This document discusses tuberculosis (TB), including its definition, causative agents, spread, epidemiology, pathogenesis, signs and symptoms, diagnosis, and treatment. It notes that TB is caused by bacteria in the Mycobacterium tuberculosis complex that usually affect the lungs. Diagnosis involves tests like smear microscopy, culture, PCR and tuberculin skin testing. Standard treatment involves a combination of antibiotics over 6-9 months. Drug-resistant forms like multi-drug resistant TB and extensively drug-resistant TB require longer and more toxic treatment regimes.

1. Tuberculosis
Therapeutics II

2. Topics to be discussed
 Definition
 Classification
 Causative agents
 Spread of disease
 Epidemiology
 Pathophysiology
 Signs and Symptoms
 Precautions
 Diagnosis
 Treatment or Management

3. Definition
 Tuberculosis (TB) is a potentially
fatal contagious disease that can
affect almost any part of the body but
is mainly an infection of the lungs.
Neo-latin word :
- Round nodule/Swelling
- Condition
“Tubercle”
“Osis”

4. Causative Organisms
Mycobacterium tuberculosis
Mycobacterium Bovis
Human
Animals

5. Other causative organisms
 Mycobacterium africanum
 Mycobacterium microti
Non-Mycobacterium Genus
 Mycobacterium leprae
 Mycobacterium avium
 Mycobacterium asiaticum
M. africanum
M. Bovis
M. Canetti
M. microti
M. tuberculosis complex

6. Anatomy of M.tuberculosis
 Discovered in 1882 by Robert Koch.

7. Classification
Tuberculosis
Pulmonary TB
- Primary Disease
- Secondary Disease
Extra pulmonary
i. Lymph node TB
ii. Pleural TB
iii. TB of upper airways
iv. Skeletal TB
v. Genitourinary TB
vi. Miliary TB
vii. Pericardial TB
viii. Gastrointestinal TB
ix. Tuberculous Meningitis
x. Less common forms

8. Epidemiology

9.  In 2011,there were an estimated 8.7million
incidence cases of TB globally.
 Its equivalent to 125 cases in 1,00,000 population.
Asian : 59%
African : 26%
Eastern Mediterranean Region: 7.7%
The European Region : 4.3%
Region of the America : 3%

12. Incidence of Tuberculosis

13. Spread of Tuberculosis
• Airborne

15. Severe Symptoms
 Persistent cough
 Chest pain
 Coughing with bloody sputum
 Shortness of breath
 Urine discoloration
 Cloudy & reddish urine
 Fever with chills.
 Fatigue

16. Based on types of TB

17. Pathogenesis

18. Pathogenesis

19.  Three important consideration for pathogenesis of
tuberculosis:
i. The basis of virulence of organism.
ii. The relationship of HSN to immunity against
infection.
iii. Pathogenesis of tissue destruction and caseous
necrosis.

20. 1. Virulence of organism.
 No endo-toxin,exo-toxins or histolytic enzymes.
 Capability to escape killing by macrophages and
delayed type HSN reaction.
M.Tuberculosis contains several important components:
1) Cord Factor
2) Sulfatides
3) LAM
4) Heat shock Protein
5) Complement on the surface

21. a. Cord Factor:
 Surface glycolipids, allows to grow organism in-vitro and in vivo.
b. Sulfatides:
 Surface glycolipids containing sulfur.
 Prevent fusion of macrophage containing tuberculosis with
lysosomes.
c. LAM
 Major hetero-polysaccharide inhibits the activation of macrophage
by IF-Ý.
 Also induces macrophages to secrete TNF-þ which causes
fever,weight loss and tissue damage and secretes IL-10,which
suppresses mycobacteria-induces T-cell proliferation.

22. d. Heat shock Protein
 Similar to human heat shock proteins.
 Responsible to carryout auto immune reactions.
e. Complement on the surface
 Opsonization and responsible for its uptake by
macrophage.

23. 2.The relationship of HSN to immunity against
infection.
 The development of delayed type IV
hypersensitivity reaction to the tubercules bacillus
probably explains the organism’s destructiveness
in tissues and also the emergence of resistance to
the organism , the inflammatory response is not
specific.

24. 3. Pathogenesis of tissue destruction and caseous
necrosis.
 Within in 2 or 3 seeks coincident with the
appearance of the positive skin reaction,the
reaction becomes granulomatus and the centers of
the granulomas become caseous, forming typical
“soft tubercles”.

26. A. Pulmonary TB :-
1. Primary Tuberculosis :-
 The infection of an individual who has not been previously
infected or immunised is called Primary tuberculosis or Ghon’s
complex or childhood tuberculosis.
 Lesions forming after infection is peripheral and accompanied by
hilar which may not be detectable on chest radiography.
Types
2. Secondary Tuberculosis :
The infection that individual who has been previously infected or
sensitized is called secondary or post primary or reinfection or
chronic tuberculosis.

27. B} Extra Pulmonary TB :-
• 20% of patients of TB Patient
• Affected sites in body are :-
1) Lymph node TB ( tuberculuous lymphadenitis):-
• Seen frequently in HIV infected patients.
• Symptoms :- Painless swelling of lymph nodes most commonly at
cervical and Supraclavical (Scrofula)
• Systemic systems are limited to HIV infected patients.
•
2) Pleural TB :-
Involvement of pleura is common in Primary TB
and results from penetration of tubercle bacilli into pleural
space.
Contd…

28.  Involvement of larynx, pharynx and epiglottis.
 Symptoms :- Dysphagia, chronic productive cough
3) TB of Upper airways :-
4) Genitourinary TB :-
• 15% of all Extra pulmonary cases.
• Any part of the genitourinary tract get infected.
• Symptoms :- Urinary frequency, Dysuria, Hematuria.
5) Skeletal TB :-
• Involvement of weight bearing parts like spine, hip,
knee.
• Symptoms :- Pain in hip joints n knees, swelling of
knees, trauma.
6) Gastrointestinal TB :-
• Involvement of any part of GI Tract.
• Symptoms :- Abdominal pain, diarrhea, weight loss

29.  5% of All Extra pulmonary TB
 Results from Hematogenous spead of 10 & 20 TB.
7) TB Meningitis & Tuberculoma :-
8) TB Pericardiatis :-
• 1- 8% of All Extra pulmonary TB cases.
• Spreads mainly in mediastinal or hilar nodes
or from lungs.
9) Miliary or disseminated TB :-
• Results from Hematogenous spread of Tubercle Bacilli.
• Spread is due to entry of infection into pulmonary vein
producing
lesions in different extra pulmonary sites.
10) Less common Extra Pulmonary TB
• uveitis, panophthalmitis, painfull Hypersensitivity
related phlyctenular conjuctivis.

30. Diagnosis
1.Bacteriological test:
a. Zeihl-Neelsen stain
b. Auramine stain(fluorescence microscopy)
2. Sputum culture test:
a. Lowenstein –Jensen(LJ) solid medium: 4-18
weeks
b. Liquid medium : 8-14 days
c. Agar medium : 7 to 14 days

31. 3.Radiography:
Chest X-Ray(CXR)
20% error by physician
4.Nucleic acid amplification:
 Species identification ; several hours
 Low sensitivity, high cost
 Most useful for the rapid confirmation of
tuberculosis in persons with AFB-positive sputa
 Utility
◦ AFB-negative pulmonary tuberculosis
◦ Extra pulmonary tuberculosis

32. 5.Tuberculin skin test
(PPD)
 Injection of fluid into
the skin of the lower
arm.
 48-72 hours later –
checked for a
reaction.
 Diagnosis is based
on height of the skin.
1 dose = 0.1 ml contains 0.04µg
Tuberculin PPD.

33. Tuberculin test interpretation

34. Pathogenesis of tuberculin
test

35. 6. Other biological examinations
 Cell count(lymphocytes)
 Protein(Pandy and Rivalta tests) – Ascites, pleural
effusion and meningitis.

36. Preventive measures
1) Mask
2) BCG vaccine
3) Regular medical follow up
4) Isolation of Patient
5) Ventilation
6) Natural sunlight
7) UV germicidal irradiation

38. BCG vaccine
 Bacille Calmette Guerin (BCG).
 First used in 1921.
 Only vaccine available today for protection against
tuberculosis.
 It is most effective in protecting children from the disease.

39. Management

40. Drugs MOA Diagram
Isoniazid Inhibits mycolic acid synthesis.
RIFAMPICIN Blocks RNA synthesis by blocking
DNA dependent RNA polymerase
PYRAZINAMIDE •Bactericidal-slowly metabolizing
organism within acidic
environment of Phagocyte or
caseous granuloma.

41. Drugs MOA Diagram
ETHAMBUTOL •Bacteriostatic
•Inhibition of Arabinosyl
Transferase
STREPTOMYCIN •Inhibition of Protein
synthesis by disruption of
ribosomal function

42. ADRs and its Management

43. Treatment

44. Treating Drug Sensitive TB

45. Dosage regimen
 Intensive phase + continuation phase
 HREZ (2 months) + HRE (4 months)

46. Treatment regimen according to WHO
ISONIAZID (H) RIFAMPICIN (R) PYRAZINAMIDE (Z)
ETHAMBUTOL (E) STREPTOMYCIN (S)

47. DOTS
DOTS - Directly observed treatment, short-course
 DOT means that a trained health care worker or other
designated individual provides the prescribed TB drugs and
watches the patient swallow every dose.

48. Multi-Drug Resistance TB
 TB caused by strains of Mycobacterium
tuberculosis that are resistant to at least
isoniazid and rifampicin, the most effective
anti- TB drug.
 Globally, 3.6% are estimated to have MDR-
TB.
 Almost 50% of MDR-TB cases worldwide
are estimated to occur in China and India.

49. MDR-TB among new TB cases

50. MDR-TB in previously treated cases

51. Treating Drug Resistant TB

52. Extensively drug resistance
TB
 Extensively drug-resistant TB (XDR-TB) is a form
of TB caused by bacteria that are resistant to
isoniazid and rifampicin (i.e. MDR-TB) as well as
any fluoroquinolone and any of the second-line
anti-TB injectable drugs (amikacin, kanamycin or
capreomycin).

53. Treating Extensively Drug Resistant
TB

54. Thank You!!!