Mycobacterium tuberculosis lecture

By – Dr.D.W.Deshkar
Assistant Lecturer Dept.of Microbiology
D.Y.Patil Medical College, Kolhapur

KOCH’S DISEASE : TUBERCULOSISKOCH’S DISEASE : TUBERCULOSIS
Robert KochRobert Koch
 Robert Koch (1882)Robert Koch (1882) ––
Isolated the mammalian tubercleIsolated the mammalian tubercle
bacillus onbacillus on
Heat Coagulated Bovine SerumHeat Coagulated Bovine Serum
and proved its causative role inand proved its causative role in
TuberculosisTuberculosis
by satisfyingby satisfying
Koch’s PostulatesKoch’s Postulates

“NO ONE IS SAFE FROM TUBERCULOSIS
UNTIL EVERY ONE IS SAFE”.

 Tuberculosis is an architypal chronic granulomatous inflammatoryTuberculosis is an architypal chronic granulomatous inflammatory
reaction of the tissues to the presence of causative agentreaction of the tissues to the presence of causative agent
Mycobacterium tuberculosis,being characterized by a localMycobacterium tuberculosis,being characterized by a local
aggregation of large number of macrophages,some of whichaggregation of large number of macrophages,some of which
undergo striking structural & functional alterations in the form ofundergo striking structural & functional alterations in the form of
their transformation to epithelioid cells,foreign body giant cells &their transformation to epithelioid cells,foreign body giant cells &
Langhan’s giant cells i.e. formation ofLanghan’s giant cells i.e. formation of TUBERCLE.TUBERCLE.

Organisms belonging to the genus
Mycobacterium are----
1.Very Thin
2.Rod shaped
3.0.2 to 0.4 X 2 to 10 µ m
4.Non motile
5.Sometimes showing filamentous branching like
fungus.
6.Forming mould like pellicle in liquid culture.

CLASSIFICATION OF MYCOBACTERIACLASSIFICATION OF MYCOBACTERIA
 Typical MycobacteriaTypical Mycobacteria
 M tuberculosisM tuberculosis
 M bovisM bovis
 M bovis BCGM bovis BCG
 M africanumM africanum
 Atypical MycobacteriaAtypical Mycobacteria
 PhotochromogensPhotochromogens
 ScotochromogensScotochromogens
 Non PhotochromogensNon Photochromogens
 Rapid GrowersRapid Growers
 Non-Cultivable MycobacteriaNon-Cultivable Mycobacteria
 M lepraeM leprae
 Saprophytic MycobacteriaSaprophytic Mycobacteria
 M butyricumM butyricum
 M pheliM pheli
 M smegmatisM smegmatis

Mycobacterium tuberculosis
Mycobacterium bovis
Mycobacterium bovis BCG
Mycobacterium africanum
Mycobacterium microti (Vole)
MYCOBACTERIUM
TUBERCULOSIS COMPLEX

MYCOBACTERIUM TUBERCULOSISMYCOBACTERIUM TUBERCULOSIS
Mycobacterium tuberculosis
Scientific classification
Kingdom: Bacteria
Phylum: Actinobacteria
Order: Actinomycetales
Suborder: Corynebacterineae
Family: Mycobacteriaceae
Genus: Mycobacterium
Species: M. tuberculosis
Binomial name

MORPHOLOGY OF MYCOBACTERIUMMORPHOLOGY OF MYCOBACTERIUM
TUBERCULOSISTUBERCULOSIS
 Straight or slightly curved rodStraight or slightly curved rod
 3 µm X3 µm X 0.3 µm0.3 µm
 Occurring slightly in pairs or small clumpsOccurring slightly in pairs or small clumps
 Are ‘ACID – FAST’ & ‘ALCOHOL FAST’Are ‘ACID – FAST’ & ‘ALCOHOL FAST’
 Resist decolourization by 20% sulphuric acidResist decolourization by 20% sulphuric acid
& absolute alcohol for 10 minutes.& absolute alcohol for 10 minutes.

STAINING BY :STAINING BY :
 ZIEHL – NEELSEN STAINZIEHL – NEELSEN STAIN
 KYNIOUN STAINKYNIOUN STAIN
 FLUORESCENT STAINFLUORESCENT STAIN
((AURAMIN O & RHODAMINEAURAMIN O & RHODAMINE.).)

Mycobacterium tuberculosis: Ziehl-Neelsen stainMycobacterium tuberculosis: Ziehl-Neelsen stain

Mycobacterium tuberculosis: Ziehl-Neelsen stain.Mycobacterium tuberculosis: Ziehl-Neelsen stain.

Mycobacterium Tuberculosis Stained with
Fluorescent Dye

Mycobacterium tuberculosisMycobacterium tuberculosis ::
Electron Micrograph.Electron Micrograph.

Mycolic acids
CMN Group: Unusual cell
wall lipids (mycolic acids,etc.)
(Purified Protein Derivative)
Lipid Rich Cell Wall Of Mycobacterium tuberculosis

Chemical Fractions & AntigenicityChemical Fractions & Antigenicity
 Protein FractionProtein Fraction –– IHR & DHRIHR & DHR
 Polysaccharide ComponentPolysaccharide Component –– IHRIHR
 Lipid FractionLipid Fraction –– Acid Fastness; MacrophageAcid Fastness; Macrophage
Transformation; Tubercle Formation.Transformation; Tubercle Formation.

ACID FASTNESS OF
MYCOBACTERIUM TUBERCULOSIS
IS DUE TO PRESENCE OF
A HIGH MOLECULAR WEIGHT
HYDROXY ACID CONTAINING
CARBOXYL GROUPS
CALLED
MYCOLIC ACID
IN THE BACTERIAL CELL WALL OR
TO A SEMIPERMIABLE MEMBRANE
AROUND THE CELL.

Resistance of M tuberculosisResistance of M tuberculosis
 Killed at 60ºC in 15 – 20 mins,Killed at 60ºC in 15 – 20 mins,
 Killed on exposure to sunlight for 2 hrs,Killed on exposure to sunlight for 2 hrs,
 Remain viable for 8 – 10 days in Droplet Nuclei,Remain viable for 8 – 10 days in Droplet Nuclei,
 Cultures remain viable at Room temp.Cultures remain viable at Room temp.
for 6 – 8 months,for 6 – 8 months,
Survive exposure to 5% Phenol, 15% Sulphuric acid, 3% NitricSurvive exposure to 5% Phenol, 15% Sulphuric acid, 3% Nitric
acid, 5% Oxalic acid and 4% NaOH.acid, 5% Oxalic acid and 4% NaOH.
Sensitive to Formaldehyde & Glutaraldehyde.Sensitive to Formaldehyde & Glutaraldehyde.
Killed with Tincture Iodine in 5 mins. & byKilled with Tincture Iodine in 5 mins. & by
80% Ethanol in 2 – 10 mins.80% Ethanol in 2 – 10 mins.

Cultural CharacteristicsCultural Characteristics
Slow Growing Bacteria.Slow Growing Bacteria.
Generation Time – 14 – 15 hrs.Generation Time – 14 – 15 hrs.
Optimum Temp - 37ºC’Optimum Temp - 37ºC’
Optimum pH – 6.4 – 7,Optimum pH – 6.4 – 7,
Eugonic (5% Glycerol – luxuriant growth),Eugonic (5% Glycerol – luxuriant growth),
Require Egg, Blood, Potato or Serum for goodRequire Egg, Blood, Potato or Serum for good
growth.growth.

CULTURE MEDIACULTURE MEDIA
SOLID MEDIASOLID MEDIA
 Egg-based Media:Egg-based Media:
 Lowenstein-Jensen (LJ)Lowenstein-Jensen (LJ)
MediumMedium
 Dorset MediumDorset Medium
 Serum containing Media:Serum containing Media:
 Loeffler’s MediumLoeffler’s Medium
 Potato-based Media:Potato-based Media:
 Pawlowsky’s MediumPawlowsky’s Medium
 Blood containing Media:Blood containing Media:
 Tarshi’s MediumTarshi’s Medium
 Agar-based Media:Agar-based Media:
 Middlebrook 7H10Middlebrook 7H10
 Middlebrook 7H11Middlebrook 7H11
 Middlebrook BiplateMiddlebrook Biplate
(7H10/7H11 S Agar).(7H10/7H11 S Agar).

MYCOBACTERIUM TUBERCULOSIS :MYCOBACTERIUM TUBERCULOSIS :
Lowenstein-Jensen Medium.Lowenstein-Jensen Medium.
 Colonies are dry,Colonies are dry,
rough, raised, irregularrough, raised, irregular
with wrinkled surface.with wrinkled surface.
 They are creamy whiteThey are creamy white
initially, becominginitially, becoming
yellowish or buffyellowish or buff
coloured on furthercoloured on further
incubationincubation..

Colonies ofColonies of Mycobacterium tuberculosisMycobacterium tuberculosis onon
Lowenstein-Jensen medium.Lowenstein-Jensen medium.

M. tuberculosisM. tuberculosis bacterial coloniesbacterial colonies

Eight Week Growth of Mycobacterium tuberculosis
on Lowenstein-Jensen Agar

CULTURE MEDIACULTURE MEDIA
LIQUID MEDIALIQUID MEDIA
 BACTEC 12 B MediumBACTEC 12 B Medium
 BACTEC 460 TBBACTEC 460 TB
 BACTEC 9000 MBBACTEC 9000 MB
 BACTEC MGIT 960BACTEC MGIT 960
 EPS Culture System IIEPS Culture System II
 Middlebrook 7H9 BrothMiddlebrook 7H9 Broth
 SeptiChek AFBSeptiChek AFB
 Dubo’s MediumDubo’s Medium
 Tween 80Tween 80
(Sorbitol Mono oleate)(Sorbitol Mono oleate)
 Continuous MonitoringContinuous Monitoring
systemsystem

Acid-Fast (Kinyoun) Stain of Mycobacterium
NOTE: cord growth (serpentine arrangement) of virulent strains

Biochemical Reactions:Biochemical Reactions:
 Niacin TestNiacin Test
 Arylsulphatase TestArylsulphatase Test
 Neutral Red TestNeutral Red Test
 Catalase-PeroxidaseCatalase-Peroxidase
TestTest
 Tween 80 HydrolysisTween 80 Hydrolysis
TestTest
 Amidase TestAmidase Test
 Nitrate Reduction TestNitrate Reduction Test
 Thiophene 2-CarboxylicThiophene 2-Carboxylic
acid Hydrazide (TCH)acid Hydrazide (TCH)
TestTest
 Tellurite Reduction TestTellurite Reduction Test

BIOCHEMICAL REACTIONS:BIOCHEMICAL REACTIONS:
SPECIES NIACIN
TEST
ARYL-
SULPH-
--ATASE
TEST
NITRATE
REDUC--
-TION
TEST
HOT
CATAL--
-ASE
TEST
PEROX--
-IDASE
TEST
TWEEN
80
HYDRO-
-LYSIS
TSET
TELLURI-
-TE
REDUCTI
ON TEST
GROWTH
ON TCH
PYRA
ZI-
NAMI
DASE
TSET
UREAS
E TEST
M
tuberculo
sis
+ - + - + - +/- + + +
M
bovis
- - - - - - +/- - - +
M
Africanu
m
- - - - - - - +/- - +

Airborne transmission ofAirborne transmission of
droplet nucleidroplet nuclei
Deposit in alveolar spaces of lungsDeposit in alveolar spaces of lungs

TransmissionTransmission
 Pulmonary tuberculosis is a disease ofPulmonary tuberculosis is a disease of
respiratory transmission, Patients with therespiratory transmission, Patients with the
active disease (bacilli) expel them into theactive disease (bacilli) expel them into the
air by:air by:
– coughing,coughing,
– sneezing,sneezing,
– shouting,shouting,
– or any other way that will expel bacilli into theor any other way that will expel bacilli into the
airair

TUBERCULOSIS IS THE MOST IMPORTANT
COMMUNICABLE DISEASE IN THE WORLD
SPARING NO AGE, NO SEX, & NO
NATIONALITY.

VIRULENCE FACTORSVIRULENCE FACTORS
 Cord FactorCord Factor
 SulphatidSulphatid
 Lipo-Arabino Mannan (LAM)Lipo-Arabino Mannan (LAM)
 Heat Shock ProteinHeat Shock Protein
 Mac-1 IntegrinMac-1 Integrin
 Antigen 85 ComplexAntigen 85 Complex

Pathogenesis of M. tuberculosisPathogenesis of M. tuberculosis

IMMUNOPATHOLOGY OF TBIMMUNOPATHOLOGY OF TB
M.
tuberculosis
Macrophage
Class II MHC
Activated Macrophage
(Phagocytosis)
Bactericidal activity
T–Cell
Receptor
CD4+ T- Cell
CYTOKINE
S
CD8+ T- Cell
Delayed
Hypersensitivity
Class I MHC
Macrophage
Caseous Necrosis

Phagocytosis of Mycobacterium tuberculosisPhagocytosis of Mycobacterium tuberculosis

 Infiltration of lymphocytesInfiltration of lymphocytes
Macrophage engulfing M. tuberculosis pathogen

Diagram
of a
Granuloma
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.

 Pneumonia
 Granuloma formation with fibrosis
 Caseous necrosis
• Tissue becomes dry & amorphous (resembling cheese)
• Mixture of protein & fat (assimilated very slowly)
 Calcification
• Ca++
salts deposited
 Cavity formation
• Center liquefies & empties into bronchi
Typical Progression of
Pulmonary Tuberculosis

Necrosis: Soft White CheeseNecrosis: Soft White Cheese

Progressive Primary InfectionProgressive Primary Infection
 local erosion bylocal erosion by
primary focusprimary focus
– pleural cavity = pleurisypleural cavity = pleurisy
– pericardium =pericardium =
pericarditispericarditis
– bronchus = tuberculousbronchus = tuberculous
bronchopneumoniabronchopneumonia
(highly infectious)(highly infectious)
 disseminated infectiondisseminated infection
– miliary tuberculosismiliary tuberculosis
– multiple discretemultiple discrete
granulomas resemblinggranulomas resembling
millet seedsmillet seeds
 metastatic infectionmetastatic infection
– tuberculous meningitistuberculous meningitis
– bone & jointbone & joint
– kidneykidney
– uterus/testisuterus/testis

GranulomaGranuloma
 Pulmonary TuberculosisPulmonary Tuberculosis
 T-lymphocytesT-lymphocytes more macrophagesmore macrophages
 Spherical granulomasSpherical granulomas  tuberclestubercles

 Extra-pulmonaryExtra-pulmonary
TuberculosisTuberculosis
– Greater emphasis onGreater emphasis on
histology of biopsyhistology of biopsy
– Caseating granulomasCaseating granulomas
are diagnosticare diagnostic
 REMEMBERREMEMBER
– any chronic cough, anyany chronic cough, any
pneumonia could bepneumonia could be
tuberculosistuberculosis
– think of it in any at riskthink of it in any at risk
patientpatient
– all down and outs haveall down and outs have
TB till proven otherwise!TB till proven otherwise!

She has tuberculosis of peripheral lymph nodes. Although lymphatic tuberculosisShe has tuberculosis of peripheral lymph nodes. Although lymphatic tuberculosis
may appear to be a localized disease process, it is not as the systemic signs andmay appear to be a localized disease process, it is not as the systemic signs and
symptoms in this child indicate. At least five lesions can be seen, but it is likelysymptoms in this child indicate. At least five lesions can be seen, but it is likely
that there are more less apparent ones in deeper structures.that there are more less apparent ones in deeper structures.

This patient was referred to the tuberculosis clinic with the question of otitis media. ThereThis patient was referred to the tuberculosis clinic with the question of otitis media. There
was no otitis. The patient had lost weight and had signs and symptoms of systemic illness.was no otitis. The patient had lost weight and had signs and symptoms of systemic illness.
The pre-auricular lesion was cold to the touch and was apparently fluctuating. The abscessThe pre-auricular lesion was cold to the touch and was apparently fluctuating. The abscess
was aspirated. A Gram stain showed no organisms and careful examination of a Ziehl-was aspirated. A Gram stain showed no organisms and careful examination of a Ziehl-
Neelsen stained smear revealed acid-fast bacilli.Neelsen stained smear revealed acid-fast bacilli.

While peripheral lymphatic tuberculosis is most frequently found around the neck,While peripheral lymphatic tuberculosis is most frequently found around the neck,
the axilla may also affected. Several lymph nodes may be matted together as inthe axilla may also affected. Several lymph nodes may be matted together as in
this patient. Some nodes have undergone liquefaction leading to discoloration ofthis patient. Some nodes have undergone liquefaction leading to discoloration of
the skin.the skin.

In this patient, any affected lymph node in the lesion had undergone completeIn this patient, any affected lymph node in the lesion had undergone complete
caseation with discoloration of the skin.caseation with discoloration of the skin.

This abscess was close to breaking through the skin, yet it felt cold to the touchThis abscess was close to breaking through the skin, yet it felt cold to the touch
and the child felt remarkably little pain when the lesion was touched. Such aand the child felt remarkably little pain when the lesion was touched. Such a
finding should raise a high index of suspicion for tuberculosis.finding should raise a high index of suspicion for tuberculosis.

This patient has chronic peripheral lymphatic tuberculosis with some lesionsThis patient has chronic peripheral lymphatic tuberculosis with some lesions
healed with scaring, while others are still showing activity.healed with scaring, while others are still showing activity.

This patient had a seven-year history of lymphatic tuberculosis. Many lesionsThis patient had a seven-year history of lymphatic tuberculosis. Many lesions
have apparently healed, but some are still active (note inflammation surroundinghave apparently healed, but some are still active (note inflammation surrounding
the most caudal axillary lesion).the most caudal axillary lesion).

At first sight, all of the lesions resulting form peripheral lymphatic tuberculosis inAt first sight, all of the lesions resulting form peripheral lymphatic tuberculosis in
this patient have healed. However, as the example of the previous patientthis patient have healed. However, as the example of the previous patient
demonstrates, one can never be certain. It thus may be good policy to offerdemonstrates, one can never be certain. It thus may be good policy to offer
curative chemotherapy to any patient with signs of tuberculosis of peripheralcurative chemotherapy to any patient with signs of tuberculosis of peripheral
lymph nodes.lymph nodes.

This boy presented with several lesions. On a chest radiograph, he had aThis boy presented with several lesions. On a chest radiograph, he had a
segmental lesion. In addition, he had a lesion in the neck (rendered dark bysegmental lesion. In addition, he had a lesion in the neck (rendered dark by
traditional medicine), an axillary lesion, and a lesion in the arm (the hump on thetraditional medicine), an axillary lesion, and a lesion in the arm (the hump on the
arm is the tuberculin skin test reaction), and the hand.arm is the tuberculin skin test reaction), and the hand.

The lesion in the hand is shown here in close-up.The lesion in the hand is shown here in close-up.

This patient with tuberculosis of the spine and a visible abscess, slightlyThis patient with tuberculosis of the spine and a visible abscess, slightly
discoloring the overlaying skin, on the lower left back almost escaped a correctdiscoloring the overlaying skin, on the lower left back almost escaped a correct
diagnosis but for an astute laboratory technician. The abscess was warm to thediagnosis but for an astute laboratory technician. The abscess was warm to the
touch and a Gram stain showed Gram-positive cocci. Nevertheless, thetouch and a Gram stain showed Gram-positive cocci. Nevertheless, the
laboratory technician insisted on rigorous examination for acid-fast bacilli andlaboratory technician insisted on rigorous examination for acid-fast bacilli and
found them, confirming tuberculosis of the spine with a super-infected abscess.found them, confirming tuberculosis of the spine with a super-infected abscess.

The vertebral lesions are usually anterior in location, often triangular in shape.The vertebral lesions are usually anterior in location, often triangular in shape.
The bony structure adjacent to both sides of the disk becomes eroded, leading toThe bony structure adjacent to both sides of the disk becomes eroded, leading to
the seemingly narrowing of inter-vertebral disk space.the seemingly narrowing of inter-vertebral disk space.

As a result of the anterior lesion, the disk or disks collapse, building aAs a result of the anterior lesion, the disk or disks collapse, building a
triangular shape, leading the typical gibbustriangular shape, leading the typical gibbus

Extensive destruction in two adjacent vertebrae.Extensive destruction in two adjacent vertebrae.

Two vertebrae collapsed to the height of one.Two vertebrae collapsed to the height of one.

In addition to the paralysis caused by the lower lumbar lesion, this childIn addition to the paralysis caused by the lower lumbar lesion, this child
also had a pyopneumothorax (and an accelerated response to a BCGalso had a pyopneumothorax (and an accelerated response to a BCG
vaccination).vaccination).

This patient has a severe gibbus in the lower thoracic region.This patient has a severe gibbus in the lower thoracic region.

This patient with a 90 degree lesion in the spine was ambulatory whenThis patient with a 90 degree lesion in the spine was ambulatory when
interviewed. He had had received a full course of anti-tuberculosisinterviewed. He had had received a full course of anti-tuberculosis
treatment and had no neurologic symptoms.treatment and had no neurologic symptoms.

The reason for the complete recovery from neurologic symptoms in theThe reason for the complete recovery from neurologic symptoms in the
majority of patients is most likely attributable to the anterior location of themajority of patients is most likely attributable to the anterior location of the
disease process that often leaves the spinal canal spared. The neurologicdisease process that often leaves the spinal canal spared. The neurologic
symptoms seen in the beginning are thus most likely attributable to edemasymptoms seen in the beginning are thus most likely attributable to edema
and compression from abscesses that resolve with chemotherapy. In someand compression from abscesses that resolve with chemotherapy. In some
patients, boney particles may, however, reach the spinal canal and then maypatients, boney particles may, however, reach the spinal canal and then may
cause permanent disability.cause permanent disability.

This girl had an almost completely destroyed hip joint.This girl had an almost completely destroyed hip joint.

The diagnosis of tuberculosis of the left hip in this boy was made from theThe diagnosis of tuberculosis of the left hip in this boy was made from the
secretion from a sinus draining through the skin by demonstrating acid-fastsecretion from a sinus draining through the skin by demonstrating acid-fast
bacilli.bacilli.

Tuberculosis of the wrist.Tuberculosis of the wrist.

This patient has a sinus draining from both the dorsal and volar aspect ofThis patient has a sinus draining from both the dorsal and volar aspect of
the thumb. He squeezed pus out from the lesions directly onto athe thumb. He squeezed pus out from the lesions directly onto a
Lowenstein-Jensen medium, on whichLowenstein-Jensen medium, on which Mycobacterium tuberculosisMycobacterium tuberculosis waswas
isolated (a smear examination for acid-fast bacilli was negative).isolated (a smear examination for acid-fast bacilli was negative).

The radiograph shows the complete destruction of the distal phalanx.The radiograph shows the complete destruction of the distal phalanx.

This patient had tuberculosis of the ankle. The bacteriologic diagnosis wasThis patient had tuberculosis of the ankle. The bacteriologic diagnosis was
made by demonstrating acid-fast bacilli from the visible secretions drainingmade by demonstrating acid-fast bacilli from the visible secretions draining
from a sinus.from a sinus.

The patient did not only have tuberculosis of the ankle, he also hadThe patient did not only have tuberculosis of the ankle, he also had
peripheral lymphatic tuberculosis, tuberculous mastitis (exceedingly rare inperipheral lymphatic tuberculosis, tuberculous mastitis (exceedingly rare in
men), pleural thickening from past pleural tuberculosis, multiple abscesses,men), pleural thickening from past pleural tuberculosis, multiple abscesses,
and had been operated for a presumable tuberculous epididymitis. Whileand had been operated for a presumable tuberculous epididymitis. While
such multi-system disease in a young man should pose little difficulties insuch multi-system disease in a young man should pose little difficulties in
making the diagnosis of tuberculosis, it had not been taken intomaking the diagnosis of tuberculosis, it had not been taken into
consideration for a prolonged period of time.consideration for a prolonged period of time.

The diagnosis of female genitourinary tuberculosis is probably made inThe diagnosis of female genitourinary tuberculosis is probably made in
only of a fraction of cases. It is believed, however, that Falloppian tubeonly of a fraction of cases. It is believed, however, that Falloppian tube
and endometrial tuberculosis may account for much female infertility inand endometrial tuberculosis may account for much female infertility in
high-incidence countries. This patient is an example to the case: anhigh-incidence countries. This patient is an example to the case: an
observant clinician requested a histological examination of anobservant clinician requested a histological examination of an
endometrium biopsy specimen and caseous granulomata wereendometrium biopsy specimen and caseous granulomata were
reported. Subsequently, the index of suspician rose, and numerousreported. Subsequently, the index of suspician rose, and numerous
other cases were diagnosed subsequently.other cases were diagnosed subsequently.

Warty skin tuberculosis is a perhaps difficult to diagnose manifestation ofWarty skin tuberculosis is a perhaps difficult to diagnose manifestation of
tuberculosis of the skin if it is not thought of. This patient testifies to thetuberculosis of the skin if it is not thought of. This patient testifies to the
remarkable efficacy of modern anti-tuberculosis chemotherapy in such aremarkable efficacy of modern anti-tuberculosis chemotherapy in such a
patient.patient.

Tuberculosis of the spine is most frequently located in the lower thoracicTuberculosis of the spine is most frequently located in the lower thoracic
and the lumber region of the spine.and the lumber region of the spine.

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