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Dhiren L Shah

Paediatrician and Neonatologist, Hon. Neonatologist - Ruxamani Lying in Hospital, Hon. Paediatrician St. Elizabeth Hospital.

Tuberculosis is the manifestation of reaction between Mycobacterium Tuberculosis and the host.

In the fight between the Host- human tissue and M Tuberculosis - 3 things can happen.

1. Host wins- Organisms are wiped out.

2. Host get upper hand but all organisms are not destroyed. Few remain dormant. Whenever host immunity goes down-

e.g. Recurrent bacterial Infections.

Measles, Whooping cough.


Long term steroid therapy young age 3 yr.

3. Organisms get upper hand and disease starts.

Mycobacterium Tuberculosis

* Acid- fast, Non- sporing, Non- motile weakly gram Positive rods.

* Lipid rich cell wall accounts for resistance to the bactericidal actions of antibody and complement.

Pathogenesis of Primary Complex

The primary complex of tuberculosis includes local infection at the portal of entry and the regional lymph nodes that drain the area. The lung is the portal of entry in 98% of cases. The tubercle bacilli multiply initially within alveoli and alveolar ducts. Most bacilli are destroyed. Some survive within non-activated macrophages which carry them via lymphatics to regional lymph- nodes.

The Development of Tubercle

* In 1st 48 hours, there is infiltration with polymorph nucleocytes.

* Within a week there is appearance of monocytes and mononuclear cells.

* By the end of two weeks, giant cells and epitheloid cells appear with small number of lymphocytes.

* In 2nd month, particularly in 2nd half, there is marked entry of lymphocytes which signals the activation of body defence mechanism - or delayed.

* Hypersensitivity reaction.

Here M. T. becomes positive.

* Meanwhile at the centre, by liquefaction necrosis caseous material is formed. Now fibroblast comes at periphery and lay down the collagen tissue to form capsule to restrict the spread.

* By 6-8 months, calcium is deposited either in the capsule or in the centre.

So the Tubercle is

A caseous material in the centre with giant and epitheloid cells at periphery surrounded by lymphocytes and then collagen capsule if the resistant power of body is good. If the body immunity is weak then lymphocytic reaction is less marked and capsule may not be formed and the disease spreads. This tubercle formation occurs at primary site or within lymph nodes or at metastatic sight in miliary or disseminated tuberculosis.

The complications and sequelae of pulmonary primary tuberculosis :

* The hallmark of pulmonary primary tuberculosis is the relatively large size of regional adenitis compared with the relatively small size of the initial lung focus. In adult it is exactly opposite i.e. - Pulmonary lesions are large.

A. Alveolar complications

1. 70% of lung foci are subpleural and localised pleurisy is common.

2. Sub pleural focus may rapture in pleural cavity — pleural Effusion.

* Uncommon - 5 years at age.

* In 75% of cases it occurs within 6 months of infections.

3. Focus may rupture into bronchus.

* Bronchial cavitation.

1. Coin shadow with laminar appearance - When body resistance is good capsule is formed with collagen and calcium deposition and when resistance lowers caseous material comes forward. So this alternating process gives rise to laminar appearance.

B.Mediastinal and regional nodes and its complications

* Occurs within 3-9 months of infection.

* The rate of these complications decreases as age advances.

1. Partially blocking the bronchus by external pressure or eroding the bronchus.-

Ball- valve mechanism i.e. the air enters during inspiration to distal alveoli but can not come out during expiration due to closure of bronchus by obstruction.

—- Localised emphysema

2. Complete obstruction —-

Collapse of distal alveoli.

3. Collapse-consolidation

Collapse of partially consolidated lung or classical segmental lesion.

4. Thick liquefied caseous material is poured in the bronchus -

Localised bronchopneumonia.

5. Subcarinal lymph node rupturing into pericardium

Pericardial effusion.

C .Bronchial complication

* Cylindrical bronchiectasis.

D.Progressive primary disease

A rare but serious complication of Tuberculous infection in a child occurs when primary focus enlarges steadily and develops a large caseous centre and may form a primary cavity with large no. of TB bacilli. Here high fever is common.

E.Lympho- haematogenous disease or disseminated disease

Tubercle bacilli are disseminated to distal sites, including liver, spleen, skin, lung apices, in all cases of Tuberculous infection. Usually, this spread is asymptomatic.

The most clinically significant form of disseminated disease is miliary tuberculosis which occurs when massive numbers of TB bacilli are released into the blood stream causing disease in two or more organs. It occurs within 2-6 months of initial infection. M.T. is negative in 40% of cases of dissemited TB. Diagnosis is difficult and a high index of suspicion by the clinician is required.

Seedling may get deposited to CNS, bones, skin, kidney, peritoneum.

Upper Respiratory Tract Disease

* Laryngeal TB have a croupy cough, dysphagia, hoarseness of voice, sore throat. - Usually has extensive. Upper lobe pulmonary disease.

Middle Ear TB

* Unilateral, painless ear discharge.

* Multiple tympanic membrane perforation.

* Preauricular or anterior cervical lymphadenopathy.

* May have tinnitus, hearing loss, facial paresis.

Tuberculin Skin Test

Tuberculosis is associated with large antibody formation but they play little part in host defence. It is the cellular immunity which produces lymphokines and lytic enzymes that kill intracellular organisms. Cellular immunity as well as tissue hypersensitivity develop by 4-8 weeks. It is the tissue hypersensitivity that promotes extracellular killing. The development of delayed type tissue hypersensitivity in most individual with TB bacillus makes the tuberculin test a very important diagnostic tool.

The Mantoux Tuberculin Test is the intradermal injection of 0.1 ml containing 5 Tuberculin Units (T.U.) of purified protein derivative (PPD). The induration - and not the erythema - is measured 48-72 hours of administration. Occasional patients will have onset of induration after 72 hours; This is positive test.

Approximately 10% if immunocompetent children with TB - upto 50% of those with Meningitis or disseminated disease do not react initially to PPD but later after few months became reactive.

The Result

0 - 5 mm-- Negative

5-10 mm -- Equivocal

10-15 mm -- +

15-20 mm -- + +

20 -- + + +

Ulceration -- + + + +

False Positive Reaction

—Can be caused by cross- sensitisation to antigens of nontuberculous mycobacteria.

— They are usually less than 10-12 mm.

—Given subcutaneously.

BCG and MT

* Approximately one half of infants who receive a BCG never develop reactive M. T. and reactivity usually wanes in 2-3 years in those with initially reactive test.

* Older children and adults who receive B.C.G. are more likely to develop tuberculin reactivity but disappear after 5-10 years of vaccination.

* In general, a tuberculin reaction of 10 mm in BCG vaccinated child or adult indicates infection with mycobacterium tuberculosis.

* Prior BCG vaccinations never a contraindication to M.T.

False Negative Test

* Improperly given M.T.

* Fulminating or Miliary TB.

* Recent attack of measles, whooping cough.

* Long term steroid therapy.

* Immunosuppressant drug/ radiotherapy.

* Severe malnutrition.

* M.T. given during incubation phase.

* Congenital TB in 1st 2-3 months.

Congenital Tuberculosis occurs in two ways.

* Primary TB in mother during pregnancy.

— Seedlings on placenta —

Haematogenous spread to foetus.

* Aspiration of infected birth canal secretions and amniotic fluid.

* It is a difficult diagnosis as the symptoms and signs mimic that of septicaemia. But the high index of suspicion with careful maternal history clinch the diagnosis. The mortality is high as diagnosis is delayed.


Microbiologic basis for treatment

* TB bacilli can be killed only during replication.

* Individual organisms that are naturally resistant to each anti-tuberculous drug are present within large population of mycobacterium tuberculosis. All known resistance to M. tuberculosis is chromosomal and not passed from one organism to another. Fortunately, the natural occurrence of resistance to one drug is independent of resistance to any other drug.

* Larger the organism population, large the numbers of resistant organism.

* Fortunately in children the population is not large, so the number of resistant organisms are less, and organisms naturally resistant to two drugs are essentially non-existent.

* The major biologic determinant of success of anti-tuberculous chemotherapy is the size of the bacillary population within the host.

For patients with large bacterial population such as adult with cavities or extensive infiltrates, many naturally drug resistant organisms are present and at least 2 or 3 drugs are required.

Conversely for a child with positive M.T. but asymptomatic, the bacterial population is small, drug- resistant organisms are rare or non-existent, and single drug can be used.

* Children with primary complex or extrapulmonary TB has moderate number of organisms, so 2 drugs are used.

Drug used most commonly -

INH — 5-10 mg/ kg/ day.

RMP— 10 mg/ kg/ day.

SM — 20-40 mg/ kg/ day.

PZA— 20-40 mg/ kg/ day.

ETB — 25 mg/ kg/ day. For 6 weeks; 15 mg/ kg/ day. Upto 6 months.

* Isoniazid, RMP - both are bactericidal for intra as well as extracellular organisms.

* SM - Bactericidal for extracellular organisms.

* PZA is not bactericidal but contributes to killing of organism.

* ETB - At 25 mg/ kg - bactericidal.

15 mg/ kg - bactereostatic.

The combination of drugs prevent emergency of resistant organisms.

Treatment with single drug -isoniazid

* Positive M.T. but no disease with X-ray chest.

* 6 year of child who comes in contact with adult having TB. The duration of treatment is for 9 months.

2 Drug Therapy - INH + RMP

* Primary complex

* Pleural effusion

* Lymph - node lesions - hilar, paratracheal.

Drug — INH + RMP + SM/ PZA/ ETB

* Endobronchial TB

* Progressive primary complex

* Bone/ Skin/ Renal/ TB

Drug - SM + INH + RMP + PZA

* Miliary TB

* Disseminated TB


* Pott’s spine.

* Cavitatory TB

Indications of using steroids in childhood TB

* CNS tuberculosis

* Miliary TB - prevents alveolar - air blocks.

* Pleural effusion -

Rapid reduction in pleural fluid but clinical treatment is not shortened.

* TB constrictive pericarditis

* Endobronchial TB.

BCG vaccine has little effect on ultimate control of TB throughout the world because 8 billion doses have been given but TB still remains the commonest disease.

* It doesn’t affect the chain of transmission.

* But in our country where TB is rampant causing high mortality and morbidity - BCG does reduce the risk of Disseminated or Miliary TB, serious CNS TB. So BCG vaccine should be given to all children during infancy.

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