Mycobacterium tuberculosis. Lecture (14) Dr.Baha, AL-Amiedi Ph. D.Microbiology

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1 Mycobacterium tuberculosis Lecture (14) Dr.Baha, AL-Amiedi Ph. D.Microbiology

2 Robert Koch German physician Became famous for isolating the anthrax bacillus (1877), tuberculosis bacillus (1882) and cholera vibrio (1883) First linked M. tuberculosis to the disease TB, winning the Nobel Prize in 1905

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5 Tuberculosis - species Mycobacterium tuberculosis In immunosuppressed people, occasionally: M. bovis M. africanum M. microti M. leprae

6 Mycobacterium tuberculosis CHARACTERISTICS rod shaped bacteria,non-spore, cell wall, Unusually with high glycolipid (mycolic acid) Special stain Ziehl-Neelsen (acid-fast stain required) non-motile Aerobic, very slow growth in Culture Lowenstein-Jonsens medium Capable of long-term survival in the human body (persistence) resistance for heat,drying,germicides and other enviremental factores,perphas because of various lipid in cell wall

7 Mycobacterium tuberculosis

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9 Transmission and Pathogenesis

10 TB: Transmition Infection = Person to Person via Airborne Infectious Aerosol: Coughing Sneezing Talking

11 Aerosolized Droplets 5 Micrometers = Bacilli Estimated Organisms Required for infection Infection

12 Microorganisms and pathogenesis

13 Virulence Factors Ability to survive in lung macrophages Cell wall components that elicit damage to tissue Ability to survive for decades in walled-off lesions Difficult to study Virulence Factors Only recently amenable to genetic studies Microarray Technology and Whole genome transcriptome ( is used to study the interaction of Mycobacterium tuberculosis with macrophages.

14 Cellular constituent: Vairluent strains have pathogenic components 1-alipid (2mycolic acid it is alarge fatty acid with disaccharide called cord factor),experimentally inhibit neutrophil migration and damage mitochondria of The infected host(stain due to mycolic acid) 2- several proteins are present that evoke tuberculin reaction in skin 3..polysaccharide of tubercule bacilli that induce the immediate Hypersensitivity type (lv)

15 Pneumonia caused by acid-fast bacterium Mycobacterium Tuberculosis Course of infection Acquired from organisms inhaled in airborne droplets Organisms lodge within pulmonary alveoli Cell-mediated immunity develops Activated macrophages attack and destroy many of the organisms Characteristic granulomas form Infection arrested in majority of cases

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18 Pathogenesis: T.B is a granulomatous inflammatory disease Infected macrophages become surrounded by Tand B lymphocytes and fibroblasts, aggregating to form a granuloma, limiting dissemination Granulomas can become necrotic in the centre

19 Primary sight of infection is the lungs Mycobacterium reach pulmonary alveoli Replicate within alveolar macrophages Bacteria enter dendritic cells (do not replicate) and travel to distant lymph nodes Enter blood and spread to any organ of the body

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21 Miliary Tuberculosis Mass of tuberculous inflammatory tissue erodes into a large blood vessel Dissemination of organisms by bloodstream Extrapulmonary tuberculosis Result of hematogenous spread of tubercle bacilli Sites Kidneys Bone Uterus Fallopian tubes

22 Tuberculosis in human body

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26 Epidemiology- Several factors increase susceptibility to TB and increase mortality among infected individuals: HIV / immunosuppression (TB is the most frequent cause of death in people with HIV) Smoking (4 fold excess risk diabities

27 1/3 World population has been exposed to the T.B infection 1 new infection per second world-wide Most infections are latent (noninfectious) 1/10 progress to active TB Of those, 50% die (1.6-2 million people/yr

28 Incidence per 100,000: Red>300, Orange , Yellow , Green , Grey<50

29 Oral aspect of pulmonary tuberculosis Pulmonary tuberculosis in open form that is actively releasing viable bacilli present in risk to the dentist, dental technical since it releases into the mouth in numerable bacilli, these may found contaminating the lips,gingival,teeth and oral mucosa membrane as well as saliva.

30 TUBERCULOSIS DIAGNOSIS Skin test indicates previous exposure to organism Chest x-ray indicates pulmonary infiltrate Culture identifies organism in sputum Detection molecular characteristic by: 1-polymerase chain reaction technique 2-high performance liquied chromotography

31 CXR with evidence of TB infection

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33 TB: Determinants of Disease Defects in Cell Mediated Immunity* Advanced Age Malnutrition Genetic Factors Immunosuppressive Meds** Co-existing Disease: Diabetes Malignancy HIV Renal Failure

34 TB: Disease Pattern Primary Tuberculosis Reactivation Tuberculosis

35 TB: Diagnosis PPD Sputum Examination Chest X-Ray Culture

36 T.B: PPD= (Tuberculin skin Test) (Purified Protein Derivative) The Tuberculin Skin Test Identifies Individuals Who Have Been Infected With Mycobacterium Tuberculosis, it Does not Differentiate Between Old and New Infection

37 TB: PPD Dose of Tuberculin = 5TU Injection Site = Intradermally Dorsal Side of Forearm Inflammatory Reaction = Hours Result Test in Hours (If Positive at 6 Days = true positive

38 Testing for TB Disease and Infection

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40 TB: BCG Vaccination (Bacilli Calmetti Guerin) Live Attenuated Vaccine Derived From M. Bovis WHO: Recommended For Young Children Vaccination = 60-80% Decrease in Disease Does Not Prevent Infection Effect of BCG on PPD Decreases With Time.It given interademally over deltoid region

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42 Principles of Tuberculosis Treatment Principles of Tuberculosis Treatment The World health Organization Advocates Directly Observed Therapy (DOT)

43 Drugs in Current Use Isoniazid Rifampin Pyrazinamide Ethambutol Streptomycin

44 Mycobacterium leprae It is causative agent of leprosy, it is acid fast bacilli and it is slightly curved occurring in bundule with characters weakly acid fast stain 5% H2SO4 is used in stain.

45 Leprosy: Leprosy is the main disease caused by (M. leprae) Which differs from all other mycobacterium in that it Can not be cultured, it is a very chronic disease the organism entirely in intercellular&extracellular. The lesion fluid of leprosy essentially involved the collar of body such as skin facial nerve the nose and pharynax

46 The End