KOCH’S DISEASE : TUBERCULOSISKOCH’S DISEASE : TUBERCULOSIS

Robert KochRobert Koch

Robert Koch (1882)Robert Koch (1882) – –

Isolated the mammalian tubercle Isolated the mammalian tubercle bacillus on bacillus on

Heat Coagulated Bovine SerumHeat Coagulated Bovine Serum

and proved its causative role in and proved its causative role in

TuberculosisTuberculosis

by satisfying by satisfying

Koch’s PostulatesKoch’s Postulates

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

Tuberculosis is an architypal chronic granulomatous inflammatory Tuberculosis is an architypal chronic granulomatous inflammatory reaction of the tissues to the presence of causative agent reaction of the tissues to the presence of causative agent Mycobacterium tuberculosis,being characterized by a local Mycobacterium tuberculosis,being characterized by a local

aggregation of large number of macrophages,some of which aggregation of large number of macrophages,some of which undergo striking structural & functional alterations in the form of undergo 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 of Langhan’s giant cells i.e. formation of TUBERCLE.TUBERCLE.

Mycobacterium

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 MYCOBACTERIUM MORPHOLOGY 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 acid Resist 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 stain Mycobacterium 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; Macrophage Acid 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% Nitric Survive 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. & by Killed with Tincture Iodine in 5 mins. & by 80% Ethanol in 2 – 10 mins.80% Ethanol in 2 – 10 mins.

Cultural Characteristics Cultural 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 good Require Egg, Blood, Potato or Serum for good growth.growth.

CULTURE MEDIACULTURE MEDIASOLID 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 Biplate Middlebrook 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, irregular rough, raised, irregular with wrinkled surface.with wrinkled surface.

They are creamy white They are creamy white initially, becoming initially, becoming yellowish or buff yellowish or buff coloured on further coloured on further incubationincubation..

Colonies of Colonies of Mycobacterium tuberculosis Mycobacterium tuberculosis on on Lowenstein-Jensen medium.Lowenstein-Jensen medium.

M. tuberculosisM. tuberculosis bacterial colonies bacterial colonies

Eight Week Growth of Mycobacterium tuberculosis on Lowenstein-Jensen Agar

CULTURE MEDIACULTURE MEDIALIQUID MEDIALIQUID MEDIA

BACTEC 12 B MediumBACTEC 12 B Medium BACTEC 460 TBBACTEC 460 TB BACTEC 9000 MBBACTEC 9000 MB BACTEC MGIT 960 BACTEC MGIT 960

EPS Culture System IIEPS Culture System II

Middlebrook 7H9 BrothMiddlebrook 7H9 Broth

SeptiChek AFBSeptiChek AFB

Dubo’s MediumDubo’s Medium

Tween 80 Tween 80 (Sorbitol Mono oleate)(Sorbitol Mono oleate)

Continuous Monitoring Continuous 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-Peroxidase Catalase-Peroxidase TestTest

Tween 80 Hydrolysis Tween 80 Hydrolysis TestTest

Amidase TestAmidase Test

Nitrate Reduction TestNitrate Reduction Test

Thiophene 2-Carboxylic Thiophene 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 REDUCTION TEST

GROWTH ON TCH

PYRAZI-NAMIDASE TSET

UREASE TEST

M tuberculosis

+ - + - + - +/- + + +

M bovis

- - - - - - +/- - - +

M African

um

- - - - - - - +/- - +

Airborne transmission of Airborne transmission of droplet nucleidroplet nuclei

Deposit in alveolar spaces of lungsDeposit in alveolar spaces of lungs

TransmissionTransmission

Pulmonary tuberculosis is a disease of Pulmonary tuberculosis is a disease of respiratory transmission, Patients with the respiratory transmission, Patients with the active disease (bacilli) expel them into the active 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 or any other way that will expel bacilli into

the air the air

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 Protein Heat 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–CellReceptor

CD4+ T- Cell

CYTO

KIN

ES

CD8+ T- Cell

Delayed Hypersensitivity

Class I MHC

Macrophage

Caseous Necrosis

Phagocytosis of Mycobacterium Phagocytosis of Mycobacterium tuberculosistuberculosis

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 by local erosion by primary focusprimary focus– pleural cavity = pleurisypleural cavity = pleurisy– pericardium = pericardium =

pericarditispericarditis– bronchus = tuberculous bronchus = tuberculous

bronchopneumoniabronchopneumonia (highly infectious) (highly infectious)

disseminated infectiondisseminated infection– miliary tuberculosismiliary tuberculosis– multiple discrete multiple discrete

granulomas resembling granulomas 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 macrophages more macrophages Spherical granulomas Spherical granulomas tubercles tubercles

Extra-pulmonary Extra-pulmonary TuberculosisTuberculosis– Greater emphasis on Greater emphasis on

histology of biopsy histology of biopsy – Caseating granulomasCaseating granulomas

are diagnosticare diagnostic

REMEMBERREMEMBER– any chronic cough, any any chronic cough, any

pneumonia could be pneumonia could be tuberculosistuberculosis

– think of it in any at risk think of it in any at risk patientpatient

– all down and outs have all down and outs have TB till proven otherwise!TB till proven otherwise!

She has tuberculosis of peripheral lymph nodes.  Although lymphatic tuberculosis She has tuberculosis of peripheral lymph nodes.  Although lymphatic tuberculosis may appear to be a localized disease process, it is not as the systemic signs and may 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 likely symptoms 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.  There This 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 abscess The 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 in the axilla may also affected.  Several lymph nodes may be matted together as in this patient.  Some nodes have undergone liquefaction leading to discoloration of this 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 complete In 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 touch This 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 a and 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 lesions This 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 lesions This patient had a seven-year history of lymphatic tuberculosis.  Many lesions have apparently healed, but some are still active (note inflammation surrounding have 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 in At first sight, all of the lesions resulting form peripheral lymphatic tuberculosis in this patient have healed.  However, as the example of the previous patient this patient have healed.  However, as the example of the previous patient demonstrates, one can never be certain.  It thus may be good policy to offer demonstrates, one can never be certain.  It thus may be good policy to offer curative chemotherapy to any patient with signs of tuberculosis of peripheral curative 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 a This 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 by segmental 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 the traditional 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, slightly This patient with tuberculosis of the spine and a visible abscess, slightly discoloring the overlaying skin, on the lower left back almost escaped a correct discoloring the overlaying skin, on the lower left back almost escaped a correct diagnosis but for an astute laboratory technician.  The abscess was warm to the diagnosis but for an astute laboratory technician.  The abscess was warm to the touch and a Gram stain showed Gram-positive cocci.  Nevertheless, the  touch and a Gram stain showed Gram-positive cocci.  Nevertheless, the  laboratory technician insisted on rigorous examination for acid-fast bacilli and laboratory 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 to The 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 a As a result of the anterior lesion, the disk or disks collapse, building a triangular shape, leading the typical gibbus triangular 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 child In addition to the paralysis caused by the lower lumbar lesion, this child also had a pyopneumothorax (and an accelerated response to a BCG also 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 when This patient with a 90 degree lesion in the spine was ambulatory when interviewed.  He had had received a full course of anti-tuberculosis interviewed.  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 the The reason for the complete recovery from neurologic symptoms in the majority of patients is most likely attributable to the anterior location of the majority of patients is most likely attributable to the anterior location of the disease process that often leaves the spinal canal spared.  The neurologic disease process that often leaves the spinal canal spared.  The neurologic symptoms seen in the beginning are thus most likely attributable to edema symptoms seen in the beginning are thus most likely attributable to edema and compression from abscesses that resolve with chemotherapy.  In some and compression from abscesses that resolve with chemotherapy.  In some patients, boney particles may, however, reach the spinal canal and then may patients, 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 the The 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-fast secretion 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 of This patient has a sinus draining from both the dorsal and volar aspect of the thumb.  He squeezed pus out from the lesions directly onto a the thumb.  He squeezed pus out from the lesions directly onto a Lowenstein-Jensen medium, on which Lowenstein-Jensen medium, on which Mycobacterium tuberculosisMycobacterium tuberculosis was was 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 was This patient had tuberculosis of the ankle.  The bacteriologic diagnosis was made by demonstrating acid-fast bacilli from the visible secretions draining made 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 had The patient did not only have tuberculosis of the ankle, he also had peripheral lymphatic tuberculosis, tuberculous mastitis (exceedingly rare in peripheral 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.  While and had been operated for a presumable tuberculous epididymitis.  While such multi-system disease in a young man should pose little difficulties in such multi-system disease in a young man should pose little difficulties in making the diagnosis of tuberculosis, it had not been taken into making 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 patient did not only have tuberculosis of the ankle, he also had The patient did not only have tuberculosis of the ankle, he also had peripheral lymphatic tuberculosis, tuberculous mastitis (exceedingly rare in peripheral 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.  While and had been operated for a presumable tuberculous epididymitis.  While such multi-system disease in a young man should pose little difficulties in such multi-system disease in a young man should pose little difficulties in making the diagnosis of tuberculosis, it had not been taken into making 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 in The diagnosis of female genitourinary tuberculosis is probably made in only of a fraction of cases.  It is believed, however, that Falloppian tube only of a fraction of cases.  It is believed, however, that Falloppian tube and endometrial tuberculosis may account for much female infertility in and endometrial tuberculosis may account for much female infertility in high-incidence countries.  This patient is an example to the case: an high-incidence countries.  This patient is an example to the case: an observant clinician requested a histological examination of an observant clinician requested a histological examination of an endometrium biopsy specimen and caseous granulomata were endometrium biopsy specimen and caseous granulomata were reported.  Subsequently, the index of suspician rose, and numerous reported.  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 of Warty skin tuberculosis is a perhaps difficult to diagnose manifestation of tuberculosis of the skin if it is not thought of.  This patient testifies to the tuberculosis of the skin if it is not thought of.  This patient testifies to the remarkable efficacy of modern anti-tuberculosis chemotherapy in such a remarkable efficacy of modern anti-tuberculosis chemotherapy in such a patient. patient. 

Tuberculosis of the spine is most frequently located in the lower thoracic Tuberculosis 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.