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Latent tuberculous infection: Mantoux, Igra and treatment

Written by Ambimed team | Aug 22, 2022 6:00:00 AM

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)

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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.

A hardening >5 mm is considered positive in

A hardening > 10 mm is considered positive in

A hardening >15 mm is considered positive in

People living with HIV

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Recent contact with a person with TB

People with organ transplants

Other immunosuppressed persons
(e.g., patients on prolonged corticosteroid therapy equivalent to/exceeding 15 mg per day of prednisone or taking TNF-a antagonists)

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?

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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?

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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

TST

IGRA

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

Requires at least two patient visits

Requires only one patient visit

Results are available 48 to 72 hours later

Results may be available in 24 hours (depending on the laboratory)

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

CBCG vaccination may cause false-positive results

BCG vaccination and infection with nontuberculous mycobacteria do not cause false-positive results

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

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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