《传染病学教学课件》8、、hiv.ppt

Acquired Immune Deficiency syndrome(AIDS)THE SECOND AFFILIATED HOSPITAL,CQUMSZHOU ZHI周周 智智Definition bbAIDS is a fatal chronic infectious disease caused by the Human Immunodeficiency Virus(HIV),transmitted mainly through sexual contacts and body fluids,characterized pathologically by selective depletion of helper T(CD4+)lymphocytes and impairment of cell-mediated immunity,and clinically by severe opportunistic infections and malignancies.bb Classification:HIV-1 and HIV-2,belong to family Retroviridae,subfamily Lentivirus,and were discovered in 1983 and 1985,respectively.Etiology吸附吸附脱衣壳脱衣壳逆转录逆转录环化环化前病毒前病毒,整合整合转录转录,翻译翻译核心颗粒装配核心颗粒装配出芽出芽HIV动态感染过程动态感染过程The replication cycle of HIV HIV genomeHIV genomeNine genes,3 structure genes,3 regulatory genes Nine genes,3 structure genes,3 regulatory genes and 3 unknown function genes.and 3 unknown function genes.bb(l)(l)GAG GAG(group(group antigen)antigen)gene gene encodes encodes main main core protein p24;core protein p24;bb(2)(2)pol pol(polymerase)(polymerase)gene gene encodes encodes reverse reverse transcriptase;transcriptase;bb(3)(3)ENV ENV gene gene encodes encodes surface surface proteins proteins gp gp 120 120 and gp 41and gp 41.Tropism:bbHigh affinity of the viral gp 120 envelope protein for the CD4 molecule (receptor),which is normally on the surface of helper T lymphocytes,10%-20%of blood monocytes and macrophages,5%of B cells,neuroglia,neurons of central nervous system,Langerhans cells in skin and colorectal epithelial cells are also know to express small amounts of CD4 on their surfaces.Initial ReportsbbJune 5,1981:5 cases of PCP in gay men from UCLA(MMWR)bbJuly 3,1981:26 additional casesbbDec 10,1981:3 NEJM papers describe casesGottlieb MS NEJM 2001;344:1788-91Other Early Developments 1bb1982:1982:Term“AIDS”coinedTerm“AIDS”coined First cases in women reportedFirst cases in women reported First transfusion and vertically transmitted cases reportedFirst transfusion and vertically transmitted cases reported1983:1983:Isolation of a retrovirus from a patient with AIDS by Isolation of a retrovirus from a patient with AIDS by Montagniers groupMontagniers groupbb1984:1984:Detection of HTLV-III in pts with and at risk for AIDS(Gallo)Detection of HTLV-III in pts with and at risk for AIDS(Gallo)Sepkowitz K NEJM 2001;344:1764-72Source:National AIDS case surveillance data,CDCMonths after OI diagnosis0.20.40.60.81.001981-1987Proportion surviving1030405060200Other Early Developments 2bb1985:1985:FDA approves first FDA approves first commercial HIV commercial HIV antibody testantibody testbb1986:1986:NIH establishes the NIH establishes the AIDS Clinical Trials AIDS Clinical Trials GroupGroupbb1987:1987:AZT=first AZT=first antiretroviral approved antiretroviral approved by FDAby FDAEpidemiologyEpidemiologybbFirst case repoted in mid-1981 from USAFirst case repoted in mid-1981 from USA；bb8080，000000，000 Infected person all over the 000 Infected person all over the wordword；bbOver 24,800,000 AIDS patients diedOver 24,800,000 AIDS patients died；bbNewly Increased 50,000,000 per year,16000 Newly Increased 50,000,000 per year,16000 patients every day,11 cases every minute.patients every day,11 cases every minute.bbAfrica AmericaAsiaEuropeAfrica AmericaAsiaEurope；bbAt least 1,000,000 infected person in China.At least 1,000,000 infected person in China.Estimated number of people newly infected with HIV globally,19902007 HIV epidemic in China bbSince the first case was reported in mid-1981 from U.S.A.,over 150 nations in the world reported AIDS.AIDS was first reported in Beijing,China,in 1985.Since then the HIV epidemic has become more visible in China.The cases reported are increasing every year and have spread throughout the country.Four phases of the HIV epidemic in ChinabbFirst phase(1985First phase(1985 1988)was marked by a small 1988)was marked by a small number of AIDS cases in coastal cities.number of AIDS cases in coastal cities.bSecond phase(1989 1993)identification of HIV infection in 146 drug users in southwestern Yunnan Province.bbThird Third phase phase(1994(1994 2000)2000)HIV HIV infection infection had had been been reported reported in in all all 31 31 provinces,provinces,regions,regions,and and municipalities.municipalities.HIV HIV infection infection had had been been reported reported in in all all 31 provinces,regions,and municipalities.31 provinces,regions,and municipalities.bbFourth Fourth phase phase(2001(2001 )the the silence silence surrounding surrounding HIV HIV in in China was beginning to end.China was beginning to end.bb20142014年年1212月月0101日国家卫计委在线访谈透日国家卫计委在线访谈透露，云南、广西、四川三个省份的感染露，云南、广西、四川三个省份的感染者和病人占全国的者和病人占全国的45%45%。bb20142014年年1-101-10月新报告的艾滋病病毒感染月新报告的艾滋病病毒感染者和病人数量上，四川省增加最多，有者和病人数量上，四川省增加最多，有1 1万余例；其次是云南万余例；其次是云南96019601例；而广东、例；而广东、广西新报告数亦都超过广西新报告数亦都超过50005000例。例。EpidemiologyEpidemiology Sources of infectionbbpatientpatientbbNon-symptom carriersNon-symptom carriersHIV exists in Blood Blood saliva salivasemen tearsemen tearVaginal discharges milkVaginal discharges milk HIV in Body FluidsHIV in Body FluidsSemen11,000Vaginal Fluid7,000Blood18,000Amniotic Fluid4,000Saliva1Average number of HIV particles in 1 ml of these body fluidsRoutes of Transmission of HIVRoutes of Transmission of HIVSexual Contact:Sexual Contact:Male-to-maleMale-to-maleMale-to-female or vice versaMale-to-female or vice versaFemale-to-femaleFemale-to-femaleBlood Exposure:Blood Exposure:Injecting drug use/needle sharingInjecting drug use/needle sharing Occupational exposureOccupational exposure Transfusion of blood productsTransfusion of blood productsPerinatal:Perinatal:Transmission from mom to babyTransmission from mom to babyBreastfeedingBreastfeedingEpidemiologyEpidemiology High risk groups bbMale homosexuals,sexual provision including prostitution,i.v.drug addicts and hemophiliacs repeated use serum products.PathogenesisPathogenesisbbCD4+T lymphocyte and other CD4+cells CD4+T lymphocyte and other CD4+cells are largely damaged by HIV in direct and are largely damaged by HIV in direct and indirect way,and lead to dysfunction and indirect way,and lead to dysfunction and deficiency in cell-mediated immune deficiency in cell-mediated immune response.response.Clinical manifestationClinical manifestation Incubation period2-10 yearsbAcute HIV infection bAsymptomatic HIV infection bPersistent generalized lymphadenopathy b(PGL)b AIDS Stage 1-PrimarybbShort,flu-like illness-occurs one to six weeks after infectionbb no symptoms at allbb Infected person can infect other peopleStage 2-AsymptomaticbbLasts for an average of ten years bbThis stage is free from symptomsbbThere may be swollen glandsbbThe level of HIV in the blood drops to very low levels bbHIV antibodies are detectable in the bloodStage 3-SymptomaticbbThe symptoms are mildbbThe immune system deteriorates bbemergence of opportunistic infections and cancersStage 4-HIV AIDSbbThe immune system weakensbbThe illnesses become more severe leading to an AIDS diagnosisClinical manifestation Clinical manifestation AIDSAIDSconstitutional symptoms:Fever,malaise,anorexia,diarrhea,loss of body weight etc.also known as AIDS related complex(ARC).Central nervous system symptoms:Headache,epilepsy,progressive dementia,paraplegia etc etc bSevere opportunistic infections:Pneumocystic Carinii Pneumonia(PCP),Cryptococcal meningitis,pulmonary tuberculosis,Candidiasis,cryptosporidiosis,Histoplasmosis,etcbbOpportunistic malignancies:Kaposi sarcoma,non-Hodgkin lymphoma etc.bbOther disorders associated with severe immune suppression:Chronic lymphoid interstitial pneumonia etc.Figure 9-22Clinical ManifestationsClinical ManifestationsbbWasting syndromeWasting syndromebbKaposis sarcomaKaposis sarcomaKaposis sarcoma in a patient with AIDS Clinical ManifestationClinical ManifestationbbHerpes zosterHerpes zosterbbMamillaMamillabbCryptozoiteCryptozoitebsporotrichosisClinical manifestation in various systems 1 11.Respiratory system1.Respiratory system1.Respiratory system1.Respiratory systembbPneumocystic Carinii Pneumonia(PCP),Pneumocystis jiroveci(耶氏肺耶氏肺孢孢子子菌菌)bbLung tuberculosisLung tuberculosisbbCytomegalovirus Cytomegalovirus infection infectionbbFungal pneumoniaFungal pneumoniabbKaposi sarcomaKaposi sarcomaClinical manifestation in various systems 222.Didestive system2.Didestive systembbOral cavity and esophagitisOral cavity and esophagitisbOral cavity hairy leukoplakiabbInfectious diarrheaInfectious diarrheabbCrissum,rectum Crissum,rectum herpesvirus infectionbbHepatic lesionHepatic lesionVarious oral lesions in HIV-infected individuals.A.Thrush Barium swallow of a patient with Candida esophagitis.Clinical manifestation in various systems33 3.Nervous systembbopportunistic infectionsopportunistic infections Cryptococcal meningitis,Cryptococcal meningitis,Etc.Etc.bbOpportunistic maliganencyOpportunistic maliganency primary lymphoma primary lymphomabbHIV direck infectionHIV direck infection dementia dementia syndromesyndromeCentral nervous system toxoplasmosis Central nervous system lymphoma Clinical manifestation in various systems 444.Skin mucous membranebbKaposis sarcomaKaposis sarcomabbMonilia infectionMonilia infectionbherpes pudendalis,cauliflower excrescenceClinical manifestation in various systems 555.Ocular regionbRetinitis(CMV)bb Toxoplasmosis of brain choroiditisbbKaposis sarcomaKaposis sarcomaLaboratory Examination1Laboratory Examination11.Routine examinations:Anemia,leucocytopenia,proteinuria.2.Immunological examinations:T lymphocytopenia,especially CD4+T lymphocytes(healthy T cell levels range from 500 to 1500),decrease in CD4CD8 ratio,less than 1(normal 1.75-2.1).Laboratory Examination2Laboratory Examination2b3.Serological findings:Positive anti-HIV by ELISA and Western blot（anti-gp24,anti-gp120 and anti-gp41,anti-gp64 and anti-gp31）.b4.Plasma HIV RNA Assays:RT-PCR,branched DNA(bDNA)bIsolation VirusDiagnosis1Diagnosis1Criteria Criteria for for adult adult AIDS AIDS patients.patients.Confirmed patients.Confirmed patients HIV infection HIV infection Epidemiolgy,Anti-HIV(+),Epidemiolgy,Anti-HIV(+),WB(+).WB(+).AIDS patients AIDS patientsbbEpidemiology and clinical manifestation.bbAnti-HIV(+),CD4 number 0.2 X109/L or 0.2-0.5X109/L，bbVarious pathogens leading to opportunistic infections or opportunistic malignancies.Diagnosis2Diagnosis22.Suspected patients Epidemiology and clinical manifestation,but anti-HIV(-)HIV(-)；Children from HIV(+)parentsChildren from HIV(+)parents；Body Body weight weight loss loss more more than than 1010，chronic chronic cough cough or or diarrhea diarrhea lasted lasted more more than than one one monthmonth，fever fever more more than than one one monthmonth，generalized generalized lymphadenopathy.lymphadenopathy.Epidemiology,no clear cilinical manifestations,CD4+lymphocytes0.2 109/L,(5)opportunistic infections and opportunistic malignancies,needing to follow anti-HIV。Differential diagnosisbb1.Idiopathic CD4+lymphocytopenia.bb2.Secondary CD4+lymphocytopenia after cancer therapy or resulting from autoimmune diseases.TreatmentTreatmentb1.Antiretroviral therapy When used in combinations,these medications are termed Highly Active Antiretroviral Therapy(HAART).HAART combines three or more anti-HIV medications in a daily regimen,sometimes referred to as a cocktail.bb(1)(1)Nucleoside Nucleoside reverse reverse transcriptase transcriptase inhibitors inhibitors(NRT1):(NRT1):Zidovudine Zidovudine(AZT,(AZT,ZDV),ZDV),Didanosine Didanosine(ddI),(ddI),Zalctabine Zalctabine(ddC),(ddC),Lamivudine(3TC),Lamivudine(3TC),Stavudine(d4T)and AbacavirStavudine(d4T)and Abacavirbb(2)(2)Non-nucleoside Non-nucleoside reverse reverse transcriptase transcriptase inhibitors inhibitors(NNRTI):(NNRTI):Delavirdine,Delavirdine,Nevirapine,Nevirapine,Efavirenz.Efavirenz.bb(3)(3)Protease Protease inhihitors inhihitors(PI):(PI):Saquinavir,Saquinavir,Ritonavir,Indinavir and Nelfinavir.Ritonavir,Indinavir and Nelfinavir.bb(4)(4)Fusion Inhibitors.bb Therapeutic principle:Combination Recommonded regimens:2 NRTIs+1 PI and so on.Indications:patients with CD4+lmyphocyte count 5,000-10,000copies/ml;patients with AIDS.bbSide effects and drug resistance.2.2.2.2.Treatment of complications:Treatment of complications:(1)(1)PCP:PCP:Pentamidine Pentamidine 4 4 mkg mkg im im or or iv iv forl4 forl4 days:days:sulfamethoxazole-trimethoprim sulfamethoxazole-trimethoprim (SMZ-(SMZ-TMP)#3 bid.TMP)#3 bid.(2)(2)Kaposi Kaposi sarcoma:sarcoma:AZT+AZT+interferon;interferon;bleomycin;vinblastine;adriamycin.bleomycin;vinblastine;adriamycin.(3)(3)Cryptosporidiosis Cryptosporidiosis and and histoplasmosis:histoplasmosis:Spiramycin.Spiramycin.(4)(4)Cytomegalovirus Cytomegalovirus(CMV)(CMV)infection:infection:Gancyclovir.Gancyclovir.(5)cryptococcal meningitis:Fluconazole.(5)cryptococcal meningitis:Fluconazole.bb3.Supportive and symptomatic treatments:(1)Blood transfusion to treat anemia.(2)Immunomodulation:Recombinant IL-2(in experiment).HIV Occupational ExposurebReview facility policy and report the incidentbMedical follow-up is necessary to determine the exposure risk and course of treatmentbBaseline and follow-up HIV testingbFour week course of medication initiated one to two hours after exposure bLiver function tests to monitor medication tolerancebExposure precautions practicedPrevention b1.Isolation of patients and concurrent disinfection.b2.Blocking routes of transmission:b(1)Education of the public.b(2)banning of drug addiction and prostitution.bb(3)Strict screening of blood and blood products.bb(4)Popularize disposal syringes and needles.bb(5)Sterilization of medical instruments and facilities used by AIDS patients.bb3.Protection of susceptibles:bb(1)Restrict the marriage with HIV carriers.bb(2)Use of condoms and avoid sexual perversion.bb(3)Vaccination:still at experimental stage.Four ways to protect yourself?bAbstinencebMonogamous RelationshipbProtected SexbSterile needlesAbstinencebbIt is the only 100%effective method of not acquiring HIV/AIDS.bbRefraining from sexual contact:oral,anal,or vaginal.bbRefraining from intravenous drug useMonogamous relationshipbbA mutually monogamous(only one sex partner)A mutually monogamous(only one sex partner)relationship with a person who is not infected relationship with a person who is not infected with HIV with HIV bbHIV testing before intercourse is necessary to HIV testing before intercourse is necessary to prove your partner is not infectedprove your partner is not infectedProtected SexbbUse condoms(female or male)every time you have sex(vaginal or anal)bbAlways use latex or polyurethane condom(not a natural skin condom)bbAlways use a latex barrier during oral sexWhen Using A CondomRemember To:bbMake sure the package is not expiredbbMake sure to check the package for damagesbbDo not open the package with your teeth for risk of tearingbbNever use the condom more than oncebbUse water-based rather than oil-based condomsSterile NeedlesSterile NeedlesbbIf a needle/syringe or cooker is shared,it must be disinfected:Fill the syringe with undiluted bleach and wai