1. 1
Prepared by : Amera saeed

2. Introduction
 TB is one of the oldest recorded
human afflictions
 Still one of the biggest killers
among the infectious diseases
 The bacillus causing tuberculosis,
Mycobacterium tuberculosis, was
identified and described on March
24, 1882 by Robert Koch

3.  One-third of the
world's population is
currently infected with
TB
 with 8 to 10 million new
cases each year.
 2 million TB related
deaths/year
Epidmiology
Incidence and prevelance

4. M. tuberculosis
M. bovis
M. africanum
M. microti
M. canettii
M. caprae
M. pinnipedii
Etiology
Human tuberculosis (TB) is caused by
infection with members of the
Mycobacterium tuberculosis complex, which
includes :

5. Characteristics of M.tuberclosis
 Slightly curved,rod shaped bacilli
 Aerobic, Non motile
 Thick lipid cell wall,resist
decolorization with acidified
alcohol
“ Acid fast bacteria”
 Multiplies slowly”every 18 - 24 hrs”
 Can remain dormant for decades

6.  Person-to-person
through the air by a
person with TB
disease of the lungs
 Less frequently transmitted by:
• Ingestion of Mycobacterium bovis
found in unpasteurized milk products
• Laboratory accident
How is TB Transmitted?
Source: CDC, 2000

7. The probability that TB will be transmitted
from one person to another depends on a
number of factors
 The concentration of TB bacteria in the air
 The environment in which exposure to the
bacteria occurs
 The length of time of exposure
 Person‘ s immune system

8. Risk factors
 Co infection with HIV
 Diabetic person
 Persons undergo chemotherapy
 Person undergo organ transplantation
 Extreme ages,children and geriatric
 Malnutration

9. Pathogenesis

14. Active TB Disease
Germs:
 Awake and multiplying
 Cause damage to the lungs
Person:
 Most often feels sick
 Contagious (before pills started)
 Usually have a positive
tuberculin skin test
 Chest X-ray is often abnormal
(with pulmonary TB)
Granuloma breaks
down and tubercle
escape and multiply
TB

15. Germs:
 Sleeping but still alive
 Surrounded (walled off) by
body’s immune system
Person:
 Not ill
 Not contagious
 Normal chest x-ray
 Usually the tuberculin skin
test is positive
Latent TB infection(LTBI(

17. Spread of TB to Other Parts of the Body
1. Lungs (85% all cases)
2. Pleura
3. Central nervous system
• (e.g., brain, meninges)
4. Lymph nodes
5. Genitourinary system
6. Bones and joints
7. Disseminated
 (e.g., miliary)
© ITECH, 2006

18. Extrapulmonary TB
Pleura
Lymph Node
Brain
Spine

19. Symptoms

20. Diagnosis
 Medical history
 Physical examination
 Sputum smear microscopy
Acid fast staining (Ziehl–Neelsen stain)
Fluorochrome stain using fluorescence microscopy
 Culture
 Immunological tests
 TB skin test(Tuberculin skin test )
 TB blood tests
 Chest radiograph (X-ray)
 PCR

21. Bacteriologic Examination of Clinical
Specimens
 The bacteriologic examination has five
parts:
 Specimen collection, processing, and review
 AFB smear classification and results
 Direct detection of M. tuberculosis in clinical specimen
using nucleic acid amplification (NAA)
 Specimen culturing and identification
 Drug-susceptibility testing

22. Specimen Collection, Processing, and
Review
 At least three consecutive sputum
specimens are needed, each
collected in 8- to 24-hour intervals,
with at least one being an early
morning specimen.
 If possible, specimens should be
obtained in an airborne infection
isolation (AII) room or other
isolated, well-ventilated area (e.g.,
outdoors)

23. Specimen
Collection Methods
 Coughing
 Induced sputum
 Bronchoscopy
 Gastric aspiration
Specimen Collection, Processing,
and Review

24. Sputum smear microscopy
a. Ziehl-Neelsen stain
 fixed smear covered with
carbol-fuchsin, heated, rinsed,
 decolorized with acid alcoholb.
b. Fluorochrome stain with phenol-
auramine
 modified acid alcohol step
 potassium permanganate
counter staining; fluorescent
 Mycobacteria visible with 20 or
40X magnification
 SMEAR POSITIVITY
MEANS AT LEAST 10,000
ORGANISMS/mL SPUTUM
Fluorochrome stain

25. Culture (Gold Standard(
a. Solid media
Lowenstein Jensen (egg based)
Middlebrook 7H11 (agar based)
 can detect colony morphology,
mixed infections; can detect 10-
100
 organisms/mL; 3-8 weeks
incubation to detect organisms
b. Liquid broth
Middlebrook 7H12, BACTEC
systems
 1-3 weeks of incubation to
detect organisms
M.Tuberclosis on
Lowenstein Jensen media
Buff colonies

26. TB skin test(Tuberculin skin test(
 Called the Mantoux
tuberculin skin test
 Result depends on the
size of the raised, hard
area or swelling
 Also depends on the
person’s risk of being
infected with TB bacteria
and the progression to
TB disease if infected.

27. TB blood tests
(Interferon-Gamma Release Assays, IGRAs(
 Measures how strong a person’s
immune system reacts to TB bacteria
 Two IGRAs

QuantiFERON®–TB Gold In-Tube test (QFT-
GIT

T-SPOT®.TB test (T-Spot)

28.  IGRAs are the preferred method of TB
infection testing for
 People who have received bacille
Calmette–Guérin (BCG). BCG is a vaccine
for TB disease.
 People who have a difficult time returning
for a second appointment to look for a
reaction to the TST.
TB blood tests
(interferon-gamma release assays, IGRAs(

29. TB treatment is challenging, requiring
accurate and early diagnosis,
drug‑resistance screening and the
administration of effective treatment
regimens for at least 6 months through
( Directly Observed Therapy (DOT) and
follow‑up support.
Treatment for tuberculosis (TB) depends
on which type you have, although a long
course of antibiotics is most often used
Treatment

30.  The goals of TB treatment are to:
1. Shorten the clinical course of TB
2. Prevent complications
3. Prevent the development of latency
and/or subsequent recurrences
4. Decrease the likelihood of TB
transmission
Treatment

31.  First-line anti-TB drugs
recommended in a four-drug
combination
for the treatment of drug-susceptible
TB.
 Second-line anti-TB drugs
for drug-resistant TB.
Treatment

32. First line

33. Drug (year
of discovery)
Target Effect activity
Isoniazid (1952) Enoyl-(acyl
carrier protein)
reductase
Inhibit mycolic
acid synthesis
bactericidal
Rifampicin
(1963)
RNA
polymerase
Beta subunit
Inhibit
transcription
bactericidal
Pyrazinamide
(1954)
Exact target
unknowen
Disrupt plasma
memb.
Disrupt energy
memb.
bacteriostatic
Ethambutol
(1961)
Arabinosyl
transferase
Inhibit
arabinogalactan
biosynthesis
bacteriostatic
First-line anti-TB drugs

34. First line

35. Spectrum of drugs

36. 1st
line drugs summary

37. Regimens Of Antituberculosis Drugs
Active disease
Treatment requires a minimum of 6 months in two phases
Intensive phase
Isoniazid,rifampin,ethambutol and pyrazinamide”given for
2 months”
Continuation phase
Isoniazid and rifampin”for 4 months
Latent disease
Daily isoniazid therapy for 9 monthes
“Monitor the patient for signs and symptoms of hepatitis and
peripheral neuropathy”

38. Regimens Of Antituberculosis Drugs

39. Second line
Drug target effect
Para-amino
salicylic
acid )PAS`)
Dihydro _pteroate
synthase
Inhibits folate
biosynthesis
Ethionamide Enoyl-[acyl-carrier-
protein] reductase
Inhibits mycolic acid
biosynthesis
Ofloxacin DNA gyrase and DNA
topoisomerase Inhibits DNA
supercoiling
Kanamycin 30S ribosomal subunit Inhibits protein
synthesis
Amikacin 30S ribosomal subunit Inhibits protein
synthesis
Cycloserin d-alanine racemase and
ligase
Inhibits
peptidoglycan

40. Second line

41. Resistance
Two types
 Primary”intrinsic” resistance
Infection with strains naturally resistant to one or
two drugs
 Hydrophobic cell wall
 Drug modifying enzymes
 Drug efflux system
 Acquired resistance
Infection with strains that become drug resistant
d.t inappropriate or inadequate treatment

42. Drug resistance in TB
 MDR (Multi-Drug Resistant)
Simultanous resistance to 2 or more drugs
from 1st
line
 XDR (Extensive Drug
Resistance)
Strains not only resistant to 1st
line but also
resist fluoroquiolones and one of injectible
drugs

43. Treating Extensively Drug Resistant
TB

44. Targets for new drugs

45. Development of anti TB drugs

46. New drugs

47. Schematic showing the site of action of various
tuberculosis drug candidates

48. How can tuberculosis be prevented?
 The BCG vaccine.
It usually protects children and infants from the
disease, but its effects wear off when the patient
reaches adulthood.
 Eating a healthful diet that boosts the immune
system
 Having regular TB tests if you work or live in
a high risk environment
 Completing a TB medication regimen.
 If you are infected, stay home, cover your mouth,
and ensure proper ventilation.