Latent tuberculosis infection: Difference between revisions

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== Background ==
 
*Prior exposure to TB leading to persistent latent tuberculosis, usually '''contained within lung granulomas'''
  
*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
  
*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 '''[http://tstin3d.com/en/calc.html TST in 3D calculator]''' and the '''[http://www.bcgatlas.org/ BCG World Atlas]''' for risk estimation
  
*Use the '''[http://tstin3d.com/en/calc.html TST in 3D calculator]''' and the '''[http://www.bcgatlas.org/ 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
  
*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===
  
===Epidemiology===
   
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*More common in older patients who would have been exposed when active tuberculosis was more prevalent
  
*More common in older patients who would have been exposed when active tuberculosis was more prevalent
   
−
===BCG vaccination===
 +
===BCG Vaccination===
   
 
*Done routinely in tuberculosis-endemic countries
  
*Done routinely in tuberculosis-endemic countries
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*Receipt of the BCG vaccine affects interpretation of the tuberculin skin test
  
*Receipt of the BCG vaccine affects interpretation of the tuberculin skin test
   
−
===Risk for progression to active tuberculosis===
 +
===Risk for Progression to Active Tuberculosis===
   
 
*HIV
  
*HIV
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==Diagnosis==
  
==Diagnosis==
−
===Tuberculin skin test (TBST/TST)===
 +
===Tuberculin Skin Test (TBST/TST)===
   
 
*Sn 90%, Sp >95
  
*Sn 90%, Sp >95
Line 33: Line 32:
 
**Especially if received after age 5 years
  
**Especially if received after age 5 years
 
**Also if received after age 1 year, or received multiple times
  
**Also if received after age 1 year, or received multiple times
  +
{| class="wikitable sortable"
  +
!Scenario
  +
!TST Cutoff (mm)
  +
|-
  +
! colspan="2" |High Risk
  +
|-
  +
|people living with HIV
  +
|≥5
  +
|-
  +
|Contact with infectious TB within last 2 years
  +
|≥5
  +
|-
  +
|Fibronodular disease on CXR
  +
|≥5
  +
|-
  +
|Transplant patient
  +
|≥5
  +
|-
  +
|Immunosuppression with biologics or other, including prednisone ≥15 mg daily or higher
  +
|≥5
  +
|-
  +
|CKD stage 4 or 5
  +
|≥5
  +
|-
  +
! colspan="2" |Moderate Risk
  +
|-
  +
|TST conversion within last 2 years
  +
|≥10
  +
|-
  +
|Diabetes mellitus
  +
|≥10
  +
|-
  +
|Malnutrition (<90% IBW)
  +
|≥10
  +
|-
  +
|Current tobacco smoker
  +
|≥10
  +
|-
  +
|Alcohol >3 drinks daily
  +
|≥10
  +
|-
  +
|Silicosis
  +
|≥10
  +
|-
  +
|Hematologic malignancy
  +
|≥10
  +
|-
  +
|Solid-organ malignancy of head-and-neck, lung, or GI tract
  +
|≥10
  +
|-
  +
! colspan="2" |Low Risk
  +
|-
  +
|Any low-risk population
  +
|≥10
  +
|}
   
−
===Interferon-gamma release assay (IGRA)===
 +
===Interferon-Gamma Release Assay (IGRA)===
   
 
*Sn 95%, Sp &gt;95%
  
*Sn 95%, Sp &gt;95%
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*QuantiFERON-TB Gold Plus (QFT-Plus) likely has better PPV than TST in a low-prevalence population
  
*QuantiFERON-TB Gold Plus (QFT-Plus) likely has better PPV than TST in a low-prevalence population
   
−
=== Choice of test ===
 +
=== Choice of Test ===
  +
  +
* Either can be used in most situations
  +
** Historically, there has been a slight preference for TST because of long history of use
  +
** Now, more and more leaning towards IGRA (though barriers due to cost)
  +
* IGRA specifically preferred when the patient has received the BCG vaccine after 1 year of age, received BCG in infancy but age 2 to 10 years, has received multiple BCG vaccines, or is unlikely to follow up to have their TST read
  +
* TST still preferred for serial testing, such as in healthcare, corrections, or prisons
  +
* Positive predictive value of both for the development of active TB is still quite poor
   
  +
=== Sequential Testing ===
−
* 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
  
   
  +
* May be indicated in some situations
−
==Evaluation of a Positive TST==
  
  +
* If high risk, but the initial test was negative, then the alternative may be ordered to increase sensitivity
  +
* If low suspicion of LTBI but TST positive, follow-up IGRA may be reasonable
  +
* If high suspicion of false positive TST, follow-up IGRA may be reasonable
  +
* Patients with discordant results are still at higher risk of progression to active TB
   
  +
=== Evaluation of a Positive TST ===
 
#Is it truly positive?
  
#Is it truly positive?
 
#*Consider IGRA
  
#*Consider IGRA
Line 65: Line 129:
   
 
==Management==
  
==Management==
  +
{| class="wikitable"
  +
!Regimen
  +
!Duration
  +
!Dose
  +
!Adverse Effects and Notes
  +
|-
  +
! colspan="4" |First-Line
  +
|-
  +
|3HP
  +
|3 months
  +
|
  +
* [[isoniazid]] 15 mg/kg weekly (max 900 mg)
  +
* [[rifapentine]] weekly
  +
** 10-14 kg: 300 mg
  +
** 14.1-25 kg: 450 mg
  +
** 25.1-32 kg: 600 mg
  +
** 32.1-49.9 kg: 750 mg
  +
** ≥50 kg: 900 mg
  +
|flu-like reaction, drug-drug interactions
  +
heavy pill burden
  +
difficult to access in Canada
  +
needs Public Health for DOT
  +
|-
  +
|4R
  +
|4 months
  +
|[[rifampin]] 10 mg/kg daily (max 600 mg)
  +
|rash, drug-drug interactions
  +
|-
  +
! colspan="4" |Second-Line
  +
|-
  +
|9H
  +
|9 months
  +
|[[isoniazid]] 5 mg/kg daily (max 300 mg)
  +
[[pyrixodine]] 25 mg daily
  +
|hepatotoxicity, peripheral neuropathy
  +
|-
  +
! colspan="4" |Alternatives
  +
|-
  +
|6H
  +
|6 months
  +
|[[isoniazid]] 5 mg/kg daily (max 300 mg)
  +
[[pyrixodine]] 25 mg daily
  +
|hepatotoxicity, peripheral neuropathy
  +
|-
  +
|9H (intermittent)
  +
|9 months
  +
|[[isoniazid]] 15 mg/kg twice weekly (max 900 mg)
  +
|hepatotoxicity, peripheral neuropathy
  +
|-
  +
|3HR
  +
|3 months
  +
|[[isoniazid]] 5 mg/kg daily (max 300 mg)
  +
[[rifampin]] 10 mg/kg (max 600 mg)
  +
[[pyridoxine]] 25 mg daily
  +
|hepatotoxicity, peripheral neuropathy, drug-drug interactions
  +
|-
  +
! colspan="4" |Under Development
  +
|-
  +
|1HP
  +
|1 month
  +
|isoniazid and rifapentine daily
  +
|
  +
|}
   
  +
* For pregnancy, either delay treatment until after delivery or prefer 4R regimen
−
*Standard regimen (9INH) [[CiteRef::CanTBStandards7e]]
  
−
**Nine months of isoniazid with daily vitamin B6
  
−
*Alternative shorter courses:
  
−
**4RIF (10 mg/kg [600 mg maximum])[[CiteRef::menzies2018fo]]
  
−
***Not yet in guidelines, but likely preferred. Slightly higher risk of hepatitis.
  
−
**6INH
  
−
**3-4INH/RMP
  
   
 
==Further Reading==
  
==Further Reading==
   
 
*[http://blogs.jwatch.org/hiv-id-observations/index.php/common-curbsides-the-tuberculin-skin-test-and-igra-that-dont-agree/2014/11/10/ TBST vs. IGRA for latent TB]
  
*[http://blogs.jwatch.org/hiv-id-observations/index.php/common-curbsides-the-tuberculin-skin-test-and-igra-that-dont-agree/2014/11/10/ TBST vs. IGRA for latent TB]
  +
*Canadian TB Standards, 8th Edition. Chapter 6: Tuberculosis preventive treatment in adults ''Canadian Journal of Respiratory, Critical Care, and Sleep Medicine''. 2022;6(sup1):77-86. doi: [https://doi.org/10.1080/24745332.2022.2039498 10.1080/24745332.2022.2039498]
   
 
==Tools==
  
==Tools==

Revision as of 21:05, 1 April 2023

Background

  • 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

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
Scenario TST Cutoff (mm)
High Risk
people living with HIV ≥5
Contact with infectious TB within last 2 years ≥5
Fibronodular disease on CXR ≥5
Transplant patient ≥5
Immunosuppression with biologics or other, including prednisone ≥15 mg daily or higher ≥5
CKD stage 4 or 5 ≥5
Moderate Risk
TST conversion within last 2 years ≥10
Diabetes mellitus ≥10
Malnutrition (<90% IBW) ≥10
Current tobacco smoker ≥10
Alcohol >3 drinks daily ≥10
Silicosis ≥10
Hematologic malignancy ≥10
Solid-organ malignancy of head-and-neck, lung, or GI tract ≥10
Low Risk
Any low-risk population ≥10

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
    • Historically, there has been a slight preference for TST because of long history of use
    • Now, more and more leaning towards IGRA (though barriers due to cost)
  • IGRA specifically preferred when the patient has received the BCG vaccine after 1 year of age, received BCG in infancy but age 2 to 10 years, has received multiple BCG vaccines, or is unlikely to follow up to have their TST read
  • TST still preferred for serial testing, such as in healthcare, corrections, or prisons
  • Positive predictive value of both for the development of active TB is still quite poor

Sequential Testing

  • May be indicated in some situations
  • If high risk, but the initial test was negative, then the alternative may be ordered to increase sensitivity
  • If low suspicion of LTBI but TST positive, follow-up IGRA may be reasonable
  • If high suspicion of false positive TST, follow-up IGRA may be reasonable
  • Patients with discordant results are still at higher risk of progression to active TB

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

Regimen Duration Dose Adverse Effects and Notes
First-Line
3HP 3 months
  • isoniazid 15 mg/kg weekly (max 900 mg)
  • rifapentine weekly
    • 10-14 kg: 300 mg
    • 14.1-25 kg: 450 mg
    • 25.1-32 kg: 600 mg
    • 32.1-49.9 kg: 750 mg
    • ≥50 kg: 900 mg
 flu-like reaction, drug-drug interactions

heavy pill burden difficult to access in Canada needs Public Health for DOT

4R 4 months rifampin 10 mg/kg daily (max 600 mg) rash, drug-drug interactions
Second-Line
9H 9 months isoniazid 5 mg/kg daily (max 300 mg)

pyrixodine 25 mg daily

hepatotoxicity, peripheral neuropathy
Alternatives
6H 6 months isoniazid 5 mg/kg daily (max 300 mg)

pyrixodine 25 mg daily

hepatotoxicity, peripheral neuropathy
9H (intermittent) 9 months isoniazid 15 mg/kg twice weekly (max 900 mg) hepatotoxicity, peripheral neuropathy
3HR 3 months isoniazid 5 mg/kg daily (max 300 mg)

rifampin 10 mg/kg (max 600 mg) pyridoxine 25 mg daily

hepatotoxicity, peripheral neuropathy, drug-drug interactions
Under Development
1HP 1 month isoniazid and rifapentine daily
  • For pregnancy, either delay treatment until after delivery or prefer 4R regimen

Further Reading

Tools

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