《优选整合》人教版高中英语选修6 UNIT 3 A HEALTHY LIFE PERIOD 3 素材(4) .doc
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1、AIDSAcquired immunodeficiency syndrome (AIDS)Classification and external resourcesThe Red ribbon is a symbol for solidarity with HIV-positive people and those living with AIDS.ICD-10B24.ICD-9042DiseasesDB5938MedlinePlus000594eMedicineemerg/253MeSHD000163List of abbreviations used in this articleAIDS
2、: Acquired immune deficiency syndromeHIV: Human immunodeficiency virusCD4+: CD4+ T helper cellsCCR5: Chemokine (C-C motif) receptor 5CDC: Centers for Disease Control and PreventionWHO: World Health OrganizationPCP: Pneumocystis pneumoniaTB: TuberculosisMTCT: Mother-to-child transmissionHAART: Highly
3、 active antiretroviral therapySTI/STD: Sexually transmitted infection/diseaseAcquired immune deficiency syndrome or acquired immunodeficiency syndrome (AIDS) is a disease of the human immune system caused by the human immunodeficiency virus (HIV).123This condition progressively reduces the effective
4、ness of the immune system and leaves individuals susceptible to opportunistic infections and tumors. HIV is transmitted through direct contact of a mucous membrane or the bloodstream with a bodily fluid containing HIV, such as blood, semen, vaginal fluid, preseminal fluid, and breast milk.45This tra
5、nsmission can involve anal, vaginal or oral sex, blood transfusion, contaminated hypodermic needles, exchange between mother and baby during pregnancy, childbirth, or breastfeeding, or other exposure to one of the above bodily fluids.AIDS is now a pandemic.6 In 2007, it was estimated that 33.2millio
6、n people lived with the disease worldwide, and that AIDS had killed an estimated 2.1million people, including 330,000 children.7 Over three-quarters of these deaths occurred in sub-Saharan Africa,7 retarding economic growth and destroying human capital.8Genetic research indicates that HIV originated
7、 in west-central Africa during the late nineteenth or early twentieth century.910 AIDS was first recognized by the U.S. Centers for Disease Control and Prevention in 1981 and its cause, HIV, identified in the early 1980s.11Although treatments for AIDS and HIV can slow the course of the disease, ther
8、e is currently no vaccine or cure. Antiretroviral treatment reduces both the mortality and the morbidity of HIV infection, but these drugs are expensive and routine access to antiretroviral medication is not available in all countries.12 Due to the difficulty in treating HIV infection, preventing in
9、fection is a key aim in controlling the AIDS epidemic, with health organizations promoting safe sex and needle-exchange programmes in attempts to slow the spread of the virus.SymptomsA generalized graph of the relationship between HIV copies (viral load) and CD4 counts over the average course of unt
10、reated HIV infection; any particular individuals disease course may vary considerably. CD4+ T Lymphocyte count (cells/mm) HIV RNA copies per mL of plasmaThe symptoms of AIDS are primarily the result of conditions that do not normally develop in individuals with healthy immune systems. Most of these
11、conditions are infections caused by bacteria, viruses, fungi and parasites that are normally controlled by the elements of the immune system that HIV damages.Opportunistic infections are common in people with AIDS.13 HIV affects nearly every organ system.People with AIDS also have an increased risk
12、of developing various cancers such as Kaposis sarcoma, cervical cancer and cancers of the immune system known as lymphomas. Additionally, people with AIDS often have systemic symptoms of infection like fevers, sweats (particularly at night), swollen glands, chills, weakness, and weight loss.1415 The
13、 specific opportunistic infections that AIDS patients develop depend in part on the prevalence of these infections in the geographic area in which the patient lives.Main symptoms of AIDS.Pulmonary infectionsX-ray of Pneumocystis pneumonia (PCP). There is increased white (opacity) in the lower lungs
14、on both sides, characteristic of PCPPneumocystis pneumonia (originally known as Pneumocystis carinii pneumonia, and still abbreviated as PCP, which now stands for Pneumocystis pneumonia) is relatively rare in healthy, immunocompetent people, but common among HIV-infected individuals. It is caused by
15、 Pneumocystis jirovecii.Before the advent of effective diagnosis, treatment and routine prophylaxis in Western countries, it was a common immediate cause of death. In developing countries, it is still one of the first indications of AIDS in untested individuals, although it does not generally occur
16、unless the CD4 count is less than 200 cells per L of blood.16Tuberculosis (TB) is unique among infections associated with HIV because it is transmissible to immunocompetent people via the respiratory route, is easily treatable once identified, may occur in early-stage HIV disease, and is preventable
17、 with drug therapy. However, multidrug resistance is a potentially serious problem.Even though its incidence has declined because of the use of directly observed therapy and other improved practices in Western countries, this is not the case in developing countries where HIV is most prevalent. In ea
18、rly-stage HIV infection (CD4 count 300 cells per L), TB typically presents as a pulmonary disease. In advanced HIV infection, TB often presents atypically with extrapulmonary (systemic) disease a common feature. Symptoms are usually constitutional and are not localized to one particular site, often
19、affecting bone marrow, bone, urinary and gastrointestinal tracts, liver, regional lymph nodes, and the central nervous system.17Gastrointestinal infectionsEsophagitis is an inflammation of the lining of the lower end of the esophagus (gullet or swallowing tube leading to the stomach). In HIV infecte
20、d individuals, this is normally due to fungal (candidiasis) or viral (herpes simplex-1 or cytomegalovirus) infections. In rare cases, it could be due to mycobacteria.18Unexplained chronic diarrhea in HIV infection is due to many possible causes, including common bacterial (Salmonella, Shigella, List
21、eria or Campylobacter) and parasitic infections; and uncommon opportunistic infections such as cryptosporidiosis, microsporidiosis, Mycobacterium avium complex (MAC) and viruses,19 astrovirus, adenovirus, rotavirus and cytomegalovirus, (the latter as a course of colitis).In some cases, diarrhea may
22、be a side effect of several drugs used to treat HIV, or it may simply accompany HIV infection, particularly during primary HIV infection. It may also be a side effect of antibiotics used to treat bacterial causes of diarrhea (common for Clostridium difficile). In the later stages of HIV infection, d
23、iarrhea is thought to be a reflection of changes in the way the intestinal tract absorbs nutrients, and may be an important component of HIV-related wasting.20Neurological and psychiatric involvementHIV infection may lead to a variety of neuropsychiatric sequelae, either by infection of the now susc
24、eptible nervous system by organisms, or as a direct consequence of the illness itself.Toxoplasmosis is a disease caused by the single-celled parasite called Toxoplasma gondii; it usually infects the brain, causing toxoplasma encephalitis, but it can also infect and cause disease in the eyes and lung
25、s.21 Cryptococcal meningitis is an infection of the meninx (the membrane covering the brain and spinal cord) by the fungus Cryptococcus neoformans. It can cause fevers, headache, fatigue, nausea, and vomiting. Patients may also develop seizures and confusion; left untreated, it can be lethal.Progres
26、sive multifocal leukoencephalopathy (PML) is a demyelinating disease, in which the gradual destruction of the myelin sheath covering the axons of nerve cells impairs the transmission of nerve impulses. It is caused by a virus called JC virus which occurs in 70% of the population in latent form, caus
27、ing disease only when the immune system has been severely weakened, as is the case for AIDS patients. It progresses rapidly, usually causing death within months of diagnosis.22AIDS dementia complex (ADC) is a metabolic encephalopathy induced by HIV infection and fueled by immune activation of HIV in
28、fected brain macrophages and microglia. These cells are productively infected by HIV and secrete neurotoxins of both host and viral origin.23 Specific neurological impairments are manifested by cognitive, behavioral, and motor abnormalities that occur after years of HIV infection and are associated
29、with low CD4+ T cell levels and high plasma viral loads.Prevalence is 1020% in Western countries24 but only 12% of HIV infections in India.2526 This difference is possibly due to the HIV subtype in India. AIDS related mania is sometimes seen in patients with advanced HIV illness; it presents with mo
30、re irritability and cognitive impairment and less euphoria than a manic episode associated with true bipolar disorder. Unlike the latter condition, it may have a more chronic course. This syndrome is less often seen with the advent of multi-drug therapy.Tumors and malignanciesKaposis sarcomaPatients
31、 with HIV infection have substantially increased incidence of several cancers. This is primarily due to co-infection with an oncogenic DNA virus, especially Epstein-Barr virus (EBV), Kaposis sarcoma-associated herpesvirus (KSHV), and human papillomavirus (HPV).2728Kaposis sarcoma (KS) is the most co
32、mmon tumor in HIV-infected patients. The appearance of this tumor in young homosexual men in 1981 was one of the first signals of the AIDS epidemic. Caused by a gammaherpes virus called Kaposis sarcoma-associated herpes virus (KSHV), it often appears as purplish nodules on the skin, but can affect o
33、ther organs, especially the mouth, gastrointestinal tract, and lungs.High-grade B cell lymphomas such as Burkitts lymphoma, Burkitts-like lymphoma, diffuse large B-cell lymphoma (DLBCL), and primary central nervous system lymphoma present more often in HIV-infected patients. These particular cancers
34、 often foreshadow a poor prognosis. In some cases these lymphomas are AIDS-defining. Epstein-Barr virus (EBV) or KSHV cause many of these lymphomas.Cervical cancer in HIV-infected women is considered AIDS-defining. It is caused by human papillomavirus (HPV).29In addition to the AIDS-defining tumors
35、listed above, HIV-infected patients are at increased risk of certain other tumors, such as Hodgkins disease and anal and rectal carcinomas. However, the incidence of many common tumors, such as breast cancer or colon cancer, does not increase in HIV-infected patients. In areas where HAART is extensi
36、vely used to treat AIDS, the incidence of many AIDS-related malignancies has decreased, but at the same time malignant cancers overall have become the most common cause of death of HIV-infected patients.30Other opportunistic infectionsAIDS patients often develop opportunistic infections that present
37、 with non-specific symptoms, especially low-grade fevers and weight loss. These include infection with Mycobacterium avium-intracellulare and cytomegalovirus (CMV). CMV can cause colitis, as described above, and CMV retinitis can cause blindness.Penicilliosis due to Penicillium marneffei is now the
38、third most common opportunistic infection (after extrapulmonary tuberculosis and cryptococcosis) in HIV-positive individuals within the endemic area of Southeast Asia.31CauseFor more details on this topic, see HIV.Scanning electron micrograph of HIV-1, colored green, budding from a cultured lymphocy
39、te.AIDS is the most severe acceleration of infection with HIV. HIV is a retrovirus that primarily infects vital organs of the human immune system such as CD4+ T cells (a subset of T cells), macrophages and dendritic cells. It directly and indirectly destroys CD4+ T cells.32Once HIV has killed so man
40、y CD4+ T cells that there are fewer than 200 of these cells per microliter (L) of blood, cellular immunity is lost. Acute HIV infection progresses over time to clinical latent HIV infection and then to early symptomatic HIV infection and later to AIDS, which is identified either on the basis of the
41、amount of CD4+ T cells remaining in the blood, and/or the presence of certain infections, as noted above.33In the absence of antiretroviral therapy, the median time of progression from HIV infection to AIDS is nine to ten years, and the median survival time after developing AIDS is only 9.2 months.3
42、4 However, the rate of clinical disease progression varies widely between individuals, from two weeks up to 20years.Many factors affect the rate of progression. These include factors that influence the bodys ability to defend against HIV such as the infected persons general immune function.3536 Olde
43、r people have weaker immune systems, and therefore have a greater risk of rapid disease progression than younger people.Poor access to health care and the existence of coexisting infections such as tuberculosis also may predispose people to faster disease progression.343738 The infected persons gene
44、tic inheritance plays an important role and some people are resistant to certain strains of HIV. An example of this is people with the homozygous CCR5-32 variation are resistant to infection with certain strains of HIV.39 HIV is genetically variable and exists as different strains, which cause diffe
45、rent rates of clinical disease progression.404142Sexual transmissionSexual transmission occurs with the contact between sexual secretions of one person with the rectal, genital or oral mucous membranes of another. Unprotected receptive sexual acts are riskier than unprotected insertive sexual acts,
46、and the risk for transmitting HIV through unprotected anal intercourse is greater than the risk from vaginal intercourse or oral sex.However, oral sex is not entirely safe, as HIV can be transmitted through both insertive and receptive oral sex.4344 Sexual assault greatly increases the risk of HIV t
47、ransmission as condoms are rarely employed and physical trauma to the vagina occurs frequently, facilitating the transmission of HIV.45Other sexually transmitted infections (STI) increase the risk of HIV transmission and infection, because they cause the disruption of the normal epithelial barrier b
48、y genital ulceration and/or microulceration; and by accumulation of pools of HIV-susceptible or HIV-infected cells (lymphocytes and macrophages) in semen and vaginal secretions. Epidemiological studies from sub-Saharan Africa, Europe and North America suggest that genital ulcers, such as those cause
49、d by syphilis and/or chancroid, increase the risk of becoming infected with HIV by about fourfold. There is also a significant although lesser increase in risk from STIs such as gonorrhea, chlamydia and trichomoniasis, which all cause local accumulations of lymphocytes and macrophages.46Transmission
50、 of HIV depends on the infectiousness of the index case and the susceptibility of the uninfected partner. Infectivity seems to vary during the course of illness and is not constant between individuals. An undetectable plasma viral load does not necessarily indicate a low viral load in the seminal li
51、quid or genital secretions.However, each 10-fold increase in the level of HIV in the blood is associated with an 81% increased rate of HIV transmission.4647 Women are more susceptible to HIV-1 infection due to hormonal changes, vaginal microbial ecology and physiology, and a higher prevalence of sex
52、ually transmitted diseases.4849People who have been infected with one strain of HIV can still be infected later on in their lives by other, more virulent strains.Infection is unlikely in a single encounter. High rates of infection have been linked to a pattern of overlapping long-term sexual relatio
53、nships. This allows the virus to quickly spread to multiple partners who in turn infect their partners. A pattern of serial monogamy or occasional casual encounters is associated with lower rates of infection.50HIV spreads readily through heterosexual sex in Africa, but less so elsewhere. One possib
54、ility being researched is that schistosomiasis, which affects up to 50 per cent of women in parts of Africa, damages the lining of the vagina.5152Exposure to blood-borne pathogensCDC poster from 1989 highlighting the threat of AIDS associated with drug useThis transmission route is particularly rele
55、vant to intravenous drug users, hemophiliacs and recipients of blood transfusions and blood products. Sharing and reusing syringes contaminated with HIV-infected blood represents a major risk for infection with HIV.Needle sharing is the cause of one third of all new HIV-infections in North America,
56、China, and Eastern Europe. The risk of being infected with HIV from a single prick with a needle that has been used on an HIV-infected person is thought to be about 1 in 150 (see table above). Post-exposure prophylaxis with anti-HIV drugs can further reduce this risk.53This route can also affect peo
57、ple who give and receive tattoos and piercings. Universal precautions are frequently not followed in both sub-Saharan Africa and much of Asia because of both a shortage of supplies and inadequate training.The WHO estimates that approximately 2.5% of all HIV infections in sub-Saharan Africa are trans
58、mitted through unsafe healthcare injections.54 Because of this, the United Nations General Assembly has urged the nations of the world to implement precautions to prevent HIV transmission by health workers.55The risk of transmitting HIV to blood transfusion recipients is extremely low in developed c
59、ountries where improved donor selection and HIV screening is performed. However, according to the WHO, the overwhelming majority of the worlds population does not have access to safe blood and between 5% and 10% of the worlds HIV infections come from transfusion of infected blood and blood products.
60、56Perinatal transmissionThe transmission of the virus from the mother to the child can occur in utero during the last weeks of pregnancy and at childbirth. In the absence of treatment, the transmission rate between a mother and her child during pregnancy, labor and delivery is 25%.However, when the
61、mother takes antiretroviral therapy and gives birth by caesarean section, the rate of transmission is just 1%.57 The risk of infection is influenced by the viral load of the mother at birth, with the higher the viral load, the higher the risk. Breastfeeding also increases the risk of transmission by
62、 about 4%.58MisconceptionsMain article: HIV and AIDS misconceptionsA number of misconceptions have arisen surrounding HIV/AIDS. Three of the most common are that AIDS can spread through casual contact, that sexual intercourse with a virgin will cure AIDS, and that HIV can infect only homosexual men
63、and drug users. Other misconceptions are that any act of anal intercourse between gay men can lead to AIDS infection, and that open discussion of homosexuality and HIV in schools will lead to increased rates of homosexuality and AIDS.59PathophysiologyThis section may require cleanup to meet Wikipedi
64、as quality standards. Please improve this section if you can. (April 2008)The pathophysiology of AIDS is complex, as is the case with all syndromes.60 Ultimately, HIV causes AIDS by depleting CD4+ T helper lymphocytes. This weakens the immune system and allows opportunistic infections. T lymphocytes
65、 are essential to the immune response and without them, the body cannot fight infections or kill cancerous cells. The mechanism of CD4+ T cell depletion differs in the acute and chronic phases.61During the acute phase, HIV-induced cell lysis and killing of infected cells by cytotoxic T cells account
66、s for CD4+ T cell depletion, although apoptosis may also be a factor. During the chronic phase, the consequences of generalized immune activation coupled with the gradual loss of the ability of the immune system to generate new T cells appear to account for the slow decline in CD4+ T cell numbers.Al
67、though the symptoms of immune deficiency characteristic of AIDS do not appear for years after a person is infected, the bulk of CD4+ T cell loss occurs during the first weeks of infection, especially in the intestinal mucosa, which harbors the majority of the lymphocytes found in the body.62 The rea
68、son for the preferential loss of mucosal CD4+ T cells is that a majority of mucosal CD4+ T cells express the CCR5 coreceptor, whereas a small fraction of CD4+ T cells in the bloodstream do so.63HIV seeks out and destroys CCR5 expressing CD4+ cells during acute infection. A vigorous immune response e
69、ventually controls the infection and initiates the clinically latent phase. However, CD4+ T cells in mucosal tissues remain depleted throughout the infection, although enough remain to initially ward off life-threatening infections.Continuous HIV replication results in a state of generalized immune
70、activation persisting throughout the chronic phase.64 Immune activation, which is reflected by the increased activation state of immune cells and release of proinflammatory cytokines, results from the activity of several HIV gene products and the immune response to ongoing HIV replication. Another c
71、ause is the breakdown of the immune surveillance system of the mucosal barrier caused by the depletion of mucosal CD4+ T cells during the acute phase of disease.65This results in the systemic exposure of the immune system to microbial components of the guts normal flora, which in a healthy person is
72、 kept in check by the mucosal immune system. The activation and proliferation of T cells that results from immune activation provides fresh targets for HIV infection. However, direct killing by HIV alone cannot account for the observed depletion of CD4+ T cells since only 0.01-0.10% of CD4+ T cells
73、in the blood are infected.A major cause of CD4+ T cell loss appears to result from their heightened susceptibility to apoptosis when the immune system remains activated. Although new T cells are continuously produced by the thymus to replace the ones lost, the regenerative capacity of the thymus is
74、slowly destroyed by direct infection of its thymocytes by HIV. Eventually, the minimal number of CD4+ T cells necessary to maintain a sufficient immune response is lost, leading to AIDSCells affectedThe virus, entering through which ever route, acts primarily on the following cells:66 Lymphoreticula
75、r system: o CD4+ T-Helper cells o Macrophages o Monocytes o B-lymphocytes Certain endothelial cells Central nervous system: o Microglia of the nervous system o Astrocytes o Oligodendrocytes o Neurones - indirectly by the action of cytokines and the gp-120 The effectThe virus has cytopathic effects b
76、ut how it does it is still not quite clear. It can remain inactive in these cells for long periods, though. This effect is hypothesized to be due to the CD4-gp120 interaction.66 The most prominent effect of the HIV virus is its T-helper cell suppression and lysis. The cell is simply killed off or de
77、ranged to the point of being function-less (they do not respond to foreign antigens). The infected B-cells can not produce enough antibodies either. Thus the immune system collapses leading to the familiar AIDS complications, like infections and neoplasms (vide supra). Infection of the cells of the
78、CNS cause acute aseptic meningitis, subacute encephalitis, vacuolar myelopathy and peripheral neuropathy. Later it leads to even AIDS dementia complex. The CD4-gp120 interaction (see above) is also permissive to other viruses like Cytomegalovirus, Hepatitis virus, Herpes simplex virus, etc. These vi
79、ruses lead to further cell damage i.e. cytopathy. Molecular basisFor details, see: Structure and genome of HIV HIV replication cycle HIV tropism DiagnosisThe diagnosis of AIDS in a person infected with HIV is based on the presence of certain signs or symptoms. Since June 5, 1981, many definitions ha
80、ve been developed for epidemiological surveillance such as the Bangui definition and the 1994 expanded World Health Organization AIDS case definition. However, clinical staging of patients was not an intended use for these systems as they are neither sensitive, nor specific. In developing countries,
81、 the World Health Organization staging system for HIV infection and disease, using clinical and laboratory data, is used and in developed countries, the Centers for Disease Control (CDC) Classification System is used.WHO disease staging systemMain article: WHO Disease Staging System for HIV Infectio
82、n and DiseaseIn 1990, the World Health Organization (WHO) grouped these infections and conditions together by introducing a staging system for patients infected with HIV-1.67 An update took place in September 2005. Most of these conditions are opportunistic infections that are easily treatable in he
83、althy people. Stage I: HIV infection is asymptomatic and not categorized as AIDS Stage II: includes minor mucocutaneous manifestations and recurrent upper respiratory tract infections Stage III: includes unexplained chronic diarrhea for longer than a month, severe bacterial infections and pulmonary
84、tuberculosis Stage IV: includes toxoplasmosis of the brain, candidiasis of the esophagus, trachea, bronchi or lungs and Kaposis sarcoma; these diseases are indicators of AIDS. CDC classification systemMain article: CDC Classification System for HIV InfectionThere are two main definitions for AIDS, b
85、oth produced by the Centers for Disease Control and Prevention (CDC). The older definition is to referring to AIDS using the diseases that were associated with it, for example, lymphadenopathy, the disease after which the discoverers of HIV originally named the virus.6869 In 1993, the CDC expanded t
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