PRIMARY TUBERCULOSIS

PRIMARY TUBERCULOSIS

Primary is considered tuberculosis that develops in firstly infected persons and comprises not more than 1 % among all patients of firstly diagnosed tuberculosis. It is predominantly observed in infantine and juvenile age.

The period from the moment of the intensity of tuberculin reaction during one year without signs of intoxication is called the period of early tuberculous infection.

Latent microbism is the condition of an organism under which MBT are found in tissues, predominantly in lymphatic nodes, but they do not contain specific changes, characteristic to tuberculous granuloma.

Characteristic signs of primary tuberculosis: the intensity of tuberculin reactions, organism hypersensibilization to MBT, injury of lymphatic system (lymphatic nodes) with the susceptibility to caseous necrosis, susceptibility to lymphogenous and haematagenous dissemination, possibility of spontaneous recovery, availability of paraspecific reactions.

Three principal clinical forms of primary tuberculosis are discriminated:

tuberculous intoxication in children (tuberculosis without established localization),

primary tuberculous complex,

tuberculosis of intrathoracic lymphatic nodes.

PRIMARY TUBERCULOUS COMPLEX

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 (fig. 1, 2).

Lung localization occurs in 90 %, abdominal – in 10 % of primary tuberculous complex cases.

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.

Fig. 1. Primary tuberculosis complex.

Fig. 2. Roentgenogramm of primary tuberculosis complex in right lung.

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, pneumoniasimilar, influenzasimilar variants of the clinical course of primary tuberculous complex (fig. 3). However, more often it develops and proceeds like tuberculous intoxication.

Fig. 3. Infiltrative stage of primary tuberculosis complex .

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, lym-phadenitis), 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 respirator diseases, having the hearths of chronic infection in nausegullit (tonsillitis, adenoiditis) and allergic diseases. Primary tubercular complex at children in modern terms, thanks to a number of factors cooperant 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 infectid, in a number of cases the early period of infectid is determined — «turn».

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 infectid by tuberculosis child can carry the unspecific protracted bronco-pulmonary process. Exactly at infectid by tuberculosis children careful differential diagnostics for the exception of possibility of development of tuberculosis must be conducted.

The origin of segmentation and by shares defeats at a child in the period of turn of tuberkulin reactions in default of preceding respirator disease testifies to the specific infection rather. At a child with the protracted segmentation pneumonia, as a rule, in anamnesis are present pointing on the frequent sharp respirator diseases. For unspecific segmentation pneumonia characteristically there is the sharp beginning. In the clinical picture of sharp period of segmentation pneumonia accordance is marked between weight of the state, prevalence of process and age of child. At by shares polisegmentation processes at the children of early age the expressed of intoxication syndrome, respirator symptoms is looked after, the state of sick children is heavy. For a primary tubercular complex characteristically there is the gradual beginning of disease, the symptoms of intoxication and respiratory insufficiency are expressed in less degree. At the roentgenologic determined by shares, segmentation process of tubercular etiology even at the considerable rise of temperature of body there is relatively good health of child, he saves activity, respiratory disorders are expressed insignificantly. At comparison of clinical displays of primary tubercular complex and pneumonia predominance of general symptoms at tuberculosis comes to light, while at pneumonia are more than expressed cough, pains in a thorax, can become separated from small prick sputum. At the physical inspection at a primary complex the perkussion changes are expressed, they prevail above auskultation data. At pneumonia the auskultation changes prevail — different moist wheezes on a background weakened, by the places of bronchial, breathing. At unspecific processes the polisegmentation defeats with primary localization in the lower stakes of lung are characteristic, simultaneous combination of defeats of two segments and more than and the bilateral changes are possible.

At broncoscopyc research of patient with pneumonia widespread, diffuse, usually bilateral hyperemia of mucous membrane of bronchial tubes is marked, in the road clearance of them — mucous-festering secret. In the difficult case for differential diagnostics conduct therapy by the antibiotics of wide spectrum of action taking into account a bacterial sensitiveness.

The Fridlender pneumonia. Roentgenologic determine vast, sometimes plural one- or bilateral focuses of infiltration with the areas of melting. More frequent the overhead stake of right lung, the volume of which is multiplied, is struck, a upper border is disposed than due level (approximately on the width of one intercostal) below, mediastinum is displaced in an opposite side. Reactive adenitis with the increase of volume, violation of structure and washed of contours of roots of easy out accompanies to infiltration. Liquid is looked after also in pleura cavities. Ekssudat of crimson color, contains microbes of sort of klebsiell. Fridlender pneumonia at children meets as small flashes usually. This heavy form of pneumonia begins usually sharply, the symptoms of intoxication and respiratory disorders prevail in a clinical picture. For a clinical picture are characteristic the persistent sickly cough attended with the separation of mokroti with the veins of blood and smell of old meat. In diagnostics characteristic disparity of grave common condition with scanty data of phyzical inspection and moderate fever is used, ordinary for this pneumonia thick ate from to look true-festering sputum at the children of early age after difficultly. In spite of the protracted flow, fridlender pneumonia unlike tuberculosis is characterized by dynamic quality of process with the displays of unfavorable local changes. The rapid forming of cavities is looked after, elimination of content and partial transformation of them in thin-walled. A similar rapid dynamics is not incident to primary tuberculosis. Bilateral reactive adenitis and vascular hyperemia in the health departments of easy are not typical also for tuberculosis.

Staphylococcus pneumonias differ by weight of flow and expressed propensity to destruction. Development of disease often takes place on a background ORVI, is characterized by the sharply expressed symptoms of intoxication — getting up of temperature of body to the febril indexes, the shortness of breath, cough, appears, a child is languid, pale, renounces a meal, vomiting can appear, sometimes liquid chair. Staphylococcus pneumonias are characterized by magnitude of defeat, quite often are accompanied by a festering bronchitis, festering pleurisy, often there is development of air cavities with the level of liquid, which from a valvular mechanism in bronchial tubes can achieve considerable sizes.

Roentgenologic staphylococcus pneumonia begins from the unhomogeneous shading in lights, more frequent in right, with unclear contours, which is quickly multiplied. The triad of characteristic symptoms is known: focuses of infiltration, rounded cavities of disintegration, pleura ekssudat.

Roentgenologic four phases (stages) of primary tubercular complex are distinguished: pneumonic (infiltratition), sucction (bipolarity), scarring and (petrifikatsii). In a doantibakterialniy period the processes of scarring began through a year and 2-3 years proceeded; at modern antimycobacterial therapy they come considerably earlier and enough rarely, because the processes of sucction and scarring prevail.

Roentgenologic primary tubercular pneumonia in the period of active phase of process is homogeneous, the contours of her were washed out, she was related to the pathologically changed root by a «path» as unclear outlined linear of shadows. Inflammatory transformation of lymphatic ways and intermediate fabric on motion of bronchial tubes, vessels and lobules is their morphological substratom lights. Intensity of shade of primary hearth is different, that is conditioned by not only a size but also expressed of caseous component of necrosis.

Treatment starts at a hospital and is done with 3 or 4 antimycobacterial preparations (isoniazidum, rifampicinum, streptomycini). In 2-3 months, after disappearance of intoxication signs, streptomycini is cancelled, the treatment proceeds with 2 remedies (isoniazidum with rifampicinum or ethambutolum) for 4-6 more months. At the same time vitamins B₁, B₆, C, desinsibilizing and symptomatic means are applied.

TUBERCULOSIS OF INTRATHORACIC LYMPHATIC NODES

It is one of the most frequent clinical forms of primary tuberculosis, that is characterised by specific injury of intrathoracic lymphatic nodes (lungs root and mediastinum) (fig. 4, 5).

Fig. 4. Tuberculosis of intrathoracic lymphatic nodes.

Pathogenesis. Infestation generally takes place by the air-droplet-dust way, through the mucous membrane of tonsils and bronchi MBT penetrate into lymphatic vessels, nodes, where a specific process develops. Depending on the state of micro- and macroorganism, infiltrative-inflammatory or necrotic changes in lymphatic nodes prevail.

Fig. 5. Roentgenogramm of tuberculosis of intrathoracic lymphatic nodes in right side.

Pathomorphism. One or some groups of lymphatic nodes may be injured at tuberculosis. Paratracheal, tracheobronchial, bronchopulmonary, bifurcating and other lymphatic nodes are hurt. The process may be uni- or bilateral, predominantly asymmetric.

According to the character of pathomorphological changes, hyperplastic and caseous forms of tuberculosis of intrathoracic lymphatic nodes are discerned. Caseous form is characterized by a severe course and is harder to treat.

The clinic of uncomplicated tuberculosis of intrathoracic lymphatic nodes is analogous to that of primary tuberculous complex.

Clinico-roentgenologically three forms of tuberculosis of intrathoracic lymphatic nodes are discerned: “small”, infiltrative and tumoursimilar, depending on the morphological substrate, first of all caseose. The “small” form is characterized by a symptom-free or small symptomatic course. The peculiarity of infiltrative bron-choadenitis is a small enlargement of lymphatic nodes with perifocal inflammation in lung tissue, that roentgenologically is manifested by the root shade dilation, bulging and obscure contours; clinically – by intoxication symptoms. For tumoursimilar bronchoadenitis the enlargement of one or some groups of intrathoracic lymphatic nodes of mediastinum or lungs root with polycyclic distinct outer contours is characteristic. Signs of intoxication are more expressed, disposition to a complicated course.

The “small” form of tuberculosis is diagnosed on the basis of indirect signs of enlargement of intrathoracic lymphatic nodes, in particular, of local enrichment, deformation of the root lung picture, lowering of the root shade structure, double contour of the middle shade at a certain level, disappearance of the shade of the interstitial bronchus.

The course and complications of tuberculosis of intrathoracic lymphatic nodes are almost analogous to those of primary tuberculous complex and are connected with a specific affection of lymph nodes with certain clinical-roengenologic signs: Фото4_rs hematogenic and lymphogenic dissemination, exudative pleuritis, affection of an adjacent bronchus with further bronchogenic dissemination or the violation of bronchial passability and atelectasis.

Complication of primary tuberculous complex

The diagnostics is made on the basis of anamnesis, clinico-roentgenologic picture (fig. 6) in the period of intensity of tuberculin reaction, laboratory, bacteriological and instrumental examination.

The differential diagnostics is made with sarcoidosis (fig. 7) (I phase), lymphogranulomatosis (fig. 8), lymphosarcoma (fig. 9), lympholeucolysis, central cancer, unspecific adenopathies. For this the following procedures are performed: roentgenograpgy in right and lateral projections, tomography on bifurcation level (middle microscopic section), tuberculin tests, bronchoscopy as well as punctured or operative biopsy.

Fig. 6. Chart of localization of the most frequent defeats of mediastinum at children and teenagers: 1 - lymphogranulomatosis ; 2 - tumors of timus; 3 - tumors of lymphoid fabric, tuberculosis, sarcoidosis; 4 - teratodermoid no the educations; 5 - celomic cysts; 6 - neurogenic tumors; 7 - cysts of pectoral lymphatic channel; 8 - enterogenic cysts.

Fig. 7. Roentgenogram of organs of thorax. Sarcoidosis of intrathoracic lymphatic knots.

Fig . 8. Roentgenogram of organs of thorax Limphogranulematosis.

Fig. 9. Roentgenogram of organs of thorax. Limphosarcoma, complicated by the left-side pleurisy of knots.

Tumular bronhoadenit with the vast caseous changes in a few groups of inrtathoracyc knots flows protractedly, saving activity. The phenomena of infiltration diminish gradually. In place of expressed caseous can be formed large kaltsinati. Massive caseous bronchoadenitis can acquire the protracted flow. Presently slowly current bronhoadenitis meet infrequently. For slowly current bronhoadenitis are characteristic undulating flow, expressed of symptoms of intoxication, increasing in the period of intensification, and the expressed complications. Under influencing of course of antytuberculosis therapy, in spite of duration of flow, it is succeeded to obtain clinical recovery.

At differential diagnostics it follows to take into account the roentgenoanatomic structure of mediastinum. Being part of pectoral cavity, mediastinum at the front is limited by the back wall of breastbone and costal cartilages, behind — by a vertebral post, from sides — by the medium sheets of pleura, down — by a diaphragm, from above — by the aperture of thorax.

It follows to begin differentiation with determination of localization of process. Expediently to use a chart, in obedience to which by the frontal planes conducted on the front and back walls of trachea, mediastinum divides by three departments — front, back and middle.

Localization of diseases in mediastinum

Front mediastinum

Tumors outgoing from fabric of thyroid Giperplaziy of forks gland of Teratom and teratodermoid cyst of the celomic cyst of pericardium the Fatty tumors of mediastinum of Aneurism of ascending department of aorta

Central mediastinum

Tuberculosis of vnutrigrudnih lymphatic knots

Lymphogranulematosis

Lymphosarkoma

Lympholeicosis

Unspecific adenopaty (measles, whooping-cough, viral infections)

Sarkoidosis

Aneurism of arc of aorta.

Mediastinal cancer

Back sredostenie

Nevrogenic educations are the Natechniy abscess of Aneurism of aorta of Tumur of gullet of the Bronho-enterogennie cyst

Giperplaziy of forks gland, timoma. Giperplaziy of forks gland meets in pectoral and early child's age. Under the term of «timoma» all types of tumors and cysts of forks gland are united. In considerable part of cases of defeat of forks gland flow asymptomatically . At development of tumor process there are the clinical displays — symptoms of pressure on neighbouring organs, and also symptoms of hormonal activity. Roentgenologic timoma is represented as expansion of mediastimun from one or both sides. More frequent she is disposed asymmetric. It is favourite localization overhead and middle departments of front mediastinum. On the sciagram of timoma, as a rule, is traced from the level of collar-bone, fills retrosternal space and, narrowing down, depending on a size, can extend to the diaphragm.Shade is homogeneous, has sharp, slightly protuberant in the sides of pulmonary fabric contour. At displacement of megascopic stakes in one side extended mediastinum has a bicyclic character. Sizes and form is tumular the transformed stakes of forks gland, at the same time, vary widely. Specify on the possible waviness of contours pear-shaped form, and also on the inclusions of calcium salts. It creates likeness with large of intrathoracic lymphatic knots.

The deciding value in differentiation has a topic diagnostician. Rentgenofunktional symptoms help: displacement of timom at swallowing, cough. Pneumomediastinography is informing.

The Dermoid cysts and teratom are also localized in front mediactinum. The Dermoid cysts are the vices of embryonic development — derivative ectodermy; according to it in them such elements are found, how a skin, hairs, sweat and greasy glands, is. In teratomah find the elements of all three embryonic sheets — ecto-, mezo- and entodermy; skin with its appendages, muscles, nervous and bone fabric and even elements of separate organs — teeth, jaws and etc.Dermoid cysts and teratom clinically, as a rule, show up nothing; usually they are exposed at roentgenologic research. The clinical displays rely on sizes and direction of growth. At localization of cyst in front mediastinum (in 30% cases) more frequent a compression syndrome is looked after. Typical localization of teratom — middle department of front mediastinum.The Dermoid cysts differ by very slow growth. In youth age their growth increases. Growth acceleration of cyst in the period of pregnancy, pubescence is sometimes marked, after a trauma or infection.Roentgenologic asymmetric expansion of mediastinum is determined.

The form of teratodermoid cysts is more frequent oval or half-round, contours are sharp, sometimes wavy. Surrounding fabric at the small sizes of cyst and absence of complications is not changed.In diagnostics the reflection of inclusions of bone fabric is deciding (teeth, fragments of jaws, phalanx). In default of visible inclusions a roentgenologic picture corresponds to the of high quality tumur.In 15% cases the calcination is looked after. In the case of necrosis of fabric appear chaotic or calcinations in parenchim of cyst, growth of her is here halted.

Nevrogenic educations on frequency take first seat among all tumors and cysts of mediastinum. Meet in any age, including at new-born. More frequent all this neurinom — of high quality tumors developing from the cages of shvannovsky shell. Symptomatic of neurinom is not typical, the flow is protracted, without symptoms. More frequent they are exposed at the prophylactic roentgenologic inspection, and at children — at the change of sensitiveness to the tuberculin or concerning the bacillus contact. Dull and aching pains in breasts which are the result of pressure of tumor on neighbouring organs and fabrics can appear at the largenesses of nevrinom. A compression syndrome is possible.The structure of shade is homogeneous, contours are clear, sometimes not sharply uneven. Neurinoms rentgenofunctional symptoms are not peculiar — such, how the change of form is at breathing. Neurinoms do not pulsate and move not at the change of position of body of inspected. To the neurogenic tumors the symptom of removing of mediastinal pleura a layer by a layer as smooth transition of outlines of tumor in an overhead department in the front contour of mediastinum is incident. Neurinom largenesses cause uzuratsiyu bone elements. Determination of typical for neurinom localization is the basic criterion of difference from megascopic lymphatic knots.

Sarkoidosis. Tuberculosis of intrathoracic lymphatic knots is differentiated from the I stage of sarkoidosis. In obedience to modern presentations, sarkoidosis — it is the chronic illness of indistinct etiology, characterized by the defeat of the lymphatic system, internal organs and skin with formation of specific granulem surrounded by the layer of gyalinous. Intrathoracic lymphatic knots at sarkoidosis are struck in 100% cases, and other organs of —rege. From the published data, women in age from 20 to 40 years are ill sarkoidosis in 2 times more frequent than men. Sarkoidosis meets at the children of senior age and teenagers.

At bronchologyc research for the I stage of sarkoidosis, characterized by the defeat of intrathoracic lymphatic knots, the indirect signs of their increase are typical, and also the extended, coiled vessels of mucous membrane. The last are the result of violation of haemo- and lymphoflowing in connection with the considerable degree of adenopaty. At tuberculosis the specific changes can be exposed in bronchial tubes or limited catarrhal endobronchitis. At sarkoidosis simultaneously with the defeat of intrathoracic lymphatic knots are often observed uveit, iridotsiklit, in the bones of brushes and feet shallow cavities are sometimes determined, salivary glands, liver, spleen, skin, heart, can be struck. In hemogramm at sarkoidosis sometimes mark leyko- and limphopeniy, monotsitosi, eosinophylyu at normal or not sharply megascopic SOE. In the whey of blood — rise of maintenance of g-globulinov in a blood, and also calcium in a blood and urine. The roentgenologic picture of sarkoidosis of intrathoracic lymphatic knots is characterized, after the rare exception, bilateral, symmetric their increase and sharp delimited. The degree of increase is considerable. Thus, the presence of calcination in intrathoracic lymphatic knots in child's and juvenile age does not eliminate sarkoidosis.

At histological research of sarkoid granulems differ monomorph, they have identical sizes, form, structure. Granulem consist of epithelioid cages. Unlike tuberculosis the centers of granulem have not necrosis. On occasion there can be the giant cages of type of the Pirogova cages — Langhansa. Granulems are delimited from surrounding fabric by a border from retikulyar fibres and gialin. A typical for tuberculosis billow from leucocytes is absent.

Limfogranulematosis. The clinic-roentgenologic displays of tuberculosis of intrathoracic lymphatic knots have likeness with the displays of lymphogranulematozsis. Such symptoms, how the decline of mass of body, weakness, is, getting up of temperature of body to the subfebril and febril sizes, determined roentgenologic megascopic intrathoracic knots, meet at both diseases. At differential diagnosticians of tubercular bronhoadenitis and lymphogranulematosis is taken into account by next positions.

Treatment. 3-4 antituberculosis remedies are prescribed: isoniazidum, rifampicinum, pyrazinamidum, streptomycin. After two months of effective che-motherapy – isoniazidum + rifampicinum (ethambutolum) daily or every other day. The duration of chemotherapy is 6-9 months. Unspecific therapy: vitamins B₁, B₆, C, desensibilizing, hormonal and symptomatic means.

Relevantly, primary tuberculosis may sometimes have chronic undulatory course, with expressed phenomena of tuberculous intoxication during the aggravation of specific process in lymphatic nodes or other organs. Chemotherapy not always results in stable clinical recovery.

Primary tuberculosis may also be found in adults, in particular in an old age, with characteristic signs of primary period, torpid course, difficult at diagnostics and treatment.

TUBERCULOUS INTOXICATION IN CHILDREN

(tuberculosis without established localization)

Tuberculous intoxication – is a clinical form of primary tuberculosis, which is characterized by a symptom complex of functional failures, but without established local manifestations of a disease.

Pathomorphism. At tuberculous intoxication minimum specific and paraspecific changes, first of all in enlarged lymphatic nodes, as well as in spleen, interstitial lung tissue, liver and other organs are observed.

Clinic. A child’s behaviour often changes, it becomes irritable, labile, loses cheerfulness, gets tired quickly, the ability to concentrate attention decreases, the appetite deteriorates, the memory weakens, disposition to perspire appears, sometimes subfebrile body temperature, dyspeptic failures.

Pallor, skin turgor decrease, sometimes paraspecific reactions (nodal fever, keratocojunctivites, blepharites, phlyctenaes), increase of peripheral lymphatic nodes are observed at objective examination.

Diagnostics. The diagnosis of tuberculous intoxication is based on the fact of availability of the intensity of tuberculin reactions, intoxication symptoms, the absence of changes on roentgenogram and tomogram, under the condition of exclusion of intoxication of another etiology. In doubtful cases it is recommended to apply test treatment with antituberculous preparations during up to 3 months.

Differential diagnostics is applied to the following illnesses: chronic tonsillitis, helminth infestation, hepatocholecystitis, pyelonephritis. It follows above all things to eliminate possibility of intoxication due to the chronic hearths of infection in the cavity of mouth and nousegullit (tooth decay, sinusitis, adenoiditis, chronic tonsillitis), rheumatism, hepatoholetsistopaty, infections of urinary ways, pyelonephritises, helmintoza, hypertireosis and other states.

Chronic tonsillitis occupies one of prominent positions in pathology of child's age, in a number of cases he accompanies to tubercular intoxication, and fully logically to assume that both processes, co-operating, strengthen each other. But, nevertheless, on the definite span of time intoxication is conditioned to one of these factors, other process exists in latency. Similar tasks (questions) everywhere get up before a doctor. It follows to take into account data of anamnesis: intensifications of tonzillogeni intoxication are related to the carried repeated quinsies usually, the more or less long periods of remissyi accompany to chronic tonsillitis. The symptoms of chronic tubercular intoxication are saved almost continuously. A child suffering by chronic tubercular intoxication differs from a patient with tonzillogenic intoxication. Usually they do not grumble neither about the shortness of breath, nor on a physical weakness, that quite often to be had to hear from children suffering by chronic tonzillogenic intoxication and rheumatism. Patients with rheumatism and children with chronic tonzillogenic intoxication are less cheerful, anymore grumble about a general weakness. The state of them on a background the rise of temperature of body to 38°S gets worse anymore, while children with chronic tubercular intoxication well carry the rise of temperature of body even higher 38°S. At examination of patients with chronic tonsillitis the corks in lakunas can be exposed, pus liquid, bad breath, union of tonsils with handles. At tuberculosis the even, painless increase of all groups of peripheral lymph nodes is marked usually. At chronic tonsillitis regional in relation to a pharynx nodes are megascopic foremost.

Rheumatism. At presence of the knotted erythema, complaints on pain in a heart, artralgii, objective data, determined from the side of the cardiovascullar system as muffling of tones of heart, systole noise and etc there are suspicions on a rheumatic infection. About rheumatism can testify defeat of the cardiovascullar system making to progress, expressed changes in hemogramm as leycocytosis, monocytosis, promoted ESR, positive tests on activity of rheumatism.

Hepatoholetsistopatis. A clinical picture at these diseases at children can be frequent to indistinct and disguised. Appearance of pains matters on an empty stomach or in connection with acceptance of food, errors in the feed, dyspepsia phenomena. During the attacks of stomach-aches are marked tension of muscles in podrebere, vomiting, increase of liver, sickliness at palpation in area of liver, diagnostics is complemented by the duodenal sounding, holetcystography, by the proper laboratory researches.

Pyelonephritis. A diagnosis is grounded by not so much the clinical phenomena, as laboratory and instrumental researches. The changes in urine at patients with chronic tubercular intoxication are absent, and at children with early tubercular intocsication — transient and moderate, the function of buds does not suffer. Sowing of urine on a banal flora matter.

Hipertireoz. He must be eliminated at the children of senior age, especially in a pubertatnom period. At hipertireoze the temperature of body is more frequent subfebril, but monotonous. Weightloss is not necessarily accompanied by oppression of appetite, the increase of thyroid, eye symptoms, matter, presence of signs of adinamy and astenisation. A basic exchange at hipertireous is promoted.

Helmintozi at children are accompanied by nausea, by vomiting on an empty stomach, by the expressed salivation, by the unpleasant feeling in an epigastric region. The temperature of body remains usually normal. Symptoms of mycropoliadenit no. In a blood often expressed eosinophya, in lights there are eozinofilnie infiltrati. For the exception of helmintosis needed repeated scraper and research of excrement on the eggs of helmints.

Prolonged subfebrility accompanying the unexposed hearths of infection meets after the carried banal infections, prophylactic inoculations and t. d, more frequent at the children inclined to the allergic reactions. It follows to mean that during tubercular intoxication the temperature of body does not carry a permanent character, considerable daily allowance scopes are marked.

In a number of cases in the tubercular separation the children at which the knotted erythema or other toxico-allergic displays served by a sole subject for it act on the inspection. The exposure of hearths of infection, anamnesis, matter for the exception of specific etiology of them, exception of local displays of tuberculosis, signs of activity of tubercular infection, possibilities of MBT infected. Own practical experience and published data testify to that at primary tuberculosis these displays of steel to meet considerably rarer, than earlier, and specific nature of them quite often is not confirmed. In conclusion it follows once again to underline that in differential diagnostics of tubercular intoxications at children, along with the exception of local displays of tuberculosis and unspecific diseases, it is necessary to draw on all complex of researches for the exposure of signs of activity of tubercular infection. It will allow to evade hiperdiagnostics of tuberculosis.

Treatment. Prophylaxis with isoniazidum is done to children and teenagers with the intensity of tuberculin reactions during 3 months and they are observed in the VI group of dispensary system survey not less than one year.

At tuberculous intoxication they are treated with isoniazidum combined with ethambutolum or rifampicinum during 4-6 months assumingthe follow of sanatorium-hygienic regime.

Children TB. Among various parameters, determining tuberculosis progress, age is an important factor. In infants tuberculous process tends to rapid progressing and generalization, development of miliary tuberculosis and meningitis. From 1 year to the period of sexual maturation primary nidi of tuberculous process predominantly heal, however they remain the source for the development of tuberculosis in an elder age. Infected persons in their mature age face a little risk of developing tuberculosis during a few next years from the infestation moment.

Children tuberculosis is characterized by a relatively benign course, without expressed local manifestations, and is only manifested by the symptom complex of tuberculous intoxication or only the range of tuberculin reaction.

Generally, classical signs of primary tuberculosis are the range of tuberculin reactions, a considerable lesion of lymphatic system (lymphatic nodes, vessels), frequent involving of bronchi and serous coats into the process; hypersensitivity of an organism, that is accompanied by the disposition to generalizing the process by haematogenous, lymphogenous and bronchogenic ways, as well as the appearance of paraspecific toxico-allergic reactions (blepharites, keratoconjunctivites, phlyctenae, nodular erythema etc.), inclination of specific process of lymphatic nodes to caseous regeneration, as well as to self-healing.

Among all children contingent of tuberculosis patients a great importance is attached to children of prepuberal age, inasmuch as at this age the main factors contributing to activizing endogenic tuberculous infection is endocrine reconstruction. The specific process is characterized by pronounced changes in lymphatic nodes, segmental and partial processes, bronchi lesions (in 14,7 %).

Big residual changes in the form of metatuberculous pneumosclerosis after complicated tuberculosis of intrathoracic lymphatic nodes may be the source of relapses and the background for the development of nonspecific illnesses in 17,6 % of children. Besides, the course of tuberculosis of prepuberal age children is greatly influenced by the acceleration factor. It is the increase of the body length and other parameters, early sexual maturity, lability of nervous processes. It has been found that in “accelerates”, who outstrip their passport age, asymptomatic tuberculosis course is often observed and comparatively often (in 1/3) and the destruction of nidus and infiltrative processes sets in rapidly. Thus, it is only early diagnostics of primary infestation (“range”), tuberculin hypersensivity, initial local manifestations of tuberculosis and treatment of children results in a considerable reduction of roentgenpositive persons, who form the bulk of adult tuberculosis patients later on.

Juvenile tuberculosis. The juvenile age is a complex period of the development of an organism, which is characterized by the diversity and instability of mutual relations of functional parameters of the main physiological systems. It has been found that at an early pubertal period chronic illnesses with immunological, infectious-allergic genesis progress with marked exudative inflammatory reactions and clinically acute development, in the second part of pubertal period, at its completion, the inflammatory process progresses with feebly marked exudative component with preferably productive character of tissue reactions, lingering latent course, inclination to the disease relapses.

In connection with physiological peculiarities, connected with hormonal re-construction, acceleration phenomena, teenagers are considered to be a “risk group”, both in the general pathology and in phthisiology. They may develop primary and secondary forms of tuberculosis. At present time primary forms are more frequent among teenagers, and not only tuberculosis of intrathoracic lymphatic nodes, primary tuberculosis complex, but also nidal, infiltrative forms, that have more favourable course than the same forms of the secondary genesis. Besides, at feebly marked clinical manifestations the destruction of lung tissue is frequently observed, as well as mycobacterial secretion, marked tuberculin sensitivity. Menstrual cycle disturbance is often (48,7 %) observed among female teenagers tuberculosis patients as a result of tuberculous intoxication. Juvenile primary tuberculosis in most cases progresses with complications, the most frequent of which are endobronchitis (in 29 %) and exudative pleurisy (14,5 %).

Treatment. The main course of antimycobacterial therapy of 3-4 preparations should last for 6-9 months (hospital, sanatorium). In some cases surgical intervention is applied in cases of isolated caverns, big tuberculomas, cirrhoses with bronchoectases.

Teenagers with big residual changes are under observation in the 3rd group of dispensary examinations.

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 disease, and (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 HIV-infected adults in the community. Little is known about tuberculosis in HIV-infected children because relatively few confirmed cases have been reported.¹³ In general, HIV-infected children may be more likely to have contact with HIV-infected adults who are at high risk for tuberculosis. Tuberculosis is probably underdiagnosed among HIV-infected children for two reasons: (1) the similarity of its clinical presentation to other opportunistic infections and acquired immunodeficiency syndrome (AIDS)-related conditions, and (2) the difficulty in confirming the diagnosis with positive cultures. Children with tuberculosis should undergo HIV serotesting because the two infections are linked epidemiologically and recommended treatment for tuberculosis is prolonged for HIV-infected children.

Although data on tuberculosis disease in children are readily available, data concerning tuberculosis infection without disease (positive skin test result) are lacking. Tuberculosis infection is a reportable condition in only four states, and national surveys were discontinued in 1971. The most efficient method of finding children infected with M. tuberculosis is through contact investigations of adults with infectious pulmonary tuberculosis. On average, the tuberculin skin test is reactive in 30% to 50% of all household contacts of an index case.

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. In a 1990 study of Boston public schools, tuberculin skin test results were positive in 5.1% of seventh graders and 8.9% of tenth graders.¹⁴ In Los Angeles and Houston public schools, 2% to 5% of elementary school children are infected. In these and other surveys, the majority of children in whom skin tests were reactive were foreign-born. The upward trend in reported pediatric tuberculosis cases in the United States, the data on tuberculosis in recent immigrants, and the results from these skin test surveys in urban areas imply that the pool of infected children and young adults in the United States is growing. Transmission

Children usually are infected by an adult or adolescent in the immediate household, most often a parent, grandparent, older sibling, boarder, 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, and candy-store keepers have been implicated in individual cases and in hundreds of mini-epidemics 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, whereas children between 6 and 12 years of age often escape infection. 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.

Wallgren, examining studies in orphanages, was the first to point out that children with tuberculosis rarely, if ever, infect other children. Many children with the disease have tuberculin-negative siblings and parents. Children with tuberculosis often have been cared for by their families or in hospitals and institutions without infecting their contacts. 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, tubercle bacilli 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. Guidelines issued by the Centers for Disease Control and Prevention (CDC) state that most children with typical pediatric tuberculosis do not require isolation in the hospital unless they have an uncontrolled productive cough, a cavitary lesion, or acid-fast organism-positive sputum smears. 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.

The risk of infection for child contacts of adults receiving anti-tuberculosis chemotherapy often is a matter of practical concern. Several studies have revealed that most contacts are infected by the index case before diagnosis and the start of treatment. Although it is not possible to carry out a definitive clinical study, evidence indicates that patients on effective chemotherapy rarely transmit M. tuberculosis. Nevertheless, it seems prudent to avoid exposing children to adults with positive sputum smears or positive cultures and to assume that adults in whom smears or cultures are positive remain infectious for at least several weeks after the start of chemotherapy. PATHOGENESIS IN CHILDREN

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. Tubercle bacilli within particles larger than 10 (xm usually are caught by the muco-ciliary mechanisms of the bronchial tree and are expelled. Small particles are inhaled beyond these clearance mechanisms. However, primary infection may occur anywhere in the body. Ingestion of milk infected with bovine tuberculosis can lead to a gastrointestinal primary lesion. Infection of the skin or mucous membrane can occur through an abrasion, cut, or insect bite. The number of tubercle bacilli required to establish infection in children is unknown, but only several organisms are probably necessary.

The incubation period in children between the time the tubercle bacilli 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 (Fig. 29-2). Occasionally, the parenchymal lesion may continue to enlarge, resulting in focal pneumonitis and thickening of the overlying pleura. If case-ation 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, tubercle

Posteroanterior chest radio-jraph of an 8-year-old girl with a calcified, left upper lobe primary complex. She had no pulmonary lymptoms or signs.

bacilli 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 parenchy-mal 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 hyperinflation in the distal lung segment. Such compression occasionally causes complete obstruction of the bronchus, resulting in atelectasis of the lung segment.More often, inflamed caseous nodes attach to the bronchial wall and erode through it, leading to endobronchial tuberculosis or a fistu-lous 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 combination of pneumonia and atelectasis. The radiographic findings of this process have been called epituberculosis, collapse-consolidation, and segmental tuberculosis. Rarely, tuberculous intra-thoracic lymph nodes invade other adjacent structures such as the pericardium or esophagus.

A fairly predictable time table for primary tuberculosis infection and its complications in infants and children is apparent.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 infectionIn general, complications of the primary infection occur within the first year.

Tuberculosis disease that occurs more than a year after the primary infection is thought to be secondary to endogenous regrowth of persistent bacilli from the primary infection and subclinical dissemination. In rare cases, exogenous reinfection results in tuberculosis disease, but most cases of postprimary or reactivation tuberculosis in adolescents are thought to be secondary to endogenous organisms. Reactivation tuberculosis is rare in infants and young children. For unknown reasons, reactivation tuberculosis among adolescents affects females twice as often as males. The most common form of reactivation tuberculosis is an infiltrate or cavity in the apex of the lung where oxygen tension is high and there is a heavy concentration of tubercle bacilli deposited during the primary subclinical dissemination of organisms. Dissemination during reactivation tuberculosis is rare among immunocompetent adolescents. The age of the child at acquisition of tuberculosis infection seems to have a great effect on the occurrence of both primary and reactivation tuberculosis. Hilar lymphadenopathy and subsequent segmental disease complicating the primary infection occur most often in younger children. Approximately 40% of untreated children less than 1 year of age develop radiographically significant lymphadenopathy or segmental lesions, compared with 24% of children 1 to 10 years of age and 16% of children 11 to 15 years of age. However, if young children do not suffer early complications, their risk of developing reactivation tuberculosis later in life appears to be low. Conversely, older children and adolescents rarely experience complications of the primary infection but have a much higher risk of developing reactivation pulmonary tuberculosis as an adolescent or adult. CLINICAL MANIFESTATIONS

How Children with Tuberculosis Are Discovere 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.³² 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.Obviously, one way is consideration of tuberculosis as the cause of a symptomatic pulmonary or extrapulmonary illness. Discovering an adult contact with

Older children and adolescents, especially those with reactivation-type tuberculosis, are more likely to experience fever, anorexia, malaise, weight loss, night sweats, productive cough, chest pain, and hemoptysis than children with primary pulmonary tuberculosis.⁴⁰'^4I Findings on physical examination, however, are usually minor or absent even when cavities or large infiltrates are present. Most signs and symptoms improve within several weeks of starting effective treatment, although cough may last for several months.

As expected, the radiographic findings in pedi-atric tuberculosis reflect the pathophysiology and are different from findings in adults. The hallmark of primary pulmonary tuberculosis is the relatively large size and importance of the lymphadenitis compared with the less significant size of the initial parenchymal focus Because of the usual pattern of lymphatic circulation within the lungs, a left-sided parenchymal focus often leads to bilateral hilar adenopathy, whereas a right-sided focus is associated only with right-sided lymphadenitis. Hilar or mediastinal lymph-adenopathy is invariably present with primary tuberculosis

Comparison of Chest Radiographs of Pulmonary Tuberculosis in Adults and Children

Characteristic	Adults	Children
Location	Apical	Anywhere (25%
		multilobar)
Adenopathy	Rare (except	Usual
	HIV-related)
Cavitation	Common	Rare (except
		adolescents)
Signs and symptoms	Consistent	Relative paucity
HIV, human immunodeficiency virus.

but may not be distinct (from the atelectasis and infiltrate) or may be too small to be clearly visible on a plain radiograph. Computed tomography (CT) may reveal small lymph nodes when the chest radiograph appears normal, but this finding appears to have no clinical implicationsIt can, however, create a dilemma in deciding on a treatment regimen and reinforces the idea that, in children, infection and disease are on a continuum with often indistinct bordersIn most cases of tuberculosis infection in children, the initial mild parenchymal infiltrate and lymphadenitis resolve spontaneously and the chest radiograph appears normal. In some children, the hilar or mediastinal lymph nodes continue to enlarge. Partial airway obstruction caused by external compression from the enlarging nodes causes air trapping and hyperinflation. As the nodes attach to and infiltrate the airway, caseum filling the lumen can cause complete obstruction, resulting in atelectasis that involves the lobar segment distal to the obstructed lumen The resulting radiographic shadows are called collapse-consolidation or segmental lesions These findings resemble those in foreignbody aspiration; in the case of tuberculosis, the lymph node is functioning as a foreign body. Multiple segmental lesions in different lobes may appear simultaneously, as can atelectasis and hyperinflation.

Other radiographic findings are noted in some children. Children occasionally have lobar pneumonia without distinct hilar adenopathy. In infants and young children, the radiographic appearance can resemble exudative pneumonia, similar to that caused by Klebsiella pneumoniae or Staphylococcus aureus. A secondary bacterial pneumonia may contribute to this appearance. When tuberculosis infection is progressively destructive, liquification of lung parenchyma leads to formation of a thin-walled primary tuberculous cavity. Rarely, peripheral bullous lesions occur that can lead to pneumothoraxEnlargement of subcarinal nodes can cause compression of the esophagus, difficulty swallowing, and rarely a bronchoesopha-geal fistula. One sign of early subcarinal tuberculosis is horizontal splaying of the mainstem bronchi.

Adolescents with pulmonary tuberculosis may develop segmental lesions with associated adenopathy, but more often they develop the infiltrates with or without cavitation that are typical of adult reactivation tuberculosis The lesions are often smaller in adolescents than adults, and lordotic views, tomograms, or even CT may be necessary to demonstrate small apical foci of disease.

The course of thoracic lymphadenopathy and bronchial obstruction can follow several paths. In most cases, the segment or lobe re-expands and the radiographic abnormalities resolve completely. The resolution occurs slowly—over months to several years—and is not affected greatly by anti-tuberculosis therapy. Of course, children still have infection with M. tuberculosis and are at high risk of reactivation tuberculosis in subsequent years if chemotherapy has not been instituted. In some cases, the segmental lesion resolves and residual calcification of the primary parenchymal focus or regional lymph nodes occurs. The calcification usually occurs in fine particles, creating a stippling effect. Calcification begins 6 months or more after infection. Even with chemotherapy, the enlarged lymph nodes and endobron-chial lesions may persist for many months, occasionally resulting in severe airway obstruction. Rarely, surgical or endoscopic removal of intra-luminal lesions is necessary. Finally, bronchial obstruction may cause scarring and progressive contraction of the lobe or segment, which is often associated with cylindrical bronchiectasis. Complete radiographic and clinical resolution without calcification occur in the vast majority of cases with early institution of adequate treatment for collapse-consolidation lesions. Pleural Disease usion is so frequent in primary tuberculosis that it is basically a component of the primary complex. Most large and clinically significant effusions occur months to years after the primary infection. Tuberculous pleural effusion is infrequent in children younger than 6 years of age and rare in those below 2 years of age.Such effusions are usually unilateral buTuberculous pleural effusions, which can be local or general, usually originate in the discharge of bacilli into the pleural space from a subpleural pulmonary focus or caseated subpleural lymph nodes.

Peripheral, reactivation-type cavity associated with pulmonary tuberculosis in an adolescent girl.

Miliary tuberculosis in an infant. The child presented with fever and respiratory distress.

Asymptomatic local pcan bleural eft e bilateral. They are virtually never associated with a segmental pulmonary lesion and are rare in miliary tuberculosis. The clinical ont of tuberculous pleurisy in children is usually fairly sudden, with low or high fever, shortness of breath, chest pain (especially on deep inspiration), dullness to percussion, and diminished breath sounds on the affected side. The presentation is similar to that of pyogenic pleurisy. The fever and other symptoms may last for several weeks after the start of antituberculosis chemotherapy. Although corticosteroids may reduce the clinical symptoms, they have little effect on the ultimate outcome. The tuberculin skin test result is positive in only 70% to 80% of cases. The prognosis is excellent; radiographic resolution takes months, however.⁴⁹ Scoliosis rarely complicates recovery of a long-standing effusion.

Extrathoracic Tuberculosis

The various forms of extrapulmonary tuberculosis are reviewed in detail in other chapters. Up to 25% to 35% of pediatric tuberculosis cases are extrapulmonary , and a careful physical examination is an essential component of the evaluation of a child with tuberculosis exposure or infection. The two forms of extrapulmonary tuberculosis that receive the most attention, because of their life-threatening nature, are disseminated (miliary) disease and meningitis. Both forms of disease occur early, often within 3 to 6 months of initial infection. Correct diagnosis requires a high index of suspicion because it is difficult to confirm these diseases microbiologically. Acid-fast stains of body fluids are almost always negative; cultures for M. tuberculosis are positive in only 50% or less of cases, and they often take weeks to grow because the initial inoculum of organisms is so low.~" In addition, the tuberculin skin test may be nonreactive initially in up to 50% of pediatric patients, and the chest radiograph in both diseases may appear normal early on. The key element to correctly diagnose each condition is an epidemio-logic history, a search for the adult from whom the child acquired M. tuberculosis. Unfortunately, an initial negative history for exposure does not really help. In a study of 31 consecutive infants and children with central nervous system tuberculosis in Houston, the initial family history was negative for tuberculosis in 30 cases, although the adult source case was ultimately identified in over 60% of cases.Because the incubation period of disseminated tuberculosis and meningitis in children may be short, the infection in the ill adult often has not yet been diagnosed correctly. When serious tuberculosis disease is suspected in a child, an evaluation of the family and other adults and adolescents in close contact with the child should be considered a public health emergency.

Miliary tuberculosis

In many urban children's hospitals in the United States, the incidence of tuberculous meningitis is higher than that due to Haemophilus influenzae type b. Although the clinical onset of tuberculous meningitis in children may occur gradually over several weeks, studies describe more rapid progression over several days. Early on, the clinical presentation may be similar to that of viral or pyogenic meningitis. However, tuberculous meningitis in children is more likely to be complicated by cranial nerve involvement, basilar leptomenin-geal involvement, hydrocephalus, and infarct caused by vasculitis. These findings in any child with meningitis, when no other cause is readily apparent, should prompt immediate initiation of antituberculosis chemotherapy while diagnostic studies and investigation of close contacts for tuberculosis are carried out as quickly as possible.

Tuderculous meningitis

The widespread use of improved cranial imaging, such as CT and magnetic resonance imaging (MRI), have shown that tuberculoma is more common than previously realized, and the distinction in children between tuberculous meningitis and tuberculoma is not as clear as once was thought. In developing countries, tuberculomas account for up to 40% of brain tumors in children. They most often occur in children less than 10 years of age, may be single or multiple, and are often located at the base of the brain, near the cerebellum. However, a recently recognized phenomenon is the paradoxical development of intra-cranial tuberculomas appearing or enlarging during treatment of meningeal, disseminated, and even pulmonary tuberculosis.This phenomenon appears to be similar to the well-described worsening of intrathoracic adenopathy that occurs in many children during the first few months of ultimately successful chemotherapy for tuberculosis. The tuberculomas seem to be mediated immu-nologically; they respond (slowly) to corticoste-roid therapy, and a change in antituberculosis therapy is not required. Some infants with pulmonary tuberculosis and subtle neurologic signs or symptoms have one or several tuberculomas; even with a negative cerebrospinal fluid evaluation, any neurologic abnormality in a child with suspected tuberculosis should be evaluated with a neuro-imaging study, when feasible. Tuberculosis in HIV-Infected Children

In adults infected with both HIV and M. tuberculosis, the rate of progression from asymptomatic infection to disease is increased greatly.The clinical manifestations of tuberculosis in HIV-infected adults tend to be typical when the CD4 ⁺ cell count is more than 500/mm³ but become "atypical" as the CD4⁺ cell count falls. Similar correlations have not been reported for dually infected children, though there is some epidemiologic evidence that tuberculosis rates are higher in HIV-infected children in the United States than in the general population.¹² When HIV-infected children develop tuberculosis, the clinical features tend to be fairly typical of disease in immunocompetent children, although the disease often progresses more rapidly and clinical manifestations are more severe. There may be an increased tendency for extrapulmonary disease, but the trend is not as dramatic as it is in HIV-infected adults.The diagnosis of tuberculosis in an HIV-infected child can be difficult to establish because skin test reactivity may be absent, culture confirmation is slow and difficult, and the clinical presentation may be similar to other HIV-related infections and conditions. A diligent search for an infectious adult in the child's environment often yields the strongest clue to the correct diagnosis. DIAGNOSIS Tuberculin Skin Test

The tuberculin skin test has been reviewed extensively in a previous chapter. The placement of the Mantoux intradermal skin test, although fairly simple and routine in a cooperative adult, can be a challenge in a squirming, scared child. The technique shown in Figure 29-9 allows for better control during placement. The skin tester anchors his or her hand along the longitudinal axis of the child's arm, which enhances stability and allows the last two fingers to become a fulcrum to guide inoculation of the solution. The tuberculin is injected laterally across the arm. As with adults, a wheal of 6 to 10 mm should be raised after injection. The test is interpreted at 48 to 72 hours after placement. Although recent formal studies are lacking, most experts believe the time course of the reaction and amount of induration produced is similar in children and adults. Infants may yield slightly less induration, on average, when infected. The interpretation of the Mantoux skin test should be similar in children and adults However, most of the "risk factors" for children are actually the risk factors of the adults in their environment—the likelihood that the child has had significant contact with an adult with contagious pulmonary tuberculosis. Correctly classifying a child's reaction supposes that the risk

Treatment support. children, their parents and other family members, and other care givers should be educated about TB and the importance of completing treatment. Treatment is usually administered by the child’s mother or other caregiver. Support from the child’s parents and immediate family is vital to ensure a satisfactory treatment outcome. Often, a health-care worker can observe and record the treatment, but if this arrangement is not convenient for the family, a trained community member (preferably someone other than the child’s parent or immediate family) can undertake this responsibility. All children should receive treatment free of charge, whether the child is smear-positive at diagnosis or not. fdcs should be used whenever possible to improve simplicity of and adherence to treatment. patient treatment cards are recommended for documenting treatment adherence.

Hospital care. children with severe forms of TB should be hospitalized for intensive management where possible. conditions that merit hospitalization include: (i) TB meningitis and miliary TB, preferably for at least the frst two months;

(ii) respiratory distress; (iii) spinal TB; and (iv) severe adverse events, such as clinical signs of hepatotoxicity (e.g. jaundice). If it is not possible to ensure ood adherence and treatment outcome on an outpatient basis, some children may require hospitalization for social or logistic reasons.

HIV-infected children. most current international guidelines recommend that TB n children infected with HIV should be treated with a six-month regimen, as for hildren who are not infected with HIV. Where possible, HIV-infected children hould be treated with rifampicin for the entire duration of treatment, as higher elapse rates among HIV-infected adults have been found when ethambutol is sed in the continuation phase. most children with TB, including those who are IV-infected, have a good response to the six-month regimen. Possible causes of failure, such as non-compliance with therapy, poor drug absorption, drug resistance and alternative diagnoses, should be investigated in children who are not improving on anti-TB treatment.

All children with TB and HIV coinfection should be evaluated to determine hether ArT is indicated during the course of treatment for TB. Appropriate rrangements for access to antiretroviral drugs should be made for patients ho meet indications for treatment. given the complexity of co-administration of anti-TB treatment and ArT, consultation with an expert in this area is recommended before initiation of concurrent treatment for TB and HIV infection, regardless of which disease appeared frst. However, initiation of treatment for TB should not be delayed. children with TB and HIV coinfection should also receive cotrimoxazole as prophylaxis for other infections. In HIV-infected children with confrmed or presumptive TB disease, initiation of anti-TB treatment is the priority; however, the optimal timing for ArT initiation is not known. The decision on when to start ArT after starting anti-TB treatment involves a balance between the child’s age, pill burden, potential drug interactions, overlapping toxicities and possible IrIS versus the risk of further progression of immune suppression with its associated increase in mortality and morbidity. many clinicians start ArT 2–8 weeks after starting anti-TB treatment.

Recording and reportingchildren with TB should always be included in the routine nTp recording and reporting system (see chapter 3). It is crucial to notify the nTp of all identifed TB cases in children, register them for treatment and record their treatment outcome. At the end of the treatment course for each child with TB, the district TB offcer should record the standard outcome in the district TB register. four of the standard outcomes are applicable to children with smear-negative pulmonary or extrapulmonary TB: treatment completion, default, death and transfer out.

recording and reporting two age groups for children (0–4 years and 5–14 years) in the TB registers is useful for drug procurement (in child-friendly formulations for young children) and to monitor trends of case-fnding and treatment outcomes. Evaluation of treatment outcome by cohort analysis in children is a valuable indicator of the quality of programmes for child TB patients. for TB/ HIV indicators in children.

Main activities to be carried out by the national TB control programme for implementation of interventions to prevent and manage tuberculosis in children Implementation by the nTp of interventions to prevent and manage childhood

TB requires the activities listed below.

1. preparations:

• advocate to health authorities for mainstreaming of “childhood TB inter-

ventions” as part of routine nTp activities, in collaboration with the mater-

nal and child health programme;

• conduct a situation analysis of the extent to which childhood TB inter-

ventions are mainstreamed as part of routine nTp activities, of currently

available data on prevention, case fnding and treatment outcome, and of

resources available for implementation of childhood TB interventions;

• adapt nTp guidelines to refect childhood TB interventions;

• adapt maternal and child health guidelines to refect childhood TB poli-

cies;

• engage with key community stakeholders (academics, activists, etc.) to

develop appropriate information, education and communication (Iec)

material;

• in settings with high HIV prevalence, ensure effective linkages with HIV

control services.2. facilitate meetings with relevant health and other authorities at national, regional or provincial and district level, to ensure engagement of all health providers (government, nongovernmental organizations, private sector, religious and charity organizations, etc.)

3. Training to implement childhood TB interventions:

• develop and produce training material for health staff based on national

guidelines;

• develop and produce training material for community participants (e.g.

those involved in contact tracing and case-fnding, and in promoting and

encouraging adherence as “treatment supporters”);

• sensitize health staff and relevant community members regarding the

nature and extent of the problem of childhood TB, and motivate them to

share responsibility for contact tracing, case-fnding and treatment sup-

port.

4. delivery of childhood TB interventions as part of routine nTp activities

• assess drug procurement system for effectiveness in ensuring availability

of quality-assured formulations of anti-TB drugs for children (and consider

obtaining these drugs through the gdf);

• monitor results of contact tracing, case-fnding and treatment support;

• check how effectively the routine nTp recording and reporting system is

capturing the data on case-fnding and treatment outcomes;

• evaluate how effectively the full range of health providers is mobilized to contribute to making high-quality childhood TB interventions universally

accessible;

• assess effectiveness of the system of procurement of tuberculin.

5. Advocacy, communications and social mobilization (AcSm) activities

• incorporate messages about childhood TB in AcSm activities for health

promotion;

• advocate for commitment and funds to ensure universal access to high-

quality childhood TB interventions as part of routine nTp activities.

	TABLE. Commonly Used Drugs for	the Treatment	of Tuberculosis in Children
Drug	Dosage Forms	Daily Dose (mg/kg/day)	Twice-Weekly Dose (mg/kg/dose)	Maximum Daily Dose
Ethambutol	Tablets:	15-25	50	2.5 g
	100 mg
	400 mg
Isoniazid* t	Scored tablets:	10-15t	20-30	Daily: 300 mg
	100 mg			Twice weekly:
	300 mg			900 mg
	Syrup: $
	10 mg/mL
Pyrazinamide	Scored tablets:	20-40	50	2g
	500 mg
Rifampin*	Capsules:	10-20	10-20	Daily: 600 mg
	150 mg			Twice weekly:
	300 mg			900 mg
	Syrup:
	Formulated in syrup
	from capsules
Streptomycin	Vials:	20-^0	20-40
(intramuscular administration) 1 g

TABLE. Drugs for Treatment of Drug-Resistant Tuberculosis in			Children
Drugs	Dosage Forms	Daily Dosage (mg/kg/day)	Maximum Daily Dose
Capreomycin	Vials: 1 g	15-30 (intramuscular)	lg
Ciprofloxacin	Tablets:	Adults:	1.5 g
	250 mg	500-1500 in two divided doses
	500 mg
	750 mg
Clofazamine	Capsules:	50-100	200 mg
	50 mg
	100 mg
Cycloserine	Capsules:	10-20	1 Й
	250 mg
Ethionamide	Tablets:	15-20, given in two or three divided doses	1 g
	250 mg
Kanamycin	Vials:	15-30 (intramuscular)	1 8
	75 mg/2 mL
	500 mg/2 mL
	1 g/3 mL
Ofloxacin	Tablets:	Adults:	800 mg
	200 mg	400-800 mg total/day
	300 mg
	400 mg
Para-aminosalicyclic acid	Packets:	200-300 given in two to four divided doses	12 g
	4g

further work-up or treatment unless a case of disease is found.

2. Mother has an abnormal chest radiograph appearance. The mother and child should be separated until the mother has been evaluated thoroughly. If the radiograph, history, physical examination, and analysis of sputum reveal no evidence of active pulmonary tuberculosis in the mother, it is reasonable to assume the infant is at low risk of infection. However, if the mother remains untreated, she later may develop contagious tuberculosis and expose her infant. Both mother and infant should receive appropriate follow-up care, but the infant does not need treatment. If the radiograph and clinical history suggest pulmonary tuberculosis, the child and mother should remain separated until both have begun appropriate chemotherapy. The infant should be evaluated for congenital tuberculosis. The placenta should be examined. If the mother has no risk factors for drug-resistant tuberculosis, the infant should receive INH and close follow-up care. The infant should undergo a tuberculin skin test at 3 or 4 months after the mother is judged to be no longer contagious; evaluation of the infant at this time follows the guidelines for other exposures of children. If no infection is documented at this time, it would be prudent to repeat the tuberculin skin test in 6 to 12 months. If the mother has tuberculosis caused by a multidrug-resistant isolate of M. tuberculosis or she has adhered poorly to therapy,

the child should remain separated from her until she no longer is contagious or the infant can be given a BCG vaccine and be kept separated until the vaccine "takes" (marked by a reactive tuberculin skin test). Infection

The recommendation for preventive therapy of tuberculosis—that is, the treatment of asymptomatic tuberculin-positive persons—is based on data from several well-controlled studies; it applies particularly to children and adolescents who are at high risk for the development of overt disease but at very low risk for the development of the main toxic manifestation of INH therapy, which is hepatitis.The large, carefully controlled U.S. Public Health Study of 1955, followed by others both in this country and abroad, demonstrated the favorable effect of 12 months of INH on the incidence of complications due to progression of tuberculosis infection. The younger the tuberculin reactor, the greater the benefitThe American Thoracic Society and the CDCrecommend that INH treatment of tuberculosis infection be given to all positive tuberculin reactors younger than 35 years. The question arises as to how long the protective effect can be expected to last. Comstock and associatesin their final report on INH prophylaxis in Alaska, demonstrated the protective effect of 1 year of chemopro-phylaxis to be at least 19 years. Hsu reported on2494 children followed for up to 30 years and showed that adequate drug treatment prevented reactivation of tuberculosis during adolescence and into young adulthood. It is likely that the decreased risk of active tuberculosis after INH therapy may be lifelong in persons infected with INH-susceptible tubercle bacilli. Failure of INH after exposure to INH-resistant M. tuberculosis has been documented. No controlled study of an alternative regimen has been reported. RIF alone is recommended and widely used.

The dosage of INH to be used has had little study. Most investigators have used a regimen based on 4 to 8 mg/kg of body weight/day, usually taken all at once, for a period of 6 to 12 months. A dose of 5 mg/kg/day was found satisfactory in one study." Most clinicians prescribe a dose of 10 to 15 mg/kg/day to a total of 300 mg/day for treatment of infection to be sure of achieving therapeutic levels even among patients whose bodies inactivate the drug rapidly by acetylation.

The duration of INH treatment initially was set arbitrarily at 12 months. A large trial was conducted on adults in Eastern Europe with old fi-brotic lesions caused by tuberculosis, comparing regimens of daily INH taken for 12, 24, and 52 weeks with a placebo for their ability to prevent tuberculosis disease.¹⁰⁰ Therapy for 1 year was most effective, especially if patients were adherent. However, therapy for 24 weeks afforded a fairly high level of protection. A subsequent analysis concluded that the 24-week duration of preventive therapy was more cost-effective for adults than the 52-week duration. Subsequently, many health departments have accepted 6 months of INH therapy as their standard regimen for adults. However, the cost-effectiveness analysis does not apply to children. There are no similar data for INH therapy in children. A duration of 9 months is currently recommended for children by the AAP and CDC. INH is taken daily under self-supervision or can be taken twice weekly under directly observed therapy (DOT). When the child is infected with an INH-resistant but RTF-susceptible strain of M. tuberculosis, RIF should be substituted for INH. If the infecting strain is resistant to both INH and RIF, two other drugs usually are used. No combination of drugs is known to be superior to the others; usually two from among pyrazinamide (PZA), ethambutol, ethionamide, cycloserine, or para-aminosalicylic acid are chosen. Disease

Clinical trials of anti-tuberculosis drugs in children are difficult to perform, mostly because of the difficulty in obtaining positive cultures at diagnosis or relapse and the need for long-term follow-up. Historically, recommendations for treating children with tuberculosis were extrapolated from clinical trials of adults with pulmonary tuberculosis. Since the 1980s, however, a large number of clinical trials involving only children have been reported. In 1983, Abernathy and colleaguesreported successful treatment of 50 children with tuberculosis in Arkansas using INH and RIF daily for 1 month, then twice weekly for 8 months. Most pulmonary infiltrates cleared by the end of therapy, but hilar adenopathy usually still was present radiographically, then gradually cleared over 2 to 3 years. Patients with only hilar adenopathy can be treated successfully with INH and RIF for 6 monthsSeveral major studies of 6-month therapy in children using at least three drugs in the initial phase have been reported." The most commonly used regimen was 6 months of INH and RIF supplemented during the first 2 months with PZA. The overall success rate has been greater than 98% and the incidence of clinically significant adverse reactions less than 2%. Regimens not using streptomycin were as successful as those that included it. Using twice-weekly medications (under DOT) during the continuation phase was as effective and safe as daily administration. Two studies used twice-weekly therapy throughout the treatment regimen with excellent success.- ^U1The 6-month, three-drug regimen is successful, tolerated well, and less expensive than the 9-moiith regimen. It also effects a cure faster, so that there is a greater likelihood of successful treatment if the child becomes nonadherent later in therapy.

Controlled treatment trials for various forms of extrapulmonary tuberculosis are rare. Several of the 6-month, three-drug trials in children included extrapulmonary cases.Most non-life-threatening forms of extrapulmonary tuberculosis respond well to a 9-month course of INH and RIF or to a 6-month regimen including INH, RIF, and PZAOne exception may be bone and joint tuberculosis, which may have a high failure rate when 6-month chemotherapy is used, especially when surgical intervention has not taken place.

Tuberculous meningitis usually is not included in trials of extrapulmonary tuberculosis therapy because of its serious nature and low incidence. Treatment with INH and RIF for 12 months generally is effective. Kendigreported 15 children who absconded from therapy for tuberculous meningitis between 4 and 9 months of therapy; only two children died, and the majority of survivors had a good outcome. A more recent study from Thailand showed that a 6-month regimen including PZA for tuberculous meningitis led to fewer deaths and better outcomes than did longer regimens that did not contain PZA. Most children are treated initially with four drugs (INH, RIF, PZA, and ethambutol or streptomycin). The PZA and fourth drug are stopped after 2 months, and INH and RIF are continued for a total of 9 to 12 months. Drug Resistance

Patterns of drug resistance in children tend to mirror those found in adult patients in the population.Outbreaks of drug-resistant tuberculosis in children occurring at schools have been reported.The key to determining drug resistance in childhood tuberculosis usually comes from the drug susceptibility results of the infectious adult contact case's isolate.

Therapy for drug-resistant tuberculosis is successful only when at least two bactericidal drugs to which the infecting strain of M. tuberculosis is susceptible are given. When INH resistance is considered a possibility on the basis of epidemi-ologic risk factors or the identification of an INH-resistant source case isolate, an additional drug—usually ethambutol or streptomycin— should be given initially to the child until the exact susceptibility pattern is determined and a more specific regimen can be designed. Exact treatment regimens must be tailored to the specific pattern of drug resistance. Duration of therapy usually is extended to at least 9 to 12 months if either INH or RIF cannot be used and to at least 18 to 24 months if resistance to both drugs is present. Occasionally, surgical resection of a diseased lung or lobe is required. An expert in tuberculosis always should be involved in the management of children with drag-resistant tuberculosis infection or disease. Adherence and Directly Observed Therapy

For many families with a child with tuberculosis, the disease is but one of many social and other problems in the family's life and, at certain times, other problems may supersede the perceived importance of tuberculosis. To combat this problem of nonadherence with treatment, most health departments have developed programs of DOT in which a third party, usually but not always a health care worker, is present during the administration of each dose of medication. DOT should be considered standard therapy for children with tuberculosis disease. The clinician should coordinate this treatment with the local health department. In my clinic, all children with tuberculosis are treated exclusively with DOT, which can be given at an office, clinic, home, school, work, or any other setting. It is highly effective and safe, and the patient satisfaction is high if it is offered as a special service to treat tuberculosis. Increasingly, high-risk children with tuberculosis infection are being treated with DOT at schools or in other locations to ensure completion of therapy. DOT also should be considered for all household contacts of adult tuberculosis patients, especially when the adult also is receiving DOT. Although specific controlled studies are lacking, twice-weekly DOT appears to be effective for treating tuberculosis exposure and infection in children and adolescents. Follow-up of children treated with antituberculosis drugs has become more streamlined in recent years. While receiving chemotherapy, the patient should be seen monthly, both to encourage regular taking of the prescribed drugs and to check, by a few simple questions (concerning appetite, well-being) and a few observations (weight gain; appearance of skin and sclerae; palpation of liver, spleen, and lymph nodes), that the disease is not spreading and that toxic effects of the drugs are not appearing. Repeat chest radiographs probably should be obtained 1 to 2 months after the onset of chemotherapy to ascertain the maximal extent of disease before chemotherapy takes effect; thereafter, they rarely are necessary. Chemotherapy has been so successful that follow-up beyond its termination is not necessary, except for children with serious disease, such as tuberculous meningitis, or those with extensive residual chest radiographic findings at the end of chemotherapy. Chest radiograph findings resolve slowly; it is typical that enlarged lymph nodes take 2 to 3 years to resolve, well beyond the completion of ultimately successful chemotherapy. A normal-appearing chest radiograph is not a necessary criterion for stopping therapy.

PUBLIC HEALTH ASPECTS OF PEDIATRIC TUBERCULOSIS

It is hoped that it has become obvious that the control of tuberculosis—for a community and for individuals—depends on close cooperation between the clinician and the local health department. It is critically important that clinicians report cases of tuberculosis to the health department as soon as possible. Public health law in all states requires that the suspicion of tuberculosis disease in an adult or child be reported immediately to the health department. The clinician should not wait for microbiologic confirmation of the diagnosis because it is this reporting that leads to the initiation of the contact investigation that may find infected children and allow them to be treated before disease occurs. If the clinician waits for confirmatory laboratory results, the child may progress from infection to disease before intervention can occur. The clinician should always feel free to contact the local health department about special issues involving tuberculosis exposure, infection, or disease in a child. Not every clinical situation can be anticipated by normal guidelines and, in some cases, an unusual intervention may be warranted.

The child was born or has resided in a country with high tuberculosis rates

There is a family history of tuberculosis (last several generations)

There is an adult with HIV infection or AIDS who has spent time in the household or with the child

An adult who has been in jail or prison has spent time in the household or with the child

The child is in foster care

The child is a member of a group identified locally to be at increased risk for tuberculosis infection (examples may include migrant worker families, the homeless, certain census tracts or neighborhoods)

Much of the focus on tuberculin skin-testing should be placed on identification of risk factors for a child being in a group with a high prevalence of infection. Although some risk factors may apply across the country, local health departments must identify those risk factors that are germane to their area. Clinicians and their organizations must work closely with local health departments to establish which children should be tested and which should not. Health departments should advise school districts as to whether any type of school-based skin testing is appropriate and what nature it should take. Obviously, social and political problems can occur when selective testing is suggested. What is correct from a public health point of view may not be easy to translate into a workable and generally acceptable policy. Local clinicians can be extremely helpful to health departments in advancing prudent and reasonable tuberculosis control policies, particularly when other government or public agencies are involved.

Tuberculosis in Children

The incidence and prevalence of pediatric tuberculosis (TB) worldwide varies sig-ficantly according to the burden of the disease in different countries. It has been estimated that 3.1 million children under 15 years of age are infected with TBworldwide. According to the World Health Organization (WHO), children with TBrepresent 10 % to 20 % of all TB cases. The majority of these cases occur in low-income countries where the prevalence of Human Immunodeficiency Vi-rus/Acquired Immunodeficiency Syndrome (HIV/AIDS) is high. TB occurs fre-quently among disadvantaged populations, such as malnourished individuals, andthose living in crowded areas. According to WHO reports, India, China, Pakistan,the Philippines, Thailand, Indonesia, Bangladesh, and the Democratic Republic ofthe Congo account for nearly 75 % of all cases of pediatric TB. Furthermore, it has also been reported that TB is re-sponsible in Sub-Saharan countries for between 7 % and 16 % of all episodes ofacute pneumonia in HIV-infected children, and for approximately one fifth of alldeaths in children presenting with acute pneumonia.On the other hand, in developed countries such as the United States (US), while anincrease in the incidence of TB of approximately 13 % was reported in all agesfrom, the rate among children younger than 15 years old increased by33 %. This was mainly attributed to the HIV epidemic, which increased the risk ofdeveloping active TB among persons with latent TB infection and HIV co-infection. As in adults, TB equally affects children of both genders (males andfemales), but an increased risk of mortality exists at the extremes of age. Therefore,young children and especially newborns are at a high life risk when they are ex-posed to a contagious source. Since most pediatric cases occur due to a

rapid progression of a recent infection with a short incubation period, this implies ahigh rate of recent transmission in the community. Therefore, the infected and illchildren in the community are an indirect, useful parameter for assessing the im-pact of Tuberculosis Control Program activities.Pulmonary TB in children has a low bacillary load and cavities are also rarely pres-ent. Children also lack the forceful cough mechanism seen in adults. In these cases, the disease is frequently associated with unfavorableconditions, such as bad nutrition.Most risk factors for the acquisition of TB are usually exogenous to the patient.Thus, the likelihood of being infected depends on the environment and characteris-

tics of the index case. However, the development of active disease also depends onthe inherent immunologic status of the host.

. Etiology, transmission and pathogenesis

In about 95 % of cases, TB is an airborne disease, transmitted by particles, or droplet nuclei that are expelled when persons who have pulmonary or laryngeal TBsneeze, cough, speak or sing. When the recipients are persons withoutprevious natural contact with M. tuberculosis, the infectious process is denominated primary infection. When this infection evolves to the disease, it is calledprimary TB. Droplet nuclei containing between one to 10 bacilli and a diameter close to 10 µmare expelled with the cough, suspended in the air and transported by air currents.

Normal air currents can keep them airborne for prolonged periods of time andspread them throughout rooms or building. Some of these droplet nuclei, usuallylarger than 10 µm, are inhaled and anchored in the upper respiratory tract. The mucus and the ciliary system of the respiratory tract avoid further pro-gression of mycobacteria.The effective infective droplet nucleus is very small; measuring 5 µm or less, it isable to avoid the mucus and ciliary system action and produce the anchorage inbronchioles and respiratory alveoli. The small size of the droplets allows them toremain suspended in the air for prolonged periods of time. Although theoretically asingle organism may cause disease, it is generally accepted that about five to 200inhaled bacilli are necessary for a successful infection. After inhalation, the bacilliare usually installed in the midlung zone, into the distal and subpleural respiratorybronchioles or alveoli.

Subsequently, alveolar macrophages phagocytose the inhaled bacilli. However,these first macrophages are unable to kill mycobacteria and the bacilli continuetheir replication inside these cells. Logarithmic multiplication of the mycobacteriatakes place within the macrophage at the primary infection site. Thereafter, trans-portation of the infected macrophages to the regional lymph nodes occurs leading to the lymphohematogenous dissemination of the mycobacteria to other lymphnodes and organs such as kidneys, epiphyses of long bones, vertebral bodies, Tuberculosis in Children be the result of dormant bacilli acquired during a past infection. In children, thedistinction may not be so clear because the disease more often progresses from an initial or primary infection. From a practical point of view, adults with TB almostalways manifest significant radiographic abnormalities and/or clinical symptoms,whereas up to 50 % of pediatric patients may remain asymptomatic with subtleabnormalities on the chest radiograph. Sometimes, erythema nodosum may be theonly clinical finding in a child recently infected with M. tuberculosis.

Primary pulmonary tuberculosis

Unfortunately, children younger than five years old may develop disseminated TBin the form of miliary disease or tuberculous meningoencephalitis before the TSTresult becomes positive. Thus, a very high index of suspicion must be adoptedwhen pediatric patients have a contact history. Children with asymptomatic infec-tion usually have a positive TST result but do not have any clinical or radiographic manifestations. These children may be identified on a routine medical examination,as children who have recently emigrated from a high prevalence country, oradopted children, or they may be identified subsequent to TB diagnosis in house-hold or other contacts.

Pulmonary TB in children can range from an asymptomatic primary infection to aprogressive primary TB. Primary TB is very often characterized by the absence ofsigns on clinical evaluation. Asymptomatic presentations are more common amongschool-age children (80-90 %) than in infants less than one year old (40-50 %).

Disease should be suspected if the child has been exposed to a contagious sourceand if the TST is positive. In contrast to pulmonary TB in adults, the TST follow-ing standard procedures is an important element for TB diagnosis in children.Sometimes these patients are identified by a positive TST that may be associatedwith allergic manifestations such as erythema nodosum and phlyctenular conjunc-tivitis. Erythema nodosum is a toxic allergic erythema with nodular lesions in theskin or under it, 2 to 3 cm large. These lesions are spontaneously painful and verypainful under pressure, and are usually located bilaterally in feet and legs. Theerythema nodosum is usually accompanied by pharyngitis, fever and joint inflam-mation and is more frequent in girls over six years. Phlyctenular conjunctivitis is anallergic keratoconjunctivitis characterized by the presence of small vesicles that usually evolve to ulcers and resolve without scars. The more frequent symptoms important exceptions since their disease closely resembles Patients with tuberculomas or tubercular brain abscesses may present with focalneurological signs. Spinal cord disease may result in the acute development ofspinal block or a transverse myelitis-like syndrome. A slowly ascending paralysismay develop over several months to years.

Skeletal tuberculosis

Osteoarticular TB complications appear in 1 % to 6 % of untreated primary infec-tions. Clinical and radiographic presentations vary widely and depend upon thestage of the disease at the time of diagnosis. Skeletal TB may remain unrecognizedfor months to years because of its lack of specific signs and symptoms and indolentnature.Bone or joint TB may present acutely or subacutely. Sites commonly involved arethe large weight-bearing bones or joints including the vertebrae (50 %), hips(15 %), and knees (15 %). Less common skeletal sites are the femur, tibia, andfibula. Destruction of the bones with deformity is a late sign of TB. Manifestationsmay include angulation of the spine or “gibbus deformity” and/or the severe ky-phosis with destruction of the vertebral bodies or “Pott’s disease”.Cervical spine involvement may result in atlantoaxial subluxation, which may leadto paraplegia or quadriplegia. TB of the skeletal system may also lead to involve-ment of the inguinal, epitrochlear, or axillary lymph nodes.

Spinal tuberculosis

Congenital tuberculosis

Congenital TB is considered a rare event in the whole spectrum of TB presentations. This infection is caused by lymphohematogenous spread during pregnancyfrom an infected placenta or aspiration of contaminated amniotic fluid.Symptoms typically develop during the second or third week of life and includepoor feeding, poor weight gain, cough, lethargy, and irritability. Other symptomsinclude fever, ear discharge, and skin lesions, failure to thrive, icterus, hepatosple-nomegaly, tachypnea, and lymphadenopathy. Congenital TB diagnosis is based onclinical features and the infant should have at least one of the following proven TBlesions; Molecular methods Nucleic acid amplification methods, such as the polymerase chain reaction (PCR),have shown sensitivity and specificity greater than 90 % for detecting smear-positive pulmonary TB in adults. Although the use of this technique in children hasnot yet been extensively evaluated, several studies have reported sensitivity rangingfrom 25 % to 83 % in children with pulmonary TB. According to several reports, the sensitivity and specificity of the nucleicacid amplification methods in smear-positive cases may exceed 95 %, but the sen-sitivity in smear-negative cases, which includes most of the pediatric cases, variesfrom 40 % to 70 %.

To distinguish TB infection from disease has been particularly difficult with thecurrently available in-house and commercial nucleic acid amplification tests. Speci-ficity is even more controversial, and false positive results have been observed inup to 20 % of control.

Tuberculin skin testing

The American Academy of Pediatrics has issued the following guidelines for pedi-atric testing:

• TST is indicated in children who have been in contact with persons with

active TB

• TST is indicated in immigrants from regions in which TB is endemic or children with travel histories to these regions

• TST is indicated in children with radiographic or clinical findings sugges-

tive of TB

• Annual TST is indicated in children who are infected with HIV or those

living in a household with persons infected with HIV; also in incarcerated

adolescents

• Testing at two- to three-year intervals is indicated if the child has been ex-

posed to high-risk individuals, including those who are homeless, adults

who are infected with HIV, drug users, residents of nursing homes, and in-

carcerated adolescents or adults

• Testing in children 4-6 years old and 11-16 years old living in high-

prevalence areas is indicated irrespective of the presence of risk factorsPerforming an initial TST before the initiation of immunosuppressive therapy is recommended in any patient. TST application should follow the principles defined in the following paragraphs.

Mantoux technique

In the accepted protocol for TST by the Mantoux technique, a standardized antigen preparation containing two tuberculin units of purified protein derivative (PPD) should be injected intradermally into the volar aspect of the fore-arm using a 27-gauge needle. The test should read by skilled personnel 48-72 hours after administration. The size of induration and not erythema must be measured by placing the ruler transversally to the long axis of the forearm (ruler-based reading). The Mantoux test is the only skin test acceptable in children evaluation. Multiple puncture techniques should no longer be used because of its intrinsic limitations and inaccuracy, International Union Against Tuberculosis and Lung BCG vaccination is used in all developing countries, and is not a contraindication for the TST, but differentiating tuberculin reactions caused by BCG vaccination from those attributable to M. tuberculosis infection is sometimes difficult. A history of contact with a person with contagious TB or emigration from a high prevalence country increases the likelihood that a TST induration of 10 mm or more is due to a true infection with M. tuberculosis. The reactivity caused by BCG vaccination, which is usually less than 10 mm, generally wanes with time, but multiple BCG vaccinations can perhaps cause a positive TST. TST result is negative and the chest X-ray does not suggest TB. Progressive disease may not develop until six months of age.

• If the mother is receiving treatment and non-infectious, separation of themother and infant is not necessary and breastfeeding should not be discouraged. The amount of drug in breast milk is very small, and there has beenno good documentation of adverse effects, although the infant should be given pyridoxine. Mothers who have received anti-tuberculosis drugs are

much less infectious than those who have not received any treatment, due primarily to the reduction in the bacillary population in the lungs.

• The mother has active disease and is contagious at the time of delivery. In this situation, separation of the mother and infant is recommended until the mother is no longer contagious. Thereafter, management is as described above.

Treatment of congenital infection

Congenital TB is not a frequent presentation, but if the possibility is suspected, a prompt Mantoux test and chest radiograph must be performed, and treatment of the infant begun immediately. INH should be administered until the infant is six months old, at which time TST should be repeated. If the TST result is positive, the infant should be treated with INH for a total of nine months.

Safety considerations for treatment of latent tuberculosis Treatment of childhood TB infection with INH has proven to be very safe. The incidence of asymptomatic elevation in serum liver enzymes in children is usually lower than 2 %, and clinical hepatitis is less than 1 %. Routine tests of blood chemistry and serum hepatic enzymes are unnecessary unless the child has hepatic disease or dysfunction, or is also taking other potentially hepatotoxic drugs. Medical examinations are recommended every four to six weeks to check for adverse reactions as well as to assure adherence to the treatment. Simultaneous administration of pyridoxine is routinely prescribed only for breastfed babies, pregnant women and persons with poor dietary intake of this vitamin.

Treatment of infection with a multidrug-resistant strain

The best treatment for latent TB in both adults and children infected with a multidrug-resistant strain (MDR-TB) is uncertain because it requires the use of less effective drugs that are associated with adverse reactions that are both more frequent and more severe. Careful follow-up and observation of the children is recommended, as none of the second-line drugs have been evaluated for preventive therapy. Drugs have been used in these circumstances include pyrazinamide, fluoroquinolones, and ethambutol, depending on the strain susceptibility pattern.

Treatment of pediatric tuberculosis disease

Treatment of pediatric TB follows the same general principles as the treatment of adults. The specific therapeutic regimen should be individually designed according to available drug susceptibility testing results, the tolerance of the patients for the drugs, and the continuous supply and availability of drugs for the whole duration of treatment. Following the standard guidelines for new patients, the child must be given at least three drugs during the first phase of the treatment. As in the HIV co-infected population, injections are avoided in children when possible, and therefore streptomycin, which also has ototoxicity, is not recommended in this age group. The second phase must include two drugs, which can be dministered twice a week

.• when the child is exposed to persons with contagious pulmonary MDR-TB,

has negative HIV and TST results, and cannot be removed from the exposure;

• the child is exposed to persons with untreated or ineffectively treated con-

tagious pulmonary TB, has negative HIV and TST results, and cannot be

removed from the exposure or treated with antitubercular medication.

From birth to two months of age, administration of BCG does not require a prior TST. Thereafter, a TST is mandatory prior to vaccination. Adverse reactions due to the vaccine include subcutaneous abscess formation and lymphadenopathy. Contraindications to the administration of the vaccine include immunosuppressed conditions, such as primary genetic mmunodeficiency syndromes or secondary immunodeficiency, for example from steroid use, and HIV infection. However, in areas of the world where the risk of TB is high, WHO recommends using the BCG vaccine in children who have asymptomatic HIV infection.

Rare complications of the BCG vaccination, such as osteitis of the epiphyses of the long bones or disseminated BCG, are generally associated with an immunocompromised status and may necessitate administration of anti-tuberculosis therapy, excluding pyrazinamide.

Prognosis of pediatric tuberculosis

The prognosis for children with TB varies according to the clinical manifestation. In general and under DOTS strategy conditions, primary TB caused by a fully drug-susceptible strain has a more than 95 % probability of being cured, but poor bprognosis is associated with disseminated TB, miliary disease and tubercular meningitis. The prognosis of tubercular meningitis varies according to the stage of the disease at the time treatment is started. Stage one has good prognosis, while patients with stage three are usually left with sequelae, such as blindness, paraplegia, deafness, mental retardation, movement disorders, and diabetes insipidus. Higher mortality rates occur in children younger than five years old (20 %) and in those with a prolonged illness of more than two months (80 %) (American Academy of Pediatrics 1994, American Academy of Pediatrics 2000, Correa 1997). The nTp should collaborate with child health services in implementing the strategic approach to prevention and management of TB in children. The overall context for providing high-quality care to sick children is provided by the ImcI strategy promoted by WHO and the United nations children’s fund (UnIcef)

Prevention of tuberculosis in children should organize a system for screening the children of household contacts of infectious pulmonary TB cases. This enables those children found to have TB to be registered and treated, and for those children not found to have TB but who are at high risk of TB (children aged less than 5 years and all HIVinfected children) to receive IpT (i.e. daily isoniazid for at least six months). The tuberculin skin test (TST) is the best way to detect M. tuberculosis infection, and chest X-ray (cXr) is the best method to screen for TB disease among contacts. These tests should be used where available to screen exposed contacts. However, tuberculin is often unavailable in low-resource settings. TST and cXr, when not readily available, should not preclude contact screening and management, as this can be conducted on the basis of simple clinical assessment Special situations

• Close contacts of MDR-TB patients

children who are close contacts of mdr-TB patients should receive careful

clinical follow-up for a period of at least two years. If active disease devel-

ops, prompt initiation of treatment with a regimen designed to treat mdr-TB

is recommended. WHO does not recommend second-line drugs for chemo-

prophylaxis in mdr-TB contacts.

• Breastfeeding infants

Infants who are being breastfed have a high risk of infection from moth-

ers with smear-positive pulmonary TB and of developing TB. Infants should

receive six months of IpT, followed by Bcg immunization. Breastfeeding may

be safely continued during this period.

Diagnosis of tuberculosis in children

KEY RISK FACTORS FOR TUBERCUlOSIS

n Household contact of a newly diagnosed smear-positive case

n Aged less than 5 years

n HIV infection

n Severe malnutrition

KEY FEATURES SUGGESTIVE OF TUBERCUlOSIS

A diagnosis of tuberculosis isstrongly suggested in the presence of three or more of the following:

n chronic symptoms suggestive of tuberculosis

n physical signs highly suggestive of tuberculosis

n a positive tuberculin skin test

n chest X-ray suggestive of TB.

he diagnosis of TB in children relies on a careful and thorough assessment of all the evidence derived from an accurate history, clinical examination and relevant investigations, e.g. TST, cXr and sputum smear microscopy. Although bacteriological confrmation of TB is not always feasible, it should be sought whenever possible, e.g. by sputum smear microscopy for children with suspected pulmonary TB who are old enough to produce a sputum sample. A trial of treatment with anti-TB medication is not recommended as a method for diagnosing TB in children. The decision to treat a child should be carefully considered; once such a decision is made, the child should be treated with a full course of therapy. Standard international case defnitions apply to adults and children. In most immunocompetent children, TB presents with symptoms of a chronic disease after they have been in contact

with an infectious source case. existing diagnostic tests for TB in children have shortcomings, and the full range of tests (including bacteriological culture and TST) is often not available in settings where the disease is diagnosed in the vast majority of cases. In some countries, score charts are used for the diagnosis of TB in children. These charts have rarely been evaluated or validated against a “gold standard” and should therefore be used as screening tools and not as the means of making a frm diagnosis. Score charts perform particularly poorly in children suspected of pulmonary TB and in children who are also HIV-infected.children are equally susceptible to drugresistant and to drug-susceptible TB. However, drug-resistant TB should be suspected if any of the features below are present.

1. Features in the source case sugges-tive of drug-resistant TB

• contact with a known case of drugresistant TB;

• remains sputum smear-positive after three months of treatment;

• history of previously treated TB;

• history of treatment interruption

2. Features of a child suspected of having drug-resistant TB

• contact with a known case of drug-resistant TB;

• not responding to the anti-TB regimen;

• recurrence of TB after adherence to treatment.

RECOMMENDED APPROACH FOR DIAGNOSIS OF TuBERCulOSIS IN CHIlDREN

1. careful history (including history of TB contact and symptoms consistent with TB)

2. clinical examination (including growth assessment)

3. Tuberculin skin testing

4. Bacteriological confrmation whenever possible

5. Investigations relevant for suspected pulmonary or extrapulmonary TB

6. HIV testing (in areas of high HIV prevalence)

Volumes of observation of children and teenagers who are on dispensary registration at the doctor – phthisiatrician

Categories and groups	Roentgenological observation	Laboratory analysis	Analysis of sputum, bronchial lavage water, gastric, bioptates (bacterioscopy and inoculation)	Tuberculin tests
1	2	3	4	5
1, 2, 3	At local forms of tuberculosis in an intensive phase of treatment roentgenograms, tomograms not less often than once in 2 months, in a supporting phase once in 3 months. At an early tubercular intoxication 2 times per one year. At indications - computer tomography of lungs	At registration and in a hospital in an intensive phase of treatment each month to make the general analysis of blood and urine to define a level of bilirubin, in blood, , alanine aminotransphera-se; ureas, residual nitrogen, the general fiber. At the receipt in a hospital it is necessary to define a group of blood and a Rhesus factor, sugar in blood and urine, analysis of blood on Hbs-Ag, AIDS, Wassermann reaction. In supporting phase of treatment not less often than 1 time in 2 months to make the general analysis of blood and urine to define a of level bilirubin, alanine- aminotranspherase	At registration thrice analysis of sputum (washout from bronchial tubes) on МВT by a method of bacterioscopy, and thrice research of the material by crop on nutrient media with obligatory definition medicinal sensitivity МВT, the further each month two-single analogical research before the termination of allocation МВT, then during 3 months each month two-single analogical research. At revealing МВT obligatory research medicamentous them resistance up to antitubercular preparations	At the beginning of treatment and after its ending
4	Roentgenograms, tomograms at local forms of disease in an intensive phase of treatment not less often than once in 2 months, in supporting phase once in 3 months. In a phase of remission once in 6 months	During treatment in a hospital analogically to volume and terms of observation of 1-st category patients. During remission not less than 1 time in 3 months to make the general analysis of blood and urine	At registration thrice analysis of sputum (washout from bronchial tubes) on МВT by a method of bacterioscopy, and thrice analysis of the material by crop on nutrient media with obligatory definition medicinal sensitivity of МВT, further each month twice analogical research before the termination of МВT excretion, then during 3 months each month twice analogical research. During remission analysis of the material on МВT once a month by a method of microscopy, and if necessary – by the cultural method	During the realization of the basic course at the beginning of treatment and after its ending. During remission once a year
5.1	The roentgenogram 2 times per one year in the first year of supervision, once a year before removal from registration	The analysis of blood and urine once half-year in the first year, at antirelapses courses - monthly	1 time in 6 months in the first year, further - under indications by a method of microscopy and crop	Once a year
5.2	The roentgenogram once to not infected and 2 times per one year to infected (to children till 3 years of age once a year)	The analysis of blood and urine once 3-6 months, at chemoprophylaxis monthly	To not infected and infected children - 1 time in 6 months by a method of microscopy	Once a year
5.4	The roentgenogram, the tomograms at a registration and removal from registration	The analysis of blood and urine once in 6 months, at chemoprophylaxis monthly	At registration and removal from the registration by a method of microscopy	Once a year
5.5	The roentgenogram, the tomograms at a registration and removal from registration	The analysis of blood and urine once at registration and removal from registration	At registration 3 analysis by a method of microscopy and 2 analysis by a cultural method	At registration

Site	Case Number (%)	Median Age (years)
Pulmonary	1,213 (77.5)	6
Lymphatic	209 (13.3)	5
Pleural	49 (3.1)	16
Meningeal	29 (1.9)	2
Bone/joint	19 (1.2)	8
Miliary	14 (0.9)	1
Genitourinary	13 (0.8)	16
Peritoneal	4 (0.3)	13
Other	16(1.1)	12
Total	1,566 (100)	6

	Infants and Young Children	Older Children and Adolescents
Symptom
Fever	Common	Uncommon
Night sweats	Rare	Uncommon
Cough	Common	Common
Productive cough	Rare	Common
Hemoptysis	Never	Rare
Dyspnea	Common	Rare
Sign
Rales	Common	Uncommon
Wheezing	Common	Uncommon
Dullness	Rare	Uncommon
Diminished	Common	Uncommon
breath sounds