1. Tuberculosis Ali Al Khader, MD Faculty of Medicine
Al-Balqa’ Applied University

2. Mycobacteria Slender Aerobic In straight or branching chains
Waxy cell wall composed of unusual glycolipids and lipids including mycolic acid
Retain stains even on treatment with a mixture of acid and alcohol…so called: acid-fast
Sometimes considered weakly gram (+)

3. Tuberculosis (TB) Chronic pulmonary and systemic disease
Caused (mainly) by: Mycobacterium tuberculosis
Source of transmission: humans with active tuberculosis who release mycobacteria present in sputum
Oropharyngeal and intestinal TB can be caused by Mycobacterium bovis (from infected cows) in milk…rare nowadays except in countries where milk pasteurization is not performed

4. TB, epidemiology Decreasing
Older adults and immigrants from high-burden areas
Infection with HIV makes people susceptible to rapidly progressive tuberculosis
Poverty, crowding, and chronic debilitating illnesses
Diabetes mellitus, Hodgkin lymphoma, chronic lung disease (particularly silicosis), chronic renal failure, malnutrition, alcoholism, and immunosuppression

5. More details in slide #7
Only a scar will remain
Progressive pulmonary or disseminated
Progressive pulmonary or disseminated

6. TB, pathogenesis in details
Entry into macrophage:
…receptors for M.TB: CR3, mannose binding lectin…etc.
M.TB continues to replicate inside the phagosome and inhibits phagolysosome formation…protected from microbicidal actions
…at this stage: bacteremia can occurs within the 1st 3 weeks with only flu-like symptoms. Seeding in different organs may occur
These “infected” macrophages will become APCs for T cells, especially presenting the peptide antigens of these “phagocytosed extracellular microbes” in the draining lymph nodes
TLR-2 on APCs (macrophages and dendritic cells) binds glycolipids and lipoproteins on M.TB (PAMPs)
After the 3 weeks: APCs will present the antigens in the draining lymph nodes and Th1 response will occur (IL-12 induced Th1 differentiation)…IL-12 can be secreted from APCs after their TLR-2 binds PAMPs
Th1 response will occur mainly in the lymph nodes and in the lung itself and this includes secretion of interferon-gamma (classical macrophage activation)…phagolysosome maturation, increased killing by the phagocyte and granuloma formation…Ghon complex is formed
Secretion of cytokines and reactive oxygen species occur with chemotaxis of lymphocytes around the granulomas and caseation

7. TB, pathogenesis…cont’d
Usually as an acute bacterial pneumonia
(lobar consolidation) with hilar lymphadenopathy & pleural effusion
Usually apical disease with caseation
Classically: the apex of the upper lobes of one or both lungs
With activity (1ry or 2ry), the granulomatous reaction which is supposed to protect will become a cause of collateral damage besides the intractable infection
Here is the start point in infection
(Ghon focus or Ghon complex)
…mainly in the upper part of the lower
lobe or lower part of the upper lobe
In active TB, erosion of the cavities into
bronchial wall will cause airborne spread by cough

8. TB, clinical features
Before becoming dormant or eliminated: may be only fever and pleural effusion
If 1ry active in the lung: similar to acute bacterial pneumonia with pleural effusion and hilar lymphadenopathy
If 2ry active localized in the lung: asymptomatic then insidious onset of manifestations (low-grade fever, weight loss, anorexia, malaise), hemoptysis, sputum, night sweats, pleuretic pain due to pleural involvement…etc.
If active outside the lung: according to the organ involved
…sometimes activity occurs in only one organ seeded by the organism

9. Miliary pulmonary disease
Millet seeds-like lesions
When organisms draining through lymphatics enter the venous blood and circulate back to the lung
Individual lesions are either microscopic or small, visible (2-mm) foci of yellow- white consolidation scattered through the lung parenchyma
Miliary lesions may expand and coalesce, resulting in consolidation of large regions or even whole lobes of the lung
Systemic military TB: Mainly liver, bone marrow, spleen or any other organ

10. Pleural involvement
With progressive pulmonary tuberculosis, the pleural cavity is invariably involved:
-Serous pleural effusions
-Tuberculous empyema
-Obliterative fibrous pleuritis

11. Isolated TB outside the lung

12. Scrofula = Cervical tuberculous lymphadenitis
The most common extrapulmonary manifestation

13. TB in GI tract
Mainly due to M. bovis in certain countries (unpasteurized milk)
In countries where milk is pasteurized: more often caused by the swallowing of coughed-up infective material in patients with advanced pulmonary disease…seeding to mucosal lymphoid aggregates with resultant granulomatous reaction then ulceration of overlying mucosa and strictures may occur
…Ileum is the most common site

14. TB, diagnosis
1- History, physical examination and radiographic findings: Cavitation and consolidation in lung apices 2-Smears of sputum (Ziehl-Neelsen special stain to demonstrate the acid-fast bacilli)…less sensitive than culture 3-Culture of sputum …the most effective and sensitive but the result needs 6 weeks …shows drug sensitivities …PCR is more rapid with good sensitivity and detects rifampin-resistant M.TB …but also: less sensitive than culture

15. TB, diagnosis *** Tuberculin (PPD, or Mantoux) skin test
About 2 to 4 weeks after infection, intracutaneous injection of purified protein derivative of M. tuberculosis induces a visible and palpable induration that peaks in 48 to 72 hours
A positive tuberculin test signifies T-cell–mediated immunity to mycobacterial antigens but does not differentiate between infection and active disease (It only detects sensitized patients)
False-negative reactions (called: anergy to skin test):
-Certain viral infections
-Sarcoidosis (abnormalities in CD4+ T cells)
-Malnutrition
-Hodgkin lymphoma
-Immunosuppression, e.g., AIDS…granulomas may be less and PPD may be negative
-Overwhelming active tuberculous disease
False-positive reactions may result from:
-Infection by atypical mycobacteria
-Prior vaccination with BCG (Bacillus Calmette-Guerin), an attenuated strain of M. bovis that is used as a vaccine in some countries

16. Treatment Multidrug resistant M. tuberculosis is an increasing problem
…Nowadays, in USA, at least 4 drugs are used to treat TB (except if the case is with known susceptibility)

17. Thank You