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Mycobacterium 1 2 Incidence and prevalence • One-third of the population worldwide is infected • Every year – 1.5 million people die from tuberculosis – 8 to 10 million are newly infected. 3 4 Main factors account for the resurgence of tuberculosis in the United States • Emergence of multidrug-resistant strains of M. tuberculosis • Immigration of infected persons from countries where TB is prevalent • Prevalence of HIV infection and AIDS • Reactivation of disease in the elderly • Socioeconomic decline in urban areas 5 6 Classification Organisms M. tuberculosis complex M. leprae Growth rate slow Typical species M. tuberculosis M. bovis No growth on artificial media Nontuberculosis mycobacteria Group Ⅰ Slow Group Ⅱ Slow M. Kansas 堪萨斯分枝杆菌 M. Marinum 海分枝杆菌 M. Scrofulaceum Group Ⅲ Slow M. avium-intracellulare Group Ⅳ Rapid(<7d) M. Fortuitum 瘰疬分枝杆菌 鸟-胞内分枝杆菌 偶发分支杆菌 7 M. tuberculosis 8 Biological properties • Shape and structure – Slender, rod-shaped bacterium, nonmotile – Compositions • peptidoglycan • arabinogalactan layer • high content lipid – Mycolic acids – Cord Factor – Wax • polypeptide 9 free lipids (wax,cord factor) 10 Biological properties • high content lipid • Mycolic acids • Cord Factor • Wax Acid-fast stain Slow growth Fastidious A virulence factor 11 Ziehl-Neelsen stain (acid-fast stain) Acid-fast positive • M.TB. smear, stained with carbolfuchsin (15minutes) • decolorized with acid-alcohol • counterstained with methylene-blue 12 Biological properties • Cultivation obligate aerobes slow growth: 18-24 hrs / 2-4 w .. fastidious: Lowenstein-Jensen medium (L-J) 13 Biological properties • Sensitivity moist heat UV radiation alcohol • Resistance dry acid and alkaline dyes: e.g., malachite green 14 Pathogenicity neither endotoxin or exotoxin nor invasive enzyme intracellular pathogen • • Lipids Protein -- induces hypersensitivity of the host Tuberculin test • • Polysaccharides Mycobactin 15 Lipid • Phospholipids ---proliferation of mononuclear cells, cause tubercles • Cord factor ---destroy mitochondria, suppress WBC wandering ,cause chronic granulomatosis • Wax D ---adjuvent, delayed-type hypersensitivity • Sulfatide 硫酸脑苷脂 suppress phagosome combine with lysosome 16 Pathogenicity • Pathogens M. tuberculosis-- only human host M. bovis-- human and cattle • Transmission – respiratory route (main) – gastrointestinal route – impaired skin 17 Pathogenicity • Lung infection (pulmonary tuberculosis ) – Primary tuberculosis – Post-primary (secondary) tuberculosis • Extrapulmonary tuberculosis 18 Pulmonary tuberculosis • Primary tuberculosis – Infected for the first time – In young children – Ghon complex (or primary complex) --combination of a single lesion in lung and caseation in regional lymph nodes in the lung’s hilum – Clinical type: usually mild and asymptomatic 19 Pulmonary tuberculosis • Post-primary (secondary) tuberculosis – in the elderly or immunosuppressed individuals who have had primary infection • the reactivation of the bacilli that survived in the primary tuberculosis • the inhalation of new bacilli from the environment – clinical type: localized and severe 20 Immunity • Intracellular pathogen • Immunological reaction – Cell-mediated immunity (3 ~ 6 weeks after infection) – Humoral immunity: circulating Abs → no defensive roles – Infection immunity: The immunity to the bacilli depends on the existence of organisms. 21 Immunity • Cell-mediated immunity & hypersensitivity – develop at the same time mediated by T cells – caused by different components of bacilli – protein antigens (tuberculin along with wax D) → hypersensitivity • Tuberculin test 22 Tuberculin test • Definition a skin test to determine the presence of the immunity and hypersensitivity of the host to M. tuberculosis based on positive reaction of subject to tuberculin 23 Tuberculin test • Materials – old tuberculin (OT): heat-killed, filtered proteins of M. Tuberculosis – purified protein derivative (PPD) • Methods – intradermal infection of tuberculin – read in 48-72 hrs – Measure induration 24 Tuberculin test • Results and interpretation – induration ≥ 5mm in diameter ---Positive ---Previous infection but not necessarily active disease ---after BCG vaccination • early stage of infections • the elderly – induration ≥ 15mm in diameter • patients with severe tuberculosis ---intensive positive and other infectious disease (AIDS) ---active disease • the use of immunosuppressive drugs – induration <5mm --- a negative reaction --- not contact with M. tuberculosis before 25 ---false reaction Laboratory diagnosis • Decontamination and concentration of specimens – Treated with NaOH (sodium hydroxide) to kill other contaminating bacteria – Concentrated by centrifugation • Smears— acid-fast stain • Culture – Use to confirm diagnosis of TB • DNA detection, serology and antigen detection – PCR (polymerase chain reaction) 26 Prevention and Treatment • Prevention – BCG, bacillus Calmette-Guerin • Made by Calmette and Guerin; since 1908 • heat-killed, filtered proteins of M. Tuberculosis • Recommended in immunization programs or TB control programs in China 27 Prevention and Treatment • Treatment – multiple drugs – usually lasts for 6-9 months – rifampin、isoniazid、streptomycin、prazinamide 28 Nontuberculosis mycobacteria Pigment formation in: Organisms Growth rate Light Dark Typical species Slow + Group Ⅰ M. Kansas 堪萨斯分枝杆菌 photochromogens M. Marinum 海分枝杆菌 Group Ⅱ scotochromogens Slow + + M. Scrofulaceum Group Ⅲ Nonchromogens Slow - - M. avium-intracellulare Group Ⅳ Rapid growers Rapid(<7d) 瘰疬分枝杆菌 鸟-胞内分枝杆菌 M. Fortuitum 偶发分支杆菌 29 Characteristics of nontuberculosis mycobacteria • much less virulent than M. tuberculosis • opportunistic pathogen in humans • combined infection with M.tuberculosis, mostly Mycobacterium avium-intracelluare complex. very prominent cause of disease in AIDS patients. • difficult to treat 30 Mycobacterium leprae 31 Biological properties • • • • Intracellular parasites Not grow on artificial media and cell culture Grow in footpads of mice Optimal temperature: 30℃ 32 4 forms of Leprosy • • • • Lepromatous Tuberculoid Borderline indeterminate 33 Pathogenesis • Transmission Respiratory tract Direct contact • Disease-- leprosy (Hansen's Disease) – Lepromatous type – Tuberculoid type – Infect skin, nerves – Chronic disease – Disfigurement 34 35 Lepromatous type Tuberculoid type CMI deficient normal lepromin negative positive skin lesion abundant acid-fast bacilli course progressive and malign infectivity high few bacilli benign and nonprogressive low 36