结核分枝杆菌

1、Mycobacterium 分枝杆菌属分枝杆菌属THIS GENUS IS COMPOSED OF: Strictly aerobic, form branched filaments,unique cell wall, rich in lipids, high Mycolic acid content-acid-fast rods, gram stain indeterminant (does not Stain well )DNA has high g+c content(61-71%), Relatively slow growth (two groups)A. RAPID GROWER

2、S (Visible colonies in 5 days)Mycobacterium 分枝杆菌属分枝杆菌属1. M. tuberculosis bacillus complex :lM. tuberculosis: lM.bovis: 2. M. leprae: 3. Atypical mycobacteria or nontuberculous mycobacteria: Mycobacterium can be divided into 3 groups:Mycobacterium tuberculosisMycobacterium tuberculosisMycobacterium t

3、uberculosisMycobacteriumStop TB in my lifetime Tell the world what you want to see in your lifetime6KEY WORDSnObligate aerobes, n(causing disease in highly oxygenated tissues such as the upper lobe of the lung and the kidney.)nGrow slowly，n(generation time of 15-20 hours, cultures of clinical specim

4、ens must be held for 6-8 weeks before being recorded as negative),nHideous colonies. nOn solid media the colonies are raised and rough with a wrinkled surface (Colony with a waxy, warty appearance）nResistancenM.tuberculosis is relatively resistant to acids and alkalis. nM.tuberculosis is resistant t

5、o dehydration nResistant to common antibiotics and antimycobacterial drug, isoniazid, Biological Characterization: resistant SensitiveDry (highly)WetMalachite green(1:3000)common antibiotics and some antimycobacterial drug, isoniazid, Heat (62-63,15min)3%HCL, 6%H2SO4, 4%NaOH(30Min)Alcohol, UVVariati

6、on ：shape, colony, virulence, antigenicity and resistanceUnique stainingZiehl-Neelsen staining (or Acid-fast Stain)The BCG vaccine (Albert Calmette, & Camille Gurin , an attenuated strain of M. bovis) Acid fast M. tuberculosisColonial Morphology of the Mycobacteria TuberculosisWarty appearancenL

7、ow infection dose (1-3 bacilli reaching the lung alveolar space can initiate an infection)pathogen: inhibits phagosome-lysosome fusion, intracellular growth in alveolar macrophages distributed within macrophages -sustain life-long infection, nDisease symptoms mostly caused by immune reaction to infe

8、ction (There are not endotoxin and cannot produce exotoxin or invasive enzyme )nPathogenicity concerned with some constituents of cell wall and some toxic substances of tubercle bacilli. nMycobacteria are rich in lipids, Lipid closely related to virulence and responsible for acid-fastness.nLong-chai

9、n (C78-C90) fatty acids called mycolic acids contribute to the organisms acid-fastnessnSulfatide硫酸脑苷脂硫酸脑苷脂 : inhibits phagosome-lysosome fusion, intracellular growth in macrophages and survive for long timenWax D adjuvant (not only to TB), delayed-type hypersensitivitynPhosphatides磷脂磷脂 , which play

10、a role in caseation necrosis.nCord factor (trehalose-6,6-dimycolate) cause chronic granulomatosis , suppress WBC wanderingnProteins: elicit the tuberculin reaction. n Polysaccharides: Their role in the pathogenesis of disease is uncertain. Constituents of Tubercle Bacillin Tuberculosis transmission:

11、 l respiratory tract: l alimentary tract: l injured skin:n PathogenesisSite of infection: TB in the lungs or throat can be infectious. TB in other parts of the body, such as the kidney or spine, is usually not infectious.l Lung infection (80%) : chronic cough, spit blood l Out lung infection :Can in

12、fect (disseminate) and cause disease in many different body locations such as: Meninges, Brain, Bone, Kidney, Essentially any organ (lung primary target)1. Primary tuberculosis ： n Infected for the first timen In young childrenn Ghon complex (or primary complex) -combination of a single lesion in lu

13、ng (primary focus) and caseation in regional lymph nodes in the lungs hilum (draining lymph nodes)n Clinical type: usually mild and asymptomaticn Exogenous infection1. Primary tuberculosis: nin the elderly or immunosuppressed individuals who have had primary infectionnEndogenous infection- the react

14、ivation of the bacilli that survived in the primary tuberculosisnthe inhalation of new bacilli from the environmentnThe common focus is lung, also occur in other well-oxygenated sites such as the kidneys, brain, and bone nClinical type: localized and severe nFeature of focus：n Often occur at apex of

15、 lung n Not involving neighbor lymph nodes 2. Secondary tuberculosisImmunityCellular immunityHumoral immunity: A lot of Ab comes out, but meaninglessTB active patient: immune complex moreTB stable patient: immune complex lessIV hypersensitivity: tuberculin reaction DiagnosisThe steps to diagnose TB

16、infection and disease include: nA medical evaluation that includes history and risk assessment, Primary infection: children, Secondary infection: age25 nThe tuberculin skin test or Skin test (exposure to the bacteria)nA chest x-ray nMicroscopic observation of specimen lSpecimen: sputum, pus, CSF, ur

17、ine, etc. (4%NaOH-3%HCL; 6% H2SO4)lMicroscopic examination: Ziehl-Neelsen stainnPCR or other molecular methods to detect species specific DNA or RNA (why not culture?)Tuberculin Skin TestnTuberculin is a mixture known as purified protein derivatives (PPD) from TB bacilli. nIt is a test for delayed t

18、ype hypersensitivity. Positive reaction, reddening and thickening ( 5mm) at the site of injection after 2-3 days, indicates cellular immunity to tubercle bacilli.n Result：red swelling and hardening at the sitel 1.5cm strong positive，may having active tuberculosis Tuberculin skin testTuberculin skin

19、testn Applicationl Choice individual for inoculation of BCG l Check the effect of BCG inoculation; l Diagnosis of tuberculosis with population that do not inoculate BCG; l Assay the function of cell-mediate immunity; l Epidemic investigationnVaccination:- BCG (Bacille Calmette-Guerin).- Efficacy in

20、clinical trials: 0 85%.- Not used in U.S.nIsolation: until the patients no longer coughing up the organism, after therapy, the patients sputum becomes noninfectious within 2-3 weeks, test the sputum for the organismTreatment and ControlTB TreatmentCombination therapy-Multiple Drug Therapy (MDT):.nIs

21、oniazid异烟肼+rifampicin利福平+pyrazinamide吡嗪酰胺nAdd ethambutol乙胺丁醇片 if drug resistance is suspectedn 6 9 months for immunocompetent adults.9 12 months for immunocompromised adults.nDuration of therapy dependent on site of infectionEmergence of drug-resistant strains of M.Tb.TB incidence nDeveloping countr

22、ies: TB continues to increase in incidence.lSoutheast Asia, sub-Saharan撒哈拉沙漠以南的 Africa, East Europe have the highest incidence nDeveloped countries: After a century of decline, the incidence of TB is currently increasing:lIn the developed nations, homeless persons, drug and alcohol abusers, and HIV

23、infected persons have the highest risk of infection Question: Why incidence of TB is increasing?difficulty in diagnosing TB during the early stages of illness.difficulty in delivering and compliance of multiple drugs for treatment of patients diagnosed with TB.HIV/AIDS.emergence of drug resistant st

24、rains of M.Tb.nChief Complaint A 20-year-old man with a cough of several weeks duration.n History The patient is a recent immigrant from Southeast Asia who noted the gradual onset of tiredness and loss of appetite about 1 month ago. A week or so later, he felt feverish and the cough began. At first

25、the cough was nonproductive, but for the past week he has brought up several tablespoons per day of greenish sputum that is streaked with blood. He has lost 101b during the past month. He is a nonsmoker and has had no exposure to industrial respiratory pollutants.Clinical casenPhysical Exam T 38, BP

26、124/70, P80, R16.The patient did not appear acutely ill. Pertinent finding include: Lungs: Rales水泡音 heard in right upper lobe. No dullness浊音 to percussion 叩诊. Heart: Normal Abdomen: Normal Lymph nodes: Not enlarged.nLaboratory Blood: Hematocrit 38; WBC11,000; Differential 3% bands, 63% polys, 30% ly

27、mphs, 4% monos. Urine: Normal Chest X-ray: Infiltrate in posterior segment of right upper lobe with suggestion of a cavity.1.Which two procedures should you do with the sputum that could provide immediate information regarding the organism causing the illness?lGram stain and acid-fast stainQuestions

28、?nCoursenGram stain of the sputum revealed mixed flora with no predominant organism. The acid-fast stain showed numerous long, slender,pink rods. A sputum specimen was sent for culture.Questions?2.In view of these results, what is the most likely diagnosis?lTuberculosis3.What is the treatment of cho

29、ice for this disease?lMultiple-drug therapy for 6-9 months is the accepted mode of treatment. Isoniazid(inh) is bactericidal and is the mainstay of treatment. It is frequently combinend with rifampin and either pyrazinamide or ethambutol or both.4.Is antibiotic resistance a problem?lSoutheast Asians

30、 have a high rate of infection with INH-resistant strains of M tuberculosis. Thereapy with four drugs, ie, INH, rifampin, pyrazinamide, and ethambutol, should be used if INH resistance is suspected.5.Approximately how long after the start of treatment is the patient considered to be infectious for o

31、thers?lApproximately 2-3 weeks, but treatment must continue for at least 6-9 months to avoid recurrences.6.How is the organism transmitted?lTransmitted by inhalation of aerosolized organisms from expectorated sputum.Questions?7.What is the natural habitat of the organism?lHuman lungs.8.Why is the organism acid-fast?lThe high concentration of lipid makes mycobacteria acid-fast. These lipid prevent the dyes used in the Gram stain