TB Infection: Diagnosis and Treatment · TB Infection and TB Disease: Diagnosis and Treatment 15 Latent TB Infection Tests •Tuberculin Skin Test (TST) •TB Blood Tests –Interferon
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Navigating Frontiers in TB Case Management: Strengthening Partnerships for Improved Patient Outcomes June 2, 2015 Curry International Tuberculosis Center
TB Infection and TB Disease: Diagnosis and Treatment 1
TB Infection:
Diagnosis and
Treatment
Michael Cooper, MD, MS
Section of Epidemiology
State of Alaska
Updated May 2015
Objectives
• Describe approved tests for diagnosing TB
infection
• Describe acceptable regimens for TB
infection treatment
Objectives
• Describe approved tests for diagnosing TB
infection
– Tuberculin Skin Test (TST)
– TB Blood Tests (IGRA – QFT, T Spot)
• Describe acceptable regimens for TB
infection treatment
– 9H, 4R, 3HP
– (6H, 6R)
Navigating Frontiers in TB Case Management: Strengthening Partnerships for Improved Patient Outcomes June 2, 2015 Curry International Tuberculosis Center
TB Infection and TB Disease: Diagnosis and Treatment 2
Objectives - Additional
• TB in Alaska history – very brief
• Basic understanding of TB Infection
• Logistics of TB control in Alaska
• Good resources*
AD 400 – probable TB – St. Lawrence Island
1500’s – probable TB – Pt. Barrow
Navigating Frontiers in TB Case Management: Strengthening Partnerships for Improved Patient Outcomes June 2, 2015 Curry International Tuberculosis Center
TB Infection and TB Disease: Diagnosis and Treatment 3
1700’s – Russian explorers and traders
1800’s – Gold/fish/whales
1880 1953
Navigating Frontiers in TB Case Management: Strengthening Partnerships for Improved Patient Outcomes June 2, 2015 Curry International Tuberculosis Center
TB Infection and TB Disease: Diagnosis and Treatment 4
Organic
Act - 1884
1931 - Alaska Native Service
Territory - 1912
Native Health = Bureau of
Education - 1930
First Health
Commissioner - 1945
USPHS – IHS - 1955
1880 1953
1926-1930
AK Native
TB death rate
655/100,000
1952
1,823/100,000
TB Incidence
AK Native
1930-1936
AK Native
TB death rate
810/100,000 1943
2,000-4,000
active TB cases
70 beds
1880 1953
Parran Report – 1953-1954
http://dhss.alaska.gov/Commissioner/Documents/PDF/Parran_Report.pdf
Navigating Frontiers in TB Case Management: Strengthening Partnerships for Improved Patient Outcomes June 2, 2015 Curry International Tuberculosis Center
TB Infection and TB Disease: Diagnosis and Treatment 5
• “Tuberculosis is the Alaskan Scourge”
• It still shows “the scars of an exploited colony.”
– “Health conditions…are deplorable”
• “We must help Alaskans to help themselves.”
– “..disgraceful burden of disease” in our own country
– Achilles heel – defense
Parran Report – 1953-1954
http://dhss.alaska.gov/Commissioner/Documents/PDF/Parran_Report.pdf
• White Alaska
– “young, vigorous, urbanized”
– “life-expectancy as favorable as…states.”
• Native Alaska
– “sickness, crippling conditions, premature death”
– “…a degree exceeded in very few parts of the world.”
Parran Report - “Two Worlds”
http://dhss.alaska.gov/Commissioner/Documents/PDF/Parran_Report.pdf
Alaska – Historical TB Rates
Navigating Frontiers in TB Case Management: Strengthening Partnerships for Improved Patient Outcomes June 2, 2015 Curry International Tuberculosis Center
TB Infection and TB Disease: Diagnosis and Treatment 6
Active TB Rate by year, Alaska, 1992-2013
Incidence of TB in Alaska by Region
2008 - 2013
Region 2008
(cases/rate)
2009 (cases/rate)
2010 (cases/rate)
2011 (cases/rate)
2012 (cases/rate)
2013 (cases/rate)
Anchorage/
Mat-Su 19 ( 5.2) 12 ( 3.2) 18 ( 4.8) 29 ( 7.5) 10 (2.5) 25 (6.3)
Gulf 2 ( 2.6) 1 ( 1.3) 0 ( 0.0) 5 ( 6.2) 3 (3.7) 4 (5.0)
Interior 4 ( 3.8) 4 ( 3.7) 11 (10.1) 4 ( 3.6) 4 (3.5) 1 (0.9)
Northern 6 (25.4) 5 (21.1) 11 (46.5) 8 (29.7) 16 (58.6) 10 (36.3)
Southeast 3 ( 4.3) 2 ( 2.9) 2 ( 2.9) 1 ( 1.4) 5 (6.7) 1 (1.3)
Southwest 17 (43.5) 13 (33.1) 15 (38.2) 20 (48.1) 28 (66.6) 30 (70.5)
STATE TOTAL 50 (7.4) 37 ( 5.3) 57 ( 8/0) 67 ( 9.3) 66 (9.0) 71 (9.6)
TB Cases, by Race, Alaska, 2001-2010
0
10
20
30
40
50
60
70
80
White AI/AN Asian/PI Afr Am
% Population
% TB cases
Navigating Frontiers in TB Case Management: Strengthening Partnerships for Improved Patient Outcomes June 2, 2015 Curry International Tuberculosis Center
TB Infection and TB Disease: Diagnosis and Treatment 7
TB Cases, by Race, Alaska, 2001-2010
0
10
20
30
40
50
60
70
80
White AI/AN Asian/PI Afr Am
% Population
% TB cases
Brief thoughts on LTBI
Brief thoughts on LTBI
• Why not screen and treat everyone?
• Challenging foe!
– Slow growing, dormant
• Suboptimal tests
• Suboptimal drug regimens
Navigating Frontiers in TB Case Management: Strengthening Partnerships for Improved Patient Outcomes June 2, 2015 Curry International Tuberculosis Center
TB Infection and TB Disease: Diagnosis and Treatment 8
Tuberculosis terminology
Tuberculosis terminology
Latent TB Disease
Active
Disease
Inactive
Disease Infection Latent
Infection
LTBI
Tuberculosis terminology
Disease
Infection
Navigating Frontiers in TB Case Management: Strengthening Partnerships for Improved Patient Outcomes June 2, 2015 Curry International Tuberculosis Center
TB Infection and TB Disease: Diagnosis and Treatment 9
TB Pathophysiology
Small, et al NEJM 2001
TB Pathophysiology
Small, et al NEJM 2001
Infection and Disease
Latent TB Infection (LTBI) TB Disease
No symptoms Symptoms may include:
•Productive cough > 3 weeks
•Weight loss
•Sweats at night
•Hemoptysis
•Fatigue
•Fever / chills
Not sick Usually feels sick
Cannot infect others Often infectious
(+) TST or IGRA (+) TST or IGRA
Normal CXR & negative AFB smears May have abnormal CXR & (+) AFB
smears or culture
Needs TX for LTBI to prevent progression
to active TB disease
Needs treatment for active disease
Navigating Frontiers in TB Case Management: Strengthening Partnerships for Improved Patient Outcomes June 2, 2015 Curry International Tuberculosis Center
TB Infection and TB Disease: Diagnosis and Treatment 10
Infection and Disease
Latent TB Infection (LTBI) TB Disease
No symptoms Symptoms may include:
•Productive cough > 3 weeks
•Weight loss
•Sweats at night
•Hemoptysis
•Fatigue
•Fever / chills
Not sick Usually feels sick
Cannot infect others Often infectious
(+) TST or IGRA (+) TST or IGRA
Normal CXR & negative AFB smears May have abnormal CXR & (+) AFB
smears or culture
Needs TX for LTBI to prevent progression
to active TB disease
Needs treatment for active disease
Infection and Disease
Latent TB Infection (LTBI) TB Disease
No symptoms Symptoms may include:
•Productive cough > 3 weeks
•Weight loss
•Sweats at night
•Hemoptysis
•Fatigue
•Fever / chills
Not sick Usually feels sick
Cannot infect others Often infectious
(+) TST or IGRA (+) TST or IGRA
Normal CXR & negative AFB smears May have abnormal CXR & (+) AFB
smears or culture
Needs TX for LTBI to prevent progression
to active TB disease
Needs treatment for active disease
Latent Infection to Active Disease-
Reactivation
• Lifetime risk estimate
– 10%
Navigating Frontiers in TB Case Management: Strengthening Partnerships for Improved Patient Outcomes June 2, 2015 Curry International Tuberculosis Center
TB Infection and TB Disease: Diagnosis and Treatment 11
Latent Infection to Active Disease-
Reactivation
• Lifetime risk estimate
– 10%
• Increased risk for disease
– HIV, tobacco, alcoholism, IDDM, malignancy,
immune suppression (glucocorticoids, TNF
inhibitors, malnutrition, renal failure…
Resource - http://www.tstin3d.com/en/calc.html
Resource - http://www.tstin3d.com/en/calc.html
Navigating Frontiers in TB Case Management: Strengthening Partnerships for Improved Patient Outcomes June 2, 2015 Curry International Tuberculosis Center
TB Infection and TB Disease: Diagnosis and Treatment 12
Resource - http://www.tstin3d.com/en/calc.html
LTBI Prevalence in AK?
True or False
• 90% of third graders in YK are infected with TB
Navigating Frontiers in TB Case Management: Strengthening Partnerships for Improved Patient Outcomes June 2, 2015 Curry International Tuberculosis Center
TB Infection and TB Disease: Diagnosis and Treatment 13
True or False
• 90% of third graders in YK are infected with TB
• True…
True or False
• 90% of third graders in YK are infected with TB
• True…in 1950
(89%)
Navigating Frontiers in TB Case Management: Strengthening Partnerships for Improved Patient Outcomes June 2, 2015 Curry International Tuberculosis Center
TB Infection and TB Disease: Diagnosis and Treatment 14
What is the prevalence of LTBI in
Alaska?
• Unknown
• LTBI is not reportable in Alaska
– SOA provides medications
– SOA manages many LTBI cases
• No database, no surveillance
– School screening (changing)
What is the prevalence of LTBI in
Alaska?
• Unknown
• Estimates:
– One third of the world infected
– ~2% of U.S. born individuals
– ~20% of Foreign Born U.S.
• (NHANES 1999-2000)
Latent TB Infection Tests
Navigating Frontiers in TB Case Management: Strengthening Partnerships for Improved Patient Outcomes June 2, 2015 Curry International Tuberculosis Center
TB Infection and TB Disease: Diagnosis and Treatment 15
Latent TB Infection Tests
• Tuberculin Skin Test (TST)
• TB Blood Tests
– Interferon Gamma Release Assays (IGRA)
• Quantiferon TB Gold In-Tube (QFT-GIT)
• T Spot
Latent TB Infection Tests
TST advantages
TST disadvantages
IGRA advantages
IGRA disadvantages
Who should use IGRA?
Navigating Frontiers in TB Case Management: Strengthening Partnerships for Improved Patient Outcomes June 2, 2015 Curry International Tuberculosis Center
TB Infection and TB Disease: Diagnosis and Treatment 16
Who should use IGRA?
Who should use IGRA?
• BCG vaccinated
• Low return rate
• Some contacts
• ?low risk - No
Who should use IGRA be
screened?
• Higher risk
– close contacts, foreign-born
• Both tests have limitations
Navigating Frontiers in TB Case Management: Strengthening Partnerships for Improved Patient Outcomes June 2, 2015 Curry International Tuberculosis Center
TB Infection and TB Disease: Diagnosis and Treatment 17
Tuberculin Skin Test (TST)
TST is:
• A) A good test
• B) A lousy test
• C) Better than TB blood tests
• D) Worse than TB blood tests
• E) All of the above
Tuberculin Skin Test (TST)
TST is:
• A) A good test
• B) A lousy test
• C) Better than TB blood tests
• D) Worse than TB blood tests
• E) All of the above
Treatment for LTBI
Navigating Frontiers in TB Case Management: Strengthening Partnerships for Improved Patient Outcomes June 2, 2015 Curry International Tuberculosis Center
TB Infection and TB Disease: Diagnosis and Treatment 18
Treatment for LTBI
Standard regimens
• 9 months of isoniazid (INH, H)
– 6 months of isoniazid
• 4 months of rifampin (RIF, R)
– 6 months of rifampin
• 3 months of isoniazid plus rifapentine (3HP)
Resources
• CDC LTBI App - http://www.cdc.gov/tb/publications/MobileLTBIApp/default.html
• http://globaltb.njms.rutgers.edu/downloads/products/ltbidrugcard.pdf
Case Presentation
• 45 yo from the Philippines – TB screening
• Denies symptoms
• Denies TB contacts
• What next?
Navigating Frontiers in TB Case Management: Strengthening Partnerships for Improved Patient Outcomes June 2, 2015 Curry International Tuberculosis Center
TB Infection and TB Disease: Diagnosis and Treatment 19
Case Presentation
• 45 yo from the Philippines – TB screening
• TB test?
• TST or IGRA?
Case Presentation
• Do they give BCG in the Philippines?
Resource - www.bcgatlas.org
Navigating Frontiers in TB Case Management: Strengthening Partnerships for Improved Patient Outcomes June 2, 2015 Curry International Tuberculosis Center
TB Infection and TB Disease: Diagnosis and Treatment 20
Case Presentation
• Does SOA pay for IGRA?
• Can your lab do an IGRA?
• Can this patient get a TST with BCG hx?
Case Presentation
• 45 yo from the Philippines – TB screening
• Patient states she had a positive TST in past
• Can you trust this?
• Can you do another TST?
Case Presentation
• 45 yo from the Philippines – TB screening
• TST is 11mm. Is that positive?
Navigating Frontiers in TB Case Management: Strengthening Partnerships for Improved Patient Outcomes June 2, 2015 Curry International Tuberculosis Center
TB Infection and TB Disease: Diagnosis and Treatment 21
TST Interpretation
• http://www.epi.alaska.gov/pubs/webtb/TB_Manual.pdf
Resource
Alaska Tuberculosis Program Manual
• http://www.epi.alaska.gov/pubs/webtb/TB_Manual.pdf
Case Presentation
• 45 yo from the Philippines – TB screening
• Do they need a chest radiograph?
• Two view or single PA?
• What if she had one three months ago?
Navigating Frontiers in TB Case Management: Strengthening Partnerships for Improved Patient Outcomes June 2, 2015 Curry International Tuberculosis Center
TB Infection and TB Disease: Diagnosis and Treatment 22
Case Presentation
• 45 yo from the Philippines – TB screening
• TST positive (could it be due to BCG?)
• Radiograph ‘normal’
• Should you request three sputa?
– Any symptoms?
Case Presentation
• 45 yo from the Philippines – TB screening
• Treatment is offered…which regimen?
TB Disease:
Diagnosis and
Treatment
Michael Cooper, MD, MS
Section of Epidemiology
State of Alaska
Updated May 2015
Navigating Frontiers in TB Case Management: Strengthening Partnerships for Improved Patient Outcomes June 2, 2015 Curry International Tuberculosis Center
TB Infection and TB Disease: Diagnosis and Treatment 23
Objectives
• Basic principles of medical management of
TB disease
Objectives
• Basic principles of medical management of
TB disease
• Use multiple drugs - RIPE
– Don’t add single drugs to failing regimen
• Use DOT
• Duration of therapy – usually 2 + 4 months
– Depends - Drugs/response/extent of disease
Drugs
• R - Rifampin
• I – Isoniazid
• P – Pyrazinamide
• E – Ethambutol
Navigating Frontiers in TB Case Management: Strengthening Partnerships for Improved Patient Outcomes June 2, 2015 Curry International Tuberculosis Center
TB Infection and TB Disease: Diagnosis and Treatment 24
Drugs
• R - Rifampin
– drug interactions
• I – Isoniazid
– hepatotoxicity
• P – Pyrazinamide
– first 2 months
• E – Ethambutol
– Optic neuritis, stop if pan-sensitive
Drug Regimens
• Initial Phase – INH, RIF, PZA, EMB
– 2 months
• Daily/daily then twice weekly/three times weekly
• Continuation Phase – INH, RIF
– 4 months
• Daily/twice weekly/three times weekly
Drug Regimens
• You’ll see all kinds of variations
– Good and bad
– Inexperienced, experienced
– Accepted, wacky
– Errors
• Practical question – what to do with unusual
med orders?
Navigating Frontiers in TB Case Management: Strengthening Partnerships for Improved Patient Outcomes June 2, 2015 Curry International Tuberculosis Center
TB Infection and TB Disease: Diagnosis and Treatment 25
TB Control in Alaska
Patient
PHN
SOE
ANMC
Regional Provider
Drug Regimens
• You’ll see all kinds of variations
– Good and bad
– Inexperienced, experienced prescribers
– Accepted, wacky
– Errors
• Practical question – what to do with unusual
med orders?
Drug Regimens
• Longer regimens
– Culture positive at 2 months/cavitary
• Needs for other drugs
– Resistance/intolerance/side effects
• Extra-pulmonary TB
– CNS TB
Navigating Frontiers in TB Case Management: Strengthening Partnerships for Improved Patient Outcomes June 2, 2015 Curry International Tuberculosis Center
TB Infection and TB Disease: Diagnosis and Treatment 26
Adverse Reactions
• Rash
• GI intolerance
• Liver toxicity
• Peripheral neuropathy
• Optic neuritis
• Gout
Monitoring Therapy
• Baseline
– Med Eval, Symptoms, Labs, Xray
• Face to face
– Assess barriers, encourage completeion
• Sputa
– Different frequency
Miscellaneous
• Infectiousness / Disposition
– Flights
– Housing
• How much TB do you see?
– Basic vs. detailed understanding
• Who can you call with questions?
Navigating Frontiers in TB Case Management: Strengthening Partnerships for Improved Patient Outcomes June 2, 2015 Curry International Tuberculosis Center
TB Infection and TB Disease: Diagnosis and Treatment 27
Resources
• Epi TB website – epi.alaska.gov/id/tb.stm
– Epi TB Manual - http://epi.alaska.gov/pubs/webtb/TB_Manual.pdf
• TB Drug Calculator - http://www.floodgap.com/biomed/tb/?wt=60.8&u=2
• TST/IGRA interpreter - http://www.tstin3d.com
• Reference cards – LTBI, TB -
http://globaltb.njms.rutgers.edu/downloads/products/ltbidrugcard.pdf
• CDC Core Curriculum - http://www.cdc.gov/tb/education/corecurr/
• Curry Center - http://www.currytbcenter.ucsf.edu/trainings
• “Must We All Die”, Robert Fortuine
http://www.epi.hss.state.ak.us/id/tb.stm
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