Latent tuberculosis infection: Difference between revisions
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− | * |
+ | *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 '''[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 |
− | == |
+ | ==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 |
||
+ | *One quarter to one third of the world population has LTBI (estimated at 1.7 billion people) |
||
− | === BCG vaccination === |
||
+ | *More prevalent in the same countries as active tuberculosis, and is highest in South-East Asia, Pacific, and African regions |
||
− | * Done routinely in tuberculosis-endemic countries |
||
+ | *More common in older patients who would have been exposed when active tuberculosis was more prevalent |
||
− | * 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 |
||
+ | ===BCG vaccination=== |
||
− | === Risk for progression to active tuberculosis === |
||
− | * HIV |
||
− | * Transplantation |
||
− | * End-stage renal disease |
||
− | * Specific biologics, including TNFa-α inhibitors |
||
− | * Corticosteroids |
||
+ | *Done routinely in tuberculosis-endemic countries |
||
− | == Investigations == |
||
+ | *Commonly causes an elevated scar as site of inoculation (often on the deltoid) |
||
− | === Tuberculin skin test (TBST/TST) === |
||
+ | **Compared to smallpox, which forms a crater |
||
− | * Sn 90%, Sp >95 |
||
+ | *Receipt of the BCG vaccine affects interpretation of the tuberculin skin test |
||
− | * 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 |
||
+ | ===Risk for progression to active tuberculosis=== |
||
− | === 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 ([[Mycobacterium intracellulare]], [[Mycobacterium chelonae]], and [[Mycobacterium fortuitum]]) |
||
− | * 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 |
||
+ | *HIV |
||
− | == Evaluation of a Positive TST == |
||
+ | *Transplantation |
||
− | # Is it truly positive? |
||
+ | *End-stage renal disease |
||
− | #* Consider IGRA |
||
+ | *Specific biologics, including TNFa-α inhibitors |
||
− | #* BCG vaccine can be considered a cause of false positive when |
||
+ | *Corticosteroids |
||
− | #** vaccine given after 12 months of age, and |
||
− | #** patient has no risk factors, and |
||
− | #** either Canadian-born non-Aboriginal, or not from endemic country |
||
− | # Rule out active TB |
||
− | #* signs/symptoms |
||
− | #* CXR or CT chest |
||
− | #* Sputum x3 if coughing or cavitary lesions |
||
− | # Evaluate risk of reactivation treatment |
||
− | #* INH 300 daily x9 mo with pyridoxine |
||
− | #* baseline liver enzymes and vision testing |
||
− | == |
+ | ==Diagnosis== |
+ | ===Tuberculin skin test (TBST/TST)=== |
||
− | * 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 |
||
+ | *Sn 90%, Sp >95 |
||
− | == Further Reading == |
||
+ | *Lower specificity after BCG vaccination, which can cause false positives |
||
− | * [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] |
||
+ | **Especially if received after age 5 years |
||
+ | **Also if received after age 1 year, or received multiple times |
||
+ | ===Interferon-gamma release assay (IGRA)=== |
||
− | == Tools == |
||
+ | |||
− | * [http://www.tstin3d.com/en/calc.html TST in 3D online TBST/IGRA Interpreter] |
||
+ | *Sn 95%, Sp >95% |
||
− | * [http://www.bcgatlas.org/ BCG World Atlas], which has a listing of every country's BCG vaccination policies |
||
+ | *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== |
||
+ | |||
+ | #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 |
||
+ | #Rule out active TB |
||
+ | #*signs/symptoms |
||
+ | #*CXR or CT chest |
||
+ | #*Sputum x3 if coughing or cavitary lesions |
||
+ | #Evaluate risk of reactivation treatment |
||
+ | #*INH 300 daily x9 mo with pyridoxine |
||
+ | #*baseline liver enzymes and vision testing |
||
+ | |||
+ | ==Management== |
||
+ | |||
+ | *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== |
||
+ | |||
+ | *[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] |
||
+ | |||
+ | ==Tools== |
||
+ | |||
+ | *[http://www.tstin3d.com/en/calc.html TST in 3D online TBST/IGRA Interpreter] |
||
+ | *[http://www.bcgatlas.org/ BCG World Atlas], which has a listing of every country's BCG vaccination policies |
||
[[Category:Tuberculosis]] |
[[Category:Tuberculosis]] |
Revision as of 16:06, 26 July 2020
- 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
- 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
- Rule out active TB
- signs/symptoms
- CXR or CT chest
- Sputum x3 if coughing or cavitary lesions
- 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
- 4RIF (10 mg/kg [600 mg maximum])2
Further Reading
Tools
- TST in 3D online TBST/IGRA Interpreter
- BCG World Atlas, which has a listing of every country's BCG vaccination policies
References
- ^ Canadian Tuberculosis Standards. 7th edition. ed. Template:ISBN. OCLC 978699031.
- ^ Dick Menzies, Menonli Adjobimey, Rovina Ruslami, Anete Trajman, Oumou Sow, Heejin Kim, Joseph Obeng Baah, Guy B. Marks, Richard Long, Vernon Hoeppner, Kevin Elwood, Hamdan Al-Jahdali, Martin Gninafon, Lika Apriani, Raspati C. Koesoemadinata, Afranio Kritski, Valeria Rolla, Boubacar Bah, Alioune Camara, Isaac Boakye, Victoria J. Cook, Hazel Goldberg, Chantal Valiquette, Karen Hornby, Marie-Josée Dion, Pei-Zhi Li, Philip C. Hill, Kevin Schwartzman, Andrea Benedetti. Four Months of Rifampin or Nine Months of Isoniazid for Latent Tuberculosis in Adults. New England Journal of Medicine. 2018;379(5):440-453. doi:10.1056/nejmoa1714283.