TUBERCULOSIS

DR. KAEM SHIR ALI

 TUBERCULOSIS
• Tuberculosis (TB) is caused by organisms of the
Mycobacterium tuberculosis complex.

• The complex includes M. tuberculosis (MTB), the most

frequent and important agent of human mycobacterial
disease, and M. bovis, previously an important cause of
disease acquired via ingestion of unpasteurized milk.

• MTB is a thin aerobic bacterium that is neutral on Gram’s

staining but that, once stained, is acid-fast—i.e., it cannot
be decolorized by acid alcohol because of the cell wall’s
high content of mycolic acids and other lipids.
 DEFINITIONS
• Primary tuberculosis (TB)
– Acute clinical illness directly following infection
• Latent TB
– Evidence of exposure without active disease
– Dormant bacilli can persist in the host for years without causing any
clinical symptom-atology.
– Only evidence may be a positive skin test to purified protein derivative
(PPD).
– Noninfectious during this stage
– Risk of reactivation and resultant secondary TB
• Secondary TB
– Also known as adult-type TB or reactivation TB
– Reactivation of previously acquired infection
– Caused by previously dormant bacilli
– Often infectious
 Reactivation TB
• Secondary (reactivation) TB
• 10% of persons infected in youth eventually
develop secondary TB.
– Reactivation risk is highest (5%) in the first 2
years after primary infection.
– 5% over remaining lifetime after 2 years
• 10% risk of reactivation per year in HIV-
infected patients
 Definitions cont’d
• Multidrug-resistant TB (MDR TB)
-Resistant to at least isoniazid and rifampin
• Extensively drug-resistant TB (XDR TB)
– Resistant to at least isoniazid, rifampin, any
fluoroquinolone, and at least 1 second-line injectable
drug (kanamycin, amikacin, or capreomycin)
• Miliary TB
– Widespread hematogenous dissemination of bacilli
– Can occur with both primary and secondary TB
 Natural history

– One-third of untreated patients die of severe

pulmonary TB within a few weeks or months after
reactivation.
– May remit spontaneously
– Potential for progressively debilitating course
("consumption")
 Risk Factors
• Acquisition: exogenous factors

– Close contact with infected person

• Poverty
• Homelessness
• Drug and alcohol abuse
• Incarceration/Imprisonment
• Residence in nursing home or other long term–care facility
– Exposure to endemic area for those from non endemic areas
• Primary TB
-Age
• Common among children ≤ 4 years of age
 Risk factors cont’d
• Secondary (reactivation) TB: Endogenous factors
• Recent infection (< 2 years)
• HIV infection
– No CD4+ count protects fully against associated risk.
– Risk is highest at low CD4+ counts.
• Immunosuppressive treatment
– Glucocorticoids
– Immunomodulating drugs
• Tumor necrosis factor α blockers (e.g., infliximab)
• Chemotherapy
• Jejunoileal bypass
• Post-transplantation period (renal, cardiac)
• Chronic renal failure/hemodialysis
• Silicosis
 Risk factors cont’d
• Fibrotic lesions on chest radiography (spontaneously healed)
• Diabetes
• Intravenous drug use
• Gastrectomy
• Malnutrition/severe underweight
• Celiac disease
• Head/neck carcinoma
– No increased risk in patients with other types of solid tumors
• Lymphomas/leukemias
• Recent immigration (< 5 years) from high-prevalence area
• Age
– Incidence highest in late adolescence and early adulthood
– Risk increased in elderly persons
• Smoking
– Risk increases with number of cigarettes smoked per day, years of smoking, and pack-years of
smoking.
 Spread
• Disease from a patient with infectious pulmonary TB is
most commonly spread by droplet nuclei that are
aerosolized by coughing, sneezing, or speaking.
• Droplets may be suspended in air for several hours.
• Transmission is determined by the intimacy and
duration of contact with a patient with TB, the degree of
infectiousness of that pt, and the shared environment.
• Patients with cavitary disease are usually most
infectious, with as many as 100,000 acid-fast bacilli
(AFB) per milliliter of sputum.
 PATHOGENESIS
• AFB that reach alveoli are ingested by activated macrophages.

• If the bacilli are not contained, they multiply, lyse the macrophages,
and spread to non activated monocytes.
• Macrophages may transport bacilli to regional lymph nodes, from
which dissemination throughout the body may occur.

• About 2–4 weeks after infection, delayed-type hypersensitivity

(DTH) destroys non activated macrophages that contain multiplying
bacilli, and a macrophage activating response activates cells capable
of killing AFB.
• DTH is the basis for the PPD skin test.
 Pathogenesis cont’d
• A granuloma forms at the site of the primary lesion and
at sites of dissemination.
• The lesions can then either heal by fibrosis or undergo
further evolution.
• Despite “healing,” viable bacilli can remain dormant
within macrophages or in the necrotic material for
years.
• Cytokines secreted by alveolar macrophages contribute
to disease manifestations, granuloma formation, and
mycobacterial killing.
Samples required for Diagnosis of TB
 Diagnosis of TB
Tuberculin skin test (Mantoux)
 Diagnosis of TB
Molecular tests
Are used on culture to detect the presence of M.
Tuberculosis DNA or the DNA from other mycobacterial
species
They have three stages:
Extraction
Amplification(Polymerase chain reaction)
Detection(Electrophoresis, line probe assays or real time
detection)
Detect presence, resistance and the species
Diagnosis summary