1. Presented By:
Nasir Nazeer

2. Sequence of the Presentation
• History of TB
• TB Transmission
• Drug-Resistant TB
• TB Pathogenesis
• Progression from LTBI to TB disease
• Sites of TB disease
• TB Classification System
• Laboratory and Physical examination of TB

3. History of TB

4. History of Tubercluosis
• TB has affected humans for
millennia
• Historically known by a
variety of names, including:
– Consumption
– Wasting disease
– White plague
• TB was a death sentence for
many

5. History of TB
Scientific Discoveries in 1800s
• Until mid 1800s, many
believed TB was hereditary
• 1865 Jean Antoine-Villemin
proved TB was contagious
• 1882
Robert
Koch
discovered M. tuberculosis,
the bacterium that causes
TB

6. Germany issued a Postal stamp to give
tribute to Robert Koch

7. History of TB
Sanatoriums
• Before TB antibiotics,
many patients were
sent to sanatoriums
• Patients followed a
regimen of bed rest,
open air, and sunshine
• TB patients who could
not afford sanatoriums
often died at home
Sanatorium patients resting outside

8. Famous personalities affected with TB

11. Breakthrough in the Fight Against
TB
• Drugs that could kill TB bacteria
were discovered in 1940s and
1950s
• Streptomycin (SM) discovered
in 1943
• Isoniazid (INH) and
paminosalicylic
acid
(PAS)
discovered between 1943 and
1952
• TB death rates in U.S. began to
drop dramatically
• Each year, fewer people got TB
• Most TB sanatoriums in U.S.
had closed by mid 1970s

12. TB Resurgence
• Increase in TB in mid 1980s
•
Contributing factors:
– Inadequate funding for TB
control programs
– HIV epidemic
– Increased immigration from
countries where TB is
common
– Spread in homeless shelters
and correctional facilities
– Increase and spread of multi
drug-resistant TB
March 16, 1992 Newsweek Magazine Cover

13. TB History Timeline
1993: TB cases decline due to
increased funding and enhanced
TB control efforts
1865:
JeanAntoine
Villemin
proved TB is
contagious
1840
1860
1884:
First TB
sanatorium
established
in U.S.
1880
1900
1882:
Robert Koch discovers
M. tuberculosis
1943:
Streptomycin
(SM) a drug used
to treat TB is
discovered
Mid-1970s: Most
TB sanatoriums in
U.S. closed
1920
1960
1940
1943-1952:
Two more drugs are
discovered to treat
TB: INH and PAS
1980
2000
Mid-1980s:
Unexpected rise in
TB cases

14. TB Transmission

15. TB Transmission
Transmission is defined as the spread of an
organism, such as M. tuberculosis, from
one person to another.

16. TB Transmission
Types of Mycobacteria
•
•
•
There are different types of
Mycobacterium
M. tuberculosis causes most TB
cases in the world
Mycobacteria that can cause TB:
– M. tuberculosis
– M. bovis (the bovine tubercle
bacillus)
– M. africanum (isolated from
•
cases in West, Central, and East
Africa)
– M. microti (the "vole" bacillus,
a less virulent and rarely
encountered organism)
– M. pinnipedii (a bacillus
infecting seals and sea lions in
the southern hemisphere and
recently isolated from humans)
Mycobacteria that do not cause
TB
– e.g., M. avium complex

17. TB Transmission
• TB is spread person to person
through the air via droplet
nuclei
• M. tuberculosis may be expelled
when an infectious person:
– Coughs
– Sneezes
– Speaks
– Sings
• Transmission occurs when
another person inhales droplet
nuclei

18. TB Transmission
Dots in air represent droplet nuclei containing
M. tuberculosis

20. TB Transmission
• Probability that TB will
transmitted depends on:
be
– Infectiousness of person with TB
disease
– Environment
occurred
in
which
exposure
– Length of exposure
– Virulence (strength) of the tubercle
bacilli
• The best way to stop transmission
is to:
– Isolate infectious persons
– Provide effective treatment to
infectious persons as soon as possible

21. Etiological Agent
•
M. tuberculosis is a rod-shaped,
non-spore-forming, thin aerobic
bacterium measuring 0.5 um to 3
um the bacilli cannot be
decolorized by acid alcohol; this
characteristic
justifies
their
classification as acid-fast bacilli.
• Acid fastness is due mainly to the
organisms' high content of
mycolic acids, long-chain crosslinked fatty acids, and other cellwall lipids
• It grows slowly .
• It can’t tolerate heat, but It can
live in humid or dry or cold
surroundings.

22. Symptoms associated with the TB
•
•
•
•
•
•
•
•
•
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

24. Pathological changes of TB
•
•
•
•
•
Following are the different
pathological changes associated
with TB.
– Infiltration
– Hyperplasia
– Calcification
These changes happen in different
stages of the tuberculosis
When
defense
system
is
predominant, there are less
number of bacteria and only
hyperplasia
and
calcification
would happen.
When defense system is weak,
there are large number of bacteria
and only calcification would
happen.
As a result of infection, infected
areas
are
enlarged
and
deteriorated.

26. Common Clinical patterns of TB
1. Primary pulmonary tuberculosis (Primary Complex
and Bronchial Lymphnod-Tuberculosis)
2. Milliary Tuberculosis (acute, subacute and
chronic hematogenous pulmonary tuberculosis)
3. Secondary pulmonary tuberculosis
Infiltrative pulmonary tuberculosis
Chronic fibrocavenous pulmonary tuberculosis
4. Tuberculous pleuritis
5. Extrapulmonary tuberculosis

27. Clinical Manifestations of TB
• Systemic signs:
Most patients present as cases of pulmonary tuberculosis
with fever, weight loss, anorexia, fatigue, night sweats wasting.
•
Respiratory signs:
Cough may vary from mild to severe, and sputum may be
scant and mucoid or copious and purulent.
Hemoptysis may be due to cough of a caseous lesion or
bronchial ulceration chest pain, tachypenea ect.
• Physical signs:
nonspecific.

28. Drug-Resistant TB

29. Drug-Resistant TB
• Caused by M. tuberculosis
organisms resistant to at
least one TB treatment drug
–
–
–
–
Isoniazid (INH)
Rifampin (RIF)
Pyrazinamide (PZA)
Ethambutol (EMB)
• Resistant means drugs can
no longer kill the bacteria

30. Drug-Resistant TB
Primary Resistance
Caused by person-to-person
transmission of drug-resistant organisms
Secondary Resistance Develops during TB treatment:
• Patient was not
given appropriate
treatment regimen
OR
• Patient did not
follow treatment regimen as
prescribed

31. Drug-Resistant TB
Mono-resistant
Resistant to any one TB treatment drug
Poly-resistant
Resistant to at least any 2 TB drugs (but not
both isoniazid and rifampin)
Multidrug
resistant
(MDR TB)
Resistant to at least isoniazid and rifampin,
the 2 best first-line TB treatment drugs
Extensively drug
resistant
(XDR TB)
Resistant to isoniazid and rifampin, PLUS
resistant to any fluoroquinolone AND at least
1 of the 3 injectable second-line drugs (e.g.,
amikacin, kanamycin, or capreomycin)

32. TB infection and the World

33. TB Pathogenesis
Pathogenesis is defined as how an infection
or disease develops in the body.

34. TB Pathogenesis
•
Occurs when tubercle bacilli are
in the body, but the immune
system is keeping them under
control
• Develops when immune system
cannot keep tubercle bacilli
under control
– May develop very soon after
infection or many years after
infection
• About 10% of all people with
normal immune systems who
have LTBI will develop TB disease
at some point in their lives
• People with TB disease are often
infectious

35. TB Pathogenesis
Droplet nuclei containing tubercle bacilli are
inhaled, enter the lungs, and travel to small
air sacs (alveoli)

36. TB Pathogenesis
2
b r o n c h io le
b lo o d v e s s e l
t u b e r c le b a c illi
a lv e o li
Tubercle bacilli multiply in alveoli, where
infection begins

37. TB Pathogenesis
3
b r a in
bone
lu n g
k id n e y
A small number of tubercle bacilli enter
bloodstream and spread throughout body

38. TB Pathogenesis
LTBI
4
s p e c ia l
im m u n e c e lls
fo r m a b a r r ie r
s h e ll (in th is
e x a m p le ,
b a c illi a r e
in th e lu n g s )
• Within 2 to 8 weeks the immune system produces
special immune cells called macrophages that
surround the tubercle bacilli
• These cells form a barrier shell that keeps the
bacilli contained and under control (LTBI)

39. TB Pathogenesis
5
s h e ll b r e a k s
dow n and
tu b e r c le
b a c illi e s c a p e
a n d m u lt ip ly
(in th is e x a m p le ,
T B d is e a s e
d e v e lo p s in
th e lu n g s )
• If the immune system CANNOT keep tubercle bacilli
under control, bacilli begin to multiply rapidly and
cause TB disease
• This process can occur in different places in the body

40. TB Pathogenesis

41. LTBI vs. TB Disease
Latent TB Infection (LTBI)
TB Disease (in the lungs)
Inactive, contained tubercle bacilli in Active, multiplying tubercle bacilli in
the body
the body
TST or blood test results usually
positive
TST or blood test results usually
positive
Chest x-ray usually normal
Chest x-ray usually abnormal
Sputum smears and cultures
negative
Sputum smears and cultures may be
positive
No symptoms
Symptoms such as cough, fever,
weight loss
Not infectious
Often infectious before treatment
Not a case of TB
A case of TB

42. TB Pathogenesis
Progression from LTBI to TB Disease

43. Progression to TB Disease
• Risk of developing TB disease is highest the first 2
years after infection
• People with LTBI can be given treatment to prevent
them from developing TB disease
• Detecting TB infection early and providing treatment
helps prevent new cases of TB disease

44. Progression to TB Disease
Some conditions increase probability of LTBI
progressing to TB disease
•
Infection with HIV
•
Organ transplant
•
Chest x-ray findings suggestive of
previous TB
•
Silicosis
•
Diabetes mellitus
•
Severe kidney disease
•
Certain types of cancer
•
Certain intestinal conditions
•
Low body weight
•
•
•
Substance abuse
Recent TB infection
Prolonged therapy with
corticosteroids and other
immunosuppressive therapy,
such as prednisone and tumor
necrosis factor-alpha [TNF-α]
antagonists

45. Progression to TB Disease
People Exposed to TB
Not
TB Infected
Latent TB
Infection (LTBI)
Not
Infectious
Not
Infectious
Negative TST or
QFT-G test result
Positive TST or
QFT-G test result
No
TB Infection
Latent TB
Infection
May go on to
develop TB
disease

46. Progression to TB Disease
TB and HIV
In an HIV-infected person,
TB can develop in one of
two ways:
• Person with LTBI becomes
infected with HIV and then
develops TB disease as the
immune system is weakened
• Person with HIV infection
becomes infected with M.
tuberculosis and then rapidly
develops TB disease
Image credit: Mississippi State Department of Health

47. TB Pathogenesis
Sites of TB Disease

48. Sites of TB Disease
Bacilli may reach any part of the body, but common sites
include:
B r a in
L a ry n x
Bone
Lym ph node
P le u r a
Lung
K id n e y
S p in e

49. TB Pathogenesis
TB Classification System

50. TB Classification System
Based on pathogenesis of TB
Class
Type
Description
0
No TB exposure
Not infected
No history of TB exposure
Negative result to a TST or IGRA
1
TB exposure
No evidence of
infection
History of TB exposure
Negative result to a TST (given at least 810 weeks after exposure) or IGRA
2
TB infection
No TB disease
Positive result to a TST or IGRA
Negative smears and cultures (if done)
No clinical or x-ray evidence of active
TB disease

51. TB Classification System
Based on pathogenesis of TB
Class
Type
Description
3
TB, clinically
active
Positive culture (if done) for M. tuberculosis Positive
result to a TST or IGRA, and clinical, bacteriological, or
x-ray evidence of TB disease
4
Previous TB
disease
(not clinically
active)
Medical history of TB disease
Abnormal but stable x-ray findings
Positive result to a TST or IGRA
Negative smears and cultures (if done)
No clinical or x-ray evidence of active TB disease
5
TB suspected
Signs and symptoms of TB disease, but evaluation not
complete

52. Laboratory and Physical
examination of TB

53. Laboratory and Physical Examination
• Following methods are used for laboratory
and physical examination of TB
– Chest radiography
– Sputum examination
– Tuberculin testing
– PCR test to detect TB
– TB antibody testing
– Bronchoscopy

54. Radiology

55. Radiology
• Chest radiography is the most important method to detect TB
• TB’s characteristics of a chest radiograph favor the diagnosis of
tuberculosis as following
• shadows mainly in the upper zone
• patchy or nodular shadows
• the presence of a cavity or cavities, although these, of course, can
also occur in lung abscess, carcinoma, etc
• the presence of calcification, although a carcinoma or pneumonia
may occur in an areas of the lung where there is calcification
due to tuberculosis
• bilateral shadows, especially if these are in the upper zones
• the persistence of the abnormal shadows without alteration in
an x-ray repeated after several weeks
• this helps to exclude a diagnosis of pneumonia or other acute
infection

57. Primary Complex

58. Milliary Tuberculosis

59. Secondary Pulmonary TB
infiltrate

60. Sputum examination
• There are direct smear
and culture methods.
• Direct smear
examination is only
positive when a large
no of bacilli begin to
excrete

61. Tuberculin testing
•
A tuberculin skin test is done to see if you have ever had tuberculosis (TB).
The test is done by putting a small amount of TB protein (antigens) under
the top layer of skin on your inner forearm. If you have ever been exposed
to the TB bacteria (Mycobacterium tuberculosis), your skin will react to
the antigens by developing a firm red bump at the site within 2 days.
•
The TB antigens used in a tuberculin skin test are called purified protein
derivative (PPD). A measured amount of PPD in a shot is put under the top
layer of skin on your forearm. This is a good test for finding a TB infection.
It is often used when symptoms, screening, or testing, such as a chest Xray, show that a person may have TB.
•
A tuberculin skin test cannot tell how long you have been infected with
TB. It also cannot tell if the infection is latent (inactive) or is active and can
be passed to others.

62. Tuberculin testing
• A reaction of less then 05nm
is considered as negative.
• 5-9mm
is
considered
positive (+)
• 10-19mm is considered
positive (++)
• More then 20mm is
considered positive (+++)
• A positive tuberculin test
indicates TB infection with
or without disease.

63. PCR to detect Tuberculosis

64. Bronchoscopy
• Bronchoscopy is a technique of
visualizing the inside of
the airways for diagnostic and
therapeutic
purposes.
An
instrument (bronchoscope) is
inserted into the airways,
usually through the nose or
mouth.
This
allows
the
practitioner to examine the
patient's
airways
for
abnormalities such as foreign
bodies,
bleeding, tumors,
or inflammation.
Specimens
may be taken from inside the
lungs. The construction of
bronchoscopes ranges from
rigid metal tubes with attached
lighting devices to flexible
optical fiber instruments with
real time video equipment.

65. White blood cells and ESR
• The white blood count is usually normal.
• In practice the white blood count is only
useful in a minority of cases, When the
patient is less ill and the radiological
shadowing less extensive the count is often
normal or high normal
• ESR is often elevate