1. Tuberculosis is a chronic disease of respiratory system that established due to Mycobacterium tuberculosis complex infection and represented clinically as progressive primary or secondary disease, or latency. Mycobacterium tuberculosis was identified and described on 24 March 1882 by a German physician Robert Koch. Mycobacterium tuberculosis complex: M. tuberculosis, M. bovis, and M. africanum.

2. Estimated incidence of T.B in 2007: N CountryCases Rate per 100,000 population India 1,962,000168 China 1,306,00098 Indonesia 528,000228 Nigeria 460,000311 South Africa 461,000948 Ethiopia 314,000378 Bangladesh 353,000223

3. WHO report for incidence of T.B in 2011: N

4. Transmission of Mycobacterium species: Mycobacterium tuberculosis: Reservoir: Human. T.B is spread from person to person through the air by droplet nuclei (0.5-5µm in diameter). Droplet nuclei could be produced by Coughing, Sneezing, or to a lesser extent speaking. Droplet nuclei may remain suspended in the air for long time;(isolation rooms of hospitals).

5. N Risk factors for rapid spreading of Mycobacterium tuberculosis: 1-Crowded living conditions. 2-Excess Alcohol use and Homelessness. 3-HIV infection. 4-Traveling to area with high prevalence rate. Mycobacterium bovis: Reservoir: Animals (Cattle and related animals) T.B is acquired due to direct contact with infected animals; inhalation of droplets. It could be transmitted to man due to drinking of unpasteurized milk or eating of contaminated milk products.

6. Pathogenesis and clinical presentation: Tubercle bacilli do not produce exotoxins or endotoxin. Instead, tissue damage is induced by host immune response (chronic inflammation) against infected area and survival of bacteria within macrophage. Primary infection: -In middle lung zone; where airflow is greatest. -Infection of alveolar macrophage. -Rupture of alveolar macrophage; death and infection of other macrophage (active primary T.B).

7. N -Infected macrophages are carried by lymphatics to regional tracheobronchial lymph nodes: 1-Activation of Lymphocytes(TH1). 2-Enlargment of lymph nodes. Ghon’s Complex could be seen in some patients: Is the inflammation of infected lung area that associated with enlarged lymph nodes.

8. N In 90% of cases, delayed type hypersensitivity causes: Latent dormant tuberculosis with granuloma formation; Patients have stronger immunity: 1- Children; More than 5 years old. 2- Puberty, and adulthood. In 10 % of cases, little or no hypersensitivity immune reaction results in Progressive primary tuberculosis, Spreading due to Lympho-hematogenous dissemination. Patients with weak immunity: 1-Infants and children younger than 5 years old. 2-Elderly persons. 3-HIV/AIDS patients.

9. N Pathogenesis and Clinical presentation: Primary Tuberculosis 90% Latent dormant tuberculosis Living bacteria &granuloma 25% arrested granuloma Fibrosis or Calcification. Enlarged Tracheobronchial lymph nodes. 3% Breaks down granuloma -Caseous material discharged; necrosis -Cavity creation. Apical lung cavities Tuberculous pneumonia Lympho-Hemo Meningitis Osteomyelitis 10% Progressive active infection AIDS, Old, Children Living- bacteria, granuloma 91 % No disease 75%

10. N N

11. A Person with Latent TB Inf.A Person with active TB (P.TB) Has no symptoms Has symptoms that may include: a bad cough that lasts 3 weeks or longer pain in the chest coughing up blood or sputum weakness or fatigue weight loss no appetite chills fever sweating at night Does not feel sick Usually feels sick Cannot spread TB bacteria to others May spread TB bacteria to others Usually has a skin test or blood test result indicating TB infection Has a normal chest x-ray and a negative sputum smear May have an abnormal chest x-ray, or positive sputum smear or culture Needs treatment for latent TB infection to prevent TB disease Needs treatment to treat TB disease n

12. Endogenous Reactivation of TB : (Secondary Tuberculosis): -It occurs within 2 years after initial infection due to impairment of cellular immunity. -Major causes of depression of cellular immunity: 1-Immunosuppressive drugs: Corticosteroids. 2-Malignancy. 3-HIV Coinfection (the most important cause). -The most common site of reactivation is the apex of lung; caseous necrosis that merge into larger lesions; rupture. -Well-aerated cavity; microbial proliferation; Tuberculous pneumonia.

13. HIV and Tuberculosis: -Worldwide, HIV infection causes inhibition of cellular immunity. -Patients with HIV infection could be infected by MTC (Mycobacterium tuberculosis complex), or MOTT (Mycobacterium other than tuberculosis). -MOTT: M. avium, M. intracellulare, and M. kansasii -Person who has both HIV infection and TB disease has an AIDS- defining condition. -Tuberculosis is the leading cause of death among adults living with HIV/AIDS. -The WHO recommends TB screening at the time that HIV infection is diagnosed and at regular intervals during follow up.

14. Diagnosis: A-Clinical tests: 1-Tuberculin skin test. (DTH:48-72 hours). Mantoux test: (PPD: Purified Protein Derivative) Results: Intermediate reaction=5-9mm. Positive reaction=greater than 9mm.

15. N

16. N A-Clinical test: 2-Radiology: Chest X-ray:

17. N B-Laboratory tests: Clinical specimens: Sputum, transtracheal aspiration, Bronchioalveolar lavage. 1-Microscopy: (Z.N stain sensitivity lower than PCR): - Mycobacteria (MTC) are acid fast, non-motile, non-spore forming rods, measuring 1-4µm x 0.2-0.6 µm. -Once stained ZN, they resist decolorization with 2% H 2 SO 4 and ethyl alcohol or 3% HCl and ethyl alcohol. -Mycolic acid waxy capsule.

18. N B-Laboratory tests: 2-Cultural characteristics: M. tuberculosis is strict aerobic grows very slowly (2-4 weeks) Egg enriched medium: Lowenstein-Jensen medium : giving dry creamy colored colonies The growth is enhanced by Pyruvate and glycerol in media. M. tuberculosis are niacin producers. Optimum temp. is 37C.

19. N M. tuberculosis is a non chromogen bacteria: 1-Does not grow on media contain p-nitrobenzoic acid 2-These characteristics help to differentiate them from MOTT :(M. avium, M. intracellulare, and M. kansasii). 2-Polymerase chain reactions test: -Has the highest sensitivity for diagnosis of T.B. -Sensitivity is approx.=95% -Detection of microbial genetic material in clinical specimens. -Can provide us with antibiotic susceptibility profile.

20. N Antibiotics sensitivity test: -Other selective media as Middle-brook 7H10, 7H11 agar and 7H9 broth: 1-Used for primary isolation 2-Used for antibiotic susceptibility test.

21. n Treatment of T.B: -Extensive time periods (6-9 months). -Direct Observation treatment. -Combined multidrug treatment to reduce the microbial resistance ability. -First line Anti-T.B drugs: Isoniazid (INH), rifampin (RIF), pyrazinamide (PZA), and ethambutol. -Phases of Treatment: 1-Initial phase: The four drugs are used for 2 months 2-Continuation phase: INH and RIF for four or seven months.

22. N Vaccination: Prevention: Vaccination: -Killed TB vaccines will not be effective in protection of adults. -BCG vaccine: 1-Attenuated low virulent M. bovis strain. 2-Effective in protection of children from serious forms of disease such as meningitis. 3-Not so effective to protect adults.