TUBERCULOSIS

“Tuberculosis is defined as an infectious disease caused by a bacterium; that most commonly affects the lungs.”

It can also be a crippling and deadly disease, and is on the rise in both developed and developing worlds. Globally, it is the leading cause of deaths resulting from a single infectious disease.

Currently, it kills “three million people” a year and could claim up to 30 million lives if not controlled.

tuberoculasis

• 1882 – Robert Koch – “one seventh of all human beings die of tuberculosis and… if one considers only the productive middle-age groups, tuberculosis carries away one-third and often more of these…”

M tuberculosis as causative agent for tuberculosis

1886Robert Koch

TB: Airborne Transmission

TB Invades/Infects the Lung

Effective immuneresponse

Infection limited to small area of lung

Immune responseinsufficient

TB – A Multi-system Infection

Natural History of TB InfectionExposure to TB

No infection (70-90%)

Infection(10-30%)

Latent TB(90%)

Active TB(10%)

Untreated

Die within 2 years Survive

Treated

Die Cured

Never develop Active disease

Common Symptoms of TB Disease

• Cough (2-3 weeks or more)

• Coughing up blood

• Chest pains

• Fever

• Night sweats

• Feeling weak and tired

• Losing weight without trying

• Decreased or no appetite

• If you have TB outside the lungs, you may have other symptoms

Antituberculosis Drugs

• Isoniazid

• Rifampin

• Pyrazinamide

• Ethambutol

• Rifabutin*

• Rifapentine

• Streptomycin

• Cycloserine

• p-Aminosalicylic acid

• Ethionamide

• Amikacin or kanamycin*

• Capreomycin

• Levofloxacin*

• Moxifloxacin*

• Gatifloxacin*

First-Line Drugs Second-Line Drugs

* Not approved by the U.S. Food and Drug Administration for use in the treatment of TB

Standard treatment Regime:

• Intensive phase (first 8 weeks)

– 4 drugs X 8 weeks in the intensive phase • INH/RMP/PZA/EMB daily X 14 doses

– If in hospital – daily until smear negative

• 5/7 X 6 weeks (30 doses) WRHA

• 3/7 X 6 weeks (18 doses) FNIH, unless drug resistance suspected, then 5/7

– Ethambutol can be dropped if organism pansensitive

• Continuation phase

– Twice weekly INH and rifampin DOT

13

Isoniazid

• Usual dose 300 mg daily (5 mg/kg)

• Inhibits mycolic acid synthesis

• Profound early bactericidal activity against rapidly dividing cells

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Rifampin• Inhibits RNA polymerase.

• The most important drug.

• Bactericidal against rapidly dividing agents.

• Usual dose 10 mg/kg max 600mg

Rifampin side effects

• Change in colour of urine, sweat

• hyperbilirubinemia or jaundice, Thrombocytopenia

Rifampin Drug Interactions

• Potent inducer of cytochrome P450