Lesson 1

1.X-ray diagnostics of lung tuberculosis. Basic X-ray syndromes.

2. Tuberculin diagnostics.

3. In-time diagnostics of tuberculosis of children, teenagers and adults Antituberculous activity of physicians of various profiles.

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Methods of  the X-ray diagnostics of tuberculosis of respiration organs. Methodical of interpretation roentgenograms of lungs and description pathological shadows

 

 

Roentgenologic examination is one of the main methods of diagnostics of tuberculosis and unspecific respiratory diseases. The following methods of roentgenologic diagnostics are used: roentgenoscopy, roentgenography, fluorography, tomography, computer tomography, target roentgenography, bronchography, fistulography, angiopulmography and bronchial arteriography, pleurography, kymography and polygraphy.

Roentgenoscopy is performed in various positions of a patient, at various respiration phases that allows to study the function of the diaphragm, heart pulsation, to choose the optimum spot for the puncture as well as prior to a target roentgenography, at performing bronchography, fistulography, angiopulmography etc.

In general, nowadays, lung roentgenoscopy is rarely done, more often by means of apparatus with electron-optical transformer. First of all an examining roentgenoscopy is done, during which the chest form is defined, transparence and the width of the lung fields, localization and the sizes of the shade of the mediastinum and the heart, mobility of the cupolas of the diaphragm and the rib front sections. After the examining roentgenoscopy the screen field is narrowed by the diaphragm and a more detailed examination of the lung tissue structure and pathologic changes is done.

Roentgenography allows to discover and fix on a film such morphological lungs structures, which are not visible at roentgenoscopia, to keep roentgenograms, to compare them in dynamics; and the most important is the fact, that radiation doze of a patient is much less, than at roentgenoscopy.

The disadvantage of the roentgenography is its statics, that doesn’t allow to judge about the organ function. However, the implication of the serial roentgenography and roentgenocinematography considerably level that shortcoming.

Normally the left lung is narrower and longer than the right one, mediastinum organs are localized between medial ends of clavicles at the background of the shadow of the sternum and the spine.

In the right lung there are 3 lobes (upper, middle and lower), in the left one – 2 (upper and lower). The lobes (upper and lower) are divided by the interlobular splits. Slanting interlobular split comes equally in the right and left lungs: from the level of the 4^th thoracal vertebra sidelong down and forward to the cross with the 7^th rib. On the right the horizontal split, that comes from the level of junction of the 4^th rib and the sternum to the cross with the slanting interlobular split, divides the upper and middle lobes. Each lung has 10 segments. But sometimes there can be oly 9 segments in the left lung (fig. 1).

 

Fig. 1.  Lobe and segmental structure of the lungs.

 

Segments of the right lung: 1-upper, 2-rear, 3-anterior, 4-exterior, 5-interior, 6-upper of the lower part, 7-inferointerior, 8-inferoanterior, 9-inferoexterior, 10-inferoposterior.

Segments of the left lung: 1-uper, 2-rear, 3-anterior, 4-upper-uvular, 5-lower-uular, 6-upper of the lower part, 8-inferoanterior, 9-inferoexterior, 10-inferoposterior.

         The tuberculosis process is most often localized in the 1^st, 2^nd and 6^th, sometimes in the forvard and basal segments. To define the localization of the process more precisely the roentgenograme in the lateral proection has to be done.

Lungs roots. The roots of the lungs are localized in the medial parts of the lungs, next to the heart shadow along two intercostals from the 3d rib down, gradually shifting the lungs picture.

Anatomic substratum of roots – large arterial and venous vessels, bronchi, groups of lymph nodes, connective tissue with lymphatic vessels and nervous trunks. Roentgenologically three parts are distinguished in the root: The head, the body and the tail. The head of the root is formed by the arcs shadows of main branches of the pulmonary artery and is localized at the level of the 3^d rib and the 3^d intercostal. The body of the root is formed by the shadows of the descending part of the pulmonary artery trunk and other vessels. The lower tail portion is formed by the shadows of lower veins and shifts the lung picture of lower lung portions.

The lungs picture is caused by the branches of pulmonary artery and veins vessels, that’s why it is also called vascular. During various pathological processes in the lungs, the picture may be intensified and indistinct. Sometimes a large vessel, having a transversal position, may form a shadow of round form resembling a fire. To specify the character of that shadow, the examination of the patient in various projections should be made.

The main roentgenologic shadows at lung tuberculosis are nidus (diameter to 1 сm), infiltrative (diameter over 1 cm), ringshaped and linear shadows. Shadows are distinguished according to their sizes as small (diameter to 2 mm), medium (3-5 mm) and large (6-10 mm) nidus ones and according to their compactness – of weak, medium and great intensity.

A shadow in diameter of over 1 cm is called infiltration or tuberculoma.

Before the analysis of the roentgenogram, the quality of its technical performance should be estimated. That should be done in the definite consequence: the completeness of the examined object scope (the whole thorax should be depicted on the roentgenogram – from the apex up to the phrenicocostal sinus); the patient’s position during the roentgenogram execution ( at the proper patient’s position, the distance between the medial edges of the clavicles and the spines of the 3d dorsal vertebrae are located symmetrically, scapulae shadows are depicted outward beyond the lungs margins; preciseness and contrastness (“preciseness and contrastness” assume nice outlining of every roentgenogram detail with different shades); and, at last, “strictness” (at optimal strictness of a roentgenogram, 3-4 upper dorsal vertebrae are clearly visible) of the roentgenogram.

Inspection roentgenography is carried out in the straight (right) (front and back), lateral and oblique projections. To define more accurately the localization and the character of the pathological process, a roentgenogram in a lateral projection is used.

The target roentgenography is done on a limited lung strip and in such a position of a patient as to get the most optimum picture of pathological changes, concealed behind the chest bone formations.

Tomography is the layer examination of a certain organ, in particular, the lungs. It allows to study in detail the structure of a pathologic formation at a respective optimum depth, chosen on the basis of the results of lateral roentgenography or roentgenoscopy .

Computer tomography is based on mathematical analysis of the intensity of absorption of the X-rays by tissues of various compactness and their transformation into the scheme, which reflects the pattern of diametrical layers of a human body on different levels (fig. 2).

 

Fig.2 Computer tomography

 

Computer tomography allows to make more precise the localization and the spread of the pathologic process of lungs and mediastinum, reveal minute changes in pleura, in intrathoracic lymphatic nodes (fig 3).

Fig.3 Comruter tomograma patient with pulmonary TB

Fluorography(fig.4) is the principal method of mass examination of population, with big productive capacity and high informativeness it being done in various projections.

Fig.4 Fluorograma

 

However, the radiation dose of a person under examination is somewhat higher than that at roentgenography; that is why children undergo inspection roentgenography.

Bronchography is applied for examining the bronchial tree, for revealing bronchoectases, their number and form, as well as for revealing cavities. The procedure is made on an empty stomach, predominantly at the local anaesthesia, after which a contrast material (propiliodon, sulphoiodlipol etc.) is introduced through the catheter under the control of roentgenoscopy and roentgenography in two projections is done (Fig.5).

 

Fig. 5 Bronchography

 

Fistulography. The method is applied for examining patients with various thoracic fistulas (thoracic and thoracobronchial). A contrast material (iodinelipol, propiliodon oil and water solutions) are introduced into the fistula and roentgenograms iecessary projections are performed.

Pleurography is predominantly performed to patients with pleural empyema to make its limits more precise. First the empyema contents is aspirated, then roentgen contrast material is introduced into the cavity (propiliodon, urographine, verographine) and roentgenograms in several projections are performed.

Angiopulmonography and bronchial arteriography are roentgenocontrasting methods of examining lung vessels of the small (angiopulmonography) and the large (bronchial arteriography) circles of blood circulation. Angiopulmonography: after catheterizing of the heart right sections and the lung artery under roentgenologic control a contrast material is introduced and a series of roentgenograms are performed. The aim of the examination is the diagnostics of thrombosis, the lung artery emboly as well as the study of pneumofibrosis degree.

Bronchial arteriography is catheterization, contrasting and roentgenography of bronchial arteries and their branches. The main indications are repeated lung haemorrhages and haemoptysis from the unknown source.

Kymography and polygraphy are applied for defining the mobility of the diaphragm and the heart.

Ultrasound examination (USE). At the respiration organs illnesses an ultrasound is applied, chiefly, for the examination of pleura, the function of the right ventricle of the heart and the pressure in the lung artery. USE is not applied for lung examination in so far as the filling of the lungs with air distorts the injures contours. The ultrasound method is applied for making pleura illnesses more precise, especially for the differentiation of a fluid and condensed (compact) elements.

Ultrasound examination, in particular, bimeasured echocardiography is applied to control the right ventricle index and the thickness of the fore-wall of the right ventricle, to define the time interval between closing the right auriculoventricular valve and opening the valve of the lung trunk. The data obtained show the degree of the correlation between hemodynamics and the parametres of the lung function.

Magneto-resonance examination. The method is applied for examining patients as it provides a sufficient contrast between fat tissue of the mediastinum, compact formations and vessel structures, allowing to indentify injures without intravenous introduction of a contrast material. The faults of the method: impossibility to define calcification, insufficient information about lung parenchyma.

 

 

 

 

TUBERCULINODIAGNOSTICS

Tuberculin testings are a specific diagnostic test, based on tuberculin property to cause in a human body, sensibilized by MBT, inflammatory reactions of dilatory type. They are used for mass examination of children and teenagers for tuberculosis, as well as for diagnostics, differential TB-diagnostics and the definition of the process activity.

It was Robert Koch who obtained tuberculin for the first time (1890) which was later named old Koch’s tuberculin (Alt Tuberculin Koch – ATK) (fig. 6). It is manufactured in ampules as 100 % solution and is a liquid of dark-brown colour, which contains, in addition to specific active substances (tuberculoproteins), products of MBT vitality, elements of their cells and the medium on which they grew.

 

 

In 1934 F.Seibert obtained a more specific (dried) tuberculin preparation – Purified Protein Derivative (PPD-S) – purified tuberculin protein derivate, for which bacteria were grown on a synthetic protein-free medium. In the former USSR in 1939 M.A.Linnykova obtained an analogical tuberculin preparation, named PPD-L (fig. 7). One ampule contains 50000 TU of dry rectified tuberculin. The solvent is isotonic solution of sodium chloride with the addition of 0,25 % carbolic acid. Preservation time is 5 years, in a dark place at the temperature of + 4⁰ C.

 

In Ukraine PPD is manufactured as a solution ready for use, the sterility of which is guaranteed by the presence in it of 0,01 % chinozol. The solution is packed in ampules of 3 ml (30 doses) or in bottles of 5 ml (50 doses). Each dose – 0,1 ml contains 2 TU. According to the WHO standard, 1 TU contains 0,00006 mg of PPD-L or 0,00002 of PPD-S.

Tuberculin is an incomplete antigen and therefore it does not cause the formation of antibodies, but it calls forth a reaction in a sensibilized organism with a complete antigen (MBT, vaccine strain of BCG).

Depending on the mode of tuberculin introduction, cutaneous Pierquet test (Pierquet, 1907), intracutaneous – Mantoux (Mantoux, 1910; Mendel F., 1909) and subcutaneous Koch test (Koch, 1890).

Mantoux test is applied at mass examinations for tuberculosis, while Koch test is applied under the conditions of a clinic with a view to diagnose and define the activity of tuberculosis process. Pierquet test has lost its diagnostic value and is extremely rarely applied nowadays.

In the basis of an organism’s reaction to tuberculin is an immunologic reaction of increased sensitivity and slow type (ISST). After MBT infecting (vaccination or revaccination) hypersensitiveness to tuberculin appears in about 6-8 weeks. The reaction intensity to tuberculin depends on the degree of the organism specific sensibilization and its reactivity as well as on various endogenic and exogenic factors (fig. 8).

Mass and individual tuberculinization is distinguished.

The aim of mass tuberculinization:

1. Early tuberculosis revealing,

2. Revealing persons with an increased risk of tuberculosis illness,

3. Contingent selection for BCG revaccination,

4. Determination of infestation index of MBT population,

5. Differential diagnostics between infectious and pastvaccinal allergy.

Fig. 8. Positive Mantoux test.

 

Mantoux testing of 2 TU of purified tuberculin in standard solution is applied in solving these tasks. 1 g. sterile syringe and a simultaneous needle are used for this purpose. 0,2 ml of tuberculin is taken with a long needle, which is then changed to a small one and tuberculin is released to 0,1 ml mark. The skin of the midle third part of the inner surface of the forearm is rubbed with 70⁰ spirits, fixed and, turning the face of the needle up, 0,1 ml (2 TU) of tuberculin solution is injected intracutaneously (fig. 9).

The results of Mantoux testing, which are estimated in 72 hours, may be as follows:

1. Negative – absence of an infiltrate  or only a sign after an injection to 1 mm (fig. 10),

2. Doubtful – a 2-4 mm infiltrate or only hyperemia (fig. 11),

3. Positive – a 5 mm or more infiltrate (fig. 12),

4. Hyperergy – with children and teenagers an infiltrate  of 17 mm and more, with adults – 21 mm and more, and also for various age groups, reactions with the availability of vesicules, necrosis or lymphangoitis, irrespective of the papule size (fig. 13).

 

Fig. 9. Engineering of realization of Mantoux test.

 

Fig. 10. Negative – absence of an infiltrate  or only a sign after an injection to 1 mm.

Fig. 11. Doubtful – a 2-4 mm infiltrate or only hyperemia.

Fig. 12. Positive – a 5 mm or more infiltrate.

 

Fig. 13. Hyperergy – with children and teenagers an infiltrate  of 17 mm and more, with adults – 21 mm and more, and also for various age groups, reactions with the availability of vesicules, necrosis or lymphangoitis, irrespective of the papule size.

 

At the needleless method the size of the papule is 2 mm less than that of tuberculieedle injection and the reaction interpretation is corresponding.

With a view of early revealing of tuberculosis, the intensity of tuberculin reaction or tuberculosis intoxication, the Mantoux test with 2 TU is made to all children and teenagers starting from 12-months age, is annually repeated irrespective of the previous result. On twin years the test is made on the right, on add ones – on the left forearm, at the same time (preferably in autumn).

Contraindications for mass Mantoux test are skin diseases, acute and chronic infectious diseases (not less than two months after clinical symptoms disappearance), allergic states, bronchial asthma, idiosyncrasy with marked skin manifestation, rheumatism in acute and subacute phases, epilepsy. Mantoux test is not performed in children collective bodies during infections quarantine. By the way, the interval between various prophylactic inoculations and Mantoux test should be not less than a month.

The following information should be taken into account for differential diagnostics of infectious and postvaccinal allergy:

1. A child’s health state, information about the contact with a tuberculosis patient;

2. Whether BCG vaccine innoculation was done, the term of the last vaccination;

3. Tuberculin reaction intensity during the last examination and in previous years.

The most distinctive features for postvaccinal allergy are: negative, doubtful or positive reactions with the infiltrate size of 5-11 mm; rarely the infiltrate of the size of 12-16 mm (in children and teenagers with postvaccinal scar of 6-9 mm size); the reaction is at most expressed in 1-1,5 years after vaccination, onward it gradually decreases.

Infectious allergy: first positive reaction (5 mm and more) in childreot vaccinated the preceding year; stable preservation during a few years of tuberculin reaction with an infiltrate size of 12 mm and more; increase of intensivity of previously doubtful or positive tuberculin reactions for 6 mm and more; hyperergic reactions (Tabl.).

                                                                                                                             Table

Characteristics of infectious and postvaccinal

tuberculin reactions

 

Postvaccinal allergy

Infectious allergy

1. Negative, doubtful or positive reactions with 5-11 mm dimension infiltrate 2. Rarely 12-16 mm dimension infiltrate (in children and teenagers with postvaccinal scar of big dimensions) 3. Maximum expressed reaction in 1-1,5 years after vaccination (rarely in 2 years) onward it gradually decreases.

1. First positive reaction (5 mm and more) in childreot vaccinated the preceding year 2. Stable preservation during a few years of tuberculin reaction with an infiltrate size of 12 mm and more 3. Increase of intensivity of previously doubtful or positive tuberculin reactions for 6 mm and more or increase of reaction less than for 6 mm, but with infiltrate formation of 12 mm and more diameter 4. Hyperergic reactions

 

A contact with a tuberculosis patient, combining first registered positive Mantoux test with the availability of clinical illness symptoms testifies of the primary MBT infestation (intensivity of tuberculin reaction), tuberculosis intoxication or even a local specific process.

Tuberculin intensifier is the appearance of first positive tuberculin reaction after a negative one within a year or its increase in persons vaccinated with BCG vaccine at 6 mm and more.

All children with tuberculin reactions intensification should be thoroughly examined for tuberculosis as well as children and teenagers with hyperergic tuberculin reactions infestated long ago or at tuberculin sensitivity increase (6 mm and more).

Individual tuberculin diagnostics. Depending on the indications at individual tuberculin diagnostics Mantoux test with 2 TU is applied, as well as with various tuberculin doses. Generally, Mantoux test with 2 TU is of importance for children and teenagers; for adults, in separate occasions, hyperergic results of Mantoux test testify of the active tuberculosis, while the negative ones of tuberculosis absence, therefore sometimes the necessity arises to apply Koch test (10-100 TU). A negative reaction to 100 TU of tuberculin with the probability of 97-98 % allows to exclude tuberculosis infestation. Koch’s testing is done with a view of diagnostics and differential diagnostics of tuberculosis, the definition of the activity of tuberculosis process. Before the Koch testing, Mantoux test with 2 TU is done for ascertaining the tuberculin titre. After this near the lower angle of a shoulder-blade or in the upper third of the outer surface of the shoulder, after rubbing the skin with 70⁰ ethylic alcohol, tuberculin is injected subcutaneously in the dose from 20 to 100 TU. Two or three days before the procedure the clinical blood analysis is done every day, the intake of lavage waters of bronchi for MBT, measuring the body temperature every 4 hours; a day prior to Koch’s test the protein fractions of the blood serum are defined. In 24-48-72 hours after subcutaneous tuberculin injection the examinations analogous to those before the tuberculin injection, are done. Roentgenological examination before and after Koch’s testing (in 48 hours and on the 7th day) is performed depending on the process localization.

Koch test results are evaluated in 24, 48 and 72 hours, based on the results of local, nidal and general reaction. The local reaction is supposed to be positive at the formation of subcutaneous infiltrate of the 15 mm size and more; the nidal – at the availability of the intensification of inflammatory reaction in the site of specific wound; the general (overall) is characterized by the worsening of the general state of the person under examination, the rising of the body temperature (not less than 0,5⁰ C), joint aches, headache, increased disposition to perspire, as well as changes of the formula and protein fractions of the blood serum etc. (each index, which has deviated not less than 20 % from the initial figure is taken into account). Simultaneous changes of not less than 3-4 indices are of diagnostics importance.

 

 

ORGANIZATION  OF  ANTITUBERCULOUS  ACTIVITY  IN  THE  PERIOD  OF  TUBERCULOSIS  EPIDEMY

 

Tuberculosis is a social disease and is a mirror of social-economic prosperity of the state and the well-being of its people, therefore antituberculous measures under present conditions must be taken on the national level by the government of the country.

At present time, the principal task in fighting tuberculosis in Ukraine is to take the epidemy of the illness under control (I stage), to stabilize the epidemiological indices (infestation, morbidity, sickliness and death rate) of tuberculosis (2 stage), and then their gradual decrease (3 stage).

For the successful organization of antituberculous measures close cooperation of the medical system, sanitary-epidemiological service and the organs of the state power is necessary. The general organization and methodological guidance of antituberculosis activity in this country is realized by the Ministry of Health Protection of Ukraine and Acad. F.G.Yanovsky Ukrainian phthisiology and pulmonology research institute (scheme 1).

Scheme 1

STRUCTURA OF ANTITUBERCULOSIS SERVICE

IN UKRAINIAN

 

 

		The Ministry of Health Protection
		Acad. F.G.Yanovsky Ukrainian phthisiology and pulmonology research institute
		Regional of antituberculous dispensary
		Distric(town) of antituberculous dispensaries
		Tubcabinet
At child’s policlinic		At policlinic		At medical parts

 

Antituberculous dispensary (Engl. dispensation – distribution) is a specialized medicative-prophylactic institution, which work is aimed at lowering morbidity, sikliness, infestation with tuberculosis and death rate caused by it as well as at conducting a complex of organizational and methodical, prophylactic antituberculous measures among the district population.

The main tasks of an antituberculous dispensary are:

1) prophylaxis;

2) early revealing;

3) treatment of tuberculosis patients;

4) registration of groups of tuberculosis patients and contingents of persons

with an increased risk of its development and their observation.

Additionally, the decisive in the organization of those main tasks is their active administration and, in the first turn, by the general medical net (prophylaxis and tuberculosis detection) and by antituberculous service (treatment and observation).

One of the priorities in the work of an antituberculous dispensary is conducting prophylactic antituberculous measures.

Other very important tasks of an antituberculous dispensary are revealing, registration and treating tuberculosis patients. The results of treating tuberculosis patients to a considerable degree depend on the disease being timely revealed. In this connection, firsty diagnozed tuberculosis patients are divided into three groups: timely, untimely and lately revealed. For children and teenagers the fourth group is separated – early revealing.

The main criteria of dividing patients into groups are the character of a specific process, the presence or absence of destruction (cavern) and bacterial excretion, peculiarities of the prognosis at treatment, the degree of a patient’s danger for healthy persons.

Children and teenagers, in whom the following factors are diagnosed, compose a group of early revealed:

 1) tuberculin test range;

2) primary tubinfestation;

3) hyperergic Mantoux test;

4) tuberculous intoxication.

To the first group – timely revealed belong patients with uncomplicated forms of primary tuberculosis: primary tuberculous complex, tuberculosis of intrathoracic lymphatic nodes, restricted (1-3 segments) forms of secondary tuberculosis: nidal, infiltrative, disseminated without decay; exudative pleurisy. Revealing MBT, the lung destruction being absent, does not exclude the possibility for a patient to belong to a group of timely revealed. At treating such patients the recovery reaches 100 %.

To the second group – untimely revealed – belong patients with complicated forms of primary tuberculosis, primary tuberculosis with a chronic course, nidal, infiltrative, tuberculoma, disseminated tuberculosis with a decay and MBT. Under conditions of modern antimycobacterial therapy the cessation of bacterial excretion sets in 88 % of cases, while the healing of decay cavities – in 76 %. The clinical recovery in such cases is frequently accompanied by the formation of big residual changes.

The third group – lately revealed (neglected tuberculosis) patients with fibrous-cavernous, cirrhotic, chronic disseminated with a cavern, pleural empyema. It is the most unfavourable group of patients with respect to clinic, prognosis and epidemiology. The reasons of untimely revealing of tuberculosis are peculiarities of the illness course (asymptomatic course, presence of accompanying maladies), inattentive and careless patient’s treatment of his health (alcohol and drug addiction, low sanitary competence), a doctor’s diagnostic errors (lowering the attention of doctors of general medical system to tuberculosis).

The principal ways of revealing tuberculosis:

1. Prophylactic examinations (children – tuberculinization; teenagers – tuber-culinization, and from the age of 15 – additionally fluorography; adults – fluorography).

2. Revealing at the application for medical aid.

3. Observing persons with higher risk of catching tuberculosis.

The principal methods of revealing tuberculosis are roentgenologaical, tuberculinodiagnostics and microbiological ones.

The principal method of early revealing of tuberculosis in children aged up to 14 is yearly mass prophylactic examinations with making Mantoux test with 2 TU. Teenagers (from 15 years of age), in addition to tuberculinodiagnostics, are examined fluorographically. The examination of persons aged before calling for service takes place at military registration and enlistment offices, if over 6 months have passed since the previous examination.

The complete (massive) examination of the population is performed from 18 years of age, once in two years. However, in areas, where tuberculosis statistics does not exceed 30 for 100000 of the population and the percentage of firstly diagnosed fibrous-cavernous tuberculosis does not exceed 0,5, the massive fluorographic examination is done once in 3 years.

During prophylactic fluorographic examinations special attention is paid to the socalled “obligatory contingents”. These are persons, who are in a direct contact with children and teenagers: 1. workers of medicative, health, educational institutions for children and teenagers up to 18 years of age, and maternity homes personnel;

2. workers of public catering, alimentary blocks, dairy farms, trade, i.e. persons who deal with foodstuffs;

3. workers of institutions of sanitary-hygienic population service, hotels, hostel tenants, students during the period of study at secondary special and higher educational institutions in professions that belong to the “obligatory contingents”. All these contingents are due to fluorographic examination while getting a job, and then – once a year. Prisoners, who stay in solitary confinement cells, are examined twice a year.

Tuberculosis revealing at applying for the medical aid reaches 50 % of cases. Their revealing, for the most part, depends on phthisiological attention of the general medical network, first and foremost, on therapeutists.

Groups with increased risk of catching tuberculosis. In polyclinics of general profile the object of observation are persons with stomach and duodenal ulcer, after operation due to these maladies; diabetes, dust professional pulmonary illnesses, LCI, after suffered exudative pleurisy, chronic insufficiency of adrenal glands, chronic unspecific illnesses, alcohol and drug addiction; persons who underwent protracted courses of corticosteroid and ray therapy; with small posttuberculous lung changes, as well as with extensive residual changes after unspecific pulmonary illnesses.

Pregnancy, postnatal period, AIDS are classified to the group of increased tuberculosis risk.

Persons, belonging to the risk group, are examined fluorographically once a year at medical institutions of the general profile.

The following groups of increased tuberculosis risk are under observation at antitubercular dispensaries:

1. III and IV groups of dispensary registration. Persons who have recovered from tuberculosis and, like contractils, they undergo fluorography once in 6 months.

2. VII group of dispensary registration – persons with extensive residual pulmonary changes after lung tuberculosis healing and with small residual changes, the aggravating factors being present. They undergo fluorography once a year.

The laboratory diagnostics  of tuberculosis. Methods of revealing mycobacterium of tuberculosis. Atipical MBT. Sensitivity of MBT

 

 

The source of infestation of human beings are tuberculosis human patients and animals secreting tuberculosis mycobacteria. The material for revealing MBT are sputum, bronchial lavage waters, faeces, urine, fistula pus (matter), pleural cavity exudate, spinal fluid, punctates and bioptates of various organs and tissues.

Sputum examination for MBT is of great epidemiological and clinical importance. When there is no sputum or it is scarce, expectorants, irritant aerosol inhalations, bronchi lavage are administered (fig.14).

 

 

Methods of Revealing Mycobacteria:

 

1. Bacterioscopy is one of the main methods of revealing MBT; it includes ordinary bacterioscopy, flotation and luminescent microscopy. An ordinary bacterioscopy is accessible to all, simple and quick to do. In smears, coloured according to Tsil-Nilsen, MBT are revealed wheot less than 50000 microbic bodies are present in 1 ml of pathologic material. According to the “instructions for bacteriologic diagnosis of the tuberculous infection” of the Ministry of Health Protection of Ukraine, order № 45 dtd. 06.02.2002, MBT can be revealed if their quantity is 5000 – 10000 bacterial cells in 1ml of the pathologic material. Under the microscope MBT look like bacilli of the red colour on the blue background (Fig.15).

 

 

 

Flotation method (enrichment or concentration of MBT in a small volume, caused by droplets of benzine, benzole, xylol or toluene on the surface of a retort ring) is applied in cases when there is a small number of MBT in the pathologic material and at negative results of ordinary bacterioscopy. Flotation method provides for 10-15 % more often revealing MBT in comparison to direct bacterioscopy.

Luminescent microscopy is based on the ability of MBT, coloured with fluorochroms, to illuminate under the influence of ultraviolet rays and performing microscopy at small magnification, increasing by 15-30 % the sensitivity of the method in comparison to direct bacterioscopy and by 10 % in comparison to the flotation method (fig.16).

 

2. Bacteriological method consists in the following: sputum or another material, after preliminary special treatment, is sown outritive media (hard, blood, semisynthetic) (fig. 17). More often hard egg Lewenstein-Yensen medium is used. 20-100 microbial bodies in 1 ml of sputum is enough for revealing MBT culture. The first colonies appear on the 14-30-th day of cultivation. The negative result is given only in 2,5-3 months from sowing. This method of revealing MBT allows to define their vitality, virulence, group (differentiate from acid resistant saprophytes and atypical MBT) and species origin, as well as their resistance to antimycobacterial preparations. In addition to this, according to the data of bacteriological examination quantitative essessment of bacterial secretion is made: miserly-up to 20 colonies on a nutrient medium, moderate – from 20 to 100 and massive – more than 100 colonies.

 

 

Fig. 17.  Culture of  mycobacteria tuberculosis at hard egg medium

 

Therefore, the culture result must depict not only the qualitative characteristics (positive or negative), but also a quantative evaluation (colonies №). For that it is recommended to use Table 1 (National Antituberculous Programme, 2000).

 

                                                                                              Table 1

WHO scheme of the evaluation of the results of cultural examination for

M.tuberculosis

 

Colonies quantity	Result evaluation	Characteristics
1-19 colonies	Positive	Individual colonies (miser bacterial emision); bacterioscopy of the pathologic material scarcely reveal individual mycobacteria
20-100 colonies	1+	Moderate bacterial emission; bacterioscopy of the pathologic material reveal individual mycobacteria in each field of vision or only single ones – in the preparation, but not less than five
100-200 colonies 200-500 colonies (almost universal growth) Over 500 colonies (universal growth)	2+ 3+   4+	Massive bacterial emission; bacterioscopically – 10 and more mycobacteria  in each field of vision
Germination of common microflora	Germination –  repeat inoculation

 

3. Biological method. It is infection with sputum or another pathologic material of guinea-pigs, which are highly sensitive to MBT. A biological testing is the most sensitive method of revealing MBT, so far as in laboratory animals tuberculosis develops after the introduction of the material in which there may be less than 5 microbial bodies in 1 ml. However, it should be noted that MBT are stable to chemical preparations, particularly to isoniazidum, avirulent for guineapigs. That is why various methods of microbiological examination should be used for revealing MBT in pathological material. Generally, before starting to treat a patient, he should undergo complex bacteriological examination: three times direct bacterioscopy of sputum or, when it is absent, three times examination of the material after provoking inhalations or bronchial rinsing waters; with negative results – three times examination by flotation method; three times sputum sowing on a nutritive medium, irrespective of the results of the previous examinations, with a view to define MBT sensitivity to antimycobacterial preparations the examinations are made in accordance with the recommendations of the World Health Organization.

The repeatedness of the patient examination for TB revealed for the first time in the dynamics of chemotherapy (acc. To WHO recommendations) is given in Table 2.

                                                                                              Table 2

The repeatedness of the patient examination for TB revealed for the first time in the dynamics of chemotherapy

 

Period from the first of therapy (month)	Obligatory minimum
	Bacterioscopy	Inoculation	Determination of drug resistance
0	х 3	х 3	х 3
At the end 2 (3)	х 2	х 1	х 1
From the first 5	х 2	х 1	х 1
At the end 6 (8)	х 2	х 1	х 1

 

         Notes:

^x if at the end of the second month of the treatment the results of bacterioscopy of MBT smear is (+), it’s necessary to make bacterioscopy at the end of the third month;

^xx if at the end of the sixth month of the treatment the results of bacterioscopy of MBT smear is (+), it’s necessary to make bacterioscopy at the end of the eighth month.

 

The usage of antimycobacterial preparations provokes the development of drug resistance to MBT. There are primary and secondary drug resistance.

The primary drug resistance – is MBT stability, in the patients who were TB revealed for the first time; this stability is the result of the infection with stable MBT strains.

The secondary drug resistance appears in the process of continuous irrational antimycobacterial therapy.

According to WHO data, the frequency of the primary drug resistance to any preparation is 10.4% average, and the secondary – 36 %. In Ukraine the primary drug resistance twice exceeds the average WHO index, and the secondary – 1,5 times.

Nowadays immunologic and molecular-genetic methods are applied for etiological identification of tuberculosis. The most promising of them are immunoenzymic and radioimmune methods of defining mycobacterial antigens which are based on the application of monoclonal antibodies. Molecular-genetic method of polymeraze chain reaction consists in revealing in biological material (sputum, tissues; lavage, pleural, spinal fluid etc.) of mycobacterial DNA. The examination results may be obtained in 3-4 hours.

The determination of MBT sensitivity to antimycobacterial preparations is of paramount importance for the treatment tactics, correction of antimycobacterial therapy and the illness prognosis. MBT sensitivity to antituberculous preparations is defined by the preparation minimum concentration, which inhibits MBT growth on the nutritive medium. MBT are considered to be sensitive to either preparation if less than 20 colonies have grown in a test-tube, with abundant growth in the control. The culture is supposed to be stable if more than 20 colonies have grown. MBT are considered to be stable if they grow at the concentrations of the preparation in 1 ml of the nutrient medium: for isoniazidum – 1mkg, rifampicinum – 20 mkg, streptomycini – 5 mkg, ethambutolum – 2 mkg, all other preparations – 30 mkg.

Blood examination. The main reasons of changes in peripheral blood of tuberculosis patients are intoxication and hypoxia. At initial forms of tuberculosis a hemogram is normal or with inconsiderable deviations. In recent years hypochromic anemia is more and more often observed, however at chronic lingering course of the spread specific process, with the intensification of the phenomena of lung insufficiency and hypoxia, compensatory increase of erythrocytes number and hemoglobin is possible. In general, for more serious clinical forms of tuberculosis slight leucocitosis (9,0-15,0 х 10⁹/l) is characteristic, percentage of bacillarnuclear neutrophiles, lymphopenia, monocytosis, eosinopenia increase, ESR is speeded up, as well as the decrease of albumin-globulin coefficient sets in with the relative increase of alpha-2 and gammaglobulins.

Urine examination. In patients with expressed tuberculosis intoxication, proteinuria, erytrocytes and leucocytes in urine may be observed. With intoxication decrease the pathological changes in urine disappear. However, if there is amiloidosis of internal organs, in particular kidneys, hypoisosthenuria is typical, stable proteinuria, increased number of erythrocytes, leucocytes in urine, as well as emergence of cylinders.

 

DIAGNOSTIC LABORATORY METHODS FOR TUBERCULOSIS

Introduction

 

In mycobacteriology labs, we continue to use mainly the old, proven methods.  This is so even in rich countries, where it would be less of a problem to use the newer and more expensive or technically demanding techniques.  Smear microscopy, for instance, a technique which is over 100 years old, continues to be included in every investigation for TB, simply because it is all over the world a valuable technique which is helpful in many cases.  Because of the higher proportion of smear-positive cases and the rarity of other mycobacterial pathogens, this is even more true in TB high-prevalence countries.  The reliance on microscopy for TB in these countries is not in the first place because of lack of money for something better.  Newer techniques exist, but some of them have serious shortcomings, while others have not yet been evaluated sufficiently to decide on when and where to use them.

In this module we will briefly discuss the main techniques for detecting MTB.  This implies examining not only test characteristics such as sensitivity and specificity, but also other factors such as technical requirements and costs.

The diagram below illustrates the various characteristics used to describe a diagnostic test.

FP = false positives of the test

FN = false negatives of the test

 

This cross-table shows the usual way to calculate the different values from results that were obtained comparing a given test against a “gold standard,” which is believed to indicate the total actually sick (“Disease present”) and the total not sick (“Disease absent”).  In TB research, the gold standard will usually be culture.  For microscopy rechecking quality control, for instance, it will be the results of the controllers.

Sensitivity and specificity are the basic characteristics, inherent to the technique but independent of the population in which it is used. Predictive values do take into account not only technique, but also the population in which it is used via the “prevalence” parameter. Prevalence indicates the frequency of the disease and will be different for different populations.  With high prevalence, sensitivity needs to be high to reach a good negative predictive value (NPV).  With low prevalence, so when the disease is rare, specificity needs to be very high, otherwise the positive predictive value (PPV) of a test will be poor.  This is illustrated in the next diagram, showing the outcome of the same test (same hypothetical sensitivity and specificity) applied in populations with highly different prevalence of HIV seropositivity.  PPV as well as NPV are dramatically different.  In the first situation, a negative result still leaves about one chance in four that the patient is seropositive; in the second, there is less than one percent chance that a positive result truly indicates seropositivity, despite a seemingly high specificity.

 

 

The performance of various laboratory methods for detecting MTB is largely dependent on the numbers of TB bacilli or their products present in the samples.  All tests will score better on specimens that are rich in bacilli, but only the most sensitive ones will also detect MTB in paucibacillary disease.  As discussed earlier, the lungs of patients with infectious disease harbor many bacilli, and in high-prevalence areas these are also the most common type of patients.  The curve below shows what this means for some tests in terms of proportions of patients that can be detected.  AFB-microscopy needs minimally +/-5000 AFB per ml of sputum to yield a consistently positive result, and this is the case for most patients who present because of symptoms.  This also shows that a distinct difference exists in sensitivity between excellent and poor AFB-microscopy.  Culture as well as PCR can detect as few as 100 TB bacilli per ml, but this represents fewer patients in low-income countries.  X-Ray is shown for comparison; it can in principle detect patients who do not excrete any TB bacilli at all.

 

 

 

 

Review of main lab methods

 

Roughly, the various tests we use can be classified as tests for detecting whole bacteria, or as those that detect compounds or products of the bacteria, and those that detect changes in the patient’s immunologic response to TB bacilli (serology).

 

 

1. Detection of whole bacteria

·        microscopy for AFB

This will be discussed in detail in a separate chapter.

 

·        culture of mycobacteria

Culture remains the gold standard in mycobacteriology because of its high sensitivity as well as specificity.  Sensitivity reaches a minimum of about 100 bacilli per ml of sputum. In high-prevalence countries this may correspond to 80-90% of patients presenting because of symptoms.  Sensitivity for cultures seems to be lower in AIDS patients with advanced immune deficiency, where fewer TB bacilli are present in sputum.  Sensitivity will also be affected by technical factors, such as centrifugation and decontamination efficiency.  In terms of specificity, culture has the big advantage by allowing differentiation between MTB and other mycobacteria, but this is less important in TB high-burden countries.  On the other hand, specificity can suffer with careless technique.  Transfer of TB-bacilli from positive samples may occur more frequently than when using microscopy.  Specificity (assuming properly executed culture technique) will be around 99%, but in practice it will regularly be less.

The main disadvantage of culture is not the need for more sophisticated resources and more qualified technicians or higher cost, but its slowness.  This is certainly so with the classical egg- or agar-based media (Löwenstein-Jensen, Ogawa, Middlebrook), for which a positive result requires on the average 3 weeks.  The commercial liquid systems (BACTEC, MGIT) may reduce this time by 50% or more, but they are more costly and place higher demands on equipment, so that they cannot be routinely used in resource-poor countries.

The diagnostic delay of culture, together with the presence of advanced disease in many cases at presentation and the high index of suspicion among clinicians in countries with a high prevalence of TB, all work to reduce the usefulness of culture under these conditions. It has been shown that, under these circumstances, three smear examinations yield about the same as one culture.  In addition, physicians will not wait for the results of culture to initiate TB treatment on other evidence.  Moreover, repeating AFB smears after a few weeks in case symptoms persist, as is generally recommended, may give the same information as culture.

The conclusion may be that establishing culture facilities outside reference laboratories should not be a priority iational programs until it becomes clear that control of the disease is well under way and resources permit.  Often these conditions will coincide, with earlier patient presentation because of economical improvement, and setting up culture facilities will automatically be part of the technological progress in general.

For reference laboratories in high-burden countries, culture will mainly serve as a first step in drug susceptibility testing (DST).  DST itself will be reserved to track drug resistance.  In these laboratories, culture may also enhance research.

 

2. Detection of compounds or products of the bacteria

·        PCR-based genetic tests

Detection is based on multiplicatioot of whole bacilli, as in culture, but of their genetic material, chromosomal DNA or ribosomal RNA.  Provided all ingredients are present in the reaction tube, this will only take place when the target genetic sequences to which the added primers can bind are found in the sample.  Specificity of the test will thus depend on the use of correct primers, using sequences typical for MTB or MTB complex.  In principle, from one target sequence, of one bacillus, the reaction can produce millions of copies and thus yield a positive result.

In practice, however, sensitivity is of the same order as that of culture or about 100 bacilli, due to the limited amount of sample that can be used and sometimes also due to the interference of reaction-inhibiting substances.  Specificity of PCR is probably also similar to that of culture, but this needs further evaluation.  Extremely careful technique is needed.  Carry-over of DNA is even more likely to happen than that of whole bacteria so that early studies found up to 50% of positive results to be false.  This places high demands on skills of the technician, as well as requiring special equipment and infrastructure (i.e. separate rooms).

The main advantage of PCR-based techniques is their speed; in principle, only 1-2 days are needed.  This is true for diagnosis of TB, and even more so for applications such as diagnosis of drug resistance (mainly rifampicin) and species identification using probes.

The main disadvantage of PCR-based tests is their extremely high cost, especially when more convenient and more sensitive commercial test kits are available.  Even in rich countries this has restricted their use, for instance, to determining the species present in smear-positive disease (FDA approval).  This restricted use may also reduce the speed of the results, since it may not be possible to schedule PCR-runs daily.

For resource-poor countries, detection of TB using PCR seems unrealistic.

 

·        Chromatography

Various techniques have been described using high-performance liquid chromatography (HPLC) or gas-liquid chromatography (GLC).  Detection targets substances from the cell-wall such as mycolic acids, or metabolic products such as tuberculostearic acid.  Results have been extremely good in terms of sensitivity and specificity as well as speed.

Nevertheless, these techniques seem to be used rarely in routine practice.  The main reason for this may be the expense of the equipment, which has no other applications in the bacteriology laboratory.

 

·        Antigen detection

See further, serology.

 

 

3. Serology

Antigen detection, antibody detection, detection of immune complexes or even immune-detection of complete bacterial cells, all have been described with many variations.  The simplicity, ease and speed of these methods are attractive.  A really good immunologic test could be applied by almost anybody and almost anywhere, and yield a result while the patient is waiting.  For this reason, the search for such a test has been continuous since the time of Koch, with a re-intensification because of new discoveries such as monoclonal antibodies or recombinant peptides and perhaps now the deciphering of the MTB genome. New tests are continuously being introduced by scientists as well as commercial companies, always with big promises.  So far, all of them have been disappointing.

The main problems seem to be that the antibody response to various TB antigens is highly variable between patients; it is very difficult to find a highly specific antigen as well.  This results in problems of sensitivity as well as specificity, especially with easy-to-use formats such as latex-agglutination or immune-chromatographic (dot) tests.  Typically, sensitivity is comparable to that of AFB-microscopy, and clearly better also in smear-positive cases.  At the same time, however, specificity remains well under that of microscopy.  At best it reaches about 95%.  While this may seem high, it will lead to about 50% of false positives in all but high-prevalence regions.  Better results are obtained with more complicated techniques, such as sandwich ELISA, but they are not useful in routine practice.  On the other hand, far poorer results seem to be obtained in HIV positives.  For instance a field evaluation of MYCODOT test in Tanzania has shown a sensitivity of only 26% in smear-positives, and 7% in culture- or X-Ray-proven cases, for a specificity of 84%.  The table below shows results from a panel evaluation of various commercialized serological tests. With this excellent panel composition, mimicking what can be expected in routine work as to proportions of pathologies to be differentiated, not a single test scored high enough to be useful.

 

 

 

To conclude, we do not yet have a serological test which is good enough, and especially not to detect the cases where microscopy remains deficient (HIV positive, children, EPTB).  Considering experiences hitherto, claims in this regard by the manufacturers should be considered as publicity until field evaluation has proven their true value.

 

 

A note oon-laboratory methods for TB diagnosis

 

Clinical diagnosis of TB is not reliable at all, because there is not a single specific symptom or sign.  In adults, the clinical picture will be used for selecting suspects who will be examined using more specific methods, especially AFB-microscopy.  In children and also in some types of EPTB, the history and clinical signs will be given more importance, mainly because most or all diagnostic methods are less efficient.

 

X-Ray diagnosis of PTB is popular with physicians everywhere in the world, thanks to its speed, simplicity and ease of use when equipment is available, and possibly also because the physician sees it as his tool which he understands better.  It is true that X-Ray has a high sensitivity, and it can detect TB in patients who do not excrete any bacilli.

We have seen that these are a small fraction of cases only in most high-prevalence countries, possibly more important where HIV is highly present, and that their prognosis is rather good with frequent self-healing.  In addition, it has also been found that X-Ray will fail to diagnose about 10% of smear-positives under routine conditions.

The main objection against this method stems from its lack of specificity.  This was shown long ago in several studies by IUATLD and others, where even specialist radiologists and chest physicians with long experience made at least 20% false-positives.  In a control program, X-Ray will mainly be used by less experienced doctors, and regularly the radiographs are technically far from perfect.  Experience has shown that its generalized use will then lead to 50-100% of over-diagnoses.  This means a big waste of resources, with attention often being focused on old, inactive cases with persisting X-Ray lesions rather than on the active transmitters of the disease.  Besides the greater expense and the unavailability of equipment in the least developed countries, this is the main reason for the objection of control programs against reliance on X-Ray to diagnose PTB.

Thus, in the control strategy, X-Ray for PTB diagnosis has been reserved for the second line, after AFB-smears have been found consistently negative.  Its value will be greater for diagnosis of PTB in children and for some types of EPTB.

 

Mantoux testing using tuberculin, a protein extract from TB bacilli, is also often misused for TB diagnosis.  The problem is that the test will be positive after any contact with TB or also after vaccination with BCG, in the absence of active disease.  Thus, most adults in high-burden countries will test positive without showing any signs of the disease.  Besides, there are many reasons why a Mantoux test can be false negative, and contact with environmental mycobacteria may cause doubtful reactions.  Since the test always needs careful interpretation, it will never provide absolute proof of the disease.

Mantoux testing is thus not recommended for routine TB diagnosis, except in the case of children.  It will then deliver only one of the arguments leading to a diagnosis when considered together with other arguments.

 

Differential

Diagnosis (Pneumonia)

 

History: A thorough history including other medical conditions (e.g., diabetes, COPD, organ transplant, sickle cell disease, HIV), occupation, travel, hobbies/recreational activities and alcohol/substance abuse is essential. Clinical presentation ranges from a mildly ill ambulatory individual to a critically ill individual in septic shock or respiratory failure. Common symptoms of pneumonia include fever or chills, shortness of breath especially with exertion (dyspnea), pain with deep breathing or coughing, headache, and muscle pain (myalgia). Cough may produce sputum and occasionally blood; the color and odor of the sputum can provide clues to the infectious agent. Chest pain may occur when inhaling because of inflammation in the membranes lining the lungs (pleurisy) and the lung tissues. Breathing may be very labored.

 

 Symptoms of viral and atypical pneumonia are different in that chills are not accompanied by fever, and initially the cough is dry and nonproductive (no sputum is coughed up). Flu-like symptoms include headache, muscle pain, and weakness. Within 12 to 36 hours, shortness of breath may increase, accompanied by a worsening cough that now produces a small amount of sputum. Typical respiratory symptoms may be more subtle in the elderly and in individuals taking corticosteroids or aspirin. These individuals may instead be lethargic, confused as a result of a lack of oxygen supply to the brain, and have labored, rapid respirations.

 

 Swallowing difficulties can cause aspiration of food or liquid into the lungs, leading to aspiration pneumonia. Conditions such as alcohol intoxication, confusion, or decreased mental alertness may also lead to aspiration.

 

Physical exam: Vital signs (i.e., heart rate, respiratory rate, blood pressure, temperature) can offer clues to the severity of the pneumonia. Physical exam may reveal labored breathing with use of accessory muscles in the neck, chest, and abdomen. In severe pneumonia, the individual may exhibit a respiratory rate above 30 breaths per minute (tachypnea). Listening through a stethoscope (auscultation) may reveal abnormal breath sounds that indicate fluid in the lungs (rales or crackles) or areas of infection where air exchange is not occurring (consolidative breath sounds). Percussion can confirm the presence of areas of consolidation. The individual may present with confusion and lethargy due to lack of sufficient oxygen in the blood.

 

Tests: Laboratory testing usually includes a complete blood count (CBC); a high white blood cell count is typical for bacterial pneumonia but not viral pneumonia. A low white blood cell count (leukopenia) may signal impending overwhelming systemic infection (sepsis) and a poor outcome. Gram stain and culture of sputum is important. Blood cultures are usually performed but yield positive results in only about 40% of individuals with bacterial pneumonia (Sharma). Antigen or antibody testing of serum or other body fluids may be indicated for some pathogens.

 

 Cultures of sputum can identify the infecting microorganism within 24 to 48 hours. A Gram stain performed at the initial visit can give the physician clues about the identity of the causative bacteria (Gram-positive or -negative) and aid in the choice of the most appropriate antibiotic even before culture results become available. Once the causative organism is identified, further testing can determine antibiotic resistance and sensitivity. This is important not only for individual medication treatment decisions but also because patterns of antibiotic resistance can help determine how infections spread in populations (epidemiology). In mild to moderate pneumonia, cultures and sensitivity may not be performed unless the individual does not respond to treatment with broad-spectrum antibiotics.

 

 Routine cultures detect only bacteria. Special cultures must be done to detect viruses and these tests are not performed in the average hospital clinical laboratory. Serology studies can identify certain microorganisms (i.e., bacteria, viruses, fungi, protozoa) by identifying antigens from the microorganism itself or antibodies the individual produces against the infecting microorganism.

 

 A chest x-ray can establish the diagnosis of pneumonia, determine the extent of lung infection, and help track progress during treatment. Certain patterns seen on x-ray may be associated with specific types of pneumonia. Non-invasive testing with pulse oximetry can monitor blood oxygen levels or blood oxygen and carbon dioxide (CO2) levels can be measured by sampling blood from an artery and analyzing it; blood oxygen levels may be low.

 

 Examination of the main airways of the lungs using a flexible, fiberoptic scope (bronchoscopy) or surgical removal of lung tissue for microscopic examination (open lung biopsy) may be necessary to determine the exact cause of pneumonia in unusual cases.

 

 The critical decision at initial presentation is “Does this individual need to be hospitalized for treatment?” The decision to hospitalize is based on risk factors including age, presence of underlying medical conditions, and findings on history, physical exam, laboratory testing, and x-ray. If the individual is not hospitalized, adequate follow-up as an outpatient is essential. This usually includes a follow-up x-ray to ensure resolution of the pneumonia.

 

Individual tuberculin diagnostics. Depending on the indications at individual tuberculin diagnostics Mantoux test with 2 TU is applied, as well as with various tuberculin doses. Generally, Mantoux test with 2 TU is of importance for children and teenagers; for adults, in separate occasions, hyperergic results of Mantoux test testify of the active tuberculosis, while the negative ones of tuberculosis absence, therefore sometimes the necessity arises to apply Koch test (10-100 TU). A negative reaction to 100 TU of tuberculin with the probability of 97-98 % allows to exclude tuberculosis infestation. Koch’s testing is done with a view of diagnostics and differential diagnostics of tuberculosis, the definition of the activity of tuberculosis process. Before the Koch testing, Mantoux test with 2 TU is done for ascertaining the tuberculin titre. After this near the lower angle of a shoulder-blade or in the upper third of the outer surface of the shoulder, after rubbing the skin with 70⁰ ethylic alcohol, tuberculin is injected subcutaneously in the dose from 20 to 100 TU. Two or three days before the procedure the clinical blood analysis is done every day, the intake of lavage waters of bronchi for MBT, measuring the body temperature every 4 hours; a day prior to Koch’s test the protein fractions of the blood serum are defined. In 24-48-72 hours after subcutaneous tuberculin injection the examinations analogous to those before the tuberculin injection, are done. Roentgenological examination before and after Koch’s testing (in 48 hours and on the 7th day) is performed depending on the process localization.

 

 

Pneumonia viral

hobbies/recreational activities and alcohol/substance abuse is essential. Clinical presentation ranges from a mildly ill ambulatory individual to a critically ill individual in septic shock or respiratory failure. Common symptoms of pneumonia include fever or chills, shortness of breath especially with exertion (dyspnea), pain with deep breathing or coughing, headache, and muscle pain (myalgia). Cough may produce sputum and occasionally blood; the color and odor of the sputum can provide clues to the infectious agent. Chest pain may occur when inhaling because of inflammation in the membranes lining the lungs (pleurisy) and the lung tissues. Breathing may be very labored.

 

 Symptoms of viral and atypical pneumonia are different in that chills are not accompanied by fever, and initially the cough is dry and nonproductive (no sputum is coughed up). Flu-like symptoms include headache, muscle pain, and weakness. Within 12 to 36 hours, shortness of breath may increase, accompanied by a worsening cough that now produces a small amount of sputum. Typical respiratory symptoms may be more subtle in the elderly and in individuals taking corticosteroids or aspirin. These individuals may instead be lethargic, confused as a result of a lack of oxygen supply to the brain, and have labored, rapid respirations.

 

 Swallowing difficulties can cause aspiration of food or liquid into the lungs, leading to aspiration pneumonia. Conditions such as alcohol intoxication, confusion, or decreased mental alertness may also lead to aspiration.

 

Physical exam: Vital signs (i.e., heart rate, respiratory rate, blood pressure, temperature) can offer clues to the severity of the pneumonia. Physical exam may reveal labored breathing with use of accessory muscles in the neck, chest, and abdomen. In severe pneumonia, the individual may exhibit a respiratory rate above 30 breaths per minute (tachypnea). Listening through a stethoscope (auscultation) may reveal abnormal breath sounds that indicate fluid in the lungs (rales or crackles) or areas of infection where air exchange is not occurring (consolidative breath sounds). Percussion can confirm the presence of areas of consolidation. The individual may present with confusion and lethargy due to lack of sufficient oxygen in the blood.

 

Tests: Laboratory testing usually includes a complete blood count (CBC); a high white blood cell count is typical for bacterial pneumonia but not viral pneumonia. A low white blood cell count (leukopenia) may signal impending overwhelming systemic infection (sepsis) and a poor outcome. Gram stain and culture of sputum is important. Blood cultures are usually performed but yield positive results in only about 40% of individuals with bacterial pneumonia (Sharma). Antigen or antibody testing of serum or other body fluids may be indicated for some pathogens.

 

 Cultures of sputum can identify the infecting microorganism within 24 to 48 hours. A Gram stain performed at the initial visit can give the physician clues about the identity of the causative bacteria (Gram-positive or -negative) and aid in the choice of the most appropriate antibiotic even before culture results become available. Once the causative organism is identified, further testing can determine antibiotic resistance and sensitivity. This is important not only for individual medication treatment decisions but also because patterns of antibiotic resistance can help determine how infections spread in populations (epidemiology). In mild to moderate pneumonia, cultures and sensitivity may not be performed unless the individual does not respond to treatment with broad-spectrum antibiotics.

 

 Routine cultures detect only bacteria. Special cultures must be done to detect viruses and these tests are not performed in the average hospital clinical laboratory. Serology studies can identify certain microorganisms (i.e., bacteria, viruses, fungi, protozoa) by identifying antigens from the microorganism itself or antibodies the individual produces against the infecting microorganism.

 

 A chest x-ray can establish the diagnosis of pneumonia, determine the extent of lung infection, and help track progress during treatment. Certain patterns seen on x-ray may be associated with specific types of pneumonia. Non-invasive testing with pulse oximetry can monitor blood oxygen levels or blood oxygen and carbon dioxide (CO2) levels can be measured by sampling blood from an artery and analyzing it; blood oxygen levels may be low.

 

 Examination of the main airways of the lungs using a flexible, fiberoptic scope (bronchoscopy) or surgical removal of lung tissue for microscopic examination (open lung biopsy) may be necessary to determine the exact cause of pneumonia in unusual cases.

 

 The critical decision at initial presentation is “Does this individual need to be hospitalized for treatment?” The decision to hospitalize is based on risk factors including age, presence of underlying medical conditions, and findings on history, physical exam, laboratory testing, and x-ray. If the individual is not hospitalized, adequate follow-up as an outpatient is essential. This usually includes a follow-up x-ray to ensure resolution of the pneumonia.

Histoplasmosis

History: In the acute form, symptoms may develop within days or weeks after exposure to a site where bird or bat droppings have accumulated. Even when infected, healthy individuals may have no symptoms (asymptomatic) or exhibit a relatively mild illness. In fact, 90% of those with acute pulmonary histoplasmosis reveal no symptoms of the disease (Chang). If symptoms are present, they may be flu-like and include chills, cough, fever, headache, abdominal pain, chest pain, or difficulty breathing. Skin lesions and joint pain may also be reported. The individual may also have a pre-existing condition such as emphysema or an immune disorder that has worsened. In the progressive disseminated form of histoplasmosis, symptoms may worsen slowly or very rapidly.

 

 Severe or chronic (chronic cavitary histoplasmosis) forms of the disease develop gradually over several weeks. Symptoms may include a feeling of illness (malaise), gastrointestinal disturbances, diarrhea, weight loss, chronic mild fever, a cough that produces yellow or green sputum (phlegm), confusion, disorientation, and neck pain. Complaints in rare cases may include impaired vision or blindness (presumed ocular histoplasmosis).

 

Physical exam: Milder cases resemble upper respiratory infections. In progressive forms of the disease, ulcers of the mucous membranes in the mouth and throat may be present. When pressure is applied by hand (palpation), enlarged lymph nodes (lymphadenopathy), spleen (splenomegaly), and/or liver (hepatomegaly) may be detected. Individuals with immune disorders or pre-existing related conditions may have difficulty breathing. Continual weight loss (wasting syndrome) may be evident.

 

Tests: The diagnosis can be confirmed by microscopic examination of specimens or tissue biopsies to confirm the presence of targeted microorganisms. Tested areas may include sputum, lung tissue, blood, cerebrospinal fluid, or bone marrow. Blood and urine tests (serology) may also help identify specific antibodies produced by the immune system as a defense against antigens associated with the disease.

 

 Investigations are being done on new laboratory methods that use polymerase chain reaction (PCR) technology to directly identify specific genes or DNA sequences of the organism.

 

 Chest x-rays may help reveal abnormalities in the lungs, but they could be variable and nonspecific. Moderately severe infections may be recognized in the x-rays as an atypical pneumonia. Other diagnostic tests may be performed to rule out complications or coexisting conditions. A complete blood count (CBC), detection of total percentage of red blood cells (hematocrit), and hemoglobin analysis can rule out anemia. Liver and kidney function tests indicate possible impending failure of these organs. Bone marrow and liver biopsies may reveal disseminated forms of the disease. CT scans obtain images of the head, chest, and abdominal areas to help detect the disease or rule out other possibilities. Tests may also be conducted to determine whether the lungs are functioning adequately (pulmonary function tests). In individuals with AIDS, bacteria in the blood (bacteremia) should be investigated. A urine antigen test is very helpful in the diagnosis and follow-up of histoplasmosis in individuals with AIDS.

 

 Skin testing is generally not useful in diagnosing histoplasmosis. Many residents living in an affected area will test positive without having symptoms. In disseminated histoplasmosis, half of those with the condition will have negative results after skin testing.

 

 

Clinical examination of tuberculosis patients

 

The methods of investigation of respiratory (tuberculosis) patients are conveniently divided into three groups.

The First group – compulsory (obligatory) methods, which embrace clinical examination of a patient (complaints, anamnesis, examination, palpation, percussion, auscultation), thermometry, X-ray investigation (fluorography, X-raygraphy, X-rayscopy), sputum analysis for MBT, Mantoux tuberculin test (with 2 TU), general blood and urine test.

The Second group – additional (supplementary) methods, which include repeated sputum analysis (bronchial lavage water) for MBT, tomography of the lungs and mediastinum, protein-tuberculin tests, immunologic tests, instrumental examinations (bronchoscopy, biopsy, bronchography, pleuroscopy).

The Third group – facultative (optional) methods: investigation of the outer breathing function, blood circulation, liver and other organs and systems.

Tuberculosis is an infectious disease, caused by MBT, and is characterized by the development of specific inflammation in injured organs and polymorphism of clinical symptoms – intoxication and local syndromes.

Within the range of the likely evidences of the general TB intoxication, the most frequent are general weakness, indisposition, drop of the ability to work, sweating, appetite drop, weight loss, sleep disturbance, body temperature rise. Body temperature in TB patients can vary – it can be normal, subfebrile, febrile and even hectic. However, the most often it is subfebrile, which is characterized with pronounced lability and the absence of monotony. Patients often endure the high temperature easily.

At the beginning of the illness the sweating is low. Profuse sweat, mainly at night, are characteristic of pronounced exudative, caseous specific processes.

The local manifestations of lung tuberculosis are: prolonged cough, sputum secretion, haemophthisis, chest pain, shortness of breath.

Cough is the most frequent symptom in patients with lung TB. At the initial stages of the process the cough is quiet, not frequent, in the form of light constant hacking cough. Persistent convulsive loud cough is characteristic for patients with tuberculous bronchoadenitis and tuberculous endobronchitis.

At the beginning of the illness, the sputum can not be secreted or can be secreted only a bit. With the progress of the tuberculous, in particular the distructive, process, the patient may secret up to 200 ml of the sputum, which can be mucous or mucous-purulent and can be without any unpleasant smell.

Chest pain is often present already at the beginning of the illness , which is caused by the extensive process in the lungs. Acute sudden pain appears at spontaneous pneumothorax.

Dyspnea is not characteristic for the initial forms of TB, except for the miliary TB and the exudative pleurisy. At the chronic extensive process, complicated with breathing or pneumo-cardial insufficiency, dyspnea can be brightly expressive.

Hemoptysis and bleeding may be present at any form and phase of the process, but more often – at destructive forms of TB, and more rarely – at posttuberculous pneumosclerosis with bronchoectasia. Hemoptysis is characterized by the presence of veins, blood admixtures in the sputum and of separate blood spits. At pulmonary bleeding, much more of pure blood is coughed up in one time (over 10 ml), continuously or with breaks. Blood is usually bright-red, foamy, with tiny air bubbles; it doesn’t have tendency to coagulation. After the bleeding or hemoptysis stops, blood clots are coughed up for several days more; and due to the blood aspiration, the boby temperature rises.

The beginning of tuberculosis illness may be without any symptoms, subacute and rarely – acute. While interviewing a patient it is very important to find out a fact about his contacts with tuberculosis patients. To the point, persons, living amidst nidi of tuberculosis infection (the patient, suffering from the tuberculosis, who excretes the mycobacteria, the place where he lives and people, who live with him), 5-10 times more often contacting tuberculosis. Of great importance is the information about endured in the past “flu”, pneumonia, exudative pleurisy, under which mass tuberculosis can run; accompanying illnesses, working conditions, harmful habits etc.

The formal examination at initial forms of tuberculosis reveals no patient’s visible abnormalities. However, in most patients, at the more advanced stages of the disease one can find manifestations of tuberculosis intoxication: eyes lustre, hectic blush on the background of a face pale skin; paraspecific tuberculosis manifestations (knotty erythema, keratoconjunctivitis, phlyctenae) enlarged peripheral lymphatic nodes, fistulas or scars after them, chest deformation. Palpably: often lowered skin turgor, muscles tone, micropolyadenite, positive “fork-shaped” symptom (putting 2 fingers above the sternum from the both sides of trahea, it is possible to feel its dislocation to the side of injury), which is observed at unilateral lung cirrhosis, atelectasis. Increased voice tremor above infiltration or cirrhosis zones, weakened – at exudative pleurisy, pneumothorax.

Percussively: shortened and dull percussioote is defined above the airless lung tissue or in the spheres of its lowered (weakened) pneumatization at infiltrates, nidus–fibrous transmutations (changes) and exudative pleurisy. Tympanic note occurs above the strenuous spontaneous pneumothorax, a gigantic cavity. However, more often shortening of percussion note is observed above the cavern.

The standing hight of the lungs apex and the width of Crening’s spheres (fields) decreases as a result of nidus, infiltrating or fibrous changes in the upper sections of the lungs.

Auscultation should be performed consistently above the symmetrical sections of the lungs at quiet deep breathing with the patient’s half-opened mouth. With a view to provoke crepitation, the patient should be asked to cough slightly at the end of the expiration. Herewith the doctor should stay at the patient’s side to avoid infestation.

It is necessary to find out the type of breathing (vesicular, bronchial, mixed) and additional murmurs (moist, dry rales, crepitation, pleura friction murmur). Weakened vesicular breathing is defined at lung emphysema, exudative pleurisy, pneumothorax and high caloric diet; strengthened – at emaciation, cirrhosis and lung infiltration process. Rough or bronchial breathing may be heard above a thickened lung tissue (infiltrate, cirrhosis, fibrosis), amphoric respiration – above a large cavern with fibrous walls and a wide draining bronchus. Important from the diagnostic point of view are local moist rales, which are auscultated after the hacking in the “alarm zones”: frontally, above and beneath the clavicle, from the behind above the lungs, near a scapula spine and between scapulae. Local small-bladdered moisty rales are the indication of the beginning of lung tissue destruction, while those of medium-and-great-bladdered – the indication of a cavern. In addition to this, medium-or-great-bladdered rales above the upper sections of the lungs is an essential indication of the decay cavity. Dry rales occur at bronchitis, whistling ones – at bronchitis with a bronchospasm. At dry (fibrinous) pleurisy the murmur of pleural rub is heard.

 

1        case detection

The detection of TB  cases  requires  that affected  individuals are aware of

their symptoms, have access to health facilities and are evaluated by health

workers (doctors, nurses, medical assistants, clinical offcers) who recognize

the symptoms of TB. Health workers must have access to a reliable laboratory

and ensure that the necessary specimens are collected for examination. This is

a complex set of activities and behaviours, and failure at any stage can cause

delays in diagnosis or misdiagnoses.

The most common symptom of pulmonary TB is a persistent, productive cough,

often accompanied by other nonspecifc symptoms. Although the presence of

a cough for 2–3 weeks is nonspecifc, traditionally having a cough of this dura-

tion has served as the criterion for defning suspected TB and is used in most

national and international guidelines.

The following symptoms of pulmonary TB may accompany cough and sputum

production:

•  respiratory symptoms: shortness of breath, chest and back pains, haemop-

tysis;

•  constitutional symptoms: loss of appetite, weight loss, fever, night sweats,

fatigue.

Symptoms of extrapulmonary TB are related to specifc extrapulmonary sites,

such as lymph nodes, pleura, larynx, meninges, genitourinary and intestinal

tracts, bone, spinal cord, eye and skin.

Sputum smear microscopy.  Sp u t um s p e c imes  s h o u l d b e  o b t a ie d f o r  mi c r o s c o p i c 

examination from all patients suspected of having pulmonary TB. microbiological

diagnosis  is  confrmed by  culturing M. tuberculosis (or, under appropriate cir-

cumstances, by identifying specifc nucleic acid sequences in a clinical specimen)

from any suspected site of disease. However, in many settings where resources

are limited, neither culture nor rapid amplifcation methods are currently availa-

ble or feasible. In such circumstances, the diagnosis of TB may also be confrmed

by the presence of acid-fast bacilli (AfB) in sputum smear examination. repeated

sputum smear microscopy may diagnose pulmonary TB  in up  to  two-thirds of

active cases.

Iearly all clinical circumstances in settings of high TB prevalence, identifca-

tion of AfB by microscopic examination is highly specifc for the M. tuberculosis

complex. Sputum smear microscopy is the most rapid method for determining

whether a person has TB; it identifes people who are at greatest risk of dying

from the disease and the most likely transmitters of infection.

Sputum specimens. The optimum number of sputum specimens to establish a

diagnosis has been evaluated. The frst specimen was found positive in 83–87%

of all patients in whom AfB are ultimately detected; the second specimen was

positive  in an additional 10–12% and  the  third specimen  in a  further 3–5%.

On this basis, WHO recommends the microscopic examination of two sputum

specimens (formerly three).

1

 Because the yield of AfB appears to be greatest

from early morning (overnight) specimens, WHO further recommends that at

least one specimen should be obtained from an early morning collection.

Sputum collection procedures. The procedures  for collecting sputum  involve

the production of droplets that are highly infectious if the patient has untreated

pulmonary TB. Sputum collection should therefore be organized in areas with

good ventilation or, if not available, outside the building (see chapter 6).

Sputum smear specimens should be examined by microscopy immediately but

no later than 5 to 7 days after they have been collected. A health unit with-

out adequate facilities for collecting and transporting sputum should refer the

patient to the nearest health unit able to collect sputum, or direct the patient

to a microscopy laboratory.

national TB guidelines should include all the details of what health workers

should do before, during and after the collection of sputum. Attention should

be  paid  to  the  characteristics  of  sputum  containers,  precautions  for  health

workers, labelling, identifcation and recording of patients’ addresses.

Diagnosis of smear-negative tuberculosis. for smear-negative and extrapulmo-

nary TB, a diagnosis by a clinician specially trained in TB may be required as

well as radiographic examination. As no chest radiographic pattern is abso-

lutely specifc for pulmonary TB, the diagnosis of smear-negative TB is always

presumptive and should be based on other clinical and epidemiological infor-

mation, including failure to respond to a course of broad-spectrum antibiotics

and exclusion of other pathology. reliance on chest radiography as the only

diagnostic test for TB results in either overdiagnosis of TB or missed diagnoses

of  TB  and  other  diseases  and  is  therefore  not  recommended. radiographic

examination, however,  is most useful when applied as part of a systematic

approach to evaluate patients whose symptoms and/or fndings suggest TB but

whose sputum smears are negative. fluoroscopy results are not acceptable as

documented evidence of pulmonary TB.

Pregnancy. case-detection methods in pregnancy should exclude radiographic

examination, particularly in the frst trimester.

Culture. While sputum smear microscopy is the frst bacteriological diagnostic

test of choice where adequate, quality-assured laboratory facilities are avail-

able,  the  evaluation  of  patients with  negative  sputum  smears  should  also

include culture. culture adds extra cost and complexity but greatly increases

the sensitivity and specifcity of diagnosis, resulting in better case detection.

Although the results of culture may not be available until after a decision to

begin  treatment has been made,  treatment may be stopped subsequently  if

cultures  from  a  reliable  laboratory  are  negative  and  if  the  patient  has  not

responded clinically to treatment and the clinician has sought other evidence

in pursuing the differential diagnosis.

figure 1.1 presents an illustrative approach to the diagnosis of pulmonary TB in

settings with a low prevalence of HIV infection. diagnostic algorithms for high

HIV-prevalent settings and for seriously ill patients are provided in section 1.3.

 Extrapulmonary  tuberculosis.  extrapulmonary  TB  (without  associated  lung

involvement) accounts for 15–20% of TB in populations with a low prevalence of

HIV infection. In populations with a high prevalence of HIV infection, the propor-

tion of cases with extrapulmonary TB is higher. Because appropriate specimens

may be diffcult to obtain from some of these sites, bacteriological confrmation

of extrapulmonary TB is often more diffcult than for pulmonary TB. relatively

few M. tuberculosis organisms are present in extrapulmonary sites, and identi-

fcation of AfB by microscopy in specimens from these sites is infrequent. for

example, microscopic examination of pleural fuid in tuberculous pleuritis and

tuberculous meningitis detects AfB in only about 5–10% of cases.

given the low yield of microscopy, both culture and histopathological examina-

tion of tissue specimens, such as those that may be obtained by needle biopsy

of lymph nodes, are important diagnostic tests for extrapulmonary TB.

1.1  Case defnitions of tuberculosis

A diagnosis of TB should be followed by specifcation of the type of TB, i.e.

the case defnition, which is necessary for prescribing treatment according to

standardized regimens, for patient registration and reporting, for cohort analy-

sis of treatment outcomes and for determining trends.

case defnitions for TB take into account the anatomical site of disease, the

bacteriological results, the severity of disease and the history of previous treat-

ment. Tables 1.1 and 1.2 present the defnitions of TB cases by site, bacteriologi-

cal status and history of previous treatment in adult patients. The defnition

of a sputum smear-positive case is the same for HIV-positive and HIV-negative

patients, i.e. requiring at least one positive smear in countries with a functional

system of external quality assurance (eQA).

1.1.1  Anatomical site of disease

The two main categories of TB by anatomical site of disease are: (i) pulmonary

TB, or disease affecting the lung parenchyma (the most common form of TB);

and (ii) extrapulmonary TB, or disease affecting sites including lymph nodes,

pleura, meninges, pericardia, peritoneum, spine, intestine, genitourinary tract,

larynx, bone and joints, and skin.

1.1.2  Bacteriological results

“Smear-positive” or “smear-negative” is the most useful bacteriological clas-

sifcation of pulmonary cases because it correlates with infectiousness. In set-

tings where culture facilities are available, the results of culture are included in

the bacteriological classifcation. Under most programmatic conditions – when

only microscopy laboratory services are available and when diagnostic criteria

are properly applied – smear-positive cases represent more than 65% of the

 

TABlE 1.1   cASe defInITIOnS BY SITe And BAcTerIOlOgIcAl STATUS In HIV-negATIVe

AdUlTS And fOr nOn-HIV preVAlenT SeTTIngS

Case classifcation  Defnition

Pulmonary tuberculosis,  One or more initial sputum smear examinations positive for

sputum smear-positive (PTB+)  Acid-fast bacilli by microscopy

Pulmonary tuberculosis,  A case of pulmonary tuberculosis who does not meet the above

sputum smear-negative (PTB–)  defnition for smear-positive tuberculosis.

  Note: In keeping with good clinical and public health practices,

  diagnostic criteria should include:

  1. At least two sputum specimens negative for acid-fast bacilli,

   and

  2. radiographic abnormalities consistent with active pulmonary

    tuberculosis, and

  3. no response to a course of broad-spectrum antibiotics, and

  4. decision by a clinician to treat with a full course of anti-

    tuberculosis chemotherapy.

  This group includes patients whose sputum smears are

  negative but whose culture is positive.

Extrapulmonary tuberculosis  A patient with tuberculosis affecting organs other than the

  lungs. diagnosis should be based on one culture-positive

  specimen, or histological or strong clinical evidence consistent

  with active extrapulmonary tuberculosis, followed by a decision

  by a clinician to treat with a full course of anti-tuberculosis

  chemotherapy.

 

 

 

 

 

 

 

 

 

 

TABlE 1.2   cATegOrY Of pATIenTS fOr regISTrATIOn On dIAgnOSIS 

(BASed On HISTOrY Of preVIOUS TreATmenT)

Diagnostic/registration category  Defnition

New    A patient who has never had treatment for tuberculosis or

    who has taken  anti-tuberculosis drugs for less than one

    month.

Re-treatment  Relapse  A patient previously treated for tuberculosis who has been

cases    declared cured or treatment completed, and is diagnosed

    with bacteriologically positive (at least one smear or

    culture) tuberculosis.

  Treatment   A patient who is started on a re-treatment regimen after

  after failure  previous treatment has failed.

  Treatment   A patient who returns to treatment with positive

  after default  bacteriology, following interruption of treatment for two

    months or more.

Transfer in    A patient who has been transferred from another

    tuberculosis register to continue treatment in a different

    register area.

Other    All cases who do not ft the above defnitions. This

    group includes patients who are sputum smear-positive

    at the end of a re-treatment regimen (previously defned

    as chronic cases) and who may be resistant to the

    frst-line drugs.

Note: Smear-negative pulmonary and extrapulmonary cases may also be relapses, failures or

other cases. Such diagnoses should be supported by pathological or bacteriological evidence.

 

total number of cases of pulmonary TB in adults, and 50% or more of all TB

cases (although those proportions may be altered in settings with high preva-

lence of HIV infection).

A patient with both pulmonary and extrapulmonary TB is classifed as a case

of pulmonary TB.

 

1.1.3  Severity of disease

Bacillary  load, extent of disease and anatomical  site are  factors  that deter-

mine the severity of TB disease, and consequently its appropriate treatment.

A case of pulmonary TB is classifed as severe if parenchymal involvement is

extensive. miliary disseminated TB is also considered severe. Involvement of an

anatomical site results in classifcation as severe disease if there is a signifcant

acute threat to life (e.g. pericardial TB), a risk of subsequent severe handicap

(e.g. spinal TB) or both (e.g. meningeal TB).

The following forms of extrapulmonary TB are classifed as severe: meningeal,

pericardial, peritoneal, bilateral or extensive pleural effusion, spinal, intestinal

and genitourinary. TB of  the  lymph nodes, unilateral pleural effusion, bone

(excluding spine), peripheral joint and skin is classifed as less severe.

1.2  Case detection of drug-resistant tuberculosis

programmatic strategies for the management of drug-resistant TB aim to iden-

tify patients and initiate adequate treatment for drug-resistant cases in a timely

manner. prompt identifcation and initiation of adequate treatment gives a bet-

ter chance of cure for patients, provides the best infection control measure, and

prevents the acquisition of further resistance and progression to a chronic state

of permanent lung damage.

WHO  recommends  that programmes have population-representative data of

drug resistance surveillance (drS) for new patients, for the different categories

of  re-treatment  patients  (failure  after  category  I,  failure  after  re-treatment,

default and relapse) and for other high-risk groups (see chapter 2). designing

an effective case-fnding strategy depends on this information. Availability of

drS data for the different groups also enables calculation of the number of

patients who should enter the programme; this in turn greatly facilitates pro-

gramme planning and drug procurement (see also chapter 14).

Some programmes may not have suffcient laboratory capacity to provide drug

susceptibility testing (dST) of all patients. Where targeted dST surveys identify

a risk group or groups of patients with a high proportion of mdr-TB (which may

exceed 80%), the use of category IV regimens in all patients in that group is

justifed.

The three risk groups commonly considered for direct enrolment for a category

IV regimen are:

•  category II failures (chronic TB cases);

•  TB patients who are close contacts of mdr-TB cases;

•  category I failures who received a full

course of treatment.

The  proportion  of  mdr-TB  in  these

three groups may vary considerably.  It

is therefore important to confrm mdr-

TB through the use of dST (to, at least,

isoniazid and rifampicin) for all patients

who start a category IV regimen.

In  most  settings,  other  groups  are

unlikely  to have  rates of mdr-TB suff-

ciently high to warrant entry into a drug-

resistant TB treatment regimen without

confrmation  of  mdr-TB  by  dST  (Box

1.1).

BOx 1.1

DEFINITIONS OF MulTIDRuG-

RESISTANT TuBERCulOSIS AND

ExTENSIVEly DRuG-RESISTANT

TuBERCulOSIS

n  MDR-TB. Tuberculosis with

resistance to, at least, isoniazid, and

rifampicin.

n  xDR-TB. Tuberculosis with

resistance to, at least, isoniazid

and rifampicin and to any of the

fuoroquinolones and to one of the

following injectable drugs: amikacin,

capreomycin, kanamycin.

1.3  Case detection of tuberculosis and human immunodefciency virus

Important differences exist  in  the diagnosis of TB  in HIV-prevalent  settings

and in settings of low HIV prevalence. HIV alters the clinical pattern of TB and

complicates its diagnosis.

Infection with HIV  increases  the  risk of progression of  recent M. tuberculo-

sis infection and of reactivation of latent M. tuberculosis infection by 5–15%

annually, depending on the degree of immune defciency. It also increases the

rate of recurrence of TB, both relapse (reactivation of latent TB) and reinfec-

tion (newly acquired infection). HIV is responsible for a large increase in the

proportion of patients with smear-negative pulmonary and extrapulmonary TB.

These  patients  have  inferior  treatment  outcomes,  including  excessive  early

mortality, compared with HIV-positive, smear-positive pulmonary TB patients.

Tackling  this problem  requires  rapid diagnosis of smear-negative pulmonary

and extrapulmonary TB in settings with high HIV prevalence.

Effect of HIV on TB. HIV infection causes reduced immune competence and the

consequent  loss of ability  to prevent  the spread of  the  tubercle bacilli  from

localized granulomas (due to a decline in the number of cd4+ T cells). rapid

progression  from  initial  infection  to TB disease may also occur  in markedly

immunosuppressed patients. patients with active TB who are HIV-positive have

a higher risk of dying from TB than those without HIV.

In the early stages of HIV infection, before host immunity is signifcantly com-

promised, patients with TB have the typical symptoms of TB, and smear micro-

scopy is usually positive. With more advanced HIV infection and compromised

immune status, TB symptoms are atypical and the smear is ofteegative. pau-

cibacillary (scanty) smears are also more frequent in HIV-infected TB patients.

HIV-positive patients with smear-negative TB are more likely to die during or

before diagnosis than HIV-negative smear-positive patients.

Radiography. The use of chest radiography to diagnose pulmonary TB may be

compromised by poor flm quality, low specifcity and diffculties with interpre-

tation. HIV infection further diminishes the reliability of chest radiographs for

the diagnosis of pulmonary TB because the disease commonly presents with

an atypical pattern.  furthermore,  the  chest  radiograph may be normal  in a

proportion of HIV-infected patients with sputum culture-positive TB (observed

in up to 14% of such cases). However, chest radiography remains an important

adjunct to the diagnosis of smear-negative pulmonary TB in people living with

HIV (plHIV).

Diagnostic algorithms. Algorithms for the diagnosis of TB in ambulatory patients

in HIV-prevalent settings and in seriously ill HIV-positive patients are provided

below (figures 1.2 and 1.3).

The diagnosis of smear-negative pulmonary TB is particularly diffcult among

HIV-positive patients, and use of the algorithm is therefore recommended.

The algorithm for HIV-negative patients (figure 1.1) includes treatment with a

course of broad-spectrum antibiotics to exclude infections other than TB, and

to improve the specifcity of the diagnosis.

The result of antibiotic treatment is not affected by HIV status. However, patients

with TB may lose their respiratory symptoms after a course of antibiotics.

The specifc aspects of TB diagnosis in HIV-prevalent settings are that:

•  the clinical assessment of the seriousness of disease is taken into account;

•  special efforts to avoid delay in establishing the diagnosis should be made;

•  the use of antibiotics (for clinical reasons) is not a step in the diagnostic

process;

•  all available  investigations, such as chest  radiography, culture of sputum

and specimen culture for cases of extrapulmonary TB, should be carried out

as soon as possible.