Mycobacterium tuberculosis Lecture (14) Dr.Baha, AL-Amiedi Ph. D.Microbiology Robert Koch 1843-1910 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 Tuberculosis - species Mycobacterium tuberculosis In immunosuppressed people, occasionally: M. bovis M. africanum M. microti M. leprae 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 Mycobacterium tuberculosis Transmission and Pathogenesis TB: Transmition Infection = Person to Person via Airborne Infectious Aerosol: Coughing Sneezing Talking Aerosolized Droplets 5 Micrometers = 1-400 Bacilli • Estimated 5-200 Organisms Required for infection Infection Microorganisms and pathogenesis 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. 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) 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 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 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 • 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 Tuberculosis in human body EpidemiologySeveral 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 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 Incidence per 100,000: Red>300, Orange 200-300, Yellow 100-200, Green 50-100, Grey<50 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. 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 CXR with evidence of TB infection TB: Determinants of Disease Defects in Cell Mediated Immunity* Advanced Age Malnutrition Genetic Factors Immunosuppressive Meds** Co-existing Disease: Diabetes Malignancy HIV Renal Failure TB: Disease Pattern Primary Tuberculosis • Reactivation Tuberculosis TB: Diagnosis • PPD • Sputum Examination • Chest X-Ray • Culture 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 TB: PPD • Dose of Tuberculin = 5TU • Injection Site = Intradermally Dorsal Side of Forearm • Inflammatory Reaction = 2472 Hours • Result Test in 48-72 Hours (If Positive at 6 Days = true positive Testing for TB Disease and Infection 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 Principles of Tuberculosis Treatment Principles of Tuberculosis Treatment The World health Organization Advocates Directly Observed Therapy (DOT) Drugs in Current Use Isoniazid • Rifampin • Pyrazinamide • Ethambutol • Streptomycin 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. 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 The End