A typical day in the TB clinic

A typical day in the TB clinicYou see the following patients in the TB clinic. All have normal CXRs:You see the following patients in the TB clinic. All have normal CXRs:

1.1. A 35 year old man from Hartford with a 16 mm positive PPD. He has no A 35 year old man from Hartford with a 16 mm positive PPD. He has no

known exposure to MTB, no risk factors, normal exam. He wants to work known exposure to MTB, no risk factors, normal exam. He wants to work

in your hospital.in your hospital.

2.2. A 64 year old woman from Jamaica with a 12 mm PPD who is referred for A 64 year old woman from Jamaica with a 12 mm PPD who is referred for

immigration purposes. She has no risk factors and her exam is negative immigration purposes. She has no risk factors and her exam is negative

3.3. An 18 year old young woman from Lima, Peru with a 14 mm PPD for An 18 year old young woman from Lima, Peru with a 14 mm PPD for

immigration purposes. Her history and exam are negativeimmigration purposes. Her history and exam are negative

4.4. A 54 year old man born and raised in Hartford, who has a 20 mm PPD. A 54 year old man born and raised in Hartford, who has a 20 mm PPD.

He cannot recall having had a previous TST. He used to be an IV drug He cannot recall having had a previous TST. He used to be an IV drug

abuser. He says his HIV was negative 3 months earlier.abuser. He says his HIV was negative 3 months earlier.

What is the risk of developing TB disease and what is the role, if any, for IGRA What is the risk of developing TB disease and what is the role, if any, for IGRA

testing in these patients, and how would you treat them?testing in these patients, and how would you treat them?

LTBI vs. TB DiseaseLTBI vs. TB Disease

LTBILTBI TB DiseaseTB Disease

Tubercle bacilli in the bodyTubercle bacilli in the body

Skin test or blood test usually positiveSkin test or blood test usually positive

Chest x-ray normalChest x-ray normal Chest x-ray abnormalChest x-ray abnormal

Bacteriology negativeBacteriology negative Bacteriology positiveBacteriology positive

No symptomsNo symptoms Cough, weight loss, night sweatsCough, weight loss, night sweats

Not infectious, not a caseNot infectious, not a case Often infectious before treatmentOften infectious before treatment

nyc.gov/health

Interpretation of TST ResultsInterpretation of TST Results

False-positive and false-negative PPDsFalse-positive and false-negative PPDsThe PPD is only about 70% sensitiveThe PPD is only about 70% sensitive

• False positive– BCG vaccination– Nontuberculous mycobacterial infection– Improper administration or interpretation

• False negative– Very young (<6 months old)– Inability to mount an immune response (e.g., HIV or TB

itself)– Recent infection (<10 weeks since exposure)– Very remote infection– Recent live virus vaccination– Improper administration or interpretation

Interferon Gamma Release Assays (IGRAs)Interferon Gamma Release Assays (IGRAs)

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

– 22ndnd/3/3rdrd generation tests generation tests

– Available from commercial labsAvailable from commercial labs

– ELISA that measures amount of IFN-gamma ELISA that measures amount of IFN-gamma

released by patient’s cellsreleased by patient’s cells

• T-Spot.TBT-Spot.TB

– Approved July 2008Approved July 2008

– ElispotElispot

Indeterminate IGRAIndeterminate IGRA

• Less frequent with QFT-GITLess frequent with QFT-GIT• Several possible reasonsSeveral possible reasons

– High background High background IFN-IFN-: patient illness, mitogen in : patient illness, mitogen in wrong well, defective tubeswrong well, defective tubes

– Low mitogen: immune suppression, defective tubes, Low mitogen: immune suppression, defective tubes, overfilling, inadequate shakingoverfilling, inadequate shaking

• Options?Options?– Repeat QFTRepeat QFT– Place TST insteadPlace TST instead

Comparison of IGRAs and TSTComparison of IGRAs and TST

IGRAIGRA• About 70% sensitiveAbout 70% sensitive

• Not affected by BCGNot affected by BCG

• Not cheapNot cheap

• New: less experienceNew: less experience

• In vitro testl; requires phlebotomyIn vitro testl; requires phlebotomy

• No boostingNo boosting

• Only need 1 patient visitOnly need 1 patient visit

• Gives numbers, lessens variabilityGives numbers, lessens variability

• Results possible in 1 dayResults possible in 1 day

• May decline in response to test after May decline in response to test after

treatmenttreatment

TSTTST• About 70% sensitiveAbout 70% sensitive

• Fairly specificFairly specific

• CheapCheap

• Been around a long timeBeen around a long time

• In vivo testIn vivo test

• Potential boosting Potential boosting

• Requires 2 patient visitsRequires 2 patient visits

• Inter-reader variabilityInter-reader variability

• Results in 2-3 daysResults in 2-3 days

• May be May be more sensitive in more sensitive in

detecting remote infectionsdetecting remote infections

Potential to cause big problems versus Potential to cause big problems versus the hassle required to reduce this riskthe hassle required to reduce this risk

Latent Tuberculosis Infection (LTBI) and progression to real disease

• About 5–10% of persons with LTBI will develop TB disease if About 5–10% of persons with LTBI will develop TB disease if untreateduntreated

– 50% in the first two years 50% in the first two years

– 50% later in life50% later in life

• The most effective treatment would be to identify and treat LTBI The most effective treatment would be to identify and treat LTBI in all these individualsin all these individuals

• However, treatment of LTBI is:However, treatment of LTBI is:

– Is lengthy: 4 to 9 months, generallyIs lengthy: 4 to 9 months, generally

– Is costly: not from medications but because patients have to Is costly: not from medications but because patients have to come in regularly for monitoring, thereby missing work, come in regularly for monitoring, thereby missing work, school, etc.school, etc.

– Carries a very small but real risk for side effectsCarries a very small but real risk for side effects

High Risk for Conversion of LTBI to TB High Risk for Conversion of LTBI to TB DiseaseDisease

• Recent infection, documented conversion (within the last 2 years)

• HIV infection

• Substance abuse (alcohol or drugs)

• Old healed TB lesions on CXR

• Children under 5 years of age

• Certain medical conditions

Medical ConditionsMedical Conditions

• HIV infectionHIV infection

• <90% of ideal body weight, recent weight loss<90% of ideal body weight, recent weight loss

• Diabetes mellitus (poorly controlled)Diabetes mellitus (poorly controlled)

• Chronic renal failureChronic renal failure

• Solid organ transplant recipientsSolid organ transplant recipients

• Certain cancers and / or treatmentCertain cancers and / or treatment

• Higher-dose steroid treatment (15mg, >4 weeks)Higher-dose steroid treatment (15mg, >4 weeks)

• Tumor necrotizing factor antagonist therapy (TNF-Tumor necrotizing factor antagonist therapy (TNF-α antagonists)α antagonists)

• History of gastrectomy or jejunoileal bypass surgeryHistory of gastrectomy or jejunoileal bypass surgery

Dealing with the uncertain

The Online TST/IGRA Interpreter: https://www.tstin3d.com

Statistics and risks derived from website (1)

• A 35 year old man from Hartford with a 16 mm positive PPD. He has A 35 year old man from Hartford with a 16 mm positive PPD. He has

no known exposure to MTB, no risk factors, normal exam, normal no known exposure to MTB, no risk factors, normal exam, normal

chest x-ray. He wants to work in your hospital.chest x-ray. He wants to work in your hospital.

• What do you think? Should he be offered LTBI rx?What do you think? Should he be offered LTBI rx?

• Stats from history as given above:Stats from history as given above:

– Likelihood of a true positive PPD: 100%Likelihood of a true positive PPD: 100%

– Annual risk of TB disease: 0.1%Annual risk of TB disease: 0.1%

– Lifetime risk of TB disease: 4.5%Lifetime risk of TB disease: 4.5%

– Risk of hepatotoxicity from treatment: 0.2%Risk of hepatotoxicity from treatment: 0.2%





• New data: the patient had diabetes:New data: the patient had diabetes:


• Likelihood of a true positive PPD: 100%Likelihood of a true positive PPD: 100%

– Annual risk of TB disease: Annual risk of TB disease: 0.28% (originally 0.1%) 0.28% (originally 0.1%)

– Lifetime risk of TB disease: Lifetime risk of TB disease: 12.6% (originally 4.5%)12.6% (originally 4.5%)






• New data: the patient had documented close contact:New data: the patient had documented close contact:



– Annual risk of TB disease: 0.10% Annual risk of TB disease: 0.10%

– Lifetime risk of TB disease: Lifetime risk of TB disease: 9.3% (originally 4.5%) 9.3% (originally 4.5%)


– Risk of developing TB in next two years: Risk of developing TB in next two years: 5% (originally 1.2%)5% (originally 1.2%)





• New data: patient had documented new infection (< 2 years):New data: patient had documented new infection (< 2 years):




– Lifetime risk of TB disease: Lifetime risk of TB disease: 5.8% (originally 4.5%) 5.8% (originally 4.5%)


– Risk of developing TB in next two years: Risk of developing TB in next two years: 1.5% (originally 1.2%)1.5% (originally 1.2%)





• New data: the patient had a granuloma on chest x-rayNew data: the patient had a granuloma on chest x-ray



– Annual risk of TB disease: Annual risk of TB disease: 0.2% (originally 0.10%)0.2% (originally 0.10%)

– Lifetime risk of TB disease: Lifetime risk of TB disease: 9% (originally 4.5%)9% (originally 4.5%)


– Risk of developing TB in next two years: Risk of developing TB in next two years: 1.5% (originally 1.2%)1.5% (originally 1.2%)





• New data: Abnormality (more than a granuloma) on chest x-ray:New data: Abnormality (more than a granuloma) on chest x-ray:







1.1. A 64 year old woman from Jamaica with a 12 mm PPD who is A 64 year old woman from Jamaica with a 12 mm PPD who is

referred for immigration purposes. She has no risk factors and her referred for immigration purposes. She has no risk factors and her

exam is negative. She came to USA 10 years ago.exam is negative. She came to USA 10 years ago.

• What do you think? Should she be offered LTBI rx?What do you think? Should she be offered LTBI rx?

• Stats: Stats:

– Likelihood of a true positive PPD: Likelihood of a true positive PPD: 62%62%


– Lifetime risk of TB disease: Lifetime risk of TB disease: 0.99%0.99%

– Risk of hepatotoxicity from treatment: Risk of hepatotoxicity from treatment: 2.3%2.3%


1.1. A 64 year old woman from Jamaica with a 12 mm PPD who is A 64 year old woman from Jamaica with a 12 mm PPD who is

referred for immigration purposes. She has no risk factors and her referred for immigration purposes. She has no risk factors and her

exam is negative. She came to USA 10 years ago.exam is negative. She came to USA 10 years ago.

• New data: she is taking a TNF alpha drug: New data: she is taking a TNF alpha drug:




– Lifetime risk of TB disease: Lifetime risk of TB disease: 5.3% (originally 0.99%)5.3% (originally 0.99%)



• A 18 year old from Lima, Peru with a 14 mm PPD for immigration A 18 year old from Lima, Peru with a 14 mm PPD for immigration

purposes. She has been in USA for 2 years. Her history and purposes. She has been in USA for 2 years. Her history and

exam are negativeexam are negative


• Stats: Stats:




– Risk of hepatotoxicity from treatment: 0%Risk of hepatotoxicity from treatment: 0%


• A 54 year old man born and raised in Hartford, who has a 20 mm A 54 year old man born and raised in Hartford, who has a 20 mm

PPD. He cannot recall having had a previous TST. He used to be PPD. He cannot recall having had a previous TST. He used to be

an IV drug abuser. He says his HIV was negative 3 months an IV drug abuser. He says his HIV was negative 3 months

earlier.earlier.


• Stats: Stats:






• A 54 year old man born and raised in Hartford, who has a 20 mm A 54 year old man born and raised in Hartford, who has a 20 mm

PPD. He cannot recall having had a previous TST. He used to be PPD. He cannot recall having had a previous TST. He used to be

an IV drug abuser. He says his HIV was negative 3 months an IV drug abuser. He says his HIV was negative 3 months

earlier.earlier.

• New data: the patient is HIV positiveNew data: the patient is HIV positive



– Annual risk of TB disease: Annual risk of TB disease: 8% (originally 0.25%)8% (originally 0.25%)



Questions?

A typical day in the TB clinic

Documents

tb clinicyou

tb diseasenyc

conversion of ltbi

treatment of ltbi

risk of developing tb

year old woman

year old man

real risk