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PULMONARY TUBERCULOSIS
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Learning Objectives
 To define pulmonary tuberculosis.
 To evaluate patients suspected of having pulmonary
tuberculosis.
 To manage patients diagnosed with pulmonary
tuberculosis.
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Definition
 Pulmonary tuberculosis (TB) is a highly contagious
granulomatous disease caused by a acid fast areobic bacilli
bacteria known as Mycobacterium tuberculosis.
 The granulomas of tuberculosis tend to contain necrosis
"caseating tubercules“ Multinucleated giant cells with
nuclei arranged like a horseshoe (Langhans giant cell) and
foreign body giant cells.
 Tuberculosis may spread to other organs like the brain,
kidney and spine.
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Epidemiology (1)
 Tuberculosis remains the leading cause of death worldwide
from a single infectious disease agent.
 Up to 1/2 of the world's population is infected with
tuberculosis.
 The registered number of new cases of tuberculosis worldwide
roughly correlates with economic conditions: the highest
incidences are in countries of Africa, Asia, and Latin America
with the lowest gross national products.
 The World Health Organization estimates that 8 million people
get tuberculosis every year, of whom 95% live in developing
countries.
 An estimated 2 million people die from tuberculosis every year.
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RISK FACTORS
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Risk factors
 Tuberculosis is caused by breathing in droplets from a
cough or sneeze of an infected person , this is called
primary tuberculosis.
 Risk factors for tuberculosis:
o Infants
o Low socioeconomic status
o Crowded living conditions
o Disease that weakens the immune system like Human
immunodeficiency virus (HIV ), alcoholism,
o Recent tubercular infection (within last 2 years).
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Risk for Development of TB Disease

Risk for Development of TB How many times higher is the
Disease risk of TB disease

HIV/AIDS 113-170

Diabetes 4.1

“old TB” on CXR 13.6

Chronic renal failure 25

Other conditions 3-16

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TRANSMISSION
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Transmission
 Tuberculosis is primarily an airborne disease.
 The bacteria are spread from person to person in tiny
microscopic droplets (1-5 micro meter diameter) when a
tuberculosis sufferer coughs, sneezes, speaks, sings, or laughs.
 Only people with active Tuberculosis can spread the disease to
others.
 Usually a person has to be close to someone with Tuberculosis
disease for a long period of time.
 Even if someone becomes infected with tuberculosis, that does
not mean they will get active tuberculosis disease.
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CLINICAL
MANIFESTATIONS
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Clinical Manifestations (1)

Inactive Tuberculosis Active Tuberculosis
 No symptoms in inactive  Symptoms develop gradually over
tuberculosis several weeks.
 Cough( with or without blood)
 weight loss
 fatigue
 fever
 night sweats
 chills
 chest pain
 shortness of breath
 loss of appetite
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Clinical Manifestations (2)

 Although the Tuberculosis bacteria can infect any organ (such as
kidney, lymph nodes, bones, joints) in the body, the disease
commonly occurs in the lungs.
 Pulmonary manifestations of tuberculosis are varied and depend
in part whether the infection is primary or post-primary.
 The primary infection is usually asymptomatic.
 Only in 5% of patients, usually those with impaired immunity will
have progressive primary tuberculosis.
 Miliary tuberculosis : severe disseminated disease .
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Post Primary Tuberculosis (PPTB)

 PPTB (reactivation TB) occurs years later, frequently with decreased
immunity
 Post-primary TB occurs in: posterior segments of the upper lobes or
superior segments of the lower lobes.
 Typical appearance: patchy consolidation or poorly defined linear
and nodular opacities on X-Rays.
 PPTB infections are more likely to cavitate than primary tuberculosis,
development of an air-fluid level implies contagion.
 Endobronchial spread along nearby airways-tree-in-bud appearance
on computed tomography scan )
 Tuberculomas account for only 5% of cases of post-primary TB
typically located in the upper lobes . In 20-30% of cases,
superimposed cavitation may develop.
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DIAGNOSIS
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Diagnostic tests
 Tuberculin skin test (PPD test)
o Injecting a small amount of protein from tuberculosis
bacteria in the derived layer of the skin usually forearm
 Sputum examination and Cultures
o Is examined under a microscope to look for TB bacteria and
used to grow the bacteria in a culture.
 Interferon-gamma Blood test
o A simple blood is mixed with synthetic proteins similar to those
produced by tuberculosis bacteria.
o If people are infected with tuberculosis, their white blood cells
produce certain substances (interferons) in response to the
synthetic proteins.
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Radiologic Findings
 Chest X-ray : The most common diagnostic test
o In primary Tuberculosis, an X-ray will show an abnormality in
the mid and lower lung fields, and lymph nodes may be
enlarged.
o Reactivated Tuberculosis bacteria usually infiltrate the upper
lobes of the lungs.
o Miliary tuberculosis exhibits diffuse nodules at different
locations in the body.
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Diagnosis
 Clinical features are not confirmatory.
 Zeil Nielson Stain - 1x104/ml has 60% sensitivity.
 Release of acid-fast bacilli from cavities is intermittent.
 3 negative smears are needed to assure low infectivity.
 Culture is the most sensitive and specific test.
o Conventional Lowenstein Jensen media 3-6 wks.
o Automated techniques within 9-16 days
 Polymerase Chain Reaction (PCR) is available, but it should only
be performed by experienced laboratories.
 Purified Protein Derivative (PPD) test also known as Tuberculin
Skin Test (TST) is used for clinical activity / exposure sometime
in life.
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Treatment of Tuberculosis- Standard Regimen

Initial phase Continuation Phase

Isoniazide

Rifampicine

Pyrazinamide

Ethambutol

0 1 2 3 4 5 6
Months
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Anti-Tuberculosis Drugs

First-line Drugs First-line Drugs

Second-line Drugs Second-line Drugs
Isoniazid Cycloserine
Rifampin Ethionamide

Rifapentine Levofloxacin*

Rifabutin Moxifloxacine
Ethambutol Gatifloxacin
Pyrazinamide p-Aminosalicylic acid
Streptomycin
Amikacin/kanamycin*
Capreomycin
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Isoniazide (1)
 Isoniazide (INH) is bactericidal
 Absorption – well absorbed
 Distribution
o Widely distributed, penetrates caseous tissue
o Cerebrospinal Fluid (CSF) concentrations = serum concentrations
 Elimination – primarily hepatic thus no need to adjust in renal
insufficiency.
 Adverse effects
o Hepatotoxicity (< 3%), risk increases with Ethambutol, age, rifampin
therapy,
o Peripheral neuropathy, risk increases with Ethambutol, malnourishment
o Rare: lupus-like syndrome
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Isoniazide (2)
 If administered with Phenytoin or Carbamazepine, INH results
in increased levels of the anti-seizure medications.
o It is important to monitor blood levels of seizure medications.

 Altered drug absorption with antacids.

 Herbal drug interaction: melatonin, an herbal product
used for insomnia and jet lag may increase INH levels.
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Rifampin
 Bactericidal
 Absorption – well absorbed
 Distribution – penetrates well into most tissue including
central nervous system (CNS)
 Elimination – primarily hepatic, thus there is no need to
adjust in renal insufficiency
 Adverse effects: gastrointestinal upset, flu-like syndrome,
hepatotoxicity, thrombocytopenia, anemia
 Causes orange discoloration of body fluid

Ethambutol
 Bacteriostatic
 Absorption – good [oral only]
 Distribution – minimal CSF
penetration
 Elimination – ~80% excreted
by kidneys
o dosage adjustment
necessary in renal
dysfunction
o Dose: 15-25 mg/kg/dose
three times/week
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 No significant CYP-450
interactions
 Altered drug absorption with
antacids – stagger
administration
 Can be taken with food
 Adverse effects
o Optic neuritis, red-green
color blindness [dose related]
o Test baseline acuity and color
discrimination
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Pyrazinamide
 Bactericidal
 Absorption – good
 Distribution – works best in acidic environment
 CSF concentrations = serum concentrations
 Elimination – hepatic
 Dose: 25 to 35 mg/kg/dose, three times/week
 No significant CYP-450 interaction
 Adverse effects: hepatitis, GI upset, polyarthralgia, rash,
hyperuricemia
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References
1. Center for Disease Control and Prevention.Tuberculosis (TB).
Accessed at www.cdc.gov/tb.
2. Jerant A. Identification and Management of Tuberculosis.Am Fam
Physician. 2000;61(9):2667-2678.
3. World Health Organization. Global tuberculosis report 2012.
Geneva: World Health Organization. Accessed at
http://apps.who.int/iris/bitstream/10665/75938/1/978924156450
2_eng.pdf
.