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

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)



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



1700’s – Russian explorers and traders

1800’s – Gold/fish/whales

1880 1953



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



• “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


• 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”


Alaska – Historical TB Rates



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



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



Tuberculosis terminology


Latent TB Disease

Active

Disease

Inactive

Disease Infection Latent

Infection

LTBI


Disease

Infection



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







•Weight loss

•Sweats at night

•Hemoptysis

•Fatigue

•Fever / chills





smears or culture








•Weight loss

•Sweats at night

•Hemoptysis

•Fatigue

•Fever / chills





smears or culture




Latent Infection to Active Disease-

Reactivation

• Lifetime risk estimate

– 10%



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





LTBI Prevalence in AK?

True or False

• 90% of third graders in YK are infected with TB



True or False


• True…

True or False


• True…in 1950

(89%)



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




• Tuberculin Skin Test (TST)

• TB Blood Tests

– Interferon Gamma Release Assays (IGRA)

• Quantiferon TB Gold In-Tube (QFT-GIT)

• T Spot


TST advantages

TST disadvantages

IGRA advantages

IGRA disadvantages

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



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



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?

http://www.cdc.gov/tb/publications/MobileLTBIApp/default.html

http://www.cdc.gov/tb/publications/MobileLTBIApp/default.html



Case Presentation


• TB test?

• TST or IGRA?

Case Presentation

• Do they give BCG in the Philippines?

Resource - www.bcgatlas.org



Case Presentation

• Does SOA pay for IGRA?

• Can your lab do an IGRA?

• Can this patient get a TST with BCG hx?

Case Presentation


• Patient states she had a positive TST in past

• Can you trust this?

• Can you do another TST?

Case Presentation


• TST is 11mm. Is that positive?



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


• Do they need a chest radiograph?

• Two view or single PA?

• What if she had one three months ago?



Case Presentation


• TST positive (could it be due to BCG?)

• Radiograph ‘normal’

• Should you request three sputa?

– Any symptoms?

Case Presentation


• Treatment is offered…which regimen?

TB Disease:

Diagnosis and

Treatment

Michael Cooper, MD, MS

Section of Epidemiology

State of Alaska

Updated May 2015



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



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?



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



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?



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

http://epi.alaska.gov/pubs/webtb/TB_Manual.pdf



http://www.floodgap.com/biomed/tb/?wt=60.8&u=2

http://www.floodgap.com/biomed/tb/?wt=60.8&u=2

http://www.tstin3d.com/

http://www.tstin3d.com/




http://www.cdc.gov/tb/education/corecurr/

http://www.cdc.gov/tb/education/corecurr/

http://www.currytbcenter.ucsf.edu/trainings



http://www.epi.hss.state.ak.us/id/tb.stm