Advertising on the portal

Hemorrhagic fever with renal syndrome in adults. Signs of hemorrhagic fever with renal syndrome: ways of transmitting a dangerous virus

Staying in an endemic focus, the nature of professional activity.

Seasonality

Cyclicity of the course with a natural change of infectious-toxic symptoms of the initial period (fever, headache, weakness, flushing of the face, neck, upper third of the chest, mucous membranes, injection of scleral vessels) with signs of increasing renal failure of the oliguric period (pain in the lower back, abdomen; vomiting, not associated with food intake; decreased visual acuity due to severe headache, dry mouth, thirst; severe hemorrhagic syndrome, decreased urine output to less than 500 ml/day).

Nonspecific laboratory diagnosis of hemorrhagic fever with renal syndrome

The information content of laboratory nonspecific (general clinical, biochemical, coagulopathic, electrolyte, immunological) and instrumental (EGD, ultrasound, CT, ECG, chest X-ray, etc.) indicators is relative, since they reflect the severity of nonspecific pathophysiological syndromes - acute renal failure, DIC and others , they should be assessed taking into account the period of illness.

Clinical blood test: in the initial period - leukopenia, an increase in the number of red blood cells, hemoglobin, a decrease in ESR, thrombocytopenia; at the height of the disease - leukocytosis with a shift to the left, an increase in ESR to 40 mm/h.

General urine analysis: proteinuria (from 0.3 to 30.0 g/l and above), micro- and macrohematuria, cylindruria, Dunaevsky cells.

Zimnitsky test: hypoisosthenuria.

Biochemical blood test: increased concentration of urea, creatinine, hyperkalemia, hyponatremia, hypochloremia.

Coagulogram: depending on the period of the disease, signs of hypercoagulation (shortening of thrombin time to 10-15 s, blood clotting time, increase in fibrinogen concentration to 4.5-8 g/l, prothrombin index to 100-120%) or hypocoagulation (extension of thrombin time up to 25-50 s, prolongation of coagulation time, decrease in fibrinogen concentration to 1-2 g/l, prothrombin index to 30-60%).

Specific laboratory diagnosis of hemorrhagic fever with renal syndrome

RNIF: studies are carried out in paired sera taken with an interval of 5-7 days. An increase in antibody titer of 4 times or more is considered diagnostically significant. The method is highly effective, diagnosis confirmation reaches 96-98%. To increase the efficiency of serodiagnosis of hemorrhagic fever with renal syndrome, it is recommended to collect the first serum before the 4-7th day of illness, and the second - no later than the 15th day of illness. Solid-phase ELISA is also used, which allows you to determine the concentration of IgM antibodies. For the purpose of early diagnosis, PCR is used to detect fragments of viral RNA in the blood.

Instrumental diagnosis of hemorrhagic fever with renal syndrome

Kidney ultrasound, ECG, chest x-ray.

The invention relates to the field of medicine, in particular to virology, and can be used in the diagnosis of hemorrhagic fever with renal syndrome /HFRS/. The goal is to increase the accuracy of diagnosis, carried out from the 5th to the 13th days of illness, and to simplify the method. Diagnosis of HFRS is carried out by a single determination in the same sample of freshly collected urine of a patient of the HFRS virus antigen using an enzyme-linked immunosorbent assay (ELISA) and antibodies to it using the indirect method of fluorescent antibodies /NMFA/ in the early period of the disease /from 5th to 13th th days/. 2 tables

The invention relates to medicine, in particular to virology, and can be used in the diagnosis of hemorrhagic fever with renal syndrome (HFRS), a severe viral natural focal disease widespread in the USSR and other countries of Europe, Asia and America. There is a known method for diagnosing HFRS by determining antibodies in the blood. However, it is not accurate enough, since the diagnosis is made on the basis of seroconversion of a fourfold increase in antibody titers using paired sera obtained in the first days of the disease and again on the 14th to 21st days. Recently, information has appeared about obtaining the results of the reaction at the beginning of the second week of the disease, and therefore there is a need for earlier blood collection. However, this is difficult, since patients are usually admitted to the hospital no earlier than the 4th day of illness. Thus, the principle of a fourfold increase in antibody titers is violated. There is also a known method for the early diagnosis of HFRS by determining the virus antigen as part of the immune complex in the blood of patients using a solid-phase immunoenzymatic method. However, the determination of the antigen by this method is achieved indirectly through a specific immune complex and needs confirmation, and the timing of the diagnosis of the disease has not been specified. All diagnostic methods that use blood as a test sample are associated with a certain degree of risk of contracting other diseases (hepatitis, AIDS). Currently, there is a known method for the early diagnosis of HFRS by determining the antigen in the urine of patients using direct enzyme-linked immunosorbent assay (ELISA). However, diagnosis by this method needs to be clarified due to the possible receipt of false positive results (2%). In addition, there are known diagnostic methods based on the content of antibodies in urine using immunoblotting and ELISA for AIDS; detection of cytomegalovirus antigens and antibodies in the urine of newborns and children using ELISA; cytomegalovirus in urine using DNA amplification in the polymerase chain reaction. Diagnosis based on the content of antibodies in the urine of patients with HFRS has not previously been carried out. NMFA has not been used to determine antibodies in urine for other diseases. The purpose of the invention is to increase the reliability and accuracy of disease diagnosis and simplify the method. This goal is achieved by the fact that the diagnosis of HFRS is carried out by a single determination in the same sample of freshly collected urine of a patient of the virus antigen using an enzyme-linked immunosorbent assay (ELISA) and antibodies to it using the indirect method of fluorescent antibodies (IFA) in the early period of the disease (with 5th to 13th day). The method is carried out as follows. In a sample of freshly collected morning urine, the antigen of the HFRS virus is determined using ELISA and antibodies to it using NMFA. 1. When determining the virus antigen, 75 μl of immunoglobulin isolated from the serum of a person who has recovered from HFRS is added to each well of the polystyrene panel for immunological reactions, in a working dilution according to the indicated titer. Contact 18 hours at 4 o C. After washing three times with 0.1 M phosphate buffer solution (PBS) pH 7.4 with 0.05% Tween, the panel is filled with a solution of 1% albumin in PBS and placed in a thermostat at 37 o C for 30 minutes. The panel is washed three times and the test native urine is added in a volume of 50 μl per immune-coated well. Urine from healthy people and patients with other diseases is used as a control. After contact for 2 hours at 37 o C, the panel is washed three times with PBS and Tween and 50 μl of horseradish peroxidase-labeled immunoglobulin is added to each well. The panel is placed in a thermostat for 1 hour, washed and 10 μl of substrate containing orthophenylenediamine in 0.1 M citrate phosphate buffer pH 5.0 and hydrogen peroxide (0.06%) is added to each well. After 50 minutes of contact in a dark chamber at room temperature, the reaction is stopped by adding a 2 M H 2 SO 4 solution. The reaction is taken into account visually, comparing the color of the test samples with the control. The presence of the HFRS virus antigen is judged by the appearance of a yellow color in the test sample. 2. In order to determine specific antibodies in the same urine sample, a cultural polyvalent diagnosticum for hemorrhagic fever with renal syndrome produced by the Institute of Poliomyelitis and Viral Encephalitis of the USSR Academy of Medical Sciences is used. At the first stage, each dilution of the test sample, starting from the maximum, is applied to a separate drop of a smear of a fixed antigen-containing diagnosticum. Serial 2-fold dilutions of the test material are pre-prepared on micropanels, starting with a 1:5 dilution. In the experiment, control sera are present on each slide: anti-HFRS immune sera of serotypes 1 and 2 in a working dilution of the corresponding titer. After incubation in a humid chamber at 37 o C for 30 minutes, the preparations are kept in PBS pH 7.2-7.4 2 times for 2 minutes, washed with distilled water and dried at room temperature. At the second stage, they are stained with luminescent serum against human globulins (produced by the Gamaleya Institute of Electromagnetic Emporium) in the working dilution indicated on the label. For the purpose of contrasting specific information, Evans Blue dye is added at a final concentration of 1:10000. Exposure and processing of the colored preparation is similar to the first stage. The preparations are viewed in a LYUMAM fluorescent microscope with an oil system (lens x 90, eyepiece x 7, filters FS 1-2, BS 8-3, SES 24-4). The last highest dilution that gives a specific glow is taken as the antibody titer in the test sample. Example. Patient K-o O.V. 42 years old. Diagnosis: HFRS, moderate severity. The antigen of the HFRS virus and antibodies to it in the patient’s urine were determined on the 6th, 9th, 13th, 16th days of illness. The HFRS virus antigen was detected by ELISA in all urine samples studied. Antibodies to the HFRS virus using NMFA were detected in a urine sample taken on the 6th day of illness at a titer of 1:160; on the 9th day at a titer of 1:20, on the 13th day - at a titer of 1:5. No antibodies were detected in urine samples taken on the 16th and 23rd days of illness. When examining 44 urine samples from 20 patients with HFRS, collected at different stages of the disease, antigen to the HFRS virus and specific antibodies were detected from the 5th to the 13th day of illness in 100% of the subjects. In patients with other diseases and clinically healthy people, virus antigens and specific antibodies were not detected (Table 1, Table 2). In the early period of the disease, due to impaired permeability of the blood vessels of the kidneys, antibodies penetrate into the urine of patients with HFRS from the blood with proteins (sweating into the ureter), which are detected using NMFA. Previously, no one had detected antibodies in the urine of NMFA. According to studies, antigens of the HFRS virus using ELISA and specific antibodies using NMFA in the urine are detected in all examined patients from the 5th to the 13th days of illness. Thus, in comparison with known diagnostic methods, the advantage of the claimed method is the newly discovered antibodies in the urine of NMFA and their use in combination with the determination of the antigen in the same sample of freshly obtained urine for the diagnosis of HFRS in the early stages of the disease (from the 5th to the 13th th days). Simultaneous single determination of the HFRS virus antigen and antibodies to it in the same urine sample of the patient simplifies the method and makes it possible to establish a final diagnosis in the first days of the disease, since the detection of the virus antigen and specific antibodies in the urine clearly indicates an acute HFRS infection is currently occurring. Simultaneous determination of the virus antigen and antibodies to it in the same urine sample by two different methods (ELISA and NMFA) increases the accuracy and reliability of the method and helps to avoid errors when making a diagnosis. The advantage of the proposed method is also the use of urine rather than blood as a material for testing, which eliminates the additional risk of infection with other diseases (hepatitis, AIDS). The amount of urine required for diagnosis (0.5-1.0 ml) is so small that it can be obtained from a patient even with anuria (with a catheter).

Formula of invention

A method for early diagnosis of hemorrhagic fever with renal syndrome by determining a specific antigen in urine using an enzyme-linked immunosorbent assay, characterized in that, in order to increase the accuracy of diagnosis carried out in the period from 5 to 13 days of illness, and to simplify the method, specific antibodies are simultaneously determined in In another sample of the same urine sample, hemorrhagic fever with renal syndrome is diagnosed using the indirect method of fluorescent antibodies and in the presence of antigen and antibodies.

Hemorrhagic fever with renal syndrome (HFRS) is a disease of viral origin, which is characterized by damage to the kidney tissue and multiple hemorrhages. Manifested by hemorrhagic rash, fever, decreased diuresis. To diagnose the disease, PCR tests, radioimmunoassays and enzyme immunoassays are used. Treatment is carried out with interferon preparations, immunostimulants, analgesics, and specific immunoglobulins.

The causative agent of HFRS and the prevalence of the disease

Hantaan virus is the causative agent of hemorrhagic fever with renal syndrome (nephrosonephritis), which was first isolated from the lungs of rodents in eastern Asia. A little later, viruses of this group were discovered in other countries:

  • Russia;
  • China;
  • Finland.

The causative agent of fever with renal hemorrhagic syndrome belongs to the Bunyaviridae family, which includes several strains:

  • Dubrava - found mainly in the Balkans;
  • Puumala – found in European countries;
  • Seul – distributed on all continents.

In virology, there are 2 types of HFRS pathogens:

  • Western - provokes a relatively mild form of kidney failure, in which the mortality rate does not exceed 2%. The vector of infection is the bank vole, which is found in the European part of the Russian Federation.
  • Eastern is a highly variable type of virus that causes severe kidney disease. Mortality reaches 15-20%. The carrier is the field mouse, which is found in the Far East.

Hemorrhagic viral fever affects young and middle-aged people from 18 to 50 years. In 90% of cases, the infection affects males. According to statistics, renal hemorrhagic syndrome is not universal. Outbreaks of disease are extremely rare. Groups of sick people number no more than 20-30 people.

After a viral fever, persistent immunity to hantaviruses occurs. Therefore, relapses of the disease are not observed.

Routes of transmission and classification of hemorrhagic fever with renal syndrome

Hantaviruses are transmitted by rodents - rat, Manchurian, red and red field mice. They become infected from each other through the bites of mosquitoes, ticks, and fleas. The natural habitats of rodents are:

  • forest-steppe areas;
  • mountain and foothill landscapes;
  • river valleys.

There are several endemic areas on the territory of the Russian Federation:

  • eastern Siberia;
  • European part of the Russian Federation;
  • Kazakhstan;
  • Far East;
  • Transbaikalia.

Every year in the Russian Federation, 10-20 thousand patients with nephrosonephritis are identified. Rodents are latent virus carriers. They excrete the causative agent of viral fever in feces, urine and saliva. Penetration of infected secretions into the human body occurs in several ways:

  • Contact. Lesions on the skin become the entry gate for virions. Therefore, infection occurs through contact with brushwood, soil, and hay, which are contaminated with rodent feces.
  • Air-dust (aspiration). The causative agent of the syndrome enters the body through the ENT organs when inhaling dust with mouse excrement.
  • Fecal-oral (nutritional). Hantaviruses enter humans through contaminated water or food.

 Tractor drivers, drivers, industrial and agricultural workers are susceptible to fever with renal hypofunction syndrome. The likelihood of disease depends on the number of infected mouse-like rodents living in a given area.

Depending on the method of infection, there are 6 types of nephrosonephritis:

  • domestic;
  • forest;
  • gardening;
  • agricultural;
  • industrial;
  • camp.

After infection, self-copying of the virus occurs in the inner lining of blood vessels - the endothelium. When the pathogen enters the bloodstream, a generalized infection occurs. It is manifested by general intoxication - nausea, malaise, fever.

In the progression of HFRS, an important role is played by the production of autoantibodies in the body, which:

  • damage the walls of capillaries;
  • reduce smooth muscle tone;
  • reduce blood clotting;
  • affect the kidney parenchyma;
  • have a toxic effect on the central nervous system.

When kidney tissue is damaged, a pathological syndrome occurs, manifested by pH disturbances, accumulation of nitrogenous components in the blood (azotemia), and protein excretion in the urine.

Symptoms by period

The first signs of hemorrhagic viral fever with renal syndrome appear 2-3 weeks after infection with hantavirus. During its course, periods are distinguished that successively replace each other. The clinical picture depends on:

  • severity of renal hemorrhagic syndrome;
  • degree of intoxication;
  • variant of the course of HFRS.

 Depending on a person’s immunity, hypofunction of the kidneys syndrome occurs in mild, moderate or severe form.

Feverish

The incubation period ranges from 2-50 days, after which the prodromal stage begins. It manifests itself:

  • rapid fatigue;
  • body aches;
  • increased temperature;
  • headaches.

After 2-3 days, a febrile period begins. Due to exacerbation of intoxication syndrome, patients complain of:

  • nausea;
  • insomnia;
  • blurred vision;
  • hemorrhages in the sclera of the eyes;
  • feeling of pressure in the eyeballs;
  • febrile fever (body temperature reaches 41°C).

A characteristic rash with HFRS appears on the mucous membranes and body - neck, chest, armpits. Puffiness of the face and decreased blood pressure are noted.

Oliguric

The oliguric period lasts from 6 to 8 or 14 days of pathology. The temperature drops to normal values, but the patients’ well-being does not improve. Due to the active self-copying of viruses in the body, the number of autoantibodies increases, which leads to increased fever, renal and hemorrhagic syndrome.

Signs of HFRS in adults:

  • increasing pain in the lower back;
  • increased blood pressure;
  • uncontrollable vomiting;
  • loose stools;
  • decreased urine output (daytime diuresis).

The urine takes on a reddish tint, which indicates red blood cells are being released with it (hematuria). Due to the syndrome of hypofunction of the kidneys, the symptoms of azotemia increase, which leads to severe poisoning of the body.


 During the oliguric period, hemorrhagic syndrome intensifies, and nasal and uterine bleeding is possible. In severe forms of HFRS, dangerous complications arise - hemorrhages in the brain.

Early convalescence

At the stage of early convalescence (recovery), the signs of HFRS subside - vomiting stops, body temperature decreases, sleep improves. There is an increase in daily diuresis to 3-4.5 l, which indicates the restoration of kidney function. Due to intoxication, dry mouth, decreased appetite, and stool disorders persist.

Recovery period

As the number of viruses in the body decreases, the severity of fever and renal hypofunction syndrome decreases. Sometimes the recovery period drags on for 1-3 years. Are stored for a long time:

  • emotional lability;
  • chronic fatigue;
  • reduced performance;
  • post-infectious asthenia.

Autonomic dystonia syndrome is manifested by excessive sweating, shortness of breath even with light exertion, low blood pressure and sleep disturbances.

Features of HFRS in children

Fever with hypofunction of the kidneys syndrome occurs mainly in children over 7 years of age. HFRS manifests itself:

  • prolonged hyperthermia (increased temperature);
  • lack of appetite;
  • muscle weakness;
  • body aches;
  • profuse subcutaneous hemorrhages;
  • headaches;
  • enlarged spleen;
  • nosebleeds;
  • repeated vomiting;
  • decreased urine output.

The disease occurs in a moderate or severe form with febrile fever and hemorrhagic syndrome. Painful sensations in the lower back occur within 2-3 days after infection with hantaviruses.

What is the danger of the disease

Viral pathology is accompanied by hemorrhagic fever, which is dangerous due to internal hemorrhages. Kidney dysfunction is accompanied by the accumulation of metabolic products in the body, which leads to azotemia.


 Febrile fever with a temperature up to 41°C is dangerous due to denaturation of proteins in the blood and death.

Possible complications of HFRS:

  • pyelonephritis;
  • nephrotic syndrome;
  • meningoencephalitis;
  • azotemic uremia;
  • pneumonia, pulmonary edema;
  • intestinal bleeding;
  • purulent otitis;
  • myocarditis;
  • arterial hypotension;
  • renal failure;
  • infectious-toxic shock;
  • tear of the renal capsule;
  • abscesses.

A decrease in daily diuresis down to anuria (complete absence of urine) is dangerous due to excessive intoxication and uremic coma. It is difficult to bring a person out of a comatose state, which increases the risk of death.

How is a fever detected?

The diagnosis is established by a nephrologist based on the clinical picture, laboratory and hardware tests. In case of increased bleeding of mucous membranes or fever of unknown origin, the following is performed:

  • enzyme immunoassay test;
  • coagulogram;
  • biochemical and general clinical urine tests;
  • Ultrasound of the kidneys;
  • X-ray of the heart and lungs;
  • PCR study for HFRS.

According to the data received, the doctor distinguishes viral fever from nephrotic syndrome, glomerulonephritis, enterovirus infection and leptospirosis.

Treatment of HFRS

If a viral disease is detected, a person is hospitalized in an infectious diseases hospital. Complex treatment includes:

  • drug therapy;
  • dietary food;
  • hardware procedures.

Drugs

Treatment of hemorrhagic fever with renal syndrome involves taking medications that destroy the infection. At the initial stage, medications with specific immunoglobulins and interferon are used:

  • Ribavirin;
  • Amiksin;
  • Altevir;
  • Hepavirin;
  • Moderiba;
  • Yodantipyrine;
  • Virorib;
  • Trivorin;
  • Maxivirin.

 During the olirugic period, the volume of solutions for infusion administration (droppers) is determined taking into account the urine excreted per day.

During other periods of the disease - oliguric, febrile, proteinuric - drugs are prescribed that alleviate symptoms:

  • angioprotectors (Etamzilat, Prodectin) – increase the strength of vascular walls, prevent thrombohemorrhagic syndrome;
  • detoxification agents (Glucose-cytocline, Ringer's solution) - reduce the concentration of toxic substances in the body;
  • diuretics (Furosemide, Lasix) – stimulate the diversion of urine and the removal of nitrogenous substances from the body;
  • analgesics (Trigan, Drotaverine) – eliminate pain in the kidney area;
  • antihistamines (Claritin, Erius) - reduce the severity of fever and rash;
  • blood circulation correctors (Clexane, Axparin) – normalize microcirculation in internal organs and prevent thrombus formation.

In case of exacerbation of renal syndrome, it is necessary to carry out hardware blood cleansing.

Diet and bed rest

Renal fever is accompanied by a violation of the filtering and excretory functions of the kidneys. To reduce the load on the urinary system, stay in bed for at least 1.5-3 weeks. For maximum kidney protection, follow diet No. 4 according to Pevzner.

For the period of treatment of viral fever, the menu includes:

  • dried apricots;
  • strawberries;
  • cabbage;
  • pears;
  • lean meat;
  • fermented milk products;
  • cereal porridge;
  • natural juices.

For a while, confectionery products, semi-finished products, canned fish, and alcohol are excluded from the diet.


 To prevent urinary retention, drink diuretic drinks - berry fruit drinks, pumpkin juice, Borjomi, Essentuki-4.

Hemodialysis

If renal hemorrhagic syndrome is complicated by kidney failure, they resort to hemodialysis - a procedure for purifying blood plasma outside the body. An “artificial kidney” device is used to remove metabolic products. The number of procedures depends on:

  • from age;
  • degree of kidney dysfunction;
  • severity of the course.

In 80% of cases, hemodialysis is used 2-3 times a week until the functions of the urinary system are restored.

Other mandatory measures

When the fever and renal hemorrhagic syndrome subsides, restorative therapy is recommended. Patients are prescribed hardware procedures:

  • Microwave therapy;
  • electrotherapy with high-frequency currents;
  • electrophoresis.

To improve blood circulation in the pelvic organs and kidneys, moderate physical activity and therapeutic massage are indicated.

Follow-up after therapy

Patients who have undergone HFRS require dynamic monitoring. For 6-12 months after the infection is eradicated, they should be regularly examined by:

  • nephrologist/urologist;
  • infectious disease specialist;
  • ophthalmologist.

Once a quarter, patients undergo a general urine test and undergo a fundus examination. Children who have had a viral disease are contraindicated from vaccination against other infections for 1 year.

Treatment prognosis

With mild and moderate forms of viral fever, recovery occurs in 98% of cases, but only with timely treatment. Post-infectious syndromes - increased fatigue, polyneuritis, asthenia - persist for several weeks in 50% of those who have recovered from a viral infection.


 Against the background of HFRS, 20% of people develop chronic pyelonephritis, another 30% develop hypertension.

In the case of a severe decrease in immunity, HFRS rapidly progresses, which leads to increased renal and hemorrhagic syndrome. Delayed therapy is dangerous due to internal bleeding and uremic coma. According to statistics, the mortality rate from the disease reaches 7-15%.

How to avoid infection

Prevention of HFRS is aimed at maintaining hygiene and exterminating rodents that carry hantaviruses. To prevent infection, you must:

  • use filters to disinfect water;
  • comply with sanitary and hygienic rules;
  • thoroughly rinse vegetables, herbs, and fruits before eating;
  • destroy rodents in houses and other premises;
  • protect grain and feed warehouses from mice.

Hemorrhagic viral fever with renal hypofunction syndrome is a serious disease that often manifests itself as renal failure. Untimely treatment can result in life-threatening complications. Therefore, at the first signs of HFRS - high temperature, decreased diuresis, pain in the renal area, fever, hemorrhagic rash - you need to contact a nephrologist or infectious disease specialist.

HFRS, in other words, is an acute viral natural focal disease (popularly called mouse fever). The disease is characterized by fever and intoxication, can affect the kidneys and develop thrombohemorrhagic syndrome.
The HFRS virus was first discovered in 1944. A.A. was in charge of it. Smorodintsev, but it was isolated by the South Korean scientist N.W. Lee a little later, in 1976. Subsequently, this virus was used for diagnostic testing of hemorrhagic fever. There were 116 patients who received a severe form of fever, and 113 of them were noted to have a diagnostic increase in the titers of immunofluorescent antibodies found in the blood serum.

After a while, a similar virus was isolated in the following countries: USA, Finland; Russia, China and others. Today it is a separate genus of virus.
The so-called Hantaan virus and Puumala virus are RNA viruses. Their diameter is 85 – 110 nm. The virus can die at a temperature of 50 °C, and it must be kept for at least half an hour. The virus can function for up to 12 hours at temperatures between 0 and 4 °C. Today, there are two main HFRS viruses:

  • Hantaan is capable of circulating in natural foci in the Far East, Russia, South Korea, North Korea, Japan and China. It can be carried by a field mouse;
  • The European type of virus - Puumala - is found in Finland, Sweden, Russia, France and Belgium. The carrier is the bank vole.

It is possible that there is a third species; it is suspicious that it is found in the Balkans.

Medical history

HFRS is related to areas of natural focality. HFRS is a hemorrhagic fever with renal syndrome. The carrier and causative agent of this kind of disease are mice and rodents of the mouse species. In the European half of our country, infections are spread by the bank vole. In epidemic foci, their infection can reach 40, or even up to 60%.
The Far East is much richer in sources of infection. Here the infection is spread by: field mice, red-and-gray field mice and Asian bats. In urban settlements, house rats can be the causative agent. The causative agent of HFRS is excreted in urine or feces.

Rodents transmit infection to each other through airborne droplets. Infection occurs by inhaling the odor from the feces of an infected individual. You can also become infected through contact with an infected rodent, as well as an infected object (for example, hay or brushwood that an infected mouse has walked on). A person can become infected by eating foods that rodents have come into contact with, including cabbage, carrots, cereals, etc.
An infected person cannot infect any other person. The HFRS virus most often spreads to men aged 16 to 50 years. The percentage of infected men can be up to 90%. Thus, during the cold winter, the number of rodents decreases, and the activity of the virus in January–May also decreases significantly. But with the end of the spring season (at the end of May), the virus begins to increase. The peak incidence occurs between June and December.
In 1960, HFRS virus diseases were observed in 29 regions of our country. If we consider the present time, the disease, first of all, can progress between the Volga and the Urals. This includes the following republics and regions: the republics of Bashkiria and Tatarstan, the republic of Udmurtia, Ulyanovsk and Samara regions.

People from all countries are susceptible to hemorrhagic fever. HFRS was observed in the following countries: Sweden, Finland, Norway, Yugoslavia, Bulgaria, Belgium, Czechoslovakia, France, China, South Korea and North Korea. A special serological survey conducted in central African countries, Southeast Asia, the Hawaiian Islands, as well as Argentina, Brazil, Colombia, Canada and the USA showed that the population of these countries has a number of specific antibodies against the HFRS virus.

To summarize, we can say that the history of HFRS disease began thanks to mouse-like rodents. They are carriers of numerous other diseases.

Pathogenesis

The door to infection is opened by the mucous membrane of the respiratory tract, in some cases it may be the skin or mucous membrane of the digestive organs. The first signs of HFRS are intoxication and viremia. The disease causes great damage to the vascular walls. Vascular damage plays a large role in the genesis of renal syndrome. Studies have shown that complications reduce glomerular filtration rate.

Presumably, the cause of the development of renal failure in most cases is an immunopathological factor. Thrombohemorrhagic syndrome may occur, which depends on the severity of the disease. People who have had HFRS have good immunity. No recurrent diseases have been identified yet.

Symptoms of GPLS

With this disease, the incubation period lasts 7-46 days, generally recovery takes 3-4 weeks. There are several stages of the disease:

  • Initial stage;
  • Oligouric period (at this moment, renal and hemorrhagic manifestations are monitored);
  • Polyuric period;
  • The period of convalescence.

The symptoms of HFRS disease in children are no different from the symptoms of the disease in adults.

  1. The initial stage of the disease lasts up to 3 days. As a rule, it has pronounced and acute symptoms (chills, high temperature, which can rise to 40 ° C). In addition, there may be such ailments as severe headache, feeling of weakness, dry mouth. When examining a patient, doctors may note hyperemia of the skin on the face, neck, and upper chest. During the disease, hyperemia of the pharynx mucosa and injection of the sclera of blood vessels occurs.

In some cases, a hemorrhagic rash appears. Some patients develop HFRS gradually. A few days before the disease, weakness, malaise may appear, and catarrhal symptoms of the upper respiratory tract may occur. Changes occurring in the internal organs of the body are quite difficult to detect at the initial stage of the disease; they will manifest themselves a little later. At the initial stage of the disease, symptoms such as dull pain in the lumbar region and moderate manifestations of bradycardia may occur. In severe cases, meningism may occur.

  1. The next oliguric period lasts somewhere from 2 or 4 days to 8 or 11 days. The patient’s body temperature remains at the same level: 38 – 40 °C. It can stay at this level for up to 7 days of illness. But, as it turned out, lowering the temperature level does not affect the patient’s well-being in any way; he does not feel any better. In most cases, as the temperature drops, the patient feels significantly worse.

The second period of the disease is often manifested by pain in the lumbar region, the degree of pain can be any. If lower back pain does not appear within 5 days, you can think about the correctness of the diagnosis and the disease HFRS. In many patients, 1 or 2 days after the cessation of pain in the lumbar region, vomiting may occur. Vomiting can occur at least 8 times a day. Vomiting does not depend in any way on food intake or medications. You may also experience abdominal pain or bloating.
Upon examination, doctors can detect dry skin, hyperemia of the face and neck, hyperemia of the mucous membrane of the pharynx and conjunctiva. Possible swelling of the upper eyelid. Manifestation of hemorrhagic symptoms.

  1. Thrombohemorrhagic syndrome of any severity manifests itself only in some patients who have an advanced form of the disease. At this stage of the disease, high vascular fragility appears. Petechia appears in approximately 10 or 15% of patients, and gross hematuria occurs in 7-8% of patients. Approximately another 5% of patients suffer from intestinal bleeding. You may also notice bruising at the site where the injection was given, nosebleeds, hemorrhages in the sclera, and in even more rare cases, bleeding may be accompanied by vomiting or sputum production. The disease is not accompanied by bleeding from the gums or uterus.

The frequency of symptoms and illnesses is accompanied only by the degree of complexity of the disease. In approximately 50-70% of cases they manifested themselves in severe forms of the disease, 30-40% less often in cases of moderate severity and in 20-25% of cases in mild forms of the disease. During epidemic manifestations of the disease, signs of the disease appear much more often and stronger.
In any case, the symptoms that appear require urgent treatment to the hospital and proper treatment.

The most characteristic manifestation of HFRS disease is kidney damage. As a rule, kidney disease is accompanied by swelling of the face, pasty eyelids, and positive Pasternatsky symptoms.
Oliguria in severe forms of the disease can develop into enuresis. When taking tests, special attention is paid to the protein content in the urine; usually it increases greatly and can reach 60 g/l. At the beginning of the period, microhematuria may appear; there is a possibility of detecting hyaline and granular cylinders, and in some cases long Dunaevsky cylinders, in the urine sediment. The level of residual nitrogen increases. More pronounced symptoms of azotemia may appear towards the end of the week of illness or by the 10th day. Restoring nitrogen levels is possible in two or three weeks.

Distinguish 6 clinical periods of the disease: incubation, initial (febrile, general toxic), period of focal symptoms and renal pathology (hemorrhagic, oliguric), polyuric, convalescence, period of residual phenomena.

The disease is characterized by a cyclical nature!

1) incubation period – 7-49 days (on average 12-18 days);
2) initial (febrile period) – 3-5 days;
3) oligoanuric period – from 7-10 days of illness to 2 weeks;
4) polyuric – 2-3 weeks to 1 month;
5) convalescence - after the 30th day of illness - up to 1-3 years.

Sometimes the initial period is preceded by prodromal period: lethargy, increased fatigue, decreased performance, pain in the limbs, sore throat. Duration no more than 2-3 days.

Initial period characterized by the appearance of headaches, chills, aches in the body and limbs, joints, and weakness.

The main symptom of the onset of HFRS is sudden increase in body temperature, which in the first 1-2 days reaches high numbers - 39.5-40.5 ° C. Fever can persist from 2 to 12 days, but most often it is 6 days. The peculiarity is that the maximum level is not in the evening (as usual with ARVI), but in the daytime and even morning hours. In patients, other symptoms of intoxication immediately increase - lack of appetite, thirst appears, patients are lethargic, sleep poorly. Headaches diffuse, intense, increased sensitivity to light stimuli, pain when moving the eyeballs. 20% have visual impairment – ​​“fog before the eyes.” When examining patients, “ hood syndrome"(craniocervical syndrome): hyperemia of the face, neck, upper chest, puffiness of the face and neck, injection of blood vessels of the sclera and conjunctiva (redness of the eyeballs is visible). The skin is dry, hot to the touch, the tongue is covered with a white coating. Already during this period, heaviness or dull pain in the lower back may occur. With high fever, it is possible to develop infectious-toxic encephalopathy(vomiting, severe headache, stiff neck, Kernig's, Brudzinski's symptoms, loss of consciousness), and also infectious-toxic shock(a rapid drop in blood pressure, first an increase in heart rate and then a decrease in heart rate). It is characterized by general toxic symptoms: headache, malaise, muscle pain, chills, lack of appetite, pain in the eyeballs. Pain when swallowing and hyperemia of the pharynx are common. There is no runny nose or cough. The tongue is covered with a white or brown coating with a pure crimson tip. The appearance of the patient is characteristic: hyperemia of the face, neck and upper chest segment, hyperemia of the conjunctiva, injection of blood vessels, sclera (“rabbit” eyes). But sometimes there are patients with HFRS with pale skin. The initial period is characterized by bradycardia. Blood pressure is often low, although there are also cases of hypertension (not higher than 200 mm Hg). Very typical for this disease (in 15-30% of patients) is a short-term visual disturbance: a feeling of fog, a grid before the eyes, blurry outlines of objects and letters. This symptom is associated with vascular pathology and disappears without a trace after 1-3 days. The temperature rises to high levels on the very first day and remains constantly at this level for 3-8 days, rarely longer. The fever ends with accelerated lysis. Repeated rises in temperature usually do not occur. With a drop in temperature, the patient’s condition not only does not improve, but, on the contrary, worsens. Only with a mild course of the disease does improvement occur. Sometimes such patients have only a low-grade fever or it does not rise at all. At the end of this period, abdominal pain appears, especially in the epigastrium, in the lower back, dry mouth, severe thirst, nausea and vomiting are observed, protein appears in the urine, and the specific gravity of urine decreases.

Oliguric period. It is characterized by a practical decrease in fever on days 4-7, but the patient does not feel better. Constants appear lower back pain of varying severity - from aching to sharp and debilitating. If a severe form of HFRS develops, then after 2 days from the moment of painful renal pain syndrome, they are accompanied by vomiting and aching abdominal pain in the area of ​​the stomach and intestines. The second unpleasant symptom of this period is decrease in the amount of urine excreted(oliguria). Laboratory tests - decreased specific gravity of urine, protein, red blood cells, casts in the urine. The content of urea, creatinine, and potassium in the blood increases, the amount of sodium, calcium, and chlorides decreases. This period is the most severe (the height of the disease). The patient is lethargic, lethargic, and there is hyperemia of the face, neck, upper segments of the body, conjunctiva and sclera. Pasternatsky's symptom is sharply positive. Despite the normal temperature, pain in the abdomen and lower back intensifies and sometimes becomes unbearable. Patients cannot find a comfortable position in bed, are deprived of sleep, and groan in pain. Thirst continues: the patient drinks liters of water. Vomiting intensifies, sometimes becoming uncontrollable. Changes appear in the urine (albuminuria, hematuria, cylindruria), which last only a few days. The specific gravity of urine decreases (below 1010), isosthenuria appears, during the day the specific gravity fluctuates slightly (by no more than 5 units), despite strong thirst, the amount of urine excreted drops sharply - to 400-500 mm per day, sometimes reaching to complete anuria. In this case, peripheral edema never develops, only facial pastiness is possible. All fluid is located in loose retroperitoneal and perinephric tissue. Abdominal pain is localized in the pit of the stomach and in the peri-umbilical region, and is explained by hemorrhages in the internal organs and retroperitoneal tissue. Even light tapping of the epigastric region can be painful. Most patients experience stool retention, but in some cases it may be liquid for a short time. The liver is usually of normal size, but sometimes protrudes from under the edge of the costal arch by 1-2 fingers. The spleen is never enlarged. The cardiovascular system is characterized by sinus bradycardia and muffled heart sounds. In some patients, at the beginning of the second period, an acute drop in cardiac activity (collapse) occurs with a decrease in temperature, cold sweat, cyanosis of the extremities, a frequent small pulse, low or undetectable blood pressure. This condition often leads to death, and only with intensive therapy can the patient be brought out of collapse.

At the same time, it appears hemorrhagic syndrome. A pinpoint hemorrhagic rash appears on the skin of the chest, in the armpits, and on the inner surface of the shoulders. The stripes of the rash may be located in certain lines, as if from a “lash”. Hemorrhages appear in the sclera and conjunctiva of one or both eyes - the so-called “red cherry” symptom. 10% of patients develop severe manifestations of hemorrhagic syndrome - from nosebleeds to gastrointestinal ones. (Appendix 4a, 4b)

The peculiarity of this period of HFRS is a peculiar changes in cardiovascular function: decreased heart rate, tendency to hypotension, muffled heart sounds. The ECG shows sinus bradycardia or tachycardia, and extrasystoles may appear. Blood pressure during the period of oliguria with initial hypotension turns into hypertension. Even within one day of illness, high blood pressure can be replaced by low blood pressure and vice versa, which requires constant monitoring of such patients. Individuals infected respiratoryly develop changes in the lungs. Pneumonia is rarely observed (in 2%), bronchitis is more common (up to 25%), and sometimes these changes are limited only to an increase in the hilar pattern of the lungs during X-ray examination. Damage to the autonomic nervous system is significantly pronounced (bradycardia, hyperemia of the face, neck, chest, pain in the area of ​​the nerve plexus - epigastrium, near the umbilical region). Damage to the central nervous system occurs as a toxic encephalopathy, and sometimes meningeal phenomena develop.

In 50-60% of patients during this period, nausea and vomiting even after a small sip of water. Pain in the abdomen of an excruciating nature is often bothered. 10% of patients have loose stools, often mixed with blood.

During this period, a prominent place was occupied by symptoms of nervous system damage: patients have severe headache, stupor, delirium, often fainting, hallucinations. The reason for such changes is hemorrhages in the brain.

It is during the oliguric period that one must be wary of one of the fatal complications - o structure of renal failure and acute adrenal failure.

Polyuric period. Characterized by gradual restoration of diuresis. Patients feel better, the symptoms of the disease weaken and regress. Patients excrete a large amount of urine (up to 10 liters per day), low specific gravity (1001-1006). After 1-2 days from the onset of polyuria, laboratory indicators of impaired renal function are restored.
By the 4th week of illness, the amount of urine excreted returns to normal. For another couple of months, slight weakness, slight polyuria, and a decrease in the specific gravity of urine persist.

HFRS is characterized by a kind of “scissors” between the amount of fluid drunk and excreted. At first, patients drink a lot of fluid, but excrete little urine, and then, on the contrary, thirst disappears, and a lot of urine is excreted. During this period, the level of residual nitrogen and urea in the blood decreases, and the phenomena of hemorrhagic diathesis disappear. Headaches, lumbar pains and weakness slowly disappear.

Convalescence. From one year to 3 years.

IN convalescence period there is a gradual restoration of health. This period lasts from 3 months in mild forms of the disease to 12 months and longer in severe forms. The first 3 months belong to the period of early and subsequent months - to the period of late convalescence. In patients who were hospitalized late, who did not strictly adhere to bed rest in the acute period, who were discharged early from the hospital, and even straight to work, the period of convalescence is difficult, especially within 4-6 months from the onset of the disease. This period is characterized by asthenia (weakness, decreased performance, fatigue, emotional lability), vegetative-vascular dystonia (blood pressure fluctuations, pulse instability, sometimes with sinus arrhythmia, skin vasomotor reactions, sweating), diencephalic syndrome (decreased potency, dysmenorrhea, baldness , sleep disturbance), myocardial dystrophy.

In 1% of convalescents, persistent changes in the heart and kidneys remain without positive dynamics. This is explained by irreversible fibrotic changes in the heart muscle and renal parenchyma. No chronic course of the disease or relapses were noted with HFRS.

Mild and erased forms of the disease were not detected before the development of laboratory diagnostic methods and were even treated in hospitals under other diagnoses. In mild forms there are no symptoms. However, the clinical picture develops in stages and retains many specific features. In the initial period, hyperemia of the face and pharynx and bradycardia are recorded. On the 2-3rd day, mild aching pain in the lower back and abdomen begins. Instead of vomiting there may be slight nausea, instead of thirst there may be dry mouth. The most common renal syndromes are pain when tapping the kidney area, polyuria and transient isohyposthenuria. Erased forms of the disease may also occur: malaise, headache, low-grade fever, mild renal syndrome. During serological examination of such patients, an increase in antibody titers to the HFRS virus is observed.

Residual symptoms and their combinations are divided into 3 groups:

Asthenia - weakness, decreased performance, dizziness, decreased appetite.
Dysfunction of the nervous and endocrine systems - sweating, thirst, itching, impotence, lower back pain, increased sensitivity in the lower extremities.
Renal residual effects - heaviness in the lower back, increased diuresis up to 2.5-5.0 l, the predominance of nighttime diuresis over daytime, dry mouth, thirst. Duration is about 3-6 months.

Clinical diagnosis of HFRS, given the characteristic picture of the disease, is not difficult, especially in the 2nd week. However, in the 1st week (it is during this period that patients go to the medical center for help) it is much more difficult to make a diagnosis. A symptom such as visual impairment facilitates diagnosis. Such a patient should have a history of visiting the forest 10-35 days before the disease. The likelihood of diagnosis increases with constant work in the forest, and in the fall and winter - with living in or near the forest. Among rural residents, forestry workers, livestock breeders, feed trucks, machine operators, drivers, and beekeepers are more likely to get sick. The diagnosis of HFRS is made based on the characteristic stages of disease development.

Complications of HFRS

1) Azotemic uremia. Develops in severe form of HFRS. The reason is the “slagging” of the body due to a serious dysfunction of the kidneys (one of the excretory organs). The patient experiences constant nausea, repeated vomiting that does not bring relief, and hiccups. The patient practically does not urinate (anuria), becomes lethargic and gradually develops coma (loss of consciousness). It is difficult to bring a patient out of an azotemic coma, and the outcome is often fatal.

2) Acute cardiovascular failure. Either symptoms of infectious-toxic shock in the initial period of the disease against the background of high fever, or on the 5-7th day of the disease against the background of normal temperature due to hemorrhage in the adrenal glands. The skin becomes pale with a bluish tint, cold to the touch, and the patient becomes restless. The heart rate increases (up to 160 beats per minute), blood pressure rapidly drops (up to 80/50 mmHg, sometimes not determined).

3) Hemorrhagic complications: 1) Tear of the renal capsule with the formation of hemorrhage in the perinephric tissue (in case of improper transportation of a patient with severe lower back pain). The pain becomes intense and persistent. 2) Rupture of the kidney capsule, which can result in severe hemorrhages in the retroperitoneal space. Pain appears suddenly on the side of the rupture, accompanied by nausea, weakness, and sticky sweat. 3) Hemorrhage into the adenohypophysis (pituitary coma). Manifested by drowsiness and loss of consciousness, 4) hemorrhage in the brain, in the heart muscle (hemorrhagic infarction).

4) Bacterial complications(pneumonia, pyelonephritis).

Diagnosis of HFRS

Differential diagnosis At different stages, HFRS is carried out with different diseases. The most difficult differentiation is in the first period of the disease. First of all, you need to rule out the flu. HFRS is characterized by a combination of epigastric, lumbar pain and vomiting, which is not typical for influenza. With influenza, with a decrease in temperature, the patient's condition improves, but with HFRS - not. The presence of hyperemia of the pharynx is often the basis for making diagnoses: “catarrhal tonsillitis” or “ARVI”. With these diseases, there is usually no epigastric and lumbar pain. Typhoid fever is characterized by pallor of the face, enlarged spleen, a specific appearance of the tongue, rumbling and pain in the right iliac region, which does not happen with HFRS. With typhus, a profuse rash is observed throughout the body, and bradycardia and pain in the epigastric region are uncharacteristic. With anicteric leptospirosis, muscle pain is more pronounced than with HFRS; characterized by a polymorphic, spotted and roseate rash, enlarged spleen and liver, improvement with a drop in temperature.

During the height of the illness making the correct diagnosis is not difficult. HFRS symptoms are distinguished from the symptoms of an acute abdomen by a febrile onset, changes in urine, and the absence of symptoms of peritoneal irritation. For banal renal pathology (pyelonephritis, acute nephritis), the febrile onset observed with HFRS, pronounced, rapidly appearing and disappearing infectious symptoms, high protein levels and other changes in the urine, the development and disappearance of isohyposthenuria are not typical. HFRS is distinguished from an exacerbation of chronic diffuse glomerulonephritis by an acute onset in the absence of a history of kidney pathology and by the dynamics of the specific gravity of urine during the course of the disease. It is most difficult to differentiate HFRS from a “toxic kidney”. Both diseases are characterized by almost the same symptoms. The diagnosis is facilitated by a serological study of paired sera and various epidemiological anamnesis: being in the forest before the disease with HFRS and contact with acute poisons (arsenic, sublimate, phosphorus, etc.) with “toxic kidney”.

1) If HFRS is suspected, such points as the presence of the sick in natural foci of infection, the level of morbidity in the population, autumn-winter seasonality and characteristic symptoms of the disease are taken into account.

2) Instrumental examination of the kidneys (ultrasound) - diffuse changes in the parenchyma, pronounced swelling of the parenchyma, venous stagnation of the cortex and medulla;

3) The final diagnosis is made after laboratory detection of IgM and G class antibodies using enzyme-linked immunosorbent assay (ELISA) (with an increase in antibody titer by 4 times or more) - paired sera at the onset of the disease and after 10-14 days.

Serological diagnosis of HFRS is carried out using the indirect method of fluorescent antibodies. To do this, upon treatment, 2 ml of blood is taken from a vein from the patient and after a clot has formed, the serum is transferred with a syringe into an empty bottle of any antibiotic, without removing the metal clip from it. There is no need to rinse the vials; you just need to remove the remaining antibiotic with a syringe. After 5-7 days, a second serum sample is taken. Before shipping, the serum must be stored in the refrigerator at 4 °C. Full name indicated in the direction. patient, age, diagnosis, date of illness, taking the first and second serum samples. Both serum samples and the referral are sent by parcel post to the laboratory of especially dangerous infections of the regional (territorial, republican) sanitary and epidemiological station. The absence of antibodies in the first serum and their presence at any titer in the second or a fourfold increase in antibody titer in the second serum confirms the diagnosis of HFRS. Only with late blood (serum) collection - in the 3rd week and later - there may not be an increase in titers. It should be borne in mind that in people who have previously had HFRS, antibodies can persist for up to 25 years or longer. Some patients with HFRS (1-2%) may be seronegative, and antibodies are not formed in their blood. In these cases, the clinical picture of the disease, epidemiological history, as well as information about the presence of natural foci of this infection in a specific area are of paramount importance.