Hemorrhagic fever with renal syndrome is a zoonotic hantavirus infection characterized by thrombohemorrhagic syndrome and predominant kidney damage. Clinical manifestations include acute fever, hemorrhagic rash, bleeding, interstitial nephritis, in severe cases – acute renal failure. Specific laboratory methods for the diagnosis of hemorrhagic fever with renal syndrome include ELISA, PCR. Treatment consists in the introduction of specific immunoglobulin, interferon preparations, detoxification and symptomatic therapy, hemodialysis.
A98.5 Hemorrhagic fever with renal syndrome
The causative agents of the disease are RNA-containing viral agents of the genus Hantavirus belonging to the family Bunyaviridae. 4 serotypes of hantaviruses are pathogenic for humans: Hantaan, Dubrava, Puumala, Seoul. In the external environment, viruses remain stable at negative temperatures for a relatively long time and are not stable at 37 °C. Viruses have a spherical or spiral shape, diameter 80-120 nm; contain single-stranded RNA. Hantaviruses have a tropicity to monocytes, kidney cells, lungs, liver, salivary glands and multiply in the cytoplasm of infected cells.
Carriers of pathogens of hemorrhagic fever with renal syndrome are rodents: field and forest mice, voles, house rats, which are infected from each other through tick and flea bites. Rodents carry infection in the form of latent virus transmission, releasing pathogens into the external environment with saliva, feces and urine. The ingress 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 food).
The group of increased risk for the incidence of hemorrhagic fever with renal syndrome includes agricultural and industrial workers, tractor drivers, drivers who are actively in contact with objects of the external environment. Human morbidity directly depends on the number of infected rodents in a given area. GLPS is recorded mainly in the form of sporadic cases; less often – in the form of local epidemic outbreaks. After the infection, a persistent lifelong immunity remains; cases of repeated morbidity are rare.
The pathogenetic essence of hemorrhagic fever with renal syndrome is necrotizing panvasculitis, DIC syndrome and acute renal failure. After infection, the 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 autoantibodies, autoantigens, CEC, which have a capillarotoxic effect, causing damage to the walls of blood vessels, blood clotting disorders, the development of thrombohemorrhagic syndrome with damage to the kidneys and other parenchymal organs (liver, pancreas, adrenal glands, myocardium), the central nervous system. Renal syndrome is characterized by massive proteinuria, oligoanuria, azotemia, violation of the CBS.
Hemorrhagic fever with renal syndrome is characterized by a cyclic course with a sequential change of several periods:
- incubation (from 2-5 days to 50 days – on average 2-3 weeks)
- prodromal (2-3 days)
- febrile (3-6 days)
- oligauric (from 3-6 to 8-14 days of GLPS)
- polyuric (from 9-13 days of GLPS)
- convalescent (early – from 3 weeks to 2 months, late – up to 2-3 years).
Depending on the severity of symptoms, severity of infectious-toxic, hemorrhagic and renal syndromes, there are typical, erased and subclinical variants; mild, moderate and severe forms of hemorrhagic fever with renal syndrome.
After the incubation period, a short prodromal period occurs, during which fatigue, malaise, headaches, myalgia, and subfebrility 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). Pain in the eyeballs, blurred vision, flickering of “flies”, seeing objects in red are characteristic. At the height of the febrile period, hemorrhagic rashes appear on the mucous membranes of the oral cavity, the skin of the chest, axillary areas, and neck. An objective examination reveals hyperemia and puffiness of the face, injection of conjunctival and scleral vessels, bradycardia and arterial hypotension up to collapse.
During the oligauric period of hemorrhagic fever with renal syndrome, the body temperature decreases to normal or subfebrile figures, but this does not lead to an improvement in the patient’s condition. At this stage, the symptoms of intoxication increase even more and there are signs of kidney damage: lower back pain increases, diuresis decreases sharply, arterial hypertension develops. Hematuria, proteinuria, and cylindruria are detected in the urine. With an increase in azotemia, acute renal failure develops; in severe cases, uremic coma.
Most patients have indomitable vomiting and diarrhea. Hemorrhagic syndrome can be expressed to varying degrees and include macrohematuria, bleeding from injection sites, nasal, uterine, gastrointestinal bleeding. In the oligauric period, severe complications may develop (hemorrhages in the brain, pituitary gland, adrenal glands), which cause 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 signs of this period are an increase in daily diuresis to 3-5 liters and isohypostenuria. During the polyuria period, dry mouth and thirst persist.
The period of convalescence in hemorrhagic fever with renal syndrome can be delayed for several months or even years. Postinfectious asthenia persists in patients for a long time, characterized by general weakness, decreased performance, rapid fatigue, emotional lability. The syndrome of vegetative dystonia is expressed by hypotension, insomnia, shortness of breath with minimal exertion, increased sweating.
Specific complications of severe clinical variants of HFRS can be infectious-toxic shock, hemorrhages in parenchymal organs, pulmonary and brain edema, bleeding, myocarditis, meningoencephalitis, uremia, etc. With the addition of bacterial infection, the development of pneumonia, pyelonephritis, purulent otitis media, abscesses, phlegmon, sepsis is possible.
Clinical diagnosis of HFRS is based on the cyclical course of infection and the characteristic change of periods. When collecting an epidemiological history, attention is paid to the patient’s stay in an endemic area, possible direct or indirect contact with rodents. When conducting a non-specific examination, the dynamics of changes in the indicators of general and biochemical analysis of urine, electrolytes, biochemical blood samples, CBS, coagulograms, etc. are taken into account. In order to assess the severity of the course and prognosis of the disease, ultrasound of the kidneys, EGD, chest X-ray, ECG, etc. are performed.
Specific laboratory diagnostics of hemorrhagic fever with renal syndrome is carried out using serological methods (ELISA, RNIF, RIA) in dynamics. Antibodies in the blood serum appear at the end of the 1st week of the disease, by the end of the 2nd week they reach their maximum concentration and remain in the blood for 5-7 years. Virus RNA can be isolated by PCR examination. GLPS is differentiated with leptospirosis, acute glomerulonephritis, pyelonephritis and enterovirus infection, and other hemorrhagic fevers.
Patients with hemorrhagic fever with renal syndrome are hospitalized in an infectious 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 of 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 appointment of interferon preparations, antiviral chemotherapy drugs (ribavirin).
In the febrile period, infusion detoxification therapy is carried out (intravenous infusions of glucose and saline solutions); prevention of DIC syndrome (administration of drugs-disaggregants and angioprotectors); in severe cases, glucocorticosteroids are used. In the oliguric period, diuresis is stimulated (administration of shock doses of furosemide), correction of acidosis and hyperkalemia, prevention of bleeding. With increasing acute renal failure, the transfer of the patient to extracorporeal hemodialysis is indicated.
In the presence of bacterial complications, antibiotic therapy is prescribed. In the polyuric stage, the main task is to perform oral and parenteral rehydration. During the period of convalescence, general restorative and metabolic therapy is carried out; full nutrition, physiotherapy (diathermy, electrophoresis), massage and physical therapy are recommended.
Prognosis and prevention
Mild and moderate forms of hemorrhagic fever with renal syndrome in most cases end in recovery. Residual phenomena (postinfectious asthenia, lower back pain, cardiomyopathy, mono- and polyneuritis) are observed for a long time in half of those who have been ill. Convalescents require quarterly dispensary observation by an infectious disease specialist, a nephrologist and an oculist 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 in the destruction of mouse-like rodents in natural foci of infection, prevention of contamination of dwellings, water sources and food with rodent secretions, deratization of residential and industrial premises. Specific vaccination against has not been developed.