Interpreting the TST

As per the CDC, at least 5 mm of induration constitutes a positive test in high-risk persons:

• HIV infection, close contact with an active TB patient, abnormal chest radiograph with fibrotic changes, organ transplant recipient, and another form of immunosuppression (taking the equivalent of > 15 mg/day of prednisone, TNF antagonists, other biologics)

Induration of 10 mm or greater indicates positivity in persons with above baseline risk of reactivation:

• Chronic kidney disease on dialysis, silicosis, diabetes mellitus, malignancy, underweight status, jejunoileal bypass, gastrectomy, injection drug abuse, age less than 4-years old, foreign-born from countries with high incidence of TB who immigrated within the past 5 years, and residents or workers in prisons, jails, healthcare facilities, and homeless or refugee shelters.

Finally, induration of 15 mm or greater is deemed positive in low-risk patients:

• Age 4-years and older with the low likelihood of TB infection.

 If  TST  is positive:

• If there is a high risk of infection and progression, the test should not be repeated.
• A chest radiograph and clinical evaluation should follow.
• If there is no evidence of active disease is noted by history, physical or radiograph, the patient is deemed to have LTBI and should be treated.
• If the chest radiograph or clinical evaluation are suggestive of tuberculosis, then active infection needs to be excluded with further testing.

If  TST is negative:

• Repeat testing with another TST or an IGRA can be performed if the patient is at high risk of infection progression or active disease to rule out the possibility of a false negative test. (See below.) Not all of these cases would be amenable to repeat testing, however, and decisions to retest should be made on a case by case basis.

Drawing attention to two situations in which repeat testing may be most important:

• TST can be negative in cases where testing occurs within the first 8 weeks of exposure when the immune response has not developed yet, or in cases with remote TB exposure where the tuberculin reaction might have waned. In the latter group, consisting primarily of the elderly where a response may have waned, a second TST (“booster”) applied a couple of weeks later often will be positive.

• A repeat positive second test increases the sensitivity for detecting TB, although in immunocompromised patients a repeated negative test can be a result of lack of immune reaction rather than an exclusion of the tuberculosis diagnosis. High suspicion of the disease has to be used in this setting to decide whether or not to treat, always considering risk and benefits of therapy. Again, a case by case evaluation is key.

On the flip side, a false positive should be suspected in patients who are at a low risk for infection and progression.

In the case of foreign-born adults who have been vaccinated with BCG and have a positive PPD reaction, the positive reaction is more likely due to TB exposure than the remote vaccination, and the immunization history should be disregarded when interpreting test results and deciding upon treatment.

If concern persists about the induration being due to childhood immunization, an IGRA test may be considered, since these would never be positive due to a prior BCG vaccine.

In the case of healthcare workers, and occupational exposure risk, LTBI screening should be repeated yearly for the purposes infection prevention and healthcare epidemiology. More importantly, because those with LTBI infection are most likely to progress to active infection within the first 2 years of infection, such screening optimises the impact of LTBI treatment.

Interpreting IGRA

Results are reported as positive, negative and indeterminate. Indeterminate tests can occur in cases of anergic response, immunosuppression, high initial levels of interferon gamma, active infection, extremes of age, and improper handling of the samples.

Tuberculin Skin Test

 False positive reactions:

• Can occur in patients with prior Bacille-Calmette-Guerin (BCG) vaccination or those with exposures to environmental mycobacteria, incorrect application, and/or interpretation.

False negative reactions:

• Causes of false negative test include anergy secondary to immunosuppression (e.g., HIV infection or corticosteroids), natural waning of immunity, recent live virus vaccination (measles, mumps, polio, smallpox), recent viral infection, recent TB infection (within 8 to 10 weeks), advanced TB, age younger than 6-months, older adults, concomitant bacterial infections, and improper technique and/or reading.  

Tuberculosis is an infection caused by Mycobacterium tuberculosis and spread through the air by coughed or sneezed contaminated droplets. It primarily affects the lungs but can affect other organs as well. Tuberculosis can be fatal which is why screening is so important. Treatment is available and effective.

People in close contact with someone diagnosed with tuberculosis, immunosuppressed, starting an immunosuppressive therapy, or if working in the healthcare field, jails, prisons, or homeless/ refugee centers should be screened for tuberculosis.

There are two tests to screen for tuberculosis: (1) a skin test called Tuberculin skin test, and (2) a blood test called the interferon gamma-release assay. A positive test does not necessarily mean that you have an active disease. However, further studies are needed to rule it out (e.g., chest x-ray, sputum cultures).

A positive test means a person was exposed to the mycobacteria, and the immune system reacted to it by:

• Fighting and removing the bacteria.

• Controlling the bacteria and keeping it dormant, also called latent tuberculosis because it does not show any symptoms or spread. For these cases, treatment and prevention are possible. 

• Not being able to control the disease which has symptoms is called active tuberculosis and requires immediate treatment.

• A positive test also can be a false positive test. For this, the doctor will reassess the patient and the past medical history.

A negative test can mean that there is no infection, or that it is a false negative test. Depending on the patient's risk factors, the doctor will decide whether to retest.

Latent TB infection is prevalent, and treatment of patients with LTBI can reduce the burden of active tuberculosis, especially if screening is performed in populations at high risk for progression to active disease. Current United States guidelines endorse the use of either the TST or IGRA test for this purpose, although there are some minor differences in their performance in some populations. In general, both types of tests should not be used routinely in individual patients. A decision to test should presuppose intention to treat LTBI if detected.