Latent tuberculosis infection

• Prior exposure to TB leading to persistent latent tuberculosis, usually contained within lung granulomas
• Goal is to identify those who are at increased risk of developing active TB and would benefit from treatment to prevent future reactivation
• Use the TST in 3D calculator and the BCG World Atlas for risk estimation
• Standard prescription is 4 months of rifampin 10 mg/kg/day (up to 600 mg); counsel patient on side effects and monitor liver enzymes weekly to start

Background

Epidemiology

• One quarter to one third of the world population has LTBI (estimated at 1.7 billion people)
• More prevalent in the same countries as active tuberculosis, and is highest in South-East Asia, Pacific, and African regions
• More common in older patients who would have been exposed when active tuberculosis was more prevalent

BCG vaccination

• Done routinely in tuberculosis-endemic countries
• Commonly causes an elevated scar as site of inoculation (often on the deltoid)
  • Compared to smallpox, which forms a crater
• Receipt of the BCG vaccine affects interpretation of the tuberculin skin test

Risk for progression to active tuberculosis

• HIV
• Transplantation
• End-stage renal disease
• Specific biologics, including TNFa-α inhibitors
• Corticosteroids

Diagnosis

Tuberculin skin test (TBST/TST)

• Sn 90%, Sp >95
• Lower specificity after BCG vaccination, which can cause false positives
  • Especially if received after age 5 years
  • Also if received after age 1 year, or received multiple times

Interferon-gamma release assay (IGRA)

• Sn 95%, Sp >95%
• Doesn't crossreact with BCG (uses ESAT-6 and CFP-10) but can crossreact with other non-tuberculous mycobacteria (most likely Mycobacterium marinum, Mycobacterium kansasii, Mycobacterium szulgai, and Mycobacterium flavescens)
• Preferred for those who have received BCG after infancy
• May be more useful in patients who are unlikely to follow up in 48 hours, or who need urgent immunosuppression and need a faster result
• QuantiFERON-TB Gold Plus (QFT-Plus) likely has better PPV than TST in a low-prevalence population

Choice of test

• Either can be used in most situations, although there is a slight preference for TST because of long history of use
• IGRA specifically preferred when the patient has received the BCG vaccine after 1 year of age, has received multiple BCG vaccines, or is unlikely to follow up to have their TST read
• IGRA should not be used when serial testing will be needed, such as in healthcare, corrections, or prisons

Evaluation of a Positive TST

1. Is it truly positive?
   • Consider IGRA
   • BCG vaccine can be considered a cause of false positive when
     • vaccine given after 12 months of age, and
     • patient has no risk factors, and
     • either Canadian-born non-Aboriginal, or not from endemic country
2. Rule out active TB
   • signs/symptoms
   • CXR or CT chest
   • Sputum x3 if coughing or cavitary lesions
3. Evaluate risk of reactivation treatment
   • INH 300 daily x9 mo with pyridoxine
   • baseline liver enzymes and vision testing

Management

• Standard regimen (9INH) 1
  • Nine months of isoniazid with daily vitamin B6
• Alternative shorter courses:
  • 4RIF (10 mg/kg [600 mg maximum])2
    • Not yet in guidelines, but likely preferred. Slightly higher risk of hepatitis.
  • 6INH
  • 3-4INH/RMP

Further Reading

• TBST vs. IGRA for latent TB

Tools

• TST in 3D online TBST/IGRA Interpreter
• BCG World Atlas, which has a listing of every country's BCG vaccination policies