Hemolytic fever with renal syndrome. GLPS infectious diseases. Symptoms of this disease

Hemorrhagic fever with renal syndrome (HFRS) is an acute viral zoonotic natural focal disease that is accompanied by a severe increase in body temperature and renal failure. It is caused by the RNA viruses Hantaan - Hantaan, distributed mainly in the east, and Puumala - Puumala, localized in the western regions of Europe.

The first virus is more dangerous; the mortality rate for HFRS incidence is up to 20%. The second one causes a disease with a less severe course and a mortality rate of up to 2%. In the Far East, there are cases of HFRS caused by the Seoul virus – Seoul. This disease is transmitted in a mild form.

Causes and pathogenesis

Viruses initially enter the body of rodent carriers (house and field mice, rats, jerboas, bats), which infect each other through airborne droplets and carry HFRS in a latent form, that is, they do not get sick. A person can become infected in the following ways:

• contact: in contact with rodents, their feces;
• airborne dust: inhalation of air containing tiny particles of dried rodent feces;
• fecal-oral: ingestion of dirty food containing particles of rodent excrement while eating.

People are susceptible to the pathogen in 100% of cases. Men aged 16 to 70 years suffer most from hemorrhagic fever with renal syndrome.

Hemorrhagic fever with renal syndrome (HFRS) is characterized by seasonality and the presence of endemic areas. Peaks of incidence occur from early summer to early winter. In Russia, the highest incidence of hemorrhagic fever with renal syndrome was recorded in Tatarstan, Udmurtia, Bashkortostan, as well as in the Samara and Ulyanovsk regions.

Frequent cases of morbidity are recorded in the Volga region and the Urals in broad-leaved zones. To a lesser extent, cases of HFRS have been recorded in the Eastern Siberian region.

A single exposure to hemorrhagic fever with renal syndrome provides lasting immunity for life.

The virus in the human body settles on the mucous membranes of the respiratory and digestive system. It then multiplies and enters the blood. During this period, the patient experiences intoxication syndrome due to infection entering the bloodstream.

Subsequently, Khantaan is localized on the inner wall of the vessel and violates its integrity. The patient develops hemorrhagic syndrome. The virus is eliminated from the body by the urinary system, so the following occurs:

• damage to the renal vessels;
• inflammation and swelling of kidney tissue;
• development of acute renal failure.

This period of HFRS is especially dangerous and is characterized by an unfavorable fatal outcome. In favorable cases, the reverse process begins: resorption of hemorrhages, restoration of excretory functions of the kidneys. The duration of the recovery period for HFRS can range from one to three years.

Species and types

Currently, there is no single accepted classification of HFRS.

Depending on the territory in which the disease is registered, the following types of HFRS are distinguished:

• Yaroslavl form of fever;
• Transcarpathian form of HFRS;
• Ural form of HFRS;
• Tula form of HFRS;
• Far Eastern form of HFRS;
• Korean form of fever, etc.

Depending on the type of RNA virus that caused HFRS, there are:

• Western type of HFRS - caused by the Puumala virus; severe course in 10%, accompanied by oligoanuria and hemorrhagic symptoms. Mortality – 1-2%; distribution on European territory;
• The eastern type of HFRS is caused by the Hantaan virus. A very severe course in 40-45% of cases, accompanied by acute renal failure syndrome and hemorrhagic syndrome. Mortality – about 8%, distribution mainly in agricultural areas of the Far East;
• HFRS is caused by the Seoul serotype. The course is relatively mild in 40-50%, accompanied by the development of hepatitis and disorders of the respiratory system. Common among urban residents in the Far East.

Depending on the zone or territory in which HFRS infection occurs:

• in the forest (forest type of HFRS) - while picking mushrooms and berries in contact with contaminated dried feces of sick rodents;
• in everyday life (domestic type of HFRS);
• in production (production type GLPS) - work in the forest zone, on oil pipelines in the taiga, on drilling rigs;
• on a personal plot (dacha type GLPS);
• on vacation in tent cities, camps, etc.;
• in agricultural fields.

Stages and symptoms of the disease

The symptomatic specificity of the disease varies depending on the stage of HFRS. There are only four stages and they are characterized by cyclical alternation. In other words, some time after the fourth stage, the first begins again, and so on.

Only the course of HFRS caused by the Seoul serotype is characterized by acyclicity.

The incubation period for hemorrhagic fever with renal syndrome lasts about 2-4 weeks, during which time symptoms do not appear.

• The initial or febrile period of HFRS is no more than 7 days, most often 3-4 days. It begins acutely: the patient’s body temperature on the first day reaches 38.5-40.5° C. The person feels headaches, back and muscle pain, general malaise, dryness in the oral cavity and thirst, flashing “midges” before the eyes and blurred images. During this period, minor hemorrhages may be observed on the mucous membrane of the palate and sclera.
• The oliguric period of HFRS is about a week. The body temperature drops, but the condition becomes worse. The patient develops nosebleeds, bruises on the body, and ulcerated sclera. In the chest area, in armpits and on lower limbs a red rash forms, which is a manifestation of numerous capillary ruptures. There is an increase in complaints of pain in the back and abdomen. The daily volume of urine decreases. Sometimes an increase in the size of the liver is diagnosed.
• The polyuric period of HFRS begins on days 10-13. The daily volume of urine increases to 6 liters. Low urine density is detected in the absence of its fluctuations, which is a sign of acute renal failure.
• The convalescent period of HFRS is the longest, begins on days 20-22 and lasts about six months. It is characterized by an improvement in the patient’s general condition and normalization of diuresis. Recovery with mild degrees of HFRS severity is observed after 1 month, and with moderate severity - only after 5-6 months. In patients who have suffered a severe form of HFRS, asthenic syndrome manifests itself throughout life.

Symptoms of various hemorrhagic fever syndromes

The three main syndromes of the disease have varying degrees of manifestation depending on the severity of HDL:

• intoxication;
• hemorrhagic;
• renal

Hemorrhagic fever with mild renal syndrome manifests itself:

• a three- or four-day increase in the patient’s temperature to 38 0C;
• minor headaches;
• temporary agnosia;
• pinpoint hemorrhages;
• there is a decrease in diuresis;
• laboratory tests in the urine reveal an increase in the level of protein and urea;

The average degree of HFRS is characterized by:

• a five- or six-day increase in body temperature to 39-40 0C;
• quite severe cephalalgia;
• hemorrhages on the skin and mucous membranes are multiple;
• periodically the patient vomits blood;
• heart rate increases, which is the appearance initial stage infectious-toxic shock;
• oliguria in patients lasts about 3-5 days;
• laboratory tests in the urine indicate an increase in the level of protein, creatinine, and urea.

Severe HFRS is accompanied by:

• prolonged (more than 8 days) increase in the patient’s body temperature to 40-41 oC;
• repeated vomiting of blood;
• systemic hemorrhages of the skin and mucous membranes.

Signs of infectious intoxication:

• digestive disorders;
• weakness;

From the urinary system:

• porteinuria;
• oliguria;
• hematuria;
• increased levels of urea and creatinine.

Children of all ages, even infants, are susceptible to HFRS. The course of the disease in them is distinguished by a very acute onset, which is not preceded by symptoms. Children become weak and tearful, lie down more, and complain of headaches and back pain in the lumbar region already at the first stage of the disease.

Diagnosis of hemorrhagic fever

To make an accurate diagnosis of HFRS, it is important to take into account the patient’s epidemiological history, the presence clinical manifestations diseases, laboratory data and serological studies. If necessary, an FGDS, ultrasound, computed tomography, or x-ray examination may be required.

If the patient has symptoms of hemorrhagic fever with renal syndrome, the possibility of contact with field mice and other rodents that are carriers of the disease is clarified. The clinical picture of HFRS is characterized by fever for 7 days, redness of the scalp and neck. In addition, hemorrhagic syndrome and symptoms of renal failure are observed with a decrease in body temperature.

Diagnosis of HFRS is carried out using the following laboratory and serological tests:

• general analysis of urine and blood;
• indirect immunofluorescence reaction;
• radioimmunoassay;
• reaction passive hemagglutination in paired serums.

Leukopenia is diagnosed in the patient's blood during the initial period, accompanied by a persistent increase in body temperature. At the following stages of HFRS it is noted increase in ESR, neutrophilic leukocytosis and thrombocytopenia, the appearance of plasma cells in the blood. The appearance of antibodies to the virus in a patient is diagnosed on the 7th-8th day of the disease, the maximum of which is observed on the 13th-14th day.

Hemorrhagic fever with renal syndrome is similar in course to other diseases that are characterized by increased body temperature: typhoid fever, tick-borne rickettsiosis and encephalitis, leptospirosis and simple influenza. Therefore, when identifying HFRS, it is important differential diagnosis.

Treatment of the disease

Treatment of patients with hemorrhagic fever with renal syndrome is carried out only in infectious diseases department hospital. The patient must be prescribed bed rest, especially during the period of illness with hyperthermia. A diet rich in carbohydrates with the exception of meat and fish is indicated ( diet table №4).

Treatment aimed at eliminating the cause of HFRS can give a positive effect only in the first 5 days of the disease.

Drug treatment is prescribed with drugs that inhibit RNA synthesis. In addition, the patient is treated with human immunoglobulin, alpha interferons and interferon inducers are prescribed orally and rectally.

Hemorrhagic fever with renal syndrome is characterized by multiple pathogenic changes in organs. Consequently, therapy is also aimed at eliminating these pathogenic changes caused by the syndrome of intoxication and renal failure, hemorrhagic syndrome. Patients are prescribed:

• glucose and polyionic solutions;
• calcium preparations;
• ascorbic acid;
• aminophylline;
• papaverine;
• heparin;
• diuretics, etc.

Patients are also treated to reduce the body's sensitivity to the virus. Symptomatic treatment of HFRS includes relief of vomiting, pain symptoms, and restoration of the cardiovascular system.

In severe forms of HFRS, hemodialysis and other methods of correcting hemodynamics and disorders of the blood coagulation system are indicated.

During the recovery period of HFRS, the patient needs restorative therapy and adequate nutrition. The patient is also prescribed physiotherapy, physical therapy complex and massage.

Prognosis and prevention

If the patient receives adequate therapy in time (at the stage of fever), then recovery occurs.

However, in most cases, after suffering from hemorrhagic fever with renal syndrome, residual effects are observed for six months. These include:

• asthenic syndrome (weakness, fatigue);
• painful manifestations of the kidneys (swelling of the face, dry mouth, lumbar pain, polyuria);
• disruption of the endocrine and nervous systems (pleurisy, pituitary cachexia);
• development of cardiomyopathy due to an infectious disease (shortness of breath, heart pain, rapid heartbeat);
• very rarely chronic pyelonephritis develops.

People who have had HFRS need to be monitored by a nephrologist, ophthalmologist and infectious disease specialist every three months for one year.

The severe course of this disease is dangerous due to the risk of complications, which in 7-10% of cases lead to death.

Prevention of hemorrhagic fever with renal syndrome consists of observing personal hygiene measures, especially for people who live in endemic areas. After being in the forests, fields, personal plots(in areas where rodents are spread), you need to thoroughly wash your hands and disinfect your clothes. Food products must be stored in airtight containers.

To avoid contracting hemorrhagic fever with renal failure, you should only drink boiled water.

When working in dusty conditions (in a field, in a barn, etc.), wear a mask or respirator over your face to prevent airborne infection.

Under no circumstances should you handle, touch or pet rodents. In natural hotspot areas, it is necessary to carry out timely deratization and thorough cleaning of residential premises.

Vaccination against HFRS is impossible due to lack of development.

Hemorrhagic fevers

Hemorrhagic fevers (febres haemorrhagica) is a group of acute viral zoonotic diseases with various mechanisms of transmission of pathogens, characterized by the development of universal capillary toxicosis and hemorrhagic syndrome against the background of an acute febrile state and occurring with symptoms of general intoxication.

Currently, 13 hemorrhagic fevers have been described in humans, most of which are endemic to tropical regions. In Russia, Congo-Crimean hemorrhagic fever, Omsk hemorrhagic fever and hemorrhagic fever with renal syndrome have been described.

The causative agents of hemorrhagic fevers are environmental group arboviruses (togavirus and bunyavirus families), arenaviruses and filoviruses.

Hemorrhagic fevers are natural focal infections. The main reservoirs of pathogens are animals - primates, rodents, large and small cattle, ticks, etc., in whose body a latent infection usually develops with long-term persistence of viruses, which ensures intensive contamination of the environment in enzootic foci. In some cases, the infection may become anthroponotic in nature.

The mechanisms of infection by hemorrhagic fevers are varied: transmissible - with arboviral hemorrhagic fevers; aerogenic, alimentary and contact - with arenavirus hemorrhagic fevers, parenteral transmission of some pathogens of hemorrhagic fevers is possible.

Susceptibility to hemorrhagic fevers is high; people who have close professional contact with animals or objects are at high risk of infection wildlife(loggers, geologists, agricultural workers, vivarium workers, etc.). The most severe forms of the disease are observed in people visiting foci of infection for the first time. Local residents often experience mild and subclinical forms of hemorrhagic fevers. Mortality in hemorrhagic fevers ranges from 1-5 to 50-70%.

Hemorrhagic fever with renal syndrome (HFRS) is an acute viral natural focal disease that occurs with high fever, severe general intoxication, hemorrhagic syndrome and a kind of kidney damage in the form of nephrosonephritis.

Historical information. Under various names (Manchurian gastritis, hemorrhagic nephrosonephritis, Songo fever, etc.), the disease has been recorded in the Far East since 1913.

In 1938-1940 in complex studies by virologists, epidemiologists and clinicians, the viral nature of the disease was established, the basic patterns of epidemiology and the features of its clinical course were studied. In the 50s, HFRS was identified in Yaroslavl, Kalinin (Tver), Tula, Leningrad,

Moscow regions, the Urals, and the Volga region. Similar diseases have been described in Scandinavia, Manchuria, and Korea. In 1976, American researchers G. Lee and P. Lee isolated the virus from rodents Apodemus agrarius in Korea, and in 1978 they isolated the virus from a sick person.

Since 1982, by decision of the WHO Scientific Group various options The diseases are united under the common name “hemorrhagic fever with renal syndrome.”

Etiology. The causative agents of HFRS are viruses of the genus hantaan (Hantaan pymela, seoul, etc.), of the family bunyaviridae - they belong to spherical RNA-containing viruses with a diameter of 85-110 nm.

Epidemiology. HFRS is a natural focal virus. The reservoir of viruses on the territory of Russia is 16 species of rodents and 4 species of insectivorous animals, in which latent forms of infection are observed; enzootics with death of animals occur less frequently. The virus is released into the external environment mainly through the urine of rodents, less often with their feces or saliva. Among animals, transmissible transmission of the virus by gamas ticks and fleas is observed.

From rodents to humans under natural or laboratory conditions, the virus is transmitted through airborne dust, nutritional and contact routes. There are no known cases of HFRS infection from a sick person.

The incidence is sporadic, and group outbreaks are also possible. Natural foci are located in certain landscape-geographical zones: coastal areas, woodlands, wet forests with thick grass, which contributes to the preservation of rodents. The incidence has a clear seasonality: the largest number of cases of the disease is recorded from May to October - December with a maximum increase in June - September, which is due to an increase in the number of rodents, frequent visits to the forest, fishing trips, agricultural work, etc., as well as in November – December, which is associated with the migration of rodents into residential premises.

Most often, rural residents aged 16-50 years old, mostly men (loggers, hunters, field farmers, etc.), are affected. The morbidity of urban residents is associated with their stay in the suburban area (visiting the forest, relaxing in holiday camps and sanatoriums located near the forest), and working in vivariums.

Immunity after an illness is quite durable. Repeated diseases are rarely observed.

After entering the human body through damaged skin and mucous membranes and replication in the cells of the macrophage system, the virus enters the blood. The viremia phase develops, which causes the onset of the disease with the development of general toxic symptoms.

Providing a vasotropic effect, the virus damages the walls of blood capillaries both directly and as a result of increased hyaluronidase activity with depolarization of the main substance of the vascular wall, as well as due to the release of histamine and histamine-like substances, activation of the kallikrein-kinin complex, which increase vascular permeability.

Immune complexes play a large role in the genesis of capillary toxicosis. There is damage to the vegetative centers that regulate microcirculation.

As a result of damage to the vascular wall, plasmorrhea develops, the volume of circulating blood decreases, its viscosity increases, which leads to a disorder of microcirculation and contributes to the formation of microthrombi. An increase in capillary permeability in combination with disseminated intravascular coagulation syndrome causes the development of hemorrhagic syndrome, manifested by hemorrhagic rash and bleeding.

The greatest changes develop in the kidneys. The impact of the virus on the renal vessels and microcirculatory disorders cause serous-hemorrhagic edema, which presses the tubules and collecting ducts and contributes to the development of desquamative nephrosis. Glomerular filtration decreases, tubular reabsorption is disrupted, which leads to oligoanuria, massive proteinuria, azotemia and electrolyte imbalances and acidotic changes in the acid-base state.

Massive desquamation of the epithelium and fibrin deposition in the tubules cause the development of obstructive segmental hydronephrosis. The occurrence of renal damage is facilitated by autoantibodies that appear in response to the formation of cellular proteins that acquire the properties of autoantigens, circulating immune complexes and fixed on the basement membrane.

A pathological examination reveals dystrophic changes, serous-hemorrhagic edema, and hemorrhages in the internal organs. The most pronounced changes are found in the kidneys. The latter are enlarged in volume, flabby, their capsule is easily removed, and there are hemorrhages underneath. The cortex is pale, bulges above the cut surface, the medulla is purplish-red with multiple hemorrhages in the pyramids and pelvis, and there are foci of necrosis. On microscopic examination, the urinary tubules are dilated, their lumen is filled with cylinders, and the collecting ducts are often compressed. The glomerular capsules are dilated, and individual glomeruli have dystrophic and necrobiotic changes. In areas of hemorrhage, the tubules and collecting ducts are grossly altered destructively, their lumen is absent due to compression or is filled with cylinders. The epithelium is degenerated and desquamated. Widespread dystrophic changes in the cells of many organs and glands are also revealed internal secretion(adrenal glands, pituitary gland) and autonomic ganglia.

As a result of immune reactions (increased antibody titers, IgM and IgG classes, changes in lymphocyte activity) and sanogenic processes, pathological changes in the kidneys regress. This is accompanied by polyuria due to a decrease in the reabsorption capacity of the tubules and a decrease in azotemia with a gradual restoration of renal function over 1 to 4 years.

Clinical picture. The main symptoms of HFRS are high fever, hyperemia and puffiness of the face, the appearance of hemorrhagic syndrome from the 3-4th day of illness and impaired renal function in the form of oliguria, massive proteinuria and azotemia followed by polyuria. The disease is characterized by a cyclical course and a variety of clinical variants from abortive febrile forms to severe forms with massive hemorrhagic syndrome and persistent acute renal failure.

The incubation period for HFRS is 4-49 days, but more often it is 2-3 weeks. During the course of the disease, 4 periods are distinguished: 1) febrile (1-4 days of illness); 2) oliguric (4-12th day); 3) polyuric (from 8-12 to 20-24 days); 4) convalescence.

The febrile period, or the initial phase of infection, is characterized by an acute increase in temperature, the appearance of painful headaches and muscle pain, thirst, and dry mouth. The temperature rises to 38.5-40 °C and remains at high levels for several days, after which it drops to normal (short lysis or delayed crisis). The duration of the febrile period is on average 5-6 days. After a decrease in temperature, a few days later it may rise again to low-grade levels - a “two-humped” curve.

A painful headache from the first days of illness is concentrated in the forehead and temples. Patients often complain of blurred vision and the appearance of a “mesh” before the eyes. On examination, puffiness and hyperemia of the face, injection of blood vessels in the sclera and conjunctiva, and hyperemia of the pharynx are naturally noted.

From the 2-3rd day of illness, hemorrhagic enanthema appears on the mucous membrane of the soft palate, and from the 3-4th day - a petechial rash in the armpits; on the chest, in the collarbone area, sometimes on the neck and face. The rash may appear in stripes that resemble a whiplash. Along with this, large hemorrhages appear in the skin, sclera, and injection sites. Subsequently, nasal, uterine, and stomach bleeding are possible, which can cause death. In some patients with mild forms of the disease, hemorrhagic manifestations are absent, but the symptoms of “tourniquet” and “pinch,” indicating increased capillary fragility, are always positive.

The pulse at the beginning of the disease corresponds to the temperature, then pronounced bradycardia develops. The boundaries of the heart are normal, the tones are muffled. Blood pressure is reduced in most cases. In severe cases of the disease, the development of infectious-toxic shock is observed. Signs of bronchitis and bronchopneumonia are often detected.

When palpating the abdomen, pain is determined, often in the hypochondrium, and in some patients, tension in the abdominal wall. Pain in the abdominal area can subsequently be intense, which necessitates differentiation from surgical diseases of the abdominal cavity. The liver is usually enlarged, the spleen – less often. Tapping on the lower back is painful. Stool is retained, but diarrhea with the appearance of mucus and blood in the stool is possible.

The hemogram in this period of the disease shows normocytosis or leukopenia with a neutrophilic shift to the left, thrombocytopenia, and an increase in ESR. IN general analysis urine - leukocytes and erythrocytes, slight proteinuria.

From the 3-4th day of illness, against the background of high temperature, the oliguric period begins. The condition of the patients noticeably worsens. Severe pain occurs in the lumbar region, often forcing the patient to take a forced position in bed. There is an increase in headache, repeated vomiting occurs, leading to dehydration. The manifestations of hemorrhagic syndrome increase significantly: hemorrhages in the sclera, nasal and gastrointestinal bleeding, hemoptysis.

The amount of urine decreases to 300-500 ml per day, in severe cases anuria occurs.

Bradycardia, hypotension, cyanosis, and rapid breathing are noted. Palpation of the kidney area is painful (examination should be carried out carefully due to the possible rupture of the renal capsule with rough palpation). From the 6-7th day of illness, body temperature decreases lytically and, less often, critically, but the condition of the patients worsens. Characterized by pale skin combined with cyanosis of the lips and limbs, severe weakness. Signs of hemorrhagic syndrome persist or increase, azotemia progresses, manifestations of uremia are possible, arterial hypertension, pulmonary edema, in severe cases coma develops. Peripheral edema is rare.

The hemogram naturally reveals neutrophilic leukocytosis (up to 10-30 * 10^9 /l of blood), plasmacytosis (up to 10-20%), thrombocytopenia, an increase in ESR to 40-60 mm/h, and with bleeding - signs of anemia. Characterized by increased levels of residual nitrogen, urea, creatinine, hyperkalemia and signs of metabolic acidosis.

A general urine test reveals massive proteinuria (up to 20-110 g/l), the intensity of which varies throughout the day, hypoisosthenuria (relative density of urine 1.002-1.006), hematuria and cylindruria; Casts containing tubular epithelial cells are often found.

From the 9-13th day of illness, the polyuric period begins. The condition of the patients noticeably improves: nausea and vomiting stop, appetite appears, diuresis increases to 5-8 liters, nocturia is characteristic. Patients experience weakness, thirst, and are troubled by shortness of breath and palpitations even with little physical exertion. Lower back pain decreases, but mild, aching pain may persist for several weeks. Long-term hypoisosthenuria is characteristic.

During the period of convalescence, polyuria decreases, body functions are gradually restored.

The lungs are isolated moderate severity and severe forms of the disease. The mild form includes those cases when the fever is low, hemorrhagic manifestations are mild, oliguria is short-lived, and there is no uremia. In the moderate form, all stages of the disease develop sequentially without life-threatening massive bleeding and anuria, diuresis is 300-900 ml, the residual nitrogen content does not exceed 0.4-0.8 g/l. In severe cases, a pronounced febrile reaction is observed, infectious-toxic shock, hemorrhagic syndrome with bleeding and extensive hemorrhages in the internal organs, acute adrenal insufficiency, and cerebrovascular accident are possible. Anuria and progressive azotemia (residual nitrogen more than 0.9 g/l) are noted. Death may occur due to shock, azotemic coma, eclampsia, or rupture of the renal capsule. There are known forms of HFRS that occur with encephalitis syndrome.

Complications. Specific complications include infectious-toxic shock, pulmonary edema, uremic coma, eclampsia, kidney rupture, hemorrhages in the brain, adrenal glands, heart muscle ( clinical picture myocardial infarction), pancreas, massive bleeding. Pneumonia, abscesses, phlegmon, mumps, and peritonitis are also possible.

Forecast. Mortality due to HFRS in the Far East has reached 6-8% in recent years, in the European part of Russia - 1-3.5%, but up to 10% is possible.

Diagnostics. Recognition of HFRS is based on identifying characteristic clinical signs. From epidemiological data, contact with environmental objects infected with rodent secretions should be taken into account.

Changes in the hemogram in the form of leukopenia followed by neutrophilic hyperleukocytosis, thrombocytopenia, and increased ESR are of important diagnostic importance. An essential diagnostic sign is massive and alternating proteinuria, persistent hypoisosthenuria. The diagnosis is confirmed using MFA, RIA and ELISA with the Hantaan virus antigen in cryostat sections of the lungs of rodents (bank voles Apodemus agrarius) and antibodies to it in NRIF.

It is carried out with influenza, typhoid and cheese typhus, leptospirosis, encephalitis, acute pyelonephritis, surgical diseases of the abdominal cavity (acute appendicitis, cholecystitis, pancreatitis, perforated gastric ulcer), etc.

Treatment. Patients with HFRS are subject to mandatory hospitalization in an infectious diseases hospital, subject to the requirements of the most gentle transportation. Therapeutic measures are carried out taking into account the period and severity of the disease with constant monitoring of the main biochemical parameters. The patient must remain in bed during acute period illness and before the onset of convalescence. Easily digestible food is prescribed without restrictions table salt(table No. 4 according to Pevzner).

In the initial period, the complex of therapeutic agents includes isotonic solutions glucose and sodium chloride, ascorbic acid, rutin, antihistamines, analgesics, antiplatelet agents. There is positive experience with the use of antiviral drugs (ribamidil).

Against the background of oliguria and azotemia, limit the intake of meat and fish dishes, as well as foods containing potassium. The amount of fluid drunk and administered to the patient should not exceed the daily volume of excreted urine and vomit by more than 1000 ml, and at high temperatures - by 2500 ml.

Treatment of patients with severe forms of HFRS with severe renal failure and azotemia or infectious-toxic shock is carried out in departments intensive care using a complex of anti-shock measures, prescribing large doses of glucocorticoids, broad-spectrum antibiotics, blood ultrafiltration methods, hemodialysis, and in case of massive bleeding - blood transfusions.

Patients are discharged from the hospital after clinical recovery and normalization of laboratory parameters, but not earlier than 3-4 weeks from the onset of the disease in moderate and severe forms of the disease. Those who have recovered are subject to dispensary observation for 1 year with quarterly monitoring of a general urine test, blood pressure, examination by a nephrologist, and an ophthalmologist.

Prevention. Preventive measures are aimed at destroying the sources of infection - mouse-like rodents, as well as interrupting the routes of its transmission from rodents to humans.

Synonym: acute infectious capillary toxicosis, hemorrhagic fever, Congo-Crimean fever

Hemorrhagic Congo-Crimean fever - a viral natural focal disease, the causative agent of which is transmitted through the bites of ixodid ticks; characterized by severe intoxication and pronounced hemorrhagic syndrome.

Historical information. The disease was first described by M.P. Chumakov et al. in 1944-1945 in Crimea and later in the republics of Central Asia. In 1956-1969 foci of similar diseases have been identified in Bulgaria, Yugoslavia, Hungary, East and West Africa, Pakistan and India. The disease is widespread in Crimea, Donetsk, Astrakhan, Rostov and Kherson regions, Krasnodar and Stavropol territories, Kazakhstan, Uzbekistan, Turkmenistan and Azerbaijan.

Etiology. The causative agent is a virus of the genus nairovirus, family Bunyaviridae.

Epidemiology. Congo-Crimean hemorrhagic fever is a natural focal virus. The reservoir of viruses is wild (hares, African hedgehogs, etc.) and domestic (cows, sheep, goats) animals, ticks of more than 20 species from 8 genera with transovarial transmission of pathogens.

The mechanism of infection is usually transmissible through the bite of an infected tick, Nualoma plumbeum (in the Crimea), Nualoma anatolicum (in Central Asia, Africa) and biting midges - Culicoideus. Aerogenic infection is possible (in laboratory conditions) and through contact with the blood of sick people (nosocomial infection).

In endemic areas, the incidence is seasonal and increases during the period of agricultural work (in our country in June - August), often acquiring an occupational nature. In non-immune individuals, the disease is severe with high mortality. After illness, strong immunity remains.

Pathogenesis and pathological picture. Pathological reactions in Crimean hemorrhagic fever are characterized by a cyclic course. After the introduction of the virus and its replication in the elements of the macrophage system, the viremia phase develops, which determines the occurrence of a general toxic syndrome. The subsequent phase of hematogenous dissemination leads to the development of universal capillary toxicosis, intravascular coagulation syndrome and various injuries (bridge-like necrosis in the liver, dystrophic changes in the myocardium, kidneys and adrenal glands), which is clinically manifested by massive hemorrhages and signs of organ pathology.

Clinical picture. The incubation period lasts 2-14 days (average 3-5 days). The disease can occur in mild, mild, moderate and severe forms. In addition to the incubation period, there are 3 periods of the disease: initial, height, or hemorrhagic phase, and outcome.

The initial period lasts 3-6 days and is characterized by sudden chills, a rapid increase in body temperature to 39-40°C, widespread myalgia and arthralgia, severe headache, and often pain in the abdomen and lumbar region. A number of patients have a positive Pasternatsky symptom. Common symptoms include dry mouth, dizziness and repeated vomiting.

Patients are usually excited, their face, mucous membranes, neck and upper chest are hyperemic, their lips are dry, and a herpetic rash is often noted. Arterial hypotension is characteristic, the pulse often corresponds to body temperature or is somewhat slow. Hematological changes during this period are manifested by leukopenia with a neutrophilic shift to the left, thrombocytopenia, and increased ESR.

The peak period of the disease lasts 2-6 days, often developing after a short-term, for 1-2 days, decrease in body temperature. In this phase of the disease, a pronounced hemorrhagic syndrome is detected in the form of a petechial rash on the lateral areas of the body, in the area of ​​​​large folds and limbs. In severe forms of the disease, purpura, ecchymosis are observed, and bleeding from the gums, nose, stomach, uterus, intestines, and lungs is possible.

Patients are depressed and pale; they have acrocyanosis, tachycardia and arterial hypotension; possible delirium. In 10-25% of cases, meningeal symptoms, agitation, convulsions are observed, followed by the development of coma. The liver is usually enlarged, and some patients show signs of hepatargia. Oliguria, microhematuria, hypoisosthenuria, and azotemia often develop. Sometimes there are complications in the form of pneumonia, pulmonary edema, thrombophlebitis, acute renal failure, shock. The duration of fever is 4-8 days.

The convalescence period is long, up to 1-2 months, and is characterized by an asthenic symptom complex. In some patients, performance is restored over the next 1-2 years.

In endemic areas, abortive forms of the disease without pronounced hemorrhagic syndrome are often observed.

At laboratory research, in addition to characteristic hematological changes, an increase in hematocrit, residual nitrogen, aminotransferase activity, and signs of metabolic acidosis are detected. Significant thrombocytopenia and high hematocrit values ​​may indicate a poor prognosis.

Forecast. Serious, mortality rate may reach 40%.

Diagnostics. Recognition of the disease is based on identifying typical signs of the disease: acute onset of the disease with high fever, facial hyperemia, rapid increase in hemorrhagic manifestations, vascular insufficiency, nephropathy and hepatopathy in patients belonging to the high-risk category (livestock breeders, hunters, geologists, etc.).

Specific diagnostics include isolation of the virus from the blood during the period of viremia, the use of serological tests: NRIF, RTNGA, RSK.

Differential diagnosis. It is carried out with meningococcal infection, influenza, leptospirosis, typhus, thrombocytopenic purpura and Henoch-Schönlein disease, and in residents of tropical countries with yellow fever and other hemorrhagic fevers.

Treatment. Carried out in accordance with general principles therapy of patients with hemorrhagic fevers. A positive effect was obtained from the use of immune serum 60-100 ml (proposed by M.P. Chumakov in 1944) or hyperimmune immunoglobulin.

Prevention. When hospitalizing patients, prevention of nosocomial infection, including parenteral routes, should be provided. A set of deratization and disinfection measures is carried out at the outbreaks of the disease. According to indications, vaccination and administration of immunoglobulin are necessary.

Hemorrhagic Omsk fever

Historical information. Hemorrhagic Omsk fever was first described in 1945-1948. during an epidemic outbreak in the Omsk and Novosibirsk regions. Since 1958, due to vector depression, case reports have been rare.

Etiology. The causative agent is the Omsk fever virus of the genus Flavivirus, family Togaviridae.

Epidemiology. Omsk hemorrhagic fever is a natural focal virus. The reservoir of viruses is muskrats, water rats and other rodents. Carriers are Dermacentor pictus ticks, possibly other ticks of this genus, gamasid ticks and fleas.

Human infection occurs through contact with infected muskrats, through tick bites, and through airborne dust in laboratory conditions.

The highest incidence of disease is usually observed in the summer months when ticks are active.

Pathogenesis and pathological picture. Not studied enough. As a result of viremia and hematogenous dissemination of viruses, characteristic capillary toxicosis develops, damage to the central and autonomic nervous system, endocrine system(adrenal glands). During the course of the disease, a strong immunity is formed.

Clinical picture. The incubation period is 3-10 days. The initial period of the disease is acute, with high fever, severe chills, headache and myalgia. Diffuse hyperemia of the face and neck, bright injection of blood vessels in the sclera and conjunctiva are noted. From the first days of the disease, petechial elements can be detected on the oral mucosa, in the pharynx and on the conjunctiva.

In contrast to Crimean hemorrhagic fever, hemorrhagic exanthema with Omsk fever is observed inconsistently (in 20-25% of patients); massive bleeding from the gastrointestinal tract and other organs is less common.

During the height of the disease, meningoencephalitis may develop. In 30% of patients, atypical pneumonia or bronchitis is detected; Hepatomegaly is often detected. In some patients, transient proteinuria may be noted.

The febrile period is 4-12 days; in the latter cases, the fever is often two-wave.

The hemogram shows leukopenia with a neutrophilic shift to the left, thrombocytopenia, and absence of eosinophils. During the second temperature wave, neutrophilic leukocytosis is possible.

Forecast. The disease is characterized by a favorable course and relatively low mortality (0.5-3%).

Diagnosis and treatment. Similar to those of Crimean-Congo hemorrhagic fever.

Yellow fever

Yellow fever (febres flava) is an acute viral natural focal disease with transmissible transmission of the pathogen through a mosquito bite, characterized by a sudden onset, high biphasic fever, hemorrhagic syndrome, jaundice and hepatorenal failure. The disease is common in tropical regions of America and Africa.

Yellow fever is a disease covered by the International Health Regulations and is notifiable by WHO.

Historical information. Yellow fever has been known in America and Africa since 1647. In the past, the infection often took the form of severe epidemics with high mortality. The viral nature and transmission of the virus by Aedes aegypti mosquitoes was established by K. Finlay and the W. Reed Commission in 1901 in Cuba. The eradication of this mosquito species has ensured the disappearance of urban foci of infection in the Americas. The yellow fever virus was isolated in 1927 in Africa.

Etiology. The causative agent, yellow fever virus (flavivirus febricis), belongs to the genus flavivirus, family Togaviridae.

Epidemiology. There are two epidemiological types of yellow fever foci - natural, or jungle, and anthropourgic, or urban.

In the case of the jungle form, the reservoir of viruses is marmoset monkeys, possibly rodents, marsupials, hedgehogs and other animals.

The carriers of viruses in natural foci of yellow fever are mosquitoes Aedes simpsoni, A. africanus in Africa and Haemagogus sperazzini and others in South America. Infection of humans in natural foci occurs through the bite of an infected mosquito A. simpsoni or Haemagogus, which is capable of transmitting the virus 9-12 days after the infectious bloodsucking.

The source of infection in urban yellow fever foci is a sick person in the period of viremia. Virus carriers in urban areas are Aedes aegypti mosquitoes.

The incidence in jungle foci is usually sporadic and is associated with human presence or economic activity in tropical forests. The urban form occurs in the form of epidemics.

Currently, sporadic incidence and local group outbreaks are being recorded in the tropical forest zone in Africa (Zaire, Congo, Sudan, Somalia, Kenya, etc.), South and Central America.

Pathogenesis and pathological picture. The inoculated yellow fever virus hematogenously reaches the cells of the macrophage system, replicates in them for 3-6, less often 9-10 days, then re-enters the blood, causing viremia and clinical manifestation of the infectious process. Hematogenous dissemination of the virus ensures its penetration into the cells of the liver, kidneys, spleen, bone marrow and other organs, where pronounced dystrophic, necrobiotic and inflammatory changes develop. The most typical occurrences of foci of colliquation and coagulation necrosis in the mesolobular parts of the hepatic lobule, the formation Councilman's corpuscle development of fatty and protein degeneration of hepatocytes. As a result of these injuries, cytolysis syndromes develop with an increase in ALT activity and a predominance of AST activity, cholestasis with severe hyperbilirubinemia.

Along with liver damage, yellow fever is characterized by the development of cloudy swelling and fatty degeneration in the epithelium of the renal tubules, the appearance of areas of necrosis, causing the progression of acute renal failure.

During the pathological examination, attention is drawn to the purplish-cyanotic coloration of the skin, widespread jaundice and hemorrhages in the skin and mucous membranes. The sizes of the liver, spleen and kidneys are increased, they show signs of fatty degeneration. Multiple erosions and hemorrhages are detected in the mucous membrane of the stomach and intestines. In addition to changes in the liver, dystrophic changes in the kidneys and myocardium are naturally detected. Hemorrhages are often detected in the perivascular spaces of the brain; The cardiovascular system is also affected.

With a favorable course of the disease, stable immunity is formed.

Clinical picture. There are 5 periods during the course of the disease. The incubation period lasts 3-6 days, less often it extends to 9-10 days.

The initial period (hyperemia phase) lasts for 3-4 days and is characterized by a sudden increase in body temperature to 39-41 ° C, severe chills, intense headache and diffuse myalgia. As a rule, patients complain of severe pain in the lumbar region, they experience nausea and repeated vomiting. From the first days of illness, most patients experience pronounced hyperemia and puffiness of the face, neck and upper chest. The vessels of the sclera and conjunctiva are clearly hyperemic (“rabbit eyes”), photophobia and lacrimation are noted. Prostration, delirium, and psychomotor agitation can often be observed. The pulse is usually rapid, and bradycardia and hypotension develop in the following days. The persistence of tachycardia may indicate an unfavorable course of the disease. Many people have an enlarged and painful liver, and at the end of the initial phase one can notice icterus of the sclera and skin, the presence of petechiae or ecchymoses.

The hyperemia phase is replaced by short-term (from several hours to 1-1.5 days) remission with some subjective improvement. In some cases, recovery occurs in the future, but more often a period of venous stasis follows.

The patient's condition noticeably worsens during this period. The temperature rises again to a higher level, and jaundice increases. The skin is pale, in severe cases cyanotic. A widespread hemorrhagic rash appears on the skin of the trunk and limbs in the form of petechiae, purpura, and ecchymoses. Significant bleeding of the gums, repeated vomiting with blood, melena, nasal and uterine bleeding. In severe cases of the disease, shock develops. The pulse is usually rare, weak filling, arterial pressure is steadily declining; Oliguria or anuria develops, accompanied by azotemia. Toxic encephalitis is often observed.

The death of patients occurs as a result of shock, liver and kidney failure on the 7-9th day of illness.

The duration of the described periods of infection is on average 8-9 days, after which the disease enters the convalescence phase with slow regression pathological changes.

Among local residents of endemic areas, yellow fever can occur in a mild or abortive form without jaundice and hemorrhagic syndrome, which makes timely identification of patients difficult.

Laboratory tests in the initial phase of the disease usually show leukopenia with a shift of the leukocyte formula to the left to promyelocytes, thrombocytopenia, and during the height of the disease - leukocytosis and even more pronounced thrombocytopenia, increased hematocrit, hyperkalemia, azotemia; in urine - red blood cells, protein, casts.

Hyperbilirubinemia and increased activity of aminotransferases, mainly AST, are detected.

Forecast, Currently, the fatality rate for yellow fever is approaching 5%.

Diagnostics. Recognition of the disease is based on identifying a characteristic clinical symptom complex in individuals classified as high risk of infection (unvaccinated people who visited jungle foci of yellow fever within 1 week before the onset of the disease).

The diagnosis of yellow fever is confirmed by the isolation of the virus from the patient’s blood (in the initial period of the disease) or antibodies to it (RSK, NRIF, RTPGA) in later periods of the disease.

Differential diagnosis. Carry out with other types of hemorrhagic fevers, viral hepatitis, malaria.

Treatment. Patients with yellow fever are hospitalized in hospitals protected from mosquitoes; carry out prevention of parenteral infection.

Therapeutic measures include a complex of anti-shock and detoxification agents, correction of hemostasis. In cases of progression of hepatic-renal failure with severe azotemia, hemodialysis or peritoneal dialysis is performed.

N. V. Gavrilova Tamara Vladimirovna Pariyskaya

by P. Vyatkin

From the book Complete Medical Diagnostics Guide by P. Vyatkin

From the book Complete Medical Diagnostics Guide by P. Vyatkin

From the book Modern Home Medical Directory. Prevention, treatment, emergency care author Victor Borisovich Zaitsev

From the book Great Protective Book of Health author Natalya Ivanovna Stepanova

Initially, the diagnosis of HFRS is established on the basis of the clinical picture of the infection with a set of certain symptoms of the early (first week) stage of the disease: acute onset, fever, syndrome of general toxicosis and hemodynamic disorders, then pain in the abdomen and lumbar region. The stage at the height of the disease is characterized by the dominance of hemorrhagic syndrome and manifestations of acute renal failure (ARF). At the same time, the polymorphism and variability of symptoms, the lack of standardized characteristics of the leading syndromes do not allow the primary diagnosis of HFRS to be established clinically with reliable accuracy.
The clinical picture of HFRS, described by numerous authors from different regions of the world and associated with different hantaviruses, demonstrates the similarity of the main manifestations of the disease. The generalized nature of the infection with the involvement of various organs and systems in the pathological process determines the polymorphism of symptoms regardless of the etiological agent (hantavirus serotype).
The disease is characterized by a cyclical course and a variety of clinical variants from abortive febrile forms to severe forms with massive hemorrhagic syndrome and persistent renal failure.
The following periods of illness are distinguished. Incubation (from 1 to 5 weeks, on average 2-3 weeks), febrile (initial, general toxic), lasting on average from 3 to 7 days; oliguric (on average 6-12 days), polyuric (on average 6-14 days), convalescence period (early - up to 2 months and late - up to 2-3 years).
In the clinical picture of the disease, 6-7 main clinical and pathogenetic syndromes are distinguished:
1) general toxic;
2) hemodynamic (central and microcirculatory disorders);
3) renal;
4) hemorrhagic;
5) abdominal;
6) neuroendocrine;
7) respiratory syndrome.
Various combination of these syndromes characterizes each of the four periods of the disease. Symptoms of dysfunction of various organs involved in the infectious process are observed during all periods of the disease.
The incubation period lasts from 4 to 49 days (most often from 14 to 21 days), with no clinical manifestations. During this period, the HFRS virus enters the body through the epithelium respiratory tract, gastrointestinal tract, as well as through damaged skin. The virus then reproduces in the cells of the macrophage system. It causes activation of specific and nonspecific defense factors, the adequacy of which, as well as the infectious dose, pathogenicity and virulence of the pathogen, determines both the fate of the virus itself and the severity of pathological changes in the patient’s body.
1.3.1 Initial (febrile) period of HFRS.
The pathogenetic basis of the initial (febrile) period of HFRS is viremia, intoxication, activation of hormonal and immune systems, production of pro-inflammatory cytokines, massive vasopathy (associated with the tropism of hantavirus to the endothelium of microcirculatory vessels), coagulopathy, microcirculation disorders, tissue destruction, formation of autoantigens with the formation of autoantibodies (in severe HFRS).
In most patients, HFRS begins acutely. Chills, headache, muscle and joint pain, dry mouth, thirst, sometimes a slight cough, and severe general weakness appear. In a small proportion of patients, the appearance of pronounced signs of the disease is preceded by a prodromal period: general malaise, fatigue, low-grade fever.
Fever in most patients reaches high levels on the first day of illness and lasts from 5-6 to 10-11 days, on average 6-7 days. The temperature curve does not have a specific pattern; in most cases it decreases lytically over two to three days. In mild forms of the disease, there is a slight short-term fever, which is often visible to the patient.
An objective examination reveals pronounced hyperemia of the skin of the face, neck, upper half of the body, associated autonomic disorders at the level of the centers of the cervical and thoracic spinal cord. Particularly noticeable is the injection of blood vessels in the sclera and conjunctiva, hyperemia of the oropharyngeal mucosa, and the appearance of spotted enanthema of the upper palate. It is possible to develop hemorrhagic syndrome in the form of a petechial rash in the area of ​​the inner surfaces of both shoulders, the lateral surfaces of the torso, on the chest (the “scourge” symptom), ecchymosis at the injection sites, and short-term nosebleeds. Positive endothelial symptoms (cuffs, pinch, tourniquet) are determined. Blood pressure is normal or tends to hypotension, and relative bradycardia is characteristic. Some patients note a feeling of heaviness in the lower back.
At the end of the initial period, the frequency of urination decreases and diuresis decreases slightly. Laboratory changes are characterized by a slight increase in serum levels of creatinine and urea, a decrease in the relative density (RD) of urine and the appearance of single fresh red blood cells and proteinuria in its sediment. The blood test in most patients is characterized by moderate leukopenia and, less often, slight leukocytosis and band shift to the left, signs of blood thickening against the background of plasmorrhea and hypovolemia in the form of an increase in the number of red blood cells and hemoglobin. The pathognomonic symptom of HFRS in early period is thrombocytopenia, caused by the damaging effect of the virus, the development of immunopathological reactions, an increase in the adhesive properties of platelets and the formation of cellular aggregates with their retention in microcirculation vessels, and a violation of the rheological properties of blood.
1,3,2 Oligouric period of HFRS.
During the oligouric period of HFRS (the height of the disease), systemic circulatory disorders, hypovolemia and hemoconcentration, hypoperfusion and hypoxia of organs, tissue acidosis and damage to vital body systems continue. The hypocoagulation phase of DIC predominates. Edema, hemorrhages, dystrophic and necrobiotic changes occur in the pituitary gland, adrenal glands, kidneys, myocardium and other parenchymal organs.
The greatest changes are observed in the kidneys, which is accompanied by a decrease in glomerular filtration and impaired tubular reabsorption. AKI in HFRS is caused by damage to the renal parenchyma, acute interstitial nephritis. On the one hand, disruption of microcirculation and increased permeability of the vascular wall contribute to plasmorrhea and serous-hemorrhagic edema of the interstitium of the kidneys, mainly pyramids, with subsequent compression of the tubules and collecting ducts, leading to dystrophy, desquamation of the tubular epithelium, sweating of protein and fibrin with obstruction of the tubules and collecting ducts tubes with fibrin clots and impaired reverse reabsorption of urine. On the other hand, an immunopathological factor is the fixation of immune complexes on the glomerular basement membrane, which reduces glomerular filtration. Interstitial edema increases the impairment of renal microcirculation, up to ischemia, in some cases to necrosis of the renal tubules, and contributes to a further decrease in glomerular filtration and tubular reabsorption. Tubular cells are especially sensitive to hypoxia, a lack of energy material that occurs during ischemia. IN pathological process autoantibodies to damaged tissue structures may also be involved. Disorders in central hemodynamics (hypovolemia, decreased cardiac output, blood pressure) aggravate renal blood flow disorders.
The oliguric period is the most striking period when the clinical picture inherent in HFRS develops. Body temperature drops to normal, sometimes rising again to subfebrile levels - a “two-humped” curve. However, a decrease in temperature is not accompanied by an improvement in the patient’s condition; as a rule, it worsens. General toxic effects reach a maximum, signs of hemodynamic disturbances, renal failure, and hemorrhagic diathesis intensify. Most constant sign The transition to the oliguric period is marked by the appearance of lower back pain of varying intensity: from an unpleasant feeling of heaviness to sharp, painful nausea, vomiting not associated with food or medication, and in severe cases, hiccups. Asthenia and adynamia increase. Many patients experience abdominal pain, mainly in the umbilical and epigastric region. The face is hyperemic, as renal failure increases, the blush gives way to pallor, hemorrhagic manifestations intensify, mainly in severe cases of the disease - hemorrhages in the sclera, ecchymosis, nosebleeds and gross hematuria, hematomas at injection sites, less often - intestinal bleeding, blood in the vomit, hemoptysis. When making a diagnosis, it is important to identify visual impairment (decreased visual acuity, “flying spots”, a feeling of fog before the eyes), caused by impaired microcirculation in the retina of the eyes, which appears on days 2-7 of the disease and continues for 2-4 days.
In most patients, at the beginning of the oligouric period, blood pressure is within normal limits, and in severe cases it develops arterial hypotension, reaching the degree of severe collapse or infectious-toxic shock. In the second half of this period, blood pressure (BP) increases in 1/3 of patients; the duration of hypertension rarely exceeds 5 days. Absolute or relative bradycardia is characteristic. Vesicular hard breathing is heard over the lungs, isolated dry rales, wet rales can be detected, in especially severe cases a picture of pulmonary edema or distress syndrome is observed.
On days 2-5 of illness, 10-15% of patients experience diarrhea. The tongue is dry, covered with a gray or brown coating. The abdomen is moderately swollen, there is pain on palpation in the epigastric and periumbilical areas, especially in the projection of the kidneys and sometimes of a diffuse nature. There may be phenomena of peritonism. The liver is enlarged and painful in 20-25% of patients. In isolated cases, signs of meningism may appear. Most specific complications of HFRS develop during this period.
Kidney syndrome is one of the leading ones. Pasternatsky's symptom is positive or sharply positive, so this symptom must be checked with the utmost caution, by applying light pressure in the area of ​​the costovertebral points to avoid tearing the renal cortex. The full picture of acute renal failure is characterized by progressive oligoanuria, increasing uremic intoxication, water and electrolyte imbalance, and increasing metabolic acidosis.
Disturbances in the activity of the central nervous system are observed in almost all patients, both as manifestations of cerebral symptoms associated with intoxication, and as a consequence of focal lesions. It is possible to develop symptoms of meningism, encephalitic reactions with the appearance of meningeal symptoms (stiff neck, Kernig, Brudzinski symptoms), focal symptoms (corresponding to areas of brain damage), and mental disorders are also observed (from sleep disturbances to various disorders of consciousness).
The hemogram naturally reveals neutrophilic leukocytosis (up to 15-30×109/l of blood), plasmacytosis, and thrombocytopenia. In severe cases, the blood picture is characterized by a leukemoid reaction. Due to blood thickening, the level of hemoglobin and red blood cells may increase, but with bleeding these indicators decrease. The ESR gradually accelerates. Characterized by increased levels of residual nitrogen, urea, creatinine, as well as hyperkalemia, hypermagnesemia, hyponatremia and signs of metabolic acidosis. A general urine test reveals massive proteinuria (up to 33-66 g/l), the intensity of which varies throughout the day (“protein shot”), hematuria, cylindruria, and the appearance of renal epithelial cells (the so-called Dunaevsky cells). From the second half of the oliguric period, hyposthenuria develops.
Significant changes occur in the state of the blood coagulation system. While hypercoagulation persists in some patients, hypocoagulation develops in severe cases of the disease. It is caused by consumption plasma factors blood clotting due to the formation of microthrombi in small vessels. It is in the oliguric period of HFRS that hemorrhagic manifestations reach their apogee and often become the cause of death.
1,3,3 Polyuric period of the disease.
The period of polyuria begins from 9-13 and lasts until 21-24 days of illness. As a result of the formation specific immunity, elimination of the pathogen, immune complexes, pathological changes in the kidneys and other organs regress, and there is a tendency towards normalization of their functions. In the stage of polyuria, glomerular filtration increases first of all. In conditions of damaged tubular apparatus, even a slight increase in filtration contributes to an increase in diuresis. Polyuria is caused by osmotic diuresis. Nitrogenous wastes accumulated in the body during oliguria, with the restoration of the functional capacity of the kidneys, exhibit their osmodiuretic effect, and the amount of urine excreted does not depend on the state of hydration of the body; excessive fluid loss with urine with insufficient replenishment can lead to dehydration, hypovolemia and re-development of oliguria . Slow restoration of the reabsorption function of the tubules leads to loss of potassium, sodium, and chlorine.
Vomiting stops, pain in the lower back and abdomen gradually disappears, sleep and appetite normalize, the daily amount of urine increases (up to 3-10 l), nocturia is characteristic. Against the background of hypokalemia, weakness, muscle hypotension, intestinal paresis, bladder atony, tachycardia, arrhythmia persist, dry mouth, and thirst appear. The duration of polyuria and isohyposthenuria, depending on the severity of the clinical course of the disease, can range from several days to several weeks. However, the rate of improvement does not always parallel the increase in diuresis. Sometimes in the first days of polyuria, azotemia still increases, dehydration, hyponatremia, hypokalemia may develop, and hypocoagulation persists, so this stage is often called the stage of “uncertain prognosis.”
Laboratory changes during this period consist of a slight decrease in the number of red blood cells, hemoglobin, and an increase in the number of platelets. The erythrocyte sedimentation rate (ESR) accelerates somewhat. Blood serum urea and creatinine levels gradually decrease, and hypokalemia often develops.
Changes in urine (Zimnitsky test) are characterized by extremely low relative density, not exceeding 1001-1005. A small amount of protein, moderate hematuria and cylindruria, sometimes leukocyturia, and small amounts of renal epithelial cells are detected in the urine sediment.
1,3,4 Period of convalescence.
The recovery period is pathogenetically characterized by the formation of stable post-infectious immunity with a high level of specific IgG, restoration of hemostasis, microcirculation, glomerular filtration of urine, but with long-term persistence of tubular disorders (tubular insufficiency). There is a noticeable improvement in the general condition, restoration of daily diuresis, normalization of urea and creatinine levels. Convalescents exhibit asthenic syndrome: general weakness, fatigue, decreased performance, emotional lability. Along with this, vegetative-vascular syndrome is observed in the form of hypotension, muffled heart sounds, shortness of breath with little physical exertion, tremor of the fingers, increased sweating, and insomnia. During this period, heaviness in the lower back, a positive Pasternatsky sign, nocturia may be noted, and isohyposthenuria may persist for a long time (up to 1 year or more). It is possible to connect a secondary bacterial infection with the development of pyelonephritis, most often observed in survivors of acute renal failure.

A complex and dangerous disease is hemorrhagic fever with renal syndrome (Ebola, Marburg disease). Its epidemiology represents abnormalities of a zoonotic nature, i.e., it is spread by animals. Hemorrhagic fever has different ways of attack, and almost the entire body is affected by the disease - the kidneys and liver are affected, and there is a destructive effect on cardiovascular system, causes deviations in hemodynamics. This disease is severe and is characterized by complications of the patient’s condition - it can cause toxic shock and result in death.

Characteristics of the pathogen

Hemorrhagic fever with renal syndrome is a virus. This was proven by scientific research in 1944. However, it was possible to study the causative agents of the disease much later. It is a bacterium that is found in the lungs of a South Korean rodent. This pathogen is called Hantanaan. Today, HFRS disease is classified as a group of so-called bunya infections. The pathogen is a sphere with a diameter of 85 to 120 nm. Its differential genome is divided into three parts, which represent with Latin letters L, M, S. Infectious propagation occurs through the cytoplasm of infected molecules. Many cells are affected by Ebola: liver, kidneys, lungs, salivary glands. When there is a focus of HFRS, an antigenic reaction occurs.

Hemorrhagic adaptation

The classification of HFRS is varied. More than 25 subspecies of bacteriophages are already known. They are developing in different countries and regions. The problem covers the territories of Japan, China, Russia, North Korea, South Korea and the Far East. The classic vector is the bank vole mouse. Marburg disease easily adapts to the environment and survives at an average temperature of 4–20 degrees. When taking blood samples, it lives in the serum for up to 4 days, after which it “falls asleep.” It becomes active again when the heat increases to 50 degrees. Ebola is sensitive to acidic conditions, chloroform, benzene, acetone, ether and ultraviolet rays.

Etiology of the disease

The source of infection in Europe is considered to be rodents: voles, rats, hamsters. The habitat for the survival and reproduction of vectors is considered to be forest-steppe zones, foothill and river valleys, and forest-steppes. You can become infected with fever with renal syndrome:

• through dust, inhaling food residues, the vital activity of infected rodents;
• by getting animal feces into the mouth (getting them into food, drinks);
• through the skin when touching infected objects, animals, excrement, which may be in feed, hay, brushwood.

There are different ways that hemorrhagic molecules enter the blood, depending on the site of transmission:

• Lesnoy - the incidence is the highest. The bacteriophage enters the body during a walk in the forest, while picking mushrooms and berries.
• Household - the possibility of disease transmission in a residential area is due to the penetration of carriers there.
• Production - due to work involving a large amount of dust and field work: drilling, laying oil pipelines.
• Gardening - you can become infected through the ground where infected rodent feces are located.
• Camp - infection occurs during recreation in public institutions located in natural conditions.
• Agricultural - the danger is seasonal and is caused by agricultural work.

Pathogenesis and its features

After an infection, strong immunity is formed. Repeated diseases do not occur in one person. The pathogenesis of the disease is still poorly understood. Therefore, there is only an approximate laboratory structure for the development of bacteria. The progressive stages of HFRS are known, according to which the disease gradually develops. Below are the 5 main steps.

Incidence and first manifestations

Hemorrhagic fever spreads through the mucous membrane of the respiratory system, digestion and skin. The infection then multiplies in the SSF and lymph nodes. Infectious molecules have a toxic effect on blood vessels and the central nervous system. At this stage it ends incubation period, pathogenic bodies penetrate the circulatory system.

Allergy, intoxication and immunity damage

Toxic-allergic and immunological reactions. When attacked by infectious organisms, protective cells try to neutralize the destructive effects. For this reason, cellular clusters or complexes are formed - IR. If the effect of hemorrhagic fever cannot be stopped, IR enters the connective tissues and organs. This has a destructive effect on the vegetative centers and blood vessels. As a result, a number of functional abnormalities develop: microthrombosis, decreased vascular tone, plasmorrhea, diathesis, acute renal failure.

Pathologies of metabolic processes

A developing infection leads to swelling in the adrenal glands, kidneys, liver, and parenchyma. Organ dystrophy and cellular necrosis may develop. Such changes lead to new diseases - hypoxia, acidosis in tissues, hypovolemia, circulatory disorders, damage to vital centers in the human body. The renal system is most susceptible to stress: glomerular filtration fails with the manifestation of oliguria, azotemia, and protoanuria. This stage can become a threat to the patient’s life, since serious complications occur in the form of collapse, uremia, paralysis, and kidney rupture.

Recovery

Polyuria is increased urine production.

With the onset of the recovery stage, immunity to the disease is formed. Due to changes in the state of the body, the amount of urine produced increases - polyuria, and the ability to absorb useful substances into the blood decreases. As a result, the amount of metabolic products contained in the blood serum decreases, which makes it possible to gradually restore kidney function over a period of up to 5 years.

What are the symptoms of the disease?

Incubation and hemorrhoidal fever

The symptoms of this disease are characterized by a certain cyclicity and appear at different periods.

Virus incubation time varies. The period lasts from a week to a month and a half. Average term- about 2 weeks. First stage- last no more than 3 days. Headaches, aches, weakness and chills are observed. First of all, the patient develops hemorrhagic fever when the fever rises to 40 degrees. It lasts about 2 weeks. The most severe fever is observed in the first half of the day. In addition, there are signs of poisoning - thirst, dry mouth, decreased appetite, sleep and vision disturbances. Disturbances occur in the muscles and joints, a coating is visible on the tongue, and redness of the mucous membrane of the eyes is observed.

Oliguric syndrome

The period of decrease in the amount of urine excreted is observed after a fever. Manifestations are observed within 10 days. At this stage, the fever stops, but this does not bring relief. Aches and pains in the lower back begin to bother me. Severe cases of Marburg virus may be accompanied by a gag reflex, and pain extends to the digestive area. General biochemical analysis blood test for HFRS will show an increase in the level of potassium, urea, chlorides, calcium, creatine. In addition, rashes appear on the skin - in the armpits, chest and shoulders. Bleeding may occur, both external (nosebleeds) and internal (hemorrhages in the gastrointestinal tract). Kidney and liver failure develops.

Manifestation of polyuria

Then there is an increase in the secreted fluid, it lasts for up to a month. At this stage, the manifestations practically disappear and the patient feels better. Polyuria is present when urine is excreted in large volumes - up to 10 liters. The functioning of the liver and kidneys is gradually restored, the content of substances in the blood is normalized. Within a month, the process of urination returns to normal, leaving only mild discomfort and a frequent urge to urinate.

Recovery

Then the recovery period begins: the patient recovers, functions return to normal, and symptoms no longer appear. This stage lasts from one to 3 years. Residual signs appear. Typically, they are divided into 3 groups:

• asthenia - accompanied by lack of appetite, weakness, dizziness;
• abnormalities in the endocrine and nervous systems- manifested by increased sweating, itching of the skin, thirst, pain at the base of the spine, impotence;
The child has a high fever for a week.

The clinical picture of HFRS in children manifests itself at any age, even in newborns. The younger generation often does not have initial symptoms of the development of the virus, but appear immediately in acute form. High fever lasts for a week, it is accompanied by severe headaches, weakness, drowsiness, general malaise, and vomiting. Painful sensations appear in the back almost immediately, gradually moving to the abdominal area.

Hemorrhagic fever with renal syndrome (hemorrhagic nephrosonephritis) is an acute viral natural focal disease that occurs in the European part of Russia and in Far East. This disease is characterized by a febrile reaction, severe intoxication of the body, specific damage to the kidneys and damage to small blood vessels with subsequent development of thrombohemorrhagic syndrome.

HFRS: classification

There is currently no unified classification of this infectious disease. Causes, factors of occurrence, methods of spread of the disease Etiology Pathogen

The Manchurian hemorrhagic or Tula fever virus was isolated only in 1976, although viral etiology HFRS (ICD-10 code – A98.5) became known three decades earlier. The pathogen that causes HFRS was found in the lungs of rodents (the main carrier is the bank vole mouse). These small mammals are intermediate hosts (natural reservoir) of the infectious agent. Microbiology classifies the causative agent of HFRS as belonging to the Bunyanvirus family. The virus dies when heated to +50°C for half an hour. At temperatures from 0 to +4°C, it can remain active in the external environment for 12 hours. At temperatures from +4° to +20°, the virus in the external environment is quite stable, i.e. can remain viable for a long time.

Routes of transmission of HFRS In nature and rural areas, the virus is spread by several species of mice. The pathogen is excreted in their feces. Infection occurs through airborne dust or nutrition. A person becomes infected through direct contact with rodents, consumption of water and food containing their feces, as well as through inhalation of dust with microparticles of dried rodent feces. Infection through household items is possible. The peak incidence occurs in the autumn-winter period, when infection carriers move into residential and auxiliary buildings. In urban environments, the virus can be carried by rats. It is impossible to catch a fever from another person. To prevent the occurrence of outbreaks of epidemics, deratization is carried out, i.e. destruction of animals that are latent carriers of the virus. Note: up to 90% of cases are males aged 16 to 50 years. Pathogenesis The effect of the virus on organs and systems The virus enters the human body through the mucous membrane of the respiratory system. In some cases, the entrance gates of infection can be the mucous membranes of the digestive organs and damaged skin. No pathological changes are observed directly at the site of virus entry. Symptoms appear after the pathogen spreads throughout the body through the bloodstream and intoxication begins to increase. The virus is characterized by pronounced vasotropy; it has a pronounced negative effect on the vascular wall. Also an important role in the pathogenesis of hemorrhagic syndrome is the disruption of the functional activity of the blood coagulation system. In particularly severe cases of the disease, glomerular filtration is significantly reduced, although the structure of the glomeruli is not disturbed. The severity of thrombohemorrhagic syndrome directly depends on the severity of the disease. Immunity After once suffering from “Korean fever”, stable immunity remains; cases of re-infection have not been described in the medical literature.

Signs of HFRS

With HFRS, the incubation period can range from 7 to 45 days (most often about 3 weeks). It is customary to distinguish the following stages of disease development: 1. initial; 2. oliguric; 3. polyuric; 4. convalescence (recovery). With HFRS, the clinical picture depends on a number of factors, including the individual characteristics of the body and the timeliness of measures taken. For HFRS disease, the main symptoms are as follows: Initial period of HFRS

• high temperature (39°-40°C);
• chills;
• Strong headache;
• sleep disorders;
• blurred vision;
• hyperemia of the skin of the neck and facial area;
• dry mouth;
• weakly positive Pasternatsky symptom.

From 3-4 to 8-11 days (oliguric period)

• rash in the form of small hemorrhages (petechiae);
• vomiting 6-8 times a day;
• pain in the lumbar region;
• hyperemia of the pharynx and conjunctiva;
• dry skin;
• injection of scleral vessels;
• 50% of patients have thrombohemorrhagic syndrome.

From 6-9 days

• pain in the abdominal area;
• hemoptysis;
• vomiting blood;
• tarry stools;
• nosebleeds;
• lower back pain;
• blood in urine;
• positive Pasternatsky symptom;
• puffiness of the face;
• pastiness of the eyelids;
• oliguria to anuria.

The polyuric period begins from the 9-13th day from the first clinical manifestations. Vomiting disappears, as well as severe pain in the lower back and abdomen, appetite returns and insomnia disappears. Daily diuresis increases to 3-5 liters. Convalescence occurs from 20-25 days. If these symptoms appear, you should immediately seek medical help. Treatment should be carried out only in a specialized hospital.

Possible complications of HFRS

The disease can cause severe complications, including:

• acute vascular insufficiency;
• focal pneumonia;
• pulmonary edema;
• kidney rupture;
• azotemic uremia;
• eclampsia,
• acute interstitial nephritis;
• acute renal failure.

In some cases, HFRS, also known as Churilov's disease, may be accompanied by pronounced brain symptoms. In this case, it is customary to talk about either a complication or a special “meningoencephalitic” form of the course. The consequences of HFRS cannot be underestimated. Lack of adequate treatment against the background of developed complications can cause death.

Diagnostics

Differential diagnosis of HFRS with such infectious diseases, like other hemorrhagic fevers, typhoid fever, leptospirosis, tick-borne rickettsiosis, tick-borne encephalitis and common influenza. The diagnosis of HFRS is made taking into account epidemiological data. The patient’s possible stay in endemic areas is taken into account, general level incidence in the area and seasonality. Much attention is paid to fairly specific clinical symptoms. Laboratory diagnosis of HFRS reveals the presence of casts in the urine, as well as significant proteinuria. A blood test for HFRS shows an increase in plasma cells, an increase in the erythrocyte sedimentation rate and pronounced leukocytosis. Of the special laboratory methods, the detection of IgM by enzyme-linked immunosorbent assay is often used. If there are complications already during treatment, some types of instrumental studies may be needed: FGDS, ultrasound, CT and radiography.

HFRS treatment

There are no standard treatment regimens for HFRS. Therapy should be comprehensive and aimed at eliminating the most important pathogenetic syndromes. It is necessary to combat DIC syndrome, renal failure and general intoxication. Treatment involves early hospitalization and strict bed rest for 1 to 4 weeks, depending on the severity of the disease. Strict control of the volume of fluid consumed and lost by the patient is necessary. Monitoring of hemodynamics, hemogram, hematocrit is required; Urine tests and electrolyte balance are regularly examined.

Drug therapy.

During the febrile period, antiviral, antioxidant and detoxification therapy is carried out and measures are taken to prevent the development of DIC syndrome.

Etiotropic therapy

For etiotropic therapy, either immunobiological drugs (interferons, hyperimmune plasma, donor specific immunoglobulin, etc.) or chemotherapy drugs - ribavirin (a nucleoside derivative), as well as amixin, cycloferon and iodantipyrine (interferon inducers) are used. The fight against intoxication involves infusions of glucose solutions and saline with vitamin C. Hemodez can be administered once. At body temperatures above 39°C, anti-inflammatory drugs with an antipyretic effect are administered. To prevent DIC syndrome, the patient is administered antiplatelet agents, angioprotectors, and in severe cases, protease inhibitors and fresh frozen plasma. Administration of antioxidants to patients (for example, ubiquinone and tocopherol) is indicated.

Antishock therapy

To prevent the development of infectious-toxic shock, early hospitalization and strict bed rest are indicated. If ITS has developed (more often this happens on days 4-6 from the onset of the disease), then the patient is given intravenous drips of rheopolyglucin (400 ml) with hydrocortisone (10 ml), glucocorticosteroid drugs, 4% sodium bicarbonate solution (200 ml intravenously), cardiotonic drugs and cardiac glycosides (cordiamin, strophanthin, korglykon) intravenously. If measures are ineffective or stage 3 shock develops, dopamine administration with glucose or saline is indicated. When disseminated intravascular coagulation develops against the background of shock, heparin, protease inhibitors and angioprotectors are indicated. After restoration of normal hemodynamics, the patient is administered diuretics (Lasix). Special instructions: In case of infectious-toxic shock, antispasmodics, sympathomimetics, hemodez and polyglucin should not be used. In the oliguric period, it is necessary to reduce protein catabolism, eliminate azotemia and reduce intoxication. Correction of acid-base and water-electrolyte balance, correction of disseminated intravascular coagulation, as well as prevention and treatment of possible complications are also necessary. Gastric and intestinal lavage with a weakly alkaline solution and intravenous infusions of glucose (with insulin) are used. Enterosorbents are prescribed orally. Protease inhibitors are also recommended. To combat overhydration, the administration of Lasix is ​​indicated, and sodium bicarbonate is used to reduce acidosis. Correction of hyperkalemia involves glucose-insulin therapy and a potassium-free diet. The pain syndrome is relieved by analgesics with desensitizing agents, persistent vomiting is eliminated by taking a solution of novocaine (orally) or atropine. The development of convulsive syndrome requires the use of relanium, aminazine or sodium hydroxybutyrate. For infectious complications, antibiotics from the groups of cephalosporins and semisynthetic penicillins are prescribed. During the period of convalescence, the patient needs general restorative drug therapy (including vitamins and ATP preparations).

Additional Methods

If conservative methods are ineffective, the patient may be indicated for extracorporeal dialysis.

HFRS: prevention

To prevent infection, it is often enough to observe the rules of personal hygiene while in the forest or rural areas. Water from open sources and containers should be boiled before drinking, hands should be washed thoroughly, and food should be stored in airtight containers. Under no circumstances should you handle rodents. After accidental contact, it is recommended to disinfect clothing and skin. When working in dusty areas (including barns and haylofts), you need to use a respirator.

Diet for HFRS and after recovery

Nutrition for HFRS should be fractional. For mild to moderate illness, patients are recommended to use table No. 4 (without limiting table salt), and for severe forms and the development of complications, table No. 1 is recommended. Against the background of oliguria and anuria, animal and plant products with high content protein and potassium. Meat and legumes, on the contrary, should be consumed during polyuria! The amount of fluid consumed should not exceed the volume excreted by more than 500-700 ml. The rehabilitation period after HFRS involves a nutritious diet with a limit on salty, fatty, fried and spicy foods.

Features in children

HFRS in children is especially severe. The principles of therapy do not differ from those in the treatment of adult patients.

Features in pregnant women

The disease poses a great danger to the fetus. If a woman falls ill during lactation, the infant is immediately transferred to artificial feeding.