TUBERCULOSISBY : M. SHA`BANI MD

TB is caused by bacteria of the M. Tuberculosis complex & usually affects lung.

If treated,is curable

If unreated ,may fatal within 5 y/o in 50-65% of cases

M. Tuberculosis is a rod shape ,nonspore-forming,aerobic

Acid- fast bacili (AFB )

TB is spread person to person through the air via droplet nuclei

M. tuberculosis may be expelled when an infectious person:◦ Coughs◦ Sneezes◦ Speaks ◦ Sings

Transmission occurs when another person inhales droplet nuclei

FROM EXPOSURE TO INFECTION

The most infectious patients :cavitary, laryngeal,sputum containing 105 – 107

AFB/ml Q: Are co-infected patients(HIV + TB) highly

infectious?

Depends on innate immunologic and non –immuonologic defenses and function of CMI

Primary disease : children and immunocompromsed persons

Secondary ( postprimary) TB dormant bacilli may persist for years before reactivation to produce this type .

Up to 10% of infected persons will develop active TB ( esp. in HIV patients)

FROM INFECTION TO DISEASE

Pathogenesis is defined as how an infection or disease develops in the body.

TB Pathogenesis (1)

Occurs when tubercle bacilli are in the body, but the immune system is keeping them under control

Detected by the Mantoux tuberculin skin test (TST) or by blood tests such as interferon-gamma release assays (IGRAs) which include:

◦ QuantiFERON®-TB Gold test (QFT-G)◦ QuantiFERON®-TB Gold In-Tube (QFT-GIT)◦ T-Spot®.TB test (T-SPOT)

People with LTBI are NOT infectious

TB Pathogenesis (2)Latent TB Infection (LTBI)

Develops when immune system cannot keep tubercle bacilli under control

◦ May develop very soon after infection or many years after infection

About 10% of all people with normal immune systems who have LTBI will develop TB disease at some point in their lives

People with TB disease are often infectious

TB Pathogenesis (3)TB Disease

Tubercle bacilli multiply in alveoli, where

infection begins

bronchioleblood vessel

tubercle bacilli

a lveoli

2

A small number of tubercle bacilli enter bloodstream and spread throughout body

brain

lung

kidney

bone3

• Within 2 to 8 weeks the immune system produces special immune cells called

macrophages that surround the tubercle bacilli

• These cells form a barrier shell that keeps the bacilli contained and under control

(LTBI)

specialim m une cells form a barrier shell (in th isexam ple,bacilli arein the lungs)

4

• If the immune system CANNOT keep tubercle bacilli under control, bacilli begin

to multiply rapidly and cause TB disease

• This process can occur in different places in the body

shell breaks down and tuberclebacilli escape

m ultip ly(in th is exam ple,TB d isease develops in the lungs)

and

5

Latent TB Infection (LTBI) TB Disease (in the lungs)

Inactive, contained tubercle bacilli in the body

Active, multiplying tubercle bacilli in the body

TST or blood test results usually positive

TST or blood test results usually positive

Chest x-ray usually normal Chest x-ray usually abnormal

Sputum smears and cultures negative Sputum smears and cultures may be positive

No symptoms Symptoms such as cough, fever, weight loss

Not infectious Often infectious before treatment

Not a case of TB A case of TB

When a person inhales air that contains droplet nuclei containing M. tuberculosis, where do the droplet nuclei go? (pg. 15)

• Most of the larger droplet nuclei become lodged in the upper respiratory tract, where infection is unlikely to develop

• However, droplet nuclei may reach the small air sacs of the lung (the alveoli), where infection begins

TB PathogenesisStudy Question

After the tubercle bacilli reach the small air sacs of the lung (the alveoli), what happens to them? (pg. 15)

Tubercle bacilli multiply in alveoli and some enter the bloodstream and spread throughout the body

Bacilli may reach any part of the body

Within 2 to 8 weeks, the immune system usually intervenes, halting multiplication and preventing further spread

TB PathogenesisStudy Question

In people with LTBI (but not TB disease), how does the immune system keep the tubercle bacilli under control? (pg. 15)

The immune system produces special immune cells that surround the

tubercle bacilli. These cells form a shell that keeps the bacilli contained and under control.

TB PathogenesisStudy Question

How is LTBI detected? (pg. 16)

LTBI is detected by the Mantoux tuberculin skin test (TST) or blood tests such as interferon-gamma release assays (IGRA), which include the QuantiFERON®-TB test (QFT-G), QuantiFERON®-TB Gold In-tube (QFT-GIT), or T-SPOT.

TB PathogenesisStudy Question

Some conditions increase probability of LTBI progressing to TB disease

In an HIV-infected person,

TB can develop in one oftwo ways:

Person with LTBI becomes infected with HIV and then develops TB disease as the immune system is weakened

Person with HIV infection becomes infected with M. tuberculosis and then rapidly develops TB disease

Progression to TB Disease TB and HIV

PULMONARY dis.: Primary dis.: 1-asymptomatic 2-fever and pleuritic c.p. -in children -middle and lower lobes -Ghon focus(after initial inf. –peripheral-hilar

or paratracheal LAP-heals spontaneously and calcified noduls)

-EN in legs

CLINICAL MANIFESTATIONS

In young child or immunosuppressed person pulmonary TB (Primary ) progress to clinical illness

PE :2/3 Cavity+ LAP Enlarged LN then... Rupture of LN and ... Hematogen distribution

Post-primary dis. : Reactivation Apex Small infiltrations to large cavities What happens? up to 1/3 will be severe others (ends to

remission or chronicity)

symptoms: -nonspecific and slowly -eventually up to 90% ,cough -C.P. -dyspnea Signs:most of them ,normal but may have

inspiratory rales and occasionally rhonchiThe most common hamatologic findings:

Mild anemia, leukocytosis, thrombocytopenia

In order of frequency: L.N., pleura, GU, skeletal, mening, peritonum and pericardium

Lympadenitis: nontender swelling ,posterior cervical and supraclavicular( scrofula) ,

Systemic signs are ucommon unless in HIV FNA or excisional Bx

EXTRAPULMONARY TB

Pleural TB : 1-postprimary 2-chronic 3-with miliary 4-empyema Dx: thoracentesis, needle bx of pleura The first one responds rapidly to chemo. For empyema surgical drainage + chemo.

Genitourinary TB Skeletal TB Meningitis and tuberculoma Gastrointestinal TB

Miliary TB -Hematogenous spread of bacilli -granuloma 1-2 mm lesions ( as millet

seeds) Nonspecific manifestations Fever,night sweat, anorexia,wt loss 1-acute 2-cryptic 3-nonreactive Dx: BAL, TBB, Bx of involved organs

A person with a pos. PPD who acquires HIV has a risk of 3-13% /year for active TB

prsentation depends onstage of HIV Extrapulmonary TB is common Dx is difficult because...(smear,radiography

granuloma,PPD)

HIV- associated TB

1-AFB MICROSCOPY ( microscopic exam of a diagnostic

specimen,e.g. sputum,tissue) Sputum: x3 in morning ( but 2 sample on

the same visit is better than 3 samples) Tissue: in normal saline( not in

formaldehyde)

DIAGNOSIS

CULTURE : because most mycobacterias grow slowly 4-

8 weeks may be required The most sensitive test PCR, radiography,invasive procedures

PPD: False negative in

immunosuppression ,malnutrition False positive in non-TB mycobacteria , BCG

vaccination IFN-gamma release assay( IGRA): It measures T cell release of IFN-gamma in

response to stimulation with the highly TB-specific antigen ESAT-6 AND CFP-10

It is more specific than PPD esp. in low-incidence setting

DIAGNOSIS OF LATENT INFECTION

4 major drugs are the first line agents : Isoniazid,rifampin ,pyrazinamide,ethambuto

l Monitoring : bacteriologic evaluation( if cx

not possible then AFB smear) Serial CXR is not recomended Drug toxicity: (patient should be educated

about hepatitis , hypersensitivity reaction, hyperuricemia and arthralgia,thrombocytopenia,optic neuritis

TREATMENT

For preventing active dis.( chemoprophylaxis) Candidates are : 1- HIV, recieving immunosuppressive

drugs,close contact, fibrotic lesions on CXR with at least 5 mm

2- recently infected persons, high risk condition( DM,hematologic dis., IDU, ESRD,,rapid wt loss) with at least 10 mm

3-low risk persons with at least 15 mm( except for employment purposes TST is not indicated for low-risk group)

Tx of latent TB infection

THANK YOU

QUESTION?