 Lecture 1

 Determination of tuberculosis
as a scientific and practical
problem. History of
development of phthisiology.
 Methods of diagnoctics
tuberculosis

 2020

 Prof. L.A. Hryshchuk

 The World Health Organization (WHO)
proclaimed tuberculosis to be the global danger.
According to its forecasts there will be 90 million new
tuberulosis cases in the world during the decade. Of
those who will fall ill approximately 30 million people
may die in the current decade unless the reaction to
this global problem radically improves.

Nowadays the world scientists distinguish threeunion

tuberculosis epidemic: the first is the epidemic of
typical tuberculosis that is treated well; the second is
the epidemic of chemioresistant tuberculosis and the
third one is the epidemic of tuberculosis and the AIDS.
TB incidence
 Tuberculosis (TB) remains a major global
health problem
 TB ranks as the second leading cause of
death from an infectious disease worldwide,
after the human immunodeficiency virus
(HIV).
 2018 – there were 9.0 million new TB cases
and 1.5 million TB deaths (1.1 million
among HIV-negative people and 0.4 million
among HIV-positive people).
 According to the WHO criteria from 1995
tuberculosis epidemic has been registered in Ukraine in
so far as tuberculosis patients comprise over 1 % of the
total number of the population.

The statistics of sickness in all the forms of

tuberculosis in 2018 was 68,1 persons per 100 thousand
of the population.

Alarming is the fact that tuberculosis “has turned

younger”, its number among children, able-bodied and
reproductive ages increases.
 HISTORICAL REVIEW

Tuberculosis, as an illness, is known since ancient

times.

Tuberculosis (TB) is believed to have been present in humans

for thousands of years. Skeletal remains show that prehistoric
humans (4000 BC) had tuberculosis, and tubercular decay has
been found in the spines of Egyptian mummies (3000-2400 BC).
 The term “phthisis”, consumption,
appears first in Greek literature. Around
460 BCE, Hippocrates identified phthisis
as the most widespread disease of the
times, and noted that it was almost
always fatal.
 Due to common phthisis-related
fatalities, he wrote something no doctor
would dare write today: he warned his
colleagues against visiting TB patients in
late stages of the disease, because their
inevitable deaths might damage the
reputations of the attending physicians.
The study of tuberculosis,
sometimes known as
phthisiatry, dates back to
''The Canon of Medicine''
written by Ibn Sina
(Avicenna) in the 1020s.
He was the first physician to
identify pulmonary
tuberculosis as a contagious
disease, the first to recognise
the association with diabetes,
and the first to suggest that it
could spread through contact
with soil and water.
The fact that tuberculosis is infectious was confirmed by
Fracastoro in the 16th century.
It was Morton who published the first monograph
“Phthisiology or a treatise on the phthisis”
( R. Morton, 1689) and named a science of
tuberculosis “phthisiology” (from the Greek word
“phthisis” ).
In the 17th century the French anatomist Sylviy,
describing the hurt lungs of patients who had died
of phthisis, used the word “hump” (tuberculum).
However, it was only in the 19th century in France that
pathologists and therapeutists G. Bayle, and then R. Laennec
proved the hump and caseous necrosis to be specific
morphological substratum of tuberculosis. In 1865 the French
physician B. Villemin experimentally proved the infectious
nature of tuberculosis, though he could not reveal the pathogene.
 In 1882 the German bacteriologist Robert Koch (fig. 1)
discovered the pathogene of tuberculosis, which was named
bacillus of Koch (BK). He was also the first who obtained
tuberculin with the hope to successful treatment of tuberculosis
patients. These expectations of the scientist did not come true,
nevertheless for the purpose of diagnostics tuberculine has been
used for over 100 years Fig. 1. R.Koch (1843-1910)
M.I. Pyrohov studied clinico-morphological properties of
tuberculosis of various localization and for the first time
described typhoid form of miliar tuberculosis, histologic
structure of tuberculous granuloma.
 In 1887 R. Philip in Edinburgh (Scotland)
founded the world first antituberculosis
dispansery. This new institution offered the
patients not only medical but also social help,
which later on laid the foundation of the
organization of antituberculosis service also in
this country.
In 1882 in Rome C. Forlanini offered
artificial pneumothorax for treating lung
tuberculosis patients.
In 1895 Wilhelm Kondrat Roentgen discovered X-rays, which
have been widely used in medicine up to today. Actually, it’s
known well enough that X-rays were discovered by Ukrainian
scientist Ivan Pulyuy (1845-1918) from Halichina 17 years
earlier. However, he made his announcement about the discovery
7 days after Mr. Roentgen had made his one, thus the preference
was given to Mr. Roentgen who received Nobel Prize.
An important achievement of the start of the 20th century was
the creation by the French scientists Calmette and Guerin (1919)
of the antituberculosis vaccine BCG (Bacilles Calmette, Guerin).
Since 1935 mass vaccination began. At the same time in 1924
Abre in Brazile introduced the method of fluorographic
observation of the population for active revealing lung
tuberculosis patients.
 CLINICAL CLASSIFICATION
OF TUBERCULOSIS
 I. TYPE OF TUBERCULOUS
PROCESS

 1. First diagnosed tuberculosis – FDTB

(date of its ascertainment)
 2. Tuberculosis relapse – TBR (date of its
ascertainment)
 3. Chronic tuberculosis – CTB (date of its
ascertainment)
 II. CLINICAL FORMS OF

TUBERCULOSIS
A 15.-A 16. – Lung tuberculosis (LTB) (from a facultative
designation of the form of injury)

 A 15.-16.- Primary tuberculous complex

 A 19.- part Disseminated lung tuberculosis
 A 15-16.- Nidus lung tuberculosis
 A 15-16.- Infiltrative lung tuberculosis
 A 15-16.- Caseous pneumonia
 A 15-16.- Lung tuberculoma
 A 15-16.- Lung fibrous-cavernous tuberculosis
 A 15-16.- Lung cirrhotic tuberculosis
 A 15-16./J65 Tuberculosis of respiratory organs
combined with dust professional lung diseases
(coniotuberculosis)
 III. CHARACTERISTIC OF
TUBERCULOUS
 1. Localization of defect
PROCESS
 Localization of defect in lungs according to the
numbers (names) of segments, names of lung sections,
and in other organs and systems – according to
anatomical names of localization of a failure.
 2. Presence of destruction
 (Destr +) destruction is present
 (Destr -) destruction is not present
facultatively it is necessary to specify a phase of
tubercular process:
 infiltration, decay (Destr +), sowing;
 suction, condensation, scarring, calcination.
 3. Etiologic confirmation of tuberculosis
diagnosis
 (MBT +) it is confirmed by the results of bacteriological analysis (code A 15), in this case
to specify:
 (M +) positive result of sputum analysis on acid-resisting bacteria (ARB);
 (C 0) cultural analysis was not done;
 (C -) negative result of cultural analyses;
 (C +) positive result of cultural analyses, in that case to specify:
 (Resist 0) MBT resistance to preparations of I line was not analysed;
 (Resist -) resistance to preparations of I line has not been established;
 (Resist +) ( abbreviation of antitubercular preparations of I line) resistance МBТ to
preparations of I line has been established (in brackets to list all the preparations of I line
to which resistance has been determined).
 (Resist II0) MBT resistance to preparations of II line was not analysed;
 (Resist II-) resistance to preparations of II line has not been established;
 (Resist II+) ( abbreviation of antitubercular preparations of II line) resistance МBТ to
preparations of I line has been established (in brackets to list all the preparations of I line
to which resistance has been determined).
 ( МBТ-) is not confirmed by the results of bacteriological analysis (the code A16), in this
case to specify:
 (S 0) sputum was not investigated;
 (S -) negative result of sputum analysis on acid-resisting bacteria (ARB);
 (C 0) cultural analysis was not done;
 (C- ) negative result of cultural analysis;
 (Hist 0) histologic analysis was not carried out;
 (Hist -) is not confirmed by the results of histologic analysis (the code A 16);
 (Hist +) it is confirmed by the results of histologic analysis (the code A 15).
 IV. COMPLICATIONS OF
TUBERCULOSIS
 Complications of lung tuberculosis (LTB):
haemoptysis, lung haemorrhage, spontaneous
pneumothorax, lung insufficiency, chronic lung
heart, atelectasis, amyloid disease etc.

 Complications of extrapulmonary tuberculosis

(EpTB): bronchus stenosis, pleura empiema,
fistulae (bronchial, thoracic), renal (adrenal)
insufficiency, sterility, commissure, ankylosis,
amyloid disease etc.
 V. CLINICAL AND DISPENSARY
CATEGORY OF THE REGISTRATION
PATIENT
 Category 1 (Cat 1) First diagnosed tuberculosis
with bacterial excretion (FDTB МBТ +), and also
other grave and wide-spread forms of the disease
without bacterial excretion (FDTB МBТ-)
 Category 2 (Cat 2) Relapses of tuberculosis
(RТB МBТ +) and (RТB МBТ-) and first
diagnosed tuberculosis inefficiently treated (
FDTB IT МBТ +) and (FDTB IT МBТ-)
 Category 3 (Cat 3) First diagnosed tuberculosis
with the limited process, without bacterial
excretion (FDTB МBТ-) and tuberculosis of
unstated localization in children (tubintoxication)
 Category 4 (Cat 4) Chronic tuberculosis (CТ) of
various localizations МBТ + and МBТ-
 Category 5 (Cat 5) Risk groups to tuberculosis or its
reactivation
 Group 5.1 residual changes of cured tuberculosis,
 Group 5.2 contact persons,
 Group 5.3 adults, tuberculosis patients of doubtful
localization,
 Group 5.4 children and teenagers with latent
tubinfection, persons from risk group, and also
children who were not vaccinated in the neonative
period and with postvaccinal complications.
 Group 5.5 children and teenagers whose etiology of
sensitivity to tuberculin it is necessary to specify, or
character of changes in the lungs with the purpose of
difdiagnosis.
 VII. TUBERCULOSIS
CONSEQUENCES
 Residual changes after healed lung tuberculosis:
fibrous, fibrous-nidus, bullous-dystrophic, calcinates
in lungs and lymphatic nodes,
pleuropneumosclerosis, cirrhosis, consequences of
surgical intervention (with the indication of the type
and the date of an operation), etc.
 Residual changes after healed tuberculosis of
extrapulmonary localisation: cicatricial changes in
various organs and their consequences, calcinosis,
consequences of surgical intervention (with the
indication of the type and the date of an operation).
 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).
 Global impact of TB

 TB occurs in every part of the world. In 2019, the

largest number of new TB cases occurred in the
South-East Asia and Western Pacific regions, with
62% of new cases, followed by the African region,
with 25% of new cases.
 In 2019, 87% of new TB cases occurred in the 30
high TB burden countries. Eight countries
accounted for two thirds of the new TB cases:
India,China, Indonesia, the Philippines, Pakistan,
Nigeria, Bangladesh and South Africa.
Incidence TB 2019 in the word
 Morbility on tuberculosis and HIV in Ukraine
The statistics of morbidity in all forms of tuberculosis in
Ukraine from 1995 to 2018 increased from 32 to 63,9 /per
100 thousand population/
 The pathogenesis of
tuberculosisInfection with
Mycobacterium tuberculosis,
the causative agent, follows a
relatively well-defined
sequence of events. The
infectious bacilli are inhaled as
droplets from the atmosphere.
In the lung, the bacteria are
phagocytosed by alveolar
macrophages and induce a
localized proinflammatory

response that leads to

recruitment of mononuclear
cells from neighbouring blood
vessels. These cells are the
building blocks for the
granuloma, or tubercle, that
defines the disease.
 The granuloma consists of a kernel of infected
macrophages, surrounded by FOAMY GIANT CELLS
and macrophages with a mantle of LYMPHOCYTES
delineating the periphery of the structure.
 This tissue response typifies the 'containment' phase of
the infection, during which there are no overt signs of
disease and the host does not transmit the infection to
others. Containment fails after a change in the immune
status of the host, which is usually a consequence of old
age, malnutrition, or HIV-co-infection.
 Under such circumstances, the centre of the
granuloma undergoes caseation and spills viable,
infectious bacilli into the airways. This leads to
development of a productive cough that facilitates
aerosol spread of infectious bacilli.
Pathogenesis of
Tuberculosis
Etiology M. tuberculosis
M. bovis
M. africanum
We will start with the
patient since they are
typically the source of
infection. This slide
shows a violent sneeze
caught on film by high
speed photography
showing large liquid
droplets.
Most of these large,
visible droplets will fall
to the ground. However,
the small droplet nuclei
that can reach the deep
lung are not visible and
are 1:5 micro meters in
size.
Automated screening molecular genetic test to identify
Mycobacterium tuberculosis and resistance R - Xpert
MBT / Rif
 Cultures were on a liquid environment: automated
microbiological analyzer BACTEC MGIT 960
 Performed in all patients
with pulmonary tuberculosis
(with positive and negative
sputum smear)
 Test drug sensitivity to drugs
and second row
 Growth of Mycobacterium
tuberculosis in 7-14 days.
 Increases confirm TB in
patients with negative
sputum smear at 20%
 At a molecular genetic test:
GenoType MTBDRplus
Perform all
patients with
Positive sputum smear
Carried out in parallel
with the classical
culture method

Detects DNK MBT , resistance to isoniazid and rifampin and

isoniazid combination
 Planting on solid medium

Performed in all TB patients

lungs (with positive and negative smear
sputum):
Bank of cultures
Test drug sensitivity
drugs II series
Culture of mycobacteria
tuberculosis at hard egg
medium
Thin section transmission electron micrograph of Mycobacterium
tuberculosis
 The granuloma consists of a kernel of infected macrophages,
surrounded by FOAMY GIANT CELLS and macrophages with a
mantle of LYMPHOCYTES delineating the periphery of the
structure
 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.
 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.
 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.1).
 Radiology
 Chest radiography is the most important
method to detect TB
 TB’s characteristics of a chest radiograph
favor the diagnosis of tuberculosis
as following :
Computer tomography
 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.
Primary complex
Milliary Tuberculosis
acute milliary
tuberculosis
 secondary pulmonary tuberculosis

infiltrate
Tuberculoma
Chronic fibro-cavitary pulmonary tuberculosis

cavity
Tuberculous effusion
Comruter tomograma patient with
pulmonary TB
Fluorography
Bronchography
Tuberculin
testing
A positive tuberculin
test although it is of
great use in children, but it
has limited diagnostic
significance in older age
groups
TUBERCULINODIAGNOSTIC
S

Old Tuberculin Koch

 Dry rectified tuberculin (50000 ТU), the
solvent is isotonic solution of sodium
chloride – 1ml with the addition of 0,25 %
carbolic acid
Positive Mantoux test.
 Diagnosis

According to the history, ,

clinical signs chest X-ray

and some other examinations, we can diagnose TB

A patient with tuberculous pulmonary disease
will come to the physician for one of three
reasons:
(1) Suggestive symptoms
(2) A positive finding on routine tuberculin
testing
(3) A suspicious routine chest roentgenogram
 How to write the diagnosis
correctly?
 Generally, we write the diagnosis
according to the site of TB, clinical
patterns, the result of sputum
examination and the history of
chemotherapy.
Differential Diagnosis 1234

Bronchiectasis may confused with chronic

fibrocavenous pulmonary tuberculosis. They also
have chronic cough, sputum production and
hemoptysis. Usually we can use chest x-ray
examination and CT scan to distinguish them.
 Differential Diagnosis 1234
Cavitary lung abscess often involves the
dorsal segments of the lower lobes and posterior
segments of the upper lobes.
Typically lung
abscess causes litt1e in the way of physical
findings, may have a fluid level, and is not
associated with patchy bronchogenic infiltrates.
In contrast, physical findings are prominent
over tuberculous cavities, fluid levels are rare.
And patchy infiltrates elsewhere are the rule.
 Differential Diagnosis 1234

Acute bacterial pneumonias may resemble

florid tuberculosis in all particulars except for
the sputum examination and response to
antimicrobial drugs.
Differential Diagnosis 1234

Neoplasm may resemble tuberculosis. As in

an isolated coin lesion. An obstructing and
inconspicuous endobronchial tumor causing
distal cbronic inflammation or a caviting
neoplastic mass. ( An irregular cavity wall
suggests necorotic neoplasm. )
LAM