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1、Acquired Immune Deficiency syndrome(AIDS),THE SECOND AFFILIATED HOSPITAL, CQUMS ZHOU ZHI 周 智,Definition,AIDS 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 de
2、pletion of helper T(CD4+) lymphocytes and impairment of cell-mediated immunity, and clinically by severe opportunistic infections and malignancies.,Classification: HIV-1 and HIV-2, belong to family Retroviridae, subfamily Lentivirus, and were discovered in 1983 and 1985, respectively.,Etiology,吸附 脱衣
3、壳 逆转录 环化 前病毒,整合 转录, 翻译 核心颗粒装配 出芽,HIV动态感染过程,The replication cycle of HIV,HIV genome,Nine genes, 3 structure genes , 3 regulatory genes and 3 unknown function genes . (l) GAG (group antigen) gene encodes main core protein p24; (2) pol (polymerase) gene encodes reverse transcriptase; (3) ENV gene encod
4、es surface proteins gp 120 and gp 41.,Tropism:,High 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, Langer
5、hans cells in skin and colorectal epithelial cells are also know to express small amounts of CD4 on their surfaces.,Initial Reports,June 5, 1981: 5 cases of PCP in gay men from UCLA (MMWR) July 3, 1981: 26 additional cases Dec 10, 1981: 3 NEJM papers describe cases,Gottlieb MS NEJM 2001;344:1788-91,
6、Other Early Developments 1,1982: Term “AIDS” coined First cases in women reported First transfusion and vertically transmitted cases reported 1983: Isolation of a retrovirus from a patient with AIDS by Montagniers group 1984: Detection of HTLV-III in pts with and at risk for AIDS (Gallo),Sepkowitz K
7、 NEJM 2001;344:1764-72,Source : National AIDS case surveillance data, CDC,Other Early Developments 2,1985: FDA approves first commercial HIV antibody test 1986: NIH establishes the AIDS Clinical Trials Group 1987: AZT = first antiretroviral approved by FDA,Epidemiology,First case repoted in mid-1981
8、 from USA; 80,000,000 Infected person all over the word; Over 24, 800, 000 AIDS patients died; Newly Increased 50,000,000 per year, 16000 patients every day,11 cases every minute. Africa AmericaAsiaEurope; At least 1,000,000 infected person in China.,Estimated number of people newly infected with HI
9、V globally, 19902007,HIV epidemic in China,Since 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
10、 year and have spread throughout the country.,Four phases of the HIV epidemic in China,First phase (19851988) was marked by a small number of AIDS cases in coastal cities. Second phase (19891993) identification of HIV infection in 146 drug users in southwestern Yunnan Province. Third phase (19942000
11、) HIV infection had been reported in all 31 provinces, regions, and municipalities. HIV infection had been reported in all 31 provinces, regions, and municipalities. Fourth phase (2001) the silence surrounding HIV in China was beginning to end.,2014年12月01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者和病人占全国的45%。 2014
12、年1-10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1万余例;其次是云南9601例;而广东、广西新报告数亦都超过5000例。,Epidemiology Sources of infection,patient Non-symptom carriers HIV exists in Blood saliva semen tear Vaginal discharges milk,HIV in Body Fluids,Semen 11,000,Vaginal Fluid 7,000,Blood 18,000,Amniotic Fluid 4,000,Saliva 1,Average n
13、umber of HIV particles in 1 ml of these body fluids,Routes of Transmission of HIV,Sexual Contact: Male-to-male Male-to-female or vice versa Female-to-female Blood Exposure: Injecting drug use/needle sharing Occupational exposure Transfusion of blood products Perinatal: Transmission from mom to baby
14、Breastfeeding,Epidemiology Routes oftransmisson,(1) Homosexual and heterosexual contact; (2) Injection via i.v. drug addiction, blood and blood products; (3) Mother to child perinatal transmission; (4) Health care workers may be infected by needle stick or by broken skin occasionally.,Epidemiology H
15、igh risk groups,Male homosexuals, sexual provision including prostitution, i.v.drug addicts and hemophiliacs repeated use serum products.,Pathogenesis,CD4+T lymphocyte and other CD4+ cells are largely damaged by HIV in direct and indirect way, and lead to dysfunction and deficiency in cell-mediated
16、immune response .,Clinical manifestation Incubation period2-10 years,Acute HIV infection Asymptomatic HIV infection Persistent generalized lymphadenopathy (PGL) AIDS,Stage 1 - Primary,Short, flu-like illness - occurs one to six weeks after infection no symptoms at all Infected person can infect othe
17、r people,Stage 2 - Asymptomatic,Lasts for an average of ten years This stage is free from symptoms There may be swollen glands The level of HIV in the blood drops to very low levels HIV antibodies are detectable in the blood,Stage 3 - Symptomatic,The symptoms are mild The immune system deteriorates
18、emergence of opportunistic infections and cancers,Stage 4 - HIV AIDS,The immune system weakens The illnesses become more severe leading to an AIDS diagnosis,Clinical manifestation,AIDS constitutional symptoms: Fever, malaise, anorexia, diarrhea, loss of body weight etc. also known as AIDS related co
19、mplex (ARC). Central nervous system symptoms: Headache, epilepsy, progressive dementia, paraplegia etc,Severe opportunistic infections: Pneumocystic Carinii Pneumonia (PCP), Cryptococcal meningitis, pulmonary tuberculosis, Candidiasis, cryptosporidiosis, Histoplasmosis, etc,Opportunistic malignancie
20、s: Kaposi sarcoma, non-Hodgkin lymphoma etc. Other disorders associated with severe immune suppression: Chronic lymphoid interstitial pneumonia etc.,Figure 9-22,Clinical Manifestations,Wasting syndrome,Kaposis sarcoma,Kaposis sarcoma in a patient with AIDS,Clinical Manifestation,Herpes zoster,Mamill
21、a,Cryptozoite,sporotrichosis,Clinical manifestation in various systems 1,1. Respiratory system Pneumocystic Carinii Pneumonia (PCP),Pneumocystis jiroveci(耶氏肺孢子菌) Lung tuberculosis Cytomegalovirus infection Fungal pneumonia Kaposi sarcoma,Clinical manifestation in various systems 2,2. Didestive syste
22、m Oral cavity and esophagitis Oral cavity hairy leukoplakia Infectious diarrhea Crissum, rectum herpesvirus infection Hepatic lesion,Various oral lesions in HIV-infected individuals. A. Thrush,Barium swallow of a patient with Candida esophagitis.,Clinical manifestation in various systems3,3.Nervous
23、system opportunistic infections Cryptococcal meningitis, Etc. Opportunistic maliganency primary lymphoma HIV direck infectiondementia syndrome,Central nervous system toxoplasmosis,Central nervous system lymphoma,Clinical manifestation in various systems 4,4.Skin mucous membrane Kaposis sarcoma Monil
24、ia infection herpes pudendalis, cauliflower excrescence,Clinical manifestation in various systems 5,5.Ocular region Retinitis (CMV) Toxoplasmosis of brain choroiditis Kaposis sarcoma,Laboratory Examination1,1. Routine examinations: Anemia, leucocytopenia, proteinuria. 2.Immunological examinations: T
25、 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 Examination2,3. Serological findings: Positive anti-HIV by ELISA and Western blot(anti-gp24, anti-gp120 and anti-gp41, anti-gp64 and anti-g
26、p31). 4. Plasma HIV RNA Assays: RT-PCR, branched DNA (bDNA) Isolation Virus,Diagnosis1,Criteria for adult AIDS patients. .Confirmed patients HIV infection Epidemiolgy,Anti-HIV(+), WB(+)., AIDS patients Epidemiology and clinical manifestation. Anti-HIV(+), CD4 number 0.2 X109/L or 0.2-0.5X109/L, Vari
27、ous pathogens leading to opportunistic infections or opportunistic malignancies .,Diagnosis2,2.Suspected patients Epidemiology and clinical manifestation, but anti-HIV(-); Children from HIV(+) parents; Body weight loss more than 10,chronic cough or diarrhea lasted more than one month,fever more than
28、 one month,generalized lymphadenopathy.,Epidemiology, no clear cilinical manifestations, CD4+ lymphocytes0.2 109/L, (5)opportunistic infections and opportunistic malignancies, needing to follow anti- HIV。,Differential diagnosis,1. Idiopathic CD4+ lymphocytopenia. 2. Secondary CD4+ lymphocytopenia af
29、ter cancer therapy or resulting from autoimmune diseases.,Treatment,1. 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 “cockta
30、il“.,(1) Nucleoside reverse transcriptase inhibitors (NRT1): Zidovudine (AZT, ZDV), Didanosine (ddI), Zalctabine (ddC), Lamivudine(3TC), Stavudine (d4T) and Abacavir (2) Non-nucleoside reverse transcriptase inhibitors (NNRTI): Delavirdine, Nevirapine, Efavirenz. (3) Protease inhihitors (PI): Saquina
31、vir, Ritonavir, Indinavir and Nelfinavir. (4) Fusion Inhibitors.,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. Side effects and drug resistance.,2. Treatment of complicatio
32、ns: (1) PCP: Pentamidine 4 mkg im or iv forl4 days: sulfamethoxazole-trimethoprim (SMZ-TMP) #3 bid. (2) Kaposi sarcoma: AZT+ interferon; bleomycin; vinblastine; adriamycin. (3) Cryptosporidiosis and histoplasmosis: Spiramycin. (4) Cytomegalovirus (CMV) infection: Gancyclovir. (5) cryptococcal mening
33、itis: Fluconazole.,3. Supportive and symptomatic treatments: (1) Blood transfusion to treat anemia. (2) Immunomodulation: Recombinant IL-2(in experiment).,HIV Occupational Exposure,Review facility policy and report the incident Medical follow-up is necessary to determine the exposure risk and course
34、 of treatment Baseline and follow-up HIV testing Four week course of medication initiated one to two hours after exposure Liver function tests to monitor medication tolerance Exposure precautions practiced,Prevention,1. Isolation of patients and concurrent disinfection. 2. Blocking routes of transmi
35、ssion: (1) Education of the public. (2) banning of drug addiction and prostitution.,(3) Strict screening of blood and blood products. (4) Popularize disposal syringes and needles. (5) Sterilization of medical instruments and facilities used by AIDS patients.,3. Protection of susceptibles: (1) Restri
36、ct the marriage with HIV carriers. (2) Use of condoms and avoid sexual perversion. (3) Vaccination: still at experimental stage.,Four ways to protect yourself?,Abstinence Monogamous Relationship Protected Sex Sterile needles,Abstinence,It is the only 100 % effective method of not acquiring HIV/AIDS.
37、 Refraining from sexual contact: oral, anal, or vaginal. Refraining from intravenous drug use,Monogamous relationship,A mutually monogamous (only one sex partner) relationship with a person who is not infected with HIV HIV testing before intercourse is necessary to prove your partner is not infected
38、,Protected Sex,Use condoms (female or male) every time you have sex (vaginal or anal) Always use latex or polyurethane condom (not a natural skin condom) Always use a latex barrier during oral sex,When Using A Condom Remember To:,Make sure the package is not expired Make sure to check the package fo
39、r damages Do not open the package with your teeth for risk of tearing Never use the condom more than once Use water-based rather than oil-based condoms,Sterile Needles,If a needle/syringe or cooker is shared, it must be disinfected: Fill the syringe with undiluted bleach and wait at least 30 seconds. thoroughly rinse with water Do this between each persons use,Needle Exchange Program,Non-profit Organization, which provides sterile needles in exchange for contaminated ones,ANY QUestions?,
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