Tuberculosis is an infection caused by the bacteria Mycobacterium tuberculosis that primarily affects the lungs. It spreads through airborne droplets when people with active TB cough, sneeze or speak. There are two types - latent TB where the bacteria are inactive and do not cause symptoms, and active TB where the person is sick and can spread the bacteria to others. Symptoms of active TB include cough, chest pain, weight loss and fever. Treatment involves a combination of antibiotics over a long period of time to prevent transmission and cure the infection.

1. Tuberculosis
Presented by Miss Sudipta Roy
Associate Professor
East Point College of Pharmacy

2. • Tuberculosis (TB) is an acute or chronic bacterial
infection found most commonly in the lungs. The
infection is spread like a cold, mainly through
airborne droplets breathed into the air by a person
infected with TB. The bacteria causes formations of
small tissue masses called tubecles. In the lungs
these tubercles produce breathing impairment ,
coughing and release of sputum. Tb may recur after
long periods of inactivity (latency) if not treated
adequately . Many variations of TB exist and are
distinguished by the area of the body affected ,
degree of severity and affected population.

3. • TB typically affects the lungs , but it can also affect
other parts of the body , including kidney, spine
and brain. Not everyone infected with TB bacteria
becomes sick. People who have latent TB infection
have the TB bacteria in their bodies but are not sick
and cannot spread the bacteria to others.
Individuals with active TB diseases, however are
sick and may also be able to transmit the bacteria
to others. Many people with latent TB never
develop active TB disease. For people with disease
is much higher than for those with normal immune
systems. Both latent TB infection and active TB
disease can be treated. Without treatment , latent

4. Clinical Manifestations.
• Although the body can harbor the bacteria that
cause tuberculosis, but our immune system usually
can prevent us from becoming sick. For this reason
, a distinction is between :
• Latent TB - When an idividual has a TB infection,
but the bacteria in the body are inactive and cause
no symptoms. Latent TB, also called inactive TB or
TB infection, is not contagious .
• Active TB - also called TB disease , this condition
makes you sick and in most cases, can spread to
others . It can occur weeks or years after infection
with the TB bacteria.

5. • Sign and Symptoms of active TB include :
• Coughing for three or more weeks
• Coughing up blood or mucus
• Chest pain , or pain with breathing or coughing
• Unintentional weight loss
• Fatigue
• Fever
• Night sweats
• Chills
• Loss of appetite

6. Etiology.
• Tuberculosis results almost exclusively from
inhalation of airbrone particles (droplet nuclei)
containing Mycobacterium Tuberculosis. They
disperse primarily through coughing , singing and
other forced respiratory maneuvers by people who
have active pulmonary or laryngeal tb and whose
sputum contains a significant number of organisms
(typically enough to render the smear positive ).
People with pulmonary cavitary lesions are
especially infectious because of the high number
number of bacteria contained within a lesion.
• Droplet nuclei (particles <5 micron in diameter)

7. • How contagious patients with untreated active
pulmonary TB are varied widely. Certain strains of
m. Tuberculosis are more contagious and patients
with positive sputum smears are more contagious
than those with positive results only on culture.
Patients with cavitary disease (which is closely
associated with mycobacterial burden in sputum)
are more contagious than those without.
• Environment factors also are important .
Transmission is enhanced by frequent or prolonged
exposure to untreated patients who are dispersing
large numbers of tubercle bacilli in overcrowded ,

8. • Thus , estimates of contagiousness vary widely,
• Some studies suggest that only 1 in 3 patients with
untreated pulmonary tb infect any close contacts,
the who estimates that each untreated patient may
infect 10 to 15 people per year. However , most of
those who are infected do not develop active
contagiousness decreases rapidly once effective
treatment begins , organisms are less infectious
even if they persist in sputum and cough decreases.
Studies of household contacts indicate that
transmissibility ends within 2 week of patients
starting effective treatment.

9. • Much less commonly , contagion results from
aerosolization of organisms after irrigation of infected
wounds , in mycobacteriology laboratories , or in
autopsy rooms.
• Tb of the tonsils , lymph nodes , abdominal organs ,
bones and joints was once commnly caused by
ingestion of milk or milk products (e.g. cheese )
contaminated with m. Bovis still occurs in developing
countries and in immigrants from developing countries
where bovine tuberculosis is endemic (e.g. some latin
american countries). The increasing popularity of
cheese made from unpasteurized milk raises new
concerns if the cheeses come from countries with a
bovine tb problem (e.g. mexico , the united kingdom).

10. Pathophysiology of Tuberculosis .
• Tuberculosis may occur in three stages.
• a. Primary infection.
• Infection requires inhalation of particles small enough to traverse the upper
respiratory defences and deposit deep in the lung, usually in the subpleural
airspaces of the middle or lower lobes. Larger droplets tend to lodge in the
more proximal airways and typically do not result in infection. Infection
usually begins from a single droplet nucleus , which typically carries few
organisms. Perhaps only a single organism may suffice to cause infection in
susceptible infection. Initiate infection, M. tuberculosis bacilli must be
ingested by alveolar macrophages. Bacilli that are not killed by the
macrophages actually replicate inside them , ultimately killing the host
microphage (with the help of CD8 lymphocytes), inflammatory cells are
attracted to the area , causing a focal pneumonitis that coalesces into the
characteristic tubercles seen histologically . In the early weeks of infection,
some infected macrophages migrate to regional lymph nodes (eg. hilar ,
mediastinal ), where they access the bloodstream. Organisms may then
spread hematogenusly to any part of the body , particularly the apical-
posterior portion of the lungs , epiphysis of the long bones , kidneys ,
vertebral bodies and meninges.

11. • Latent infection.
• It occurs after most primary infections . In about 95 % of cases , after about 3
week of unihibited growth, the immune system suppresses bacillary replication ,
usually before signs or symptoms develop. Foci of bacilli in the lung or other
sites resolve into epithelial cell granulomas , which may have caseous and
necrotic centres. Tubercle bacilli can survive in this material for years , the
balance between the host's resistance and microbial virtulence determines
whether the infection ultimately resolves without treatment, remains dormant ,
or becomes active . Infectious foci may leave fibronodular scars in the apices of
one or both lungs (simon foci, which usually result from hematogenous seeding
from another site of infection) or small areas of consodilation (Ghon foci). A
Ghon focus with lymph node involvement is a Ghon complex, which usually
result from hematogenous seeding from another site of infection) or small areas
of consodilation (Ghon foci). A Ghon focus with lymph node involvement is
Ghon Complex, which if calcified, is called a Ranked complex. The tuberculin
skin test and interferon-gamma release blood assays (IGRA) become positive
during the latent stage of infection. Sites of latent infection are dynamic
processes , not entirely dormant as once beleived.

12. • Extrapulmonary TB at any site can sometimes manifest without evidence of
lunginvolvement. TB lymphadenopathy is the most common extrapulmonary
presentation, however meningitis is the most feared because of its high mortality in
the very young and very old.
• Active disease :
• Any organ initially seeded may become a site of reactivation , but reactivation occurs
most often in the lung apices, presumably because of favourable local conditions
such as high oxygen tension. Ghon foci and affected hilar lymph nodes are much less
likely to be sites of reactivation. Other conditions that facilitate reactivation , but to a
lesser extent than HIV infection, include Diabetes, Head and neck cancer,
Gastrectomy, Jejunoileal bypass surgery, Dialysisdependent chronic kidney disease,
Significant weight loss , Drugs that suppresss the immune system. Patients who
require immunosuppression after soild organ transplantation are at higher risk, but
other immunosuppressants such as corticosteroids and TNF inhibitors also commonly
cause reactivation. Tobacco use also is a risk factor. In some patients , active disease
develops when they are reinfected rather than when latent disease reactivates.
Reinfection is more likely to be the mechanism in areas where TB is prevalent , and
patients are exposed to a large inoculum of bacilli. Reactivation of latent infection
predominates in low prevalence areas. In a given patient , it is difficult to determine
whether active disease resulted from reinfection or reactivation.

13. • TB damages tissues through delayed-type hypersensitivity
(DTH) , typically producing granulomatous necrosis with a
caseous histologic appearance . Lung lesions are
characteristically but not invariably cavitary , especially in
immunosuppressed patients with impaired DTH. Pleural
effusion is less common than in progressive primary TB but
may result from direct extension or hematogenous spread.
Rupture of a large tuberculous lesion into the pleural space
may cause empyema with or without bronchopleaural
fistula and sometimes causes pneumothorax . In the
prechemotherapy era , TB empyema sometimes
complicated medically induced pneumothorax therapy and
was usually rapidly fatal, as was sudden massive
heamoptysis due to erosion of a pulmonary artery by an
enlarging cavity.

14. • Pharmacological Management of Tuberculosis :
• Measures to prevent transmission , someimes including respiratory
isolation.
• a. Antibiotics :
• Most Patients with uncomplicated tuberculosis and all patients with
complicating illlness (e.g. AIDS , hepatitis , Diabetes), adverse drug reactions
or drug resistance should be referred to aTB specialist.
• b. Most Patients with TB can be treated as outpatients , with instructions on
how to prevent transmission usually including -
• Staying at home
• Avoiding visitors (except for previously exposed family members)
• Covering coughs with a tissue or an elbow.
• c. Hospitalization - The main indications for hospitalization are-
• Serious concomitant illness
• Need for diagnostic procedures
• Social issues (eg. homelessness)

15. • Need for respiratory isolation, as for people living in congregate
settings where previously unexposed people would be regularly
encountered (important primarily if effective treatment cannot be
ensured).
• d. Directly observed therapy (DOT) :
• DOT is becoming part of optimal patient case management , DOT
involves supervision by public health personnel of the ingestion of
every dose of drug. DOT increases the likelihood that the full
treatment course will be completed from 61% to 81% (91% with
enhanced DOT , in which incentives and enables such as
transportation vouchers , childcare , outreac workers , and meals
provided).
• DOT is particularly important for children and adolescents , for
patients with HIV infection , psychiatric illness, or substance
abuse , After treatment failure , relapse , or developmen of drug
resistance.

16. • e. First Line Drugs :
• First line drugs isoniazid (INH) , Rifampin (RIF) and
ethambutol (EMB) are used together in initial
treatment.
• Isoniazid (INH) is given orally once/day , has good
tissue penetration (including CSF), and is highly
bactericidal . It remains the single most useful and
least expensive drug for TB treatment. Adverse
effects of isoniazid include rash , fever and rarely ,
anemia and agranulocytosis is given orally
once/day, has good tissue penetration (including
CSF) , and is highly bactericidal .It remains the

17. • Rifampin (RIF) , given orally is bactericidal , is well-
absorbed , penetrates well into cells and CSF , and
acts rapidly . It also eliminates dormant organisms
in macrophages or caseous lesion that can cause
late relapse.
• Thus RIF should be used throughout the course of
therapy.
• Adverse effects of rifampin include cholestatic
jaundice (rare ), fever , thrombocytopenia and renal
failure.

18. • Pyrazinamide (PZA) is an oral bactericidal drug. When
used during the itensive initial 2 mo of treatment, it
shortens the duration of therapy to 6 months and
prevents develooment of resistance to RIF. The major
adverse effects of pyrazinamide are GI upste and
hepatitis. I often causes hyperuricemia which is
generally mild and only rarely induces gout. PZA is
commonly used during pregnancy , but its safety has
not been confirmed.
• Ethambutol (EMB) is given orally and is the best-
tolerated of the first line drugs . Its main toxicity is optic
neuritis, which is more common at higher doses (eg. 25
mg/kg) and in patients with impaired renal function.

19. • Second line drugs.
• Other antibiotics are active against TB and are used
primarily when patients have drug-resistant TB (DR-
TB) or do not tolerate one of the first line drugs.
The 2 most important classes are aminoglycosides
(and the closely related polypeptide drug ,
capreomycin ) and fluoroquinolones ,
aminoglycosides are available only for parenteral
use.

20. • Streptomycin , once the most used aminoglycoside
, is veryy effective and bactericidal . CSF
penetration is poor , and itrathecal administration
should not be used if other effective drugs are
available . Adverse effects of streptomycin include
rash , fever , agranulocytes and serum sickness.
Flushing and tingling around the mouth commonly
accompany injection but subside quickly.
Streptomycin is contraindicated during pregnancy
because it may cause vestibular toxicity and
ototosicity in the fetus.

21. • Kanamycin and amikacin may remain effective even
if streptomycin resistance has developed . Their
renal and neural toxicities are like those of
streptomycin . Kanamycin is the most widely used
injectable for MDR-TB.

22. • Capreomycin , a related nonaminoglycoside
parenteral bactericidal drug , has dosage ,
effectiveness and adverse effects like those of
aminoglycosides. It is an important drug for MDR-
TB beause isolates resistant to streptomycin are
often susceptible to capreomycin and it is
somewhat better tolerated than aminoglycosides
when prolonged administration is required.