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2.1. Motivation. TB Disease in Children Under 15 Years of Age (Also Called
2.1. Motivation. TB Disease in Children Under 15 Years of Age (Also Called
2.1. Motivation. TB Disease in Children Under 15 Years of Age (Also Called
2. Primary TB.
2.1. Motivation
2.2. Definition
2.3. Route and manner of infection
2.4. The lung changes after infection.
2.3.1. Basic types of tissue change
2.3. The lymph nodes at the root of the lung.
2.1. Motivation. TB disease in children under 15 years of age (also called
pediatric tuberculosis) is a public health problem of special significance
because it is a marker for recent transmission of TB. Also of special
significance, infants and young children are more likely than older
children and adults to develop life-threatening forms of TB disease (e.g.,
disseminated TB, TB meningitis). Among children, the greatest numbers
of TB cases are seen in children less than 5 years of age, and in
adolescents older than 10 years of age. BCG, or bacille Calmette-Guerin, is
a vaccine to prevent TB disease. BCG is used in many countries to prevent
childhood TB disease. However, the BCG vaccine is not generally used in
the United States, because of the low risk of infection with TB bacteria and
the variable effectiveness of the vaccine. The BCG vaccine should only be
considered for very select persons who meet specific criteria and in
consultation with a TB doctor.
2.2. Definition. The clinical form of primary tuberculosis, which is
characterized by specific inflammation in lungs (by primary affect), lesion
of intrathoracic lymphatic nodes (lymphadenopathy) and lymphangitis.
Lung localization occurs in 90 %, abdominal – in 10 % of primary
tuberculous complex cases.
2.3. Route and manner of infection. M. tuberculosis is a species of the
genus Mycobacterium, family mycobacteriaceae, order Actinomy-cetales.
The organisms are nonmotile, nonsporulating, aerobic, acid-fast rods.
Growth is slow, the organisms ordinarily not becoming visible for 2 weeks
or more, depending on the size of the inoculum and the medium. Colonies
are opaque, dry, off-white to cream-colored, with a nodular or wrinkled
surface and irregular edges. Optimum growth temperature is 37°C.
Multiplication does not occur at 25° or at 45°C. Ordinary laboratory
media do not support growth, and special substances such as egg,
potato, blood, or albumin are necessary for enrichment. A lipid substance
known as cord factor causes the bacilli to orient themselves parallel to one
another so that growth occurs in the form of serpentine cords, especially
on slide and membrane cultures and in liquid media without wetting
agents. Endogenous catalase is present in all strains except those resistant
to isoniazid. The human tubercle bacillus produces significantly greater
amounts of niacin than any other species of Mycobacterium.
M. tuberculosis is highly pathogenic for guinea pigs but not for rabbits or
chickens. Progressive disease can be produced in mice with the inoculation
of large numbers of bacilli. Many strains highly resistant to isoniazid lose
their pathogenicity for guinea pigs as well as their catalase activity.
In the vast majority of children, infection is acquired by inhaling
airborne infected droplet-nuclei derived from the sputum of an adult with
cavitary pulmonary tuberculosis. The source person need not be sick and
may not even be aware that he is dangerous to others. Most newly acquired
infections are from household contacts, especially in small children
exposed to adults with cavitary disease. Such factors as overcrowding and
an impoverished mode of living have an important effect upon the
infection rate. Numerous reports of "contained" or micro epidemics
tuberculosis support the concept of airborne infection as the chief mode of
transmission.
Tuberculosis organisms may also gain entrance into the body by
direct inoculation through the skin. Ingestion is rarely implicated since
pasteurization of milk and tuberculosis eradication among cattle have
become enforced public health measures. Infection is not transmitted by
fomites or by contact with clothing, bed linens, or personal articles of a
source person, as was once believed. Contaminated materials such as
urine, feces, fluid from draining sinuses, and sputum may serve as sources
of infection unless properly handled and disposed of. Children are often
infected from coughing or spitting adults. When an adult coughs many
small drops of liquid (spit) are forced into the air. If that adult has
tuberculosis in his or her lungs many of the drops carry bacilli. The largest
of the drops fall to the ground. But the smallest, which cannot be seen,
remain in the air and move with it. Out of doors or in well ventilated
rooms the small drops are carried away in the moving air. But in сlosed
rooms, huts or small spaces they remain in the air and increase in number
as the person continues to cough. Everyone sharing the room with the
'cougher' and breathing the same air runs the risk of breathing in tubercle
bacilli (ТВ). Those nearest to the person coughing are most likely to do so.
The danger is greatest when the 'cougher' does not take any care. He
should cover his or her mouth, turn away from the other persons or
children and spit into something which is then covered and kept closed.
So the infectious mother is a danger to her infant or children. Both
parents are dangerous in small living or sleeping spaces. Almost always
when young children are infected the infection comes dangerous in small
living or sleeping spaces. So would be an infectious teacher in the
classroom, an infectious doctor or dentist in the clinic or health center or
an infectious nurse or midwife or health worker in the home or hospital, a
shopkeeper in his shop or a bus driver in his bus. Almost always when
young children are infected the infection comes from a member of the
family group or a near neighbor. When older children are infected and the
immediate family is clear, look for a possible infector in school, in clinic,
in church, in public transport or wherever children come in contact with
adults inside buildings or small spaces. In these situations, the bacteria are
taken into the lungs with the breath and this is much the commonest way
of infection. But it is not the only way.
ТВ can reach children in milk or food and infection can then begin in
the mouth or intestine. Milk can carry bovine ТВ if cows in the area have
tuberculosis and the milk is not boiled before use. When that happens the
primary infection is in the intestine, or sometimes in the tonsils. But
human infection with bovine badly seems to be uncommon in many high
prevalence countries.
Unbroken skin seems to resist ТВ if they fall upon its surface. But if
there has been a recent cut or break ТВ may get in and cause an infection
as they do in the lungs. As might be expected, skin infection is most likely
on exposed surfaces such as the face or legs or feet or less often on the arm
or hand. These primary lesions are not common. But it is easy to forget
that such a lesion may be tuberculous, even when the nearest lymph nodes
are enlarged.
2.4. The lung changes after infection.. The concepts herein
presented have been gleaned in part from animal experimentation and from
the older records of pathologic observations on human autopsy material, to
which have been added more recent data from surgically resected
specimens as presented in die important monographs by Medlar and
Canetti. Aside from studies of pathologic tissues, we largely depend on
observations made on die behavior of pulmonary lesions as seen
roentgenographically for detecting the various patterns of development of
clinical tuberculosis. Newer information on cellular immunity has
provided some insight into the specific mechanisms underlying the tissue
changes subsequently described.
When the fine drops carrying the bacilli are breathed in they may
cross over defense mechanism of clearance and are carried through the air
passages to just under the surface of the lung. There they remain and the
ТВ slowly multiply in numbers. As that happens some are carried through
the Cohn’s pores into the interstitial tissue to begin travelling along the
lymph vessels to the nearest lymph nodes beside the bronchi. In BCG
vaccinated organism they meet with the place of hypersensitivity
surrounding BCG granulomata and may be broken forming the first
cockpit for struggle between TB and host defences. In well-nourished
children small quantity TB are swallowed by macrophages and
disintegrated without a trace (complete phagocytosis). In other cases the
presence of the bacilli causes a reaction and the defence cells of the body
begin to collect. In about 4-8 weeks there is a small area at the centre of
this process where the host tissues are dead (caseation) and around that
area is an increasing ring of defence cells. About this time most people
become sensitive to tubercle bacilli, as shown by a positive tuberculin skin
test. The changes in the lung and the same changes in the lymph nodes are
together known as the Primary Complex. In the immune body these
changes are small and can’t be recognized with the help of any known
techniques excluding the Mantoux test. From that time the result depends
upon the power of the child to resist the multiplication of the bacilli and
limit the amount of caseation.
That power varies with age, being least in the very young. It also
varies with nutrition. Poor nutrition lowers body defences. Most people
manage, slowly over many months, to heal both the focus in the lung and
that in the lymph nodes. But it takes time and ТВ can remain inactive but
living and capable of multiplication for many years.
The understanding of allergy and immunity in tuberculosis began
with the work of Lurie, followed by development of modern concepts of
delayed hypersensitivity and cellular immunity. The relation between
immunity and delayed hypersensitivity, however, remains controversial
even today. Immunity to tuberculosis may be either natural or acquired,
and it is the latter which is so intimately associated with the development
of allergy.
The former response presumably would be associated with a more
favorable outcome. Canetti has described the effects and histologic sites of
action of immune responses in humans in his quantitative studies on the
occurrence of tubercle bacilli in the various lesions and in the morphologic
patterns of disease as seen in surgically resected lungs and autopsy
specimens. The basic tissue elements thought to be responsible for
immunity are the macrophages, which phagocytize and destroy tubercle
bacilli, and caseation necrosis, in which bacilli are destroyed in large
numbers. There is now little doubt that the macrophages are an important
part of the complexity of chemical mechanisms involved in cellular
immunity to be described later.
More important basically than the places where tubercle bacilli are
destroyed are the mechanisms by which the bacillary destruction is
completed. The effectiveness of these immune mechanisms is influenced
by a number of environmental, hereditary, and developmental factors,
including age (infancy, puberty, and senility are periods of highest disease
ate), race, nutrition, stress, cellular immunodeficiency states, diabetes, and
silicosis. Essential to the patient's recovery is the predominance of immune
forces over tubercle bacilli, despite liquefaction of the caseum and spread
of the disease, so that ultimately the tissues may effectively contain or
preferably destroy bacilli.
From the time of infection bacilli escape into the blood stream and
are carried to other parts of the body. This is more probable in no
vaccinated body. Fortunately disease does not always result. The risk may
be small for any individual child. But in a community where there are
many adults spreading infection many children will become ill because
superinfection.
The Host Immune Response to Tuberculosis.
1) Organism is phagocytosed by macrophage which is not able to destroy
virulent microorganism.
2) In the early phase of primary tuberculosis, (in the unimmunized person),
there's uncontrolled proliferation of bacilli within pulmonary alveolar
macrophages with resulting bactremia and seeding of multiple sites.
3) After 3 weeks of infection, cell mediated immunity develops.
Macrophages process mycobacterial antigen and present it to unstimulated
CD4+Tн0 cells. Under effect of IL-12 secreted by macrophages,
CD4+Tн0 cells mature into CD4+Tн1 cells which secrete IFN-γ.
4)IFN-γ activates macrophages to secrete a group of mediators including:
-1-TNF... causing recruitment of monocytes, their activation,
differentiation to epithelioid cells. It also causes:
a. Increased NO production which generate free radicals able to destroy
the microorganism.
b. Secretion of IL-8 which is chemotactic for lymphocytes and monocytes.
2-IFN-γ.... which helps in
a. Macrophage activation for more phagocytosis, antigen presentation and
microbial killing.
b. Secretion of TGF-β which stimulate fibroblastic proliferation
We must now look at the serious changes which occur when the
infection progresses and the child becomes ill.
Primary tuberculosis complex.
Pathogenesis. After the penetration of MBT into the lungs,
primary lesion (primary affect), of the size from a millet grain to a section
of a lung, is predominantly localized subpleurally in the II, III, VIII, IX
segments. From the primary affect the infection spreads along lymphatic
vessels to intrathoracic lymphatic nodes. However, lymphadenopathy may
also be primary or develop simultaneously with the lung affect.
Pathomorphism. Primary tuberculous complex consists of three
components: primary affect (pneumonitis), lymphadenitis (lesion of
intrathoracic lymphatic node) and lymphangitis (a “path” which joins the
primary affect with lymphadenitis). Specific inflammation spreads to
pleura and causes pleurisy.
The clinic of primary tuberculous complex depends on spreading
pathomorphologic lung changes, intrathoracic lymphatic nodes, as well as
on various complications. There may be asymptomatic, little symptomatic,
pneumonia similar, influenza similar variants of the clinical course of
primary tuberculous complex. However, more often it develops and
proceeds like tuberculous intoxication.
Roentgenologically four phases (stages) of primary tuberculous
complex are discerned: pneumonic (infiltrative), suction (bipolarities),
scarring and calcification (petrification). At preantibacterial period
calcification processes started in a year and lasted for 2-3 years; under
present day antimycobacterial therapy they set in considerably earlier and
rather rarely, because suction and scarring processes prevail.
Complications: pleurisy, lympho-hematogenic dissemination, decay
(primary cavern on the site of lung component), bronchi tuberculosis,
atelectasis of a segment or a particle, caseous pneumonia, primary
tuberculosis with a chronic course, that develops as a result of considerable
complications or inferior treatment.
The diagnostics is based on the anamnesis (contact), tuberculin test
intensity, hyperergic reaction to Mantoux test, availability of intoxication
symptoms and paraspecific reactions, roentgenologic picture (primary
affect, lymphangitis, lymphadenitis), changes of haemogram (little
leucocytosis with an insignificant shift to the left, lymphopenia,
monocytosis, speeded up ESR), MBT are rarely to be found.
The differential diagnostics is performed, first of all, with
pneumonia, eosinophilic infiltration, peripheral or central cancer.
In etiology of segmentation pneumonia anchorwomen the part is
acted by respirator viral infections, adenovirus, rarer they complicate a
measles, whooping-cough, sepsis and other diseases. Segmentation
pneumonias can be and cleanly bacterial (streptococcus, staphylococcus,
caused by the Fridlendera stick, pneumococcus and i.e.).
The protracted flow is usually adopted by sharp segmentation
pneumonia at the children of early age, being often ill the sharp respiratory
diseases, having the hearths of chronic infection in nasopharynx tonsillitis,
adenoiditis) and allergic diseases. Primary tubercular complex at children
in modern terms, thanks to a number of factors cooperate to the rise of
reactivity of child's organism, and also under influencing of intensive
antituberculosis therapy can have the normal flow. In this connection the
protracted segmentation pneumonias and primary tubercular complex can
have a similar clinico-roentgenologic picture. At both diseases look after
small symptoms displays, similar segmentation localization, involving in
the process of intrathoracic lymphatic knots. In this connection distinctive
feature extraction, which it is possible to use for differential diagnostics of
these processes, is a necessity. For diagnostics of primary tubercular
complex it follows to follow next criteria.
The analysis of sensitiveness to the tuberculin in a dynamics at
consumptive allows to set infected, in a number of cases the early period
of infected is determined — «conversion».
At most patients with pneumonia the analysis of sensitiveness to the
tuberculin specifies on a post-vaccine allergy, some patients negatively
react on a tuberculin. However it follows to take into account that in a
number of cases an infected by tuberculosis child can carry the unspecific
protracted bronco-pulmonary process. Exactly at infected by tuberculosis
children careful differential diagnostics for the exception of possibility of
development of tuberculosis must be conducted.
Literature
J. Crofton. Text book.