Medical Presentation

1. TUBERCULOSIS
D O N E BY
N O E L C H R I S T I A N

2. INTRODUCTION
• Most prevalent communicable infectious disease.
• Chronic specific inflammatory infectious disease caused by Mycobacterium
tuberculosis which is a non-motile, slow-growing, rod-shaped bacillus.
• It is a delayed type hypersensitivity (hypersensitivity 4).
• Belongs to cell mediated immunity.
• Usually attacks the lung but can also effect other parts of the body.
• Tuberculosis can produce atypical signs and symptoms in infants, elderly
persons, and immunocompromised people and it can progress rapidly in these
patients.

3. ETIOLOGY
• Mycobacterium Tuberculosis:
1) Present as latent Tb infection or as progressive active disease.
2) In patients with progressively active disease, Mtb can cause lung
destruction
and the patient can die without treatment.
• Other causes :
M. avium intracellulare, M. scrofulaceum
M. ulcerans, M. fortuitum, etc.

4. SITE OF INFECTION
• Pulmonary Tb (85% of all TB cases)
• Extra-pulmonary Tb (hematogenously) :
1. Lymph node
2. Genito-urinary tract
3. Bones & Joints
4. Meninges
5. Intestine
6. Skin

5. HOW IS TB TRANSMITTED?
• Tuberculosis is spread via respiratory droplets that contain the tubercle
bacillus.
• These are expelled from individuals with active TB and subsequently inhaled.
• Most droplets will be stopped from entering the body by the physical barriers
found in the upper respiratory tract.
• Those that are small (1-2 µm) in size are able to bypass these barriers and
reach the lower respiratory tract and lungs. Here the bacteria encounter cells of
the immune system.

6. OUTCOME OF INFECTION
• Depends on the :
1) Host’s immune system and
2) The pathogenicity of the bacteria.
• Majority of individuals will be able to control infection and contain it within
a granuloma, which is an aggregate of immune cells that walls off the
mycobacteria, but does not eradicate them. As bacteria are still present, it’s
called latent infection and the individual is at risk of future reactivation of
disease if they become immunocompromised.

8. IMMUNE RESPONSE
• The first cells encountered by the mycobacteria is the alveolar macrophages.
• Macrophages and other antigen presenting cells (APCs) recognize and phagocytose
the mycobacteria, engulfing them into a phagosome.
• Typically upon phagocytosis, the bacteria-containing phagosome matures and fuses
with lysosomes. The bacteria are then exposed to enzymes which degrade the bacteria.
• Pathogenic mycobacteria have developed a mechanisms to protect themselves from
the host defense by blocking phagosomal maturation in resting macrophages.
• Instead, the cytokine interferon-γ (IFNγ) activate macrophages promotes bacterial
killing by the formation of toxic
1) Reactive oxygen intermediates (ROI) and
2) Reactive nitrogen intermediates (RNI).
• Activated macrophages also release tumour necrosis factor α (TNFα), which induces
inflammatory response and direct immune cells to the site of infection.

9. • Dendritic cells, together with activated macrophages, process antigen and present it
to MHC class II molecules.
• In the lymph nodes, dendritic cells encounter naive T-cells.
• Naive CD4+ T cells, they sample antigen/MHC complex on the surface of migrating
APCs. After recognizing the antigen/MHC complex specific for the TCR, the CD4+
become activate and proliferate in the presence of cytokines IFNγ and IL12, and
differentiate into
Th-1 cells.
• Th1 effector cells migrate back to the lungs (chemokine) where the activated T cells
interact with MHC/antigen complexes on the surface of infected macrophages and
produce a range of cytokines including IFNγ; leading to further activation of
macrophages.
• Combination of Innate and Th1-dominant adaptive immune responses culminates the
development of granulomas.

11. • During the early innate response primary granuloma is formed with centrally
located macrophages.
• This leads to the formation of a larger well-organised solid granuloma when
adaptive immunity is initiated with the infiltration of specific T lymphocytes.
Macrophages at the center will be infected and be differentiated into
epitheloid cells. Some also combine to form giant multinucleated cells.
• The centre of the granuloma may exhibit caseous necrosis.

13. • If the infection continues, the center may liquefy, producing an environment in
which the bacteria can grow.
• Cavitation may occur if the liquefied contents are released into the bronchial
tree where they can then be expelled externally and the infection transmitted
to others.
• The granulomas will undergo fibrosis or calcification and the infection is
contained and becomes latent.

15. CLINICAL FINDINGS

16. DIAGNOSES
• Infection with M. tuberculosis typically leads to the development of delayed
hypersensitivity, M. tuberculosis antigens, which can be detected by the tuberculin
(mantoux) test.
• A positive tuberculin test result signifies cell-mediated hypersensitivity to tubercular
antigens.
• About 2 to 4 weeks after infection, intra-cutaneous injection of purified protein
derivative of M. tuberculosis (PPD) induces a visible and palpable induration that
peaks in 48 to 72 hours.

17. • Sputum Examination:
Are essential to confirm TB.
Best collected in morning before any meal.
Sputum examination on 3 days, increase chances of detection.
• Smear should be prepared from thick dirty part of sputum & stained with
Ziehl-Neelson technique.

18. TREATMENT
• Always treat with multiple drugs. Never add a single drug to a failing regimen.
• Course of drug for 6 months, sometimes 9 months.
• 4 drugs for two months : Isoniazid, Rifampicin, Ethambutol, Pyrazinamide.
• 2 drugs for four or seven months : Isoniazid, Rifampicin.
• Latent TB :
Isoniazid is the preferred drug for treating latent TB infection.
Generally, isoniazid alone is given for 9 months for latent TB infection (LTBI)
reduces a person’s lifetime risk of active TB.

19. REFERENCES
1. Charles A. Peloquin. Tuberculosis. In: Pharmacotherapy: A Pathophysiologic Approach, 7th ed. Dipiro
JT,
Talbert RL, Yee GC, et al., eds. New York: McGraw-Hill; 2008:1839–1856.
2. Charles A. Peloquin. Tuberculosis. In: Pharmacotherapy: Principle & Practice, 7th ed. Dipiro JT,
Talbert RL, Yee GC, et al., eds. New York: McGraw-Hill.
3. Cotran RS, Kumar V, Collins T. Tuberculosis. In: Cotran RS, Kumar V, Collins T, 7th eds. Robbins’
Pathologic Basis of Disease. Philadelphia: WB Saunders, 1999: 260–328.
4. CDC. Guidelines for preventing the transmission of Mycobacterium tuberculosis in health-care settings,
2005.
MMWR 2005; 54 (No. RR-17). www.cdc.gov/mmwr/preview/mmwrhtml/rr5417a1.htm?s_cid=rr5417a1_e
5. World Health Organization Report on the Global Tuberculosis Epidemic. Geneva: WHO, 2008.
6. Pathology and therapeutics for pharmacist: A B for clinical pharmacy practice-Green and Harris,
Chapman and hall publication.