Definition of tuberculosis as scientific and practical problem. Epidemiology of tuberculosis. The etiology and pathogenesis of tuberculosis. Immunity of tuberculosis. Clinical classification of tuberculosis.

1. LECTURE №1.
Definition of tuberculosis as scientific and practical problem.
Epidemiology of tuberculosis.
The etiology and pathogenesis of tuberculosis.
Immunity of tuberculosis.
Clinical classification of tuberculosis.
PHEE Kyiv Medical
University
Lector: Ivashchenko Oleksandr Andriiovych, assistant of Infectious diseases, pulmonology and phthisiology department.

2. Mission, vision and values
MISSION
In relentless pursuit of excellence, to teach, to search, to heal and to
serve humanity
VISION
To transform health care for the benefit of the people and communities
by becoming a national leader in educating health care professionals
VALUES
Excellence, innovation, commitment, integrity, respect, accountability

3. TUBERCULOSIS (tuberculum-tubercle + osis) – the infectious
disease caused by mycobacterium of tuberculosis (MTB).
The science about tuberculosis is called a phthisiology (phthisis-
tuberculosis, -logy - science). In literature and in life tuberculosis has
name:
• Phthisis;
• An evil phthisis;
• Tubercle disease;
• Coxofemoral disease;
• Hair-worm.
• What is tuberculosis?

4. • Historical stages in a phthisiology
1. Ancient times:
• Tuberculosis has been present in human history for thousands of years.
• Ancient civilizations, such as Egypt, Greece, and Rome, described symptoms resembling tuberculosis in their medical texts.
• The disease was often associated with wasting, cough, and the consumption of bodily tissues.
2. 17th-18th centuries:
• Tuberculosis gained the nickname "consumption" due to its progressive wasting nature.
• Medical understanding of tuberculosis was limited, and there were no effective treatments.
• Sanatoriums, places of rest and fresh air, were established to isolate and care for tuberculosis patients.
3. Late 19th century:
• With advancements in microscopy and bacteriology, the discovery of the tubercle bacillus by Robert Koch in 1882 revolutionized the understanding of tuberculosis.
• Koch's identification of Mycobacterium tuberculosis as the causative agent allowed for improved diagnosis and research.
4. Early 20th century:
• The rise of the germ theory and the development of tuberculosis control programs led to increased efforts to combat the disease.
• Public health measures, such as improved sanitation, isolation of patients, and education on respiratory hygiene, were implemented.
5. Mid-20th century:
• The introduction of the BCG vaccine, developed by Albert Calmette and Camille Guérin in the 1920s, provided some protection against tuberculosis, particularly in
children.
• The discovery of streptomycin, the first effective anti-tuberculosis drug, in the late 1940s marked a turning point in treatment.
6. Late 20th century:
• The development of multiple drugs, including isoniazid, rifampin, and ethambutol, created the basis for combination therapy, known as Directly Observed
Treatment Short-course (DOTS), the standard treatment for tuberculosis.
• The World Health Organization (WHO) launched the Global Tuberculosis Control Program in 1987, aiming to reduce the global burden of tuberculosis.
7. 21st century:
• Efforts to control tuberculosis have continued, with expanded access to diagnostics, improved treatment regimens, and increased funding for research and
prevention programs.
• However, challenges such as drug resistance, co-infection with HIV, and the persistence of social determinants of tuberculosis hinder global progress.

5. • Epidemiology of tuberculosis
Based on tuberculin skin testing surveys, it is estimated that about one fourth of the world’s
population is infected. Of those infected, perhaps 15 million have active disease at any given
time.
In 2020, an estimated 9.9 million (127/100,000) new tuberculosis cases occurred worldwide.
Most new cases occurred in Southeast Asia (43%), Africa (25%), and the Western Pacific (18%).
Case rates vary widely by country, age, race, sex, and socioeconomic status. In 2020, two thirds
of new cases occurred in 8 countries; most occurred in India (26%), followed by Indonesia
(8.4%), China (8.5%), the Philippines (6.0%), Pakistan (5.8%), Nigeria (4.6%), Bangladesh
(3.6%), and South Africa (3.3%). A few countries, including North Korea, Lesotho, Mozambique,
the Philippines, and South Africa, had incidence rates above 500/100,000.
Globally, drug-susceptible TB incidence and mortality are slowly decreasing. The cumulative
reduction from 2015 to 2019 was 9% (from 142 to 130 new cases per 100,000), including a
reduction of 2.3% between 2018 and 2019. These trends are likely due in part to global TB
control efforts that have provided more people with access to drugs for TB and HIV infections.
However, the 2020 to 2021 global COVID-19 pandemic disrupted other public health programs,
including TB control, and although it is too soon to quantify, the WHO predicts a stalling or
reversal of these decreasing global trends.

6. • Ways of transmission
• Aerogenic (80 %) air-dust (mostly) and air-drop
• Alimentary (meat, milk, cheese, eggs) – 1-2 %
• Contact (through broken skin and mucous membranes) – 5-6
%
• Intrauterine (transplacental)

7. • Epidemiological indices of tuberculosis-1
Epidemiological indices of tuberculosis:
• Statistics of sickness (incidence)
• Prevalence (morbidity)
• Infestation (contamination)
• Mortality
• Lethality

8. • Epidemiological indices of tuberculosis-2
• Statistics of sickness (incidence) is the number of
first revealed active tuberculosis patients at year-
end counted per 100 thousand population.
• Prevalence (morbidity) – the total number of
patients with active tuberculosis per 100 000
inhabitants of the region at the end of the year.
• Infestation (contamination) – is the percent of
people who respond positively to tuberculin,
compared to the number of examined patients,
except the person with postvaccination immunity.
• Mortality – the number of deaths from tuberculosis
during the year per 100 000 population of the area.
• Lethality – is the number of deaths per year from
tuberculosis to the number of TB patients being in
the same year registered at the dispensary.

9. • Etiology of tuberculosis
Tuberculosis properly refers only to disease caused
by Mycobacterium tuberculosis (for which humans
are the main reservoir). Similar disease occasionally
results from the closely related mycobacteria, M.
bovis, M. africanum, and M. microti. These three
bacteria, together with M. tuberculosis and other less
common mycobacteria, are known as the
Mycobacterium tuberculosis complex.
TB results almost exclusively from inhalation of
airborne particles (droplet nuclei) containing M.
tuberculosis. They disperse primarily through
coughing, singing, and other forced respiratory
maneuvers by people who have active pulmonary or
laryngeal TB and whose sputum contains a large
number of organisms (about 10,000 organisms/mL,
the limit of detection by fluorescent microscopy).
People with pulmonary cavitary lesions are
especially contagious because of the large number of
bacteria contained within a lesion.

10. • Groups of mycobacteria
1 group - pathogenic mycobacteria of tuberculosis:
• M. tuberculosis – the causative agent of tuberculosis of the person;
• M. bovis – the causative agent of tuberculosis of a cattle;
• M. africanum.
2 group - acid-resistant saprophytes – nonpathogenic for people and
animals.
3 group - opportunistic mycobacteria (atypical strains) – under some
conditions can cause mycobacteriosis that reminds tuberculosis.

11. • Forms of mycobacteria
Bacterial form:
• L – form;
• Filtration form;
• Fragmentation form.
Persistence – crossing bacterial form
MBT in L-form, filtration form or
fragmentation form.
Reversion – return from persistence
form to bacterial form. Light microscopy of Mycobacterium tuberculosis colonies. (A) Control rough microcolony (S14
strain). (B–F) L-form colonies and growth of M. tuberculosis. (B, C) S14 strain; (D, E, F) H 37
Rv strain. (B, D, E) Typical L-form colonies with a " fried-egg " appearance; (C, F) confluent L-
type growth with granular appearance of the edges of the colonies.
Magnifications: (A, D, E) 800×; (B, C, F) 200×.

12. • Structure of mycobacterium tuberculosis

13. • Mycobacterium tuberculosis under a microscope
Visualization of Mtb capsule by electron microscopy
(A) Micrograph of ultra-thin sections of Mtb grown in
the absence of detergent for 24 h processed for
transmission electron microscopy (TEM).
(B) Model of the Mtb cell envelope as observed from
(A). Note the trilaminar appearance of membrane
organization.
(C) Micrograph of ultra-thin sections of Mtb grown in
the absence of detergent for 5 days processed for
TEM.
(D) Electron micrograph of an Mtb cell immunostained
with an anti-LAM monoclonal antibody processed
for negative staining. Secondary nano-gold antibody
size is 10 nm. The capsule appears as fragmented
clusters of electron-dense material surrounding the
bacterium.
(E) Scanning electron micrograph of Mtb grown in the
absence of detergent. Arrow indicates the capsular
material adhered to the bacterial clump. Cryo-
electron micrograph of Mtb grown in the absence of
detergent.

14. • Pathophysiology of tuberculosis-1
Transmission
TB is primarily transmitted through the inhalation of respiratory droplets containing
M. tuberculosis. When an infected individual coughs, sneezes, or talks, they release
infectious droplets that can be inhaled by others, leading to primary infection.
Primary infection
After inhalation, M. tuberculosis reaches the alveoli of the lungs, where it is engulfed
by alveolar macrophages, the primary immune cells in the lungs. However, M.
tuberculosis can resist killing by the macrophages and multiply inside them. Infected
macrophages transport the bacteria to regional lymph nodes, initiating an immune
response.
Granuloma formation
Granulomas are organized structures formed by the immune system in response to
M. tuberculosis infection. Granulomas consist of a central core of infected
macrophages surrounded by immune cells, including T cells, B cells, and other
macrophages. The purpose of granuloma formation is to contain the infection and
prevent dissemination of the bacteria.
Latent TB infection
In some individuals, the immune response effectively controls M. tuberculosis,
leading to the formation of latent TB infection (LTBI). In LTBI, the bacteria remain
dormant within the granulomas, and the person does not exhibit any symptoms or
transmit the disease. However, the bacteria can reactivate and cause active TB
disease in the future, especially when the immune system is weakened.

15. • Pathophysiology of tuberculosis-2
Reactivation and Active TB disease
In individuals with weakened immune systems, such as those with HIV infection,
malnutrition, or other medical conditions, the latent M. tuberculosis can reactivate and lead
to active TB disease. Reactivation can occur years or even decades after the initial infection.
Pathology of Active TB
Active TB disease primarily affects the lungs but can also involve other organs, such as the
lymph nodes, bones, and kidneys. The progression of active TB is characterized by the
following steps:
• a. Bacterial Proliferation: Reactivated M. tuberculosis multiplies within the macrophages,
leading to the formation of caseating necrotic lesions.
• b. Tissue Destruction: The immune response triggered by M. tuberculosis causes
inflammation, leading to tissue damage and the formation of cavities within the lungs.
These cavities contain the bacteria and are responsible for the characteristic symptoms of
TB, such as persistent cough, sputum production, chest pain, and hemoptysis (coughing
up blood).
• c. Dissemination: In some cases, M. tuberculosis can spread from the lungs to other
organs through the bloodstream or lymphatic system, leading to extrapulmonary TB.
Immune response
The immune response to M. tuberculosis infection involves both innate and adaptive
immunity. Macrophages, dendritic cells, and neutrophils play critical roles in the early
recognition and containment of M. tuberculosis. T cells, particularly CD4+ T cells, are crucial
for the control of the infection and the formation of granulomas. However, M. tuberculosis has
developed mechanisms to evade and manipulate the host immune response, contributing to
its persistence and ability to cause disease.

16. • Pathogenesis of tuberculosis

17. • Clinical classification of tuberculosis-1
I. THE TYPE OF TUBERCULOSIS PROCESS:
• First diagnosed tuberculosis – FDTB (the date of diagnosis)
• Relapse of TB – RTB (the date of diagnosis)
• The cases are treated after a failed previous treatment (TF) (the date of
diagnosis)
• The cases with resumed treatment after being dropped out from supervision
(the date of diagnosis)
• Other cases that previously treated for tuberculosis (OTB) (the date of
diagnosis)
• Mono-resistant tuberculosis (the date of diagnosis)
• Poly-resistant tuberculosis (the date of diagnosis)
• Multidrug-resistant tuberculosis (MDR TB) (the date of diagnosis)
• Tuberculosis with extended resistance (XDR TB) (the date of diagnosis)
• Tuberculosis with resistance to rifampicin (Rif TB) (the date of diagnosis)

18. • Clinical classification of tuberculosis-2
II. CLINICAL FORM OF TUBERCULOSIS: (codes of the international disease classification (IDC-10)
A15-А16 Pulmonary tuberculosis (PTB)
A15-A16 Primary tuberculosis complex
A15-A16 Disseminated pulmonary tuberculosis
A15-A16 Focal pulmonary tuberculosis
A15-A16 Infiltrative pulmonary tuberculosis
A15-A16 Caseous pneumonia
A15-A16 Pulmonary tuberculoma
A15-AI6 Fibrous-cavernous pulmonary tuberculosis
A15-A16 Cirrhotic pulmonary tuberculosis
A15-A16 Pulmonary tuberculosis combined with the dusty professional pathology of the lungs
(anthracotic tuberculosis)
A15-A18 Extrapulmonary tuberculosis (EPTB)
A15-A16 Tuberculosis of the bronchi, trachea, upper respiratory tract and other (nasal, oral, pharyngeal)
A15-A16 Tuberculosis of the intrathoracic lymph nodes
A15-A16 Tuberculous pleurisy (including empyema)
A17 Tuberculosis of the cerebral membranes and the central nervous system
A18 Tuberculosis of the bones and joints
A18 Urogenital tuberculosis
A18 Tuberculosis of the peripheral lymph nodes
A18 Tuberculosis of the intestine, peritoneum, mesenterial lymph nodes
Al 8 Tuberculosis of the skin and subdermal fat
A18 Tuberculosis of the eye
A18 Tuberculosis of the ear
A18 Tuberculosis of the adrenal glands
A18 Tuberculosis of the other organs and systems of known localization
A19 Miliary tuberculosis
A18 Tuberculosis of unknown localization

19. • Tuberculosis process characteristics
1. Localization of damages:
Pulmonary form is estimated by name of separate lobes, numeration (name) of segment, if tuberculosis occurs in other organs –
then with the use of anatomic classification.
2. The presence of destruction
• (Destr+) – destruction is present;
• (Destr-) – destruction is absent
3. Etiological confirmation of tuberculosis diagnosis
(MTB+) bacteriological confirmation is present (code A15):
• (M+) - positive results of the smear investigation on acid-fast bacteria;
• (M-) - negative results of the smear investigation on acid-fast bacteria;
• (M0) – smear not investigated;
Molecular genetic techniques:
• (MG+) - molecular genetic techniques revealed the presence of the MBT in the test material;
• (MG-) - molecular genetic techniques have not revealed the presence of the MBT in the test material;
• (MG0) - molecular genetic studies not conducted;
Culture investigation:
• (C0) - culture investigation was not carried out;
• (C-) - a negative result of culture investigation;
• (C+) - a positive result of culture investigation; in this case to clarify:
Resistance:
• (Resist 0) – the resistance to the drugs of the first-line was not investigated;
• (Resist-) – the resistance to the drugs of the first-line was not defined;
• (Resist+) – (the abbreviation of the first-line antituberculosis drugs) the resistance to the drugs of the first-line was
defined;
• (Resist II0) – the resistance to the drugs of the second-line was not investigated;
• (Resist II-) – the resistance to the drugs of the second-line was not defined;
• (Resist II+) – (the abbreviations of the second-line antituberculosis drugs) the resistance to the drugs of the second rank
was defined.
Histological investigation: (HIST+) confirmed by the results of the histological investigation.

20. • Effectiveness of treatment
1. Cure – the full course antimycobacterial therapy was completed (including after
surgical treatment), stop of bacterial excretion occurs, caverns are healed,
resorption of infiltration and tuberculosis focuses.
2. Complete treatment – the full course antimycobacterial therapy was conducted
(including after surgical treatment), but there is no evidence of healing: not
conducted examination and the patient does not meet the criteria of "cure" and
"ineffective treatment." For DOTS "treatment completed" recorded among MBT-.
3. Termination of bacterial excretion – the bacterial excretion was stopped
(confirmed by microscopically and culturally at least a double research) but
destruction (cavity) is not healed.
4. Ineffective treatment – the full course antimycobacterial therapy was completed
but bacterial excretion is not stopped or bacterial excretion is stopped but the
cavity is not healed, and in patients who are not bacterial excretion and who have
never had cavities and destruction, infiltration and tuberculosis focuses haven’t
dissolved (or last isn’t condensed), that is not achieved cure after standard
treatment.
5. Interrupted treatment – break taking the drugs for more than 2 months or more
and the main course of treatment wasn’t completed.
6. The lethal consequence – death of the patient for any reason during the main
course AMBT or after ineffective treatment.
7. Transferred to patients who change residence transferred to another district.

21. • Consequences of tuberculosis
1. Residual changes in cured
tuberculosis: fibrous, fibro-focal, bullous
and dystrophic, calcification in the lungs
and lymph nodes,
pleuropneumosclerosis, cirrhosis, the
effects of surgery (indicating the type
and date of the transaction) and others.
2. Residual changes in cured
tuberculosis extrapulmonary
localization: scar changes in various
organs and their consequences,
calcification, the effects of surgery
(indicating the type and date of
transaction).
A chest radiograph shows calcification
at both the lung apices
Pulmonary fibrosis causes reticular
(net-like) shadowing of the lung
peripheries which is typically more
prominent towards the lung bases
Spinal tuberculosis, also known as
Pott's Disease

22. Thank you
for your attention!