Introduction
Disease
Important Properties
Transmission & Epidemiology
Risk factor of reactivation
Pathogenesis
Clinical Findings
Laboratory Diagnosis
Approaches to the diagnosis of latent infections
Treatment
Prevention
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Mycobacterium tuberculosis
1. Dr. Dina M. Bitar
Prepared By:
Diaa M. Srahin
Muath A. Baniowda
March, 2016
Al-Quds University
Faculty of Medicine
Microbiology
2. Introduction
Mycobacteria are aerobic, acid-fast bacilli (rods).
Nocardia asteroides, is also acid-fast.
The high lipid content (approximately 60%) of their
cell wall makes mycobacteria acid-fast.
3. Disease
M. tuberculosis causes tuberculosis.
one-third of the world’s population is
infected with this organism.
An estimated 500,000 people are infected
with a MDR strain of M. tuberculosis.
Each year, it is estimated that 1.7 million
people die of tuberculosis and 9 million
new cases occur.
4. Important Properties
Cell wall contains lipid with long chain (C78 – C90) fatty
acids called mycolic acids.
Mycobacterium tuberculosis grows very slowly
( doubling time is 18 hrs ) , taking up to 6 weeks for visible
growth. The colonies that form lump together due to their
hydrophobic lipid nature, resulting in clumped colonies on
agar -and floating blobs on liquid media.
Media used for its growth (e.g., Löwenstein-Jensen medium)
5.
6. Transmission & Epidemiology
M. tuberculosis is transmitted from person to person
by respiratory aerosol.
(1 - 10) organisms / droplet Infection.
Initial site of infection is the lung.
In developing countries, M.bovis also causes tuberculosis
in humans. M. bovis is found in cow’s milk, which, unless
pasteurized, can cause GI tuberculosis in humans.
Endogenous transmission : reactivation within respiratory
tract (M. tuberculosis) or extra pulmonary-latent in GI
(M. bovis).
8. Pathogenesis
M. tuberculosis produces no exotoxins and does not
contain endotoxin in its cell wall.
The organism infects macrophages and other
reticuloendothelial cells (REC), then produces a
protein called “exported repetitive protein” that
prevents the phagosome from fusing with the lysosome.
Approximately 90% of infections are asymptomatic.
Video (pathogenesis of TB).
9. Clinical Findings
Protean; “many organs can be involved”.
Fever, fatigue, night sweats, and weight loss.
Cough and hemoptysis in pulmonary tuberculosis.
Scrofula ; cervical lymphadenitis , that can caused by both
M. tuberculosis and M. scrofulaceum .
Erythema nodosum.
Miliary tuberculosis.
Tuberculous meningitis and tuberculous osteomyelitis.
Gastrointestinal tuberculosis.
Oropharyngeal tuberculosis.
Renal tuberculosis.
10.
11. Virulence Factors
To remember the names of the mycosides and their relationship to
M. tuberculosis, picture the surfing dude Mike (mycosides). He is
WAXING (wax D) his Surfboard (sulfatides) and has his surfboard
CORD (cord factor) attached to his leg (so as not to lose his stick).
Notice Mike has a cough and some weight loss
12. Laboratory Diagnosis
Acid-fast staining of sputum or other specimens is the usual
initial test.
Digestion of the specimen by treatment with NaOH and
concentration by centrifugation, the material is cultured on special
media, such as Löwenstein-Jensen agar, for up to 8 weeks. It will
not grow on a blood agar plate.
Liquid BACTEC medium, radioactive metabolites are present,
and growth can be detected by the production of radioactive carbon
dioxide in about 2 weeks. A liquid medium is preferred for isolation
because the organism grows more rapidly and reliably than it does on
agar.
Nucleic acid amplification tests can be used to detect the
presence of M. tuberculosis directly in clinical specimens such as
sputum.
Luciferase assay, which can detect drug-resistant organisms in a
few days. Luciferase is an enzyme isolated from fireflies that
produces flashes of light in the presence of (ATP).
13. Approaches to the diagnosis of latent infections
Purified Protein Derivative (PPD) skin test
This screening test indicates an exposure sometime in the past.
False negative test: Some patients do not react to the PPD even if they have
been infected with tuberculosis.
These patients are usually anergic, which means that they lack a normal
immune response due to steroid use, malnutrition, AIDS, etc.
To determine whether a patient is anergic or just has not been infected with
tuberculosis, a second injection (with Candida antigen) is given in the other
arm. Most people have been exposed to these antigens, so only individuals
who are anergic will not respond to the Candida or mumps injection with
induration after 48 hours.
Interferon-gamma release assay (IGRA).
In this assay, blood cells from the patient are exposed to antigens from
M. tuberculosis, and the amount of interferon-gamma released from the
cells is measured.
14. Treatment
Combination drug therapy is the rule to delay or prevent the
emergence of resistance and to provide additive effects against
Mycobacterium tuberculosis.
The primary drugs in combination regimens are isoniazid
(INH), rifampin, ethambutol, pyrazinamide Regimens may
include two to four of these drugs.
A convenient way to remember that regimen is to give four drugs
(isoniazid, rifampin, pyrazinamide and ethambutol) for 2 months
and two drugs (isoniazid and rifampin) for 4 months.
In patients who are immunocompromised (e.g., AIDS patients),
who have disseminated disease, or who are likely to have INH-
resistant organisms, a fourth drug, ethambutol, is added, and
all four drugs are given for 9 to 12 months.
15. Treatment (cont.)
Prophylaxis: usually INH, but rifampin if intolerant. In suspected
multidrug resistance, both drugs may be used in combination.
Strains of M. tuberculosis resistant to multiple drugs (MDR strains)
have emerged, primarily in AIDS patients.
The most common pattern is resistance to both INH and rifampin,
but some isolates are resistant to three or more drugs.
In this case other agents may also be required include
aminoglycoside, fluoroquinolones, capreomycin and cycloserine.
16. Treatment (cont.)
In 2013, a new drug, bedaquiline, was approved for the treatment of
MDR strains. It should be used in combination with other drugs, not
as monotherapy. It is diarylquinoline that inhibit an ATP synthase
unique to M. tuberculosis.
Non-compliance (i.e., the failure of patients to complete the full
course of therapy) is a major factor in allowing the resistant
organisms to survive.
One approach to the problem of non-compliance is directly
observed therapy (DOT), in which health care workers observe the
patient taking the medication.
The strains of M. tuberculosis resistant to
INH, rifampin, fluoroquinolone, and at least one additional drug are
called extensively drug resistant (XDR) strains. XDR strains
emerged in 2005 among HIV-infected patients in South Africa.
17.
18. Treatment (cont.)
Mnemonics for TB drugs:
If you forget your TB drugs, you'll die and might
need a ” PRIEST ” :
Pyrazinamide
Rifampin
Isoniazid (INH)
Ethambutol
Streptomycin
19. Prevention
An important component of prevention is the use of the PPD skin test
to detect recent converters and to institute treatment for latent
infections.
Pasteurization of milk and destruction of infected cattle are important
in preventing intestinal tuberculosis.
BCG vaccine can be used to induce partial resistance to tuberculosis.
The vaccine contains a strain of live, attenuated M. bovis called :
bacillus Calmette-Guerin.
the vaccine is its variable effectiveness, which can range from 0% to 70%.
Chest x-ray
Editor's Notes
Induration (thickening & hardening)
15 mm or more is positive in a person who has no known risk factors.
10 mm or more is positive in a person with high-risk factors, such as a homeless person, intravenous drug users, or nursing home residents.
5 mm or more is positive in a person who has deficient cell-mediated immunity (AIDS) or has been in close contact with a person with active tuberculosis.
Positive: exposure to M. tuberculosis or M. bovis
Negative: absence of infection , anergy.