What is Hemorrhagic Fever with Renal Syndrome?
Hemorrhagic fever with renal syndrome (hemorrhagic nephrosonephritis, Churilova disease, epidemic nephrosonephritis, Far Eastern Hemorrhagic Fever, Korean hemorrhagic fever, Manchurian hemorrhagic fever, Scandinavian epidemic nephropathy, Tula fever; Nephrosonephritis haemorragica – lat.) – acute infectious disease characterized by selective lesion of blood vessels and proceeding with fever, intoxication and damage kidney.
Causes of Hemorrhagic Fever with Renal Syndrome
In 1938-1940 Complex studies have been conducted in the Far East of Russia, as a result of which the viral nature of the disease and its main epidemiological and clinical patterns have been established. (Chumakov A.A., Smorodintsev M.P.). The disease was named Far Eastern hemorrhagic nephrosonephritis. At the same time, in North Manchuria, a similar disease was registered among the personnel of the Japanese Kwantung Army, called the Songo disease. Somewhat later, cases of the disease were noted in the Tula Region, Sweden, Norway and Finland, and South Korea (more than 2,000 patients during the Korean-American War of 1951-1953). Later, natural foci were identified in many regions of the Russian Federation (especially in the Urals and in the Middle Volga region), in Ukraine, Moldova, Belarus, Yugoslavia, Romania, Hungary, the Czech Republic, Slovakia, and Bulgaria. In 1976-1978 the pathogen is isolated first from rodents, and then from a sick person. The common name for various variants of the disease “hemorrhagic fever with renal syndrome” was introduced by the decision of the WHO scientific group in 1982.
Currently, the pathogen of hemorrhagic fever with renal syndrome belongs to the family of bunyaviruses (Bunyaviridae) and is divided into a separate genus Hantavirus, which includes the Hantaan virus (Korean hemorrhagic fever), the Puumala virus (epidemic nephropathy), and two viruses, the rathythemathatrus and the two viruses and the viruses, the rathympurus, and the rathyme; for a man.
There are 8 known virus serovars, isolated in different places from different rodents and causing diseases with unequal severity. The first 4 serotypes cause diseases in people united by the name hemorrhagic fever with renal syndrome. The most difficult diseases are caused by viruses of the 1st serovar (the main reservoir is a field mouse); most easily caused by viruses of the 2nd serovar. Malopathogenic viruses are considered the so-called undifferentiated serovar.
Hantaan and Puumala viruses – spherical RNA-containing viruses with a diameter of 85-110 nm. The virus is inactivated at 50 ° C for 30 minutes, at 0–4 ° C it is stable for 12 hours. Currently, the presence of antigenic differences between the two variants of the pathogen of hemorrhagic fever with renal syndrome has been proven. The Hantaan virus circulates in the natural foci of the Far East, Russia, South Korea, the DPRK, China, and Japan. The main carrier is a field mouse. The second variant of the hemorrhagic fever virus with renal syndrome – European (Western), Puumala – was found in Finland, Sweden, Russia, France, and Belgium. Its reservoir is a red vole. The existence of a third antigenic variant in the Balkans is assumed.
Pathogenesis During Hemorrhagic Fever with Renal Syndrome
The gateway of infection is the mucous membrane of the respiratory tract, less commonly the skin and the mucous membrane of the digestive organs. At the site of the gate of infection significant changes are not observed. The initial manifestations of the disease are caused by viremia and intoxication. The HFRS pathogen has pronounced vasotropicity, and the main feature in the pathogenesis of the disease is damage to the vascular wall, although the state of the coagulation and anti-coagulation systems also plays a role in the development of the hemorrhagic syndrome. Vascular disease also plays a significant role in the genesis of renal syndrome. It was found that in severe HFRS, glomerular filtration significantly decreases and that this decrease is not accompanied by destructive disorders of glomeruli. It can be assumed that among the causes leading to the development of acute renal failure, the immunopathological factor is also important. Depending on the severity of the disease, a different severity of the thrombohemorrhagic syndrome is noted. After suffering HFRS, strong immunity remains. Repeated diseases are not observed.
Symptoms of Hemorrhagic Fever with Renal Syndrome
The incubation period lasts from 7 to 46 days (most often from 21 to 25 days). During the course of the disease, the following periods are distinguished: initial, oligouric (period of renal and hemorrhagic manifestations), polyuric, and convalescence.
The initial period (the period of prodromal phenomena) lasts from 1 to 3 days and is characterized by an acute onset, an increase in body temperature up to 38-40 ° C, which is sometimes accompanied by chills. There is a severe headache (but no pain in the superciliary arches and eyeballs), weakness, dry mouth, signs of inflammation of the upper respiratory tract is not observed. When examining patients, there is a hyperemia of the skin of the face, neck, upper chest (a symptom of the “hood”). The mucous membrane of the pharynx is hyperemic, the vessels of the sclera are injected, and a hemorrhagic rash can sometimes be seen on the background of hyperemic conjunctiva. In some patients, the onset of the disease may be gradual, and 2-3 days before the disease, there may be prodromal effects (weakness, malaise, catarrhal symptoms of the upper respiratory tract). On the part of the internal organs in the initial period, no special changes can be identified. Possible moderate bradycardia, in some patients, dull pain in the lower back, a positive symptom of Pasternack. Relatively rare in severe forms may be the phenomenon of meningism.
Oliguric period (febrile) (from 2-4th to 8-11th day of illness). The body temperature remains at 38–40 ° C and lasts until the 4–7th day of illness, but the decrease in body temperature is not accompanied by an improvement in the patient’s condition, more often it even worsens. The most typical manifestation of the oligouric period is back pain of varying severity (sometimes they begin at the end of the initial period). The absence of pain after the 5th day of the disease with the severity of fever and symptoms of intoxication makes one doubt the diagnosis of HFRS. In most patients, 1-2 days after the onset of back pain, vomiting occurs up to 6-8 times per day or more. It is not related to the ingestion of food or medicine. At the same time, abdominal pain occurs, abdominal distension is often noted.
When viewed during this period, the skin is dry, the face and neck are hyperemic, the hyperemia of the mucous membranes of the pharynx and the conjunctiva is preserved, there may be a slight swelling of the upper eyelid, the sclera vessels are injected. Hemorrhagic symptoms appear.
Thrombohemorrhagic syndrome of varying severity develops only in half of patients with more severe HFRS. First of all, and most often there is an increased fragility of blood vessels (tourniquet, more objective data can be obtained when determining the resistance of blood vessels according to Nesterov), then comes petechiae (in 10-15% of patients), gross hematuria (in 7-8%), intestinal bleeding (about 5%), hemorrhages at injection sites, nasal bleeding, hemorrhages in the sclera, very rarely blood in the vomit and sputum. Not characteristic bleeding from the gums and uterine bleeding. The frequency of hemorrhagic manifestations depends on the severity of the disease, they are more often observed in severe form (50-70%), less often in moderate (30-40%) and mild (20-25%). During epidemic outbreaks, hemorrhagic signs are observed more frequently and are more pronounced. In the Scandinavian countries, HFRS occurs more easily (“epidemic nephropathy”) than diseases caused by the eastern variant of the virus, for example, with the disease of 2,070 US military personnel in Korea.
A characteristic manifestation of the disease is kidney damage. It manifests itself in puffiness of the face, pastosity of the eyelids, a positive symptom of Pasternatsky (check carefully, as vigorous beating, as well as careless transportation of patients can lead to rupture of the kidneys). Oligouria develops from the 2nd-4th day, in severe cases it can reach anuria. The protein content in the urine increases significantly (up to 60 g / l), there may be microhematuria at the beginning of the oligouric period, hyaline and granular cylinders are found in the sediment, sometimes long, rough fibrin cylinders appear. Residual nitrogen builds up. The most pronounced azotemia occurs by the 7-10th day of illness. Normalization of residual nitrogen occurs in 2-3 weeks.
Period of organ lesions. It occurs more often against the background of normal body temperature and is primarily manifested by signs of increasing azotemia. Increased thirst, vomiting (may be hemorrhagic), lethargy, lethargy, headache. Persistent insomnia develops. Severe back pain can be projected on the stomach, because of lumbar pain, it is difficult for a patient to lie on his back. Note dry skin.
As a result of the breakdown of tissue proteins in the foci of necrobiosis and impairment of the nitrogen-excretory function of the kidneys in the blood, the level of nitrogenous slags increases progressively. Oligo-or anuria develops. The amount of daily urine secreted corresponds to the severity of the disease: a slight decrease in its light forms, 300-900 ml / day for moderate and less than 300 ml in severe cases of the disease.
The relative density of urine decreases sharply; further, most patients develop isohypostenuria. The amount of protein in the urine increases, fresh red blood cells, hyaline and granular cylinders, vacuolation cells of the renal epithelium (Dunaevsky cells) are detected.
In the blood, as a result of organ lesions, leukocytosis increases and the ESR begins to increase.
The polyuria period begins on the 9th-13th day of illness. Vomiting stops, pain in the lower back and abdomen gradually disappears, sleep and appetite are normalized, the daily amount of urine increases (up to 3-5 liters), weakness and dry mouth persist, the recovery period gradually (from 20-25 days).
Period of convalescence. Lasts from 3 to 12 months. For a long time, there is marked asthenia, pathology of the kidneys, especially in cases of developing acute or chronic pyelonephritis. With persistent preservation (more than 6 months) of polyuria, thirst and dry mouth, one should think about chronic tubulo-interstitial nephropathy with a violation of the tubule excretory-secretory function and an increase in the daily electrolyte excretion. The condition may persist for up to 10 years, however, no outcomes in chronic renal failure are observed.
The described clinical stages of the disease may not have clear transitional boundaries between themselves or occur simultaneously.
Complications are caused by the development of infectious-toxic shock, acute renal failure, pulmonary edema, organ hemorrhages and bleeding, kidney ruptures. In rare cases, eclampsia is observed with arterial hypertension, tonic and clonic convulsions, trisism, loss of consciousness, dilated pupils, slow pulse and respiration. Subarachnoid hemorrhages are possible. In China (1988), cases of encephalitis with hemorrhagic fever with renal syndrome are described.
With the development of uremia as the terminal stage of acute renal failure, nausea and vomiting increase, hiccups appear, then drowsiness, involuntary twitching of certain muscle groups (facial muscles, arm muscles) and other brain symptoms progress. Significantly increases the level of urea and creatinine in the blood.
Diagnosis of Hemorrhagic Fever with Renal Syndrome
In addition to general clinical and biochemical analyzes, apply the RNIF with the study of serum taken at the earliest possible period of the disease and then again after 5 days. Confirmation of the diagnosis is an increase in titer of antibodies not less than 4 times. In the blood of hemorrhagic fever with renal syndrome, antibodies persist for many years.
Hemorrhagic fever with renal syndrome should be distinguished from leptospirosis, influenza, enterovirus infection, pyelonephritis and acute glomerulonephritis, various types of other hemorrhagic fevers.
When examining a patient, it is necessary to pay attention to the successive change of periods of the disease. During the febrile period, high body temperature, redness and puffiness of the face, vascular injection of the sclera and conjunctiva, swelling of the upper eyelids and hyperemia of the pharynx are noted. At the same time, most patients complain of muscle pain, as well as back pain. Already during this period, the symptom of tapping on the lumbar region is positive. In the next, hemorrhagic, period, a massive, mild, rash is added to the listed symptoms. In more severe cases, exanthema and enanthema are replaced by hemorrhagic manifestations (bleeding from the gums, nose), urine becomes reddish. In the oliguric period, as a rule, the body temperature is normalized, but the pathology of the kidneys is clearly manifested – oliguria or anuria, an increase in the content of nitrogenous slags in the blood. In the study of urine detect an increased amount of protein, fresh red blood cells, hyaline and granular cylinders. In the differential diagnosis can help information about direct or indirect contact of the patient with rodents.
Treatment of Hemorrhagic Fever with Renal Syndrome
Since patients with hemorrhagic fever with renal syndrome are non-contagious, they can be hospitalized in any hospital equipped with appropriate laboratory services, which allows for the systematic monitoring of renal function. Patients are transported on a stretcher with a mattress with the utmost care due to the danger of rupture of the renal capsule.
Strict bed rest, including the early days of polyuria. Careful care, toilet of the oral cavity, control of urine output and bowel movements are necessary.
Diet number 4 with no restrictions on protein and salt. If severe, temporarily limit the intake of foods containing large amounts of protein and potassium (as patients develop hyperkalemia). Prescribe abundant drinking, including mineral water (Borjomi, Yessentuki number 4, and others.).
Etiotropic therapy is effective in the first 3-4 days of illness. Recommended virazol intravenously or ribamidil tablets 15 mg/kg/day for 5 days.
Pathogenetic treatment is carried out taking into account the severity of the disease and leading clinical syndromes. In mild cases, rutin, ascorbic acid, calcium gluconate, diphenhydramine, salicylates up to 1.5 g / day are prescribed.
In more severe cases, intravenous administration of 5% glucose solution, 500 ml isotonic sodium chloride solution with the addition of 200-400 ml hemodesis and 10 ml of 5% ascorbic acid solution is indicated. With increasing signs of vascular insufficiency, infusions of reopolyglucin (200-400 ml) are shown. In the period of oliguria, an infusion of isotonic sodium chloride solution is canceled. The nature and volume of the infusion detoxification therapy carried out determines the filtration function of the kidneys: the total daily amount of intravenous solutions should not exceed the volume of daily urine by more than 750 ml, and for severe renal insufficiency by 500 ml.
Indications for the use of glucocorticoids are the threat of severe renal failure (anuria, repeated vomiting), oliguria for 2 weeks or more, the development of meningoencephalitis. In these cases, prednisone is used parenterally in a daily dose of 1 to 2 mg/kg in a course of 3-6 days. With the development of toxic shock or acute vascular insufficiency, the daily dose of prednisolone is increased to 10-12 mg/kg.
Antihistamines, protease inhibitors are shown (trasilol, kontrikal in/in up to 50 thousand units), drugs of anti-bradykinin action, improving microcirculation (progestin 0.25 g 4 times a day).
To improve diuresis, 5-10 ml of a 2.4% solution of aminophylline (added to the dropper) is used. Lasix is ineffective, mannitol is not shown.
If there is no clinical effect from the treatment within 2-4 days and the signs of acute renal failure increase (urea more than 30 mmol/l and creatinine more than 600 µmol/l), as well as with the development of renal eclampsia or meningoencephalitis, patients are transferred to hemodialysis.
With pronounced hemorrhagic manifestations, dicine, aminocaproic acid, replacement blood doses are shown. With strong renal pains, promedol, aminazine, dimedrol, droperidol, seduxen are used in the form of lytic mixtures. In cases of cardiovascular insufficiency, Korglikon and strophanthin are injected intravenously.
For the prevention of secondary bacterial infections of the urinary tract used nitrofurans, nitroxoline (after restoring diuresis). In the polyuric period, the drug therapy is gradually canceled, continuing the intravenous administration of isotonic sodium chloride solution.
The discharge of patients is carried out at clinical recovery; at the same time residual polyuria and isohypostenuria are possible.
After discharge, convalescents are disabled for 1-4 weeks. In the future, they are released from hard physical work, sports for 6-12 months. During the recovery period, they recommend good nutrition, abundant drinking (alkaline mineral waters, dogrose and diuretic extracts), use of vitamin preparations, physiotherapy (diathermy, electrophoresis), massage and physical therapy.
Prevention of Hemorrhagic Fever with Renal Syndrome
Preventive measures include the improvement of the forest park area, barrier and house disinfestation in the territory of natural foci and sanitary-educational work among the population. Specific prevention is not developed.