TUBERCULOSIS
Dr. Jeena N.K. BHMS,MD(Hom)

       Tuberculosis is one of the most widely prevalent chronic infectious diseases affecting mankind. Every year 2 million persons in India develop tuberculosis and half a million die of disease. The annual global incident of disease is eight million and mortality is 3 million.

Definition:-
Tuberculosis is infectious disease caused by Mycobacterium Tuberculosis and characterized by inflammation, abscess formation, cavities, fibrosis and calcification.

Epidemiology:-Infection occurs primarily by inhalation. Infectious droplets, which are aerosolized by coughing and dry while suspended in air, may contaminate the air in the closed spaces for long periods
The present estimate of WHO is that there are about 15-20 million infectious cases in the world at any one time and that 3 million death occurs annually. In India prevalence figure for radiology demonstrate pulmonary disease as 1.3% to 2.5% and bacteriological proved lesions as .2% to .9% among the population aged 5 years and above.
Despite vigorous measures to control the disease undertaken by NTCP( National tuberculosis control programme) the disease tends to persist because of poor socioeconomic and education, level of the population, resistance to accept the treatment and noncompliance with the prolonged drug regimen. Immunodeficiency states both iatrogenic and AIDS, vitamin deficiency leads to resurgence of disease in several parts of India

Aetiology:-
Types of Mycobacteria causing diseases in man
1. Mycobacterium tuberculosis-Causes most infections.
2. Mycobacterium bovis- endemic in cattle, spread to man by milk
3. A typical or opportunistic mycobacteria- Rare, causes pulmonary and generalized infection immunocompromised.

Sources of infection:-There are two sources of infection
Human and bovine Source
Human Source:-The most common source of infection is the human case, whose sputum is positive for tubercle bacilli and who has neither received treatment nor treated fully.
Bovine source:-The bovine source of infection is usually infected milk.
Communicability:-persons are infective as long as they remain untreated
The development of clinical illness depends on several factors. They are:
1. Age-Tuberculosis affect all ages
2. Sex more prevent in Males than females
3. Hereditary: - though Tuberculosis is not a hereditary disease, inherited susceptibility is an important risk factor
4. Nutrition: - Malnutrition is believed to predispose to tuberculosi
5. Immunity: - Man has no inherited immunity against tuberculosis. It is acquired as a result of natural infection or BCG vaccination.

Conditions predispose to tuberculosis are
Diabetes mellitus, Gastric surgery, Silicosis, Alcoholism etc.

Those at great risk are
1. Children, adolescents and young adults
2. Contacts of patients with smear positive pulmonary diseases
3. Immunocompromised individuals
4. Those in contact with many potential patients (e.g.: health workers)
5. People living in overcrowded conditions.

Transmission:-
Mycobacterium Tuberculosis is transmitted from person to person, mostly by respiratory route. Tubercle bascilli from respiratory tract is expelled by coughing, sneezing etc. as droplets. These droplets evaporate within a short distance from mouth and thereafter desiccated bacilli remain air borne for long periods. Infection of susceptible host occurs when a few of these bacilli are inhaled.

Pathogenesis and pathology:-
The portal of entry of the organism is inhalation, Ingestion, or Inoculation. Primary site of infection depends on the mode of entry. It may be in lungs, tonsils, mucous membranes, intestine or skin.
The host reaction to bacilli is initially exudative and later proliferative. Initially exudates is composed of neutrophils, later lymphokine activated macrophage accumulate and engulf the organisms. These macrophage with engulf organism gets transformed to epitheloid cells. These epitheloid cells fuse to form langhan’s giant cells. They are surrounded by lymphocytes and fibroblast. At the centre of the lesion caseation necrosis occurs. The secret of success of the organism is its ability to invade the immune system without being destroyed by them.
The pathological hallmark of tuberculosis is the tubercles or tuberculous granulomas. It consists of an area of central caseation, around which there is infiltration by epitheloid cells, giant cells, round cells and periphery by fibroblast. Several such microscopic tubercles form macroscopic tubercles which are seen in affected tissues.

Pulmonary tuberculosis:  2types
1. primary tuberculosis
2. Post primary pulmonary tuberculosis

Primary pulmonary tuberculosis:-
The pathological process occurring in an individual who has not been sensitized to the organism is known as primary tuberculosis.
Pathology:-
The pathological lesion in primary tuberculosis show prominent lymph node enlargement usually hilar with only minimal parenchymal lesions. Initially primary tuberculosis occurs in the lung, but occasionally in the tonsils or alimentary tract. In the lung the initial lesion is a ghon’s lesion. (i.e. a sub pleural tubercle located in the lower part of upper lobe, upper part of lower lobe or in the middle lobe). This ghon’s lesion with its enlarged regional lymph nodes and interconnecting lymphangitis is known as Ghon’s complex. Lesion heals spontaneously in more than 80% of cases. Tuberculin test becomes positive within 4 to 6 weeks of infection. Once it becomes positive, it remains as such for life.
In 10-15% of children primary lesion goes on to progressive disease. This may be due to poor general resistance, immunosuppressant, high infective dose, or virulent strains of bacilli. AIDS, measles and whooping cough favours progression. The hilar lymph nodes enlarge progressively and undergo caseation. Compression of the neighboring bronchi, especially of middle lobe, leads to collapse- consolidation and bronchiectatic changes. This may present later as the ‘middle lobe syndrome’. When a caseated node ruptures into a bronchus, spread occurs into other parts of lungs and tuberculous bronchopneumonia develops. Erosion of blood vessels and discharge of caseated material into the blood stream leads to military tuberculosis. Spread to pleura results in pleurisy with effusion.

Clinical features:-
Onset- acute or insidious
Early symptoms- Fever, Loss of appetite, loss of weght and cough
In children--- Lethargy, vague ill- health, failure to thrive and delay in the milestones of development, at this stage disease can be diagnosed only if the clinical suspicion is strong.

Others: - Phlyctenular conjunctivitis, Erythema nodosum, recurrent respiratory tract infections, acute pleural effusion, tuberculous pneumonia. Hemoptysis or asthma.

Physical examination: - Normal,
Diagnosis is based on history of contact, Clinical symptomotology, X-ray findings, and recent tuberculine positivity. In some cases signs of pulmonary consolidation, collapse or pleural effusion are present. Blood examination shows raised ESR and lymphocytosis.

Post-Primary Tuberculosis.
Pathogenesis and pathology:-occurs in one of the four ways:
1. The direct progression of primary lesion,
2. Reactivation of a quiescent primary focus.
3. Hematogenous infection of lung from Lymph nodes, tonsils, etc. And
4. RE infection or Super infection

Post-primary Pulmonary tuberculosis is characterized by tendency for early cavitation, limitation of the disease process and healing. The upper lobes are more commonly affected.

Depending upon the resistance two pathological forms are seen
1. Slowly progressive nodular form in individuals who possess resistance and
2. Fibrocaseous form with tendency for cavitation If the resistance is low
In the nodular form sputum shows only less number of tubercle bacilli
Lung parenchyma shows lesions, the lymph node changes are minimal. The initial lesion is an exudative pneumonia. Subsequently tubercles form. They coalesce to give rise to large macroscopic lesions. The caseous material is discharged into a bronchus and coughed out, Leaving behind a cavity. The wall of the cavity teems with the bacilli and its surroundings show many tubercles. The blood vessels in the cavity become aneurismal (Rassmussen’s aneurysms). They may rupture and give rise to massive haemoptysis. Healing occurs with replacement fibrosis.

Clinical features:-
Age- adolescents and young adults are commonly affected.
Onset –insidious
Classified into two groups:-
Systemic effects:-
Anorexia, Weight loss, Lassitude, Sleep sweats, evening pyrexia
Local effects:-
Cough - Persistent, sputum is mucoid or mucopurulent
Hemoptysis- Initially streaky, later profuse
Laryngitis results in hoarseness of voice
Others- pleural effusion, empyema and Pneumothorax

Signs:-
The earliest physical sign consists of a few crepitations usually situated over one or other lung apex posteriorly. There are signs of consolidation, cavitation, collapse, fibrosis, pleural effusion and Pneumothorax
As the condition is progressing, the patient becomes emaciated, productive cough becomes more pronounced and extreme cachexia develops. If left untreated death occurs due to cachexia, intercurrent infections or complications.

Complications
Early-
Occurs within months
Mild hemoptysis
Pneumothorax
Pleural effusion

Intermediate-
Occurs within several months
Massive hemoptysis
Secondary infection of cavities
Pneumothorax, pleural effusion and empyema
Progressive fibrosis with Dyspnoea
Spread to other organs such as larynx, pericardium and others
Non healing lesion due to drug resistance
Late:-
Occurring after several years:-
Pulmonary fibrosis with compensatory emphysema
Bronchiectasis
Aspergilloma
Secondary amyeloidosis
Persistence open cavities without healing

Diagnosis:-
From clinical features
From investigations-
1. Sputum examinations- Repeated examination for acid fast organisms in sputum by ziehl nelson method. Positivity of smear and culture depends on the bacterial counting the sputum. While examining sputum smear atleast 100 fields should be seen for 10 minutes before declaring it as negative. Atleast 3 bacilli should be seen before the smear is declared positive
2. Chest X-ray:- Features include
A, presense of opacities mainly in the upper zone with a patchy or nodular appearance
B, Cavitation
C, Calcification
D, Dense nodular, rounded or oval lesions
3. Increased ESR
4. Mantoux test
5. Heaf test

Differential diagnosis:-
1. Bronchiectais
2. Lung abscess
3. Cystic disease of the lung
4. Chronic pneumonia
5. tropical eosinophilia
 
Treatment:-
General
Give rest to the patient, No need of bed rest
Isolation
Rehabilitation
The control of tuberculosis
Tuberculosis control means reduction in the prevalence and incidence of disease in the community. WHO defines that the tuberculosis control is said to be achieved when the prevalence of natural infection in the age group0-14 years is of the order of 1%
The basic principle of prevention and control include two component—preventive and curative component. Curative component includes case finding and treatment. Preventive component includes BCG vaccination

National tuberculosis programme (1962)
The long term goal of NTP is to reduce the problem of tuberculosis in the community quickly to the level where it ceases to be a public health problem.
District tuberculosis programme
DTP is the backbone of NTP. The function of DTP is to plan, organize and implement the DTP in association with general health services.

Their activities includes
1. Case finding
2. Treatment
3. BCG vaccination
4. Recording and reporting of sputum positive cases
5. Supervision of peripheral health institution by giving guidance

Miliary Tuberculosis
Syn: Acute hematogenous tuberculosis
Tubercle bacilli entering the blood stream are diffusely disseminated and results in military tuberculosis. This is more common in young children as a complication of primary tuberculosis. Post-primary tuberculosis may also leads to hematogenous spread.

Pathogenesis and pathology:-
Entry of the bacilli into the blood stream is through lymphatics or by erosion of blood vessels by caseating lesions. Areas of caseaous vasculitis occurring in veins or arteries may result in the discharge of bacilli into the circulation. Numerous tubercles develop in the affected tissues. These coalesce to form multiple lesions of the size of millet seeds. All organs are affected especially lungs, liver, spleen, meninges, kidney, brain, bones and joints, intestine, skin etc. Lesions may become confluent with progress of the disease.

Clinical features:-
Disease may suddenly or may preceded by few weeks of vague ill health. There is high pyrexia with drenching night sweat during sleep, marked tachycardia, Loss of weight and progressive anemia. Cough and breathlessness occasionally present. Wide spread crepitations heard in the later stages. The liver and spleen are enlarged and palpable. Generalized lymphadenopathy present. Leucocytosis is usually absent or slight. Choroid tubercles are seen on ophthalmoscopy.

Diagnosis:-
Skiagram of the chest shows numerous small round shadows- military mottling
Choroid tubercles on ophthalmoscopy.
Tuberculous meningitis
Child suffers most
Pathogenesis and pathology:-
It occurs as a complication of miliary tuberculosis. The organisms reach the CNS in the blood stream. Small granulomas are formed in the superficial layers of the brain (Rich foci”). Bacteria reach the subarachnoid space and develop leptomeningitis. There is increased CSF. Adhesions develop in the base of the brain and these block the foramina. CSF pressure is increased. Surface of the brain covered with thick white exudates. In advanced cases the whole of the base of the brain may be covered by thick granulation tissue, which envelops the cranial nerves and major arteries. The cerebral vessels may develop endarteritis obliterans and thrombosis, this leads to cerebral infarcts.

Clinical features:-
Onset- insidious
Non specific symptoms include fever, restlessness, irritability, vomiting, and loss of appetite.
Acute onset may present with convulsions, high fever and signs of intracranial tension.
Death occurs in 4 to 8 weeks in untreated cases

Signs of meningeal irritation present in late stages
Papilledema
Complications:-
Acute complications-
Internal hydrocephalus
Cerebral infarction
Cranial nerve palsies
Convulsions
Bedsore
Chronic complications:-
Obstructive hydrocephalus
Optic atrophy
Subdural effusions
Spinal cord compression
Development of tuberculoma in the brain and spinal cord

Diagnosis:-
Early diagnosis depends on clinical features
Examination of CSF
Differential diagnosis:-
Encephalitis
Acute or subacute demyelinating lesions
Brain abscess
Tumors
Extra pulmonary tuberculosis
Tuberculosis can affect any organ and tissues of the body.
1. Gastrointestinal TB
i. Diarrhoea, malabsorbtion, intestinal obstruction, and ascitis can result from tuberculosis of intestine and peritoneum

2. Pericardium:-
i. Give rise to pericardial effusions and tamponade. Constructive pericarditis occurs as a late result of infection due to fibrosis and calcification.

3. Genito- Urinary tuberculosis:-
i. Haematuria and increased frequency of urine can be caused by renal TB

4. Lymph node tuberculosis:-
i. Lymph node involvement in any sites can occur; cervical lymph node involvement is common. Enlargement of lymph node is painless. When the caseation and liquefaction occurs, swelling becomes fluctuant and sinus formation is common.

5. Bone and Joint TB
i. Causes vertebral collapse, osteomyelitis and cold abscess formation

6. Other sites:-
i. In eyes- Phlyctenular conjunctivitis, Iritis and choroditis
ii. In skin- Lupus vulgaris and erythema nodosum

Therapeutics of TB:-
Kent’s repertory:
Chest phthisis pulmonalis:-
3 marks: Agar, Calc, Cal.phos, Hep. Iod, kali carb, lyco, phos, psor, puls, silicea, spong, sulph, ther, tub, zinc
Abdomen; Tabes mesenterica:
3 marks: - Calc
2 marks:-Ars, aur., bar-c., bar-m., calc-p., calc-s.,
1 mark :carb-an., carb-s., con., hep., iod., kreos., lyc., nat-s., tub.