Tuberculosis or TB is a common and
often deadly infectious disease caused
by mycobacteria, usually Mycobacterium
tuberculosis in humans.
Tuberculosis usually attacks
the lungs but can also affect other parts
of the body.
The classic symptoms are
a chronic cough with blood-tinged
sputum, fever, night sweats, and weight
The primary cause of TB, Mycobacterium tuberculosis ,
is a small aerobic non-motile bacillus.
The M. tuberculosis complex includes four other TB-
causing mycobacteria: M. bovis, M. africanum, M.
canetti and M. microti.
M. africanum is not widespread, but in parts of Africa
it is a significant cause of tuberculosis.
It is currently estimated that 1/2 of the
world's population (3.1 billion) is infected
with Mycobacterium tuberculosis.
Mycobacterium avium complex is associated
with AIDS related TB.
The proportion of people who become sick
with tuberculosis each year is stable or
falling worldwide but, because of
population growth, the absolute number
of new cases is still increasing.
In 2007 there were an estimated 13.7 million chronic
active cases, 9.3 million new cases, and 1.8 million
deaths, mostly in developing countries.
The distribution of tuberculosis is not uniform across
the globe; about 80% of the population in many Asian
and African countries test positive in tuberculin tests,
while only 5-10% of the US population test positive.
10 - 24
25 - 49
50 - 99
100 - 299
300 or more
No estimate Highest estimated
TB rates per capita
were in Africa
Pulmonary tuberculosis is a disease
of respiratory transmission, Patients
with the active disease (bacilli) expel
them into the air by:
or any other way that will expel
bacilli into the air
Transmission is dependent on closeness and time of
Once inhaled by a tuberculin free person, the
bacilli multiply 4 -6 weeks and spreads
throughout the body. The bacilli implant in areas
of high partial pressure of oxygen:
When the disease becomes active, 75% of the cases
are pulmonary TB, that is, TB in the lungs.
Symptoms include chest pain, coughing up blood,
and a productive, prolonged cough for more than
Systemic symptoms include fever, chills, night
sweats, appetite loss, weight loss, pallor, and
often a tendency to fatigue very easily.
In the other 25% of active cases, the infection moves
from the lungs, causing other kinds of TB, collectively
denoted extrapulmonary tuberculosis. This occurs
more commonly in immunosuppressed persons and
Extrapulmonary infection sites include the pleura in
tuberculosis pleurisy, the central nervous system
in meningitis, the lymphatic system in scrofula of the
neck, the genitourinary system in urogenital
tuberculosis, and bones and joints in Pott's disease of
Infection via inhalation of droplet nuclei.
Transport of bacilli to terminal alveoli (especially lower
segments of lungs)
Ingestion of organisms by macrophages followed by
multiplication within macrophages
Transport of organisms to regional lymph nodes by infected
macrophages with continue multiplication and minimal
Extension of organisms( within 4-6 weeks after inhalation) into
the bloodstream from the regional nodes
Cell mediated immunity / hypersensitivity reaction
Development of clinical infection
Chest x-rays: Multi nodular
infiltrate above or behind
the clavicle with or without
pleural effusion unilaterally
• Cultures will reveal the
presence of mycobacterium
• Patients stay infectious for
as long as the bacilli are
excreted in the sputum
Skin test. PPD (purified protein
derivative) antigens are injected
intradermally. A positive reaction
is a helpful adjunct in diagnosis.
Tuberculin test positivity
indicated hypersentivity to
According to their clinical utility the drugs are:
First line drugs : High antitubercular efficacy and low
toxicity which are used routinely.
Second line drugs: Either low antitubercular efficacy
or high toxicity or both, used in special
First line drugs include:
HIGH EFFICACY AND LOW TOXICITY
Second line drugs include:
LOW EFFICACY AND HIGH TOXICITY
NEWER SECOND LINE DRUGS:
Flouroquinolones are active against M.tuberculosis.
Newer macrolides and some rifampin congeners are
the recent additions.
Considered the drug of choice for the
chemotherapy of TB. discovered in 1945 a
hydrazide of isonicotonic acid
bacteriostatic for resting bacilli,
bactericidal for growing bacilli.
Most active anti-tb drug.
It inhibits cell wall sythesis or mycolic acid synthesis.
Important assets are
Useful for tb meningitis.
Effective for both extra cellular & intracellular tb.
If combined with other drug it has good resistance
Kat G( catalase peroxidase
AcpM & Kas AcpM- Acyl Carrier protein
KasA ( ß ketoAcyl Carrier protein
Block Mycolic Acid Synthesis
II. Peripheral Neuropathy
IV. Transient loss of Memory
VI. Pleural effusion
Semisynth. deri of Rifamycin B-from St.meditarranei.
Acts both extra & intracellularly.
Bactericidal efficacy ≈ INH
&>any other 1st line drug
Analogue of RIFAMPIN is RIFABUTIN.
obtained from Rifamycin S.
Dose: 10mg/kg daily or 2-3 times weekly
DNA dependent R.N.A.polymerase
Rifampin bind to β S.U of D.D.R.P
Drug –Enz Complex
Supression of chain initiation
Hepatitis, a major adverse effect.
Respiratory syndrome: breathlessness.
Purpura, haemolysis, shock and renal failure.
Cutaneous syndrome : flushing, pruritis + rash.
Flu like syndrome : fever, headache, bone pain.
Synthetic analogue of Nicotinamide.
Though weakly tuberculocidal
More active in acidic medium.
Highly effective during 1st 2months.
More effective against Slow Growing.
Active both intra & extracellularly.
Dose : 20-25mg/kg daily
loss of diabetes control
Rapid Growers are more susceptible.
Prevent the emergence of Resistant bacilli.
C/I ; Cr. Clearance <50ml/min
Doses of Ethambutol : 15mg/kg/day
Mycobact. Arabinosyl Transferase
Polymerisation reaction of
Essential component of Myco.Cellwall
Loss of visual acuity
Early recognition &stoppage of drug-
visual toxicities is largely reversible
Contra-indication ;In children <6yrs
a) they are unable to report early.
b) may not permit the assessment of
red green color blindness discrimination
Renal uric acid excretion
First drug used for the treatment of TB.
It is aminoglycoside antibiotic.
It is tuberculocidal .
It acts only on extracelluluar bacilli.
Limitation of its use
i)dose related toxicity
ii)development of resistant org.
iii)pt compliance is poor due to i. m
acts by protein synthesis inhibitor and decreases the
fidelity mRNA and garbles the message, leads to nonsense
Streptomycin only binds to the 30s subunit.
Dose: 15mg/kg 3 times weekly for first 2-3 months for
H1 receptor blockers cause ototoxicity, with other
aminoglycosides, diuretics and vancomycin
OTOTOXICITY-drugs get conc. In labrynthine fluid,
both vestibular & cochlear damage
Sterile abscess at the inj. site
Aminoglycosides: least effective and more toxic
Capreomycin - Viomycin – Kanamycin
These drugs are: Nephrotoxic will cause Proteinuria,
Hematuria, Nitrogen metabolism, and Electrolyte
However effect is reversible when drug is stopped
Capreomycin has replaced viomycin because of less toxic
effects, but all three drugs have the same effects.
Can cause CNS disturbances
Therapeutic States :
Cycloserine should be used when re-treatment is
necessary or when the micro-organism is resistant to the
It must be given in combination with other anti-
Dose: 500 mg to 1g per day
Mechanism of Action :
An analog of D- alanine synthetase, will block bacterial
cell wall synthesis.
These are first anti tubercular drugs.
It is a tuberculostatic drug.
Low efficacy drug.
Dose: 150mg per day
PAS is a tuberculostatic and one of least active drugs.
It inhibits denovo folate synthesis.
PAS is completely absorbed by oral route and
distributed all over .
Dose : 150 mg/kg/day
Patient acceptability of PAS is poor.
Adverse effects ;
Rashes, fever, liver dysfunction
To control tuberculosis requires:
Effective, inexpensive, simple and standardised technology.
The success of the DOTS strategy depends on:
Government commitment to a national tuberculosis
Case detection –finding by smear microscopy examination
of TB susceptible in general health services.
Regular uninterrupted supply of essential anti-TB drugs.
Monitoring system for programme supervised and
Short Course Chemotherapy:
These are regimens of 6-9 month duration.
All regimens have an initial intensive phase lasting 2-3
months to kill the TB bacilli and afford symptomatic
This is followed by continuation phase for 4-6 months
so that relapse does not occur.
Multiple Drug Resistance(MDR):
Resistance to both Isoniazid and Rifampin and number of
other anti-TB drugs . MDR-TB has a more rapid course
,(some die in 4-16 weeks).
Treatment is difficult as second line drugs
are less efficacious, less convenient, more expensive and
Therapy depends on drugs used in earlier regimen, dosage
and regularity with which they have been taken.
In India>200,000patients have been treated under DOTS
by early 2001 with cure rate of 75-80%.
In other countries 80-93%cure rates have been obtained.
Treatment of TB is categorised by:
Site of disease (pulmonary or extra pulmonary), its
severity: the bacillary load and acute threat to life are
taken into consideration.
Sputum smear positivity/negativity :positive cases are
History of previous treatment: risk of drug resistance
is more in irregularly treated patients.