About tuberculosis

1. Tuberculosis as
infectious disease.
Lecture № 1.
Doc. Fedorova S.V.

2. Tuberculosis
is infectious disease caused by
Mycobacterium tuberculosis, which leads
to specific granulomas (tubercles)
development in affected organs and
tissues and polymorphic clinical
symptoms.
TB can involve lymphatic system, bones,
joints, genitourinary system, nervous
system and other organs, but mainly
lungs.
TB is a social disease, because it’s rate
depends on social and economical live
level in a country.

3. Tuberculosis
• The genus Mycobacterium
originated more than 150 million
years ago (Daniel, 2006)
• The modern members of M.
tuberculosis complex seem to have
originated from a common
progenitor about 15000-35000
years ago (Gutierrez, 2005)

4. Tuberculosis
• was documented in Egypt, India,
and China as early as 5000, 3300,
and 2300 years ago, respectively
(Daniel 2006)
• Typical skeletal abnormalities,
including Pott’s deformities, were
found in Egyptian mummies

5. Tuberculosis
• Mummy, Museum
«Arqueológico de la
Casa del Marqués de
San Jorge», Bogota,
Colombia.
• Right: Computerized
tomography showing
lesions in the
T10/T11 vertebral
bodies.

6. The greatest scientific
discovery happened in 1882
The famous germen
microbiologist Robert
Koch discovered M.
tuberculosis and
confirmed, that it was
the causative agent of
tuberculosis. It was
reported at the session
of phtisiological society
on the 24th of March in
1882. Robert Koch was
awarded the Nobel Prize
for his discovery in
1911. Now the 24th of
March is the World TB
Day.

7. TB cases definitions by
WHO
• A bacteriologically
confirmed TB case –
when one sputum (or
other biological
material) specimens
at least is positive
by microscopy, or
culture, or fast
methods of
diagnosis (WRD -
WHO recommended
rapid diagnosis), as
XpertMTB/Rif.
• A clinically diagnosed TB
case – is one that does
not correspond the
criteria for bacteriological
confirmation, but has
been diagnosed as active
tuberculosis by a
specialist who has decided
to prescribe a course of
TB treatment. This
definition includes cases
diagnosed on the basis of
radiographic or
histopathological
abnormalities and EPTB
cases without laboratory
confirmation.

8. TB classification by WHO
based on the anatomical
focus of the disease
• Pulmonary TB refers to any
bacteriologically confirmed
or clinically diagnosed TB
case affecting the lung
parenchyma or
tracheobronchial tree.
Miliary tuberculosis is
classified as pulmonary
tuberculosis because there
are lesions in the lungs.
• Extrapulmonary TB
refers to any
bacteriologically
confirmed or clinically
diagnosed TB case
affecting organs other
than the lungs, such as
pleura, lymph nodes,
abdomen, urogenital
tract, skin, joints,
bones, meninges etc.

9. Pulmonary TB cases
• Smear-positive TB
case – when one
specimens of
sputum at least is
positive by simple
microscopy.
• Smear-positivity of
pulmonary TB cases
indicates
contagiousness of
TB patients.
• Smear-negative TB cases
– when all specimens of
sputum are negative by
simple microscopy, but
the case diagnosed by
specialist as active TB on
the base of typical
clinical symptoms, an/or
X-ray abnormalities,
and/or histopathological
abnormalities, and/or
bacteriological
confirmation by culture or
WRD.

10. Extrapulmonary
tuberculosis
Tuberculous spondylitis (pathological rupture of
affected vertebras with constriction of spinal
cord)

11. Extrapulmonary
tuberculosis
Tuberculous gonitis (tuberculosis of knee joint)

12. Extrapulmonary
tuberculosis
Cavitary tuberculosis of kidney

13. Extrapulmonary
tuberculosis
Tuberculosis of tongue

14. Extrapulmonary
tuberculosis
Tuberculous chorioretinitis

15. Extrapulmonary
tuberculosis
Tuberculosis of skin (lupus tuberculosis)

16. Extrapulmonary
tuberculosis
Cervical lymphatic nodes TB

17. Estimated number of new
TB cases
Estimated number of
deaths from TB
1,2 mln *
10,0 mln
465000 mln R/R TB
(78% HR/R TB)
All forms TB
Multidrug-resistant TB
HIV/TB 0,82 mln (8,2%) additionally 208 000
(14,8% of all TB deaths)
Source: WHO Global Tuberculosis Report 2019 * Including deaths attributed to HIV/TB
Global tuberculosis situation
WHO report, 2020
unknown, but more
than > 150 000
woman: 32%
kids: 12%

18. Methods of TB
detection
• Radiological methods
• Microbiological methods
• Immunological methods
• Hystological methods

19. Microbiological methods
of TB detection
• Conventional
methods
• Microscopy
• Culture
• Biological method
• WRD (WHO-
recommended rapid
methods of diagnosis)
• Xpert MTB/RIF
• Xpert MTB/RIF Ultra
assay
• Truenat MTB, MTB Plus
and MTB-RIF Dx assays
• TB-LAMP assay
• Line Probe Assays
• Urine LF-LAM assay

20. МBТ belongs to the Order of
Actinomycetae (radiant mushrooms),
the Family of Mycobacteriaecae,
the Genus of Mycobacterium
There are three related microorganisms
called «MBT-complex» (Mycobacterium
of tuberculosis):
• М. tuberculosis (МBТ) – is especially
pathogenic kind for people
• М. bovis – is especially pathogenic for
the cattle
• М. africanum – the main reason of TB
cases in Africa

21. Basic properties МBТ
• acid-alcohol-
alkalai fastness
• variability
• pathogenicity
• virulence

22. Methods of sputum
microscopy
• Method of simple
(direct) microscopy
(Ziehl-Neelsen staining)
• Method of fluorescent
microscopy
• Electron microscopy

23. Sputum slides

24. Mycobacterium tuberculosis
(Ziehl-Nilsen staining)

25. Method of direct
sputum microscopy
Advantages
• Fast method
• Cheap
method
• Simple
method
• Informative
method –
detection of
MBT is
confirmation
of diagnosis
Disadvantages
• Method isn't sensitive (result is
positive when there are more than
5000 of microorganisms in 1 ml of
sputum)
• Possibility MBT-transmission to the
health care workers during the
procedure of sputum collection and
examination
• Low informative in some categories of
patients (children, extrapulmonary TB
patients, TB/HIV patients)
• It is not possible to define drug
susceptibility of MBT to TB drugs,
type of MBT, viability of MBT and
other properties

26. Culture on solid media
Colonies of Mycobacterium tuberculosis on
Lewenstain-Jensen medium

27. Culture on solid media
Advantages
• Sensitive (result is
positive when there
are 20-50 MBT in 1
ml of sputum)
• Ability of МBТ type
definition, MBT drug-
susceptibility to
antituberculous
medicines, the level of
МBТ elimination etc.
Disadvantages
• Expensive method
equipment and
laboratory
• Long time of MBT
growth (14-70 days)
+ 45 days DST (drug
susceptibility test)
• Possible transmitting
of MBT during
process of culture

28. Culture on liquid media
(rapid diagnosis)
• BACTEC MJIT
Positive samples show up
as yellow in the well,
negative samples are
colourless
The BACTEC TB-460 instrument
MGIT tube

29. Biological method
(infection of experimental
animals)
Advantages
• Very sensitive
method (from 1 to 5
microbic cells may
cause generalized
tuberculosis in
experimental animal)
• Experimental model
of tuberculosis
Disadvantages
• High prices
• Hard-worked
• Long time
• Inhumane

30. WRD (WHO-recommended
rapid methods of diagnosis)
• Xpert MTB/RIF
• Xpert MTB/RIF
Ultra assay
• Truenat MTB, MTB
Plus and MTB-RIF
Dx assays
• TB-LAMP assay
• Line Probe Assays
• Urine LF-LAM assay
Truenat MTB and MTB plus
XpertMTB/Rif

31. Xpert MTB/Rif
• Time – 2 hours 5 minutes
• Detection of MBT DNA
• Definition of drug-susceptibility to
rifampicine

32. Diagram of amplification
Positive result – MBT DNA
detected/Rif resistant
Negative result - MBT
DNA not detected

33. All microbiological
methods
of МBТ detection are high-
reliable, i.e. detection of MBT is
100% confirmation of diagnosis
«TB»

34. Radiological methods
are important in the diagnosis and
management of TB, especially in clinically
diagnosed cases. But X-ray findings could
never be confirmation of clinical diagnosis
«Tuberculosis», because:
• Chest X-ray findings, associated with
pulmonary TB (PTB), are non-specific.
• Each pulmonary disease can cause the
both as «classical», as «atypical» chest
X-ray findings.
• Different diseases may be similar to
each other on chest X-ray.

36. X-ray methods
• Roentgenoscopy
• Roentgenography
• Fluorography
• Electroroentgenography
• Tomography
• Roentgenokimography
• Brochography
• Computed tomography
etc.

37. Total and subtotal
opacity
• TB pneumonia
• thromboembolism of
pulmonary artery
• lung atelectasis
• pneumonia
• etc.
Tuberculous pneumonia of the left lung
with destruction and bronchogenous
dissemination

38. Round opacity
• tuberculoma
• peripheral cancer
• ecchinococcal cyst
• interlobar pleurisy
• etc.
Tuberculoma of the left upper lobe
with destruction

39. Focal opacity
• focal tuberculosis
• peripheral cancer at
early stage
• ecchinococcal cyst at
early stage
• focal fibrosis
• focal pneumonia
• etc.
Focal tuberculosis
of the left upper lobe

40. Dissemination
• miliary tuberculosis
• disseminated tuberculosis
• oncological diseases
• professional diseases
• sarcoidosis
• pneumonias
• etc.
Miliary tuberculosis
of the both lungs

41. Cavity
• cavitary tuberculosis
• lung cancer with
destruction
• ecchinococcal cyst after
rupture
• abscess after rupture
• bullous emphysema
• etc.
Cavitary tuberculosis
of the right upper lobe

42. Enlargement of
intrathoracic lymph nodes
• tuberculosis of hilar
lymph nodes
• lymphogranulomatosis
• sarcoidosis
• retentional cyst of
bronchi
• etc.
Tuberculosis of mediastinal
lymphatic nodes with calcification

43. Mediastinum pathology
• tuberculosis of
mediastinal lymph
nodes
• oncological diseases
• aneurism of large
vessels
• diverticulum of
esophagus
• hernia of esophageal
foramen of
diaphragm
• etc.
Lymphosarcoma

44. Lung-pattern pathology
• miliary tuberculosis
at early stage
• diseases of
connective tissue
• viral pneumonia
• initial stage of lung
edema
• cancer lymphangitis
• pneumofibrosis
• etc.
Sclerodermia

45. Pleural pathology
• pleurisy
• pleural mesothelioma
Total pleuritis
of the right pleural cavity

46. Total transparency
• spontaneous
pneumothorax
• emphysema
Spontaneous pneumothorax
of the right lung

47. The most typical X-ray
signs of TB
• In adults
• Upper lobe
localization
• Infiltrates
• Cavities
• Foci of
bronchogenous
dissemination in low
parts of lung tissue
• In children
• Enlargement of
mediastinal and hilar
lymph nodes, usually
unilateral
• Might be involvement
of lung tissue
• Calcification of
intrathoracic lymph
nodes and lung tissue

48. Detection of TB cases
by screening pathway
• Examination of population (groups at high
risk of tuberculosis) – screening by
fluorography or tuberculin skin test

49. Detection of TB cases
by patient-initiated pathway
• Examination of suspected persons (cough
2 weeks and more) by WRD and sputum
microscopy – patient-initiated approach

50. Clinical symptoms are
suspected on TB
• cough for 2 weeks
and more
• chest pain
• dyspnea
• haemophthysis
• weight loss
• night sweats
• fever
• weakness

51. Main steps of TB cases
definition by microscopy
• Each person with
cough, chest pain,
weight loss, night
sweats and other
suspected
symptoms must
come to the
health care
facility
• The health care
worker must
suspect TB
• prescribe
XpertMTB/Rif and
direct microscopy
of sputum
specimen
• use diagnostic
WHO algorithm

52. Algorithm 1A: re-evaluation patient
clinically and conducting additional testing
to confirm or exclude TB
TB suspects (cough, sputum production for 2 weeks and more)
XpertMTB/RIF
Sputum microscopy
-
TB
Chest X - ray
Broad-spectrum AB,
Except R, Fq, Amg
Control chest X -
ray
Improvement
No improvement
No
TB
XpertMTB/RIF
mWRD
+
+
-
-
TB treatment
DST by l-J,
BACTEC, mWRD
Case management
by specialist
+

53. Thank you
for attention!