4. TB Transmission
How can you catch TB?
TB is spread through tiny drops
sprayed into the air when an
infected person coughs, sneezes,
or speaks, or another person
breathes the air into their lungs
containing the TB bacteria.
5. How Are TB Germs Spread?
TB germs are passed through the air when a person
who is sick with TB disease coughs, sings, sneezes, or
laughs
To become infected with TB germs, a person usually
needs to share air space with someone sick with TB
disease (e.g., live, work, or play together)
The amount of time, the environment, and how sick
the person is all contribute to whether or not you get
infected
In most cases, your body is able to fight off the germs
6. TB Infection vs. TB Disease
There is a difference between TB “infection” and TB
“disease”
TB infection: TB germs stay in your lungs, but they
do not multiply or make you sick
You cannot pass TB germs to others
TB disease: TB germs stay in your lungs or move to
other parts of your body, multiply, and make you
sick
You can pass the TB germs to other people
7. Tuberculosis in Humans
- Reservoir: Humans
- Transmission: Airborne disease (aerosol transmission)
- Symptoms:
Latent TB infection: Active TB infection:
No symptoms Bad cough
*Cannot spread TB Coughing up blood/sputum
Chest pain
Loss of appetite
Weight loss
Fever
Chills
Night sweats
Swollen glands
*Contagious
Extra-pulmonary TB: Symptoms depend on location of infection
General symptoms: fatigue, fever, loss of appetite, weight loss.
TB of lymph nodes: swelling of lymph nodes
TB meningitis: neurological symptoms including headache
Spinal TB: Mobility impairments, pain
8. Mycobacterium Tuberculosis
General Characteristics
- Family – Myobacteria
- Gram-positive aerobic rod-shaped bacilli
- “Acid fast” bacteria
- Lack of spore formation and toxin production
- No capsule, flagellum (non-motile)
- Generation time of 18- 24 hours but requires 3-4
weeks for visual colonies
Pathological Features
- Principle cause of Human Tuberculosis
- Intracellular pathogen (alveolar macrophages)
- Waxy, thick, complex cellular envelope
- Cell envelope components ex) sulfolipids
- Produces tubercles, localized lesions of M.
tuberculosis
SEM of M. tuberculosis
M. Tuberculosis
(stained in purple)
9. Mycobacterial Cellular Envelope
General Features
- Thick, waxy and complex
- Higher fluidity in more external
regions than internal regions
- Relatively impermeable to
hydrophilic solutes
- Contain porins (selective cationic
channels)
Main Components
- Peptidoglycan
contains N-glycolylmuramic
acid instead of N-acetylmuramic
acid
- Arabinogalactan
- Mycolic Acids (60% of cellular
envelope)
- Lipoarabinomannan (LAM)
11. Contribution of Mycobacterial Cellular
Envelope to Pathogenesis
Resistance to Drying and Other Environmental Factors
- Thick, waxy nature of cellular envelope protects M. tuberculosis
from drying, alkali conditions, and chemical disinfectants
- Hinders entrance of antimicrobial agents
Entry into Host Cells
- Lipoarabinomannan (LAM) binds to mannose
receptors on alveolar macropages leading to
entry into the cell
Interference of Host Immune Response
- Glycolipids and sulfolipids decrease the effects of oxidative
cytotoxic mechanism
- Inhibition of phagosome and lysosome fusion inside macrophage
- Waxy cellular envelope prevents acidification of the bacteria inside
the phagosome
12. Factors Affecting Pathogenicity
Active Infection
- Only individuals with an active infection
can transmit the disease
Transmission
- Aerosolized droplets need to be <10μm in
order to evade the ciliated epithelium of
the lung to establish infection in the
terminal alveoli
Growth & Structure
- Only require a very few number of
bacteria to establish an infection (1-10
bacteria)
- Slow generation time
M. Tuberculosis in sputum
(stained in red)
13. Common Symptoms of TB Disease
Cough (2-3 weeks or more)
Coughing up blood
Chest pains
Fever
Night sweats
Feeling weak and tired
Losing weight without trying
Decreased or no appetite
If you have TB outside the lungs, you may have
other symptoms
14. Diagnosis of Latent & Active TB
Tools for Diagnosing TB Infection
Mantoux skin test (PPD)
Chest x-ray
Sputum cultures
15. Diagnosis for Latent & Active TB
Tools for Diagnosing TB Infection
Mantoux Skin Test(PPD)
Mantoux tuberculin skin test (PPD) is a skin
test for identifying exposure to the TB
bacteria, Mycobacterium tuberculosis
(latent infection)
The Mantoux test is recommended because
it provides the most consistent and reliable
result.
The Mantoux test is read 48-72 hours after
administration. Induration or “knot-like”
swelling at the test site is significant and the
reaction is measured in millimeter units.
Redness at the test site is not measured.
16. Diagnosis for Latent & Active TB
Tools for Diagnosing TB Infection
Sputum
A sputum specimen is necessary to
confirm that the TB bacteria is present
in the lung.
The sputum specimens should:
-come from deep within the lungs;
-be obtained from the first coughed
up sputum of the day, for 3 consecutive
days
-may be obtained through special
respiratory therapy procedures.
17. Treatment for TB Disease
TB disease is treated with medicine to kill the TB germs
Usually, the treatment will last for 6-9 months
TB disease can be cured if the medicine is taken as
prescribed, even after you no longer feel sick
18. Treatment
Antibacterial chemotherapy:
- Combination of first and second line drugs for the
first 2 months which could include:
- Isoniazid
- Rifampicin
- Pyrazinamide
- Streptomycin or Ethambutol
- Next 4 months, combination of:
- Isoniazid
- Rifampicin
- Early resistance to isoniazid: other first-line drugs
such as ethambutol, streptomycin, pyrazinamide and
fluoroquinolones can be added to drug arsenal
(treatment period also extended).
- These drugs are relatively effective in killing the bacteria,
however, they also produce a wide variety of side effects.
19. Treatment
First line drugs:
- Bactericidal agents: kill active bacteria, important in the early
stages of infection.
Second line drugs:
- Bacteriostatic: hinder bacterial growth.
- Strengthen treatment in the case of resistant bacteria.
- Less efficient and generally more toxic than first line drugs.
Inappropriate chemotherapy:
- Monotherapy (single drug treatment)
- Decreased treatment period
- Low absorption of drugs
20. Drug Bactericidal or
Bacteriostatic
Mechanism of Action Mutation
Rate
Side Effects
Isoniazid Bactericidal to
rapidly dividing
bacteria and
bacteriostatic
to slowly
dividing
bacteria
Pro-drug: activated by a
bacterial catalase.
Inhibits enoyl-ACP reductase
(key enzyme in fatty acid
synthesis, different than
equivalent mammalian
enzymes)
1 in 105 - 106 Rash, abnormal liver function,
anemia, peripheral
neuropathy, mild CNS effects
Rifampicin Bactericidal Inhibits transcription by RNA
polymerase
1 in 108 Fever, immune reactions, GI
irritation, liver damage, can
cause tears and urine to turn
red/orange
Streptomycin Bactericidal Inhibits initiation of protein
synthesis
1 in 108 - 109 Damage to the ears, nausea,
rash, vomiting, vertigo
Ethambutol Bacteriostatic Prevents formation of the
cell wall
1 in 107 Decrease in visual acuity,
colourblindness and other
visual defects, joint pain,
nausea, vomiting, fever,
malaise, headache, dizziness
Fluoroquinolones Bactericidal Act manly on DNA gyrase
(DNA gyrase: introduces
negative supercoils into
DNA)
Tendon damage, heart
problems, swelling of face and
throat, shortness of breath,
rash, loss of consciouness
Pyrazinamide Bacteriostatic,
Bactericidal
Accumuates causing
cellular damage
Joint pain, nauseau, vomiting,
rash, malaise, fever,
photosentivity
Treatment
21. Drug Resistance and Tuberculosis
- M. tuberculosis: naturally resistant to
certain antibiotics due to presence of:
- Drug-modifying enzymes
- Drug-efflux systems
- Hydrophobic cell wall
- Mycobacteria undergo natural mutations
which can lead to development of drug
resistance.
- TB is treated by administration of
combination chemotherapy:
decreases probability of development
of drug resistance.
- Development of increasingly resistant
strains mainly due to: Patient non-
compliance
22. MDR and XDR Tuberculosis
MDR: Multidrug-resistant strains:
- Strains of tuberculosis resistant at least to rifampicin and isoniazid.
- Mortality rate: 40-60%
- Estimated that 50 million people are infected with MDR-TB.
- MDR-TB is approximately 125 times more expensive to treat than drug
susceptible TB.
XDR: Extensively-drug resistant strains:
- Strains of tuberculosis resistant to rifampicin,
isoniazid and at least three of the following
classes of second-line drugs: aminoglycosides,
polypetides, fluoroquinolones, thioamides,
cycloserine and para-aminosalicylic acid.
23. MDR and XDR Tuberculosis
- Emergence due to lack of patient compliance during TB
treatment and inappropriate administration of TB drugs.
- Results in more aggressive forms of TB.
- Drug resistance does not increase infectiousness.
- MDR and XDR-TB: uncommon in developing nations lacking TB
drugs (high drug-susceptible TB rates)
- MDR and XDR-TB rates are higher in developed nations with
access to anti-TB drugs.
24. - HIV pandemic has reversed much of the progress made in the past
few decades in combating TB.
- People with latent TB have a 10-20% of developing active TB in their
lifetime. People with HIV and latent TB are 100 times more likely to
develop active TB.
- HIV/AIDS leads to a compromised immune system:
- HIV infects CD4+ T cells, macrophages, dendritic cells.
- Result: decreased CD4+ T cells due to apoptosis of infected cells, CD8+ T
cell mediated killing of infected cells
- The numbers of CD4+ T cells progressively decline (loss of cell-mediated
immunity) and the body is much more susceptible to infection
Tuberculosis and HIV/AIDS
T cell
25. - A person with HIV/AIDS will have a harder
time fighting off the M. tuberculosis
infection due to a compromised immune
system.
- HIV infection can cause latent M.
tuberculosis infection to become
reactivated.
- TB is the leading cause of death for
people with HIV/AIDS: mean survival rate
is 430 days.
- MDR and XDR-TB and HIV/AIDS:
- Additional symptoms: excessive weight loss,
respiratory problems (including the
formation of lesions in the lungs).
- Mean survival rate: 45 days.
Tuberculosis and HIV/AIDS
26. Directly Observed Treatment
Why? Many patients don’t take medicines regularly,
even if excellent health education provided
Who? All patients... impossible to predict which
patient will take medicine (1/3 not adherent)
What? Observer watches and helps patient swallow
tablets
Where? Anywhere! (home, clinic, work, school, etc)
Who does it? HCW, community liaisons, teachers,
Direct observation ensures treatment for entire course
with the right drugs, in the right doses, at the right
intervals
27. DOT is necessary even when
drug supply ensured
88%
61%
0%
20%
40%
60%
80%
100%
Chaulk CP. JAMA 1998;279:943-8
Treatment Success
DOT No DOT
