1. 1 Mycobacterium

2. 2

3. 3 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.

4. 4

5. 5 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

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7. 7 Classification OrganismsGrowth rateTypical species M. tuberculosis complex slowM. tuberculosis M. bovis M. lepraeNo growth on artificial media Nontuberculosis mycobacteria Group Ⅰ Slow M. Kansas 堪萨斯分枝杆菌 M. Marinum 海分枝杆菌 Group Ⅱ SlowM. Scrofulaceum 瘰疬分枝杆菌 Group Ⅲ SlowM. avium-intracellulare 鸟－胞内分枝杆菌 Group Ⅳ Rapid(<7d)M. Fortuitum 偶发分支杆菌

8. 8 M. tuberculosis

9. 9 Biological properties Shape and structure –Slender, rod-shaped bacterium, nonmotile –Compositions peptidoglycan arabinogalactan layer high content lipid –Mycolic acids –Cord Factor –Wax polypeptide

10. 10 free lipids (wax,cord factor)

11. 11 Biological properties high content lipid Mycolic acids Cord Factor Wax Acid-fast stain Slow growth Fastidious A virulence factor

12. 12 Ziehl-Neelsen stain (acid-fast stain) Acid-fast positive M.TB. smear, stained with carbolfuchsin (15minutes) decolorized with acid-alcohol counterstained with methylene-blue

13. 13 Biological properties Cultivation obligate aerobes slow growth: 18-24 hrs / 2-4 w fastidious: Lowenstein-Jensen medium (L-J)..

14. 14 Biological properties Sensitivity moist heat UV radiation alcohol Resistance dry acid and alkaline dyes: e.g., malachite green

15. 15 Pathogenicity neither endotoxin or exotoxin nor invasive enzyme intracellular pathogen Lipids Protein -- induces hypersensitivity of the host Tuberculin test Polysaccharides Mycobactin

16. 16 Lipid Phospholipids ---proliferation of mononuclear cells, cause tubercles Cord factor ---destroy mitochondria, suppress WBC wandering ， cause chronic granulomatosischronic granulomatosis Wax D ---adjuvent, delayed-type hypersensitivity Sulfatide 硫酸脑苷脂 suppress phagosome combine with lysosome

17. 17 Pathogenicity Pathogens M. tuberculosis-- only human host M. bovis-- human and cattle Transmission –respiratory route (main) –gastrointestinal route –impaired skin

18. 18 Lung infection (pulmonary tuberculosis ) –Primary tuberculosis –Post-primary (secondary) tuberculosis Extrapulmonary tuberculosis Pathogenicity

19. 19 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 Pulmonary tuberculosis

20. 20 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 Pulmonary tuberculosis

21. 21 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.

22. 22 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

23. 23 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

24. 24 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 Tuberculin test

25. 25 Results and interpretation –induration ≥ 5mm in diameter ---Positive ---Previous infection but not necessarily active disease ---after BCG vaccination –induration ≥ 15mm in diameter ---intensive positive ---active disease –induration <5mm --- a negative reaction --- not contact with M. tuberculosis before ---false reaction Tuberculin test early stage of infections the elderly patients with severe tuberculosis and other infectious disease (AIDS) the use of immunosuppressive drugs

26. 26 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)

27. 27 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

28. 28 Treatment –multiple drugs –usually lasts for 6-9 months – rifampin 、 isoniazid 、 streptomycin 、 prazinamide Prevention and Treatment

29. 29 Nontuberculosis mycobacteria OrganismsGrowth rate Pigment formation in: Typical species LightDark Group Ⅰ photochromogens Slow+- M. Kansas 堪萨斯分枝杆菌 M. Marinum 海分枝杆菌 Group Ⅱ scotochromogens Slow++M. Scrofulaceum 瘰疬分枝杆菌 Group Ⅲ Nonchromogens Slow--M. avium-intracellulare 鸟－胞内分枝杆菌 Group Ⅳ Rapid growers Rapid(<7d)M. Fortuitum 偶发分支杆菌

30. 30 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

31. 31 Mycobacterium leprae

32. 32 Biological properties Intracellular parasites Not grow on artificial media and cell culture Grow in footpads of mice Optimal temperature: 30 ℃

33. 33 4 forms of Leprosy Lepromatous Tuberculoid Borderline indeterminate

34. 34 Pathogenesis Transmission Respiratory tract Direct contact Disease-- leprosy (Hansen's Disease) –Lepromatous type –Tuberculoid type –Infect skin, nerves –Chronic disease –Disfigurement

35. 35

36. 36 Lepromatous typeTuberculoid type CMIdeficientnormal leprominnegativepositive skin lesionabundant acid-fast bacilli few bacilli courseprogressive and malign benign and nonprogressive infectivityhighlow