DIPLOMA LECTURE SERIES

DEFINITION
Tuberculosis, one of the oldest diseases

known to affect humans, is caused by bacteria

belonging to the Mycobacterium tuberculosis
complex.
The disease usually affects the lungs,
although in up to one-third of cases other
organs are involved.

ETIOLOGIC AGENT
M. tuberculosis complex, the most frequent

and important agent of human disease is M.

tuberculosis. The complex includes;
M. bovis
M. africanum
M. microti
M. canettii

Epidemiology
The WHO estimated that 8.8 million new

cases of tuberculosis occurred worldwide in

2005.
95% of new cases occur in developing
countries of Asia (4.9 million), Africa (2.6
million)
1.6 million deaths from tuberculosis occur
yearly 95% of them in developing countries.

BURDEN OF THE DISEASE

o Nigeria ranks 4th of 22 high burden Countries globally and has

the highest No of new TB case in Africa.

o Estimated incidence of TB: High burden countries, 2005.
Per 100,000
Country
All cases
population
1. India
1,852,000
168
2. China
1,319,000
100
3. Indonesia
533,000
239
4. Nigeria
372,000
283
5. Bangladesh
322,000
227
6. Pakistan
286,000
181
7. South Africa
285,000
600
8. Ethiopia
266,000
344
9. Phillipines
242,000
291
10.Kenya
220,000
641

Transmission
It is transmitted by droplet nucle(<5-10 m in

diameter) .
Aerosols are formed by coughing, sneezing, or
speaking and may remain suspended in the
air for several hours.
There may be as many as 3000 infectious
nuclei per cough.

3
Factors that influence infection;
Contact with a case of tuberculosis.
The intimacy and duration of that contact.
The degree of infectiousness of the case.
The shared environment of the contact .
The risk of acquiring M. tuberculosis infection

is determined mainly by exogenous factors.

Factors that influence disease;

The individuals innate susceptibility to
disease .
The level of function of cell-mediated immunity.
The risk of developing disease after being

infected depends largely on endogenous

factors

Clinical illness directly following infection is

classified as primary tuberculosis.

Dormant bacilli, however, may persist for
years before reactivating to produce
secondary illness.
Re-infection of a previously infected
individual, may also favor the development of
disease.

NATURAL HISTORY OF
DISEASE

Untreated tuberculosis is often fatal.

About one-third of patients will die within 1
year after diagnosis.
One-half will die within 5 years.
Five-year mortality among sputum smear
positive cases is about 65%.
Of survivors at 5 years, 60% will have
undergone spontaneous remission, while the
remainders will still be excreting tubercle
bacilli.

PATHOGENESIS
A fraction of inhaled aerosols (usually 10%)

reach the alveoli.

In the alveoli, nonspecifically activated
alveolar macrophages ingest the bacilli.
The balance between the bactericidal activity
of the macrophage and the number and
virulence of the bacilli determines the events
following phagocytosis of the bacilli.

In the initial stage of host-bacterium interaction,

either the hosts macrophages contain bacillary

multiplication or the bacilli begin to multiply.
If the bacilli multiply, their growth quickly kills
the macrophages, which lyse.
Non-activated monocytes attracted from the
bloodstream to the site ingest the bacilli
released and are carried in the lymphatics.
These initial stages of infection are usually
asymptomatic.

About 2 to 4 weeks after infection, two

additional host responses to M. tuberculosis

develop:
A tissue-damaging response and a
macrophage- activating response.
The tissue-damaging response is the result of
a delayed type hypersensitivity
reaction(DTH) .
It destroys non-activated macrophages that
contain multiplying bacilli.

The macrophage-activating response is a cell-

mediated phenomenon.
It results in the activation of macrophages
that are capable of killing and digesting
tubercle bacilli.
Although both of these responses can inhibit
mycobacterial growth, it is the balance
between the two that determines the form of
tuberculosis that will develop subsequently.

Cell-mediated immunity confers partial

protection against M. tuberculosis.

Two types of cells are essential:
Macrophages, which directly phagocytize
tubercle bacilli.
T cells (mainly CD4 lymphocytes), which
induce protection through the production of
lymphokines, especially interferon (IFN-).

After infection with M. tuberculosis, alveolar

macrophages secrete a number of cytokines:

Interleukin (IL) 1 contributes to fever.
IL-6 contributes to hyperglobulinemia.
TNF contributes to the killing of mycobacteria;

The formation of granulomas.

Fever
Weight loss

In the early stages of infection, bacilli are

usually transported by macrophages to

regional lymph nodes, from which they
disseminate widely to many organs and
tissues.

CLINICAL MANIFESTATIONS
PRIMARY DISEASE
In the majority of cases, the lesion heals

spontaneously and may later be evident as a

small calcified nodule.

Primary dz. cont.

In children and in persons with impaired

immunity it may progress to;

Pleural effusion
In severe cases, the primary site rapidly

enlarge, undergoes necrosis and cavitation.

Enlarged lymph nodes may compress bronchi,
causing obstruction
Partial obstruction may cause obstructive
emphysema, and bronchiectasis

Primary dz. Cont.

Bacilli may reach the bloodstream and

disseminate into various organs.

Immunocompromised persons may develop
military tuberculosis and/or tuberculous
meningitis.

POSTPRIMARY DISEASE
This results from endogenous reactivation of

latent infection and is usually localized to the

upper lobes.
Early in the course of disease, symptoms and
signs are often nonspecific and insidious;
Fever and night sweats.
Weight loss,
Anorexia,
General malaise, and weakness.

Secondary TB cont.
In the majority of cases, cough eventually

develops.
Often initially nonproductive and
subsequently accompanied by the production
of purulent sputum.
Blood streaking of the sputum is frequently
documented.

Secondary TB cont.
Pleuritic chest pain sometimes develops from

involvement of the pleura.

It can also result from muscle strain due to
persistent coughing.
Extensive disease may produce dyspnea

Physical examination
This may be normal or may produce the

following;
Chest asymmetry with apical flattening.
Mediasternal shift.
Asymetric chest wall movement.
Dull percussion notes.
Bronchial breathing.
Coarse crepitations

EXTRAPULMONARY
TUBERCULOSIS
TUBERCULOUS LYMPHADENITIS
This presents as painless swelling of the lymph nodes.
Mostly at cervical and supraclavicular sites.
Lymph nodes are usually discrete in early disease but

may become matted.

Lymph nodes may become inflamed and have a
fistulous tract draining caseous material.
Systemic symptoms are usually limited to HIV-infected
patients.
Concomitant lung disease may or may not be present.

PLEURAL TUBERCULOSIS
This results from penetration by bacilli into the
pleural space.
The effusion may be small, remain unnoticed,
and resolve spontaneously or may be large.
Fever, pleuritic chest pain, and dyspnea may be
present.
A chest radiograph reveals the effusion and, in
1/3 of cases, also shows a parenchymal lesion.

TUBERCULOUS EMPYEMA.
It is usually the result of the rupture of a cavity
or of a bronchopleural.
A chest radiograph may show
pyopneumothorax with an air-fluid level.
The effusion is purulent and thick.

TUBERCULOSIS OF THE UPPER AIRWAYS

Nearly always a complication of advanced
cavitary pulmonary tuberculosis.
Tuberculosis of the upper airways may involve
the larynx, pharynx, and epiglottis.
Symptoms include hoarseness and dysphagia in
addition to chronic productive cough.

GENITOURINARY TUBERCULOSIS
Genitourinary tuberculosis accounts for 15% of
all extrapulmonary cases.
May involve any portion of the genitourinary
tract.
It is due to hematogenous seeding following
primary infection.
Symptoms include urinary frequency, dysuria,
hematuria, and flank pain.

Genito-urinary TB cont.
Urinalysis gives abnormal results in 90% of

cases, revealing pyuria and hematuria.

The documentation of culture-negative pyuria
in acidic urine raises the suspicion of
tuberculosis.
Calcifications and ureteral strictures are
suggestive findings on x-ray.

Genitourinary TB cont.
Genital tuberculosis is more common in female

than in male patients.

In female patients, it affects the fallopian tubes
and the endometrium and may cause infertility,
pelvic pain, and menstrual abnormalities.
In male patients, tuberculosis affects the
epididymis, producing a slightly tender mass,
orchitis and prostatitis may also develop.
In almost half of cases of genitourinary
tuberculosis, urinary tract disease is also present.

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