Tuberculosis infections (Latent) (Fouty)

Additional material (lecture)

Gibbus spine POTS infection in vertebral column compression fractures

TB

Robert Koch developed tuberculin

severe skin reaction when injected into the skin of patients with active TB

Some people without TB also reacted to tuberculin

People without disease but who lived with people who had TB

Tuberculin testing was used to control _____ tuberculosis first 

bovine 

____ testing of cows and pasteurization of milk eliminated bovine transmission of TB

Tuberculin

precipitated protein fraction from a single strain of human tubercle bacillus

purified and potent

non-sensitizing

dose could be standardized and delivered SQ

PPD

Standard PPD __ TU= 0.001 mg 

5

High strength PPD increases ______ rates

false positives

Tools required for chemoprophylaxis available by late 1940’s

Standardized skin test to reliably detect infection.

chest radiographs.

drugs for chemotherapy

- streptomycin, PAS (1944)

Fork in the road image 

Logmarithmic growth from 5-21 days

then CMI and DTH cell mediated immunity start to work to try to kill and control

Location Of Primary Calcified Foci

primarily in lower lobes 

Location Of Re-Infection Tuberculosis

cluster in upper lobes

Location Of Single Tuberculosis Cavities

RML interestingly spared

There is ________While CMI/DTH Controls Initial Infection

dissemination 

dissemination

access through alveolar macrophages

Secondary lesions not completely eradicated

Distal Disease Progresses While Primary Focus Is Controlled

TB life graph 

Classic TB radiograph

White in upper lobe and cavities

Reactivation

TB reactivation is more common in ____ ____ lobe

Right upper

1. Does the skin test represent a true Tuberculosis Infection?

Infected without clinical symptoms and with negative cultures (latent disease)

2. What is the risk of progressing to Tuberculosis Disease?

Infected with clinical symptoms with positive cultures (active disease)

Question to ask yourself

Greater than 5 mm

HIV infected or at risk

close contacts of newly diagnosed tuberculosis

fibrotic lesions on CXR c/w old healed TB

Greater than 10 mm

IVDU known to be HIV (-)

foreign born from high prevalence countries (Mexico, Vietnam, Phill, Korea)

Medical conditions increasing risk of TB

Medically underserved low income

High-risk racial groups (Hispanics, Blacks, Native Americans)

Recent converters (> 10 mm increase within 2 years)

Greater than 15 mm

Low risk groups

18 y/o white male who lives in Beverly Hills has 12 mm of induration on his PPD during a screen to obtain a food handler’s card.  He has no known exposures to TB and has lived his entire life next to the Kardashians.  He is asymptomatic with a normal chest radiograph.

No treatment

Does the skin test represent a true Tuberculosis Infection? NO

size of induration

risk of exposure

Value Of Skin Testing Is Related To ______ Of Disease

prevalence 

99 false positives in low prevalence groups. Only 8 percent actually have it.

Medical Conditions That Increase The Likelihood That Tuberculosis Infection Will Become Tuberculosis Disease

Silicosis (sandblaster)

diabetes (mainly insulin dependent)

chronic renal failure

gastrectomy

malnutrition

jejunoileal bypass

diseases requiring immunosuppressive drugs

TNF-alpha blockers, steroids, cyclophosphamide (RA, Chrons, UC)

malignancies (esp. hematologic)

A 52 y/o woman whose husband has smear-positive Mycobacterium tuberculosis has a PPD of 8 mm induration. She does not remember the results of her old skin test 20 years prior. She is asymptomatic with a normal chest radiograph.

Treatment

45 y/o nurse who after years of non-reactive skin tests develops a 12 mm induration on her annual screen after years of no induration. She works at a county hospital which treats patients with tuberculosis. She is ASX and has a normal CXR. She has no other medical problems.

Treatment

Risk of developing TB disease after infection with M TB lifetime risk:

10%

Risk of developing TB disease after infection with M TB lifetime risk in first 18-24 months after infection

5-7%

Increased risk of developing TB disease immediately following ___ conversion

PPD 

_____ prophylaxis decreases incidence of progression form TB infection to TB disease

Isoniazid

45 y/o man immigrating from Vietnam has 14 mm of induration on his initial skin test. He has not had a prior skin test, but his father died of tuberculosis 30 years prior. He has no symptoms and his CXR is normal. He has no other medical problems.

Treatment

TB risk compared to the US 

Immigrants Have The Same Rate Of Progression To TB Disease As That Of Their Native Country For First ____ Years

5

High-risk immigrants treated with chemoprophylaxis if in US less than __ years.

5

The Vietnamese man described previously goes to live with his 55-year-old brother who immigrated to the US 35 years prior. His brother did not have a skin test at that time. His brother’s PPD now is 18 mm. He is asx with a normal chest radiograph and no medical problems.

 How do you manage the brother?

No treatment

TB infection is present by test

low rate of progression to TB disease because he has been in the US for 35 years.

Do not treat because of risk of isoniazid (INH) induced hepatitis with low risk of reactivation 

Isoniazid induced hepatitis is ____ related 

age

•AST (SGOT) > 5 times normal (about 250)

•increases with age

  - 1.0 - 1.8% incidence overall

•resolves with discontinuation (usually)

•incidence of fatal hepatitis in over 35 age group with regularly monitored LFT’s (1983- 1992): 0.002%

INH-Induced Hepatitis

Risk Of Hepatitis from isoniazid Increases With _____ Therapy

longer

Immigrants from high-risk countries in US greater than _ years are only treated if another risk is present.

5

Same 55 y/o Vietnamese who has lived in US for 30 years, but he has the following CXR.

How do you manage him?

Treat 

high risk of progressing to TB disease 

TB Disease Case Rate By CXR Classification In Alaskan Natives

RUL some trouble

Infiltrate

Increase risk of disease progression 

No increased risk of disease progression

Cavity in LUL

Even if culture negative is concerning

still concerning

Longer prophylaxis _____ progression to tuberculosis disease in patients with fibrotic lesions

decreases

A patient admitted to a nursing home one week prior is found to have smear positive TB. Three 45 y/o workers are exposed and tested immediately:

- Worker 1: initial S.T. (-), repeat S.T. (-) @ 3 mos.

- Worker 2: initial S.T. (-), repeat S.T.: 12 mm

- Worker 3: initial S.T.: 18 mm (no previous Tx)

All are ASX with normal CXR’s.

For each worker:

Worker 1: No treatment

Worker 2: Treat

Worker 3: No treatment because the initial was done 1 week after not enough time to build a response this means he already was infected with TB

TB infection appears to protect against progression to TB disease after 

re-infection 

In children always ____ pending repeat PPD

always

28 y/o woman from Mexico has a 12 mm induration on immigration screen. She had received BCG vaccination at age 2. She denied any known exposure to TB. She is well with a normal CXR.

Treatment

•attenuated (but live) strain of M.Bovis (1924)

•used to prevent tuberculosis disease in developing (and some developed) countries.

•not used in U.S.

•results regarding efficacy are equivocal

  - probably effective at preventing disseminated tuberculosis disease (esp. meningitis) in children

BCG vaccine

Bacille-calmette-querin vaccine

Most Non-infected People Vaccinated With BCG Are PPD ______

Negative 

Prior BCG Vaccination Is ____ A Factor In Considering Need For Chemoprophylaxis even though BCG vaccination does change skin test

not

people from high-risk countries are considered TB infected if PPD > 10 mm regardless of ___ status.

BCG

people from low-risk countries still using BCG are considered TB infected if PPD > __ mm.

15

Measures interferon gamma release from sensitized T cells in patients blood 

IFN gamma release assays 

QuantiFERON gold 

ESAT-6

CFP-10

TB7.7

TB antigens

Inexpensive

Does not require blood draw or lab

Relatively easy to perform

Long history

Tuberculin skin test (PPD)

Does not require return patient visit

Results within 24 hours

Is not affected by prior BCG vaccination

Interferon gamma release assay 

Both tests can lose ______ in immunosuppressed individuals

sensitivity

TB pathways

The worst thing you can do it treat a patient for TB ____ if they have TB _____

Infection

Disease

Who Gets Treated for a Tuberculosis Infection?

•Under 35 years of age

  Or

•Any age who is a/has a:

–Recent converter

–Medical condition/medications that increase risk

–Abnormal CXR deemed high risk

Approved Treatment Regimens For TB Infections

(PPD/IFRA (+) Without Symptoms Or Positive Culture):

Isoniazid + Rifapentin weekly for 12 weeks

Rifampin daily for 4 months

Isoniazid + Rifampin daily for 3 months

Isoniazid daily for 6-9 months

Things Many People Do, But Shouldn’t:

Repeat a skin test on a person with known TB infection

Check routine yearly CXRs on asymptomatic people with TB infections

• should check CXR only for symptoms