Latent tuberculosis infection: Difference between revisions
From IDWiki
(added some epidemiology) |
mNo edit summary |
||
(10 intermediate revisions by the same user not shown) | |||
Line 1: | Line 1: | ||
− | * 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 == |
== Background == |
||
+ | *Prior exposure to TB leading to persistent latent tuberculosis, usually '''contained within lung granulomas''' |
||
− | === Epidemiology === |
||
+ | *Goal is to identify those who are at increased risk of developing active TB and would benefit from treatment to prevent future reactivation |
||
− | * One quarter to one third of the world population has LTBI (estimated at 1.7 billion people) |
||
+ | *Use the '''[http://tstin3d.com/en/calc.html TST in 3D calculator]''' and the '''[http://www.bcgatlas.org/ BCG World Atlas]''' for risk estimation |
||
− | * More prevalent in the same countries as active tuberculosis, and is highest in South-East Asia, Pacific, and African regions |
||
+ | *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 |
||
− | * More common in older patients who would have been exposed when active tuberculosis was more prevalent |
||
+ | ===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 |
||
+ | {| 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)=== |
||
+ | |||
+ | *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 (i.e. possible false-positive), 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? |
||
+ | #*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== |
||
+ | {| 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 |
||
+ | | |
||
+ | |} |
||
+ | === Timing of Treatment === |
||
− | == Investigations == |
||
+ | * For pregnancy, either delay treatment until after delivery or prefer 4R regimen |
||
− | * Tuberculin skin test (TBST) |
||
+ | * For medical immunosuppression, most guidelines recommend delaying immunosuppression until after the first month of LTBI treatment, where possible, though there is variation in this recommendation<ref name=":0">Hasan T, Au E, Chen S, Tong A, Wong G. Screening and prevention for latent tuberculosis in immunosuppressed patients at risk for tuberculosis: a systematic review of clinical practice guidelines. BMJ Open. 2018 Sep 12;8(9):e022445. doi: [https://doi.org/10.1136/bmjopen-2018-022445 10.1136/bmjopen-2018-022445]. PMID: [https://pubmed.ncbi.nlm.nih.gov/30209157/ 30209157]; PMCID: [http://www.ncbi.nlm.nih.gov/pmc/articles/pmc6144320/ PMC6144320].</ref> |
||
− | ** Sens 90%, Spec >95 |
||
+ | * For transplantation, guidelines recommend starting treatment while they are still on the transplant list, and that treatment should not delay transplantation<ref name=":0" /> |
||
− | * Interferon-gamma release assay (IGRA) |
||
+ | * For patients with HIV, no specific recommendations, likely can start LTBI and HIV treatment concurrently<ref name=":0" /> |
||
− | ** Sn 95%, Sp >95% |
||
− | ** Preferred for those who have received BCG after infancy |
||
+ | ==Further Reading== |
||
− | === Positive TBST Interpretation === |
||
− | # 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 |
||
+ | *[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] |
||
− | == Management == |
||
+ | *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] |
||
− | * Standard regimen (9INH) [[CiteRef::CanTBStandards7e]] |
||
− | ** Nine months of isoniazid with daily vitamin B6 |
||
− | * Alternative shorter courses: |
||
− | ** 4RIF (10 mg/kg [600 mg maximum]): not yet in guidelines, but likely preferred. Slightly higher risk of hepatitis. |
||
− | ** 6INH |
||
− | ** 3-4INH/RMP |
||
+ | ==Tools== |
||
− | == 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://www.tstin3d.com/en/calc.html TST in 3D online TBST/IGRA Interpreter] |
||
− | == Tools == |
||
+ | *[http://www.bcgatlas.org/ BCG World Atlas], which has a listing of every country's BCG vaccination policies |
||
− | * [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: |
+ | [[Category:Tuberculosis]] |
Latest revision as of 10:13, 15 April 2024
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 (i.e. possible false-positive), 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?
- 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
Regimen | Duration | Dose | Adverse Effects and Notes |
---|---|---|---|
First-Line | |||
3HP | 3 months |
|
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 |
Timing of Treatment
- For pregnancy, either delay treatment until after delivery or prefer 4R regimen
- For medical immunosuppression, most guidelines recommend delaying immunosuppression until after the first month of LTBI treatment, where possible, though there is variation in this recommendation[1]
- For transplantation, guidelines recommend starting treatment while they are still on the transplant list, and that treatment should not delay transplantation[1]
- For patients with HIV, no specific recommendations, likely can start LTBI and HIV treatment concurrently[1]
Further Reading
- 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: 10.1080/24745332.2022.2039498
Tools
- TST in 3D online TBST/IGRA Interpreter
- BCG World Atlas, which has a listing of every country's BCG vaccination policies
- ↑ 1.0 1.1 1.2 Hasan T, Au E, Chen S, Tong A, Wong G. Screening and prevention for latent tuberculosis in immunosuppressed patients at risk for tuberculosis: a systematic review of clinical practice guidelines. BMJ Open. 2018 Sep 12;8(9):e022445. doi: 10.1136/bmjopen-2018-022445. PMID: 30209157; PMCID: PMC6144320.
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.