Tuberculosis (TB) remains a major global health problem, infecting one third of the world's population. It is caused by the bacterium Mycobacterium tuberculosis which primarily affects the lungs. TB is transmitted via airborne droplets when people with active pulmonary TB cough, sneeze or spit. Common symptoms include cough, chest pain, and weight loss. Diagnosis involves microscopic examination of sputum samples and culture testing. Treatment requires a combination of antibiotics over a period of 6-9 months. Improving living conditions and developing more effective vaccines are important for tuberculosis control and elimination.

1. Tuberculosis
Robert L. Copeland, Jr., Ph.D. Brian Tracy .
Hong Fan
Department of Respiratory Diseases,
West China Hospital, Sichuan University

2. Introduction:
Infects 1/3 to ½ of world population..!
3 million deaths due to TB every year
Under privileged population -
Crowding, Poverty, malnutrition, single
male..!
Since 1985 incidence is increasing in west
AIDS, Diabetes, Immunosuppressed
patients, Diabetes, Drug resistance.
Fan H.

3. Tuberculosis (TB) remains the leading cause of death
worldwide from a single infectious disease agent.
Indeed up to 1/2 of the world's population is
infected with TB. The registered number of new
cases of TB worldwide roughly correlates with
economic conditions: the highest incidences are seen
in those countries of Africa, Asia, and Latin America
with the lowest gross national products. WHO
estimates that eight million people get TB every year,
of whom 95% live in developing countries. An
estimated 2 million people die from TB every year.
Fan H.

4. It is estimated that between 2000 and 2020, nearly
one billion people will be newly infected, 200
million people will get sick, and 35 million will die
from TB - if control is not further strengthened. The
mechanisms, pathogenesis, and prophylaxis
knowledge is minimal. After a century of decline TB
is increasing and there are strains emerging which
are resistant to antibiotics. This excess of cases is
attributable to the changes in the social structure in
cities, the human immunodeficiency virus epidemic,
and failure of most cities to improve public health
programs, and the economic cost of treating.
Fan H.

5. With the increased incidence of AIDS, TB has
become more a problem in the U.S., and the
world.
It is currently estimated that 1/2 of the world's
population (3.1 billion) is infected with
Mycobacterium tuberculosis. Mycobacterium
avium complex is associated with AIDS
related TB.
Fan H.

6. TB is an ancient infectious disease caused by
Mycobacterium tuberculosis. It has been
known since 1000 B.C., so it not a new
disease. Since TB is a disease of respiratory
transmission, optimal conditions for
transmission include:
overcrowding
poor personal hygiene
poor public hygiene
Fan H.

7. Transmission
Pulmonary tuberculosis is a disease of
respiratory transmission, Patients with the
active disease (bacilli) expel them into the air
by:
coughing,
sneezing,
shouting,
or any other way that will expel bacilli into the air
Fan H.

8. Once inhaled by a tuberculin free person, the
bacilli multiply 4 -6 weeks and spreads
throughout the body. The bacilli implant in
areas of high partial pressure of oxygen:
lung
renal cortex
reticuloendothelial system
Fan H.

9. This is known as the primary infection. The patient
will heal and a scar will appear in the infected loci.
There will also be a few viable bacilli/spores may
remain in these areas (particularly in the lung). The
bacteria at this time goes into a dormant state, as long
as the person's immune system remains active and
functions normally this person isn't bothered by the
dormant bacillus.
When a person's immune system is depressed., a
secondary reactivation occurs. 85-90% of the cases
seen which are of secondary reactivation type occurs
in the lungs.
Fan H.

10. Fan H.

11. Pathogenesis of TB:
Type IV hypersensitivity – T cells –
Macrophages Granuloma
Activated macrophages – epithelioid cells.
Remain viable inside macrophages (Mycolic
acid wax coat)
Cord Factor - surface glycolipid Antigenic.
Self destruction by lysosomal enzymes.
Fan H.

12. Fan H.

13. Hypersensitity – Immunity
Fan H.

14. Microbiology of TB:
Mycobacteria – ‘fungus like..
Bacilli, Aerobic, non motile, no toxins,
no spore.
Mycolic acid wax in cell wall
Carbol dye - Acid & alcohol fast (AFB)
M. tuberculosis & M. bovis
M. avium, M.intracellulare in AIDS -
Atypical TB
Fan H.

15. AFB - Ziehl-Nielson stain

16. Colony Morphology – LJ Slant

18. Classification of TB
1. Primary Pulmonary TB
2. Miliary TB (acute, subacute, chronic)
3. Secondary TB
(invasive, carvitary, caseation ,
Tuberculous Granulomas …)
4. Tuberculous Pleuritis
5. Extra-pulmonary TB
(bone, joints, renal, adrenal,skin… )
Fan H.

19. Primary tuberculosis
In a non immunized individual – children* adult*
Deep inhalation of airborne droplet ~ 3 microns.
Bacilli locate in the subpleural mid zone of lung
Localized "atypical" pneumonia
Brief acute inflammation – neutrophils.
5-6 days invoke granuloma formation.
2 to 8 weeks – healing – single round -Ghon focus.
If lymph node is also involved Ghon complex.
Fan H.

20. Primary or Ghon’s Complex
Primary tuberculosis is
the pattern seen with
initial infection with
tuberculosis in children.
Reactivation, or
secondary tuberculosis,
is more typically seen in
adults.
Fan H.

21. Primary Tuberculosis
In Non Immunized individuals (Children)
Primary Tuberculosis:
Self Limited disease
Ghons focus, complex or Primary complex.
Primary Progressive TB ( in US. )
Miliary TB and TB Meningitis.
Common in malnourished children
10% of adults, Immuno-suppressed individuals
Fan H.

22. Secondary Tuberculosis:
Post Primary in immunized individuals.
Cavitary Granulomatous response.
Reactivation or Reinfection
Apical lobes or upper part of lower lobes – O2
Caseation, cavity - soft granuloma
Pulmonary or extra-pulmonary
Local or systemic spread / Miliary
Vein – via left ventricle to whole body
Artery – miliary spread within the lung
Fan H.

23. Secondary Tuberculosis:
Reactivation occurs in 10-15% of patients.
Most commonly males 30-50 y
Slowly Progressive (several months)
Cough, sputum, Low grade fever, night sweats,
fatigue and weight loss.
Hemoptysis or pleuritic pain = severe disease
Fan H.

25. Ghon Complex
Fan H.

26. Miliary TB

27. Miliary TB
Millet like – grain.
Extensive micro spread.
Through blood or
bronchial spread
Low immunity
Pulmonary or Systemic
types.

28. Miliary TB Lung

29. Cavitary Tuberculosis
When necrotic tissue is
coughed up cavity.
Cavitation is typical for
large granulomas.
Cavitation is more
common in the
secondary reactivation
tuberculosis - upper
lobes.
Fan H.

30. Fan H.

31. Fan H.

32. Fan H.

33. Tuberculous Granulomas

34. Caseation Necrosis

35. Epitheloid cells in Granuloma

36. Cells in Granuloma

37. Morphology of Granuloma
1. Rounded tight collection of chronic
inflammatory cells.
2. Central Caseous necrosis.
3. Active macrophages - epithelioid cells.
4. Outer layer of lymphocytes, plasma cells
& fibroblasts.
5. Langhans giant cells – joined epithelioid
cells.
Fan H.

38. Tuberculous Granuloma

39. Cavitary Secondary TB

40. Systemic Miliary TB

41. Adrenal TB - Addison Disease

42. Spinal TB - Potts Disease

45. Diagnosis of TB
Clinical features are not confirmatory.
Zeil Nielson Stain - 1x104/ml, 60% sensitivity
Release of acid-fast bacilli from cavities intermittent.
3 negative smears to assure low infectivity*
Culture most sensitive and specific test.
Conventional Lowenstein Jensen media 3-6 wks.
Automated techniques within 9-16 days
PCR is available, but should only be performed by
experienced laboratories
PPD for clinical activity / exposure sometime in life.
Fan H.

46. PPD Tuberculin Testing
Sub cutaneous
Weal formation
Itching – no scratch.
Read after 72 hours.
Induration size.
5-10-15mm (non-ende)
< 72 hour is not diag*
+ve after 2-4 weeks.
BCG gives + result.

47. PPD Testing

48. Granuloma or LH giant cell is not
pathagnomonic of TB…!
Foreign body granuloma.
Fat necrosis.
Fungal infections.
Sarcoidosis.
Crohns disease.

49. "Troubles are often
the tools by which God
fashions us for better
things."
- Henry Ward Beecher

50. Classification of Drugs
3 Groups depending upon the degree of effectiveness and
potential side effects
First Line: (Primary agents)
are the most effective and have lowest toxicity. Isoniazid
(H), Rifampin(R)
Second Line:
Less effective and more toxic effects
include (in no particular order): p-amino salicylic acid,
Streptomycin(S), pyrazinamide(Z), Ethambutol(E),
Third Line
are least effective and most toxic. Amikacin, Kanamycin,
Capreomycin, Viomycin, Kanamycin, Cycloserine
Fan H.

51. Isoniazid
Considered the drug of choice for the
chemotherapy of TB. discovered in 1945 a
hydrazide of isonicotonic acid
is bacteriostatic for resting bacilli,
bactericidal for growing bacilli.
Fan H.

52. Treatment
2HRZE/4HRE, 2HRSE/4HRE
( 6---18months ) in China
(in the U.S. ,Isoniazid, Ethambutol, & Rifampin are
given for 2 months. Isoniazid & Rifampin are given for 4
months. If you suspect resistance to isoniazid use
(HRZE)Isoniazid, Ethambutol, Rifampin & Parazinamide.
Incidence of drug resistance is 2-5% in the U.S. )
Prolonged bed rest is not necessary or helpful in obtaining
a speedy recovery. The patient must be seen at regular and
frequent intervals to follow the course of the disease and
treatment. Look for toxic effects
Fan H.

53. Chemoprophylaxis of TB
Used only in high risk groups
Household members and other close contacts
of a patient with active TB.
A positive skin test in persons less than 35
years.
A positive skin test reactive in the
immunosuppressed, persons with leukemia,
and Hodgkin's Disease,
HIV + patients with a positive TB test,
( INH 300mg/d, 6—8m. )
Fan H.

54. The drug of choice for chemoprophylaxis is
isoniazid. Prophylaxis uses only one drug.
In patients who are HIV+ and TB+ and have
the disease; they are treated for a minimum of
9 months, 2HR/7HR?? ?
(The first 2 months using HR(isoniazid and
rifampin) and for the next 7 months or longer,
use only 2 or 3 of the 2nd/3rd line drugs and
Isoniazid/Rifampin. )
Fan H.

55. Conclusions:
A chronic, common, infectious disease - Weight loss,
fever, night sweats, lung damage.
Commonest fatal infectious disease in the world.
CXR – apical of upper lob, basal of lower lob lesions
(CXR atypical AIDS)
AIDS, Diabetes, malnutrition (poverty), crowding.
Five / (Two forms Primary, Secondary in US.)
Pulmonary,miliary,invasive,pleuritis,extrapulmonary,.
AFB(sputum stain +) - infectiousness - isolation
to prevent selection of resistance
Prevention depends on PPD & INH prophylaxis
Fan H.

56. WARNING!
Rifampin and Isoniazid are the most effective drugs for
the treatment of TB, The drug enjoys high patient
compliance and acceptability. But these 2 drugs should
never be given alone! They are always used in
combination because resistance occurs to one drug alone
very rapidly. They are used in combination with each
other initially as well as other drugs. Bacilli must become
resistant to two drugs in order to remain viable.
Statistically, the chances are verv small of the bacilli
becoming resistant to both. . Prophylaxis is with one drug
usually isoniazid.
Fan H.

57. What is New…?
14-30% of TB patients also HIV infected.
New drugs - Rifapentine, Interferons,
Thalidomide.
Immune therapy : Killed M. vaccine stimulates
CD8 cells (increased INF and IL-12).
The genome of TB has been identified (~4000
genes) potential to develop new vaccines and
tests.
Fan H.

58. "When you are faced by
the consequences of past
choices, You see the gift
of a lesson rather than a
curse of a fall.
Brian Tracy