When coming into contact with Mycobacterium Tuberculosis, two events can occur:
- The latent tuberculous infection
- The tuberculous disease
Latent tuberculous infection (LTI) is defined as a persistent immunological response to M.tuberculosis antigens in the absence of signs or symptoms of disease.
Tuberculosis infection is a primary infection that can also remain silent for life and give no symptoms or disease, and positive individuals are not contagious.
Globally, it is estimated that up to one-quarter of the population has latent tuberculous infection, for which the risk of developing full-blown disease, causing morbidity and possibility of infection, is 5-10% over a lifetime.
Therapeutic regimens are available to treat latent infection, with a cure rate of 60-90%.
Two categories of diagnostic tests are currently available to identify individuals with ITL: the tuberculin skin test (TST) and blood tests to identify interferon gamma production after lymphocyte-specific antigen stimulation (IGRA test).
Mantoux's tuberculin skin test (TST)
.The Mantoux tuberculin skin test (TST), named for the physician who invented it in the early 1900s, is a method of determining whether a person is infected with Mycobacterium tuberculosis. The TST is performed by injecting 0.1 ml of purified tuberculin protein derivative (PPD) into the inner surface of the forearm. The injection should be performed with a tuberculin syringe, intradermally. When properly placed, the injection should produce a swelling in the skin, like a pimple.
The skin test reaction should be read 48 or 72 hours after administration by a health care provider. If for any reason the reading cannot be taken within the 72 hours, another test must be rescheduled. The reaction should be measured in millimeters of induration (swelling), not erythema (redness). Below is a summary table on the evaluation of induration.
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A hardening >5 mm is considered positive in |
A hardening > 10 mm is considered positive in |
A hardening >15 mm is considered positive in |
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People living with HIV .Recent contact with a person with TB People with organ transplants Other immunosuppressed persons Fibrotic changes at chest radiography compatible with previous TB |
Recent immigrants (within 5 years) from high-endemic countries Persons abusing drugs Mycobacteriology laboratory staff Residents and employees of environments and High-risk communities: prisons, nursing homes, hospitals and residential health institutions, homeless shelters Subjects with the following diseases and conditions: silicosis, diabetes mellitus, chronic renal insufficiency, some oncohematological diseases, some neoplasms (e.g. carcinoma of head and neck), weight reduction≥10% of ideal weight, gastrectomy, digiunoileal bypass People with low body weight (<90% of ideal body weight) Children younger than 5 years |
People without known risk factors for TB |
From CDC
Can there be false positives?
.Some people may react to TST even if they do not have M. tuberculosis infection. Causes of these false-positive reactions may include, but are not limited to:
- Previous tuberculosis vaccination with Bacille Calmette-Guérin (BCG) vaccine.
- Infection with nontuberculous mycobacteria (mycobacteria other than M. tuberculosis, atypical)
- Mismeasurement or misinterpretation of induration
Can there be false negatives?
.Some people may not react to TST even though they have been infected with M. tuberculosis. Reasons for these false-negative reactions may include, but are not limited to:
- Anergy
- Recent TB infection (within the last 8 to 10 weeks)
- Very young age (less than 6 months)
- Recent vaccination against morbillus or smallpox
- Performance, measurement or misinterpretation of TST reaction
The IGRA blood test
Interferon-Gamma Release Assays (IGRA) is a blood test designed to diagnose Mycobacterium tuberculosis infection. Like the Mantoux test, it cannot make the differential diagnosis between latent infection and disease.
IGRA measures a person's immune reactivity to M. tuberculosis. The Quantiferon test, the test that adopts the IGRA technique, detects the cytokine Interferon Gamma released upon stimulation of T lymphocytes with two highly specific TB antigens (substances that can produce an immune response).
Four tubes are used to perform the blood test.
What are the advantages of IGRA over the Mantoux test?
- It requires only one patient visit to conduct the test, and thus the risk of invalidation is lower
- Preventive BCG (Bacille Calmette-Guérin) vaccination does not cause false-positive results
- Infection with nontuberculous mycobacteria does not cause false-positive results
What are the disadvantages and limitations of IGRA?
- Blood samples must be processed within 8-30 hours after collection
- Mistakes in the collection or transportation of blood samples or in the operation and interpretation of the test can decrease the accuracy of IGRA
- The tests can be expensive
- It is an invasive procedure and may be less accepted by the patient
- Few scientific data exist regarding the performance of IGRA testing in children, especially those younger than 5 years
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TST |
IGRA |
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Tuberculin is injected under the skin and produces a delayed-type hypersensitivity reaction if the person has been infected with M. tuberculosis |
Blood sample. The test measures the immune response to tuberculosis bacteria in whole blood |
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Requires at least two patient visits |
Requires only one patient visit |
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Results are available 48 to 72 hours later |
Results may be available in 24 hours (depending on the laboratory) |
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The test result is influenced by the assessment of the health care provider |
The result of the laboratory test is not influenced by the assessment of the health care provider |
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CBCG vaccination may cause false-positive results |
BCG vaccination and infection with nontuberculous mycobacteria do not cause false-positive results |
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A negative test reaction does not exclude the diagnosis of ITL or tuberculosis disease |
A negative test reaction does not exclude the diagnosis of ITL or tuberculosis disease |
From CDC
Diagnosis of latent tubercular infection
In order to make the diagnosis of latent tuberculous infection, after detecting positivity to one or both tests (TST or IGRA or sequential TST and IGRA), a chest X-ray should be performed to rule out active tuberculous disease. If the radiograph confers a picture of normality, in the absence of symptoms, a diagnosis of latent tuberculous infection is made and, if deemed necessary, treatment will be prescribed.
Below is the diagnostic algorithm for latent tubercular infection.
Therapeutic treatment for latent tuberculosis infection
.Currently, several treatment regimens are recommended for ITL. The choice of regimen will vary according to the patient, considering tolerability, adherence, or possible drug interactions. The treatment scheme options are:
- Isoniazide 300 mg/day daily for 6 months
- Isoniazide 300 mg/day daily for 9 months
- Rifampicin 600 mg/day daily for 4 months
- Rifampicin 600 mg/isoniazide 300 mg daily for 3 months
