3. INTRODUCTION
• Neo-Lattin word Tubercle: Round nodule/swelling & Osis: Condition.
• Tuberculosis is an infectious disease of humans and animals caused by
a species of mycobacterium mainly infecting the lungs where it causes
tubercles.
• In Humans: Mycobacterium tuberculosis
• In animals: Mycobacterium bovis
• Definition: Tuberculosis is the infectious disease primarily affecting
lung parenchyma is most often caused by Mycobacterium tuberculosis.
It may spread to any part of the body including meninges, kidney,
bones, and lymph nodes.
4. HISTORY
• Johann Schonlein coined the term “tuberculosis” in 1834.
• In 1700s, TB was called “the white plague”due to the
paleness of patients. Johann schonlein
• On March 24, 1882, Dr. Robert Koch announces the
discovery of tuberculosis, the bacteria that causes
TB.
• In 2018 as a part of “We can make history: End TB”
world TB day theme, CDC honored TB leaders and
history-makers through the TB chronicles.
Robert Koch
5.
6. BIOLOGY OF TB INFECTION
Inoculation with M. tuberculosis through inhalation into the respiratory tract.
M. tuberculosis reaches the alveoli
M. tuberculosis phagocytosed by alveoli
Formation of granuloma and progression to caseous
necrosis “mass of cheese” appearance.
Incomplete granuloma formation & breakdown –
liquefaction.
Latent inactive TB
Active pulmonary
TB
Errosion of incomplete granuloma
into blood vessels with
haematogenous spread to
extrapulmonary sites. E.g. bones.
7.
8. TB PATHOGENESIS
• Tubercle bacilli are inhaled in aerosol droplets, enter into the lungs and,
when the host innate immune defenses fail to eliminate the bacteria, Mtb
start multiplying inside alveolar macrophages and then spreads to other
tissues and organs through the bloodstream and lymphatics. Once the cell-
mediated immune response kicks in, bacterial replication is usually
controlled and in 90-95% of cases non overt signs or symptoms of disease
ensue (Latent TB). During latent infection a dynamic equilibrium between
the bacilli and host immune responses is established and any event that
weakens cell mediated immunity may lead to active bacterial replication,
tissue damage and disease occurs.
9. STAGES OF TB INFECTION
Stage-1:
• The large droplet nuclei reaches upper respiratory tract, & the small
droplet nuclei reaches air sacs of the lung(alveoli) where the infection
begins.
• Disease onset when droplet droplet nuclei reaches the alveoli.
Stage-2:
• Begins after 7-12 days after initial infection.
• TB multiplies within the inactivated macrophages until macrophages
burst.
10. Stage-3:
• Lymphocytes, specially T cells recognize TB antigen. This results in T-
cells activation & the release of cytokines including interferon(IFN).
• Release of IFN causes the activation of macrophages which can
release lytic enzymes & reactive intermediates that facilitates
immunue pathology.
• Tubercles forms, which contains semi-solid “cheesy” consistency. TB
cannot multiply within tubercles due to low pH & anoxic environment
but TB can persist within this tubercles for extended periods.
11. Stage-4:
• TB uses surrounded macrophages to replicate causing the tubercle to
grow.
• Causes infection to branches, lungs etc.
• Spreading causes milliary TB which can cause secondary lesions. (in
bones, joints, genitourinary system & peritoneum)
Stage-5:
• The caseous centers of tubercles liquify.
• The liquid is very crucial for the growth of TB, and therefore it
multiply rapidly(extracellularly).
13. VIRULENT MECHANISMS OF TB
• For cell entry:
Binds on Mannose receptor on macrophages via cell wall associated LAM
(Monoacylated Glycolipid).
• Intracellular growth:
Inhibits phagosome-lysosome fusion. TB can remain in the phagosome or
escape from the phagosome.
• Slow generation time:
Immune system cannot recognize TB, or cannot be triggered to eliminate
TB.
• High lipid concentration in cell wall:
Accounts for impermeability & resistance to antimicrobial agents. Also
accounts resistant to killing by acidic or alkaline compounds. Accounts for resistance
to osmotic lysis also.
14. VIRULENT MECHANISMS
• Antigen 85 complex:
This protein can aid in walling of the bacteria from the immune system.
• Cord factor:
Toxic in mammalian cells.
15. PREVALENCE OF TB
• Tuberculosis is still one of the main causes of morbidity and mortality
worldwide. The World Health Organization (WHO) estimates that, In
2020, an estimated 10 million people fell ill with tuberculosis (TB)
worldwide. 5.6 million men, 3.3 million women and 1.1 million
children. TB is present in all countries and age groups. But TB is
curable and preventable.
• The average prevalence of all forms of tuberculosis in India is
estimated to be 5.05 per thousand, prevalence of smear-positive cases
2.27 per thousand and average annual incidence of smear-positive
cases at 84 per 1,00,000 annually.
18. END TB STRATEGY BY WHO
Projected global trajectory of tuberculosis (TB) incidence rate
2015–2035 required to reach 2035 targets of the End TB Strategy.
19. WHO RECOMMENDATIONS FOR TB
1) Standards for early TB detection:
• performing prompt clinical evaluation is essential to ensure early and rapid
diagnosis.
• All persons who have been in close contact with patients who have pulmonary TB
should be evaluated.
• All persons living with HIV and workers who are exposed to silica should always be
screened for active TB in all settings.
2) Standards for TB diagnosis:
• All patients with signs and symptoms of pulmonary TB who are capable of
producing sputum should have to do initial diagnostic test.
• DST using WHO-recommended rapid tests should be performed for all TB patients
prior to starting therapy
20. 3) Standards for treating drug-susceptible TB:
• While awaiting DST results, patients with drug-susceptible TB and TB patients who
have not been treated previously with anti-TB agents and do not have other risk factors
for drug resistance should receive a WHO-recommended first-line treatment regimen
using quality assured anti-TB agents.
• In patients who require retreatment for TB, the category II regimen should no longer be
prescribed and DST should be conducted to inform the choice of treatment regimen.
4) Standards for HIV infection and other comorbid conditions:
• HIV testing should be routinely offered to all patients with presumptive TB and those
who have been diagnosed with TB.
• Persons living with HIV should be screened for TB by using a clinical algorithm.
• ART and routine CPT should be initiated among all TB patients living with HIV,
regardless of their CD4 cell count.
21. 5) Standards for managing TB in children:
• The diagnosis of TB in children relies on the thorough assessment of all evidence derived
from a careful history (including history of TB contacts and symptoms consistent with TB).
• In settings where TB is highly endemic or where there is a high risk of exposure to TB, a
single dose of BCG vaccine should be given to all infants.
• All children younger than 5 years and HIV-positive children of any age should be included
in contact screening and management efforts, with the aim of identifying undiagnosed TB
disease and providing preventive therapy for contacts without TB disease that are
susceptible to developing disease following exposure to a contact with active TB disease
22. 6) Standard for monitoring and evaluation:
• All providers must report both new and re-treatment TB cases and their treatment
outcomes to national public health authorities in conformance with applicable legal
requirements and policies; TB mortality should be monitored by using standard
cause-of-death data from vital registration systems.
7) Standards for supportive approaches to TB patient management:
• Digital technologies can be adapted to increase the effectiveness or efficiency of
different components of TB programmes.
• Prior to starting TB treatment, each patient’s need for support should be assessed,
and interventions to encourage adherence to treatment be offered to improve
outcomes.
• Before starting TB treatment, all patients should be assessed to determine the risk
of treatment interruption and appropriate options for treatment administration
should be offered to each patient.
23. PREVENTIVE MEASURES FOR TB
• BCG vaccination to childrens.
• Washing of hands after coughing and sneezing.
• Always cover your mouth with tissue when cough or sneeze.
• Contact doctor if any symptoms are observed.
• Take a fresh air.
• Balanced diet.
• Adequate rest.
• Use mask in public places which can also help to protect from COVID-
19.
24. REFERENCES
• World Health Organization. Global Tuberculosis Report 2017. Document
WHO/HTM/TB/2017.23. Geneva, World Health Organization, 2017. Available from:
http://apps.who.int/iris/bitstream/10665/259366/1/ 9789241565516-eng.pdf?ua=1.
Date last accessed: January 15, 2018.
• Gutierrez, M.C., Brisse, S., Brosch, R., Fabre, M., Omais, B., Marmiesse, M., Supply,
P. and Vincent, V. Ancient origin and gene mosaicism of the progenitor of
Mycobacterium tuberculosis. PLoS. Pathog. 1, e5.
http://dx.doi.org/10.1371/journal.ppat.0010005 PMid:16201017 PMCid:PMC1238740
• Hershberg, R., Lipatov, M., Small, P.M., Sheffer, H., Niemann, S., Homolka, S.,
Roach, J.C., Kremer, K., Petrov, D.A., Feldman, M.W. and Gagneux, S. High
functional diversity in Mycobacterium tuberculosis driven by genetic drift and
human demography. PLoS. Biol. 6, e311.
http://dx.doi.org/10.1371/journal.pbio.0060311 PMid:19090620
