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To Be Or Not To Be – Morning Report November 23rd

In morning report this week we reviewed a case of respiratory tuberculosis (TB) with adenopathy in the mediastinum and hilar adenopathy. Some pearls around testing and treatment for TB are listed below:

1. Tuberculosis Infection and Disease

World Health Organization (WHO) estimated 8.8 million incident cases of TB worldwide in 2010.

Due to the global Stop TB Strategy, annual incident cases have been falling since 2006 and global TB incidence is falling at about 2% per year. Between years 2015 and 2020, the cumulative incidence reduction was 11%.

The highest prevalence is in Southeast Asia, Western Pacific, and Africa.

TB infection is different from disease. Of the patients who develop TB infection, 5% develop primary disease within 18 to 24 months. 90% of those with infection, go on to develop latent TB infection, of which 5% will have reactivation with pulmonary or extra-pulmonary manifestations.

2. Risk Factors for TB

See UpToDate reference below

3. Testing for Latent TB

There are two accepted tests for identification of latent TB infection: the tuberculin skin test (TST) and the interferon gamma release assay (IGRA).

When interpreting the induration of the TB skin test, the following table from the 2014 Canadian TB standards is helpful:

TST ResultSituation in which reaction is considered positive
0-4 mmIn general this is considered negative, and no treatment is indicated
Child under 5 years of age and high risk of TB infection
>= 5 mmHIV infection
Contact with infectious TB case within the past 2 years
Presence of fibronodular disease on chest x-ray (healed TB, and not previously treated)
Organ transplantation (related to immune suppressant therapy)
TNF alpha inhibitors
Other immunosuppressive drugs, e.g. corticosteroids (equivalent of ≥15 mg/day of prednisone for 1 month or more; risk of TB disease increases with higher dose and longer duration)
End-stage renal disease
≥10 mmAll others, including the following specific situations:TST conversion (within 2 years)
– Diabetes, malnutrition (<90% ideal body weight), cigarette smoking, daily alcohol consumption (>3 drinks/day)
– Silicosis
– Hematologic malignancies (leukemia, lymphoma) and certain carcinomas (e.g. head and neck)
From the 2014 Canadian TB Standards (linked below)

The Bacille Calmette-Guérin (BCG) should be considered the likely cause of a positive TST under the following circumstances:

  • BCG vaccine was given after 12 months of age AND
    • There has been no known exposure to active TB disease or other risk factors AND
      • the person is either Canadian-born non-Aboriginal OR
      • an immigrant/visitor from a country with low TB incidence.

This means that a positive TBST should NOT be attributed to BCG vaccine when:

  • BCG vaccine was given before 12 months of age
  • There is a high probability of TB infection based on
    • Exposure to an active case or known TB risk factors
    • Aboriginal Canadian
    • From a TB endemic region in the world
  • There is a high risk of progression to active TB (i.e. immunocompromise)

4. Testing for Active TB

Thinking specifically about pulmonary TB (given that TB can manifest in pretty much any other organ)! — this is how you would test: the diagnosis is made by demonstration of acid-fast bacilli on smear and culture of Mycobacterium tuberculosis, or requires amplification and detection of M. tuberculosis complex (MTBC) nucleic acids using nucleic acid amplification tests (NAATs). If collecting sputum, three samples are ideally required to send for smear and culture.

Chest X-ray is not specific to make the diagnosis of TB which is why microbiologic diagnosis is ultimately required.

The use of serology is not recommended for TB diagnosis.

In our patient, biopsy showing necrotizing (caseating) granulomas pointed towards a diagnosis of respiratory TB.

5. Treatment for Active TB

Four drugs are the first line therapy for active TB (including a fifth which is vitamin B6 or pyridoxine). If the isolate of TB is fully susceptible to all first-line drugs, ethambutol can be stopped, and pyrazinamide should be given for the first 2 months. Then for another four months patients are usually on isoniazid and rifampin but this can be extended for other reasons.

See some side effects in this table:

Isoniazid INHINH can produce liver dysfunction, may interfere with pyridoxine metabolism and cause peripheral neuropathy or psychotic episodes (so we give vitamin B6 or pyridoxine with INH), drowsiness, fatigue, hair loss
Rifampin RMP Hypersensitivity reactions and drug interactions: main ones to know / consider estrogens, coumadin, anticonvulsants, glucocorticoids, digoxin, antiarrhythmics, sulfonylureas, theophylline, cyclosporin, methadone and ketoconazole
Pyrazinamide PZAHepatotoxicity and rash, arthralgias, can rarely cause gout usually in those with pre-existing gout, GI upset
Ethambutol EMBVisual impariemnt (decreases in visual acuity, visual fields or colour vision), if taking for longer should be referred to ophthalmology

The above is for treatment of ACTIVE TB.

Read more on the Canadian TB standards below for management of latent TB infection (see specific chapter).

References:

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