives are the opposite problem. People whose immune systems are weakened, whether by HIV, cancer treatment, malnutrition, or certain medications, may not mount a strong enough T-cell response to produce measurable induration, even if they carry TB infection. Very recent infections can also be missed because the immune system needs several weeks after exposure to develop the memory T-cells that react to PPD. Newborns and the elderly are also more prone to false-negative results.
PPD Skin Test vs. Blood Tests
The main alternative to the PPD skin test is a blood test called an interferon-gamma release assay, or IGRA. Instead of injecting proteins under the skin, an IGRA draws a blood sample and measures whether your T-cells release a signaling molecule (interferon-gamma) when exposed to TB-specific proteins in a lab dish. The key advantage of IGRAs is that they use proteins found only in TB bacteria and not in BCG, so they are far less likely to produce false positives in vaccinated individuals.
In terms of raw accuracy, the two tests perform similarly. A large meta-analysis published in The Lancet found that in lower-incidence countries, the PPD skin test had a specificity of about 76% and a sensitivity of about 63% for predicting active TB. The most common IGRA showed nearly identical numbers: 74% specificity and 65% sensitivity. Neither test meets the World Health Organization’s ideal target of 75% or higher for both measures, which is why a positive result on either test typically leads to further evaluation, including a chest X-ray and sometimes sputum testing.
The practical differences matter more than the statistical ones. A skin test requires two visits (one for injection, one for reading), costs less, and needs no laboratory equipment. A blood test requires one visit and a functioning lab, costs more, but eliminates the BCG false-positive problem. For someone who received BCG vaccination as a child, a blood test is generally the better choice.
What a Positive Result Means
A positive PPD result does not mean you have active tuberculosis. It means your immune system has encountered TB bacteria at some point. Most people with a positive skin test have latent TB infection, meaning the bacteria are present in the body but dormant, causing no symptoms and posing no risk of spreading to others. Only about 5 to 10 percent of people with latent TB ever develop active disease, though the risk is much higher for those with weakened immune systems.
After a positive PPD, the next step is typically a chest X-ray to look for signs of active lung disease. If the X-ray is clear and you have no symptoms like a persistent cough, fever, or unexplained weight loss, you likely have latent infection. Treatment for latent TB is shorter and simpler than treatment for active disease, and it dramatically reduces the chance of the infection ever becoming active.
Once you have tested positive, you will generally test positive for the rest of your life, even after successful treatment. Repeating a PPD skin test in someone with a known positive history is unnecessary and can cause unnecessarily large local reactions. Blood tests or chest X-rays are used instead for any future screening.