Aquired immunodeficiency syndrome 349

benign cells. Biopsy specimens show follicular hyperplasia, with the normal architecture distorted by greatly expanded germinal centers composed of  lymphocytes. It is now known that active viral replication is occurring in these follicular cells and dendritic cells, although the patient may appear well clinically.Most patients with PGL require no invasive evaluation and can be managed expectantly for the occurrence of other AIDS-related manifestations.

A limited differential diagnosis of isolated thrombocytopenia in an HIV-infected person includes drug-induced thrombocytopenia, particularly in heroin addicts and alcoholics, consumptive thrombocytopenia, or splenic sequestration. Some patients with thrombocytopenia may also present with leukopenia or anemia. The presence of constitutional symptoms and pancytopenia suggests an opportunistic infection, particularly disseminated mycobacterial or fungal infection, or a lymphoma.

Treatment

Basic therapy consists of indication of antiviral agents. There are used preparations, that inhibit the return transcriptasa of the virus: azydotymidin (AzT), didanosin (ddi), zalcytobyn (ddc), stavodin (d4T), lamivudin, abacavir (ABC), nevirapapin (NVP).

Till now monotherapy AZT (retrovir, zidovudin) was used. The preparations are prescribed 0.2 gm 3 times per day constantly or courses, duration is not less than 3 months. Treatment will be carried out under the control of the general blood analysis with 2 times per one month during the first 2 months and subsequently once per month. In a stage of preAIDS (secondary diseases) AZT is necessary to indicate till disappearance of a clinical symptomatology. If the clinical picture is not better zidovudin is indicated only for that patient in which blood concentration are less than 500 cells in 1 mkL. With such treatment it is possible to prolong patients life, the number of resistant viruses to a preparation however is marked. So, monotherapy AZT is recommended only for prophylaxis of infection of fetus from mother.

Among new means with other mechanism of action a specific inhibitor of proteases krixivan is used, which is effective concerning resistant to AZT populations of a virus 0.8 gm every 8 hour. Preparations of a choice may be rotonavir, nelfinavir, sacvinar-SGC, amprenavir.

Recently it is proved, that efficiency of treatment essentially can be increased using a combination of two or three antiviral preparations. Therefore monotherapy was changed for polytherapy. The most frequently combination of two inhibitors of virus return transcriptasa (stavudin + didanosin, stavudin + lamivudin, zidovudin+didanosin, zidovudin + lamivudin, zidovudin+abacavir) and one inhibitor of a protease is used. At patients with high risk of disease progress (viraemia over 1 million copies/mL), and also in urgent cases the two inhibitors of proteases and 1-2 inhibitors of virus return transcriptasa are used.

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Efficiency of specific treatment is controlled by monitoring with following criteria: 1) level HIV RNA in plasma; 2) quantity of T-lymphocytes CD4; 3) a clinical condition of the patient; 4) morphology and biochemistry of a blood (for detection of undersirable effects of an organism). Level HIV RNA in plasma is researched after 4-8 and 12-16 weeks from the beginning of treatment and subsequently each 3-4 months. The major condition of successful antiretrovirus therapy is its usage during all life of the patient, however it is interfered by a high toxicity of preparations and the complications connected with them. Complete treatment of patients with AIDS remains an unsolved problem. Last combination is considered the most effective, but also it does not cure patients with AIDS.

It is not less important preventive treatment of secondary diseases at AIDS. Against pneumocystic pneumonias the basic agent is bactrim. For initial prophylaxis of this disease bactrim is indicated 1 tablet during 3 days each week. At occurrence of pneumonia daily reception of preparation is prescribed. In case of an intolerance of bactrim it is possible to indicate dapsone or primachin in a combination with clindamicin. At presence of herpetic infections indicate acyclovir.

Against criptococus and other funguses amphotericinum is used, against bacteria - the appropriate antibiotic. At Kaposi's sarcoma freezing of eruption elements by liquid nitrogen, irradiation, chemotherapy is indicated. The immunotherapy of AIDS is at developing stage.

Prophylaxis

Most infections occur as a result of repeated and close contact with a carrier of HIV, specifically mucous membrane contact with blood or body fluids of the carrier. Sexual relationships are the major source of such contacts,and people must be educated to modify sexual practices, to avoid sexual encounters with persons in high-risk groups, reduce the number and frequency of sexual contacts, avoid high-risk practices (e.g., anal intercourse), and use protective devices such as condoms. Consistent use of condoms should reduce transmission of HIV by preventing exposure to semen and infected lymphocytes. Whether symptomatic or not, persons who know they carry the HIV virus should be counseled to avoid sexual contacts in which body fluids may be exchanged with uninfected persons.

Since HIV may be transmitted in utero or during or after birth, women carriers and those in high-risk groups should be counseled, and testing for antibody to HIV should be offered to women in high-risk groups. Women known to be HIV-positive should be advised to defer pregnancy.

Parenteral drug users need to be educated and counseled with regard to the risk of sharing needles with other drug users.

Testing for- antibody to HIV should be offered on a confidential basis to anyone requesting it,but only in conjunction with pre- and post-test counseling by someone familiar with its significance. Confidentiality is necessary because

Aquired immunodeficiency syndrome

the patient's job, insurability, and social life can be jeopardized. Counseling is necessary because test results require sophisticated analysis; patients need to be well informed before the tests are performed, and the results must be fully explained afterward.

HIV carriers and persons belonging to a high-risk group (even if their HIV antibody test results are negative) should not donate their blood (or organs for transplantation), and should inform medical and dental professionals of their status. The latter should wear gloves when examining all patients if contact with mucous membranes may occur, and body fluids and tissue samples should be handled in the same manner as those from patients with hepatitis B.

Accidental needle sticks of health care personnel are remarkably common and special emphasis must be placed on teaching all health care students and professionals how to avoid these potentially very dangerous accidents. While the risk of HIV transmission appears to be much less than that of hepatitis  transmission,the potential consequences are much worse.

Surfaces contaminated by blood or other body fluids should be cleaned and disinfected; HIV is readily inactivated by heat and commonly used disinfecting agents, including peroxide, alcohols, phenolics, and hypochlorite. Although AIDS patients are not particularly contagious to other hospital personnel or patients, their body fluids and blood should be handled with extreme care, following the same procedures used with patients who carry hepatitis  virus.

Control questions:

1. Infectious agent of AIDS, its biological properties.

2. Epidemiology of AIDS, contingents of the promoted risk of AIDS infection.

3. Mechanisms and ways of contamination.

4. Pathogenesis of AIDS.

5. Basic periods of AIDS development, their clinical symptoms.

6. Manifestation of AIDS in children.

7. Epidemiological and clinical criteria of diagnosis.

8. Laboratory diagnosis.

9. Principles of medical treatment.

10. Prophylaxis of AIDS.

352 Infectious diseases

SEPSIS

The term "sepsis" has been used for a clinical situation in which there is evidence of infection plus a systemic response as manifested by an elevated temperature, tachycardia, increased respiration, leukocytosis or an impaired peripheral leukocyte response, and/or the presence of immature band forms of peripheral circulation.

Sepsis has essential differences from the other infectious diseases:

1. Sepsis is polyetiological disease. The agents of sepsis may be different microorganisms — aerobia and anaerobia.

2. There is no united entrance gates.

3. There is no cyclicy of the course.

4. There is no immunity development in sepsis.

Etiology

The most frequent etiologic factor of sepsis are auto- or external microflora. These agents are staphylococci, streptococci, colibacilli and other so called conditionally pathogenic microorganisms. Rarely, a reason of the sepsis may be obligate parasites. Septic agent may be the blue pus bacilli, gonococci, meningococci, Bacillus anthracis, Salmonella, fungi and other. But, at last time staphylococcus is found more often than others, so it should be on the first place by significance. According to international classification 3 types of staphylococci are detached: Staphylococcus aureus, Staphylococcus epidermidis, Staphylococcus saprophyticus. Staphylococcus aureus plays the most important role in the pathology of human.

Epidemiology

Staphylococcous infection is widely spread among hospitalized persons. Intrahospital distribution is typical feature of epidemiology of staphylococcous infection.

Intrahospital infections are characterized by large quantity of the sources of infection, multiply ways and factors of transmission of the agent multiply persons with increased risk of the infection. The sources intrahospital infection are patients with different forms of staphylococcous purulent infection, carriers of staphylococcus. Carriers of staphylococcus from medical personnel play an important role in the conditions of the hospital.

The ways and factors of transmission of staphylococcous infections are different: respiratory-drug, contact and alimentary. Transmission of the agent may be realized by alimentary way. For example, it is possibly infection of infants in maternity

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hospital by solutions for drink and milk, using for supplementary nourishment. Staphylococcous infection have sporadic character in observance of sanitary-antiepidemic regime. Epidemic outbreaks of intrahospital staphylococcous infections may be in violation of regime.

Staphylococcous infection develops as rule in persons with decreased nonspecific resistance, with different infectious diseases (especially of viral etiology), after chronic diseases, in persons after massive doses of immunodepressors, antibiotics, hormones, X-ray therapy.

Pathogenesis

The factors of risk, promoting the penetration of normal germs of skin and mucous membranes into internal mediums of the macroorganism system, may be different causes injuries, inflammations, trophic disorders, aggression of different microflora, congenital anomalies. The following distribution of microbes in macroorganism may go by different ways - via blood, lymph and direct methastasing. The intermediate localization of the process appears. It may be phlegmona, abscess or other destructive processes. The process is sepsis, when it has generalized character with damage liver, spleen, lungs, kidneys, vessels and other organs and systems.

The agents of sepsis, penetrating into tissues, causes an inflammatory process. In some cases the process develops impetuously. The purulent inflammatory focus arises on the place of the penetration with reproduction of microbes (primary focus). But in other cases inflammatory manifestations are less expressive and rapidly disappear, but agent penetrates inside tissues by lymphatic and blood ways and causes inflammatory focus in distant place. This inflammatory focus may lead to development of sepsis, in corresponding change of reactivity and resistance of the organism.

Portal of infection may be in any organ and tissue. The primary focus is in tissues with large quantity of lymphatic and blood vessels more frequently. For example,in wound sepsis the skin is a portal more frequently. In urosepsis and gynecological sepsis mucous membranes are portal. Prolonged course of sepsis is marked in patients with localization septic and primary foci in bones, muscles, urogenital system. In some cases, there are no visual foci, except the primary septic focus. These forms are called septicemia. But in other cases, metastatic secondary purulent foci are formed. These forms are named pyemia. But, also there is possible a transitional form - septicopyemia.

The distribution of infection is realized from the primary focus via blood and lymphatic ways. The distribution of the agents is realized by veins too, with formation of thrombosis and thrombophlebitis. Microbes and their toxins may penetrate to lymphatic vessels and cause lymphangites and lymphadenites. Metastases may be as an infiltrations, phlegmons, abscesses. Purulent infiltrates may appear in intestine too. In the serous cavities they are characterized by purulent exudations (arthritis, pleurisy, peritonitis, pericarditis).

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The localization of metastases in the lungs is on the first place, kidneys are on the second place, then - other organs.

Allergic component has an important role in pathogenesis of the septic process. Primary and secondary septic foci transfer into a source of sensibilisation of human organism.

In sepsis the violations of metabolism, acid-alkaline balance, deep changes of balance of proteins and vitamins are observed. Anemia develops due to damage of bone marrow.

DIC-syndrome plays an important role in the development of septic state and complications. In some cases of sepsis DIC-syndrome comes out on the first plan and cause fatal outcome in considerable degree.

DIC-syndrome is "proteolytic explosion" with activation and following exhaustion of coagulation, fibrinolytic, kallekrein-kinine systems and system of complement.

In sepsis dysbalance of immune system has the pathogenetic meaning. Immune deficiency is manifested by decrease of quantity of T-helpers,reduce of activity natural killers and phagocytic activity of granulocytes. These changes lead to development of generalized infectious inflammatory process.

Anatomic pathology

In sepsis pathologoanatomy alterations are very various. Petechial rash is marked on the skin. Hemorrhages are observed in organs and tissues, especially on mucous membranes. The alteration of myocardium are marked from turbid swelling till excessive lipid dystrophy. Erosions are revealed in endocardium. Thrombosis of veins are often observed. Spleen is enlarged. There is a turbid swelling or lipid infiltration in liver. Lymphatic nodes are increased. There are a plural hemorrhages in kidneys. Also, they are marked in the gastrointestinal tract. Hemorrhages are observed in the suprarenal glands. There is edema in the lungs. Sometimes there are foci of bronchopneumonia. The infarction foci are not rare. There are edema and hyperemia of brain matter. In sepsis with metastases (pyemia) purulent process are observed in brain (purulent meningoencephalitis), lungs (like abscessing infarctions), kidneys, thyroid gland. Besides that, purulent pleurisies, peritonitis, pericarditis, phlegmons are observed in different places.

Classification

I. According to spreading of the disease:

1. Purulent-resorptive fever is characterized by presence of purulent foci, wave-like course, general intoxication.

2. Septicemia is characterized by severe general state, hectic temperature, severe disorders of central nervous system and cardiovascular system.

3. Septicopyemia. This is combination of septicemia and presence of

secondary purulent foci in different organs.

4. Chronic sepsis. There is purulent foci in anamnesis during this form.

The diseases is accompanied by prolonged wave-like fever, presence of

period of remission and relapses, periodical formation of purulent foci.

Sepsis

II. According to prolongation of course the next form of the diseases are differed:

1. Fulminant sepsis (24-48 hours).

2. Acute sepsis (from 5-7 days till some weeks).

3. Subacute sepsis (3-4 months).

4. Chronic sepsis (from some month till one year and more).

III. According to date of process appearance the next variants are differed:

1. Early sepsis (till 3 months from appearance of the primary focus).

2. Late sepsis ( later than 3 months).

IV. According to character of microorganism sepsis is differed on:

1. Sepsis, caused by gram-positive flora. It leads, inrarely, to development of septicopyemia.-

2. Sepsis, caused by gram-negative flora. Infectious-toxic shock may be in such cases.

Clinical manifestations

There is no specific incubation in septic patients. In some cases, septic process develops through weeks and months after localized focus (abscess), but in other cases sepsis may be on its background.

Complains of these patients are different as a clinical manifestations -weakness, headache, pain in joints, chill with following sweats or chilling, dry mucous membrane of the mouth, poor appetite, sometimes - diarrhea.

Fever is frequently of hectic character in patients with sepsis. Different variants of the temperature may be - remittent and intermittent types, sometimes, the temperature is higher in the morning (the reversal type). The temperature may be not high in weak, cachectic patients and elders, but it doesn't report about mild course of sepsis.

Patient's skin is pale, moist, even icteric in severe cases. Different rashes are observed. Rash of hemorrhagic type is marked more frequently, sometimes -pustules, ulcers, erythema. Eruption may be on skin of trunk, limbs and face.

Mucous membranes of lips, oral cavity are dry and may have erosions, ulcers, fissures, bleeding sickness. Often, there are hemorrhages on conjunctiva.

Pulse is frequent. Arterial pressure decreases. Heart is enlarged. There are a systolic murmur above cardiac apex, tachycardia and "pendulous" rhythm during auscultation the alterations of myocardium are revealed during cardiogram. The type of these alteration is diffuse or diffuse-focal. Sometimes, the signs of damage of endocardium and large peripheral vessels are revealed (arteritises,phlebitises).

The alterations of respiratory tract are revealed frequently in the patients with sepsis: dyspnoe, bronchitis and pneumonia. Pneumonia has tendency to formation of abscesses. Inrarely, serous, purulent, hemorrhagic and mixed pleurisy arises in the patients.

There is a dry coated tongue in these patients. Appetite is poor. Sometimes, vomiting arises. Spleen is frequently enlarged, soft consistence. Liver also is

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enlarged and painful during palpation. The abscesses may arise inside abdominal cavity.

Septic patient, often, have a disorders of kidneys and urinary track. Sometimes toxic nephrites, purulent paranephrites arise. The alterations of uterus, perimetrium may be in women. The primary location of inflammatory process is marked inrarely in urogenital organs. It may give generalization of the process.

Osseous-muscular system is involved to pathologic process too. There are reports about the serous and purulent mono- and polyarthritis, foci of osteal destruction, degeneration of born marrow, myocytes. Also, the osteal tissue may be site of the primary foci (osteomyelitis).

Different manifestations may be from nervous system, such as meningismus, purulent meningitis, cerebral and spinal hemorrhages, hemorrhages into the vegetative ganglions.

The signs of anemia are revealed in the blood: decreased erythrocytes quantity and hemoglobin. Also,there are signs of the anisocytosis,poikilocytosis, thrombocytopenia. Neutrophilic leukocytosis with shift to myelocytes, increased ESR are marked; leukopenia may be in cachestic patients with fulminate forms of sepsis.

Biochemical changes of the blood are expressive in the patient with sepsis. Increased content of bilirubin and increased activity of transaminases are marked.

In sepsis the proteins of serum blood are sharply changed. A quantity of albumines decreases and globulines increased. The changes of concentration of IgA, IgG, IgM depend upon gravity of the course and outcomes of sepsis.

Fulminate sepsis is a rare form, the example, meningococcal sepsis. It has several synonyms. There are - fulminate meningococcemia, acutest meningococcal sepsis, Waterhouse-Friedrichen syndrome. It is the most severe, unfavorable form of meningococcal infection. Its base is infectious-toxic shock. Fulminate sepsis is characterized by acute sudden beginning and impetuous course. Temperature of body rises up to 40-41 °Ñ. It is accompanied by a chill. However, hypothermia may be through some hours. Hemorrhagic plenty rash appears at the first hours of the disease with tendency to confluence and formation large hemorrhages, necroses. A purple-cyanotic spots arise on the skin ("cadaveric spots")- The skin is pale, but with a total cyanosis. Moist, covered with a clammy sweat. Patients are anxious and excited. The cramps are observed frequently,especially in children. The recurrent bloody vomiting arises inrarely. Also, a bloody diarrhea may be too. Gradually, a prostration becomes expressive and it results in a lose of the consciousness.

Acute sepsis is the most frequent form of sepsis. Staphylococcus sepsis is occurred more frequently. It is accompanied by considerable fatal outcomes. In majority of the cases the onset of disease is an acute with chill and increase of the temperature. Fever may be of different character: constant, intermittent, remittent and irregular. Sometimes sepsis may be with subfebrile temperature.

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Anemia increases in majority of the patient, the skin is pale. Sometimes skin has jaudiwish shade due to haemolysis or toxic hepatitis.

The rash is petechial. Rash is localized on the skin of the chest, forearms, hands, upper extremities, on the mucous membrane of the mouth, conjunctiva and all gastrointestinal tract. Hemorrhages on the mucous membrane of gastrointestinal tract may evoke bloody vomiting and diarrhea. The sizes of hemorrhages are different - from small points till large hemorrhages. An appearance of hemorrhagic rash is explained by present of hemorrhagic vasculitis. Rash may be purulent or erythematosus character due to infectious-allergic dermatitis. The damage of joints is observed in 25-30 % of the causes. The large joints are damaged more frequently, but small joints may be damaged too. The joints are edematous. There is hyperemia of the skin over joints. The motions are painful.

In sepsis symptoms, connecting with damage of different organs and systems are always expressed. They appear as a result of expressive intoxication, or as primary or secondary purulent inflammatory process. The symptoms, connecting with damage of cardiovascular system is revealed more frequently. Staphylococcous sepsis may be without damage of endocardium. In this case the clinical symptoms are evoked by distrophic changes of myocardium. Tachycardia, decreased arterial pressure, cardial pain of indefinite character, enlargement of the borders of the heart, muffled heart sounds are observed. The damage of the vessels may be manifested in form of phlebitis, development of thromoembolism and also embolism of small vessels of the skin and internal organs, in violation of coronaric circulation.

Oxygenic insufficiency and damage of respiratory center leads to breathlessness. In some patient bronchitis, pneumonia, abscesses and pleurisy are observed. Hemorrhagic pleurisy is more typical for staphylococcus sepsis.

In staphylococcous sepsis the typical sign is increased liver. The severe septic hepatitis may be observed with development of jaundice and violation of all functions of liver and also cholangitis, abscesses. Enlarged spleen (septic mesenchymic spleenitis) is frequent symptom. Spleen is soft in an acute period,and it is difficulty to define spleen in pulpation. However, enlarged spleen is clearly defined in percussion. During prolonged course of sepsis spleen becomes dense. The damage of kidneys has essential meaning in clinic of sepsis. In acute process the local nephrite of microbial embolic origin develops, diffusive nephritis develops later.

The symptoms of damage of nervous system are the principal clinical manifestations in the patient with sepsis. In acute sepsis consciousness is preserved even in high temperature. In this period severe headache, sweat, violation of the sleep and dizziness are usual complaints of the patients. In severe cases depression, irritation, sometimes excitement are observed in the patients. Due to edema of the brain meningeal syndrome may be too. It is possible development of secondary purulent meningitis. The appearance of meningitis is characterized by intensification of headache, addition of vomiting, development of meningeal symptoms.

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Date: 2014-12-21; view: 938