医学微生物学资料：Tuberculosis

1、2022/9/161Tuberculosis from a view of microbiologistA global goal of World Health Organization2022/9/163Minimal Essential information for tuberculosisDisease burden and epidemiological profile.Classification and morphology of the germCell and/or sub-cellular structure of the germ which are related t

2、o pathogenic factors and pathogenesis of the bacteria 2022/9/164Minimal essential information for a given bacteriumLaboratory diagnosis of the infectionInfection control and prevention Principle of clinical management something more?2022/9/165Mycobacterium Tuberculosis Mycobacteriaceas Mycobacterium

3、2022/9/166Age-based prevalence of tuberculosis2022/9/167Current Situation of TB in China 4.5 million pulmonary TB cases 2.0 million infectious cases 1.5 million smear positive cases More than 500 million persons infected with TB 130,000 patients were died from TB every year2022/9/169The Goal of TB C

4、ontrol in China(Ministry of health,2005)To the year 2010, detect and Cure TB Cases 4 million；To the year 2010,the DOTS coverage to 95%；To the year 2010, the Cure rate of new sm+ cases 85%。2022/9/1610The percent of reduce cases = detection rate rate of treatment treatment complete rate cure rate 0.4

5、0.90.90.9 0.5 0.90.90.9 0.6 0.90.90.9 0.7 0.90.90.9 0.290.360.440.51 0.3 0.90.90.9 0.222022/9/1611Type of health clinics for first clinical consultation (2009)General hospital ： 38.1%Township or village clinics： 28.7%Private clinics： 18.2%Traditional health clinics： 3.7%Tuberculosis control units： 4

6、.3%Others: 7.0%Challenge?2022/9/1612DOTS Expansion from 1991 to 2005100%95%85%0%10%20%30%40%50%60%70%80%90%100%199119921993199419951996199719981999200020012002200320042005yearDOTS Expansion %2022/9/1613Cure rate of new sm+ cases in 1991-20040%10%20%30%40%50%60%70%80%90%100%19911992199319941995199619

7、971998199920002001200220032004yearCure rate %2022/9/1614Classification the germ Mycobacteriaceas Mycobacterium M. tuberculosis and M. leprosy2022/9/1615Common features of mycobacteriumAerobic, slightly curved or straight rods 0.20.6 1.010 m in size.The most unique structure is the thick (20nm) cell

8、wall.2022/9/1616M. tuberculosisAcid-fast, nonmotile, non-sporogenous, nonencapsulated Gram positive? (difficult to stain!)Acid-fastness is explained by lipid barrier of cell Physical integrity of cell wall2022/9/1617M. tuberculosisMorphology Slender, straight or slightly curved rod with rounded ends

9、 width 0.20.5 m, length 14 m.2022/9/16182022/9/16192022/9/16202022/9/1621Cultural characteristics Very slow-growing organism even under optimal conditionMedium: enriched with serum or eggIncubation: 37 C, 1020 daysColonies: small, dryDoubling time: 1824 hoursTween 80, which prevents the agglutinatio

10、n of cells in broth, can improve the growth of M. tuberculosis.2022/9/1622Resistance Highly resistant to drying (12 years in 37C) (68 months in sputum)(810 days in droplets)More resistant to chemical disinfectantAs sensitive to moist heat as other bacteria2022/9/1623AntigenCell wallCytoplasmic prote

11、inPPD Seibers protein A. B. C.2022/9/16242022/9/1625Pathogenesis and Clinical InfectionM. tuberculosis produces neither exotoxins nor endotoxins No single structure or antigen can be identified to be virulent factor except Cord Factor (Trehalose66dimycolate)Humans are very sensitive to tuberculosis

12、infection but rather resistant to tuberculosis disease.2022/9/16262022/9/16272022/9/1628Virulence factors No spore, no flagellum, no exotoxin,no endotoxin, no invasive enzymeCapsule : polysaccharide Lipid/Lipo- arabinomannanHeat-shock protein/Tuberculin protein: antigenicity, old tuberculin; associa

13、te with wax D can cause hypersensitivity and form tubercle2022/9/1629Lipida. Phospholipid monocytes proliferate,cause tuberclesb. Wax D adjuvent(not only to TB), delayed-type hypersensitivityc. Sulfatide (硫酸脑苷脂) suppress phagosome combine with lysosomed. Cord factor (trehalose-6,6-dimycolate) destro

14、y mitochondria, cause chronic granulomatosis, suppress WBC wandering2022/9/1630TB infectionEntry of the bacteria into human body through respiratory tractBacteria bind to complement receptors (CR1,3 and 4) of alveolar macrophages and followed by phagocytosisAcidification of phagosome is blocked whic

15、h inhibited phago-lysosome formationBacteria multiplication in cytoplasm of phagocytes and travel along lymphatic channels2022/9/1631TB infection (Cont. )Triggering Th1 responseInitiation of Delayed Type Hypersensitivity (DTH)Cytokines stimulate an inflammatory process with enhanced function of macr

16、ophages by IFN-r and release of digestive enzymes by TNF, IL12.Formation of granuloma consisting of macrophages, lymphocytes, epithilioid cells ,fibroblasts and multinucleated cellsNecrosis in the lesion (caseous necrosis) 2022/9/1632TransmissionThrough respiratory tract, alimentary tract, injured s

17、kin。TB in the lungs or throat can be infectious. So the bacteria can spread to other people. TB in other parts of the body, such as the kidney or spine, is usually not infectious.2022/9/1633Primary TuberculosisThe organisms are transmitted among human via aerosol. TB bacilli lodge into the alveoli o

18、r lung alveolar ducts and most of bacilli are phagocytosed by alveolar macrophages.Macrophages migrate to the lymph node and generate T cell-mediated immune response.2022/9/1634Tuberculosis: picture seen with Added and un-added eye2022/9/1636Clinical syndromes fatigue, weakness, weight loss and feve

19、r pulmonary involvement: chronic cough,spit blood meningitis or urinary tract involvement bloodstream dissemination: miliary tuberculosis with lesions in many organs and a high mortality rate.2022/9/1637Latent & Re-infection of tuberculosis Almost exclusively a disease of lung (endogenous?) Tubercul

20、osis of bone and joint2022/9/1638中国医学摄影的创始人： 蒋汉澄2022/9/16392022/9/1640The lipids-rich cell walls of M. Tuberculosis are responsible for1. Poor staining by Grams2. Acid-fast mechanisms3. Resistant to phagocytosis by macrophages4. Resistant to dry environment by keeping water in cell 2022/9/1641Who is

21、 at risk: Victim of primary infection: nave people and vaccinated but not protected people Victim of secondary infection : people with compromised immunity 2022/9/1642Prevention and control of TBWhy BCG cannot induce effective immunity against tuberculosisImportant anti-TB immunity: cell-mediated im

22、munity of Th1, Th2 and Tc cellsStrategy of development of novo vaccine against tuberculosis2022/9/1643Diagnosis1. Specimen: sputum, pus, CSF, urine, etc. 2. Microscopic examination: Ziehl-Neelsen stain3. Concentration: 4%NaOH-3%HCL; 6% H2SO44. Culture: solid culture (2-4 weeks 37) ; liquid culture (

23、1-2 weeks)5. Animal inoculation: guinea pig6. quick Diagnosis: PCR ?2022/9/1644Tuberculin Skin TestTuberculin is a mixture of bacterial components and its purified protein is called purified protein derivatives (PPD) It is a test for delayed type hypersensitivity. Positive reaction, reddening and thickening ( 5mm) at the site of