Team of authors: Doctor of Medical Sciences, Professor D.Kh. Khunafina, Associate Professor O.I. Kutuev, associate professor A.M. Shamsieva, Doctor of Medical Sciences, Professor D.A. Valishin, Doctor of Medical Sciences R.T. Murzabaeva, associate professor A.P. Mamon, assistant A.N. Kurganova, assistant R.S. Sultanov, graduate student T.A. Khabelova

Synonyms: hemorrhagic nephrosonephritis, Churilov's disease, epidemic nephrosonephritis, Far Eastern hemorrhagic fever, Korean hemorrhagic fever, Manchurian hemorrhagic fever, Scandinavian epidemic nephropathy, Tula fever; hemorrhagic fever with renal syndrome, Korean hemorrhagic fever - English. Nephrosonephritis haemorrhagica - lat.

Hemorrhagic fever with renal syndrome (HFRS) is an acute viral natural focal disease characterized by systemic damage to small vessels, hemorrhagic diathesis, hemodynamic disorders and peculiar kidney damage such as acute interstitial nephritis with the development of acute renal failure (Sirotin B.Z., 1994).

Etiology

The viral nature of hemorrhagic fever with renal syndrome was proven back in 1944 by A. A. Smorodintsev, but only in 1976 did the South Korean scientist N. W. Lee (1976) manage to isolate the Hantaan virus from the lungs of the rodent Apodemus agrarius coreae (according to the name of the Hantaan River, which flows along the 38th parallel of the Korean Peninsula). Subsequently, viruses were used to diagnose hemorrhagic fever. Similar viruses were subsequently isolated in Finland, the USA, Russia, China and other countries.

Currently, the causative agent of HFRS belongs to the family of bunya viruses (Bunyaviridae) and belongs to an independent genus - Hantavirus. It has a spherical shape, its diameter is 85-120 nm. The genome of the virus consists of three segments: L -, M -, S - single-stranded (minus strand) RNA. The structure of the virus includes 4 polypeptides: nucleocapsid (N), membrane glycoproteins (G1 and G2), RNA polymerase. It reproduces in the cytoplasm of infected cells. Hantaviruses can infect monocytes, cells of the lungs, kidneys, liver, and salivary glands. Recent studies show that hantaviruses do not cause cytolysis of endothelial cells, the damage of which is primarily due to immune mechanisms.

The antigenic properties of the virus are due to the presence of nucleocapsid protein antigens and surface glycoprotein antigens, which cause the formation of virus-neutralizing antibodies. When studying various monoclonal antibodies to the Puumala virus, it was revealed that the nucleocapsid protein causes the formation of antibodies that are unable to neutralize infectious activity, while surface glycoproteins stimulate the formation of neutralizing antibodies.

To date, more than 25 serologically and genetically different hantaviruses are known. To date, two clinical forms of hantavirus infection in humans are known: hemorrhagic fever with renal syndrome, caused by the Hantaan, Seul, Puumala, and Dobrava/Belgrade viruses and hantavirus pulmonary syndrome, caused by the hantaviruses Sin-Nombre, Black Creek, New York, Bayou , Andes, Laguna Negra. More than 120 strains of the HFRS virus are isolated in the CIS. In the regions of the European part of Russia and the Trans-Urals, including the Republic of Bashkortostan (RB), the predominant serotype is Puumala. The possibility of circulation has also been shown for Hantaan and Seul, i.e. There is a mosaic pattern of distribution of hantaviruses in natural foci of HFRS. Hantaan and Seoul viruses circulate in natural foci of the Far East of Russia, South Korea, North Korea, China, and Japan. The main carrier is the field mouse. The Puumala virus has been found in Russia, Finland, Sweden, Norway, Czech Republic, Germany, France, and Belgium. Its reservoir is the bank vole. The Belgrade virus is widespread in the Balkans.

The HFRS virus is relatively stable in the external environment at temperatures from 4° to 20°C. In blood serum taken from sick people, it persists for more than 4 days at 4°C. Inactivates at a temperature of 50°C for 30 minutes, at 0-4°C it is stable for 12 hours. Stores well at temperatures below -20°C. The virus is acid labile - completely inactivated at a pH below 5.0. Sensitive to ether, chloroform, acetone, benzene, sodium deoxycholate, ultraviolet rays. The virus is capable of multiplying in chicken embryos of 6-7 days of age, and is passaged on field mice, steppe pieds, Djungarian and golden hamsters, Wistar and Fisher rats.

Epidemiology

HFRS is a severe natural focal zoonosis. The reservoir of the pathogen is mouse-like rodents. Literary data indicate that the virus has now been found in more than 80 species of mammals on 4 continents of the globe. In the European part of Russia, the source of infection is the bank vole (infection of these rodents in endemic foci reaches 40-57%). In the Far East, the main sources of infection are: field mouse, red-gray vole and Asian wood mouse. In cities, the reservoir of infection is likely to be house rats and mice. Rodents carry this infection as latent virus carriers. In field mice caught in natural foci, the viral antigen was found in the tissues of the lungs, kidneys, liver, lymph nodes, spleen, and rectum. The pathogen is released into the external environment with feces, urine, and saliva. Transmission between rodents occurs primarily through the respiratory tract.

Natural foci of HFRS in the European part are located in certain landscape-geographical zones: floodplain forests, forests, ravines, wet forests with dense grass. The most active foci are in linden forests, 30% of which in Russia are in the Republic of Belarus. Abundant fruiting of linden provides bank voles with food, helps maintain their high numbers, early reproduction and, consequently, the preservation of epizootics among them. Dry, hot summers also contribute to the development of epizootics. In recent years, outbreaks have also been recorded in park areas.

Human infection occurs primarily through airborne dust (up to 80%), through inhalation of dried feces of infected rodents. Transmission of the virus is also possible by contact, through damaged skin and mucous membranes, in contact with rodents or infected environmental objects (brush, straw, hay, etc.). It is possible that a person can become infected through nutritional means, for example, by consuming foods that have not been subjected to heat treatment (cabbage, carrots, etc.) that are contaminated by infected rodents. There is no transmission of infection from person to person.

The disease most often affects men (70-90% of patients) of the most active age (from 16 to 50 years), mainly industrial workers, drivers, tractor drivers, and agricultural workers. The incidence is recorded less frequently in children (3-5%), women and the elderly due to less contact with the natural environment and, probably, immunogenetic characteristics. Among the sick people in the Republic of Belarus, urban residents predominate (up to 70-80%), which is due both to their large number and the level of the immune layer, which is 6-12% among urban residents, and up to 35-40%. There are sporadic, industrial, agricultural, gardening, camp and household types of morbidity.

The incidence of HFRS is characterized by pronounced seasonality: from May to December. According to long-term data in the Republic of Belarus, the peak is observed in September-November. From January to May, diseases are almost non-existent, which is associated with a sharp reduction in the number of mouse-like rodents in winter. In addition to seasonal ones, there are also annual fluctuations in incidence (frequency), which amount to 3-4 years (1985,1988,1991,1994,1997). There is a direct relationship between human morbidity and the number of rodents and their infection rate in a given area.

In terms of incidence, HFRS ranks first in the Russian Federation among natural focal diseases (Tkachenko E.A., 2000). The most active outbreaks are in the Middle Volga region and the Urals. Natural foci in the Republic of Belarus are characterized by high epidemic activity and are the most intense in the world. In the Republic of Belarus, the incidence rate is 5-10 or more times higher than the federal average and amounts to 40-60% of the incidence rate in Russia. From 1957 to 2003, more than 70 thousand people became ill in the republic. The highest figures were achieved in 1997: in the Republic of Belarus - 224.5 per 100,000 of us, in the city of Ufa - 512.6, and in the Blagoveshchensk district - 1059.5. The annually registered high incidence of HFRS in the city of Ufa is 50-60% of the incidence rate in the republic.

HFRS is distributed throughout the world. It was observed in the Scandinavian countries (Sweden, Norway, Finland), Bulgaria, Yugoslavia, Czechoslovakia, Belgium, France, and the Far East (PRC, DPRK, South Korea). A serological examination showed the presence of specific antibodies against the HFRS pathogen in residents of Argentina, Brazil, Colombia, Canada, the USA, including the Hawaiian Islands and Alaska, Egypt, the countries of Central Africa, and Southeast Asia.

The transferred infection leaves persistent, lifelong type-specific immunity. There are isolated cases of recurrent disease.

Pathogenesis

The mechanisms of development of HFRS remain poorly understood. Disclosure of the nature of the pathological process is also limited by the lack of an adequate experimental model of the disease. A comparison of the clinical and morphological data of HFRS by many researchers has led to the conclusion that the main pathogenetic essence of the disease is a universal alterative-destructive panvasculitis, leading to the development of DIC syndrome, hemodynamic disorders and acute renal failure. In this case, the predominant mechanism of development of vasculitis is considered to be immunopathological.

Based on the available facts, it is possible to present only a general scheme of pathogenesis and its individual fragments, which is currently presented as follows. The pathological process with HFRS develops in stages; During its course there are 5 phases:

I. Infection. The introduction of the virus through the mucous membranes of the respiratory tract, digestive tract, and damaged skin. Reproduction of the virus in the lymph nodes and SSF. Restructuring of the body's reactivity, sensitization is possible.

II. Viremia and generalization of infection. The virus has an infectious-toxic effect on vascular receptors and the nervous system. Dissemination of the virus with the possible participation of blood cells and the hematopoietic system. Phases I and II correspond to the incubation period of the disease.

III. Toxic-allergic and immunological reactions. The virus circulates in the blood, most of it is captured by SSF cells and removed from the body. The formation of immune complexes (IC) is a normal reaction indicating the body's immunoreactivity. However, under unfavorable conditions, the regulatory mechanisms for the formation of antigen-antibody complexes are disrupted, in particular, when the phagocytic activity of macrophages is disrupted or when the level of antibody formation is low, and IR enters organs and tissues, damaging the walls of arterioles and higher autonomic centers. This increases the activity of hyaluronidase, the release of histamine and histamine-like substances, and the kallikrein-kinin system is activated. A destructive process develops in loose connective tissue, impaired vascular permeability and tone, hemorrhagic diathesis with plasmorrhea in the tissue, DIC, microthrombosis and other blood circulation disorders. The phase corresponds to the febrile period of the disease.

IV. Visceral lesions and metabolic disorders. Correspond to the end of the febrile period and the beginning of the oliguric period. As a result of developed disorders under the influence of the virus, edema, hemorrhages, dystrophic and necrobiotic changes occur in the pituitary gland, adrenal glands, kidneys, myocardium and other parenchymal organs. The manifestation of DIC syndrome occurs. All these processes ultimately cause a disorder of the systemic circulation, hypovolemia and hemoconcentration, hypoperfusion and hypoxia of organs, tissue acidosis and deep damage to the vital systems of the body. The greatest changes are observed in the kidneys, which is accompanied by a decrease in glomerular filtration, impaired tubular reabsorption, leading to oligoanuria, massive proteinuria, azotemia, disturbances in water-electrolyte balance and CBS, i.e. development of acute renal failure. The development of antirenal autoantibodies also contributes to the occurrence of renal damage. During this phase, life-threatening complications are possible: acute cardiovascular failure, collapse, shock, massive bleeding, spontaneous renal rupture, pulmonary edema, cerebral edema, azotemic uremia, paralysis of the autonomic centers.

V. Anatomical repair, restoration of impaired functions, formation of stable immunity. As a result of immune reactions and sanogenic processes, pathological changes in the kidneys regress, which 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.

There are several phases of pathological changes in the kidneys: 1) circulatory disorders, venous congestion in the cortex and medulla; 2) ischemia of the cortex, plethora of the pyramids; 3) swelling of the pyramidal stroma as a result of impaired vascular permeability; 4) hemorrhagic apoplexy of the medulla; 5) necrosis of the kidney pyramids; 6) the phenomenon of de-epithelialization; 7) regeneration phase.

Clinical picture

To date, there is no unified classification of HFRS. 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 main clinical syndromes of HFRS are: general toxic, hemodynamic, renal, hemorrhagic, abdominal and neuroendocrine. Most authors, based on the leading syndrome of the disease - acute renal failure, have proposed to distinguish the following periods of the disease: initial (febrile), oliguric (renal and hemorrhagic manifestations), polyuric, convalescence (early - up to 2 months and late - up to 2-3 years).

The incubation period lasts from 4 to 49 days (most often from 14 to 21 days). Sometimes prodromal phenomena lasting 2-3 days are observed, which are manifested by malaise, fatigue, headache, myalgia and low-grade fever.

The initial period lasts up to 3-10 days (on average 4-6) and is characterized by an acute onset, an increase in body temperature to 38-40 ° C, which is sometimes accompanied by chills. Severe headache, weakness, dry mouth, decreased appetite, nausea, body aches. There are no signs of inflammation of the upper respiratory tract. Characteristic complaints are pain in the eyeballs and decreased visual acuity (“fog” before the eyes, “floaters”), which are short-lived and disappear without a trace after 1-5 days. Bloody discharge from the nose and the formation of hemorrhagic “crusts” in the nasal passages are possible. In severely ill patients during this period, pain in the lower back and abdomen, vomiting, gross hematuria, and oliguria occur.

When examining patients, hyperemia of the skin of the face, neck, and upper chest is noted. The mucous membrane of the pharynx is hyperemic, the vessels of the sclera are injected, and against the background of hyperemic conjunctiva, a hemorrhagic rash can sometimes be seen. From the 2-3rd day of illness, in most patients, hemorrhagic enanthema appears on the mucous membrane of the soft palate, and from the 3-5th day (in 10-25% of patients) - a petechial rash in the armpits, on the chest, in the clavicle area, sometimes on the neck, face. The rash is not abundant, is grouped in nature and lasts from several hours to 3-5 days. It is not possible to detect any significant changes in the internal organs in the initial period. Moderate bradycardia is possible, some patients have dull pain in the lower back, a positive Pasternatsky sign. Relatively rarely, in severe forms, there may be phenomena of meningism. On the 4th-6th day of illness, especially if the medical and protective regime is violated (physical labor, visiting the bathhouse, alcohol abuse, etc.), the risk of developing ITS (collapse) increases.

The hemogram during this period of the disease reveals normocytosis or leukopenia with a neutrophilic shift to the left, moderate thrombocytopenia, and the appearance of plasma cells. In a general urine test, a small amount of fresh red blood cells and renal epithelial cells can be detected. Protein in the urine during this period is absent or detected in small quantities.

Oligouric period (from 3-6 to 8-14 days of illness). Body temperature drops to normal in the form of a short lysis or delayed crisis, sometimes rising again to subfebrile levels - a “two-humped” curve. However, a decrease in body temperature is not accompanied by an improvement in the patient’s condition; more often it even worsens. General toxic manifestations reach a maximum: headache, dry mouth, nausea intensify, uncontrollable vomiting, hiccups, anorexia appear, and severe adynamism is noted. The most typical manifestation of this period is lower back pain of varying severity. At the same time, abdominal pain appears, and flatulence is often noted. Most patients (50-65%) experience diarrhea up to 2-10 times. The severity of oliguria (less than 500 ml of urine per day) in most cases correlates with the severity of the disease. Hemorrhagic manifestations also depend on the severity of the disease and can be expressed in nasal, gastrointestinal, uterine bleeding, macrohematuria. Hemorrhages in vital organs - the central nervous system, pituitary gland, adrenal glands - during this period can cause death.

On examination, puffiness of the face, pasty eyelids, and dry skin are noted. Hyperemia of the face and neck, mucous membranes of the pharynx and conjunctiva, scleral injection, exanthema, and decreased visual acuity persist. Severe patients are characterized by the appearance of hemorrhage on the mucous membranes and skin (at injection sites). Signs of bronchitis often appear (in smokers). Bradycardia and hypotension are noted, followed by hypertension towards the end of the period. When palpating the abdomen, pain is determined, often in the area of ​​​​the projection of the kidneys, and in severe patients, tension in the abdominal wall (peritonism phenomena). The liver is usually enlarged, the spleen - less often. Pasternatsky's symptom is positive; sometimes even palpation of the projection of the kidneys from the lower back causes sharp pain. Due to the possibility of rupture of the kidney capsule, these symptoms must be checked very carefully. In isolated cases, signs of meningism may appear. Most specific complications of HFRS develop during this period.

The hemogram naturally reveals neutrophilic leukocytosis (up to 15-30/l of blood), plasmacytosis, and thrombocytopenia. Due to blood thickening, the level of hemoglobin and red blood cells may increase, but with bleeding these indicators decrease. ESR, as a rule, is not changed. Characterized by increased levels of residual nitrogen, urea, creatinine, 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, the appearance of renal epithelial cells, etc. Dunaevsky cells. Significant changes occur in the blood coagulation system, most often expressed in hypocoagulation.

The polyuric period begins from the 9-13th day of illness. 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), nick-turia is characteristic. Weakness persists, dry mouth, thirst appears. 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. The patient's condition is progressively improving. However, the rate of improvement does not always parallel the increase in diuresis. Sometimes, in the first days of polyuria, azotemia continues to increase, and dehydration, glutonatremia, and hypokalemia may develop.

The period of convalescence begins with a noticeable improvement in general condition, restoration of daily diuresis, normalization of urea and creatinine levels. Its duration is determined by the rate of recovery of renal function and ranges from 3 weeks to 2-3 years. Asthenic syndrome is detected in convalescents: 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 one year or more). It is possible that a secondary bacterial infection may occur with the development of pyelonephritis, which is most often observed in survivors of acute renal failure.

The division of HFRS according to the severity of the disease does not have uniform generally accepted criteria. Assessment of the severity of the disease corresponds to the severity of the main clinical syndromes (primarily acute renal failure) and developed complications (ITS, LVS, etc.).

Complications of HFRS are divided into two groups: a) specific - ITS, disseminated intravascular coagulation syndrome, azotemic uremia, pulmonary edema, cerebral edema, cerebral hemorrhages, pituitary gland, adrenal glands, myocardium, profuse bleeding, eclampsia, acute cardiovascular failure, infectious myocarditis, tear or rupture of the kidney capsule, serous meningoencephalitis, etc.; b) nonspecific - pyelonephritis, pneumonia, purulent otitis, abscesses, phlegmon, mumps, sepsis, etc.

Forecast

The mortality rate in China ranged from 7 to 15%, in Korea in 1951-1976. the average was 6.6%. In Russia, from 1962 to 1990, mortality fluctuated between 1-3.5% (in the Far East up to 8-10%). From 1957 to 1999 in the Republic of Belarus, the mortality rate was 0.7%.

Diagnostics

The basis for making a clinical diagnosis is a characteristic combination of a picture of an acute febrile illness occurring with kidney damage (development of acute renal failure) and hemorrhagic syndrome. In this case, it is necessary to take into account epidemiological data, seasonality and cyclicality of the course of the disease: the natural change of infectious-toxic manifestations of the initial period with signs of increasing renal failure of the oligouric period. The likelihood of a correct diagnosis increases even more with the appearance of such almost specific symptoms of HF1TS, such as: short-term decrease in visual acuity, pronounced manifestations of acute renal failure without signs of liver failure, massive proteinuria with rapid positive dynamics.

The value of absolute values ​​of laboratory general clinical, biochemical, electrolyte, CBS, coagulopathic, immunological, instrumental and other indicators in establishing the final clinical diagnosis is relative, since they reflect the severity of nonspecific pathophysiological syndromes (infectious-toxic, acute renal failure, disseminated intravascular coagulation, etc.). The dynamics of changes in these indicators (given above) is of greater importance in diagnosis. They also serve as criteria for the severity, complications and prognosis of the disease.

The final diagnosis must be verified using specific diagnostic methods. This is especially important when determining erased and mild forms of the disease. For this purpose, serological research methods (RNIF, ELISA, RIA) are used.

Today, the method of choice is the indirect immunofluorescence reaction using the fluorescent antibody (MFA) method. The method is highly informative with diagnosis confirmation up to 96-98%. It is possible to identify seronegative (up to 4-6%) forms of the disease. The study is carried out using paired sera. An increase in antibody titer by 4 or more times is considered diagnostic. To increase the efficiency of serodiagnosis of HFRS, the earliest collection of the first serum is necessary (before 4-7 days of illness). When serum is taken after the 15th day of illness, no increase in antibody titer is detected.

Antibodies to the HFRS virus after an infection remain for life, regardless of the severity of the disease.

For the purpose of early diagnosis, it is more promising to use ELISA methods with the detection of antibodies of the Ig M class and PNR with the detection of viral RNA fragments.

Treatment

There are no standard treatment regimens for HFRS. Therefore, it is complex, carried out taking into account the correction of the main pathogenetic syndromes - intoxication, acute renal failure, disseminated intravascular coagulation and developed complications, as well as concomitant diseases. The amount of assistance depends on the severity and period of the disease. Thus, treatment of a patient with HFRS should be individualized.

Principles of hospitalization and patient care:

The earliest hospitalization is necessary - at the beginning of the febrile period, i.e. in the first 3 days of illness. Outpatient observation of a patient with suspected HFRS is unacceptable.

Transportation of the patient is as gentle as possible - by ambulance, or, if this is not possible, by passenger vehicle with an accompanying medical worker.

Transfer from hospital to hospital and surgical interventions are unacceptable.

It is necessary to comply with bed rest until polyuria stops, on average: for mild form - 7-10 days, moderate - 2-3 weeks and severe - at least 3-4 weeks from the onset of the disease.

Strict accounting of fluid input (drinking, infusion) and its losses (diuresis, vomit, stool) is required.

Treatment is carried out under the control of water balance, hemodynamics, hemogram, hematocrit, urine tests, urea, creatish, electrolytes (potassium, sodium), acid-base balance, coagulogram; in case of complications - instrumental studies: FGDS, ultrasound, CT, radiography of the OGK, etc.

Diet: Table No. 4 without salt restriction is recommended; in severe forms and complications - table No. 1. Meals should be complete, in small portions, and warm. With oligoanuria, foods rich in protein (meat, fish, legumes) and potassium (vegetables, fruits) are excluded. In polyuria, on the contrary, these products are most necessary. The drinking regimen should be dosed, taking into account the allocated liquid. The amount of liquid drunk and injected should not exceed the volume excreted (urine, vomit, stool) by more than 500-700 ml.

Drug therapy.

In the initial febrile period of the disease, the main principles of treatment are: antiviral therapy, detoxification, prevention of DIC syndrome, antioxidant therapy, prevention and treatment of ITS.

1. Etiotropic treatment can be carried out using two main approaches:

a) immunobiological agents - hyperimmune plasma, donor specific immunoglobulin against HFRS, complex immunoglobulin preparation (CIP), interferon preparations, both parenterally (leukinferon, reaferon) and rectally (suppositoferon /CHLI/, viferon), and

b) chemotherapy drugs: nucleoside derivatives - ribavirin (ribamidil, virazol, rebetol), as well as interferon inducers - amixin, cycloferon, iodantipyrine, anandin, interleukin-2, etc. A mandatory condition for antiviral therapy is the prescription of drugs in the first 3-5 days of the disease.

2. Detoxification therapy includes intravenous infusions of glucose 5-10%, physical. solution up to 1.0-1.5 l/day with ascorbic acid, cocarboxylase. A single administration of hemodez or rheopolyglucin is acceptable. Anti-inflammatory drugs (analgin, aspirin, paracetamol) are prescribed for hyperpyrexia (39-41°C).

3. Prevention of DIC syndrome includes:

a) disaggregants - pentoxifylline (trental, pentilin, agapurin, pentomer, flexitam), xanthinol-nicotinate (complamin, teonicol, xavin), dipyridamole (chimes); In order to improve microcirculation during this period, heparin up to 5000 units/day is also indicated. 1500 units are administered intravenously or under the skin of the abdomen. 2-3 times a day, and low molecular weight heparins: nadroparin calcium (Fraxiparin) 0.3 ml/day, enoxaparin sodium (Clexane) 0.2 ml/day, dalteparin sodium (Fragmin) 0.2 ml/day, reviparin sodium ( Kliva-rin) 0.25 ml/day, s.c.;

b) angioprotectors - calcium gluconate, rutin, sodium ethamsylate (dicinone), prodectin (parmidin, angina), calcium dobesilate (doxium);

c) in severe forms of the disease, early administration of fresh frozen plasma (FFP) and protease inhibitors (contrical, gordox, trasylol) is advisable.

4. Antioxidants: tocopherol, ubiquinone (ubinone, coenzyme Q).

5. Timely (early) hospitalization, strict bed rest and the above measures, as a rule, prevent the development of ITS. However, as statistics show, about 3-4% of patients with HFRS are admitted to the clinic with varying degrees of shock, cat. develops most often on the 4th-6th day of illness. In this case, the following urgent measures must be taken:

a) rheopolyglucin 400 ml + hydrocortisone 10 ml. (250 mg.) IV drip; if possible, it is better to use FFP or albumin;

b) GCS (calculated for prednisolone) -1 tbsp. ITS: 3-5 mg/kg/day, max, up to 10 ;P st. ITS: 5-10 mg/kg/day, max, up to 20; W st. ITS: 10-20 mg/kg/day, max, up to 50, the first dose should be 14 times the daily dose, subsequent doses are administered every 4 hours, IV bolus; cancellation - after stabilization of hemodynamics;

c) sodium bicarbonate 4% 200 ml., IV drip, simultaneously into another vein or after rheopolyglucin;

d) cardiac glycosides and cardotonics - strophanthin, korglykon, cordiamine, i.v.;

e) if primary measures are ineffective, there is no urine after 1.2-1.5 liters. administered fluid or the patient’s admission to stage III. ITS, prescribed - DOPAMINE (dopmin, dopamine) 0.5% or 4%, 5 ml. (25 or 200 mg.), cat. diluted respectively in 125 or 400 ml of 5% glucose or saline. solution and injected dropwise at a rate of 15-20 drops/min.;

f) correction of DIC syndrome developing during ITS: for hypercoagulation - heparin up to 10,000-15,000 units/day, for hypocoagulation - up to 5,000 units/day, i.v.; FFP up to 600-800 ml/day, IV drop; protease inhibitors (contrical up to 1000 units/kg/day); angioprotectors (dicinone up to 6-8 ml/day); for gastrointestinal bleeding: cimetidine (histodil, quamatel, omeprazole) 200 mg 2-3 times a day, intravenously, 5% chilled aminocaproic acid (per os), antacids (almagel, maalox);

g) diuretics are prescribed after normalization of hemodynamics (or central venous pressure > 120 mm H2O) - lasix 40-80 mg/day; in case of HFRS, the administration of mannitol is contraindicated;

h) DOXA 10 mg 1-2 times a day, intramuscularly (at stage P-III of ITS); i) oxygen therapy.

The total amount of administered fluid is up to 40-50 ml/kg/day (under the control of diuresis), of which colloidal solutions make up at least 1/3.

In case of ITS, sympathomimetics (mezaton, adrenaline, norepinephrine) cannot be used; antispasmodics, hemodez, and polyglucin are also not indicated.

During the oliguric period, the main principles of treatment are: detoxification therapy, combating azotemia and reducing protein catabolism; correction of water-electrolyte balance and acid-base balance; correction of DIC syndrome; symptomatic therapy; prevention and treatment of complications (cerebral edema, pulmonary edema, tear or rupture of the kidney capsule, azotemic uremia, hemorrhages in the pituitary gland and other organs, bacterial, etc.).

1. Conservative treatment of uremic intoxication includes:

a) washing the stomach and intestines with 2% soda solution;

b) intravenous infusion of 10-20% glucose with insulin, physical. solution, with aminophylline, ask. acid, cocarboxylase; in severe forms - albumin;

c) taking enterosorbents - enterosorb, polyphepan, enterosgel, etc.;

d) to reduce protein catabolism, the following are indicated: protease inhibitors (contrical, gordox), prodectin, methandrostenolone, parenteral nutrition (intralipid, neframin).

Colloidal solutions of dextran (reopolyglucin, polyglucin, reogluman), hemodez, corticosteroids (except in cases of collapse, cerebral and pulmonary edema) are not administered to oliguria.

2. The main goal of therapy during this period is to combat overhydration, acidosis and electrolyte disturbances. Treatment of oligoanuria (urine less than 500-600 ml/day) should be based on the main principle “do no harm”, “it is better to underfill than overfill”. To do this you need:

a) calculation of the administered fluid not exceeding 500-700 ml of the volume of losses (with urine, vomiting and diarrhea);

b) stimulation of diuresis with Lasix in loading doses (200-300 mg simultaneously, intravenously in a stream) after alkalization (4% sodium bicarbonate 100-200 ml) and administration of protein preparations (albumin, FFP). If at least 100-200 ml of urine is obtained during the first dose, after 6-12 hours it is possible to re-administer Lasix at the same dose. The total dose of the drug should not exceed 800-1000 mg. In anuria (urine less than 50 ml/day), the use of Lasix is ​​undesirable.

c) correction of acidosis is carried out by prescribing 4% sodium bicarbonate, the volume of administration (in ml) of which is calculated by the formula: 0.6 x patient’s body weight (kg) x BE (mmol/l). If it is impossible to determine the pH and BE of blood, patients with oligoanuria are allowed to administer up to 200-300 ml of solution per day;

d) correction of hyperkalemia (more often observed in patients without vomiting and diarrhea) includes glucose-insulin therapy, administration of calcium poconate 10% up to 30-40 ml/day, a potassium-free diet; It is also necessary to avoid the administration of drugs containing potassium and magnesium ions.

3. During this period, hemorrhagic manifestations continue and often manifest themselves. Therefore, the correction of disseminated intravascular coagulation syndrome begun during a febrile period is carried out according to the same principles.

4. An important component of therapy for patients with HFRS is the elimination of adverse symptoms of the disease:

a) the most pronounced of them is pain, cat. relieved with analgesics (analgin, baralgin, trigan, spasmalgon, spazgan, etc.) in combination with desensitizing agents (diphenhydramine, suprastin, pipolfen, etc.); in cases of their ineffectiveness, chlorpromazine, droperidol, fentanyl, tramadol, promedol are recommended;

b) for persistent vomiting, hiccups, gastric lavage, novocaine (per os), metoclopramide (cerucal, raglan, perinorm), pipolfen, atropine, aminazine are indicated;

c) for arterial hypertension - aminophylline, dibazol, papaverine, calcium antagonists (verapamil, corinfar, cordafen);

d) for convulsive syndrome - Relanium (seduxen, sibazon), chlorpromazine, droperidol, sodium hydroxybutyrate; after restoration of diuresis - piracetam (nootropil).

5. All of the above measures help prevent the development of complications. If there is a detailed picture of cerebral and pulmonary edema, therapy is carried out according to general principles, taking into account water and electrolyte balance. The treatment program for patients with renal capsule rupture is carried out jointly with a urologist.

Antibacterial therapy in the first two periods of the disease is carried out only in the presence of infectious bacterial complications (pneumonia, abscesses, sepsis, etc.), usually in no more than 10-15% of patients. Semi-synthetic penicillins and cephalosporins can be used. Early unjustified prescription of antibiotics can delay recovery and hospitalization.

If conservative measures are ineffective, extracorporeal hemodialysis is indicated, the need for which may arise on days 8-12 of illness.

Indications for hemodialysis:

A. Clinical: anuria for more than 3-4 days; toxic encephalopathy with symptoms of incipient cerebral edema and convulsive syndrome, incipient pulmonary edema against the background of oligoanuria.

B. Laboratory: azotemia - urea more than 26-30 mmol/l, creatinine more than 700-800 µmol/l; hyperkalemia - 6.0 mmol/l and above; acidosis with BE - 6 mmol/l and above, pH 7.25 and below.

The defining indications are clinical signs of uremia, because even with severe azotemia, but moderate intoxication and oliguria, treatment of patients with acute renal failure is possible without hemodialysis.

Contraindications to hemodialysis:

A. ITS. B. Hemorrhagic stroke, hemorrhagic infarction of the adenopituitary gland. B. Massive bleeding. D. Spontaneous rupture of the kidney.

During the polyuric period, the main principles of treatment are: correction of water and electrolyte balance; correction of rheological properties of blood; prevention and treatment of complications (hypovolemia, tear or rupture of the kidney capsule, hemorrhages in the pituitary gland, eclampsia, myocarditis, bacterial, etc.); symptomatic therapy; general restoratives

1. Considering the development during this period of dehydration (both extracellular and, in especially severe cases, cellular), hypokalemia, hyponatremia, hypochloremia, patients are advised to:

a) replenishment of water and salts by ingesting mineral waters, decoctions of raisins and dried apricots, solutions of “Rehydron” and “citroglucosolan”, etc., in an amount not less than the volume of urine excreted per day;

b) with daily diuresis exceeding 5% of body weight, about half of the lost fluid is replaced by the introduction of saline solutions - acesol, hlo-sol, lactosol, quartosol, quintasol;

c) in case of severe hypokalemia, additional administration of potassium preparations is necessary - CO4% 20-60 ml/day, panangin, asparkam, potassium orotate.

2. Correction of the rheological properties of blood is carried out while continuing to prescribe antiplatelet agents.

3. The most common complications during this period are inflammatory diseases of the urinary system (ascending pyelitis, pyelonephritis, etc.), the treatment of which requires the use of uroseptic drugs: oxyquinoline derivatives - nitroxoline (5-NOK, nitrox); quinolones - nevigramon (negram), gramurin, palin, urotractin; fluoroquinolones - norfloxacin (police, normax), ofloxacin (tarivid, zanocin), ciprofloxacin (ciprolet, tsifran, siflox), enoxor; nitrofurans - furodonin, furagin; sulfonamides - co-trimoxazole (biseptol, septrin, groseptol); antibiotics - penicillins, chloramphenicol, cephalosporins.

4. Elimination of symptoms that often accompany the polyuric period (arterial pshertensia, headache, lower back pain, nausea, vomiting, etc.) is carried out according to the same principles as during the oliguric period.

5. General strengthening therapy includes vitamins, riboxin, ATP, co-carboxylase, etc.

Check out rules

Patients with HFRS are discharged with normalization of diuresis, azotemia parameters (urea, creatinine), hemogram, absence of pyuria and microhematuria. Isohyposthenuria is not a contraindication for discharge.

Terms of discharge of HFRS convalescents from the hospital for:

mild form - no earlier than 17-19 days of illness;

moderate - no earlier than 21-23 days of illness;

severe form - no earlier than 25-28 days of illness.

Given the possibility of complications, it is not recommended to reduce the length of hospitalization. Patients are discharged with an open sick leave certificate. should be continued for at least 2 weeks, under the supervision of an infectious disease specialist and a general practitioner at the place of residence.

Prevention

No specific prevention has been developed. It comes down to the destruction of rodents in areas of HFRS and to protecting people from contact with rodents or objects contaminated with their secretions. In populated areas located near forests, it is necessary to store food in warehouses protected from rodents. The area around housing should be cleared of bushes and weeds. When placing in summer camps, tourist centers, etc. choose places not inhabited by rodents, free from thickets of weeds. In these cases, garbage pits are located at least 100 m from the tents.

Literature

1. Alekseev O.A., Suzdaltsev A.A., Efratova E.S. Immune mechanisms in the pathogenesis of hemorrhagic fever with renal syndrome. // Ter. archive.-1998.-No.11.-P.39-42.

2. Gavrilovskaya I.N., Boyko V.A. Hemorrhagic fever with renal syndrome: Review information. - VNIIMI, M, 1985. - 74 p.

3. Hemorrhagic fever with renal syndrome (HFRS) in the Middle Volga region./ Kolpachikhin F.B. and others (in two parts). - Kazan, 1989. - 128 and 124 pp.,

4. Germash E.I. and others. Pathogenetic therapy of patients with severe hemorrhagic fever and acute renal failure. // Ter. archive.-1997.- No. 11.- P.26-30.

5. Dekonenko A.E. and others. Genetic differentiation of hantaviruses using polymerase chain reaction and sequencing.// Vopr. Virol.-1996.-No.1.-P.24-27.

6. Ivanov A.P. and others. Enzyme immunoassay system using biotinylated monoclonal antibodies for typing hantavirus antigens.// Vopr. Virol.- 1996.- No. 6.- P.263-265.

7. Korobov L.I. et al. On the incidence and prevention of hemorrhagic fever with renal syndrome in the Republic of Bashkortostan.// JMEI.-2001.-No.4.-P.58-60.

8. Lukashevich I.S. and others. Virus-specific proteins and RNA of the hemorrhagic fever virus with renal syndrome. // Issues. Virol.- 1990.- No. 1, - P. 38-42.

9. Magazov R.Sh., Khaibulliya S.F., Kulagin V.F. Laboratory diagnosis of hemorrhagic fever with renal syndrome.// Hemorrhagic fever with renal syndrome - ways to solve the problem. - Ufa, 1995. - SL 1-16.

10. Mirsaeva G.Kh., Fazlyeva R.M., Kamilov F.Kh., Khunafina D.Kh. Pathogenesis and treatment of hemorrhagic fever with renal syndrome. - Ufa, 2000. - 236 p.

11. Nalofeev A.A., Ibragimova S.Kh., Moleva L.A. Specific laboratory diagnostics of HFRS. // Epidem. and infectious Bol, - 2002. - No. 2. - P. 48.

12. Roshchupkin V.I., Suzdaltsev A.A. Hemorrhagic fever with renal syndrome. - Samara, 1995. - 48 p.

13. Sirotin B.Z. Hemorrhagic fever with renal syndrome.-Khabarovsk, 1994.-300 p.

14. Tkachenko E.A. Epidemiological aspects of the study of hemorrhagic fever with renal syndrome in Russia.// Infectious diseases at the turn of the 21st century. - M., 2000, - Part 2. - P.58.

15. Tkachenko E.A., Dekonenko A.E., Filatov F.P. and others. Hantaviruses // Far Eastern honey. magazine - 2003. - JVs 3. - P. 50-55.

16. Fazlyeva R.M., Khunafina D.Kh., Kamilov F.Kh. Hemorrhagic fever with renal syndrome in the Republic of Bashkortostan. - Ufa, 1995. - 245 p.

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, it has a destructive effect on the cardiovascular system, and 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 are designated by the 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, the incubation period ends, 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.

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. The average period is about 2 weeks. The initial stage lasts 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. A general biochemical blood test for HFRS will show an increase in the level of potassium, urea, chlorides, calcium, and 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;
• deviations 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. In the younger generation, there are often no initial symptoms of the development of the virus, but appear immediately in an acute form. High fever lasts for a week, it is accompanied by severe headaches, weakness, drowsiness, general malaise, and vomiting. Painful sensations in the back appear almost immediately, gradually moving to the abdominal area.

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 systems. 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, dry mouth 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. A red rash forms in the chest area, in the armpits and on the lower extremities, 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;
• the heart rate increases, which is the appearance of the initial stage of 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 of clinical manifestations of the disease, and data from laboratory 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;
• passive hemagglutination reaction in paired sera.

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, an increase in ESR, neutrophilic leukocytosis and thrombocytopenia, and the appearance of plasma cells in the blood are noted. 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, differential diagnosis is important.

Treatment of the disease

Treatment of patients with hemorrhagic fever with renal syndrome is carried out only in the infectious diseases department of the 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 (dietary table No. 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 forests, fields, or garden plots (in areas where rodents spread), you need to thoroughly wash your hands and disinfect your clothes. Food products must be stored in airtight containers.

To avoid infection with hemorrhagic fever with renal failure, you need to drink only 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 fever is a disease whose history began in 1935 in the Far East. Later, to this day, outbreaks of the disease in Russia began to occur in the Central region of the country and the Urals.

Hemorrhagic fever with renal syndrome

Hemorrhagic fever with renal syndrome (HFRS) is an acute viral disease transmitted by small rodents, which is characterized by vascular damage and negatively affects primarily renal function.

The causative agent of hemorrhagic renal fever is Hantaviruses from the Bunyavirus family. There are 4 varieties of this type of infection, but only one is found in Russia - Puumala.

Any person is susceptible to Hantavirus, that is, entry into the blood of Puumala becomes a catalyst for the pathological process in all people who have not previously suffered hemorrhagic fever. But, according to statistics, the vast majority of people experiencing HFRS are men aged 18 to 50 years.

There are two types of HFRS, divided according to the source of infection:

• Type I (eastern) is spread by the field mouse, the clinical picture is severe, the mortality rate as a result of therapy is 20%;
• Type II (western) is spread by the bank vole, the symptoms of the disease are milder than with type I, and the mortality rate during treatment is less than 2%.

Basics of hemorrhagic renal fever with renal syndrome

Etiology

There are six methods of infection, but all of them are united by human contact with the virus that enters the environment from the saliva and feces of rodents:

1. The forest type is the most common, with a person becoming infected during hiking in the forest, searching for mushrooms, or picking berries.
2. The household type means that the source of Hantavirus is inside a person’s home - this occurs in private houses located near a forest.
3. Production type - occurs during drilling, oil pipeline and other work in the forest.
4. The gardening type is popular among summer residents.
5. The camp type of infection is recorded among children and adolescents vacationing in summer suburban camps.
6. The agricultural route is marked by activity in the fall and winter.

In the overwhelming majority of cases, the virus enters the body by contacting the mucous membrane of the upper respiratory tract, and less often through lesions on the skin.
On video the etiology of hemorrhagic fever:

Pathogenesis

After entering the body, the virus begins to attack the walls of blood vessels from the inside, destroying the inner layer - the endothelium. The vessels become permeable, plasma leaves the vascular system through perforations, and the blood thickens.

Damage to blood vessels negatively affects the activity of absolutely all systems, but the kidneys suffer most from HFRS: as the stages of this disease progress, the rate (GFR) drops, and the risk of chronic renal failure increases, requiring hemodialysis in the terminal stage.

Clinical picture

Incubation period

The incubation period of HFRS lasts from 1 to 7 weeks, more often – 3 weeks. At this stage, the patient does not feel symptoms of the disease, but pathology in the body already takes place: the walls of blood vessels are affected, the composition of the blood changes, and disturbances in the functioning of all systems begin.

Prodromal manifestations

The prodromal period does not always occur and lasts no more than 3 days.

It occurs after the incubation period of HFRS and has the following symptoms:

• weakness;
• headache;
• chills;
• aching bones;
• low-grade fever.

Fever

Hemorrhagic fever with renal syndrome is characterized by a sharp onset of fever, with an increase in body temperature to 39-40 degrees. It lasts from 2 to 8 days, the peak of the thermometer readings occurs not in the evening and night hours, as with the flu or ARVI, but in the morning.

High temperature serves as a source of intoxication, which causes a person to experience nausea, pain, and chills. In approximately 3 out of 10 cases, patients experience visual impairment.

Hemorrhagic period

The hemorrhagic period begins with the appearance of traces of a rash and hemorrhages on the sclera of the eyes on the skin. This stage occurs simultaneously with the oliguric stage.

With hemorrhagic syndrome, the following phenomena occur:

• “red cherry” syndrome - hemorrhages on the whites of the eyes;
• infectious-toxic shock - the body’s reaction to the presence of a virus in it, expressed in a decrease in blood pressure and pathological work of several systems at once;
• internal bleeding.

The photo shows the main manifestations of hemorrhagic fever

Oliguria

It develops from the third day from the onset of HFRS symptoms and, statistically, can last up to 1 month, but usually goes away after 9-12 days.

Oliguria is a decrease in the quantity of urine excreted during normal drinking conditions. During this period, changes in the blood are actively occurring: substances previously excreted by the urinary system remain in the blood, poisoning the body.

Pathological processes in the systems are simultaneously recorded:

• cardiovascular (hypotension, bradycardia, extrasystole);
• digestive (nausea, vomiting, sometimes with blood);
• nervous (delirium, hallucinations, fainting).

Polyuria

Polyuria begins after the oliguric period, that is, after 9-12 days from the onset of HFRS, and lasts up to 4 weeks.

During this period, the amount of urine, on the contrary, increases sharply, and diuresis can reach 10 liters. Due to the large amount of urine, its density decreases, and protein and casts are also found in it.

A day after the onset of polyuria, the dynamics of restoration of the filtration capacity of the kidneys becomes positive.

Convalescence period

After the completion of polyuria, the person recovers. But abnormalities in laboratory tests can persist for up to three years.

During the period of recovery of the body, a person may experience fatigue, encounter functional disorders of the nervous and endocrine systems, and kidney function.

On the video, the symptoms and pathogenesis of hemorrhagic fever:

Diagnostics

Differential diagnosis for hemorrhagic fever with nephrological syndrome is required to exclude pathologies:

• flu;
• typhoid fever;
• leptospirosis;
• glomerulonephritis;
• tick-borne rickettsiosis;
• encephalitis;
• pyelonephritis.

To make a diagnosis, the main tool can be called observation of the patient, questioning and examination, with the help of which they record:

• strict alternation of the described stages in this order;
• the fact of a decrease in the amount of urine excreted after temperature stabilization;
• presence of traces of hemorrhages on the skin.

The second factor confirming HFRS is epidemiological data on the possibility of HFRS infection in a given area.

Laboratory tests are performed to confirm the diagnosis:

• general urine test to detect (the presence of traces of protein in the urine), cylindruria;
• general blood test to detect an increase in leukocytes, erythrocyte sedimentation rate, plasma cells;
• biochemical blood test to detect increased creatinine and urea levels, decreased albumin;
• , which determines GFR;
• detection of IgM type antibodies.

At the stage of nephrological symptoms, kidney ultrasound and radiography with contrast are prescribed.

Treatment

HFRS therapy is carried out in a hospital setting, subject to strict bed rest and therapeutic nutrition, which reduces the load on the kidneys. The amount of urine drunk and excreted per day is monitored.

Drug therapy is used primarily to relieve symptoms:

• to relieve intoxication, intravenous infusions of glucose (20-40%) and saline solution are prescribed;
• to restore kidney function and improve microcirculation of the glomeruli, the drugs “Curantil”, “Trental”, “Eufillin” are used; in severe cases of the disease, hormonal drugs (glucocorticosteroids) - “Prednisolone”, “Metypred” - can be prescribed;
• in case of severe internal hemorrhages, blood and albumin transfusions are performed;
• during the period of oliguria, a hemodialysis machine is used to normalize blood composition and remove excess fluid from the body;
• To reduce body temperature, antipyretics are used: Paracetamol, Nise.

If the patient was hospitalized in the hospital in the first 3-5 days from the onset of symptoms, it is recommended to prescribe immunomodulators and antiviral drugs.

Complications and consequences

1. Infectious-toxic shock and azotemic uremia - poisoning of the body with decay products during a decrease in renal GFR or cessation of urination, resulting in multiple organ failure, and then uremic coma.
2. Rupture of the kidney capsule, which occurs against the background of vascular damage and high load on the cardiovascular system due to accumulating fluid during oliguria.
3. Edema of the lungs and brain - also occurs with oliguria, when a large amount of fluid remains in the body, which is not excreted by inactive kidneys.
4. Lethal outcome - on average, is recorded in 8 percent of cases and depends on the presence of concomitant somatic pathologies, age, and the moment of initiation of adequate therapy.
5. Infectious processes (pyelonephritis, sepsis) belong to a nonspecific category of complications, since their development requires the penetration into the body of bacteria that are catalysts for the described pathologies during HFRS.

On the video about the prevention of hemorrhagic renal fever:

The content of the article

Hemorrhagic fever with renal syndrome (disease synonyms: Far Eastern hemorrhagic fever, Transcarpathian hemorrhagic fever, Ural, Yaroslavl, Korean, hemorrhagic nephrosonephritis, epidemic Scandinavian nephropathy) - an acute infectious natural focal disease, which is caused by a virus, characterized by damage mainly to small vessels, fever, hemorrhagic syndrome and manifestations of kidney failure.

Historical data of hemorrhagic fever

In the Far East, the disease has been registered since 1913. Its viral nature was proven in 1940 by A. S. Smorodintsev, and in 1956 it was confirmed by M. P. Chumakov. The virus was first isolated from a sick person in 1978 in Korea by P. Lee and N. Lee. The name “hemorrhagic fever with renal syndrome” was proposed in 1954 p. M.P. Chumakov and recommended in 1982 by WHO in order to eliminate the numerous synonyms that the disease had in different countries.

Etiology of hemorrhagic fever

The causative agent of the HPA axis is a virus from the genus Hantaan, family Bunyaviridae, containing RNA. Numerous representatives of this family of viruses have identical virion structures and cause similar GPD.

Epidemiology of hemorrhagic fever

The source of infection is rodents (field and forest mice, lemmings, etc.). And some insectivores. Rodents excrete the virus mainly in urine, excrement, and less often with saliva. Transmissible transmission of infection is observed among animals. In natural foci, human infection occurs primarily aerogenically through inhalation of dust containing infected rodent excrement, as well as through nutrition (vegetables) and contact (by contact with sick rodents or infected objects). Sporadic cases of the disease develop throughout the year, mainly among rural residents. Group diseases are observed in summer and autumn, which is associated with the migration of rodents to populated areas and the more frequent presence of people in natural foci. Men are more often affected (70-80% of cases). Although the virus is excreted in urine, infection of the HPA axis from an infected person has not been described.
GGNS is registered in Russia (northwestern, Far Eastern regions), Belarus, Ukraine, Transcaucasian countries, Scandinavian countries, Bulgaria, Hungary, Poland, Korea, Japan, China, Belgium, etc.

Pathogenesis and pathomorphology of hemorrhagic fever

After the virus enters the body and reproduces it in the cells of the mononuclear phagocyte system, viremia occurs, which leads to the onset of the disease. Due to vascular damage and hemorrhages at the height of the disease, the development of infectious-toxic shock is possible. The vasotropic nature of the virus leads to venous stasis in the kidneys along with serous-hemorrhagic edema, which leads to compression of the nephron tubules and collecting ducts of the kidneys, degenerative changes in epithelial cells, and filling of the tubules with fibrin. The picture of bilateral serous-hemorrhagic nephritis and acute destructive-obstructive hydronephrosis is characteristic of the GGNS. Pathological changes in the kidneys are complicated by anemia of the renal cortex due to the discharge of blood into the veins of the renal pyramids through Truett shunts. A significant role in damage to the kidney vessels is played by the formation of circulating immune complexes. At autopsy, the kidneys are enlarged, hemorrhages are found under their capsule, and foci of necrosis are found in the renal pyramids. The glomeruli are less affected than the tubular apparatus of the kidneys, where signs of destruction and necrosis are observed.

Hemorrhagic fever clinic

The incubation period lasts from 8 to 45 days, with an average of 20 days. The disease is characterized by cyclicity.
Its clinical course is divided into four stages:
1) initial (1-4th day of illness)
2) oliguric (from 3-4 to 8-12 days),
3) polyuric (from 9-13 to 21-25 days)
4) convalescence.

Initial (febrile) stage

The disease begins acutely, body temperature rises with chills to C-40 ° C and lasts for several days. After its reduction to normal, it may again rise to low-grade fever. Patients complain of severe headache, muscle pain, dry mouth. The face and neck are hyperemic, the vessels of the sclera and conjunctiva are injected, the mucous membrane of the pharynx is bright red. On the 3-4th day of illness, signs of hemorrhagic syndrome appear - hemorrhagic enanthema on the soft palate, petechial rash in the axillary areas, under and above the collarbones, shoulder blades, on the inner surfaces of the shoulders, sometimes on the neck, face. The rash can be located in the form of chains, stripes (“blow of a whip”).

Oliguric stage

In the oliguric stage, despite a decrease in body temperature, the patient’s condition worsens, headaches and hemorrhagic manifestations intensify, and extensive hemorrhages in the skin, sclera, nasal, pulmonary, gastric, and uterine bleeding are possible. At the same time, renal syndrome develops. Pain occurs in the lumbar region, Pasternatsky's symptom is positive, the amount of urine decreases to 200-400 ml per day, it may have a pink or red tint, and sometimes takes on the color of meat slop. Anuria may develop. Due to impaired excretory function of the kidneys, azotemia progresses, sometimes uremia develops, and in severe cases - coma. Pagognomonic is massive proteinuria, which reaches 30-90 g/l.
It turns out hypoisosthenuria, hematuria, cylindruria. Edema occurs rarely.
Damage to the nervous system is characterized by lethargy, often meningeal symptoms, anisoreflexia, sometimes pyramidal signs, and infectious delirium. During a spinal puncture, cerebrospinal fluid flows out under increased pressure, and the amount of protein is increased. From the circulatory system - bradycardia, moderate arterial hypotension, which is modified by hypertension. The tongue is dry, the abdomen is moderately swollen, painful in the epigastric region.
A blood test reveals neutrophilic leukocytosis up to 20-60-109 in 1 l, plasmacytosis up to 5-25%, thrombocytopenia, significantly increased ESR.

Polyuric stage

From the 9-13th day of illness, the patient’s condition improves, daily diuresis increases to 5-8 l, and nocturia appears. Pain in the lower back and abdomen decreases, appetite and thirst appear, but weakness, moderate pain in the lower back, palpitations, and hypoisosthenuria remain for a long time. Blood biochemical parameters are gradually normalized.
The convalescence stage can last up to 3-6 months and is characterized by slow normalization of kidney function and lability of circulatory function.

Complications of hemorrhagic fever

Infectious-toxic shock, azotemic coma and pulmonary edema, circulatory failure, eclampsia, kidney rupture, hemorrhages in the brain, adrenal glands, myocardium and other organs, as well as pneumonia, phlegmon, and abscess are possible.
The prognosis for mild to moderate disease is favorable. In severe cases, the mortality rate is 1-10%.

Diagnosis of hemorrhagic fever

The main symptoms of the clinical diagnosis of HPA axis are the acute onset of the disease, fever, hyperemia and puffiness of the face, a combination of hemorrhagic syndrome and renal failure with massive proteinuria and hypoisosthenuria, leukocytosis with plasmacytosis. Epidemiological history data are taken into account - stay in a zone endemic for the HPA tract.

Specific diagnosis of hemorrhagic fever

The virus is isolated by intracerebral infection with the blood of sick mice and piglets, identified in RN in mice and cell cultures. To detect antibodies against the HPA tract virus, RNIF, ELISA, and RIA are used. The production of concentrated and purified viral preparations made it possible to use RTGA and RSK. Serological studies are carried out in the dynamics of the disease (paired serum method).

Differential diagnosis of hemorrhagic fever

HGNS should be differentiated from other hemorrhagic fevers, typhus, leptospirosis, sepsis, encephalitis, capillary toxicosis, acute glomerulonephritis, renal failure of a toxic-allergic nature, and sometimes with surgical diseases of the abdominal cavity.

Treatment of hemorrhagic fever

All patients are subject to hospitalization with the most careful transportation. Pathogenetic and symptomatic agents are used. Strict bed rest, detoxification therapy, and the use of drugs that increase vascular resistance (angioprotectors) are required, and in severe cases, glycocorticosteroids. In the oliguric stage, desalted albumin, 5% glucose and other drugs are prescribed intravenously; analgesics are prescribed to eliminate pain; in case of circulatory failure, cordiamine, corglycone, polyglucin, oxygen.
If kidney failure is severe, blood ultrafiltration methods and hemodialysis are used. In the polyuric phase, measures are taken to regulate the water-electrolyte state.

Prevention of hemorrhagic fever

In endemic foci, measures to exterminate mouse-like rodents, prevent contamination of food and water, and adherence to the sanitary and anti-epidemic regime for housing and the surrounding area are mandatory.