Zoonotic hantavirus infection characterized by thrombohemorrhagic syndrome and predominant defeat kidney Clinical manifestations include acute fever, hemorrhagic rash, bleeding, interstitial nephritis, and in severe cases, acute renal failure. Specific laboratory methods for diagnosing hemorrhagic fever with renal syndrome include RIF, ELISA, RIA, and PCR. Treatment consists of administering specific immunoglobulin, interferon preparations, detoxification and symptomatic therapy, and hemodialysis.
ICD-10
A98.5
General information
Hemorrhagic fever with renal syndrome (HFRS) is a natural focal viral disease, the characteristic signs of which are fever, intoxication, increased bleeding and kidney damage (nephrosonephritis). On the territory of our country, endemic areas are the Far East, Eastern Siberia, Transbaikalia, Kazakhstan, European territory, therefore HFRS is known under various names: Korean, Far Eastern, Ural, Yaroslavl, Tula, Transcarpathian hemorrhagic fever, etc. Every year in Russia from 5 to 20 thousand cases of hemorrhagic fever with renal syndrome. The peak incidence of HFRS occurs between June and October; the main contingent of cases (70-90%) are men aged 16-50 years.
Causes of HFRS
The causative agents of the disease are RNA-containing viral agents of the genus Hantavirus (hantaviruses), belonging to the Bunyaviridae family. Four serotypes of hantaviruses are pathogenic for humans: Hantaan, Dubrava, Puumala, Seoul. In the external environment, viruses remain stable for a relatively long time at negative temperatures and are less stable at a temperature of 37°C. Viruses are spherical or spiral in shape, with a diameter of 80-120 nm; contain single-stranded RNA. Hantaviruses have tropism for monocytes, kidney, lung, liver cells, salivary glands and multiply in the cytoplasm of infected cells.
The carriers of the causative agents of hemorrhagic fever with renal syndrome are rodents: field and forest mice, voles, house rats, which become infected from each other through the bites of ticks and fleas. Rodents carry the infection in the form of latent virus carriage, releasing pathogens into the external environment with saliva, feces and urine. The entry of material infected with rodent secretions into the human body can occur by aspiration (by inhalation), contact (by contact with the skin) or alimentary (by eating) route. The high-risk group for the incidence of hemorrhagic fever with renal syndrome includes agricultural and industrial workers, tractor drivers, and drivers who are actively in contact with environmental objects. The incidence of human disease directly depends on the number of infected rodents in a given area. HFRS is recorded mainly in the form of sporadic cases; less often - in the form of local epidemic outbreaks. Remains persistent after infection lifelong immunity; cases of repeated incidence are rare.
The pathogenetic essence of hemorrhagic fever with renal syndrome consists of necrotizing panvasculitis, disseminated intravascular coagulation syndrome and acute renal failure. After infection, primary replication of the virus occurs in the vascular endothelium and epithelial cells of internal organs. Following the accumulation of viruses, viremia and generalization of infection occur, which are clinically manifested by general toxic symptoms. In the pathogenesis of hemorrhagic fever with renal syndrome, an important role is played by the resulting autoantibodies, autoantigens, CIC, which have a capillary toxic effect, causing damage to the walls of blood vessels, impaired blood clotting, and the development of thrombosis hemorrhagic syndrome with damage to the kidneys and other parenchymal organs (liver, pancreas, adrenal glands, myocardium), and central nervous system. Renal syndrome is characterized by massive proteinuria, oligoanuria, azotemia, and impaired CBS.
Symptoms of HFRS
Hemorrhagic fever with renal syndrome is characterized by a cyclic course with a succession of several periods:
- incubation (from 2-5 days to 50 days - on average 2-3 weeks)
- prodromal (2-3 days)
- febrile (3-6 days)
- oliguric (from 3-6 to 8-14 days of HFRS)
- polyuric (from 9-13 days HFRS)
- convalescent (early - from 3 weeks to 2 months, late - up to 2-3 years).
Depending on the severity of symptoms, the severity of infectious-toxic, hemorrhagic and renal syndromes, typical, erased and subclinical variants are distinguished; mild, moderate and severe forms of hemorrhagic fever with renal syndrome.
After the incubation period, a short prodromal period begins, during which fatigue, malaise, headaches, myalgia, and low-grade fever are noted. The febrile period develops acutely, with an increase in body temperature to 39-41°C, chills and general toxic symptoms (weakness, headache, nausea, vomiting, sleep disorders, arthralgia, body aches). Characterized by pain in the eyeballs, blurred vision, flashing “spots”, seeing objects in red. At the height of the febrile period, hemorrhagic rashes appear on the mucous membranes of the oral cavity, skin of the chest, axillary areas, and neck. An objective examination reveals hyperemia and puffiness of the face, vascular injection of the conjunctiva and sclera, bradycardia and arterial hypotension up to collapse.
During the oliguric period of hemorrhagic fever with renal syndrome, body temperature decreases to normal or low-grade levels, but this does not lead to an improvement in the patient’s condition. At this stage, the symptoms of intoxication intensify even more and signs of kidney damage appear: lower back pain increases, diuresis sharply decreases, and arterial hypertension develops. Hematuria, proteinuria, and cylindruria are detected in the urine. As azotemia increases, acute renal failure develops; in severe cases - uremic coma. Most patients experience uncontrollable vomiting and diarrhea. Hemorrhagic syndrome can be expressed to varying degrees and include gross hematuria, bleeding from injection sites, nasal, uterine, and gastrointestinal bleeding. During the oliguric period, they can develop severe complications(hemorrhages in the brain, pituitary gland, adrenal glands), causing death.
The transition of hemorrhagic fever with renal syndrome to the polyuric stage is marked by subjective and objective improvements: normalization of sleep and appetite, cessation of vomiting, disappearance of lower back pain, etc. Characteristic features of this period is an increase in daily diuresis to 3-5 l and isohyposthenuria. During polyuria, dry mouth and thirst persist.
The period of convalescence for hemorrhagic fever with renal syndrome can be delayed for several months and even years. In patients, post-infectious asthenia persists for a long time, characterized by general weakness, decreased performance, fatigue, and emotional lability. Autonomic dystonia syndrome is expressed by hypotension, insomnia, shortness of breath with minimal exertion, and increased sweating.
Specific complications of severe clinical options HFRS can be infectious-toxic shock, hemorrhages in parenchymal organs, pulmonary and cerebral edema, bleeding, myocarditis, meningoencephalitis, uremia, etc. With the addition of a bacterial infection, the development of pneumonia, pyelonephritis, purulent otitis, abscesses, phlegmon, sepsis is possible.
Diagnosis of HFRS
Clinical diagnosis of HFRS is based on the cyclical course of the infection and the characteristic change of periods. When collecting an epidemiological history, attention is paid to the patient’s stay in an endemic area and possible direct or indirect contact with rodents. When conducting a nonspecific examination, the dynamics of changes in indicators of general and biochemical urine analysis, electrolytes, biochemical blood samples, CBS, coagulogram, etc. are taken into account. In order to assess the severity and prognosis of the disease, ultrasound of the kidneys, FGDS, chest radiography, ECG, etc. are performed.
Specific laboratory diagnosis of hemorrhagic fever with renal syndrome is carried out using serological methods (ELISA, RNIF, RIA) over time. Antibodies in the blood serum appear at the end of the 1st week of illness, reach their maximum concentration by the end of the 2nd week and remain in the blood for 5–7 years. Viral RNA can be isolated using PCR testing. HFRS is differentiated from leptospirosis, acute glomerulonephritis, pyelonephritis and enterovirus infection, and other hemorrhagic fevers.
Treatment of HFRS
Patients with hemorrhagic fever with renal syndrome are hospitalized in an infectious diseases hospital. They are prescribed strict bed rest and diet No. 4; water balance, hemodynamics, indicators of the functioning of the cardiovascular system and kidneys are monitored. Etiotropic therapy for hemorrhagic fever with renal syndrome is most effective in the first 3-5 days from the onset of the disease and includes the introduction of donor specific immunoglobulin against HFRS, the prescription of interferon drugs, antiviral chemotherapy drugs (ribavirin).
During the febrile period, infusion detoxification therapy is carried out (intravenous infusions of glucose and saline solutions); prevention of DIC syndrome (administration of antiplatelet drugs and angioprotectors); in severe cases, glucocorticosteroids are used. In the oliguric period, diuresis is stimulated (administration of loading doses of furosemide), acidosis and hyperkalemia are corrected, and bleeding is prevented. With increasing acute renal failure, transfer of the patient to extracorporeal infectious disease specialist, nephrologist and ophthalmologist is indicated throughout the year. Severe course is associated with a high risk of complications; Mortality from HFRS ranges from 7-10%.
Prevention of hemorrhagic fever with renal syndrome consists of exterminating mouse-like rodents in natural foci of infection, preventing contamination of homes, water sources and food products with rodent secretions, and deratization of residential and industrial premises. No specific vaccination against HFRS has been developed.
Hemorrhagic fever with renal syndrome (hemorrhagic nephrosonephritis) is an acute viral natural focal disease that occurs in the European part of Russia and in Far East. This disease characterized by a febrile reaction, severe intoxication of the body, specific kidney damage and damage to small blood vessels with subsequent development of thrombohemorrhagic syndrome.
HFRS: classification
There is currently no unified classification of this infectious disease. Causes, factors of occurrence, methods of spread of the disease Etiology PathogenThe Manchurian hemorrhagic or Tula fever virus was isolated only in 1976, although the viral etiology of HFRS (ICD-10 code - A98.5) became known three decades earlier. The pathogen that causes HFRS was found in the lungs of rodents (the main carrier is the bank vole mouse). These small mammals are intermediate hosts ( natural reservoir) infectious agent. Microbiology classifies the causative agent of HFRS as belonging to the Bunyanvirus family. The virus dies when heated to +50°C for half an hour. At temperatures from 0 to +4°C, it can remain active in the external environment for 12 hours. At temperatures from +4° to +20°, the virus in the external environment is quite stable, i.e. can remain viable for a long time.
Routes of transmission of HFRS In nature and rural areas, the virus is spread by several species of mice. The pathogen is excreted in their feces. Infection occurs through airborne dust or nutrition. A person becomes infected through direct contact with rodents, consumption of water and food containing their feces, as well as through inhalation of dust with microparticles of dried rodent feces. Infection through household items is possible. The peak incidence occurs in the autumn-winter period, when infection carriers move into residential and auxiliary buildings. In urban environments, the virus can be carried by rats. It is impossible to catch a fever from another person. To prevent the occurrence of outbreaks of epidemics, deratization is carried out, i.e. destruction of animals that are latent carriers of the virus. Note: up to 90% of cases are males aged 16 to 50 years. Pathogenesis The effect of the virus on organs and systems The virus enters the human body through the mucous membrane of the respiratory system. In some cases, the entrance gates of infection can be the mucous membranes of the digestive organs and damaged skin. No pathological changes are observed directly at the site of virus entry. Symptoms appear after the pathogen spreads throughout the body through the bloodstream and intoxication begins to increase. The virus is characterized by pronounced vasotropy; it has a pronounced negative effect on the vascular wall. Also an important role in the pathogenesis of hemorrhagic syndrome is the disruption of the functional activity of the blood coagulation system. In particularly severe cases of the disease, glomerular filtration is significantly reduced, although the structure of the glomeruli is not disturbed. The severity of thrombohemorrhagic syndrome directly depends on the severity of the disease. Immunity After once suffering from “Korean fever”, stable immunity remains; cases of reinfection in medical literature not described.Signs of HFRS
With HFRS, the incubation period can range from 7 to 45 days (most often about 3 weeks). It is customary to distinguish the following stages of disease development: 1. initial; 2. oliguric; 3. polyuric; 4. convalescence (recovery). With HFRS, the clinical picture depends on a number of factors, including the individual characteristics of the body and the timeliness of measures taken. For HFRS disease, the main symptoms are as follows: Initial period of HFRS- high temperature (39°-40°C);
- chills;
- strong headache;
- sleep disorders;
- blurred vision;
- hyperemia of the skin of the neck and facial area;
- dry mouth;
- weak positive symptom Pasternatsky.
- rash in the form of small hemorrhages (petechiae);
- vomiting 6-8 times a day;
- pain in the lumbar region;
- hyperemia of the pharynx and conjunctiva;
- dry skin;
- injection of scleral vessels;
- 50% of patients have thrombohemorrhagic syndrome.
- pain in the abdominal area;
- hemoptysis;
- vomiting blood;
- tarry stools;
- nosebleeds;
- lower back pain;
- blood in urine;
- positive Pasternatsky symptom;
- puffiness of the face;
- pastiness of the eyelids;
- oliguria to anuria.
Possible complications of HFRS
The disease can cause severe complications, including:- acute vascular insufficiency;
- focal pneumonia;
- pulmonary edema;
- kidney rupture;
- azotemic uremia;
- eclampsia,
- acute interstitial nephritis;
- acute renal failure.
Diagnostics
A differential diagnosis of HFRS with infectious diseases such as other hemorrhagic fevers, typhoid fever, leptospirosis, tick-borne rickettsiosis, tick-borne encephalitis and regular flu. The diagnosis of HFRS is made taking into account epidemiological data. The patient’s possible stay in endemic foci, the general level of morbidity in the area and seasonality are taken into account. Much attention is paid to fairly specific clinical symptoms. Laboratory diagnosis of HFRS reveals the presence of casts in the urine, as well as significant proteinuria. A blood test for HFRS shows an increase in plasma cells, an increase in the erythrocyte sedimentation rate and pronounced leukocytosis. Of the special laboratory methods, the detection of IgM by enzyme-linked immunosorbent assay is often used. If there are complications already during treatment, some types of instrumental studies may be needed: FGDS, ultrasound, CT and radiography.HFRS treatment
There are no standard treatment regimens for HFRS. Therapy should be comprehensive and aimed at eliminating the most important pathogenetic syndromes. It is necessary to combat DIC syndrome, renal failure and general intoxication. Treatment involves early hospitalization and strict bed rest for 1 to 4 weeks, depending on the severity of the disease. Strict control of the volume of fluid consumed and lost by the patient is necessary. Monitoring of hemodynamics, hemogram, hematocrit is required; Urine tests and electrolyte balance are regularly examined.Drug therapy.
During the febrile period, antiviral, antioxidant and detoxification therapy is carried out and measures are taken to prevent the development of DIC syndrome. Etiotropic therapy
For etiotropic therapy, either immunobiological drugs (interferons, hyperimmune plasma, donor specific immunoglobulin, etc.) or chemotherapy drugs - ribavirin (a nucleoside derivative), as well as amixin, cycloferon and iodantipyrine (interferon inducers) are used. The fight against intoxication involves infusions of glucose solutions and saline with vitamin C. Hemodez can be administered once. At body temperatures above 39°C, anti-inflammatory drugs with an antipyretic effect are administered. To prevent DIC syndrome, the patient is administered antiplatelet agents, angioprotectors, and in severe cases, protease inhibitors and fresh frozen plasma. Administration of antioxidants to patients (for example, ubiquinone and tocopherol) is indicated.Antishock therapy
To prevent the development of infectious-toxic shock, early hospitalization and strict bed rest are indicated. If ITS has developed (more often this happens on days 4-6 from the onset of the disease), then the patient is given intravenous drips of rheopolyglucin (400 ml) with hydrocortisone (10 ml), glucocorticosteroid drugs, 4% sodium bicarbonate solution (200 ml intravenously), cardiotonic drugs and cardiac glycosides (cordiamin, strophanthin, korglykon) intravenously. If measures are ineffective or stage 3 shock develops, dopamine administration with glucose or saline is indicated. With the development of internal combustion engine against the background state of shock heparin, protease inhibitors and angioprotectors are indicated. After restoration of normal hemodynamics, the patient is administered diuretics (Lasix). Special instructions: In case of infectious-toxic shock, antispasmodics, sympathomimetics, hemodez and polyglucin should not be used. In the oliguric period, it is necessary to reduce protein catabolism, eliminate azotemia and reduce intoxication. Correction of acid-base and water-electrolyte balance, correction of disseminated intravascular coagulation, as well as prevention and treatment of possible complications are also necessary. Gastric and intestinal lavage with a weakly alkaline solution and intravenous infusions of glucose (with insulin) are used. Enterosorbents are prescribed orally. Protease inhibitors are also recommended. To combat overhydration, the administration of Lasix is indicated, and sodium bicarbonate is used to reduce acidosis. Correction of hyperkalemia involves glucose-insulin therapy and a potassium-free diet. The pain syndrome is relieved by analgesics with desensitizing agents, persistent vomiting is eliminated by taking a solution of novocaine (orally) or atropine. The development of convulsive syndrome requires the use of relanium, aminazine or sodium hydroxybutyrate. At infectious complications Antibiotics from the groups of cephalosporins and semisynthetic penicillins are prescribed. During the period of convalescence, the patient needs general strengthening drug therapy(including vitamins and ATP preparations).Additional Methods
If ineffective conservative methods The patient may be indicated for extracorporeal dialysis.HFRS: prevention
To prevent infection, it is often enough to observe the rules of personal hygiene while in the forest or rural areas. Water from open sources and containers should be boiled before drinking, hands should be washed thoroughly, and food should be stored in airtight containers. Under no circumstances should you handle rodents. After accidental contact, it is recommended to disinfect clothing and skin. When working in dusty areas (including barns and haylofts), you need to use a respirator.Diet for HFRS and after recovery
Nutrition for HFRS should be fractional. For mild to moderate illness, patients are recommended to use table No. 4 (without limiting table salt), and for severe forms and the development of complications, table No. 1 is recommended. Against the background of oliguria and anuria, animals and herbal products high in protein and potassium. Meat and legumes, on the contrary, should be consumed during polyuria! The amount of fluid consumed should not exceed the volume excreted by more than 500-700 ml. The rehabilitation period after HFRS involves good nutrition with a limit on salty, fatty, fried and spicy foods.Features in children
HFRS in children is especially severe. The principles of therapy do not differ from those in the treatment of adult patients.Features in pregnant women
The disease poses a great danger to the fetus. If a woman falls ill during lactation, the infant is immediately transferred to artificial feeding.RCHR (Republican Center for Health Development of the Ministry of Health of the Republic of Kazakhstan)
Version: Clinical protocols of the Ministry of Health of the Republic of Kazakhstan - 2018
Hemorrhagic fever with renal syndrome (A98.5)
Short description
Approved
Joint Commission on Healthcare Quality
Ministry of Health of the Republic of Kazakhstan
dated March 29, 2019
Protocol No. 60
Hemorrhagic fever with renal syndrome(GLPS)- an acute viral natural focal disease characterized by fever, general intoxication, peculiar kidney damage such as acute interstitial nephritis and the development of thrombohemorrhagic syndrome.
INTRODUCTORY PART
Protocol name: Hemorrhagic fever with renal syndrome
ICD-10 code(s):
Date of development of the protocol: 2018
Abbreviations used in the protocol:
| HELL | arterial pressure |
| ICE | disseminated intravascular coagulation |
| mechanical ventilation | artificial ventilation lungs |
| ITS | infectious-toxic shock |
| ELISA | linked immunosorbent assay |
| CT | CT scan |
| MRI | Magnetic resonance imaging |
| ICD | international classification diseases |
| UAC | general blood analysis |
| OAM | general urine analysis |
| AKI | acute kidney injury |
| ICU | intensive care unit |
| PCR | polymerase chain reaction |
| RNA | ribonucleic acid |
| RN | neutralization reaction |
| RNGA | indirect hemagglutination reaction |
| RSK | complement fixation reaction |
| SZP | fresh frozen plasma |
| CSF | cerebrospinal fluid |
| ESR | erythrocyte sedimentation rate |
| Ultrasound | ultrasonography |
| CNS | central nervous system |
| EVI | enterovirus infection |
| ECG | electrocardiography |
| EchoCG | echocardiography |
| EEG | electroencephalography |
Protocol users: emergency doctors emergency care, paramedics, general practitioners, infectious disease specialists, therapists, neurologists, ophthalmologists, dermatovenerologists, otorhinolaryngologists, nephrologists, surgeons, anesthesiologists-resuscitators, healthcare organizers.
Level of evidence scale:
| A |
A high-quality meta-analysis, systematic review of RCTs, or large RCTs with a very low probability (++) of bias, the results of which can be generalized to an appropriate population. |
| IN |
High-quality (++) systematic review of cohort or case-control studies or High-quality (++) cohort or case-control studies with very low risk of bias or RCTs with low (+) risk of bias, the results of which may be distributed to the relevant population. |
| WITH |
Cohort or case-control study or controlled trial without randomization with low risk of bias (+). The results of which can be generalized to the relevant population or RCTs with very low or low risk of bias (++ or +), the results of which cannot be directly generalized to the relevant population. |
| D | Case series or uncontrolled study or expert opinion. |
| GPP | Best Clinical Practice |
Classification
Table 1. Clinical classification of HFRS
|
Periods of the disease: |
-
initial (febrile), -oliguric, - polyuric, - convalescent (early - up to 2 months and late - up to 2-3 years). |
|
Severity |
- light - moderate severity - heavy |
| Complications |
Specific: - ITS; - DIC syndrome; - azotemic uremia; - swelling of the lungs and brain; - hemorrhages in the pituitary gland, myocardium, adrenal glands, brain; - eclampsia; - acute cardiovascular failure; - profuse bleeding; - tear or rupture of the kidney capsule; - infectious myocarditis; - hemorrhagic meningoencephalitis, - intestinal paresis; - viral pneumonia. Non-specific: - pyelonephritis; - ascending pyelitis; - purulent otitis media; - abscesses; - phlegmon; - pneumonia; - mumps; - sepsis |
Diagnostics
DIAGNOSTIC METHODS, APPROACHES AND PROCEDURES
Diagnostic criteria
Complaints and anamnesis:
initial period (duration 1-3 days)
- fever (38-40°C);
- chills;
- Strong headache;
- weakness;
- sleep disturbance;
-
deterioration of vision (decreased visual acuity, “flying spots”, a feeling of fog before the eyes - appears on days 2-7 of illness and continues for 2-4 days ;
- dry mouth;
-
weakly positive Pasternatsky symptom.
oliguric period (from 3-4 to 8-11 days of illness)
- body temperature drops to normal, sometimes rising again to subfebrile levels - a “two-humped” curve;
- headache;
- weakness;
- lower back pain;
- stomach ache;
- diarrhea (on days 2-5 of illness in 10-15% of patients)
- oliguria (300-900 ml/day);
- anuria (in severe cases);
- vomiting up to 6-8 times a day or more;
- thrombohemorrhagic syndrome (in severe form in 50-70% of patients, in moderate form - 30-40%, in mild form - 20-25%)
From 6-9 days
- nose bleed;
- blood in urine;
- tarry stools.
polyuric period(from 9-13 days of illness)
-
pain in the lower back and abdomen disappears;
- vomiting stops;
- the daily amount of urine increases (up to 3-10 l);
- weakness persists.
Physical examination:
- hyperemia of the skin of the face, neck, upper sections breasts (symptom of “hood”);
- the mucous membrane of the oropharynx is hyperemic, from the 2-3rd day of illness in most patients on the mucous membrane soft palate hemorrhagic enanthema appears;
- vessels of the sclera and conjunctiva are injected;
- there may be a hemorrhagic rash on the conjunctiva and sclera;
- puffiness of the face, pastiness of the eyelids;
- moderate bradycardia
-
vesicular in the lungs hard breathing, isolated dry rales, wet rales may be detected, in especially severe cases - pulmonary edema or distress syndrome;
- the tongue is dry, covered with a gray or brown coating;
- the abdomen is moderately swollen, pain in the epigastric and peri-umbilical areas, especially in the projection of the kidneys and sometimes of a diffuse nature. There may be phenomena of peritonism;
- the liver is enlarged and painful in 20-25% of patients;
- in isolated cases, signs of meningism may appear;
- positive Pasternatsky symptom;
- positive tourniquet test;
- 3-5 days (in 10-15% of patients) - petechial rash in the armpits, on the chest, in the collarbone area, sometimes on the neck, face. The rash is not abundant, is grouped in nature and lasts from several hours to 3-5 days;
- gross hematuria (in 7-8%);
- intestinal bleeding (up to 5%);
- bruising at injection sites;
- nosebleeds, hemorrhages in the sclera.
Anamnesis It is necessary to clarify the following risk factors for infection:
. poor personal hygiene
. eating fresh vegetables without heat treatment from storage (cabbage, carrots, etc.);
HFRS and pregnancy.
A newborn can become infected in utero, but more often during childbirth or immediately after it. The outcome depends on the virulence of the particular circulating serotype, the mode of transmission, and the presence or absence of passively transmitted maternal antibodies.
The life of a pregnant woman is threatened by the development of specific and nonspecific complications, in particular infectious-toxic shock, disseminated intravascular coagulation syndrome, pulmonary and cerebral edema, hemorrhages in the brain, myocardium, adrenal glands, eclampsia, acute cardiovascular failure, sepsis, etc.
Laboratory research:
- UAC: neutrophilic leukocytosis (up to 15-30x10 9 l), plasmacytosis, thrombocytopenia, due to blood thickening, the level of hemoglobin and red blood cells may increase, but with bleeding these indicators decrease, moderate increase in ESR
- OAM: proteinuria (up to 66 g/l), cylindruria (gealine and granular), hematuria
- Determination of blood group and Rh factor.
- Coagulogram.
- Biochemical analysis blood: total protein, albumin, increase in the level of residual nitrogen, urea, creatinine, also hyperkalemia, hypermagnesemia, hyponatremia, bilirubin, ALT, AST.
- Stool analysis to detect intraintestinal bleeding.
- Serological diagnostics: (RNIF, ELISA, RPGA), paired sera are used, obtained with an interval of 10-12 days (the first on the 4-5th day of illness, the second - after the 14th day of illness). The diagnostic criterion is an increase in antibody titer by 4 times or more.
- Determination by ELISA of AT class Ig M, IgG
- PCR method: isolation of virus RNA from nasopharyngeal mucus, CSF, feces, blood and other secretions
Instrumental studies (according to indications):
Table 2. Methods instrumental diagnostics
| Methods | Indications |
| Ultrasound of the abdominal organs and kidneys | Patients with clinical symptoms HFRS to clarify the size of the enlargement of the liver, spleen, kidneys and assess their structure (nephrozonephritis) |
| X-ray of the chest organs | Patients with catarrhal symptoms in the initial period, auscultatory changes in the lungs, if pneumonia is suspected |
| Electrocardiogram (ECG) | Patients with auscultatory changes in the heart, with hypertension to clarify the violation of the trophism of heart tissue |
| EchoCG | To identify signs of dystrophy of individual areas of the myocardium, dilatation of cavities, myocardial hypertrophy, ischemic zones, assessment of the ejection fraction |
| Fibrogastroduodenoscopy | Patients with abdominal pain, vomiting “coffee grounds” to clarify the nature of damage to the mucous membrane of the esophagus, stomach, duodenum |
| CT and MRI of the brain | To identify possible focal changes in the brain. |
Indications for consultation with specialists:
Table 3. Indications for specialist consultations
Picture 1.Algorithm for diagnostic search in the initial periodhemorrhagic fever with renal syndrome
Diagnostic algorithm for HFRS:
Figure 2. Algorithm for diagnostic search for hemorrhagic fever with renal syndrome according to hemorrhagic syndrome
Differential diagnosis
Differential diagnosis and rationale for additional studies
Table 4. Criteria for differential diagnosis of HFRS
| Diagnosis |
Rationale for differential no diagnostics |
Surveys | Diagnosis exclusion criteria |
|
Omsk hemorrhagic fever |
Acute onset fever, hemorrhagic syndrome |
Discover specific antibodies in RSC and RN |
Two-wave fever hemorrhagic syndrome is mild, proteinuria is low. ARF does not develop. Abdominal and lower back pain missing or minor. Damage to the central nervous system and lungs is typical. |
| Rickettsial diseases from the group spotted fevers | Acute onset, fever, hemorrhagic syndrome, kidney damage | Specific antibodies are detected in RIF and RSC | The fever is prolonged and damage to the central nervous system and cardiovascular system predominates. Primary affect, profuse rash, predominantly roseate maculopapular, with secondary petechiae, enlarged spleen, polyadenopathy. In severe cases - nosebleeds. Kidney damage is limited to proteinuria. |
| Meningococcemia | Acute onset, fever. Hemorrhagic syndrome. Kidney damage with the development of acute renal failure | In the blood and CSF, meningococcus and positive RNGA are detected bacterioscopically and bacteriologically | During the first day, a hemorrhagic rash, acute renal failure, and hemorrhagic syndrome appear only against the background of ITS, which develops on the first day of the disease. The majority of patients (90%) develop purulent meningitis. Leukocytosis is noted. |
| Acute surgical diseases of the abdominal organs | Abdominal pain and tenderness on palpation, a symptom of peritoneal irritation, fever, leukocytosis. | Neutrophilic increasing leukocytosis in the blood from the first hours of illness | Pain syndrome precedes fever and other symptoms. Pain and signs of peritoneal irritation are initially localized. Hemorrhagic syndrome and kidney damage are not typical. |
| Acute diffuse glomerulonephritis | Fever, kidney damage with oliguria, possible acute renal failure, hemorrhagic syndrome | Specific antibodies to the HFRS virus are detected in ELISA | Fever, sore throat, acute respiratory infections precede kidney damage in a period of 3 days to 2 weeks. Characterized by pale skin, swelling, and a persistent increase in blood pressure. Hemorrhagic syndrome is possible against the background of azotemia, manifested by a positive tourniquet symptom, new bleeding |
| Leptospirosis | Acute onset, fever, hemorrhagic rash, kidney damage. | Detection of leptospira in blood smears, urine, CSF Microneutralization reaction and RNGA - positive | The onset is violent, the fever is prolonged, myalgia is pronounced, often meningitis, jaundice from the first day, high leukocytosis. Proteinuria. Moderate or low. Anemia. |
Treatment abroad
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Treatment
Drugs ( active ingredients), used in the treatment
Treatment (outpatient clinic)
OUTPATIENT TREATMENT TACTICS: no.
Treatment (inpatient)
TREATMENT TACTICS AT THE INPATIENT LEVEL
Patient observation card: inpatient card;
Patient routing:
Non-drug treatment:
- 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.
- Diet: Table No. 4 without salt restriction is recommended; for severe forms and complications - table No. 1. Meals should be complete, fractional, 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 regime 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.
Etiotropic treatment: the choice of route of administration (intravenous, per os) is determined by the severity of the disease. Treatment is more effective in the first 5 days from the onset of the disease.
- Ribavirin: first dose 2000 mg once (10 capsules), then 1000 mg every 6 hours for 4 days, then 500 mg every 6 hours for 5 days, course of treatment is 14 days.
- Ribavirin(intravenous form) - initially 33 mg/kg (maximum 2 g) is administered diluted in 0.9% NaCl solution or 5% dextrose solution, then 16 mg/kg (maximum single dose 1 g) every 6 hours for the first 4 days , then the next 3 days 8 mg/kg (maximum 500 mg) every 8 hours, treatment course is 14 days.
Table 5. WHO recommended doses and treatment regimen for ribavirin
Adults
| Route of administration | Starting dose | 1-4 days of illness | 5-10 days of illness |
| oral | 30 mg/kg (maximum 2000 mg) once | 15 mg/kg (maximum 1000 mg) every 6 hours | 7.5 mg/kg (maximum 500 mg) every 6 hours |
| intravenous |
33 mg/kg (maximum 2 g) |
16 mg/kg (maximum single dose 1 g every 6 hours) |
8 mg/kg (maximum 500 mg every 8 hours) |
Pathogenetic therapy:
In the initial (febrile) period illnesses pathogenetic therapy carried out for the purpose of detoxification, prevention and treatment of DIC, ITS. Drink plenty of fluids - up to 2.5-3.0 liters per day. The basis of treatment is the correction of circulating blood volume (CBV) and water-salt balance(VSB). For this purpose, infusions of crystalloids (0.9% sodium chloride solution, Ringer-Locke solution, lactasol, etc.) and 5-10% glucose solutions with the addition of potassium and insulin are prescribed according to generally accepted schemes in a 1:1 ratio. Volume infusion therapy averages 40-50 ml/kg/day under diuresis control. The criterion for the sufficiency of prescribed infusion therapy is a decrease in hematocrit to 36-38%, normalization of hemodynamic parameters (pulse, blood pressure, central venous pressure) and hourly diuresis.
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.).
Colloidal solutions of dextran and corticosteroids are not administered to oliguria (except in cases of collapse, cerebral and pulmonary edema).
The introduction of excess fluid parenterally, especially isotonic sodium chloride solution, is fraught with the risk of developing pulmonary and cerebral edema. Therefore, the total amount of fluid administered parenterally before the 5th-6th day of illness can exceed the volume excreted by no more than 750, and later at the height of renal failure - by 500 ml.
- If hypoproteinemia develops (a decrease in total blood protein below 52 g/l, albumin below 20 g/l), albumin 20% - 200-300 ml or plasma preparations should be included in the infusion program.
- If signs of hypercoagulation appear, heparin up to 10,000-15,000 units/day, hypocoagulation (decrease in coagulation rates by 1/3 of the norm), heparin up to 5,000 units/day, fresh frozen plasma (FFP) at a dose of 15 ml/kg intravenous drip are indicated.
- Hemostatic therapy (etamzilate) 250 mg every 6 hours.
- Nutritional support is provided through enteral nutrition and, if necessary, artificial nutritional mixtures. If enteral nutrition is not possible, parenteral nutrition is performed.
- For hyperthermia, the drug of choice is paracetamol 500 mg, orally; rectal suppositories 0.25; 0.3 and 0.5 g (for hyperthermia above 38°C). Acetylsalicylic acid preparations (aspirin) are absolutely contraindicated, which is associated with irreversible inhibition of cyclooxygenase in circulating platelets and endothelium.
- If there is a history peptic ulcer stomach and duodenum, already during this period of the disease, hydrogen pump inhibitors or H2 histamine receptor blockers are recommended.
- Diuretics should be prescribed after hemodynamic normalization (or CVP > 120 mm H2O); in case of HFRS, administration of mannitol is contraindicated;
- To relieve pain, non-narcotic analgesics are recommended; in cases of their ineffectiveness, antipsychotics and narcotic analgesics should be prescribed;
- For persistent vomiting and hiccups, gastric lavage, novocaine (peros), metoclopramide, atropine, chlorpromazine are indicated;
- For arterial hypertension (ACE inhibitors, beta blockers and etc.).
- Antibacterial therapy in the first two periods of the disease, it is carried out only in the presence of bacterial complications (pneumonia, abscesses, sepsis, etc.); it is recommended to use semi-synthetic penicillins and cephalosporins.
- Desensitizing therapy.
- If conservative measures are ineffective, extracorporeal hemodialysis is indicated, the need for which may arise on days 8-12 of illness.
a) Clinical: oligoanuria for more than 3-4 days or anuria during the day, 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:
- ITS decompensated,
- hemorrhagic stroke,
- hemorrhagic infarction of the adenohypophysis,
- massive bleeding
- spontaneous kidney rupture.
For bacterial complications- azithromycin on the first day 10 mg/kg, from the second to the fifth days 5 mg/kg daily, once a day or beta-lactam antibacterial drugs for 5-7 days.
List of essential medicines(having a 100% probability of application) :
| Drug group |
Medicinal nal means |
Mode of application | Proven leveleflaxOsti |
| Nucleosides and nucleotides | Ribavirin | 2000 mg once (10 capsules), then 1000 mg every 6 hours for 4 days, then 500 mg every 6 hours for 5 days (capsules); | IN |
List of additional medicines(less than 100% probability of application).
| Drug group |
Medicinal nal means |
Mode of application | Level of evidence |
| Anilides | Paracetamol | 500-1000 mg orally | WITH |
|
Gastrointestinal motility stimulants intestinal tract |
Metoclopramide | 10 mg orally | WITH |
| Heparin and its derivatives | Heparin group (sodium heparin) | subcutaneously (every 6 hours) 50-100 units/kg/day 5-7 days | C |
|
Antiplatelet agents, myotropic vasodilators actions |
Dipyridamole | 75 mg 3-6 times a day | C |
|
Other system hemostatics |
Sodium ethamsylate | 250 mg every 6 hours intravenously 3-4 times a day. | C |
| Plasma proteinase inhibitors | Aprotinin | 200000ATRE, i.v. | C |
| Glucocorticoids | Prednisolone | 5-10 mg/kg, i.v. | C |
| Dexamethasone | 8-12 mg IV, bolus | C | |
| Adrenergic and dopaminergic drugs | Dopamine | 10.5-21.5 mcg/kg/min | B |
| Sulfonamides | Furosemide |
20-40 mg (2-4 ml), i.v. |
C |
| Purine derivatives | Pentoxifylline | 2% solution 100 mg/5 ml, 100 mg in 20-50 ml 0.9% sodium chloride, IV drop, course from 10 days to 1 month | C |
| Other irrigation solutions | Dextrose | 0.5% solution, 400.0 ml, IV, drip | C |
| Electrolyte solutions |
Sodium chloride Potassium chloride |
0.9% solution, 400 ml IV, drip | B |
| Blood substitutes and blood plasma preparations | Human albumin | 20% - 200-300 ml, i.v. | C |
| Fresh frozen plasma | 15 ml/kg intravenous drip | C | |
| Benzodiazepine derivatives | Diazepam | 10 mg (0.5% - 2 ml) per 10.0 ml 0.9% sodium chloride, IV bolus | B |
| Piperazine derivatives | Cetirizine hydrochloride | 5-10 mg orally | B |
| Triazole derivatives | Fluconazole | 200 mg IV once a day, every other day, 3-5 times | B |
| 3rd generation cephalosporins | Ceftriaxone | 1.0g x 1-2 times/day, IM, IV, 10 days. | C |
| Fluoroquinolones | Ciprofloxacin |
200 - 400 mg x 2 times/day, intravenously for 7-10 days |
C |
| 4th generation cephalosporins | Cefepime | 1.0 g every 12 hours (i.m., i.v.). | C |
Surgical intervention: No.
Indicators of treatment effectiveness and safety of diagnostic and treatment methods described in the protocol:
Normalization:
- body temperature;
- diuresis;
- azotemia indicators;
- hemograms;
- absence of pyuria and microhematuria;
- isohyposthenuria is not a contraindication for discharge.
- mild form - no earlier than the 12th day of illness;
- moderate - no earlier than the 16th day of illness;
- severe form - no earlier than 21 days of illness.
Clinical examination of HFRS convalescents:
- for 2 years after discharge (once per quarter during the first year and 2 times during the second year).
Hospitalization
INDICATIONS FOR HOSPITALIZATION, INDICATING THE TYPE OF HOSPITALIZATION:
Indications for planned hospitalization: No
Indications for emergency hospitalization:
- fever,
- intoxication,
- hemorrhagic syndrome.
Information
Sources and literature
- Minutes of meetings of the Joint Commission on the Quality of Medical Services of the Ministry of Health of the Republic of Kazakhstan, 2018
- 1. Sirotin B.Z. Hemorrhagic fever with renal syndrome.-Khabarovsk, 1994.-302 p. 2. Classifications of major infectious diseases Reference materials for students of the 5th and 6th years, in the discipline “Infectious Diseases” Ivanovo 2014, P43-44 3. Lobzin Yu.V. Guide to Infectious Diseases - Study Guide. - St. Petersburg: 2000. - 226 p. 3. Infectious diseases: national leadership/ Ed. N.D.Yushchuk, Yu.Ya.Vengerova. - M.: GEOTAR-Media, 2009. - 1040 p. 4. Ma C, Yu P, Nawaz M, Zuo S, Jin T, Li Y, Li J, Li H, Xu J. J. 2012. Hantaviruses in rodents and humans, Xi’an, PR China. Vol. 93(10):2227-2236 doi:10.1099/vir.0.043364-0 5. Krautkramer, E., Zeier, M. and Plyusnin, A. 2012. Hantavirus infection: an emerging infectious disease causing acute renal failure. Kidney International (2012) 83, 23–27; doi:10.1038/ki.2012.360 6. Fulhorst F, C., Koster T, F., Enria A, D., Peters C, J. 2011. Hantavirus Infections. In: Tropical Infectious Diseases: Principles, Pathogens and Practice, Third Ed., Philadelphia: Elsevier. p. 470-480 7. Jonsson B, C., Figeiredo T M, L. and Vapalathi, O. 2010. A Global Perspective on Hantavirus Ecology, Epidemiology, and Disease, Clinical Microbiology Reviews, Vol. 23. p. 412-441 8. Wichmann, D., Josef Grone, H., Frese, M., Pavlovic, J. Anheier, B. 2002. Hantaan Virus Infection Causes an Acute Neurological Disease That Is Fatal in Adult Laboratory Mice, Journal of Virology , Vol. 76, No. 17. p. 8890-8899. doi: 10.1128/JVI.76.17.8890–8899.2002 9. Xu ZY, et al. Epidemiological studies of hemorrhagic fever with renal syndrome: analysis of risk factors and mode of transmission. Journal of Infectious Diseases1985; 152: 137–144. 10. Denecke, B., Bigalke, B., Haap, M., Overkamp, D., Lehnert, H., and Haas, C. S. (2010). Hantavirus infection: a neglected diagnosis in thrombocytopenia and fever? Mayo Clin. Proc. 85, 1016–1020. doi: 10.4065/mcp.20 09.0040 11. Kruger DH, Figueiredo LT, Song JW, Klempa B. Hantaviruses are globally emerging pathogens. J Clin Virol 2015; 64:128.
Information
ORGANIZATIONAL ASPECTS OF THE PROTOCOL
List of protocol developers with qualification information:
1. Kosherova Bakhyt Nurgalievna - doctor medical sciences, professor, vice-rector for clinical work and continuous professional development of the Karaganda Medical University.
2. Dmitrovsky Andrey Mikhailovich - Doctor of Medical Sciences, Professor of the Department of Infectious and Tropical Diseases of JSC National Medical University;
3. Egemberdieva Ravilya Aitmagambetovna, Doctor of Medical Sciences, Professor of the Department of Infectious and Tropical Diseases of JSC National Medical University, highest medical category;
4. Kurmangazin Meirambek Saginaevich - Candidate of Medical Sciences, Head of the Department of Infectious Diseases of the NAO West Kazakhstan Medical University named after. Marat Ospanov";
5. Yukhnevich Ekaterina Aleksandrovna - clinical pharmacologist, acting associate professor of the department clinical pharmacology And evidence-based medicine NJSC "Medical University of Karaganda".
Disclosure of no conflict of interest: No.
Reviewers:
Begaidarova Rozalia Khasanovna - Doctor of Medical Sciences, Professor of the NAO Department of Infectious Diseases and Phthisiology of the NAO "Medical University of Karaganda", a doctor of the highest category.
Indication of the conditions for reviewing the protocol:
revision of the protocol after 5 years and/or when new diagnostic and/or treatment methods with more high level evidence.
Attached files
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Initially, the diagnosis of HFRS is established on the basis of the clinical picture of the infection with a set of certain symptoms of the early (first week) stage of the disease: acute onset, fever, syndrome of general toxicosis and hemodynamic disorders, then pain in the abdomen and lumbar region. The stage at the height of the disease is characterized by the dominance of hemorrhagic syndrome and manifestations of acute renal failure (ARF). At the same time, the polymorphism and variability of symptoms, the lack of standardized characteristics of the leading syndromes do not allow the primary diagnosis of HFRS to be established clinically with reliable accuracy.
The clinical picture of HFRS, described by numerous authors from different regions of the world and associated with different hantaviruses, demonstrates the similarity of the main manifestations of the disease. Generalized nature of the infection with involvement in the pathological process various organs and systems causes polymorphism of symptoms regardless of the etiological agent (hantavirus serotype).
The disease is characterized by a cyclical course and a variety of clinical variants from abortive febrile forms to severe forms with massive hemorrhagic syndrome and persistent renal failure.
Distinguish following periods diseases. Incubation (from 1 to 5 weeks, on average 2-3 weeks), febrile (initial, general toxic), lasting on average from 3 to 7 days; oliguric (on average 6-12 days), polyuric (on average 6-14 days), convalescence period (early - up to 2 months and late - up to 2-3 years).
In the clinical picture of the disease, 6-7 main clinical and pathogenetic syndromes are distinguished:
1) general toxic;
2) hemodynamic (central and microcirculatory disorders);
3) renal;
4) hemorrhagic;
5) abdominal;
6) neuroendocrine;
7) respiratory syndrome.
Various combination of these syndromes characterizes each of the four periods of the disease. Symptoms of dysfunction of various organs involved in infectious process, are observed during all periods of the disease.
The incubation period lasts from 4 to 49 days (most often from 14 to 21 days), with no clinical manifestations. During this period, the HFRS virus enters the body through the epithelium of the respiratory tract, gastrointestinal tract, and also through damaged skin. The virus then reproduces in the cells of the macrophage system. It causes activation of specific and nonspecific defense factors, the adequacy of which, as well as the infectious dose, pathogenicity and virulence of the pathogen, determines both the fate of the virus itself and the severity of pathological changes in the patient’s body.
1.3.1 Initial (febrile) period of HFRS.
The pathogenetic basis of the initial (febrile) period of HFRS is viremia, intoxication, activation of the hormonal and immune systems, production of pro-inflammatory cytokines, massive vasopathy (associated with the tropism of hantavirus to the endothelium of microcirculatory vessels), coagulopathy, microcirculation disorders, tissue destruction, formation of autoantigens with the formation of autoantibodies ( in severe HFRS).
In most patients, HFRS begins acutely. Chills, headache, muscle and joint pain, dry mouth, thirst, sometimes a slight cough, and severe general weakness appear. In a small proportion of patients, the appearance of pronounced signs of the disease is preceded by a prodromal period: general malaise, fatigue, low-grade fever.
Fever in most patients reaches high levels on the first day of illness and lasts from 5-6 to 10-11 days, on average 6-7 days. The temperature curve does not have a specific pattern; in most cases it decreases lytically over two to three days. In mild forms of the disease, there is a slight short-term fever, which is often visible to the patient.
An objective examination reveals pronounced hyperemia of the skin of the face, neck, upper half of the body, associated autonomic disorders at the level of the centers of the cervical and thoracic spinal cord. Particularly noticeable is the injection of blood vessels in the sclera and conjunctiva, hyperemia of the oropharyngeal mucosa, and the appearance of spotted enanthema of the upper palate. It is possible to develop hemorrhagic syndrome in the form of a petechial rash in the area of the inner surfaces of both shoulders, the lateral surfaces of the torso, on the chest (the “scourge” symptom), ecchymosis at the injection sites, and short-term nosebleeds. Positive endothelial symptoms (cuffs, pinch, tourniquet) are determined. Blood pressure is normal or tends to hypotension, and relative bradycardia is characteristic. Some patients note a feeling of heaviness in the lower back.
At the end of the initial period, the frequency of urination decreases and diuresis decreases slightly. Laboratory changes are characterized by a slight increase in serum levels of creatinine and urea, a decrease in the relative density (RD) of urine and the appearance of single fresh red blood cells and proteinuria in its sediment. The blood test in most patients is characterized by moderate leukopenia and, less often, slight leukocytosis and band shift to the left, signs of blood thickening against the background of plasmorrhea and hypovolemia in the form of an increase in the number of red blood cells and hemoglobin. The pathognomonic symptom of HFRS in early period is thrombocytopenia, caused by the damaging effect of the virus, the development of immunopathological reactions, an increase in the adhesive properties of platelets and the formation of cellular aggregates with their retention in microcirculation vessels, and a violation of the rheological properties of blood.
1,3,2 Oligouric period of HFRS.
During the oligouric period of HFRS (the height of the disease), systemic circulatory disorders, hypovolemia and hemoconcentration, hypoperfusion and hypoxia of organs, tissue acidosis and damage to vital body systems continue. The hypocoagulation phase of DIC predominates. Edema, hemorrhages, dystrophic and necrobiotic changes occur in the pituitary gland, adrenal glands, kidneys, myocardium and other parenchymal organs.
The greatest changes are observed in the kidneys, which is accompanied by a decrease in glomerular filtration and impaired tubular reabsorption. AKI in HFRS is caused by damage to the renal parenchyma, acute interstitial nephritis. On the one hand, impaired microcirculation and increased permeability of the vascular wall contribute to plasmorrhea and serous-hemorrhagic edema of the interstitium of the kidneys, mainly pyramids, with subsequent compression of the tubules and collecting ducts, leading to dystrophy, desquamation of the tubular epithelium, sweating of protein and fibrin with obstruction of the tubules and collecting ducts tubes with fibrin clots and impaired reverse reabsorption of urine. On the other hand, an immunopathological factor is the fixation of immune complexes on the glomerular basement membrane, which reduces glomerular filtration. Interstitial edema increases the disturbance of renal microcirculation, up to ischemia, in some cases to necrosis renal tubules, contributes to a further decrease in glomerular filtration and tubular reabsorption. Tubular cells are especially sensitive to hypoxia, a lack of energy material that occurs during ischemia. IN pathological process autoantibodies to damaged tissue structures may also be involved. Disorders in central hemodynamics (hypovolemia, decreased cardiac output, blood pressure) aggravate renal blood flow disorders.
The oliguric period is the most striking period when the clinical picture inherent in HFRS develops. Body temperature drops to normal, sometimes rising again to subfebrile levels - a “two-humped” curve. However, a decrease in temperature is not accompanied by an improvement in the patient’s condition; as a rule, it worsens. General toxic effects reach a maximum, signs of hemodynamic disturbances, renal failure, and hemorrhagic diathesis intensify. Most constant sign The transition to the oliguric period is indicated by the appearance of lower back pain of varying intensity: from discomfort heaviness to sudden, painful nausea, vomiting not associated with food or medication intake, in severe cases - hiccups. Asthenia and adynamia increase. Many patients experience abdominal pain, mainly in the umbilical and epigastric region. The face is hyperemic, as renal failure increases, the blush gives way to pallor, intensifies hemorrhagic manifestations, mainly in severe cases of the disease - hemorrhages in the sclera, ecchymosis, nosebleeds and gross hematuria, hematomas at injection sites, less often - intestinal bleeding, blood in the vomit, hemoptysis. Important upon diagnosis, visual impairment is detected (decreased visual acuity, “flying spots”, a feeling of fog before the eyes), caused by impaired microcirculation in the retina of the eyes, appears on days 2-7 of the disease and lasts for 2-4 days.
In most patients, at the beginning of the oligouric period, blood pressure is within normal limits, and in severe cases, arterial hypotension develops, reaching the degree of severe collapse or infectious-toxic shock. In the second half of this period, blood pressure (BP) increases in 1/3 of patients; the duration of hypertension rarely exceeds 5 days. Absolute or relative bradycardia is characteristic. Vesicular hard breathing is heard over the lungs, isolated dry rales, wet rales can be detected, in especially severe cases a picture of pulmonary edema or distress syndrome is observed.
On days 2-5 of illness, 10-15% of patients experience diarrhea. The tongue is dry, covered with a gray or brown coating. The abdomen is moderately swollen, there is pain on palpation in the epigastric and periumbilical areas, especially in the projection of the kidneys and sometimes of a diffuse nature. There may be phenomena of peritonism. The liver is enlarged and painful in 20-25% of patients. In isolated cases, signs of meningism may appear. Most specific complications of HFRS develop during this period.
Kidney syndrome is one of the leading ones. Pasternatsky's symptom is positive or sharply positive, so this symptom must be checked with the utmost caution, by applying light pressure in the area of the costovertebral points to avoid tearing the renal cortex. The full picture of acute renal failure is characterized by progressive oligoanuria, increasing uremic intoxication, water and electrolyte imbalance, and increasing metabolic acidosis.
Disturbances in the activity of the central nervous system are observed in almost all patients both as manifestations of general cerebral symptoms associated with intoxication, and as a consequence of focal lesions. It is possible to develop symptoms of meningism, encephalitic reactions with the appearance of meningeal symptoms (stiff neck, Kernig, Brudzinski symptoms), focal symptoms (corresponding to areas of brain damage), and mental disorders are also observed (from sleep disturbances to various disorders of consciousness).
The hemogram naturally reveals neutrophilic leukocytosis (up to 15-30×109/l of blood), plasmacytosis, and thrombocytopenia. In severe cases, the blood picture is characterized by a leukemoid reaction. Due to blood thickening, the level of hemoglobin and red blood cells may increase, but with bleeding these indicators decrease. The ESR gradually accelerates. Characterized by increased levels of residual nitrogen, urea, creatinine, as well as hyperkalemia, hypermagnesemia, hyponatremia and signs of metabolic acidosis. A general urine test reveals massive proteinuria (up to 33-66 g/l), the intensity of which varies throughout the day (“protein shot”), hematuria, cylindruria, and the appearance of renal epithelial cells (the so-called Dunaevsky cells). From the second half of the oliguric period, hyposthenuria develops.
Significant changes occur in the state of the blood coagulation system. While hypercoagulation persists in some patients, hypocoagulation develops in severe cases of the disease. It is caused by the consumption of plasma clotting factors due to the formation of microthrombi in small vessels. It is in the oliguric period of HFRS that hemorrhagic manifestations reach their apogee and often become the cause of death.
1,3,3 Polyuric period of the disease.
The period of polyuria begins from 9-13 and lasts until 21-24 days of illness. As a result of the formation of specific immunity, elimination of the pathogen, immune complexes pathological changes in the kidneys and other organs regress, and there is a tendency towards normalization of their functions. In the stage of polyuria, glomerular filtration increases first of all. In conditions of damaged tubular apparatus, even slight increase filtration helps to increase diuresis. Polyuria is caused by osmotic diuresis. Nitrogenous wastes accumulated in the body during oliguria, with the restoration of the functional capacity of the kidneys, exhibit their osmodiuretic effect, and the amount of urine excreted does not depend on the state of hydration of the body; excessive fluid loss with urine with insufficient replenishment can lead to dehydration, hypovolemia and re-development of oliguria . Slow restoration of the reabsorption function of the tubules leads to loss of potassium, sodium, and chlorine.
Vomiting stops, pain in the lower back and abdomen gradually disappears, sleep and appetite normalize, the daily amount of urine increases (up to 3-10 l), nocturia is characteristic. Against the background of hypokalemia, weakness, muscle hypotension, intestinal paresis, bladder atony, tachycardia, arrhythmia persist, dry mouth, and thirst appear. The duration of polyuria and isohyposthenuria, depending on the severity of the clinical course of the disease, can range from several days to several weeks. However, the rate of improvement does not always parallel the increase in diuresis. Sometimes in the first days of polyuria, azotemia still increases, dehydration, hyponatremia, hypokalemia may develop, and hypocoagulation persists, so this stage is often called the stage of “uncertain prognosis.”
Laboratory changes during this period consist of a slight decrease in the number of red blood cells, hemoglobin, and an increase in the number of platelets. The erythrocyte sedimentation rate (ESR) accelerates somewhat. Blood serum urea and creatinine levels gradually decrease, and hypokalemia often develops.
Changes in urine (Zimnitsky test) are characterized by extremely low relative density, not exceeding 1001-1005. A small amount of protein, moderate hematuria and cylindruria, sometimes leukocyturia, and small amounts of renal epithelial cells are detected in the urine sediment.
1,3,4 Period of convalescence.
The recovery period is pathogenetically characterized by the formation of stable post-infectious immunity with a high level of specific IgG, restoration of hemostasis, microcirculation, glomerular filtration of urine, but with long-term persistence of tubular disorders (tubular insufficiency). There is a noticeable improvement in the general condition, restoration of daily diuresis, normalization of urea and creatinine levels. 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 1 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.
A severe disease of natural origin affects not only the kidneys, but also adjacent vessels.
It has several names, the main one of which is HFRS, which stands for “hemorrhagic fever with renal syndrome.” The virus is widespread in the European part of Russia and the Far Eastern District, as well as in Siberia and Transbaikalia. The disease is widespread throughout the world.
What is it - disease clinic
Manchurian gastritis, Far Eastern hemorrhagic fever, hemorrhagic nephrosonephritis, Songo fever are synonyms of the same thing viral disease – hemorrhagic fever with renal syndrome (HFRS). The source of infection is sick small rodents, for example, the field mouse. In cities, rats can serve as carriers.
In ICD-10 hemorrhagic nephrosonephritis is under code A98.5. Here the pathology has a classification:
- Crimean hemorrhagic fever A98.0;
- Omsk hemorrhagic fever A98.1;
- Kyasanur forest disease A98.2;
- Disease caused by Marburg virus A98.3;
- Ebola A98.4 virus disease;
- Hemorrhagic fever with renal syndrome A 98.5.
In turn, hemorrhoidal fever with renal syndrome divided into several types: Korean, Russian, Tula, Scandinavian epidemic.
Causes of infection and routes of transmission of the virus
The hemorrhagic nephrosonephritis virus is known to have a diameter of approximately 90–100 nm. The medical history begins since 1976, when it was first discovered in the lungs of mice. Then the official name was given: the genus Hantanaan of the family Bunyaviridae. And now HFRS has not lost its relevance.
The virus is quite tenacious and active: it ceases to act only at a temperature of +50 C, but even in this case it remains viable for almost an hour. And the external temperature of +20 C is generally the most comfortable. That is why the peak of cases occurs in the summer. At zero degrees, viruses are active for 13 hours.
What you need to know about hemorrhagic fever with renal syndrome:
- Method of transmission of the virus to humans: rodents, or rather their feces. People can get the disease by airborne droplets, that is, inhaling dusty air that contains the virus.
- Who is susceptible to infection: agricultural workers, farmers, agrarians, foresters, hunters, ordinary vacationers who spend time in nature. Men 17 – 40 years old are more prone to this disease;
- There is a tendency for the disease to be seasonal: in the winter months the virus is not active, and the risk of infection tends to zero. From the beginning of summer to the end of October, the probability increases several times;
- The main foci of virus activity in recent years have been observed in the Samara, Saratov, Ulyanovsk regions, as well as in Udmurtia, Bashkiria and Tatarstan.
The risk of transmission is present through direct contact with carriers, as well as through consumption of contaminated food or water, as well as through household objects (for example, when spending time in nature);
The disease is not transmitted from person to person. The patient is completely safe for others.
It is worth noting that the disease always occurs in an acute form. There is no chronic course. After suffering from the disease, lifelong immunity is acquired.
Symptoms and signs
HFRS has a fairly long incubation period. It can last more than a month - up to 50 days. But most often the pathogen begins to show its activity after two weeks. This time is enough for the virus to break through the body’s defenses and enter the bloodstream, quite severely affecting the blood vessels.
On initial stage symptoms develop quickly and violently:
- The temperature rises sharply to high levels - 39.5–40 C;
- The person has a fever and a severe headache;
- Vision is impaired: pain in the eyes, feeling of fainting, decreased clarity of vision. False sensation of seeing the surroundings in red;
- From the 3rd day of illness, reddish rashes appear in the mouth, in the collarbone area, on the neck and armpits;
- Nausea and then vomiting up to 9 times a day;
- Pain in the lower back during the Pasternatsky test, which indicates possible kidney damage;
- Development of conjunctivitis;
- Feeling of dryness both in the mouth and throughout the body;
- Oliguria;
- Blood pressure is low, which leads to possible dizziness.
Approximately on day 9-10 of illness temperature body goes to decline, but the patient does not feel better.
Join kidney symptoms: arterial hypotension is replaced by high blood pressure, the patient cannot find a place for himself due to lower back pain, and the amount of urine increases, nosebleeds appear. Characteristic loose stool, swelling of the face, increased coagulability blood.
From 15-16 days of illness the patient's condition begins to gradually return to normal: vomiting and diarrhea stop, pain subsides, and general condition improves. Blood clotting indicators also improve.
In general, the course of hemorrhagic fever with renal syndrome is usually divided into several degrees: mild, moderate and severe.
The most dangerous is the severe degree, in which case coma may develop, which can be fatal.
Patients of any severity during the recovery period retain asthenia, increased anxiety, and shortness of breath for a long time. This can lead to the development of hypochondria and neuroses.
Differential diagnosis
If acute symptoms of HFRS appear, it is necessary consult a doctor immediately because the signs of this disease are very similar to other equally dangerous diseases: typhoid fever, influenza, pyelonephritis, leptospirosis.
The doctor collects the patient's medical history, as well as finds out his whereabouts recently. This is a mandatory item if HFRS is suspected, because in this way possible contact with infected animals is revealed.
Difficulties for diagnosis are erased and atypical forms HFRS.
First, an external examination is carried out. The doctor pays attention to the persistent cyclical nature of the disease, symptoms characteristic of hemorrhagic fever, such as muscle pain, vision problems, rashes, oliguria, etc.
Special methods - enzyme immunoassay - ELISA, immunofluorescence reaction - RNIF, RIA - radioimmunoassay must be done dynamically. After all, the effect of antibodies in HFRS is not constant, and their maximum concentration is achieved only by the 13th day of illness.
The RNIF method must be applied as early as possible and repeated after 6 days of disease activity. Such a study will definitely confirm the diagnosis if antibody titers increase at least 3 times.
In severe cases and in the presence of complications, the doctor prescribes to the patient additional research : FGDS, x-ray or.
After the diagnosis has been formulated, treatment of hemorrhagic nephrosonephritis is carried out only in a hospital setting. As a rule, this is an infectious diseases hospital.
Moreover, a late visit to a doctor or self-medication can end in disaster.
In the hospital, doctors carry out complex therapy , which includes:
- Mandatory bed rest;
- Replenishing fluid losses and eliminating possible dehydration, as well as intoxication: intravenous glucose, sodium chloride, saline;
- Fighting the virus: prescribing antiviral drugs: “Vitaferon”, “Grippferon”, “Ingraverin” and others;
- Anti-inflammatory drugs: Nurofen;
- Control of blood clotting: “Aspirin”, “Thromboass”;
- For renal syndrome, diuretics are prescribed: Furosemide, Tolvaptan;
- Vitamin preparations: any;
- Appointment possible antibacterial agents: “Ceftriaxone”, “Flemoxin”, “Ampicillin”;
- Antispasmodics: “Ketorol”, “”;
- Antishock therapy for toxic shock.
It must be remembered that in case of shock, painkillers and hemodesis should not be used.
When severe kidney damage is observed, it is carried out. Extracorporeal dialysis is used when the patient’s condition is very serious, when other means do not help.
If the HFRS virus found in children, then, as a rule, special monitoring is established for such patients, because their course of the disease is especially severe. The principles of therapy do not differ from adults, the only differences are in adjusting the doses of drugs.
Patients are prescribed mandatory diet No. 4. You can take salt, but meat is even necessary during polyuria. You need to drink enough fluids, especially healthy mineral waters (Essentuki, etc.). If oliguria is present, then it is necessary to exclude foods high in protein.
At severe forms illness to the patient table number 1 is prescribed. During the recovery period, you must also adhere to a diet. Try to eat well, limit fried, salty and smoked foods.
With properly organized treatment, the patient recovers completely, although “echoes” of the disease may persist for some time.
Complications after illness
Hemorrhagic fever with renal syndrome is a serious disease that threatens the development of such complications, How:
- various pneumonias,
- acute vascular insufficiency,
- lung problems
- gap,
- bleeding,
- acute renal failure and others.
Prevention of infection
At the beginning of the summer season, during the period of activity of the HFRS virus (May-October), SanPin introduces control over the activities of individual entrepreneurs, agricultural workers, agricultural enterprises and other organizations working in one way or another in agriculture. They must comply with all sanitary and epidemiological rules.
In hotspots measures are being taken to exterminate dangerous rodents.
Summer residents and vacationers are recommended to thoroughly clean the house (necessarily wearing protective gloves); when being in nature, they should be careful: wash your hands especially thoroughly and hide food, do not touch wild animals with your hands!
If you suspect a developing fever, you should immediately call an ambulance!
Hemorrhagic fever with renal syndrome is a common disease, but nevertheless, the risk of contracting it is not so great. It is important, if possible, not to travel to areas where the virus is active and to try maintain personal hygiene.
Find out how to protect yourself from this virus from the video:
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