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Primary tuberculosis

doc. Kravchenko N.S.

Tuberculosis which develops in primary infected people is called

primary tuberculosis. It is diagnosed often in children and teenagers.
More rarely in young people.
Topical sings of primary tuberculosis are:
a) The intensity tuberculin test reaction;
b) lesion of lymphatic system (especially lymphatic nodes);
c) tendency to lymphogenous and hematogenous dissemination;
d) state of hypersensibilization of organism to pathogenic agent;
e) possibility of spontaneous recovery.
Tuberculin intensifier is the appearance of first positive tuberculin reaction
after a negative one within a year or its increase in persons vaccinated.
Primary tuberculosis usually displays in three main forms:
- tuberculous intoxication in children and teenagers (tuberculosis without
established localization);
- primary tuberculous complex;
- tuberculosis of intrathoracic lymphatic nodes.

The clinical expression of disease caused by

Mycobacterium tuberculosis is greatly different in infants,
children, and adolescents than in adults. Whereas most adult
pulmonary tuberculosis is caused by a reactivation of dormant
organisms that are lodged in the apices of the lungs during
hematogenous dissemination at the time of infection, pediatric
tuberculosis is usually a complication of the pathophysiologic
events surrounding the initial infection. The interval between
infection and disease is usually long - years to decades - in
adults but is often only weeks to months in small children.
Children are more prone to extrapulmonary tuberculosis but
rarely experience infectious pulmonary disease. As a result of
the basic difference in pathophysiology of tuberculosis
between adults and children, the approach to diagnosis,
treatment, and prevention of infection and disease in children
is very different.

The terminology used to describe various stages and presentations
of pediatric tuberculosis often has been a source of confusion for
physicians. It follows the pathophysiology, but the stages are often less
distinct in children.
Exposure means that the child has had significant contact with an
adult or adolescent with infectious pulmonary tuberculosis. The contact
investigation examining those persons close to a suspected case of
tuberculosis with a tuberculin skin test, chest radiograph, and physical
examination is the most important activity in a community to prevent
tuberculosis in children. The most frequent setting for exposure of a
child is the household, but it can occur in a school, day care center, or
other closed setting. In this stage, the tuberculin skin test result is
negative, the chest radiograph appears normal, and the child lacks
signs or symptoms of disease. Some exposed children may have
inhaled droplet nuclei infected with M. tuberculosis and have early
infection, but the clinician cannot know it because it takes up to 3
months for delayed hypersensitivity to tuberculin a positive skin test
result to develop.

Infection occurs when a person inhales droplet nuclei containing

M. tuberculosis, which becomes established intracellularly within the lung
and associated lymphoid tissue. The hallmark of tuberculosis infection is a
reactive tuberculin skin test. In this stage, the child has no signs or
symptoms and the chest radiograph either appears normal or reveals only
granuloma or calcifications in the lung parenchyma, regional lymph nodes,
or both. In many countries, all children with tuberculosis infection should
receive treatment, usually with isoniazid (INH), to prevent the development
of disease in the near or distant future.
Disease occurs when signs or symptoms or radiographic
manifestations caused by M. tuberculosis become apparent. The word
tuberculosis refers to disease. Not all infected patients have the same risk
of developing disease. An immunocompetent adult with untreated
tuberculosis infection has approximately a 5% to 10% lifetime risk of experi
encing disease; one half of the risk occurs in the first 2 to 3 years after
infection. Historical studies have shown that up to 40% of
immunocompetent infants with untreated tuberculous infection develop
disease often serious, life threatening forms within 1 to 2 years.

EPIDEMIOLOGY Disease and Infection

Because most children with tuberculous infection and disease
acquired the organism from an adult in their environment, the
epidemiology of childhood tuberculosis tends to follow that in adults.
The risk of a child acquiring tuberculous infection is environmental,
determined by the likelihood that he or she will be in contact with an
adult with contagious tuberculosis. In contrast, the risk of a child
developing tuberculous disease depends more on host immunologic
and genetic factors.
It is estimated that the worldwide annual burden of tuberculosis
on children is 1.5 million cases and 500,000 deaths. Adult tuberculosis
case numbers have increased over the past decade in every region of
the world except Western Europe. There are no comparable data, but it
is likely that childhood tuberculosis has grown in numbers as well.
Most children are infected with M. tuberculosis in the home, but
outbreaks of childhood tuberculosis centered in elementary and high
schools, nursery schools, family day-care homes, churches, school
buses, and stores still occur. In most cases, a high-risk adult working in
the area has been the source of the outbreak.

The recent epidemic of human immunodeficiency virus (HIV)

infection has had a profound effect on the epidemiology of
tuberculosis among children as a result of two major mechanisms:
(1) HIV-infected adults with tuberculosis may transmit M.
tuberculosis to children, some of whom will develop tuberculosis
(2) children with HIV infection may be at increased risk of
progressing from tuberculosis infection to disease. Several studies of
childhood tuberculosis have demonstrated that increased case rates
have been associated with a simultaneous increase among HIVinfected adults in the community.
In developing countries, tuberculosis infection rates among the
young population average 20% to 50%. In most children in the United
States, the risk is less than 1%, but in some urban populations the risk
is much higher.

Children usually are infected by an adult or adolescent in the
immediate household, most often a parent, grandparent, or
household employee. Casual extrafamilial contact is the source of
infection much less often, but babysitters, schoolteachers, music
teachers, school-bus drivers, parishioners, nurses, gardeners, have
been implicated in individual cases and in hundreds of mini-epi
demics within limited population groups. Within the household of an
infectious adult, the infants and toddlers almost always are infected.
Also at high risk are the older children and teenagers who help the
ailing adult. Adults with pulmonary disease who are receiving regular,
appropriate chemotherapy probably rarely infect children; much more
dangerous are those with chronic tuberculous disease that is
unrecognized, inadequately treated, or in relapse because of
development of resistance.
Children with tuberculosis rarely, if ever, infect other children.
Many children with the disease have tuberculin-negative parents.

When transmission of M. tuberculosis has been documented in

children's hospitals, it almost invariably has come from an adult with
undiagnosed pulmonary tuberculosis. In tuberculous children, M.
tuberculosis in endobronchial secretions are relatively sparse, and
productive cough is not at all characteristic of endothoracic
tuberculosis or of miliary disease. When young children cough, they
lack the tussive force of adults.
Adolescents with typical reactivation-type pulmonary tuberculosis
may be as infectious as adults. Children nevertheless play an
extremely important role in the transmission of tuberculosis, not so
much because they are likely to contaminate their immediate
environment but because they harbor a partially healed infection that
lies dormant, only to reactivate as infectious pulmonary tuberculosis
many years later under the social, emotional, and physiologic stresses
arising during adolescence, adulthood, or old age. Thus, children
infected with M. tuberculosis constitute a long-lasting reservoir of
tuberculosis in the population.

Primary tuberculosis is always result of exogenous infection.
The infection penetrates into organism by:
- aerogenic (the most often way of penetration)
- alimentary;
- contact way.
1. The primary complex of tuberculosis consists of local disease at the
portal of entry and the regional lymph nodes that drain the area of the
primary focus. In more than 95% of cases the portal of entry is the
lung. M. tuberculosis within particles larger than 10 (xm usually are
caught by the mucociliary mechanisms of the bronchial tree and are
expelled. Small particles are inhaled beyond these clearance
mechanisms. However, primary infection may occur anywhere in the
2. Ingestion of milk infected with bovine tuberculosis can lead to a
gastrointestinal primary lesion.
3. Infection of the skin or mucous membrane can occur through an
abrasion, cut, or insect bite.

The number of M. tuberculosis required to establish infection in

children is unknown, but only several organisms are probably
necessary. The incubation period in children between the time the
M. tuberculosis enter the body and the development of cutaneous
hypersensitivity is usually 2 to 12 weeks, most often 4 to 8 weeks.
The onset of hypersensitivity may be accompanied by a febrile
reaction that lasts from 1 to 3 weeks. During this phase of
intensified tissue reaction, the primary complex may become
visible on chest radiograph. During this time, the primary focus
grows larger but does not yet become encapsulated. As
hypersensitivity develops, the inflammatory response becomes
more intense and the regional lymph nodes often enlarge. The
paren-chymal portion of the primary complex often heals
completely by fibrosis or calcification after undergoing caseous
necrosis and encapsulation. Occasionally, the parenchymal lesion
may continue to enlarge, resulting in focal pneumonitis and
thickening of the overlying pleura. If caseation is intense, the
center of the lesion may liquefy, empty into the associated
bronchus, and leave a residual primary tuberculous cavity.

During the development of the parenchymal lesion and the

accelerated caseation brought on by the development of hypersensitivity,
M. tuberculosis from the primary complex spread via the bloodstream and
lymphatics to many parts of the body. The areas most commonly seeded
are the apices of the lungs, liver, spleen, meninges, peritoneum, lymph
nodes, pleura, and bone. This dissemination can involve either large
numbers of bacilli, which leads to disseminated tuberculous disease, or
small numbers of bacilli that leave microscopic tuberculous foci scattered in
various tissues. Initially, these metastatic foci are usually clinically
inapparent, but they are the origin of both extrapulmonary tuberculosis and
reactivation pulmonary tuberculosis in some children.
The tubercle foci in the regional lymph nodes develop some
fibrosis and encapsulation, but healing is usually less complete than in the
parenchymal lesions. Viable M. tuberculosis may persist for decades after
calcification of the nodes. In most cases of primary tuberculosis infection,
the lymph nodes remain normal in size. However, because of their location,
hilar and paratracheal lymph nodes that become enlarged by the host
inflammatory reaction may encroach upon the regional bronchus. Partial
obstruction caused by external compression may lead at first to hyperinfla
tion in the distal lung segment. Such compression occasionally causes
complete obstruction of the bronchus, resulting in atelectasis of the lung

More often, inflamed caseous nodes attach to the bronchial

wall and erode through it, leading to endobronchial
tuberculosis or a fistulous tract. The extrusion of infected
caseous material into the bronchus can transmit infection to the
lung parenchyma and cause bronchial obstruction and
atelectasis. The resultant lesion is a combination of pneumonia
and atelectasis. The radiographic findings of this process have
been called epituberculosis, collapse-consolidation, and
segmental tuberculosis. Rarely, tuberculous intrathoracic lymph
nodes invade other adjacent structures such as the pericardium
or esophagus.
Massive lympho-hematogenous dissemination leading to
meningitis or miliary or disseminated disease occurs in 0.5% to
2% of infected children, usually no later than 3 to 6 months after
infection. Clinically significant lymph node or endobronchial
tuberculosis usually appears within 3 to 9 months. Lesions of the
bones and joints usually take at least a year to develop; renal
lesions may be evident 5 to 25 years after infection. In general,
complications of the primary infection occur within the first year.

How Children with Tuberculosis Are Discovered

In the developing world, the only way children with
tuberculosis disease are discovered is when they present
with a profound illness that is consistent with tuberculosis.
Having an ill adult contact is an obvious clue to the correct
diagnosis. The only available laboratory test usually is an
acid-fast smear of sputum, which the child rarely produces.
In many regions, chest radiography is not available. To aid in
diagnosis, a variety of scoring systems have been devised
that are based on available tests, clinical signs and
symptoms, and known exposures. However, the sensitivity
and specificity of these systems can be very low, leading to
both over- and under-diagnosis of tuberculosis.

In industrial countries, children with tuberculosis usually

are discovered in one of two ways.
1) One way is consideration of tuberculosis as the cause of
a symptomatic pulmonary or extrapulmonary illness.
Discovering an adult contact with infectious tuberculosis is an
invaluable aid to diagnosis; the yield from a contact investi
gation usually is higher than that from cultures from the child.
2)The second way is discovery of a child with pulmonary
tuberculosis during the contact investigation of an adult with
tuberculosis. Typically, the affected child has few or no symp
toms, but investigation reveals a positive tuberculin skin test
result and an abnormal chest radiograph appearance. In some
areas of the United States, up to 50% of children with
pulmonary tuberculosis are discovered in this manner, before
significant symptoms have begun.

Tuberculous intoxication in children and teenagers is a

clinical form of primary tuberculosis, which is characterized
by complex of symptoms of functional derangement without
local manifestation of disease.
Morfological substrat of tuberculous intoxication are
minimal specific (tuberculous granuloma with areas of
microcaseose) and paraspecific changes, usually in
lymphatic system.

Clinical manifestations.
Complaints on aggravation of appetite, sweating, not
constant subfebrile body temperature, emotional instability,
decreasing of memory.
Objectively: paleness, decreasing of skin turgor,
micropoliadenitis (increasing of quantity and sizes of periferal
lymphatic nodes more than five groups). During percussion
changes over the lungs are absant. Auscultation: sometimes
dry rales.
Laboratory and other methods of investigation.
In hemogram can be slight leukocytosis with an insignificant
shift to the left, lymphopenia, eosinophilia, monocytosis, ESR is
normal or increased.
Roengenological examination.
In reviewable roentgenogram and tomogram of lungs there
are no changes usually. Sometimes it can be strengthen of
lungs picture.

Differential diagnosis.
It is necessery to exclude diseases accompanied by
intoxication: chronical sourses of infection of oral cavity and
epipharynx: chronical tonsillitis, pielonephritis, rheumatism,
hepatocholecystitis, helminthic invasions.
Main diagnostic criterions of tuberculous intoxication are:
- tuberculin intensifier
- symptoms of intoxication
- absence of roentgenological changes
- excluding of intoxication with different ethiology
Isoniazidum 10mg/kg of weight + rifampicinum10 mg/kg or
etambutol 20mg/kg for 4-6 months, vitamins B1, B6, C.

Primary tuberculous complex

Primary tuberculous complex is characterized by
development of specific general changes in lungs (primary
effect), lesion of intrathoracic lymphatic nodes and
Patological anatomy: zone of tuberculous granulations and
caseous necrosis is forming in lungs. Zone of perifocal toxic
edema and serofibrinous inflammation is forming around zone
of specific inflammation. These changes form primary affect.
Infection extence in lymphatic vessels from primary affect to
the root of lungs (lymphangitis) and injury of root lymphatic
nodes is taking place (lymphadenitis).
fig. 1

Clinical manifestations.
Asymptomatic course of disease can be present under little specific
changes in lungs. Complaints: subfebrile temperature, decrease of
body weight, bad appetite, quick tiredness. Coughing happens seldom.
Inspection: paleness, decrease of skin turgor, paraspecific changes,
micropolyadenitis. These changes can be absent.
Percussion: dullness over lung component with a big size.
Weakend breathing with streached exhale.
Hemogram: Leucocytosis 10-13 T/l, insignificant shift to the left,
lymphopenia, monocytosis, SSE 20-25 mm/h.
Tuberculin test - intensivity of tuberculin reaction, hyperergic reaction.
MBT are rarely to be found.
X-ray diagnostics:
Phases: 1) infiltrative or pneumonic;
2) resorbtion (suction,bipolarities);
3) scarring
4) calcification.
fig. 2

Complications are connected with lung component:

- decomposition of primary affect with primary cavern forming
Complications connected with regional lymphadenitis:
- hematogenic dessimination
- lymphogenic dessimination
- pleuritis
- extencing of specific process from lymphatic node to
Its results:
a) formation of fistula
b) dispersion of caseous masses, bronchogenic
c) disorder of bronchial permeability
fig. 3

The differential diagnostics is performed with :

1) Pneumonia;
2) Eosinofilic infiltration;
3) Peripheral or central cancer.
Unspecific pneumonia usually beging sharply after
catching cold, respiratory infection with the high body
temperature, general weakness, pespiration,
considerable shortness of breath.
Auscultatorily is defned many dry and moist rales.
Blood examination: high leucocitosis and high ESR.

Tuberculosis of intrathoracic lymphatic nodes is specific

injury of lymphatic nodes of lungs root and mediastinum.
Pathomorphological forms:
a) hyperplastic
b) caseous form
fig. 4

The clinic of uncomplicated tuberculosis of intrathoracic lymphatic

nodes is similar to that of primary tuberculous complex.
Clinical-radiological forms of tuberculosis of intrathoracic nodes:
1) Small form deformation and strengthening of pulmonary
picture near lung root, decreasing of root structure.
2) Infiltrative root shadow is widened with not clear contour
3) Tumorshaped widening of mediastinum or lung root with
polycicle clear contour

Differntial diagnosis is conduction with:

Lymphogranulomatosis, lymphosarcoma, lymphoid leukemia,
unspecific adenopathy, mediastinal cancer, sarcoidosis.
For this the following procedures are performed:
1) X-ray examination in right and lateral projections;
2) Tomography on bifurcation level ( middle microscopic section);
3) Tuberculin tests, bronchoscopy as well as punctured or operative
Treatment of local forms of:
Stationary :
2 months - Isoniazidum 10 mg/kg of body weight + Rifampicinum 10
mg/kg of body weight + Pyrazinamidum 25 mg/kg of body weight.
Under extend process, complications prescribe: + streptomycinum
15-20 mg/kg of body weight.
Next 4 months - Isoniazidum + rifampicinum or ethambutolum.
General course of treatment lasts for 6-9 mounths. Vitamins B1, B6,
C, desensibilizinig preparations are also prescribed.