acquired immunodeficiency syndrome
Introduction
Introduction to Acquired Immunodeficiency Syndrome Acquired immunodeficiency syndrome (AIDS), or AIDS, is a serious infectious disease caused by human immunodeficiency virus (HIV). The virus specifically invades and destroys CD4 T lymphocytes (helper T cells), causing impaired cellular immune function. In the early stage of infection, there may be symptoms like flu-like or serum-like symptoms, and then enter a long period of asymptomatic infection, followed by the development of pre-acquired immunodeficiency syndrome, and finally all kinds of serious opportunistic infections and malignant tumors become acquired. Immunodeficiency syndrome. So far, there is no effective prevention and treatment method, and there are few cases of successful treatment, so it is called super cancer. basic knowledge The proportion of illness: this disease is rare, the incidence rate is about 0.0001% - 0.0002% Susceptible people: no special people Mode of transmission: mother-to-child transmission, sexual transmission, blood transmission Complications: sepsis
Cause
Acquired immunodeficiency syndrome
(1) Causes of the disease
Since the United States reported in 1981 that a retrovirus capable of destructive to the human immune system, in 1983, the French Pasteur Institute Montagnier et al first isolated a virus, which was named lymph node disease-associated virus (lymphadenopathy associated). Virus,LAV), in 1984, Gallo et al. isolated a virus from a living tissue of a patient with acquired immunodeficiency syndrome, named as human T lymphocyte virus type III (HTLV-III). In the same year, Levy was isolated and obtained. The immunodeficiency syndrome-associated virus (ARV), which was identified as the same virus, was classified in the retroviral family and subsequently named by the International Classification of Viruses as human immunodeficiency virus (HIV) in July 1986. ), also known as HIV, human immunodeficiency virus is an RNA virus that can be cultured in an in vitro lymphocyte lineage. It belongs to the retroviridae Lentivirus. So far, human immunodeficiency virus has been found to have two types. : Human immunodeficiency virus type 1 (HIV-1) and human immunodeficiency virus type 2 (HIV-2).
1.HIV-1 originates in Central Africa and spreads to Haiti, Europe, North America and the world. It selectively invades CD4 T lymphocytes and mononuclear macrophage subpopulations, and also infects B cells, microglia. And bone marrow stem cells, which are the main strains causing acquired immunodeficiency syndrome.
(1) Morphology and structure of HIV-1: Under the electron microscope, HIV-1 is a round particle with a diameter of about 110 nm. The outer membrane of the virus is composed of two layers of lipids. It is a newly formed virus that sprouts from human cells to extracellular. When formed, both viral protein components and proteins of the host cell membrane, the outer membrane glycoprotein (Env) anchored on the outer membrane is composed of three molecules of globular gp120 and three molecules of backbone gp41, and gp120 is spherically prominent in the virus. In addition to the envelope, gp41 is linked to gp120, and the other end runs through the viral envelope. The envelope is a blunt-conical nucleus, located in the center, the nucleocapsid protein is p24, and the nucleus contains two identical single-stranded viral RNAs. The chain, Mg2-dependent reverse transcriptase, integrase and protease, and a matrix protein P18 between the outer membrane and the nucleocapsid of the virus, see Figure 1.
(2) HIV-1 genome and its function: The HIV-1 virus genome is about 10 kb in length, and each end has an RNA sequence called 1ong terminal repeat (LTR), which is about 634 bp long. LTR contains HIV. The gene-expressed DNA sequence controls the production of new viruses and can be triggered by host cells or HIV proteins. The HIV-1 viral genome also contains three genes, including three structural genes and six regulatory genes (Fig. 2).
The three structural genes are gag, pol and env, and the gag gene (310-1869 bp) encodes a structural protein of the viral core, producing a precursor protein (p55) with a molecular weight of 55×103, which is cleaved into four smaller proteins. Ingredients: P18, P24, P9 and P7, which together constitute the core protein structure of the virus, the pol (1629~4673bp) gene encodes a larger precursor polypeptide, which includes three protein products: protease p13, reverse transcriptase P66/p51 and integrase p31, env (5781-8369 bp) encode a glycopeptide precursor gpl60, which is then cleaved into the outer membrane glycoprotein gpl20 and the transmembrane glycoprotein gp41.
The six regulatory genes are tat, rev, nef, vif, vpr and vpu, which encode some proteins, which control the ability of the virus to infect cells, viral replication and disease, such as: tat (5358 ~ 5635bp) gene encoding molecular weight of 14 a protein of ×103 (p14), which up-regulates the expression of HIV-1 at the transcriptional and post-transcriptional levels, and the rev (4493 to 4542 bp) gene is required for HIV-1 replication, which promotes the transfer of unspliced viral mRNA from the nucleus to Cytoplasm, has a positive regulatory effect on structural proteins, has a negative regulatory effect on regulatory proteins, in the absence of gag and env protein can not be synthesized, vif (4588 ~ 5196bp) encodes a protein with a molecular weight of 23 × 103 (P23), with it In order to produce infectious virions, vpr (5592 ~ 5828bp) encodes a protein with a molecular weight of 15 × 103 (p15), which helps transport the pre-integration complex to the nucleus, with weak reverse transcriptional activation. It promotes viral protein production. The vpu encodes a protein with a molecular weight of 16×103 (p13), which may affect the assembly and release of new viral particles. The nef (49705043 bp) gene encodes a protein with a molecular weight of 27×103 (p27). ), can lower LTR Expression reduces CD4 expression in HIV-1 infected cells and negatively regulates HIV replication.
According to the PCR amplification and sequence determination of viral genes, it has been determined that HIV-1 has 3 groups of 13 subtypes, namely M group A, B, C, D, E, F, G, H, I, J, K. Subtype, O subtype of O group, and N subtype of N group; HIV-2 also has 6 subtypes, namely, A, B, C, D, E, F subtypes, HIV-1 group M virus Globally, O group virus and HIV-2 are mostly confined to certain local areas in Africa. The main epidemic in China is HIV-1 A, B, B' subtype, C, E type 5, and some endemic areas. There are also B/C recombinant strains.
(3) How HIV-1 infects cells and replicates: When free HIV-1 encounters CD4 cells, more than one HIV-1 envelope glycoprotein (gp120) binds tightly to CD4 molecules on the surface of target cells, resulting in The internal structure of gp120 changes, so that gp120 binds to the co-receptor on the surface of the target cell. The receptor is further divided into CC system, such as CCR2, CCR5, etc. and CXC system, such as CXCR4. Usually, gp120 binds to CCR5. Macrophages, which bind to CXCR4 and infect T cells, followed by the fusion of the outer membrane of HIV with the membrane of the target cell membrane with the participation of gp41, and then the core of the virus is injected into the cytoplasm, although CD4 T cells are HIV-infected The main target cells, but other cells of the immune system with or without CD4 molecules can also be infected by HIV. Mononuclear macrophages can hide a large number of viruses and become a storage repository for HIV. Some CD4 T cells are also a An important HIV repository that harbors HIV in a stable, inactive form that activates these cells, causing HIV replication and new virions.
Recent studies have found that HIV-1 infects CD4 and CCR5 macrophages without the aid of dendritic cell-specific HIV-1 binding protein (DC-SIGN), which cannot be completed. DC-SIGN is a molecular weight of 44. The surface protein of dendritic cells (DC) of ×103, after HIV-1 invades the human body, first infects DC, which is accomplished by the specific binding of gpl20 to DC-SIGN, and then the virus is swallowed by DC. In the cell, DC processes the foreign viral antigen and presents the antigen information to the T cell to stimulate the antiviral immune response. At the same time, during the antigen presentation process, the DC directly contacts the T cell and also transmits the virus to the virus. T cells, causing infection of T cells.
In the cytoplasm, HIV RNA is transcribed into a single-stranded DNA under the action of reverse transcriptase, and the single-stranded DNA is used as a template to replicate the second DNA strand under the action of DNA polymerase. This double-stranded DNA can be used. The free form remains in the cytoplasm and is transcribed into HIV RNA; it can move into the nucleus, and can also integrate into the host's genomic DNA via HIV integrase to form a "proviral" that persists in the nucleus for a long time. Under certain conditions, the "pre-virus" generates HIV RNA and mRNA by transcription and is transferred to the cytoplasm. HIV mRNA is translated to produce new HIV reverse transcriptase, genomic RNA, structural protein, regulatory protein, envelope sugar. Proteins, etc., and assembled into new virions, erupted out of the cell in a sprouting manner.
The HIV-1 provirus covalently integrated into the host cell's chromosome has become part of the host genome, which replicates with the host cell DNA and is inherited to the daughter cells, so the integrated provirus is permanently synthesized into the host cell genome. Or secretive transcription, or high-level expression of its genes, resulting in a large number of progeny viruses.
2. HIV-2 is another retrovirus that causes acquired immunodeficiency syndrome isolated from West African patients in the mid-1980s, mainly limited to West Africa, but now in the United States, Europe, South Africa, India. There are cases of HIV-2 infection in other countries and regions. There are also a few cases in China. Recently, HIV-2 has different plant differences. The ultrastructure and cellular tropism of HIV-2 is similar to that of HIV-1. In contrast, HIV-2 is similar to simian immunodeficiency virus (Muum immunodeficiency virus) SIV, and has a large difference in structural protein from HIV-1, especially the outer membrane protein, whose nucleotide and amino acid sequences are significantly higher than that of HIV-1. Different, only 40% to 50% are similar to HIV-1, while 75% are similar to some SIV. The HIV-2 genome also has three structural genes, gag, env and pol, and may also have tat, rev, nef, vif and vpr. The gene (Fig. 2) differs in that HIV-2 does not have a vpu gene, but has a vpx gene (viral protein x) in its central region, which is not found in HIV-1. Its function is still unclear, HIV- The antigenic properties of 2 are different from those of HIV-1, and the structural proteins of the two have the strongest cross-reaction, while the outer membrane proteins cross-react. The weakest, like HIV-1, HIV-2 also selectively invades CD4 T lymphocytes, but its virulence is not as strong as HIV-1, and HIV-1 and HIV-2 are not strong in the outside world. Heat sensitive, 56 ° C, 30 min can be inactivated, general disinfectant such as 70% ethanol, 0.2% sodium hypochlorite, 5% ~ 8% formaldehyde solution and 5000 × l0-6 ~ 10000 × l0-6 organic chlorine solution can be extinguished Live virus.
(two) pathogenesis
1. The principle of disease
It is not entirely clear that, according to current research, it may be related to the following mechanisms.
(1) Immune response caused by HIV infection: In the early stage of HIV infection, HIV-sensitized lymphocytes can produce specific cytotoxic T cells (CTL). Cells expressing HIV antigen components can be destroyed by CTL, and HIV can be killed or killed. Clearance; natural killer cells (NK cells) can destroy HIV-expressing cells by the action of antibody-dependent cytotoxic cells (ADCC) mediated by HIV antibodies, so that the immune response can remove HIV from some infected cells in the blood circulation. And limit HIV infection to new cells, making HIV-infected people asymptomatic for a long time.
(2) Immunosuppression caused by HIV infection: HIV has special affinity for CD4 cells (including helper T cells, monocytes and macrophages, etc.), and HIV binds to CD4 molecules on the surface of target cells by means of gp120. With the help of gp41, the cells enter the cell, causing the cells to be infected. After infection, the function of the helper T cells is abnormal or lacking. The production of cytokines such as interleukin (IL-2) is reduced, and the reactivity to alloantigens is reduced. For the decrease of the auxiliary function of B cells, the abnormal number of T cells is mainly due to the decrease in the number of CD4 helper T cells. When the number of CD4 T cells is reduced to 200×106/L or less, opportunistic infection or tumor is prone to occur.
Experiments have confirmed that a small amount of CD4 molecules are expressed on the surface of B cells, and thus may be infected by HIV-1, but more importantly, abnormal B cell function. In the early stage of infection, strong polyclonal B cell activation may occur, which is expressed as IgG. Increased levels of IgA, circulating immune complexes, increased peripheral blood B cells, abnormal antibody response to antigen stimulation and autoimmune phenomena; defects in helper T cell function leading to sustained B cell activation; other viral infections For example, CMV and EBV infection are also one of the factors that cause B cell activation. Mononuclear macrophages can be infected by both surface CD4 molecules. Unlike CD4 T cells, macrophages appear to be cytopathic to HIV. It is more tolerant and acts more as a virus depot. In addition, macrophages play an important role in carrying the virus through the blood-brain barrier to the central nervous system. In the late stage of infection, mononuclear - The antigen presentation function of macrophages is impaired. In AIDS patients, some abnormalities of these cells may be the result of chronic activation of cells in the body, for example, an increase in IL-2 receptor expression. IL-1 secretion, which may be related to chronic activation of various factors such as: the role of the viral protein or a cytokine, or a direct effect of HIV infection and the like.
(3) Reduction of CD4 cells caused by HIV infection: According to current understanding, the mechanism may be as follows.
1 Immunoreactive injury: Because HIV infection is mainly CD4 T cells, when the immune response (including CTL, ADCC, etc.) caused by HIV infection persists or is too strong, it can lead to the reduction and depletion of CD4 T cells.
2 Direct cytopathic effect of HIV: HIV infection can cause cell death through its direct cytopathic effect (CPE). When the HIV-env gene of infected CD4 T cells is highly expressed, it passes through the envelope glycoprotein (gp120). Mediated by gp41), fused with adjacent normal CD4 T cells to form multinucleated giant cells, ie, syncytial somatic cells. Syncytial cells usually die and dissolve within 48 hours after formation, and thymus and peripheral blood T cell precursors may also be due to HIV. Infection does not proliferate and replenish mature T cell populations.
3 Apoptosis: A large number of studies have confirmed that both HIV and its products can induce apoptosis, gp120/gp41 can increase the apoptotic rate of activated CD4 T cells, and envelope proteins induce T cell apoptosis through CD4 receptor signaling. Death, signaling through the co-receptor CXCR4 can also induce apoptosis, which may be triggered by p38-dependent signaling.
4 Superantigen effect: It is speculated that a viral protein may stimulate and eventually deplete CD4 T cells with specific T cell receptors.
5 Innocent injury: Free gp120 binds to CD4 molecules on the surface of uninfected CD4 T cells, causing them to be attacked by immune and innocent.
6 produces reduced thymic function loss caused by HIV-infected hematopoietic stem cells or HIV infection, resulting in decreased production of CD4 T cells.
(4) Effects of HIV antigen variation and virulence variation: Since the provirus integrated in the host cell chromosome needs to be transcribed and translated by means of the transcription and translation system of the host cell, the progeny virus is highly susceptible to mutation, especially the virus. In the outer membrane area, due to the rapid replication rate of HIV-1, about 1010~1012 viruses are released into the blood every day. It is estimated that there is 1 mismatch in every 10,000 transcriptions, and about 107 mutant viruses are produced every day. Particles, HIV variants can escape specific body fluids and cellular immune attacks. In addition, the virulence of mutant strains is also changing during infection. Different virulence may affect the progress and severity of the disease. In the early stage of infection, HIV replication is slow. It does not induce syncytium, which is a low-virulence mutant. In the late stage of infection, although it is still asymptomatic, the number of T cells is gradually reduced, and it is seen that the replication is fast, and the highly virulent mutant strain of the syncytium is induced.
(5) The influence of other factors: HIV infection often lurks for many years without developing into AIDS, but it may progress rapidly at a certain time, which may be related to the influence of other factors, such as lymphocytes and mononuclear giants at various stages of infection. The replication of HIV (usually a low virulent strain) can be seen in the phagocytes, but the provirus in the CD4 T cell genome is almost static, thus causing no damage and depletion of T cells, once the body is affected by certain factors. Stimulation, such as drugs, CMV, EBV or other viral infections, lymphocytes and mononuclear-macrophages are activated, the provirus within it begins to transcribe and replicate, causing a large number of cell damage and depletion, in addition, genetic The behavioral, environmental factors can also affect the rate of development of AIDS. For example, some MHC haplotypes may develop AIDS earlier. These MHC-linked gene clusters may be an important factor in the pathogenesis of AIDS.
Therefore, it is speculated that the possible pathogenesis of AIDS is: when an individual is infected with HIV, in the early stage of infection, the body has an excellent immune response to HIV, high virulence, high expression of HIV clones are inhibited or eliminated, and due to infection The number of cells is still small, so there is no significant change in the number of CD4 T cells, but hidden in lymphocytes, HIV variants and integrated proviruses in mononuclear macrophages are not lurked by immune attack, in the future At the same time, due to certain factors, after activation of these cells, the HIV and provirus that are latent in the cell begin to transcribe and replicate, and the HIV strains that produce higher virulence are continuously produced. Under the above-mentioned mechanism of reduction of CD4 T cells, The rapid reduction and depletion of CD4 T cells leads to the collapse of the entire immune system and the rapid development of infected individuals into AIDS patients.
2. Pathology
The pathological changes of acquired immunodeficiency syndrome are diverse and non-specific, mainly manifested by pathological infections, lymph node lesions and central nervous system lesions.
(1) Opportunistic infections and tumors: Repeated overlapping infections of multiple opportunistic pathogens due to severe immunodeficiency, pathogens in the tissues multiply and less inflammatory reactions, common with herpes simplex, herpes zoster and fungal infections Skin mucosal lesions caused by oral Candida albicans infection, Pneumocystis carinii pneumonia caused by Pneumocystis infection, ulcerative colitis lesion caused by cytomegalovirus infection, tuberculosis lesion caused by Mycobacterium infection, etc. Due to severe immunodeficiency, there may be Kaposi's sarcoma, lymphoma or other systemic malignant tumors. These opportunistic infections and tumors may manifest as corresponding histopathological changes.
(2) Lymph node lesions: including reactive lesions and neoplastic lesions
1Reactive lesions: Most of the early stage is follicular proliferative lymphadenopathy, mainly lymphoid follicular hyperplasia, enlargement, fusion, followed by diffuse lymphocytosis, blistering germinal center, large amount of lymph Cell infiltration, which becomes a nest of immunoblasts mixed with lymphocytes, followed by fibrosis of lymph nodes, normal structure disappears, replaced by fiber edema or fibrosis, containing plasma cells, immunoblastic tissue cells, a small number of lymphocytes .
2 neoplastic lesions: including Kaposi's sarcoma and other lymphomas, meaning that the disease has progressed to the stage of acquired immunodeficiency syndrome.
(3) Central nervous system lesions: HIV often invades the central nervous system. The pathological changes are mainly glial cell hyperplasia, focal necrosis, perivascular inflammatory infiltration, syncytium formation and demyelination.
Prevention
Acquired immunodeficiency syndrome prevention
Because acquired immunodeficiency syndrome is mainly through sexual contact, injection route, blood or blood products and perinatal transmission, especially by injecting drug use and sexual transmission, the principle of prevention is to avoid direct contact with HIV-infected people's blood, saliva, Tears, milk, urine, feces, semen and vaginal secretions, etc., the following preventive measures are available for reference.
1. Avoid sexual contact with human immunodeficiency virus
Anal or vaginal intercourse can cause damage to the rectum or vaginal mucosa. Human immunodeficiency virus in semen and vaginal secretions can be transmitted to the other through the broken mucous membrane and strengthen the sexual knowledge related to HIV and AIDS. Health education, self-sufficiency, prevent sexual contact with HIV-infected people, resolutely ban and crack down on prostitution, ugly and other ugly behavior.
2. Prevent the spread of the injection route
It is strictly forbidden to take drugs, especially injecting drugs, strengthening anti-drugs, detoxification work, strengthening poison education, eliminating poisons, not sharing needles, syringes and drugs, using disposable syringes and acupuncture needles to prevent needles or instruments contaminated by HIV.
3. Strengthen blood product management
Strengthen the management of the blood products market. All blood products such as blood and plasma should be collected by blood stations with relevant qualifications for blood collection, testing, blood supply, illegal mining and blood supply. The relevant national law enforcement agencies should resolutely ban underground blood stations and crack down on underground blood. Head, blood tyrant, strict physical examination of blood donors, including HIV antibody testing, high-risk groups should ban the donation of whole blood, plasma, organs, tissues or semen, it is strictly forbidden to import all kinds of blood products from abroad, including whole blood, plasma, Human albumin, gamma globulin, various blood components, etc.
4. Cut off mother-to-child transmission
Female HIV-infected persons, especially those infected with HIV-1, should try to avoid pregnancy to prevent mother-to-child transmission. Since HIV can be transmitted to infants through breastfeeding, HIV-infected lactating women should not be breastfed and replaced with artificial feeding.
5. Strengthen disinfection and isolation measures
For articles or instruments contaminated with blood or body fluids, use effective disinfectant drugs such as freshly prepared sodium hypochlorite or a 1:10 concentration of 500×10-6 to 5000×10-6 (1:10 to 1:100 dilution). Wipe or soak the diluted chlorine-containing lime solution. The used waste products should be disinfected before being treated or incinerated to avoid direct contact with the patient's blood or body fluids. Wear gloves, wear gowns, and be contaminated by blood or body fluids. When thoroughly cleaned and disinfected immediately.
6. Strengthen business training
Personnel for epidemic prevention and medical institutions should be trained in relevant business knowledge, improve their business level, standardize diagnosis and treatment, including the promotion of international standard treatment programs, and develop treatment guidance programs suitable for rural areas in China.
7.HIV vaccine
Studying the effective HIV vaccine may be the hope of eradicating acquired immunodeficiency syndrome, but because of the high mutation rate of HIV gene, the integration of viral genes into human host cells, and the direct invasion of the host's immune system, HIV vaccines are available. The difficulty of development has been greatly increased. Although a lot of manpower and material resources have been invested at home and abroad, long-term research and various vaccine research, such as inactivated vaccine, attenuated vaccine, subunit vaccine, nucleic acid vaccine, neutralizing antibody vaccine, etc., have been carried out. However, there are still no successful vaccines. At present, some mature vaccines abroad are undergoing preclinical or clinical trials, but most of them are subtype B HIV strains, while China is popular with A, B, B' subtypes, C, E. The five types are the main ones, so whether the vaccine developed abroad can be applied to China is still unknown. Therefore, it is extremely important to develop an HIV vaccine based on the epidemic strains in China. However, from the current situation in China, there is still a long way to go.
8. Strengthen monitoring of acquired immunodeficiency syndrome
Due to the economic and cultural development in various parts of China, most people, including a considerable number of medical personnel, lack understanding of acquired immunodeficiency syndrome knowledge; people's sexual attitude changes, casual cohabitation, multiple sexual partners; prostitution, prostitution and other ugly phenomena Flooding; the gradual spread of drug trafficking; the extremely weak medical conditions at the primary level; and the uneven monitoring of medical, health, and epidemic prevention agencies at all levels, etc., have caused the spread of acquired immunodeficiency syndrome in China, HIV in China The infection rate and the incidence of acquired immunodeficiency syndrome have entered a period of rapid growth, and China's population base is huge. Its development trend is likely to have a negative impact on social politics and economic life, thus strengthening China's acquired immunodeficiency. Monitoring the syndrome and perfecting the monitoring network so that the country can accurately grasp the changes in the epidemic situation is very important for the country to formulate corresponding laws and regulations and take timely and effective prevention and control measures.
(1) Implement and strengthen the epidemic reporting system: especially the epidemic situation report of primary health care institutions should be implemented.
(2) Strengthen monitoring of high-risk groups: China's current key monitoring targets include:
1 person who has applied foreign blood products;
2 People who have had sexual relations with foreigners;
3 Chinese students studying abroad, laborers, long-term foreigners and visitors;
4 Foreign foreigners who have been stationed in China for a long time, tourists to China, international students, diplomats, etc.;
5 prostitution, defamation and drug abusers;
6 People who have had close contact with HIV-infected patients and patients with acquired immunodeficiency syndrome.
(3) Strengthening border quarantine: prohibiting entry of HIV-infected persons and patients with acquired immunodeficiency syndrome.
Complication
Acquired immunodeficiency syndrome complications Complications sepsis
Other serious infections, cryptococcal meningitis, various bacterial infections and sepsis.
Symptom
Acquired immunodeficiency syndrome symptoms Common symptoms HIV infection Unexplained fever Fever nausea and vomiting Dysphagia Immune Deficiency Fatigue Depression Swallowing pain Anorexia
The incubation period varies from 2 to 10 years. The clinical manifestations are very complicated. They are mostly related to opportunistic infections or tumors. Usually, at the beginning of HIV infection, there may be a clinical manifestation of acute infection, and then, for a long period of time. There may be no symptoms in the time, or only the lymph nodes in the whole body, and then opportunistic infections and tumors appear as acquired immunodeficiency syndrome, which is clinically divided into four phases, showing a gradual and coherent development process. .
Acute infection
After HIV infection, HIV stimulates the body to cause an immune response. Some patients have transient infectious mononucleosis-like symptoms. The onset is rapid, sweating, headache, sore throat, nausea, anorexia, general malaise, joints. Symptoms such as muscle pain, accompanied by erythematous rash, vomiting, diarrhea, systemic lymphadenopathy or thrombocytopenia, and some acute aseptic meningitis, manifested as headache, neurological symptoms and meningeal irritation.
Peripheral blood examination, the total number of white blood cells is normal, or lymphocytes are reduced, monocytes are increased, and the proportion of CD4/CD8 cells in lymphocyte subsets can be unchanged. This period lasts for one or two weeks, because the symptoms are not characteristic during this period, and It is mild, often misdiagnosed as a cold and neglected. After 2 to 6 weeks of infection, serum HIV antibodies can be positive, and then enter a relatively healthy, asymptomatic infection period.
2. Asymptomatic infection period
In this stage, the infected person can be free of any symptoms except for the serum HIV antibody. The number of T cells can be progressively reduced, but the virus continues to replicate, and the infected person is already infectious. The length of the individual varies greatly. 2 to 10 years, usually 6 to 8 years, which is very difficult for early detection of patients and prevention.
3. Acquired immunodeficiency syndrome
Also known as "persistant generalized lymphadenectasis syndrom (PGLS)", "Acquired Immunodeficiency Syndrome Related Syndrome (ARC)", etc., the outstanding clinical manifestations of this period are persistence Systemic lymphadenopathy, in addition to the inguinal lymph nodes, other parts of the two or more lymph nodes, 1cm in diameter, lasting more than 3 months, no other reasons can be explained in this period, lymph nodes mostly symmetrical, touch The texture is tough, free to move, no tenderness, no response to general treatment, often accompanied by fatigue, fever, general malaise and weight loss, etc., some cases of swollen lymph nodes dissipate after a year, can also re-swell, about 30% Patients may have only superficial lymph nodes, but no other systemic symptoms, some patients have headaches, depression or anxiety, some have sensory nerve ending lesions, and even neuropsychiatric symptoms such as reactive mental disorders may be associated with viral invasion Systematic, some patients have immunodeficiency, in addition to the above superficial lymphadenopathy and systemic disease In addition, various specific or recurrent non-fatal infections occur repeatedly.
In recent years, many scholars have advocated the abolishment of the early stage of acquired immunodeficiency syndrome, and classified lymphadenopathy into the asymptomatic infection period, but some of the systemic manifestations were classified into the stage of acquired immunodeficiency syndrome.
4. Acquired immunodeficiency syndrome
In addition to the characteristics of the pre-acquired immunodeficiency syndrome, there may be significant fever, fatigue, night sweats, uncontrollable weight loss (>10%), persistent diarrhea, persistent fever (>38 °C) for 3 months The above clinical manifestations; and clinical manifestations of severe immunodeficiency, such as: slow cellular immune response, opportunistic infections and malignant tumors, can affect various systems and organs of the body, and often have multiple pathogens (Table 1) causing infection and The tumor coexists.
The clinical manifestations of the main affected system or organ are as follows.
(1) Respiratory system: mainly pneumonia caused by opportunistic infection, Kaposi sarcoma and tuberculosis.
1 Pneumocystosis carinii: Pneumocystis carinii (Pneumocystis) was previously considered to belong to the protozoa, known as Pneumocystis carinii, and is now confirmed to be a fungus based on morphological and molecular genetic analysis. Infection is the most common, accounting for 80% of the lung infection of acquired immunodeficiency syndrome. It is the main cause of death of acquired immunodeficiency syndrome. This disease is interstitial plasma cell pneumonia caused by Pneumocystis. The main pathological changes were diffuse, interstitial and alveolar edema in the lungs. The alveoli were filled with foamy edema and a large number of Pneumocystis, degeneration and necrosis of the alveolar wall, and a large number of lymphocytes and plasma cells infiltrated in the interstitial lung. Clinical manifestations For fever, dry cough, rapid breathing, difficulty breathing, cyanosis, ventilatory dysfunction; X-ray examination showed interstitial pneumonia, symptoms progressively worsened, can die of respiratory failure, sputum, pleural effusion, tracheal lavage Or find the pathogen in the endotracheal biopsy to diagnose the disease.
In addition, cytomegalovirus, Toxoplasma gondii, Cryptococcus, roundworm, Legionella, etc. can also cause pneumonia.
2 Kaposi sarcoma: In patients with acquired immunodeficiency syndrome with extensive skin lesions, the clinically diagnosed pulmonary Kaposi sarcoma is about 20%, the autopsy rate is 50%, but without skin In patients with acquired immunodeficiency syndrome of mucosal damage, pulmonary Kaposi sarcoma is rare, and most patients with this disease have fever, dry cough, and difficulty breathing, but about 40% of patients may not have any such manifestations, large areas. There may be wheezing when the endobronchial damage occurs, and wheezing may occur when the throat is involved. When the damage causes bleeding, there may be hemoptysis, bronchoscopy or endotracheal biopsy can diagnose the disease, and chest X-ray examination can also help diagnose.
3 tuberculosis: tuberculosis in acquired immunodeficiency syndrome is most common in the lungs, in addition to common symptoms such as cough, cough, dyspnea and chest pain, as well as common tuberculosis symptoms such as fever, night sweats, anorexia and weight loss Etc. Sometimes, its clinical manifestations are indistinguishable from Pneumocystis carinii pneumonia or other opportunistic infections, and pathogens and X-ray examinations are needed to differentiate the diagnosis.
(2) central nervous system: the main clinical manifestations are dizziness, headache, progressive dementia, hallucinations, epilepsy, limb paralysis, spastic ataxia, bladder rectal dysfunction and encephalitis, etc., progressive subacute caused by HIV In addition to encephalitis, the most common is cryptococcal meningitis. The clinical manifestations can be found in the relevant chapters. Others include subacute encephalitis caused by cytomegalovirus, toxoplasma encephalitis, roundworm infection, and mycobacterial infection. Brain lymphoma and Kaposi sarcoma, especially the disseminated A. elegans infection is serious, often life-threatening, the diagnosis mainly depends on cerebrospinal fluid examination, head X-ray and CT examination.
(3) Digestive system: About 3/4 of patients with acquired immunodeficiency syndrome may have digestive system diseases, affecting various parts of the gastrointestinal tract, Candida (Candida), cytomegalovirus and herpes virus, etc. Invasion of the oropharynx and esophagus, causing ulcers, clinical manifestations of swallowing pain, dysphagia and burning of the sternum, fiberoptic esophagoscopy can be diagnosed, relatively less stomach involvement, occasionally cellulitis inflammatory gastrin caused by Candida albicans , gastroenteritis caused by cytomegalovirus, Kaposi sarcoma can also invade the stomach, causing the corresponding clinical manifestations, cytomegalovirus, Mycobacterium avium, Mycobacterium tuberculosis and drugs can cause granulomatous hepatitis, acute, chronic hepatitis, Fatty liver and cirrhosis, Kaposi sarcoma and other lymphomas can also invade the liver, various infections and tumors can also invade the pancreas, but the diagnosis is difficult, Cryptosporidium, cytomegalovirus, Mycobacterium avium and card Boqi sarcoma and other violations of the intestine, causing diarrhea and malabsorption syndrome, cytomegalovirus infection caused ulcerative colitis, diarrhea, pus and bloody stools, etc., of which intestinal cryptosporidium infection Common, manifested as chronic persistent diarrhea, water samples can last for several months, easy to cause death, diagnosis depends on fecal examination, X-ray, intestinal fiber microscopy or intestinal mucosal biopsy, rectal anal cancer in male homosexuals It is more common in patients with acquired immunodeficiency syndrome and may be caused by chronic perianal herpes or by infection with papillomavirus during sexual contact.
(4) urinary system: mainly renal damage, the incidence of renal damage in patients with acquired immunodeficiency syndrome is about 20% to 50%, opportunistic infection is one of the main factors causing kidney damage, body fluids and electrolytes caused by infection Abnormalities, sepsis, shock, use of nephrotoxic antibiotics, and malignant tumors can cause kidney damage. Cytomegalovirus and Epstein-Barr virus can cause immune complex nephritis. Pathological changes are focal or diffuse membrane proliferative glomerulonephritis. , acute tubular necrosis, tubular atrophy and focal interstitial nephritis, HIV itself may also cause kidney damage, leading to HIV-related nephropathy, pathological changes are most common with focal segmental glomerulosclerosis, characteristic Changes include glomerular vascular plexus collapse, glomerular visceral epithelial cells significantly swelling and hypertrophy, interstitial edema, fibrosis and inflammatory cell infiltration, tubular microvesicle formation, glomerular endothelial cell tubules under electron microscope Reticulated inclusion bodies, etc., in patients with acquired immunodeficiency syndrome, intravenous drug addicts are more common, heroin and its pollutants as antigens, can cause immunoreactive renal damage, lead Heroin-related nephropathy, its pathological changes are also more common in focal segmental glomerulosclerosis, but the glomerular vascular plexus collapses, renal tubular microvesicles and glomerular endothelial cell tubule corpuscular inclusions are not as good as HIV-related nephropathy is obvious, clinically may have proteinuria, azotemia, or manifested as acute renal failure or uremia, among which heroin-related nephropathy can progress to uremia in six to six years, and HIV-related nephropathy It can develop rapidly to uremia within 2 to 4 months.
(5) Skin mucosal manifestations: Most patients with acquired immunodeficiency syndrome have skin mucosal infections. Common mucosal infections are caused by oral mucosal Candida albicans infection, which is generally asymptomatic and causes severe dysphagia when it affects the pharynx and esophagus. Skin infections include recurrent herpes simplex stomatitis, chronic herpes simplex perianal ulcer, herpes zoster, chickenpox, fungal skin infections and hyperthyroidism, etc., homosexuals may also have perianal condyloma acuminata and contagious soft palate, seborrheic Sexual dermatitis-like lesions often occur in the genitals, scalp, face, ears and chest of the patient. They are characterized by erythema-like, hyperkeratotic scaly plaques, which are often distributed in the face and the cause is unknown.
(6) Blood system: abnormal blood system is more common in patients with acquired immunodeficiency syndrome, including granulocyte and thrombocytopenia, anemia and non-Hodgkin's lymphoma.
(7) Others: Ocular involvement in patients with acquired immunodeficiency syndrome is also common, but it is easily overlooked. Retinitis caused by cytomegalovirus and Toxoplasma infection, Kaposi sarcoma of the eye, etc., HIV itself and opportunity Sexual infections or tumors may also involve the cardiovascular and endocrine systems, but the clinical manifestations are often inconspicuous or mild, and may be related to the clinical manifestations of these systemic lesions that are already dying, some patients often have Unexplained long-term fever, accompanied by weight loss, general malaise and fatigue, etc. In some cases, mycobacterial intracellular infections have been confirmed in bone marrow, lymph node or liver biopsy specimens, and the prognosis may be more than the simple combination of Mycobacterium genus The infection is even worse.
Examine
Examination of acquired immunodeficiency syndrome
Blood routine
Often red blood cells, hemoglobin decreased, mild positive pigment, positive cell anemia, white blood cells often fell below 4.0 × 109 / L, classified neutrophils increased, there is a nuclear left shift phenomenon, a few showed neutropenia, lymph The cells were significantly reduced, <1.0×109/L, and there were plasmacytoid lymphocytes and vacuolar-containing monocytes. The platelets were generally unchanged. Once there was a change, the platelets were significantly reduced.
2. Immunological changes
The changes in the cellular immune system are mainly characterized as follows.
(1) Lymphocyte subsets examination: CD4 T cells decreased, CD4/CD8 ratio decreased, normal human CD4/CD8 ratio was 1.75 to 2.1, and patients with acquired immunodeficiency syndrome often <1.0.
(2) Decreased T cell function: negative for delayed type allergic skin test, when non-specific mitogen stimulation in vitro, lymphocyte transformation is reduced, cytotoxicity of T cells is reduced, and T cells produce interleukin-2 and interferon gamma cut back.
(3) B cell dysfunction: There are different levels of immunoglobulins and immune complexes, and autoantibodies, such as RF, anti-nuclear antibodies and anti-lymphocyte antibodies.
(4) The activity of natural killer cells is decreased.
3.2-microglobulin and neopterin (neopterin)
Determination of serum 2 microglobulin and neopterin by radioimmunoassay (RIA), which are products of activated macrophages, whose elevated serum levels imply immune activation, with absolute counts of CD4 T cells, lymphocytes Percentage, the proportion of CD4/CD8 cells decreased with the same clinical significance, indicating that the disease progressed to acquired immunodeficiency syndrome.
4. Lymph node biopsy
In high-risk areas and high-risk groups of acquired immunodeficiency syndrome, lymph node biopsy is an important measure for lymph node enlargement in areas other than the inguinal region, especially in patients with persistent cervical lymphadenopathy. Lymph node reactivity can be seen. Pathological manifestations such as lesions and neoplastic lesions that have non-specific, but certain diagnostic value, some patients with acquired immunodeficiency syndrome, superficial lymph nodes disappear, difficult to do biopsy.
5. Other
Urinary examination often has proteinuria, and blood creatinine and urea nitrogen can be elevated.
6. Pathogen examination
(1) Etiology of HIV-1:
1 HIV-1 serum antibody detection: including anti-gp120 and anti-P24, most HIV-1 infected patients have positive serum antibody within 3 months, therefore, the determination of serum antibodies is the easiest to determine the presence or absence of HIV infection. Fast and effective methods, commonly used methods are enzyme-linked immunosorbent assay (ELISA), indirect immunofluorescence assay (IFA), radioimmunoassay (RIA), etc., generally used ELISA for initial investigation, the sensitivity is 99.5%, but Because it uses HIV-1 as an antigen for detection and cross-antibodies with lymphocyte antigens, there may be false positives. Therefore, those who are positive for initial detection are confirmed by Western blot (WB).
The nitrocellulose membrane hybridization test has strong specificity and the false positive rate is extremely low. The diagnostic criteria are: if the ELISA is positive twice, and the WB test is positive for any two of the p24, gp41, gp120 or gp160 bands, then Can be confirmed as HIV infection, if there is no two bands positive, it can only be diagnosed as "indeterminate pattern", then the polymerase chain reaction (PCR) can be used to detect its specific viral nucleic acid, or continue to observe closely Repeat the above tests to confirm the diagnosis.
HIV-1P24
HIV-1(RT-PCR)HIV RNA
100%CD4 THIV
(2)HIV-280%HIV- 1HIV-2HIV-1ELISARIBAHIV-2HIV-lHIV-2HIV-2ELISAWBHIV-2HIV-1HIV-2ELISAHIV-1HIV-2HIV-2WBHIV-1WBHIV-1WBHIV-2ELISA
HIV-1HIV-2ELISAHIV-1HIV-1HIV-2HIV-1
X
7. Chest X-ray examination
(Kaposi)
(1)XXXX;;XX
(2)X80%<1cmXCT
8.X
(1)XXXX
(2)X
Diagnosis
diagnosis
;;CD4 TCD4/CD8HIV
Diagnostic criteria
WHOCDCHIVAIDS1996HIVAIDSHIVHIVAIDS
1.HIV
(1)
HIV
HIV/AIDS
HIV
HIV
(2)
(3)
CD4/CD8>1
HIV236
P24
2.HIV
(1)HIV
(2)
(3)
HIV
CD4CD4/CD8>1
P24
3.AIDS
(1)HIV
(2)
>1
(>1cm)
>4/d3>10%
()(CMV)
(3)
HIV
p24()
CD4 0.2×109/L(0.20.5)×109/LCD4/CD8<1
2
Differential diagnosis
1.
2.
3.
