Acquired immune deficiency syndrome (AIDS)

A new disease observed in homosexual persons, characterized by acquired cellular immune deficiency and accompanied by different opportunistic infections and neoplasms was described in the USA in 1979. The disease was termed acquired immune deficiency syndrome (AIDS), later it was given the name HIV infection. The first 13 patients were registered in the USA in 1979. Then the number of the patients increased progressively. According to WHO, in 1990 the cases of the illness and infection were observed in 163 countries of the world. In 1998 the total number of the infected persons was 20 mln.

Hypothesis of AIDS appearance. For the first time human retrovirus of T-lymphotropic type 1 (HTLV-1) was isolated by a group of American scientists headed by Robert Hallo in 1980. Two years later the same scientists isolated HTLV-2 virus causing some forms of hairy-cell leukemia (leukemic endotheliosis), T-cell leukemia and lymphomas. In 1983 French scientists (the group headed by L. Montan) isolated HTLV-3 from the lymphatic node taken from the patient with generalized adenopathy.

Etiology. The causative agent was called HIV (human immune deficiency virus) on the International Conference on AIDS problems (Paris, 1986). The theories of AIDS appearance are discussed widely, they represent different and even opposite views.

The evolution theory has the largest number of supporters. According to it: 1) the virus came from an isolated focus where it existed from ancient times; 2) the virus was transmitted from the host animal to the human being; 3) the virus got the new properties due to mutation.

The theory of artificial HIV selection is also known. The technology to obtain artificial clones of retroviruses has been known since the 1960th. The supporters of this theory insist on beginning of AIDS epidemics because of biological diversion.

In contrast to the above, a group of American scientist believes that HIV is not the causative agent of AIDS. According to their views the virus is a

pathogenic retrovirus persisting in the organism. Its activation is observed when the immunity becomes weak.

Nevertheless, the majority of the researchers believe that AIDS causative agents are HIV-1, -2, -3 belonging to subfamily of Lentivirinae, family of human retroviruses.

High mutation rate is typical for HIV, thus, mutations in its genome are observed 1 mln times more often than in the genome of DNA and RNA viruses.

Epidemiology. The source of HIV is a sick person or a virus carrier. The patients are infective during all the life. Virus-carrying is observed for 8—9 years. The virus can be found in the blood, milk, sperm, saliva, urine, tears.

The main ways of transmission are: 1) sexual; 2) parenteral; 3) transplasentation.

Classification of HIV infection. One of the first classifications was created by Robert Redfield and coauthors in 1984. The criteria for staging of the disease were the indices of T-4 lymphocytes in the blood and their activity as well as the beginning of persistent lymphadenopathy, reactions to specific skin tests and presence of opportunistic diseases.

Clinical picture. Incubative period of HIV-1 at sexual way of infection lasts from 2—3 weeks to 2— 3 months, sometimes 1 year. The early signs of the disease are increase of temperature, cough, nausea, vomiting, diarrhea, presence of antibodies to HIV

infection with simultaneous loss of body mass (20 kg during the last 2—3 years). After that lymphatic nodes of different localization as well as the liver and spleen enlarge, lymphopenia and hypergammaglobulinemia develop. The signs of the disease also depend on the lesion in the definite system, i.e. meningoencephalitis, pneumonia, gastritis, duodenitis, nephritis. Next stage is appearance of oncological diseases or generalized infection.

The signs of suspected AIDS (according to WHO).

1. Prolonged fever of unclear origin.

2. Chronic diarrhea (not less than 2 months).

3. Unexplainable body weight loss (by 10% or more).

4. Pneumonia of unclear origin resistant to standard therapy.

5. Lymphopenia

There are AIDS-indicating diseases (according to WHO).

1. Candidosis of the esophagus, trachea, bronchi, lungs.

2. Extrauterine cryptococcosis.

3. Cryptosporiosis with diarrhea for more than 1 month.

4. Pneumocyst pneumonia.

5. Cytomegalovirus lesion of some organs (except for the liver, spleen, lymphatic nodes in the patients over 1 month).

6. Infection caused by herpes simplex, persisting more than 1 month in the patients aged over 1 month.

7. Toxoplasmosis of the CNS in the patients aged over 1 month.

8. Brain lymphoma in the patients under 60.

9. Kaposi's sarcoma in the patients under 60. Morphology. The morphological and clinical

manifestations of the disease are due to the pathogenetic peculiarities of the virus and its capability to injure CD4 lymphocytes (helpers), monocytes, dendritic cells of the lymphoid organs as well as glial, endothelial cells and fibroblasts of the other systems. HIV enters the structure of the chromosomes of the cell nucleus and provides virus carrying. All target cells express receptor for the virus (CD4 molecule).

In general, pathologic features of AIDS are those characteristic of widespread opportunistic infections, Kaposi's sarcoma, and lymphoid tumors.

Biopsy specimens from enlarged lymph nodes in the early stages of HIV infection reveal marked follicular hyperplasia. The enlarged follicles have irregular, sometimes serrated borders and they are present not only in the cortex but also in the medulla and may even extend outside the capsule. The mantle zones surrounding follicles are markedly attenuated, and hence germinal centers seem to merge with the interfollicular area. These changes, affecting primarily B-cell areas of the node, are the morphologic reflections of the polyclonal B-cell activation and

hypergammaglobulinemia seen in patients with AIDS. In addition to B-cell expansion within germinal centers, activated monocytoid B cells are present within and around the sinusoids and trabecular blood vessels. During the early phase of HIV infection, viral DNA can be found with nuclei of CD4+ T cells located predominantly the follicular mantle zone. With disease progression, the frenzy of B-cell proliferation subsides and gives way to a pattern of severe follicular involution. The follicles are depleted of cells, and the organized network of follicular dendritic cells is disrupted. The germinal centers may even become hyalinised. During this advanced stage, viral burden in the nodes is reduced, in part because of the disruption of the follicular dendritic cells. These «burnt-out» lymph nodes are atrophic and small and may harbor numerous opportunistic pathogens. In the empty-looking lymph nodes and in other organs, the presence of infectious agents may not be readily apparent without the application of special stains.

In later stages of AIDS, spleen and thymus also appear to be «wastelands».

Non-Hodgkin's lymphomas, involving the nodes as well as extranodular sites, such as the liver, gastrointestinal tract, and bone marrow, are primarily high-grade diffuse B-cell neoplasms.

AIDS commonly affects the nervous system. The AIDS dementia complex (HIV cognitive/motor complex) is a clinical syndrome that has elements of

intellectual impairment, and behavioural and motor changes. Several pathologically defined changes underlie this clinical syndrome.

Lymphocytic meningitis is seen in patients around the time of seroconversion and is defined as occurring in the absence of any demonstrable opportunistic pathogens.

HIV encephalitis is a multifocal process characterized by inflammatory foci including multinucleated giant cells, mainly seen in white matter, basal ganglia and brain stem.

HIV leukoencephalopathy is characterized by myelin loss, gliosis, phagocytic macrophages and scattered multinucleate giant cells in white matter. There is little or no inflammatory infiltration.

Diffuse poliodystrophy is the term applied to neuronal loss, microglial activation and gliosis in CNS grey matter.

Vacuolar myelopathy is the term used to describe vacuolation in myelin sheaths, with myelin loss in spinal cord.

Cerebral vasculitis is seen most prominently in childhood HIV disease of the brain.

Methods for HIV diagnosis: 1) Serology study. 2) Bacterio- and virological study. 3) Histological study. Thymus, bone marrow, spleen, lymphatic nodes from different regions, brain from the area of subcortical nuclei and the white substance, spinal cord, lungs, digestive organs, tongue, esophagus, liver, kidneys,

heart, eye retina, testes, oral mucosa, placenta are taken for analysis. 4). Lnmunohistochemical techniques.

Smallpox

As a result of the successful campaign sponsored by the World Health Organization, smallpox (variola) has been eradicated worldwide. Variola infection is limited to humans. There are at least two strains of variola virus; the most virulent causes variola major with a mortality of 20% to 50%. Variola minor, or alastrim, has a mortality of less than 1%. The two strains can be differentiated by their temperature-sensitive growth characteristics on chorioallantoic membrane.

Variola virus is transmitted by close contact and is spread through the air, gaining entrance to the respiratory tract where it multiplies in the epithelium and regional lymph nodes. This first replicative period is followed by viremia with dissemination of the virus to the reticuloendothelial system. There follows a second replicative phase, in which a second viremia spreads to the skin, lymphatics, and internal organs. This secondary viremia marks the beginning of clinical symptoms.

Pathology. Clinically, smallpox is characterized by fever followed a few days later by a centrifugal papular rash that appears first on the face and the skull and spreads to the back, chest, arms, and legs. The

macules become papules, vesicles, and finally pustules. The pustules dry up, forming scabs during the second week of the rash. The clinical disease produced by smallpox has a spectrum of severity that ranges from the very mild to the very severe and often fatal form. WHO describes four clinical types of smallpox: ordinary, modified, flat, and hemorrhagic. The third and fourth are the most severe.

The cutaneous lesions in the papular stage have a diameter of 2 to 4 mm and are partially buried in the skin. Microscopically the cutaneous lesions first show vascular congestion with mononuclear cell infiltrate in the dermis. The epidermal cells show ballooning degeneration with formation of an intraepidermal vesicle. There is involvement of the adnexal elements.

Cells with cytoplasmic inclusion bodies (Guarnieri bodies) can be found in early vesicles and disappear with healing. These inclusion bodies are variable in size, granular, eosinophilic, round to oval, and surrounded by a halo. In fatal cases pneumonia of the interstitial type is often seen. The viral lesions are often obscured by superimposed bacterial infection.

Complications that result from vaccination are postvaccination encephalitis, vaccinia gangrenosa seen in patients with T-cell immune deficiencies, eczema vaccinatum seen in patients with atopic dermatitis, generalized vaccinia, and erythematous urticarial lesions.

Causes of death are intoxication, sepsis, secondary bacterial infections.

Tetanus

Tetanus results from the absorption of the potent exotoxin produced by Clostridium tetani. This free-living saprophyte, widespread in nature, especially in cultivated soil, is commonly found in the feces of cattle and horses and less commonly of humans. It therefore tends to colonize manured areas of cultivation. Once introduced into an area, spores of C. tetani persist almost indefinitely.

Tetanus results from the introduction of spores of C. tetani into tissue, where anaerobic conditions favorable to germination and toxin production may be present. Puncture wounds as from a nail or splinter are particularly dangerous. Tetanus was once a frequent complication of abortion and was also commonly seen in infants as tetanus neonatorum, which resulted from infection of the umbilical stump.

Tetanus toxin is absorbed from the local site of production and is transmitted into the central nervous system along the axons of neurons. Tetanus toxin is a potent neurostimulatory agent. Clinical features of tetanus may appear several weeks or even months after the responsible injury, and in a considerable number of cases no injury can be demonstrated. Symptoms begin with headache, followed shortly by difficulty in swallowing and stiffness of the jaw. Muscle stiffness or spasm may initially be confined to the region of the local infection (local tetanus). Spasm of the muscles

of the trunk may lead to opisthotonos. Contraction of facial muscles produces the characteristic risus sardonicus. Consciousness is undistributed, and perception of pain is undiminished. Death results from inanition or secondary complications such as bronchopneumonia. Specific morphologic changes have not been described.

RICKETTSIOSES

TYPHUS

Epidemic louse-borne typhus fever is one of the classic scourges of mankind. In times of war, famine, and other disasters, louse infestation, crowding, and malnutrition join forces with R. prowazekii to cause explosive epidemics of typhus. It has been postulated that more wars have been lost as a result of epidemic typhus than have been won by battlefield victories. Infections by R. prowazekii occur as a zoonosis with a reservoir in flying squirrels and their fleas and lice.

Organisms of R. prowazekii proliferate in the intestinal epithelial cells of the human louse, are shed in its feces, and eventually kill the louse. After entry through human skin, the pathogenic events of typhus parallel those of Rocky Mountain spotted fever (RMSF) and the other rickettsioses with spread via the bloodstream to skin, brain, and other organs.

In contrast to RMSF, rickettsial infection involves only endothelial cells, and the rash begins on the trunk between days 4 and 8 of illness and spreads centri-fugally to involve the arms and legs. Pathologic lesions comprise disseminated mononuclear vasculitis of skin, typhus nodules of brain, interstitial myocarditis, mild

interstitial pneumonia, perivascular interstitial nephritis, and portal triaditis. The earliest lesion was swelling of endothelial cells parasitized by rickettsiae. Subsequently, leukocytic infiltration of the vessel wall was observed.

Typhus rickettsiae contain a lipopolysaccharide that is relatively nontoxic. The bursting of heavily infected cells is an overt cytolytic effect of R. prowa-zekii infection. The so-called mouse toxin phenomenon is unlikely to be caused by a toxin. Intravenous injection of nonviable typhus rickettsiae does not cause a toxic death in mice. Moreover, no toxin has been identified that produces this phenomenon. Some other mechanism, such as massive rickettsial penetration involving phospholipase activity, may explain the mouse toxicity.

Q FEVER

Q fever refers to the disease caused by Coxiella burnetii. The letter Q is for query, designating the unknown etiology during the early days of recognition the illness. Derrick first described Q fever in 1937 an occupational disease among slaughterhouse work and dairy farmers in Australia. C. burnetii differs remarkably from organisms of genus Rickettsia in its capability to remain infectious under adverse extracellular conditions probably by the formation of spores. It differs also in its cellular location within phagolysosomes where it functions most efficiently

in the acid milieu. In contrast, members of genus Rickettsia are usually found in cytosol, with spotted-fever group organisms occasionally in nucleoplasm. Q fever may have a chronic as well as an acute form, and pneumonia without vascular infection or rash contrasts with the disseminated vasculitis and microvascular injury of the rickettsioses. Chronic Q fever is a systemic granulomatous disease that may also include infective endocarditis.

Pathology. Because Q fever is rarely fatal, few tissues have been examined from the acute stage of the illness. Those cases have shown bronchopneumonia with a component of interstitial pneumonia also. Alveolar, bronchiolar, and bronchial exudates contain many macrophages with variable quantities of lymphocytes, erythrocytes, and polymorphonuclear leukocytes. Alveolar septa are slightly to moderately thickened by mononuclear cell infiltration. The intracellular location of the Coxiella and the microscopic lesions resemble other unusual pneumonias such as psittacosis and Legionnaires' disease. Some patients develop granulomas of the liver or bone marrow. The hepatic granulomas often have a characteristic doughnut appearance with a central clear zone surrounded by layers of fibrin and epithelioid macrophages. Similar and other nonspecific granulomas have also been observed in bone marrow and spleen. Chronic Q fever may manifest chronic infective endocarditis, hepatic involvement, and thrombocytopenia.

Stages of individual work in class Study and describe macrospecimens

Hemorrhagic laryngotracheobronchitis in influenza. Pay attention to the state of the tracheal mucosa: its appearance, colour, presence of a film on its surface. Determine, what form of influenza this preparation demonstrates.

Hemorrhagic pneumonia in influenza. Pay attention to dimensions of the lung, its appearance on section; give the name of the preparation, explain the morphological picture of changes in the lung in influenza; indicate the form of influenza in this case.

Spleen in malaria. Describe its dimensions, state of the capsule, colour on section. Explain, what causes a change in the colour. List complications and causes of death in malaria patients.

Skin in smallpox. Describe appearance of ulcerous formations on the skin, explain mechanisms of their development. Name clinical-morphological forms, complications and causes of death in patients with smallpox.






Дата добавления: 2016-07-27; просмотров: 1436; ЗАКАЗАТЬ НАПИСАНИЕ РАБОТЫ


Поиск по сайту:

Воспользовавшись поиском можно найти нужную информацию на сайте.

Поделитесь с друзьями:

Считаете данную информацию полезной, тогда расскажите друзьям в соц. сетях.
Poznayka.org - Познайка.Орг - 2016-2022 год. Материал предоставляется для ознакомительных и учебных целей.
Генерация страницы за: 0.052 сек.