Mycobacterium

General properties

 Slender, slightly curved rods.Slow growing.Aerobic.

 Thic cell wall contain long chain fatty acid (wax), mainly mycolic acid.Difficult to
stained by Gram stain.
 Slow-growing with a generation time of 12 to 18 hours (c.f. 20-30 minutes for
Escherichia coli). Colonies appear after 6-8 weeks
 us includes
– Obligate parasites
– Opportunist pathogens
– Saprophytes
Mycobacteria cell wall structure
Contain large amount of fatty waxes
(mycolic acid) within their cell wall
resist staining by ordinary methods
Require a special stain for diagnostic
Acid Fast stain.
 SPECIES

Species of Medical Importance

 M. tuberculosis
 M. leprae
 M. avium-intracellulare
 M. kansasii
 M. scrofulaceum
 M. marinum
Atypical mycobacterium.( Opportunistic mycobacterium).(MOTT).
a-M.para T.B.
b-M.saprophyticus.
c-M.pheli.
d-M.intercellular.

Mycobacteria
Obligate aerobes growing most successfully in tissues with a high oxygen content,
such as the lungs.
Facultative intracellular pathogens usually infecting mononuclear phagocytes (e.g.
macrophages).
 Mycobacterium T.B.
Pathogenisityand virulence factors

The most virulent strain is H37Rv because it is characterized by

 Facultative intracellular organism (most important)
 Sulfatides (sulfolipids in cell envelope)
− Inhibit phagosome-lysosome fusion, allowing intracellular
survival (if fusion occurs, waxy nature of cell envelope reduces
killing effect)
 Cord factor (trehalose dimycolate)
− Causes serpentine growth in vitro
− Inhibits leukocyte migration; disrupts mitochondrial
respiration and oxidative phosphorylation
 Tuberculin (surface protein) along with mycolic acid → delayed
hypersensitivity and cell-mediated immunity (CMI)
− Granulomas and caseation mediated by CMI
− No exotoxins or endotoxin; damage done by immune system
 Antibiotic resistance ,which results from its ability to produce
mutation on the drug target.
 How tuberculosis spreads
Tuberculosis (TB) is a contagious disease. Like the common cold, it spreads
through the air. Only people who are sick with TB in their lungs are
infectious. When infectious people cough, sneeze, talk or spit, they propel TB
germs, known as bacilli, into the air. A person needs only to inhale a small
number of these bacilli to be infected. Tuberculosis spread by Respiratory
route. Tuberculosis spread by Respiratory route

Source of Infection – Open case of Pulmonary Tuberculosis.

Every open case has potential to infect 20 – 25 healthy persons before cured
or dies ,( Coughing , Sneezing, or Talking). One cough produces 500 droplets.
Each act can spill 3000 infective nuclei in the air,
Infective particles are engulfed by Alveolar Macrophages.

Dr.T.V.Rao MD 4
 Predisposing Factors
Genetic basis, Age ,Stress,Nutrition,Co existing infections Eg HIV
Mechanisms of Infection
 Mycobacterium do not produce toxins.
 Allergy and Immunity plays the major role.
 Only 1/10 of the infected will get disease.
 Cell Mediated Immunity plays a crucial role.
 Humoral Immunity – not Important.
 CD4 Cell plays role in Immune Mechanisms.
 Within 10 days of entry of Bacilli clones of Antigen specific T
Lymphocytes are produced
 Can actively produce Cytokines,
 Interferon γ which activate Macrophages form cluster or Granuloma
Immunity in Tuberculosis.
CD4 T- Lymphocytes with Th 1 or Th 2 secrete Cytokines, Interleukin 1,2,
Interferon's γ ,Tumor necrosis factor. Th 1 secrete Cytokines Activate
Macrophages Results in protective Immunity, Th 2 manifests with Delayed
Hypersensitivity DTH causes Tissue destruction. and disease will progress.
Activated Macrophages - Epitheliod cells Forms cluster a granuloma Activated
macrophages turn into Giant cells (multinucleated cell).
.
5
 Basis of Tubercle formation.
• NOTE: ultimately a fibrin layer develops around granuloma (fibrosis),
further “walling off” the lesion.
• Typical progression in pulmonary TB involves caseation, calcification and
cavity formation

NOTE: ultimately a fibrin layer develops around granuloma (fibrosis), further

“walling off” the lesion.

Dr.T.V.Rao MD 6
 Clinical diseas.
 Primary pulmonary tuberculosis
− Organisms replicate in naive alveolar macrophages, killing the
macrophages until CMI is set up (Ghon focus)
− Macrophages transport the bacilli to the regional lymph node (Ghon
complex) and most people heal without disease
− Organisms that are walled off within the Ghon complex remain viable
unless treated
 Reactivational tuberculosis
− Erosion of granulomas into airways (high oxygen) later in life under
conditions of reduced T-cell immunity leads to mycobacterial
replication and disease symptoms
− Complex disease with the potential of infecting any organ system
− May disseminate (miliary TB) it is characterized by numerous small
tubercles (granulomatous nodules), and typically a necrotic tubercle cases
erosion of a blood vessel ,leading to the hematogenous spread of bacteria, and
this type mainly affected a very young or elderly individual and immuno-
compromised patients are most frequently affected, and this disease associated
with high mortality rate.

Dr.T.V.Rao MD 7
 Multiorgan Involvementin Tuberculosis.

Extra pulmonary Tuberculosis

Bacteria on circulation leads to
bacteremia leads to involvement of
GUT, Genito urinary system,
Meningitis ,Gastro Intestinal
system, skin, Lymph nodes, Bone
marrow. Spinal infection Potts
spine, Arthritis.

Complication of Tuberculosis

Meningitis.
Pleurisy,
Involvement of Kidney,
Spine ( Potts spine )
Bone Joints,
Miliary tuberculosis

. Dr.T.V.Rao MD 8
 Clinical Illness with Tuberculosis

• Pulmonary Disease – Major

manifestation with involvement of
Lungs, Cough, Hemoptysis, Chest
pain ,Fever ,sweets, Anorexia ,
weight loss,Cavity formation in
Lungs

Dr.T.V.Rao MD 9
 Treatment
Increasing prevalence of resistance strains ,so antimicrobial sensitivity
testing of isolates is essential ;
1-Regimen; administration of at least two drugs to avoid emergence of
resistance strains of M.TB. ,and also recommended that four drugs
be used at same time fore initial treatment in an effort to counteract
the emergence and rapid spread of drug resistance particularly
among close contact patient;
2-Duration; should be continued for several months depending on the
severity of disease;
First 2 months: rifampin + isoniazid + pyrazinamide + ethambutol
(RIPE)
− Next 4 months: rifampin and isoniazid
Ethambutol or streptomycin added for possible drug-resistant cases until
susceptibility tests are back (if area acquired has >4% drug-resistant
mycobacteria

Multidrug resistant tuberculosis has become a global threat.

 Control and prevention
 Immunoprophylaxis ;administration of bacille Calmette-Guerin (BCG),an
attenuatted strain derived from mycobacterium –bovis has been used
successfully.
 Isoniazid taken for 9 months can prevent TB in persons with infection but
no clinical symptoms.

 Screening by tuberculin test .(Mantoux test)

the strong CMI elicited by this organism is used as the basis for a skin test
(Tuberculin test) by injection of 5-10 ml of M-tuberculosis antigen which
is (a protein –purified derivative PPD )intra-dermaly ,the results are read
48-72h later .The appearance of an indurated erythematous reaction
measuring at least 10mm considered a positive test result.
 Interpretation
1-A positive PPD test, not necessary patient has T.B ,it is mean the
patient has been previously exposed to the bacterium or its protein (primary
exposure has taken). Also vaccination can lead to with positive test.
2-False positive reaction may occur as a result of a cross reaction with other
mycobacterium.
3-False negative occur in cases associated with immuno- suppression ,or in case
of milliary T.B due to the shortage time of sensitization and low grade of
CMI.
Interpretation of PPD and X –ray .;
1-Positive PPD and –ve X-ray (no cavity )----patient has previous
contact with mycobacterium Ag the patient immunonized
2-Positive PPD and positive X –ray (cavity and shadow ) ----------
patient suffering from T.B and should be confirmed by culture .
3-Negative PPD and – ve X-ray ---------- mean the patient have no
previous contact with mycobacterium T.B, and he is highly susceptible to
T.B infection and need vaccination.

Positive skin test indicates only exposure but not necessarily active
disease.