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PRIMARY COMPLEX

&

B. C. G. Vaccination

By

Dr. KUL BAUSHAN

Research Officer

National Tuberculosis Institute

Bangalore.
 PRIMARY COMPLEX AND
BCG VACCINATION
BY :

Dr. KUL BHUSHAN

Research Officer

National Tuberculosis Institute, Bangalore

Lodgement or implantation of tubercle bacilli, at any site, in the body of an animal or human
being is called the primary infection. The tissue response, consisting of mainly the
polymorphonuclear leucocytic accumulation, to begin with, at the site of primary infection is
termed as primary focus. The tubercle bacilli from the primary focus are soon transported along
the lymphatics to the regional draining lymph nodes, causing inflammatory response both in the
lymphatics, where tiny nodular foramations occur, and in the lymph nodes which enlarge. The
primary focus, the lymphangitis and regional lymphadenitis together constitute primary complex.

The initial polymorphic leucocytic reaction in the primary focus and the lymphnodes are
soon augmented by large monocytes, which later transform into epithelioid cells, and the
Langhans' giant cells. Occasionally foreign body giant cells may also be seen. In about 2 to 4
weeks the reticuloendothelial system, particularly that in the thymus which plays major role,
develops cell mediated (through activated large monocytes) tuberculo hypersentitivity and
immunity. At this time person becomes tuberculin reactor and caseous necrosis occurs in the
centre of both the primary focus and the lymphnode which liquefies to different degree Serous
pleural effusion, phlyctenular conjuctivitis, iritis or iridocyclitis and erythema nodosum
sometimes seen at sites far removed from primary complex, are the different tuberculo-allergic
manifestations. In fact these conditions may draw attention to tuberculous infection for the first
time.
 The primary complex generally exists singly and only occasionally in multiple units. In
overwhelming majority of cases primary complex occurs in the lungs and only in about 5% cases
they are distributed among the intestines, Oropharynx, the skin and other rarer sites. The primary
focus in the lungs is called as Ghon focus.' It generally occurs in the subpleural region of any
lobe. Mostly hilar and inter-pleural lymph nodes are involved to form the primary complex.
Some times, however, even the tracheobronchial glands are also affected. The pulmonary
primary focus spreads to the adjacent parenchymal tissue leading to extensive caseation necrosis,
liquefaction and cavitation, extension of lesion through bronchi to other parts of the same and
even the opposite lung. Even the necrosed material from the hilar glands can be drained to the
bronchus. In both cases tuberculous pneumonia can occur in the related lung segments.

The drainage of excessive necrosed material into the bronchus or pressure from the enlarged
lymphnodes on the bronchus lead to complete or partial obstruction causing collapse of
corresponding degree. Some times failure on the part of a lobe to re-expand may result in
bronchiectatic changes. In vast majority of cases, however, the constituents of the primary
complex resolve completely leaving no radiological sign, and it is only occasionally that a few
cases of pulmonary primary complex are indisputably diagnosed

The lymphnode involement in the other rare sites of primary focus and spread of lesion to
adjoining areas through spil over of necrotic liquefied tuberculous material or through
lymphatics and or the blood stream are well known The massive haematogenous disseminotion
of tubercle bacilli from the primary focus or its lymphnode component, to distant parts of the
body gives rise to a few to widely disseminated multiple active lesions particularly when spread
is through venous channels. The commonest lesions caused by dissemination through blood
stream are the tuberculous meningitis and miliary disease.

Primary complex of the lungs is mostly an over diagnosed entity in paediatric age, where
children are put to unnecessary treatment. The misleading feature is the normal hilar vascular
region being mistaken for the enlarged lymph nodes. They are mostly due to difficulties in taking

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X-ray pictures of young subjects and the fact that much more tuberculous infection is suspected
in paediatric age than justified. It is difficult to locate cause for presenting symptoms of cough,
rise of temperature and failure to thrive etc., elsewhere. Similarly, the cervical lymph adenopathy
is also excessively misdiagnosed as due to tuberculous pathology though it is mostly due to scalp
conditions which predominantly includes lice infestation, the caries of teeth and various other
non tubercular oropharyngeal conditions

Most of the primary complexes (lesions) become inocuous after a short time harbouring the
tubercle bacilli with arrested activity, but live and potentially virulent. There is always a lurking
danger of these bacilli flaring up in the future to progressive tuberculous disease. This generally
occurs when general body resistance is lowered due to any of the well known reasons.

BCG vaccination is aimed at establishing a' controlled primary complex' ,by, intradermal
injection of attenuated (harmless) live, bovine strain of tubercle bacilli, in an attempt to forestall
the infection with virulent tubercle bacilli among the previously uninfected persons. At the site
of injection, generally the lower half of the left deltoid region, a primary focus is created from
where some bacilli are transported through the lymphatics to the axillary lymphnodes to
complete the formation of primary complex. If the injection is given in th upper parts of the
deltoid region the lymphnodes in infra-clavicular, suprs-clavicular or cervical regions are also
involved. Most of the injected BCG organisms remain at the site of vaccination, some migrate
through the blood stream to other parts of the body. If and when they settle at other sites in the
body, simultaneous multiple primary foci involve relevant draining lymphnodes and benign
multiple primary complexes are established.

In about 2 to 4 weeks time, as in the case of virulent tuberculous infection described earlier,
cell mediated immunity and delayed hyper-sensitivity are initiated. The latter is evidenced by
inflammatory process at the site of BCG vaccination. It is characterised by erythema and
induration, followed soon by nodule formation which on caseation necrosis and liquefaction
changes into a pustule. This pustule bursts forming an ulcer with undermined edges. Healing of
the ulcer takes place in 4 to 6 weeks from its appearance leaving a thin, depressed, shining scar

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with undermined margins. The cell mediated delayed hypersensitivity is completed in about 6 to
8 weeks time and the vaccinated persons show positive reaction to tuberculin test.

In more than 99% cases regional lymphnode enlargement and caseation etc., after BCG
vaccination go un-noticed. It is only when too many BCG organisms or too large a volume of
BCG vaccine are injected or injection is deep, that clinical lymphnode enlargements are likely to
occur (in India from 0-1 to 0.3%). In some cases among them only on liuefaction of caseous
material lymphnodes become soft and a few burst into a sinus formation. But, they are painless
without any constitutional symptoms. Clinical lymphnode enlargements also occur when
needles, syringes or vaccine are contaminated. Lymphnode enlargements due to contaminants
are easily distinguishable from those caused only by BCG organisms, as they are painful tend to
suppurate much faster, and are likely to be accompanied by constitutional symptoms.

From the above it is clear that the events following BCG vaccination are completely benign,
causing no disease or spread of lesion laterally or to distant organs but at the same time inducing
immunity and hypersensit vity.

A subsequent BCG vaccination and infection occuring in a person, who has had a primary
infection or prior BCG vaccination, results in Koch's phenomenon, which is characterised by an
acute anflammatory process starting within 24 hours. This is soon followed by local necrosis and
liquefaction and seems to be an effort on the part of defensive mechanism to restrict the activity
of the invading organisms, if not eliminate them from the body. It may also be stated here that in
the Koch's phenomenon, though caseation, necrosis etc., occur at the site of subsequent entry of
tubercle bacilli the regional lymph nodes are not involved.

This, however, should not be construed to mean the BCG vaccinanation is likely to prevent
tuberculous infection. Depending on the environment of vaccinated population or individual
repeated infections continue to occur. They are treated as secondary, infections. Given the
appropriate host conditions and virulence and dose of disease producing tubercle bacilli these
infections may result in disease. It is only the secondary type of disease that is likely to occur

5
after these infections in BCG vaccinated individuals. It is for this reason mainly that immunity in
tuberculosis (also after BCG vaccination) is stated as incomplete.

The advantages of primary complex established with BCG vaccination prior to a change of
natural infection are that primary tuberculosis disease caused by it can be ruled out; there is no
chance of spread of disease to adjoining parts; haematogenous dissemination of disease leading
to milliary meningeal tuberculosis is prevented and so also the danger of future focal flare up and
chances of disease after infection are reduced

Besides these, the dissemination of attenuated BCG organisms from site of vaccination or
lymph nodes to other organs or parts of the body through blood stream does not result into
disease.

To obtain maximum advantage from the BCG vaccination it should be given at the earliest
possible time in life of an individual. For reasons of operational convenience and acceptability,
BCG vaccination is best given soon after birth. It is easily manageable in the maternity homes or
hospitals in urban areas. In the rural areas because of very obvious reasons it is, so far, not
possible to vaccinate the new borns. According to recently introduced integrated approach of
BCG vaccination’ it is envisaged to be given within one year of birth of a child. If it become
operationally possible to arrange BCG vaccination at birth in rural areas, one need not postpone
it to another date.

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REFERENCES. ......
1. Boyd. W , A Text Book of Pathology (Eighth Edition 1977), Lea and Febigec,
Philadelphia

2. Robins S L., Pathologic Basis of Disease (1974), W B. Saunders Company, Philadelphia.

3. Willis. R. A:, The Principles of Pathology (Second Edition 1961) Butterworths, London

4. Pagel. W, Simonds FAH., Nacdooald N, Pulmonary Tuberculosis. (Third Edition, 1953)

Oxford University Press, London

5. Rao, K. N., (Editor) Text Book on Tuberculosis (First Edition 1972), Kohtari Book
Depot, Bombay.

6. Kirk Patrick. C. H. Raynolds. H. Y. (Editors) Immunologic and infectious reactions in the

lung (1976), Marccl Dekker. Inc. New york.

7. Nossal. G. J. V. Antibodies and Immunity (1969) Basic Books Publication. New York

8. Rosenthal. S BCG Vaccination against Tuberculosis (1957) Little Brown & Co.,

9. Irwine. N., BCG and Vole Vaccine (1951) NAPT, London

10. Mande R., BCG Vaccination (1968) Dawson's of Pall Mall, London

11. Patel T. B , Shah V. D., Nature of allergy in 1000 new born BCG vaccinated infants
(1960), Proceedings of the Sixteenth TB Workers Conference held in poona, India.

12. Naidu C. R., Somayya K. A. Study of allergy in 1000 new born vaccinated with BCG
(1961) Proceedings of the Seventeenth TB Worker's Conference held in Cuttack, India.

13. Kul Bhushan Tuberculin test and its limitations (1975), Guest lecture in Karnataka State
TB Conference, Hassan.