TUBERCULOSIS Respiratory Block PROF HANAN HABIB PROF A
![TUBERCULOSIS Respiratory Block PROF. HANAN HABIB & PROF A. M. KAMBAL DEPRTMENT OF PATHOLOGY, TUBERCULOSIS Respiratory Block PROF. HANAN HABIB & PROF A. M. KAMBAL DEPRTMENT OF PATHOLOGY,](https://slidetodoc.com/presentation_image/6614f80ef8c2e325b220eef861b90e08/image-1.jpg)
TUBERCULOSIS Respiratory Block PROF. HANAN HABIB & PROF A. M. KAMBAL DEPRTMENT OF PATHOLOGY, MICROBIOLOGY UNIT KSU
![Objectives l Recognize that tuberculosis as a chronic disease mainly affecting the respiratory system. Objectives l Recognize that tuberculosis as a chronic disease mainly affecting the respiratory system.](http://slidetodoc.com/presentation_image/6614f80ef8c2e325b220eef861b90e08/image-2.jpg)
Objectives l Recognize that tuberculosis as a chronic disease mainly affecting the respiratory system. l Know the epidemiology of tuberculosis world wide and in the kingdom of Saudi Arabia l Understand the methods of transmission of tuberculosis and the people at risk.
![l Know the causative agents and their characteristic and classification and methods of detection. l Know the causative agents and their characteristic and classification and methods of detection.](http://slidetodoc.com/presentation_image/6614f80ef8c2e325b220eef861b90e08/image-3.jpg)
l Know the causative agents and their characteristic and classification and methods of detection. l Understand the pathogenesis of tuberculosis. l Differentiate between primary and secondary tuberculosis and the clinical features of each.
![l Understand the method of tuberculin skin test and result interpretation. . l Know l Understand the method of tuberculin skin test and result interpretation. . l Know](http://slidetodoc.com/presentation_image/6614f80ef8c2e325b220eef861b90e08/image-4.jpg)
l Understand the method of tuberculin skin test and result interpretation. . l Know the laboratory and radiological diagnostic methods. l Know the chemotherapeutic and other methods of management of tuberculosis cases. l Describe the methods of prevention and control of tuberculosis.
![Introduction l Tuberculosis (TB) is an ancient , chronic disease affects humans, caused by Introduction l Tuberculosis (TB) is an ancient , chronic disease affects humans, caused by](http://slidetodoc.com/presentation_image/6614f80ef8c2e325b220eef861b90e08/image-5.jpg)
Introduction l Tuberculosis (TB) is an ancient , chronic disease affects humans, caused by Mycobacterium tuberculosis complex. l A major cause of death worldwide. l Usually affects the lungs, other organs can be affected in one third of cases. l If properly treated is curable, but fatal if untreated in most cases.
![Epidemiology Ø TB affects 1/3 of human race ( 2 billions) as a latent Epidemiology Ø TB affects 1/3 of human race ( 2 billions) as a latent](http://slidetodoc.com/presentation_image/6614f80ef8c2e325b220eef861b90e08/image-6.jpg)
Epidemiology Ø TB affects 1/3 of human race ( 2 billions) as a latent dormant tuberculosis. Ø Incidence: a world wide disease , more common in developing countries. Ø Affects all age groups who are subject to get the infection.
![](http://slidetodoc.com/presentation_image/6614f80ef8c2e325b220eef861b90e08/image-7.jpg)
![Epidemiology l The WHO estimated 8. 9 million new cases in 2004 & 2 Epidemiology l The WHO estimated 8. 9 million new cases in 2004 & 2](http://slidetodoc.com/presentation_image/6614f80ef8c2e325b220eef861b90e08/image-8.jpg)
Epidemiology l The WHO estimated 8. 9 million new cases in 2004 & 2 - 4 million death. l Incidence : l in KSA : 32 -64 cases /100, 000 l in USA : 5. 2 cases/100, 000 l in South Ease Africa : 290 cases /10, 000 due to coupling with HIV infection.
![Epidemiology Ø Transmission mainly through inhalation of airborne droplet nuclei ( < 5 μm) Epidemiology Ø Transmission mainly through inhalation of airborne droplet nuclei ( < 5 μm)](http://slidetodoc.com/presentation_image/6614f80ef8c2e325b220eef861b90e08/image-9.jpg)
Epidemiology Ø Transmission mainly through inhalation of airborne droplet nuclei ( < 5 μm) in pulmonary diseases case , rarely through GIT & skin Ø Reservoir: patients with open TB. Ø Age: young children & adults Ø People at risk : lab. technicians, workers in mines, doctors , nurses. HIV pts. , diabetics end stage renal failure, contacts with index case.
![Characteristics of the Genus Mycobacteria Ø Slim, rod shaped, non-motile, do not form spores. Characteristics of the Genus Mycobacteria Ø Slim, rod shaped, non-motile, do not form spores.](http://slidetodoc.com/presentation_image/6614f80ef8c2e325b220eef861b90e08/image-10.jpg)
Characteristics of the Genus Mycobacteria Ø Slim, rod shaped, non-motile, do not form spores. Ø Do not stain by Gram stain. Why ? Ø Contain high lipid conc. ( Mycolic acid ) in the cell wall which resist staining. It is called Acid- alcohol fast bacili (AFB), Why ? It resists decolorization with up to 3% HCL, 5%ethanol or both.
![](http://slidetodoc.com/presentation_image/6614f80ef8c2e325b220eef861b90e08/image-11.jpg)
![](http://slidetodoc.com/presentation_image/6614f80ef8c2e325b220eef861b90e08/image-12.jpg)
![Mycobacterium tuberculosis (approx. x 1000) Mycobacterium tuberculosis (approx. x 1000)](http://slidetodoc.com/presentation_image/6614f80ef8c2e325b220eef861b90e08/image-13.jpg)
Mycobacterium tuberculosis (approx. x 1000)
![Acid-Fast Bacilli (AFB) Ø Stain used : Ziehl-Neelsen stain (ZN stain) Ø Strict aerobe Acid-Fast Bacilli (AFB) Ø Stain used : Ziehl-Neelsen stain (ZN stain) Ø Strict aerobe](http://slidetodoc.com/presentation_image/6614f80ef8c2e325b220eef861b90e08/image-14.jpg)
Acid-Fast Bacilli (AFB) Ø Stain used : Ziehl-Neelsen stain (ZN stain) Ø Strict aerobe Ø Multiply intracellularily Ø Delayed hypersensitivity reaction type of immune response Ø Slowly growing ( 2 - 8 wks. )
![Mycobacterium tuberculosis complex Ø 1 - M. tuberculosis (Human type) Ø 2 - M. Mycobacterium tuberculosis complex Ø 1 - M. tuberculosis (Human type) Ø 2 - M.](http://slidetodoc.com/presentation_image/6614f80ef8c2e325b220eef861b90e08/image-15.jpg)
Mycobacterium tuberculosis complex Ø 1 - M. tuberculosis (Human type) Ø 2 - M. bovis (Bovine type) Ø 3 - M. Africanum Ø 4 - BCG strains All are called Mycobacterium tuberculosis Complex and cause tuberculosis ( TB).
![Pathogenesis of Tuberculosis l Mycobacteria acquired by airborne droplet reaches the alveolar macrophages , Pathogenesis of Tuberculosis l Mycobacteria acquired by airborne droplet reaches the alveolar macrophages ,](http://slidetodoc.com/presentation_image/6614f80ef8c2e325b220eef861b90e08/image-16.jpg)
Pathogenesis of Tuberculosis l Mycobacteria acquired by airborne droplet reaches the alveolar macrophages , able to survive their ( main virulence factor). l This starts cell mediated immune response which controls the multiplication of the organism but does not kill it. l Granuloma formed , organism lives in dormant state ( latent tuberculosis infection)
![Pathogenesis of Tuberculosis l Patient show evidence of delayed cell mediated immunity ( CMI Pathogenesis of Tuberculosis l Patient show evidence of delayed cell mediated immunity ( CMI](http://slidetodoc.com/presentation_image/6614f80ef8c2e325b220eef861b90e08/image-17.jpg)
Pathogenesis of Tuberculosis l Patient show evidence of delayed cell mediated immunity ( CMI ). l Disease results due to destructive effect of CMI. l Clinically the disease is divided into primary or secondary.
![Pathogenesis of Tuberculosis Ø Primary Tuberculosis Occurs in patients not previously infected. Inhalation of Pathogenesis of Tuberculosis Ø Primary Tuberculosis Occurs in patients not previously infected. Inhalation of](http://slidetodoc.com/presentation_image/6614f80ef8c2e325b220eef861b90e08/image-18.jpg)
Pathogenesis of Tuberculosis Ø Primary Tuberculosis Occurs in patients not previously infected. Inhalation of bacilli Phagocytosis lymph nodes calcify to produce GHON focus (or Primary Complex) at the periphery of mid zone of lung.
![Pathogenesis of TB Pathogenesis of TB](http://slidetodoc.com/presentation_image/6614f80ef8c2e325b220eef861b90e08/image-19.jpg)
Pathogenesis of TB
![](http://slidetodoc.com/presentation_image/6614f80ef8c2e325b220eef861b90e08/image-20.jpg)
![](http://slidetodoc.com/presentation_image/6614f80ef8c2e325b220eef861b90e08/image-21.jpg)
![Primary Tuberculosis Ø Microscopy of lesion shows Granuloma. Ø Clinically: primary TB usually asymptomatic Primary Tuberculosis Ø Microscopy of lesion shows Granuloma. Ø Clinically: primary TB usually asymptomatic](http://slidetodoc.com/presentation_image/6614f80ef8c2e325b220eef861b90e08/image-22.jpg)
Primary Tuberculosis Ø Microscopy of lesion shows Granuloma. Ø Clinically: primary TB usually asymptomatic or / minor illness. Ø Non-pulmonary TB: may spreads from pulmonary infections to other organs eg. : § TB of lymph nodes ( cervical, mesenteric). § TB meningitis § TB bone & joint
![](http://slidetodoc.com/presentation_image/6614f80ef8c2e325b220eef861b90e08/image-23.jpg)
![Primary Tuberculosis Ø Genitourinary TB Ø Miliary TB (blood and other organs) Ø Soft Primary Tuberculosis Ø Genitourinary TB Ø Miliary TB (blood and other organs) Ø Soft](http://slidetodoc.com/presentation_image/6614f80ef8c2e325b220eef861b90e08/image-24.jpg)
Primary Tuberculosis Ø Genitourinary TB Ø Miliary TB (blood and other organs) Ø Soft tissue (cold abscess): lack of inflammation with caseation. Ø Caseation: due to delayed hypersensitivity reaction. Contains many bacilli , enzymes, O 2, N 2 intermediates, necrotic centre of granuloma cheezy material.
![Secondary TB (reactivation) Ø Occurs later in life Ø Lung more common site Ø Secondary TB (reactivation) Ø Occurs later in life Ø Lung more common site Ø](http://slidetodoc.com/presentation_image/6614f80ef8c2e325b220eef861b90e08/image-25.jpg)
Secondary TB (reactivation) Ø Occurs later in life Ø Lung more common site Ø Immunocompromised patients. Ø Lesion localized in apices Ø Infectious & symptomatic Ø Microscopy: many bacilli, large area of caseous necrosis cavity (open TB) with granuloma and caseation.
![Secondary TB Ø Clinically: fever, cough, hemoptysis , weight loss & weakness. Ø Source Secondary TB Ø Clinically: fever, cough, hemoptysis , weight loss & weakness. Ø Source](http://slidetodoc.com/presentation_image/6614f80ef8c2e325b220eef861b90e08/image-26.jpg)
Secondary TB Ø Clinically: fever, cough, hemoptysis , weight loss & weakness. Ø Source of secondary TB : - Endogenous (reactivation of an old TB) or - Exogenous (re-infection in a previously sensitized patient who has previous infection with the organism).
![Immunity to Tuberculosis Ø Cell-mediated immunity associated with delayed hypersensitivity reaction. Ø Detected by Immunity to Tuberculosis Ø Cell-mediated immunity associated with delayed hypersensitivity reaction. Ø Detected by](http://slidetodoc.com/presentation_image/6614f80ef8c2e325b220eef861b90e08/image-27.jpg)
Immunity to Tuberculosis Ø Cell-mediated immunity associated with delayed hypersensitivity reaction. Ø Detected by tuberculin skin test. Ø Tuberculin test takes 2 -10 weeks to react to tuberculin and becomes positive.
![Tuberculin Skin Test Ø Uses purified protein derivative (PPD). Ø Activity expressed by Tuberculin Tuberculin Skin Test Ø Uses purified protein derivative (PPD). Ø Activity expressed by Tuberculin](http://slidetodoc.com/presentation_image/6614f80ef8c2e325b220eef861b90e08/image-28.jpg)
Tuberculin Skin Test Ø Uses purified protein derivative (PPD). Ø Activity expressed by Tuberculin unit. Ø Activates synthesized lymphocytes to produce CMI which appear as skin induration. Ø May not distinguish between active and past infection except in an individual with recent contact with infected case. Ø Low level activity induced by environmental mycobacteria , previous vaccination.
![Methods of Tuberculin Skin Test Ø Intradermal inoculation of 0. 1 ml of PPD Methods of Tuberculin Skin Test Ø Intradermal inoculation of 0. 1 ml of PPD](http://slidetodoc.com/presentation_image/6614f80ef8c2e325b220eef861b90e08/image-29.jpg)
Methods of Tuberculin Skin Test Ø Intradermal inoculation of 0. 1 ml of PPD , 5 TU. Ø Read after 48 -72 hrs. Ø Methods of tuberculin skin test : 1 - Mantoux test. 2 - Heaf test (for screening, rarely used).
![](http://slidetodoc.com/presentation_image/6614f80ef8c2e325b220eef861b90e08/image-30.jpg)
![Positive Tuberculin Skin Test Ø 1 - >5 mm § § § Recent contact Positive Tuberculin Skin Test Ø 1 - >5 mm § § § Recent contact](http://slidetodoc.com/presentation_image/6614f80ef8c2e325b220eef861b90e08/image-31.jpg)
Positive Tuberculin Skin Test Ø 1 - >5 mm § § § Recent contact with active TB. HIV or high risk for HIV Chest X-ray consistent with healed TB. Ø 2 - > § § induration positive in : 10 mm induration positive in: IV drugs user, HIV seronegative patient. Medical conditions eg. diabetes , malignancy.
![Positive Tuberculin Test Residents & employee at high risk § Patients from country with Positive Tuberculin Test Residents & employee at high risk § Patients from country with](http://slidetodoc.com/presentation_image/6614f80ef8c2e325b220eef861b90e08/image-32.jpg)
Positive Tuberculin Test Residents & employee at high risk § Patients from country with high incidence. § Children < 4 yrs or exposed to adult high risk group. § Mycobacteriology lab. personnel. Ø 3 - >15 mm induration positive in : § any persons including those with no risk factors for TB. §
![](http://slidetodoc.com/presentation_image/6614f80ef8c2e325b220eef861b90e08/image-33.jpg)
![Negative Tuberculin Skin Test Ø No induration , either due to: § § § Negative Tuberculin Skin Test Ø No induration , either due to: § § §](http://slidetodoc.com/presentation_image/6614f80ef8c2e325b220eef861b90e08/image-34.jpg)
Negative Tuberculin Skin Test Ø No induration , either due to: § § § No previous infection Pre-hypersensitivity stage Lost TB sensitivity with loss of antigen. Ø AIDS patients are anergic and susceptible to infection.
![Laboratory Diagnosis of TB Ø 1 - Specimens: § Pulmonary TB: 3 early morning Laboratory Diagnosis of TB Ø 1 - Specimens: § Pulmonary TB: 3 early morning](http://slidetodoc.com/presentation_image/6614f80ef8c2e325b220eef861b90e08/image-35.jpg)
Laboratory Diagnosis of TB Ø 1 - Specimens: § Pulmonary TB: 3 early morning sputum samples ( or induced cough), or bronchial lavage, or gastric washing (infants) , …etc. Ø Cerebrospinal fluid ( CSF) ( TB meningitis) Ø 3 early morning urine Ø Bone , joint aspirate Ø Lymph nodes, pus or tissues NOT Ø Repeat sample. swab.
![Laboratory Diagnosis of TB Ø 2 - Direct microscopy of specimen : § Z-N Laboratory Diagnosis of TB Ø 2 - Direct microscopy of specimen : § Z-N](http://slidetodoc.com/presentation_image/6614f80ef8c2e325b220eef861b90e08/image-36.jpg)
Laboratory Diagnosis of TB Ø 2 - Direct microscopy of specimen : § Z-N or (Auramine ) stain. Ø 3 - Culture: the gold standard test for identification and sensitivity. § Media used: Lowenstein-Jensen media (L J). Media contains: eggs, asparagin, glycerol, pyruvate/ malachite green.
![Laboratory Diagnosis of TB Colonies appear in LJ media after 2 -8 weeks as Laboratory Diagnosis of TB Colonies appear in LJ media after 2 -8 weeks as](http://slidetodoc.com/presentation_image/6614f80ef8c2e325b220eef861b90e08/image-37.jpg)
Laboratory Diagnosis of TB Colonies appear in LJ media after 2 -8 weeks as eugenic, raised, buff, adherent growth enhanced by glycerol (MTB) or by pyruvate (M. bovis). Ø Other media plus LJ media may be used: Ø Fluid media (middle Brook) MGIT ( mycobacteria growth indicator test ) Automated methods : - eg. Bactec MGIT. Measurement of interferon –gamma ( IF-γ) secreted from sensitized lymphocytes challenged by the same mycobacterial proteins in a patient previously exposed to disease, will produce interferon gamma. Has a specific significance than tuberculin skin test. § PCR: molecular test directly from specimen (CSF) and Prob. Tech directly from respiratory samples. . § §
![](http://slidetodoc.com/presentation_image/6614f80ef8c2e325b220eef861b90e08/image-38.jpg)
![Identification Ø Morphology , growth at 37 C + 5 -10 % CO 2 Identification Ø Morphology , growth at 37 C + 5 -10 % CO 2](http://slidetodoc.com/presentation_image/6614f80ef8c2e325b220eef861b90e08/image-39.jpg)
Identification Ø Morphology , growth at 37 C + 5 -10 % CO 2 Ø Biochemical tests : Niacin production & Nitrate test. Ø Sensitivity testing Ø Guinea pig inoculation: rarely done.
![Management of a TB case Ø 1 - Isolation for 10 -14 days ( Management of a TB case Ø 1 - Isolation for 10 -14 days (](http://slidetodoc.com/presentation_image/6614f80ef8c2e325b220eef861b90e08/image-40.jpg)
Management of a TB case Ø 1 - Isolation for 10 -14 days ( for smear positive cases i. e. > 1000 organisms / ml of sputum considered infectious case ). Ø Triple regimen of therapy. Why ? § To prevent resistant mutants § To cover strains located at different sites of the lung. § To prevent relapse Ø 2 - Treatment must be guided by sensitivity testing.
![First Line Treatment Isoniazide (INH) Ø Rifampicin (RIF) Ø Ethmbutol (E) Ø Pyrazinamide (P) First Line Treatment Isoniazide (INH) Ø Rifampicin (RIF) Ø Ethmbutol (E) Ø Pyrazinamide (P)](http://slidetodoc.com/presentation_image/6614f80ef8c2e325b220eef861b90e08/image-41.jpg)
First Line Treatment Isoniazide (INH) Ø Rifampicin (RIF) Ø Ethmbutol (E) Ø Pyrazinamide (P) Ø Streptomycin (S) (sometimes added to first line) INH+ RIF +P for 2 months then continue with INH+RIF for 4 -6 months. Multidrug resistant TB is resistance to INH & RIF. Ø Directly Observed Therapy (DOT). Ø
![Second Line Used if the bacteria was resistant to first line drugs. More toxic Second Line Used if the bacteria was resistant to first line drugs. More toxic](http://slidetodoc.com/presentation_image/6614f80ef8c2e325b220eef861b90e08/image-42.jpg)
Second Line Used if the bacteria was resistant to first line drugs. More toxic than the first line drugs. Ø PASA ( Para-Amino Salicylic acid) Ø Ethionamide Ø Cycloserine, Ø Kanamycin, Ø Fluroquiolones
![Tuberculosis: (a) Chest X-ray of a patient with tuberculosis bronchopneumonia. (b) Chest X-ray of Tuberculosis: (a) Chest X-ray of a patient with tuberculosis bronchopneumonia. (b) Chest X-ray of](http://slidetodoc.com/presentation_image/6614f80ef8c2e325b220eef861b90e08/image-43.jpg)
Tuberculosis: (a) Chest X-ray of a patient with tuberculosis bronchopneumonia. (b) Chest X-ray of the same patient 10 months after antituberculous therapy. (Courtesy of Dr. R. S. Kennedy)
![Prevention of TB Ø Tuberculin testing of herds. Ø Slaughter of infected animals. Ø Prevention of TB Ø Tuberculin testing of herds. Ø Slaughter of infected animals. Ø](http://slidetodoc.com/presentation_image/6614f80ef8c2e325b220eef861b90e08/image-44.jpg)
Prevention of TB Ø Tuberculin testing of herds. Ø Slaughter of infected animals. Ø Pasteurization of milk to prevent bovine TB Ø Recognition of new cases. Ø Prophylaxis with INH of contacts. Ø Follow up cases. Ø Immunization with BCG to all new borne.
- Slides: 44