Tuberculosis is caused by Mycobacterium tuberculosis. The micobacteria are rod shaped, aerobic bacteria that do not forms spores. M.tuberculosis was isolated by Robert Koch in 1882.The tuberculosis is most prevalent infection world wide.The most common site of infection is lungs ( Pulmonary tuberculosis ) but glands, menings, and many other internal organs may be effected.

ETIOLOGY OF TUBERCULOSIS:
M.tuberculosis is a thin, straight or slightly curver rods with round ends, measuring 2-5Mm.They may be uniform width but more often appear beaded with irregularly, unstained vacuoles or heavily stained knobs.On isolation on synthetic media,the cells may vary from coccoidal filamentous forms or as aggregated long strands called Serpentine cords.They are non -sporing , non-capsulated and non-motile.They are acid fast and acid-alcoholic fast.They are usually stained by Ziel-Neelson technique. They may also be stained by fluorescent dyes (e.g, auramine, Rhodamine).

CULTIVATION:
Three types of media are employed for the cultivation of M.tuberculosis.

1. Simple Synthetic Media
2. Oleic acid-albumin media
3. complex Organic Media.

GROWTH CHARACTERISTICS:
M.tuberculois is obligate aerobe.It grows well at pH 6-7.6.Increased carbondioxide  enhances the growth.Optimum temperature is 37 C°Doubling time of the bacilli is 18 hrs or more.Tubercle bacilli produce pale yellow or cream coloured colonies which are usually rough and granular.Saprophytic  forms grow more rapidly and proliferate well at 22 C° producing more pigmentation.

PATHOGENESIS:
Tubercle bacilli are excreted in the sputum by active patient of pulmonary T.B. Organism gain entry into the human body by inhalation, ingestion or directly through the skin.Inhalation is the most common method of infection and invasion through skin is most usual. When inhaled, the organisms reach alveoli where they settle and produce primary leision.The production and the development of leision and their healing and progression depends on the following factors:

1. Virulence of the organism
2. Resistance and hypersensitivity of the host
3. Size of entry of organisms
4. Route of entry of organisms

PATHOLOGY:
In case of pulmonary tuberculosis, the primary leision develops in the lungs, and the intrabronchial lymph nodes are effected most extensively.Histologycally the organisms evokes 2 types of leisions.

1. Exudative type
2. Productive type

• EXUDATIVE TYPE: Within a few days after tubercle bacilli first gain entry into the body,they cause an acute inflammatory reaction that results in the formation of characteristic tissue leision called Tubercle ( Latin; tubercle means small lymph).A tubercle consist of one or few tubercle bacilli surrounded by a small mass of pus, edema fluid,PMNLs and later on monocytes.It appears as a grey mass of pin-head size or smallIt may heal by resolution so that the entire exudate becomes absorbed or it may develop into second ( Productive ) type of leision.

• PRODUCTIVE TYPE:When virulence is high or microbial dosage is large or individual’s resistance is low, and person is hypersensitive, the leision fully develops within 2-4 weeks into a granuloma, this leision consists of 3 zones.

a- A Central Zone: Where a few cells may have fused to form one or more multinucleated giant cells with viable tubercle bacilli in their cytoplasm.

b- A Mid Zone: of pale epithelial cells often arranged rapidly.

c- A Peripheral Zone:consisting of fibroblasts, lyphocytes and monocytes leading eventually to extensive fibrosis.

In the next stage, the bacilli continue to grow,enlarging the tubercles and killing the tissues in the center.This necrotic process is known as Caseation necrosis.The dead tissues become coagulated into a cheesy mass.If the process continues, a number ofcaseous abcesses are formed which may fuse to form one large caseous mass.

A caseous tubercle may break into a bronchus, empties its contents there and forms a cavity.It may subsequently heal by fibrosis or calcification.The healed and calcified primary complex leisions are reffered to as Ghon Complex.

DISSEMINATION OF ORGANISMS INTO HOST:
Tubercle bacilli spread from the initial site via lymphatics to regional lymph nodes.The bacilli may spread farther to reach the thoracic duct and blood stream which in turn disseminate them to other organs ( Miliary T.B).The blood stream can be directly invaded by erosion of a vein by a caseating tubercle or lymph node.
If a caseated leision discharges its contents into a bronchus, the bacilli are aspirated and distributed to other parts of the lungs or ore swallowed and passed into stomach and intestine.

REINFECTION ( ADULT) TYPE OF TUBERCULOSIS:
Reinfection (adult) type tuberculosis occurs when tubercle bacilli re enter the host body after a primary infection is completely or partially healed. Bacilli may be introduced from an outside source or internally from a partially healed tubercle. This type is characterized by chronic tissue leision, the formation of tubercle, caseation and fibrosis. The healing is rapid and tissues are highly defensive because of the allergy( Hypersensitivity) to primary infection. The differences between primary and reactivation tuberculosis are attributed to Acquired resistance and Hypersensitivity induced by the first infection of the host with tubercle bacilli.

TUBERCULIN TEST:
Delayed type of hypersensitivity to tuberculin is highly specific for tubercle bacilliand closely related mycobacteria.Tuberculin is a diluted proteinaceous antigenic sterile extract of tubercle bacilli.Two types of tuberculin are widely used.

1. Old tuberculin
2. Purified protein derivative

PURPOSE OF THE TEST:
Tuberculin test is performed to determine hypersensitive or allergic state to tuberculin.This reactivity appears about one month after infection and lasts for many years.

REACTION AND INTERPRETATION OF TUBERCULIN TEST:

• Negative Reaction: If no reaction develops at the site of inoculation, It shows the person has not been exposed to tubercle bacilli. Such individuals are not at the risk of developing disease from reactivation of primary infection.however, they are highly susceptible to primary infection and should be given BCG.

• Positive Reaction:The person develops induration exceeding 10mm in diameter, edema, erythema in 24-48hrs.This reaction persists for several days.Such positive reaction indicates past infection but does not show recent active infection.Such persons although have some degree of resistanse to the disease,are at the risk of developing disease from reactivation of primary infection.BCG vaccination may also lead to positive tuberculin reaction that may last for 3-7years.

CLINICAL FINDINGS:
Since the tubercle bacilli may involve every organ, its clinical manifestations are variable.Fatigue, weakness, weight loss, fever are the signs of tuberculosis.In pulmonary tuberculosis, chronic cough and spitting of blood is associatedwith far advanced leision.Meningitis and urinary tract involvement can occur in the absence of other signs of disease.Blood stream dissemination leads to Miliary tuberculosis.

LABORATORY DIAGNOSIS:
Specimens required for diagnosis consist of fresh sputum, castric washing, urine,pleural fluid, joint fluid, cerebral spinal fluid (CSF) and other suspected material.

• Stained smear: Staining of smear with Ziehl-Neelson technique or by fluorescent microscopy may reveal typical tubercle bacilli.If direct smear is negative,sputum may be concentrated by the addition of 20% cholorox (1% HCl solution), centrifuged and sediments are then stained.

• Culture: For primary isolation, solid media are preferred, such as Lowan stain-Jenson medium, Dosel’s egg medium, Dubos medium etc. The cultural characteristics and antigenic studies are helpful in diagnosis.For better results, the sputum should be concentrated by treating with 2% NaOH or other bactericidal agents and then neutralized and centrifuged.This kills the contamination in the sputum.

TREATMENT:
The most widely used drugs at present are isonicotinic acid hydrazide (INH),Rifampin , streptomycin and ethambutol. Unfortunately,resistant variants of tubercle bacilli against each of these drugs emerge very rapidly. Treatment is most successful when these drugs are used in combination (e.g, INH + rifampin or INH + Ethambutol) Other drugs ethionamide, pyrizineamide, veomycin, cycloserine are less frequently used because of their side effects. Clinical cure can usually be achieved within 6-18 months.

PREVENTION AND CONTROL:

1. Early detection of cases and source of infection ( Tuberculin test, X-ray) ant their prompt treatment until patients are non infectious.
2. Eradication of tuberculosis in cattles ( Test and Slaughter ) and pasteurization of milk.
3. Drug treatment of asymptomatic tuberculin converters in the age groupmost prone to develop complications ( Childrens) and in tuberculin positive persons who must receive immunosuppressive drugs.
4. IMMUNIZATION: Various living virulent tubercle bacilli, particularly BCG ( Bacillus Calmette Guerin) ;an attenuated bovine organism have been used to induse an amount of resistance in those heavily exposed to infection.
5. INDIVIDUAL HOST RESISTANCE: Non specific factors may reduce host resistance,thus favouring the conversion of asymptomatic infection into disease.Among such activators of T.B are starvation, gastrectomy and suppression of cellular immunityby drugs e.g, Cortico steroids or by disease e.g, AIDS.such patients may receive INH prophylaxis at any age.