流感病毒 ppt課件

1、1,INFLUENZA VIRUS,2002,,2,‘FLU’,True influenzainfluenza virus A or influenza virus B (or influenza virus C infections - much milder)Febrile respiratory disease with systemic symptoms caused by a variety of other organ

2、isms often called ‘flu’,3,South Carolina 1996-1997 DHEC bulletin,http://www.state.sc.us/dhec/LAB/labbu017.htm,no virus,influenza A,influenza B,,,,CULTURE RESULTS,malathia influenzae per le stelle,4,THE IMPACT OF INFLUEN

3、ZAPANDEMICS,Deaths:,5,THE IMPACT OF INFLUENZA,1972-1994 (19 influenza seasons)>20,000 US deaths in 11 seasons>40,000 US deaths in 6 of thesemany more hospitalizations (~110,000 per year),6,THE IMPACT OF INFL

4、UENZA,recently some increase in morbidity and mortality - possible factors?more elderly peopleCF patients live longermore high risk neonatesmore immunosuppressed patients,7,ORTHOMYXOVIRUSES,http://www.uct.ac.za/depts

5、/mmi/stannard/fluvirus.html,pleomorphicinfluenza types A,B,Cfebrile, respiratory illness with systemic symptoms,8,ORTHOMYXOVIRUSES,type A, B, C : NP, M1 protein sub-types: HA or NA protein,9,TRANSMISSION,AEROSOL100

6、,000 TO 1,000,000 VIRIONS PER DROPLET18-72 HR INCUBATIONSHEDDING,10,NORMAL TRACHEAL MUCOSA,3 DAYS POST-INFECTION,7 DAYS POST-INFECTION,Lycke and Norrby Textbook of Medical Virology 1983,11,DECREASED CLEARANCERISK B

7、ACTERIAL INFECTIONVIREMIA RARE,Lycke and Norrby Textbook of Medical Virology 1983,12,RECOVERY,INTERFERON - SIDE EFFECTS INCLUDE:FEVER, MYALGIA, FATIGUE, MALAISECELL-MEDIATED IMMUNE RESPONSETISSUE REPAIRCAN TAKE S

8、OME TIME,13,An immunological diversion,INTERFERON,14,INTERFERON,timecourse of virus production will vary from virus to virus,15,INTERFERON,16,INTERFERON,,,,,,,,,,,,,,,,,17,INTERFERON,,,,,,,,,,,,,,,,,,,,18,INTERFERON,,,,,

9、,,,,,,,,,,,,,,,19,INTERFERON,THE VIRUSES ARE COMING!,http://www.paulreverehouse.org/midnight.html,PAUL REVEREhttp://www.mfa.org/collections/one_hour/6.htm,20,TYPES OF INTERFERON,TYPE IInterferon-alpha (leukocyte interf

10、eron, about 20 related proteins)- leukocytes, etcInterferon-beta (fibroblast interferon)- fibroblasts, epithelial cells, etcTYPE IIInterferon-gamma (immune interferon)- certain activated T-cells, NK cells,21,INDUC

11、TION OF INTERFERON,interferon-alpha and interferon-beta- viral infection (especially RNA viruses), double stranded RNA, certain bacterial components- strong anti-viral propertiesinterferon-gamma - antigens, mitogenic

12、 stimulation lymphocytes,22,INTERFERON,induce various proteins in target cellsmany consequences, not all fully understood,23,INTERFERON-ALPHA AND INTERFERON-BETA,24,interferon-alpha, interferon-beta,,interferon recepto

13、r,,,,,induction of 2’5’oligo A synthase,induction of aprotein kinase,,2’5’oligo A,induction of ribonuclease L,activated ribonuclease L,,ATP,,ds RNA,,ds RNA,activatedprotein kinase,activated2’5’oligo A synthase,,,AT

14、P,2’5’oligo A,,mRNA degraded,phosphorylated initiation factor (eIF-2),,inhibition of protein synthesis,25,interferons,only made when needed,26,OTHER EFFECTS OF INTERFERONS,ALL TYPESINCREASE MHC I EXPRESSIONCYTOTOXIC T-

15、CELLSACTIVATE NK CELLSCAN KILL VIRALLY INFECTED CELLS,27,OTHER EFFECTS OF INTERFERONS,INTERFERON-GAMMAINCREASES MHC II EXPRESSION ON APCHELPER T-CELLSINCREASES ANTIVIRAL POTENTIAL OF MACROPHAGES INTRINSICEXTRINSIC

16、,28,THERAPEUTIC USES OF INTERFERONS,ANTI-VIRAL e.g. interferon-alpha is currently approved for certain cases of acute and chronic HCV and chronic HBVMACROPHAGE ACTIVATIONinterferon-gamma has been tried for e.g. leprom

17、atous leprosy, leishmaniasis, toxoplasmosisANTI-TUMORhave been used in e.g. melanoma, Kaposi’s sarcoma, CMLMULTIPLE SCLEROSISinterferon-beta,29,Viral response to host immune system,Viruses may :block interferon bin

18、dinginhibit function of interferon-induced proteinsinhibit NK functioninterfere with MHC I or MHC II expressionblock complement activationinhibit apoptosisetc!,30,SIDE EFFECTS OF INTERFERONS,FEVERMALAISEFAT

19、IGUEMUSCLE PAINS,31,BACK TO INFLUENZA,32,PROTECTION AGAINST RE-INFECTION,IgG and IgAIgG less efficient but lasts longerantibodies to both HA and NA importantantibody to HA more important (can neutralize),33,SYMPTOM

20、S,FEVERHEADACHEMYALGIACOUGHRHINITISOCULAR SYMPTOMS,34,CLINICAL FINDINGS,SEVERITYVERY YOUNGELDERLYIMMUNO-COMPROMISEDHEART OR LUNG DISEASE,35,PULMONARY COMPLICATIONS,CROUP (YOUNG CHILDREN)PRIMARY INFLUENZA VIRUS

21、PNEUMONIASECONDARY BACTERIAL INFECTIONStreptococcus pneumoniaeStaphlyococcus aureusHemophilus influenzae,36,NON-PULMONARY COMPLICATIONS,myositis (rare, > in children, > with type B)cardiac complicationsrecent

22、 studies report encephalopathystudies of patients <21 yrs in Michigan - 8 cases seen last seasonliver and CNSReye syndromeperipheral nervous systemGuillian-Barré syndrome,37,Reye’s syndrome,liver - fatty dep

23、ositsbrain - edemavomiting, lethargy, comarisk factorsyouthcertain viral infections (influenza, chicken pox)aspirin,38,NON-PULMONARY COMPLICATIONS,myositis (rare, > in children, > in type B)cardiac complicat

24、ionsencephalopathyliver and CNSReye’s syndromeperipheral nervous systemGuillian-Barré syndrome,39,Guillian-Barré syndrome,1976/77 swine flu vaccine35,000,000 doses354 cases of GBS 28 GBS-associated dea

25、thsrecent vaccines much lower risk,40,MORTALITY,MAJOR CAUSES OF INFLUENZA VIRUS- ASSOCIATED DEATHBACTERIAL PNEUMONIACARDIAC FAILURE90% OF DEATHS IN THOSE OVER 65 YEARS OF AGE,41,DIAGNOSIS,ISOLATIONNOSE, THROAT SWA

26、BTISSUE CULTURE OR EGGSSEROLOGYRAPID TESTS provisional - clinical picture + outbreak,42,HA protein - attachment, fusion,,,,43,,,,,NA protein - neuraminidase,,,,,,,44,ANTIGENIC DRIFT,HA and NA accumulate mutationsRN

27、A virusimmune response no longer protects fullysporadic outbreaks, limited epidemics,45,ANTIGENIC SHIFT,“new” HA or NA proteinspre-existing antibodies do not protectmay get pandemics,46,INFLUENZA A PANDEMICS,Ryan

28、 et al., in Sherris Medical Microbiology,47,where do “new” HA and NA come from?,13 types HA 9 types NAall circulate in birdspigsavian and human,48,where do “new” HA and NA come from?,,,,49,why do we not have influen

29、za B pandemics?,so far no shifts have been recordedno animal reservoir known,50,SURVEILLANCE,CDC/Katherine Lord,51,actual percentage of deaths,,(CDC MMWR 2003 / Vol. 52 / No. RR-8),52,,,,,,,53,VACCINE,‘BEST GUESS’ OF MA

30、IN ANTIGENIC TYPESCURRENTLYtype A - H1N1type A - H3N2type Beach year choose which variant of each subtype is the best to use for optimal protection,54,VACCINE,inactivatedegg grownsub-unit vaccine for childrenrea

31、ssortant live vaccine approved 2003for healthy persons (those not at risk for complications from influenza infection) ages 5-49 years,55,CDC,56,RECOMMENDATIONS,Persons at High Risk for Influenza-Related Complications&

32、#183; $ 65 years· residents of nursing homes and other chronic-care facilities · adults/children who have chronic pulmonary or cardiovascular disorders, including asthma· adults/children who have re

33、quired regular medical follow-up or hospitalization during the last year because of chronic metabolic diseases (including diabetes mellitus), renal dysfunction, hemoglobinopathies, or immunosuppression (including immuno

34、suppression caused by medications),57,RECOMMENDATIONS,Persons at High Risk for Influenza-Related Complications · children and teenagers (6 mths to 18 yrs) receiving long-term aspirin therapy - might be at risk for

35、 developing Reye syndrome after influenza · women who will be in the 2nd or 3rd trimester of pregnancy during the influenza season.,58,RECOMMENDATIONS,Persons aged 50-64 years increased prevalence of high-risk

36、conditionsfrom public health point of view, easier to target by age than by high-risk condition (which may not have been discovered),59,RECOMMENDATIONS,Persons Who Can Transmit Influenza to Those at High RiskPerso

37、ns who are clinically or subclinically infected can transmit influenza virus to persons at high risk for complications from influenza.,60,RECOMMENDATIONS,· physicians, nurses, and other personnel in both hospital an

38、d outpatient-care settings· employees of nursing homes and chronic-care facilities who have contact with patients or residents· employees of assisted living and other residences for persons in high-risk gr

39、oups· persons who provide home care to persons in high-risk groups · household members (including children) of persons in high-risk groups.,61,RECOMMENDATIONS,Children from 0-23 mths are at increased risk f

40、or hospitalization from influenza, vaccination is encouraged for their household contacts and out-of-home caretakers, particularly for contacts of children aged 0–5 months because influenza vaccines have not been approve

41、d for use among children aged <6 months.,62,RECOMMENDATIONS,others, including travellers and the general population may wish to be vaccinated,63,PREVENTION - DRUGS,RIMANTADINE (M2)type A onlyAMANTADINE (M2)ty

42、pe A onlyZANAMIVIR (NA)types A and B, not yet approved for preventionOSELTAMIVIR (NA)types A and B,64,TREATMENT - DRUGS,RIMANTADINE (M2)type A only, needs to be given earlyAMANTADINE (M2)type A only, need

43、s to be given earlyZANAMIVIR (NA)types A and B, needs to be given earlyOSELTAMIVIR (NA)types A and B, needs to be given early,65,,,,,NA protein - neuraminidase,,,,,,,.,.,.,.,.,.,.,.,.,.,.,.,.,.,.,.,.,.,.,66,OTHER

44、TREATMENT,REST, LIQUIDS, ANTI-FEBRILE AGENTS (NO ASPIRIN FOR AGES 6MTHS-18YRS)BE AWARE OF COMPLICATIONS AND TREAT APPROPRIATELY,67,TYPE A++++yesyesyesshift, driftyessensitivesensitive2,severity of illnessani

45、mal reservoirhuman pandemicshuman epidemicsantigenic changessegmented genomeamantadine, rimantidinezanamivirsurface glycoproteins,TYPE B++nonoyesdriftyesno effectsensitive2,TYPE C+nonono (sporadic)