2. BY : M. SHA`BANI MD

3.  TB is caused by bacteria of the M. Tuberculosis complex & usually affects lung.  If treated,is curable  If unreated,may fatal within 5 y/o in 50-65% of cases

4.  M. Tuberculosis is a rod shape,nonspore- forming,aerobic  Acid- fast bacili (AFB )

5.  TB is spread person to person through the air via droplet nuclei  M. tuberculosis may be expelled when an infectious person: ◦ Coughs ◦ Sneezes ◦ Speaks ◦ Sings  Transmission occurs when another person inhales droplet nuclei

6.  The most infectious patients :cavitary, laryngeal,sputum containing 10 5 – 10 7 AFB/ml  Q: Are co-infected patients(HIV + TB) highly infectious? 

7.  Depends on innate immunologic and non – immuonologic defenses and function of CMI  Primary disease : children and immunocompromsed persons  Secondary ( postprimary) TB dormant bacilli may persist for years before reactivation to produce this type.  Up to 10% of infected persons will develop active TB ( esp. in HIV patients)

8. Pathogenesis is defined as how an infection or disease develops in the body.

9.  Occurs when tubercle bacilli are in the body, but the immune system is keeping them under control  Detected by the Mantoux tuberculin skin test (TST) or by blood tests such as interferon-gamma release assays (IGRAs) which include: ◦ QuantiFERON ® -TB Gold test (QFT-G) ◦ QuantiFERON ® -TB Gold In-Tube (QFT-GIT) ◦ T-Spot ®.TB test (T-SPOT)  People with LTBI are NOT infectious

10.  Develops when immune system cannot keep tubercle bacilli under control ◦ May develop very soon after infection or many years after infection  About 10% of all people with normal immune systems who have LTBI will develop TB disease at some point in their lives  People with TB disease are often infectious

12. Tubercle bacilli multiply in alveoli, where infection begins

13. A small number of tubercle bacilli enter bloodstream and spread throughout body

14. Within 2 to 8 weeks the immune system produces special immune cells called macrophages that surround the tubercle bacilli These cells form a barrier shell that keeps the bacilli contained and under control (LTBI)

15. If the immune system CANNOT keep tubercle bacilli under control, bacilli begin to multiply rapidly and cause TB disease This process can occur in different places in the body

16. Latent TB Infection (LTBI) TB Disease (in the lungs) Inactive, contained tubercle bacilli in the body Active, multiplying tubercle bacilli in the body TST or blood test results usually positive Chest x-ray usually normalChest x-ray usually abnormal Sputum smears and cultures negativeSputum smears and cultures may be positive No symptomsSymptoms such as cough, fever, weight loss Not infectiousOften infectious before treatment Not a case of TBA case of TB

17. When a person inhales air that contains droplet nuclei containing M. tuberculosis, where do the droplet nuclei go? (pg. 15) Most of the larger droplet nuclei become lodged in the upper respiratory tract, where infection is unlikely to develop However, droplet nuclei may reach the small air sacs of the lung (the alveoli), where infection begins

18. After the tubercle bacilli reach the small air sacs of the lung (the alveoli), what happens to them? (pg. 15)  Tubercle bacilli multiply in alveoli and some enter the bloodstream and spread throughout the body  Bacilli may reach any part of the body  Within 2 to 8 weeks, the immune system usually intervenes, halting multiplication and preventing further spread

19. In people with LTBI (but not TB disease), how does the immune system keep the tubercle bacilli under control? (pg. 15) The immune system produces special immune cells that surround the tubercle bacilli. These cells form a shell that keeps the bacilli contained and under control.

20. How is LTBI detected? (pg. 16) LTBI is detected by the Mantoux tuberculin skin test (TST) or blood tests such as interferon-gamma release assays (IGRA), which include the QuantiFERON ® - TB test (QFT-G), QuantiFERON ® -TB Gold In-tube (QFT-GIT), or T-SPOT.

22. In an HIV-infected person, TB can develop in one of two ways:  Person with LTBI becomes infected with HIV and then develops TB disease as the immune system is weakened  Person with HIV infection becomes infected with M. tuberculosis and then rapidly develops TB disease

23.  PULMONARY dis.:  Primary dis.:  1-asymptomatic  2-fever and pleuritic c.p.  -in children  -middle and lower lobes  -Ghon focus(after initial inf. –peripheral-hilar or paratracheal LAP-heals spontaneously and calcified noduls)  -EN in legs

24.  In young child or immunosuppressed person pulmonary TB (Primary ) progress to clinical illness  PE :2/3  Cavity+ LAP  Enlarged LN then...  Rupture of LN and...  Hematogen distribution

25.  Post-primary dis. :  Reactivation  Apex  Small  infiltrations to large cavities  What happens?  up to 1/3 will be severe  others (ends to remission or chronicity)

26.  symptoms:  -nonspecific and slowly  -eventually up to 90%,cough  -C.P.  -dyspnea  Signs:most of them,normal but may have inspiratory rales and occasionally rhonchiThe most common hamatologic findings:  Mild anemia, leukocytosis, thrombocytopenia

27.  In order of frequency: L.N., pleura, GU, skeletal, mening, peritonum and pericardium  Lympadenitis: nontender swelling,posterior cervical and supraclavicular( scrofula),  Systemic signs are ucommon unless in HIV  FNA or excisional Bx

28.  Pleural TB :  1-postprimary  2-chronic  3-with miliary  4-empyema  Dx: thoracentesis, needle bx of pleura  The first one responds rapidly to chemo.  For empyema surgical drainage + chemo.

29.  Genitourinary TB  Skeletal TB  Meningitis and tuberculoma  Gastrointestinal TB

30.  Miliary TB  -Hematogenous spread of bacilli  -granuloma 1-2 mm lesions ( as millet seeds)  Nonspecific manifestations  Fever,night sweat, anorexia,wt loss  1-acute  2-cryptic  3-nonreactive  Dx: BAL, TBB, Bx of involved organs

31.  A person with a pos. PPD who acquires HIV has a risk of 3-13% /year for active TB  prsentation depends onstage of HIV  Extrapulmonary TB is common  Dx is difficult because...(smear,radiography granuloma,PPD)

32.  1-AFB MICROSCOPY  ( microscopic exam of a diagnostic specimen,e.g. sputum,tissue)  Sputum: x3 in morning ( but 2 sample on the same visit is better than 3 samples)  Tissue: in normal saline( not in formaldehyde)

33.  CULTURE :  because most mycobacterias grow slowly 4-8 weeks may be required  The most sensitive test  PCR, radiography,invasive procedures

34.  PPD:  False negative in immunosuppression,malnutrition  False positive in non-TB mycobacteria, BCG vaccination  IFN-gamma release assay( IGRA): It measures T cell release of IFN-gamma in response to stimulation with the highly TB- specific antigen ESAT-6 AND CFP-10 It is more specific than PPD esp. in low-incidence setting

35.  4 major drugs are the first line agents :  Isoniazid,rifampin,pyrazinamide,ethambutol  Monitoring : bacteriologic evaluation( if cx not possible then AFB smear)  Serial CXR is not recomended  Drug toxicity: (patient should be educated about hepatitis, hypersensitivity reaction, hyperuricemia and arthralgia,thrombocytopenia,optic neuritis

36.  For preventing active dis.( chemoprophylaxis)  Candidates are :  1- HIV, recieving immunosuppressive drugs,close contact, fibrotic lesions on CXR with at least 5 mm  2- recently infected persons, high risk condition( DM,hematologic dis., IDU, ESRD,,rapid wt loss) with at least 10 mm  3-low risk persons with at least 15 mm( except for employment purposes TST is not indicated for low-risk group)

37.  THANK YOU   QUESTION?