Tuberculosis

Tuberculosis Etiology, Pathogenesis, Clinical features, Diagnosis, Management

1. TUBERCULOSIS
DR SHAHNAWAZ F SHAH
MD, FPM, FIAPM,FCPM (MUHS)
Interventional Spine & Pain Physician
Surat

2. TUBERCULOSIS
Is the most prevalent communicable infectious
disease on earth and remains out of control in many
developing nations

It is a chronic specific inflammatory infectious disease
caused by Mycobacterium tuberculosis in humans

Usually attacks the lungs but it can also affect any
parts of the body

Also Known as “ KOCH’s Disease”, “wasting disease”
and the “white plague.”

3. Tuberculosis can produce atypical signs and
symptoms in
Infants,
Elderly, and
Immunocompromised hosts

It can progress rapidly in these patients

4. EPIDEMIOLOGY

5. EPIDEMIOLOGY

Roughly one of every three people on earth is
infected by M. tuberculosis (WHO, 2008)

The distribution is very uneven, with the highest
incidences found in southern Asia and sub-Saharan
Africa

In the United States, about 13 million people have
LTBI, evidenced by a positive skin test [purified
protein derivative (PPD)] but no signs or symptoms of
disease

6. EPIDEMIOLOGY
Every year approximately 1.7 million people
develop TB

Tuberculosis (TB) kills about 2 million people
each year

The emergence of drug resistant organism
threatens to make this disease once again
incurable

India has the highest number of TB cases in the
world, accounting for around one in four cases
globally, according to the WHO.

7. ETIOLOGY
MYCOBACTERIUM TUBERCULOSIS
It presents either
as latent TB infection (LTBI) or
as progressive active disease.

The latter typically causes progressive destruction
of the lungs, leading to death in most patients who
do not receive treatment

8. CHARACTERISTICS OF
M. TUBERCULOSIS
Rod shaped,
0.2-0.5 µ in D, 2-4 µ in L
Mycolic acid present in its cell wall,
makes it acid fast
It resists decolourization with acid &
alcohol
Aerobic and non motile
It multiplies slowly, can remain
dormant for decades

9. Main species of mycobacterium
causing tuberculosis:
TYPICAL MYCOBACTERIA
1.Mycobacterium tuberculosis
2.Mycobacterium hominis
3.Mycobacterium bovine

ATYPICAL MYCOBACTERIA
1.Saprophytic mycobacteria
2.Mycobacterium avium

10. RISK FACTORS OF TUBERCULOSIS
Low socioeconomic status
Crowded living conditions
Diseases that weakens immune
system like HIV
Person on immunosuppressant
like steroid
Health care workers
Migration from a country with a
high number of cases
Alcoholism
Recent Tubercular infection
(within last 2 years)

11. CO-INFECTION WITH
HUMAN IMMUNODEFICIENCY VIRUS (HIV)
HIV is the most important risk factor for active TB,
because the immune deficit prevents patients from
containing the initial infection

Coinfection with HIV
Accelerates the progression of both diseases

Requiring rapid diagnosis and treatment of both
diseases

12. Classification of TB
TB
Pulmonary (85-90%) Extra-pulmonary (10-15%)
Sputum
Positive TB
(Those who
have
bacteria in
sputum)
Sputum
Negative TB
(Those who
do not have
bacteria in
sputum)
Lymph Nodes
Bones & Joints
Genitourinary tract
Meninges
Intestines
Skin

13. How is TB Transmitted?
Person-to-person through the
air by a person with active TB
disease of the lungs

Less frequently transmitted
by: Ingestion of M. bovis
found in unpasteurized milk

Inoculation (in skin
tuberculosis)

Transplacental route (rare
route)

14. Type of tuberculosis infection
Pulmonary TB :

1. PRIMARY TUBERCULOSIS :
The infection of an individual who has not been previously infected or
sensitized is called Primary tuberculosis or Ghon’s complex or childhood
tuberculosis.

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.

15. PRIMARY TUBERCULOSIS
PRIMARY INFECTION
The progression to clinical disease in a previously
unexposed, immunocompetent person depends on
three factors:
1.The number of M. tuberculosis organisms inhaled
2.Infecting dose and the virulence of these organisms
3.The development of anti-mycobacterial cell-mediated
immunity

Immunity to M. tuberculosis is primarily mediated by
TH1 cells, which stimulate macrophages to kill the
bacteria

16. PRIMARY TUBERCULOSIS
Disease that develops in a previously unexposed
person.

Almost always begins in lungs

Inhaled bacilli implant in the distal airspaces of lower
part of upper lobe or upper part of lower lobe

1-1.5 cm area of grey white inflammation with
consoldation develops, called as Ghon focus which
often caseates

17. FATE OF PRIMARY TUBERCULOSIS
No progression
Healing by fibrosis and calcification
Ghons complex after undergoing progressive fibrosis
produces radiologically detectable calcification called
as RANKE COMPLEX

Progressive primary tuberculosis
Primary miliary tuberculosis
Dissemination to organs like liver, spleen, kidney,
..etc.

19. FATE OF SEC. PULMONARY TB
The lesion may heal with fibrous scarring and
calcification

The lesions may coalesce together to form large area
of tuberculous pneumonia and produce progressive
secondary pulmonary tuberculosis producing
pulmonary & extra pulmonary lesions:
Tuberculous caseous pneumonia
Fibrocaseous tuberculosis
Miliary tuberculosis

20. MILIARY TUBERCULOSIS

Extensive infection via hematogenous spread

In lung: lesions are either microscopic or small, visible
foci (2mm) of yellow white consolidation scattered
through out lung parenchyma
Miliary pulmonary disease can cause pleural
effusion, tuberculous empyema or obliterative
fibrous pleuritis.
Extra pulmonary miliary tuberculosis is most
prominent in the liver, spleen, bone marrow,
adrenals, meninges, kidneys, fallopian tubes and
epididymis but can involve any organ

21. MILIARY TUBERCULOSIS
Miliary tuberculosis of the spleen
The cut surface shows numerous gray-white granulomas

22. EXTRA PULMONARY TUBERCULOSIS
In tissues or organs seeded hematogenously

Commonly involved organs include:
Intestinal tuberculosis (Primary, Secondary and
hyperplastic)
Meninges (Tuberculous meningitis)
 Kidneys (Renal tuberculosis)
Adrenals (Addison disease)
Bones (Osteomyelitis)
Vertebrae (Pott disease)
Fallopian tubes (Salpingitis)

23. SYMPTOMS OF TB
Most common symptom of TB
•Cough for 2 weeks or more
Other symptoms of TB are:
•Fever, especially evening rise
•Pain in the chest
•Loss of weight
•Loss of appetite
•Coughing up blood-stained
sputum
•Shortness of breath,
•Tiredness

25. DIAGNOSTIC STEPS
HISTORY AND CLINICAL
EXAMINATION


RADIOGRAPHIC
FEATURES


BACTERIOLOGIC
EVALUATION

26. Tests may include:
Chest CT scan
Chest X-ray
Tuberculin skin test (also called a PPD test)
Sputum examination and cultures
Interferon-gamma release blood test such as
the QFT-Gold test
Bronchoscopy
Thoracentesis
Biopsy of the affected tissue (rare)

27. Chest X-ray
Tuberculosis creates cavities
visible in x-rays like this one in the
patient's right upper lobe.
Abnormalities on chest
radiographs may be suggestive, but
are never diagnostic of TB.
However, chest radiographs
may be used to rule out.

28. BACTERIOLOGIC
EVALUATION

29. SPUTUM EXAMINATION
Are essential to confirm TB
Best collected in morning before any meal
Sputum examination on 3 days, increase chances of detection
Sputum can be collected from laryngeal swab or bronchial
washing In small children, gastric lavage can be examined.
Smear should be prepared from thick dirty part of sputum &
stained with Ziehl-Neelson technique

30. Acid Fast Bacilli “AFB”
Smear Test
Specimen examined for acid fast bacilli by staining:
Ziehl-neelson Acid Fast
Staining
Auramine-rhodamine
Staining

31. Tuberculin skin Test / Mantoux test / PPD test
Purified Protein Derivative (PPD) :
Is a concentrated filter of broth in which tubercle bacilli have
grown for 6 weeks(old).

Standard method for screening & measuring of a person’s
cellular response.
Measuring the size of induration 48-72 hours.

32. Tuberculin skin Test
1 2
Positive If ≥ 10 mm Induration Size.

34. Positive Reaction
Person infected in the past or latent TB infection.

After BCG vaccination, but this may last for only 3-7 years .
Persons are retested 2 weeks later; their ppd skin test “boosted” by
the recent antigen injection. High risk of (endogenous infection)

35. Negative Reaction
Persons who have NEVER been infected, they are not
subject to that risk, though they may become infected
from an external source (exogenous infection)

36. A positive tuberculin test result signifies cell-
mediated hypersensitivity to tubercular antigens.

It does not differentiate between infection and
disease

False-negative reactions may be produced by certain
viral infections, sarcoidosis, malnutrition,
immunosuppression

False-positive reactions may also result from
infection by atypical mycobacteria

37. γ-Interferon release assays (GIRA)
Test rely on the fact that T-lymphocytes will release γ-
interferon when exposed to specific antigens.

QFT-gold test measures interferon-gamma in the testee's
blood after incubating the blood with specific antigens
from m. Tuberculosis proteins

38. FIRST LINE DRUG
1.Isoniazid (H)
2.Rifampin (R)
3.Pyrazinamide (Z)
4.Ethambutol (E)
5.Streptomycin (S)
SECOND LINE DRUG
1.Thiacetazone (Tzn)
2.Paraaminosalicylic acid (PAS)
3.Ethionamide (Etm)
4.Cycloserine (Cys)
5.Kanamycine (Am)
6.Capriomycine (Cpr)

NEWER DRUG
1.Ciprofloxacin
2.Ofloxacine
3.Clarithromycine
4.Azithromycine
5.Rifabutine
6.Bedaquiline(Recently)
ANTI-TUBERCULAR DRUG

39. ANTI-TUBERCULAR DRUGS
Medication Drug action Dose(Thrice a
week)***
Dose in
children(mg/kg)
Isoniazid Bactericidal 600 mg 10-15
Rifampicin Bactericidal 450 mg* 10
Pyrazinamide Bactericidal 1500 mg 30-35
Ethambutol Bacteriostatic 1200 mg 20-25
Streptomycin Bactericidal 0.75 g** 15
* Patients who weigh 60 kg or more at the start of treatment
are given an extra 150mg dose of Rifampicin
** Patients over 50 years of age are given 0.5g of streptomycin
*** Adult patients weighing <30kg receive drugs in patients-
wise from the weight band suggested for pediatric patients

40. ISONIAZIDE(H)-Pyridine hydrazide.
Action
 Bacteriostatic for resting mycobacteria, bactericidal for proliferating
mycobacteria.
Mechanism of Action
Inhibit cell wall synthesis

41. Adverse reaction
Peripheral neuritis
Liver damage.
Optic neuritis, Convulsions, Hypersensitivity reactions

42. RIFAMPICIN (R)-Rifamycine
Action
Bactericidal for mycobacteria; also effective against most Gram-positive
and many Gram-negative bacteria.
Mechanism of Action
Binds to the β subunit of DNA-dependent RNA polymerase (rpoB) .
Inhibit RNA synthesis
Dose
10 mg/kg (600 mg),OD
Oral

43. Adverse reaction
Flu like symptoms.
Thrombocytopenic purpura.
GIT disturbances &
Harmless orange tint to saliva, sweat &
tears

44. PYRAZINAMIDE (Z)-Nicotinamide analogue
Action
Bactericidal for actively dividing intracellular mycobacteria.
Main effect occur in first few months.
Mechanism of Action
PYRAZINAMIDE
Enter M.tuberculosis
Pyrazinoic acid (POA
+)
Kill the mycobacteria
Pyrazinamidase/Nicotinamidase
Inhibit FAS
Inhibit growth mycobacteria
Go extra-
cellular

45. Adverse reaction
Sideroblastic Anemia.
Hepatotoxic &
Joint pains

46. STREPTOMYCIN (S)-aminoglycoside
Action
Bactericidal for actively dividing intracellular mycobacteria.
Mechanism of Action
Bind 30S ribosomes.
False pair of
codon:anticodone
False reading of genetic
code
Inhibit protein synthesis

47. Adverse reaction
Ototoxicity
Nephrotoxicity
Neuromuscular blockade- ↓release of Ach by inhibiting fusion
of vesicles with terminal membrane

48. ETHAMBUTOL(E)-Ethylenediamine derivative
Action
Tuberculostatic drug.
Mechanism of Action
Inhibit Arabinosyl transferase-Ш enzyme
Disrupt the transport of Arabinose sugar
Arbinogalactan biosynthesis impaired
Disruption in mycobacterial cell wall formation

49. Adverse reaction
Optic neuritis
Colour blindness

50. FLASH CARD OF ANTITUBERCULAR DRUG

51. Revised National Tuberculosis Control
Programme

52. Goal
1.To decrease the mortality and morbidity
2.To cut down the chain of transmission of infection
until TB ceases to be a public health problem
Objectives
To achieve and maintain:
1.Cure rate of at least 90% among newly detected
smear positive (infectious) pulmonary TB cases
2.Case detection of at least 85% of the expected new smear
positive PTB cases in the community

53. Implementation
•Case finding- by passive surveillance on patient with
symptoms of
i)Persistent cough for 2weeks or more.
ii)Haemoptysis
iii)Night sweats
iv)Evening rise of temperature
v)Chest pain
In lab.-
i)Sputum collection for diagnosis
ii)Radiography
iii)Tuberculin test

54. Sputum examination is the best method to diagnose TB
Pulmonary TB diagnosis can be confirmed by sputum
examination.
Two sputum samples are collected over one/two consecutive
days
If the health facility is a DMC, spot sample is collected
immediately and the patient is given a sputum container to
collect early morning sample & brought to the lab
Diagnosis of TB

55. Alternatively the patient can be asked to collect a
morning sample and go to a DMC where a spot
sample can be taken
In case the patient is not able to reach a DMC, both
samples - morning and spot, can be collected and
transported

56. The sputum samples are subjected to microscopy
examination as early as possible
A patient is diagnosed positive if one or both the
samples is positive for bacteria
If the bacteria are not visible in any sputum sample,
the patient is negative and should be referred to a
medical officer for further evaluation
TB of other organs is diagnosed by a medical officer

57. RNTCP revised diagnostic algorithm (2009)
Note: RNTCP has
separate diagnostic
algorithm for
pediatric pulmonary
TB and common
forms of extra-
pulmonary TB

58. DOTS
Directly Observed Treatment
Short Course
Tuberculosis control strategy recommended by the World Health Organization
as the strategy that ensures cure of TB

59. Directly
observed
treatment
(DOT) is one
element of
the DOTS
strategy
An observer
watches and
helps the
patient
swallow the
tablets

Direct observation
ensures treatment for the
entire course
•with the right
drugs
•in the right doses
•at the right
intervals
Directly Observed Treatment Short Course

60. Directly Observed Treatment Short Course
There are two phases in DOTS treatment
1Intensive Phase(IP):-
Intensive phase is of 2 to 3 months duration
Patient swallow medicine under the observation of a
health worker during IP
Medicines are taken 3 times a week on alternate
days
If the sputum is negative for bacteria after IP,
continuation phase is started

61. Directly Observed Treatment Short Course
2. Continuation Phase
•This phase is of 4 or 5 months duration
•The patient is provided with a weekly blister pack to
take home
•The medicines from the blister pack are taken on
alternate days, three times a week and in the
remaining days, Vitamin tablets are taken
•The first dose of the weekly blister pack is taken under
direct observation of the health worker
•Empty blister packs are collected to ensure that the
medicines are taken at home by the patient

62. H: Isoniazid (300 mg), R: Rifampicin (600 mg), Z: Pyrazinamide (1500 mg), E:
Ethambutol (1000 mg), S: Streptomycin (1000 mg)
1.Patients who weigh 60kg or more receive additional Rifampicin
150mg.
2.Patients who are more than 50 years old receive Streptomycin
500mg.
3.Patients who weigh less than 30kg receive drugs as per Paediatric
weight band boxes according to body weight.
Category Type of Patient Regimen Duration in months
Category I
Color of box:
RED
New Sputum Positive ,
Seriously ill sputum negative,
Seriously ill extra pulmonary,
2 (HRZE)
3, 6
4 (HR)
3
Category II
Color of box:
BLUE
Sputum Positive relapse,
Sputum Positive failure
Sputum Positive treatment after
default
2 (HRZES)
3, 8
1 (HRZE)
3
5 (HRE)
3

63. ADVANTAGES
The patient is supported to successfully complete the full
course of medication

The patient is monitored closely for side effects of
medications and supported to work through the side
effects appropriately

The patient is encouraged and support.

Reduces the possibility of tuberculosis germs becoming
resistant to the medication.

64. DRUG RESISTANT TB
1.MULTIPLE DRUG RESISTANCE TB (MDR-TB)
An MDR-TB suspect who is sputum culture positive and whose
TB is due to Mycobacterium tuberculosis that are resistant in-
vitro to at least ISONIAZID AND RIFAMPICIN.


2.EXTENSIVELY DRUG RESISTANT TB (XDR–TB)
subset of MDR-TB where the bacilli, in addition to being
resistant to R and H, are also resistant to any
fluoroquinolones and any one of the second-line injectable
drugs (namely Kanamycin, Capreomycin, or Amikacin).

65. For the treatment of MDR-TB cases
STANDARDISED TREATMENT REGIMEN
6 drugs
- kanamycin
- ethionamide
- ethambutol
- ofloxacin
- pyrazinamide
- cycloserine
for 6-9 months of the INTENSIVE PHASE

66. CONTINUATION PHASE-
4 drugs
Ofloxacin
Ethionamide
Ethambutol
Cycloserine

for 18 months.
For the treatment of MDR-TB cases

67. BCG VACCINE
Protective effect against
meningitis and
disseminated TB in
children.

It does not prevent
primary infection and
does not prevent
reactivation of latent
pulmonary infection

68. ROLE OF PHYSIOTHERAPISTS
PT's should be prepared to take a thorough history and a
proper examination in order to better identify TB.
Recognize your patient's signs and symptoms
Patients may present in clinic with musculoskeletal problems
with unknown causes or arthritic pain.
A patient could also be seen in physical therapy if they have
had surgery on their back, in which case the normal
rehabilitation protocols would be followed

69. ROLE OF PHYSIOTHERAPISTS
All physical therapists should be aware of the proper
personal protective equipment (PPE) that should be
worn.

Therapists are able to provide percussion and postural
drainage to clear secretions out of the lung

71. For more updates:

thepainkillerMD