overview on tuberculosis

1. LIFE CYCLE AND PATHOGENESIS OF
Mycobacterium tuberculosis
Presented by
T.N.Jaya Ganesh
Cell and Molecular Biology
I - M.Sc Biotechnology
Dept. of Biotechnology
Bharathiar University.

2. INTRODUCTION
 TB is an airborne disease caused by the bacterium Mycobacterium
tuberculosis.
 M. tuberculosis and seven very closely related mycobacterial species (M. bovis,
M. africanum, M. microti, M. caprae, M. pinnipedii, M. canetti and M.
mungi) together comprise what is known as the M. tuberculosis complex.
 Most, but not all, of these species have been found to cause disease in humans.
 The majority of TB cases are caused by M. tuberculosis. M. tuberculosis
organisms are also called tubercle bacilli.

3. TB HISTORY TIMELINE
1840 19201860 1900 1940 1960 1980 20001880
1993: TB cases decline due to
increased funding and enhanced TB
control efforts
Mid-1970s: Most TB
sanatoriums in U.S.
closed
1884:
First TB
sanatorium
established
in U.S.
1865:
Jean-Antoine
Villemin
proved TB is
contagious
1943:
Streptomycin
(SM) a drug used
to treat TB is
discovered
1882:
Robert Koch discovers
M. tuberculosis
Mid-1980s:
Unexpected rise in
TB cases
1943-1952:
Two more drugs are
discovered to treat
TB: INH and PAS

4. TB TRANSMISSION

5. TB TRANSMISSION
 M. tuberculosis is carried in airborne particles, called droplet nuclei, of 1– 5
microns in diameter.
 Infectious droplet nuclei are generated when persons who have pulmonary or
laryngeal TB disease cough, sneeze, shout, or sing.
 Depending on the environment, these tiny particles can remain suspended in the
air for several hours.
 M. tuberculosis is transmitted through the air, not by surface contact.
 Transmission occurs when a person inhales droplet nuclei containing M.
tuberculosis, and the droplet nuclei traverse the mouth or nasal passages, upper
respiratory tract, and bronchi to reach the alveoli of the lungs.

6. TB TRANSMISSION (1)
TB is spread from person to person through the air. Dots in
air represent droplet nuclei containing M. tuberculosis

7. TB TRANSMISSION (2)
 Probability that TB will be transmitted depends on:
 Infectiousness of person with TB disease
 Environment in which exposure occurred
 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

8. M.tuberculosis (scanning EM) M.tuberculosis on Lowenstein-Jensen medium
LIFE CYCLE
It is an obligate aerobe and grow very slowly.
15-20 hour doubling vs. 30 minutes for E. coli.
It require 6-8 weeks to grow on plates

9. DRUG-RESISTANT TB

10. DRUG-RESISTANT TB (1)
 Caused by M. tuberculosis
organisms resistant to at least one
TB treatment drug
 Isoniazid (INH)
 Para-aminosalicylate sodium
(PAS)
 Rifampin (RIF)
 Pyrazinamide (PZA)
 Ethambutol (EMB)
 Resistant means drugs can no
longer kill the bacteria

11. DRUG-RESISTANT TB (2)
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

12. DRUG-RESISTANT TB (3)
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)

13. TB PATHOGENESIS

14. LATENT TB INFECTION (LTBI)
 Persons with LTBI have M. tuberculosis in their bodies, but do not have TB
disease and cannot spread the infection to other people.
 A person with LTBI is not regarded as having a case of TB.
 The process of LTBI begins when extracellular bacilli are ingested by
macrophages and presented to other white blood cells.
 This triggers the immune response in which white blood cells kill or
encapsulate most of the bacilli, leading to the formation of a granuloma. At this
point, LTBI has been established.

15. TB DISEASE
 In some people, the tubercle bacilli overcome the immune system and multiply,
resulting in progression from LTBI to TB disease.
 Persons who have TB disease are usually infectious and may spread the
bacteria to other people.

 The progression from LTBI to TB disease may occur at any time, from soon to
many years later.

16. TB PATHOGENESIS (1)
Droplet nuclei containing tubercle
bacilli are inhaled, enter the
lungs, and travel to small air sacs
(alveoli)
bronchiole
blood vessel
tubercle bacilli
alveoli
2
Tubercle bacilli multiply in
alveoli, where
infection begins

17. TB PATHOGENESIS (2)
A small number of tubercle
bacilli enter
bloodstream and spread
throughout body
brain
lung
kidney
bone
3 special
immune cells
form a barrier
shell (in this
example,
bacilli are
in the lungs)
4
• 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)

18. TB PATHOGENESIS (3)
shell breaks
down and
tubercle
bacilli escape
multiply
(in this example,
TB disease
develops in
the lungs)
and
5
• 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

19. LTBI VS. TB DISEASE
Latent TB Infection (LTBI) TB Disease (in the lungs)
Inactive, contained tubercle bacilli in
the body
Active, multiplying tubercle bacilli in
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

20. PROGRESSION FROM LTBI TO TB
DISEASE (1)
 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.

21. PROGRESSION TO TB DISEASE (2)
People Exposed to TB
Not
TB Infected
Latent TB
Infection (LTBI)
Not
Infectious
Positive TST or
QFT-G test result
Latent TB
Infection
May go on to
develop TB
disease
Not
Infectious
Negative TST or
QFT-G test result
No
TB Infection
Figure 1.5

22. PROGRESSION TO TB DISEASE (4)
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

23. SITES OF TB DISEASE (1)
Bacilli may reach any part of the body, but common
sites include:
Brain
Lymph node
Pleura
Lung
Spine
Kidney
Bone
Larynx

24. SITES OF TB DISEASE (2)
Location Frequency
Pulmonary TB Lungs Most TB cases are
pulmonary
Extrapulmonary TB
Places other than
lungs such as:
• Larynx
• Lymph nodes
• Pleura
• Brain
• Kidneys
• Bones and joints
Found more often in:
• HIV-infected or
other
immunosuppressed
persons
• Young children
Miliary TB
Carried to all parts of
body, through
bloodstream
Rare

25. TB CLASSIFICATION SYSTEM (1)
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 8-
10 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
Based on pathogenesis of TB

26. TB CLASSIFICATION SYSTEM (2)
Class Type Description
3 TB, clinically
active
Positive culture (if done) for M. tuberculosis Positive
result to a TST 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
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
Based on pathogenesis of TB

27. DIAGNOSIS AND TREATMENT

28. LABORATORY DIAGNOSIS OF
MYCOBACTERIAL DISEASE
Detection:
Skin test – using PPD
Microscopy
Carbolfuchsin acid fast stain
Direct nucleic acid probes
Culture
Solid agar based or egg-based media
Broth based media
Identification:
Morphologic properties
Biochemical properties
Analysis of cell wall lipids
Nucleic acid probes
Nucleic acid sequencing

29. TREATMENT PREVENTION AND
CONTROL
Multiple-drug regimens and prolonged treatment are required to prevent
development of drug resistant strains.
Regimens recommended for treatment include isoniazid and rifampin
for 9 months, with pyrazinamide and ethambutol or streptomycin added
for drug resistance strains.
Prophylaxis for exposure to tuberculosis can include isoniazid for 9
months, rifampin for 4 months, or rifampin and pyrazinamide for 2
months.
Pyrazinamide and ethambutol or levofloxacin are used for 6 to 12
following exposure to drug-resistant M.tuberculosis.
Immunoprophylaxis with BCG in endemic countries.
Control of disease through active surveillance, prophylactic and
therapeutic intervention, and careful case monitoring.

30. CONCLUSION
TB is easily tranmissable.
Curable under proper medication.
Preventive measures are the convienient way.