Hemorrhagic fever symptoms
GL can cause 6 pathogens from a group of arboviruses distributed by arthropods, 4 togavirus from a group of flavoviruses and 3 representatives of bunia viruses.
The causative agents of GI most often penetrate the human body with the help of carriers( mosquitoes, mosquitoes, mites), however in some cases, infection can occur through contact with infected animals, their excrement, sick people( HFRS, Rift fever, Ebola, etc.).The spread of GL is limited to certain regions in which there are favorable conditions for the survival of viruses. So, natural centers of KGL exist in the Crimea, the Rostov region, Astrakhan;Omsk GL is found in some areas of Omsk, Novosibirsk regions, kyasanur forest disease in Mysore in India.
For GL, first of all, characterized by increased bleeding. In this case, the onset of the disease can be either acute or gradual. Often, cerebrospinal symptoms persisting for about 3 days, followed by a short period of remission for several hours, followed by a sudden rapid deterioration of the condition. Among the clinical manifestations of this critical period, the most typical
are the tendency to bleeding, especially skin hemorrhages, epistaxis, bleeding from the gums, hemorrhagic conjunctivitis;typical internal bleeding, manifested bloody vomiting, melena, hematuria, metrorrhagia.
Another distinguishing feature of GL is the frequent occurrence in patients of cardiovascular syndrome, acute disorders of vascular tone, up to the development of shock and collapse - reversible or irreversible. Among other manifestations of GH, dehydration, uremia, hepatic coma, hemolysis, jaundice, nervous system damage, secondary bacterial infection can occur. At the same time for each of the GL can be identified a certain organ-specificity. Thus, yellow fever is characterized by liver damage and jaundice, Dengue fever - joints, muscles and tendons, Marburg fever - development of diarrhea, hemorrhagic fever with kidney syndrome - kidney damage, etc.
The incidence of human GL can be sporadic or epidemiccharacter. Among all known clinical forms, hemorrhagic fever with renal syndrome, Crimean and Omsk haemorrhagic fevers are of the greatest importance for Russia.
Hemorrhagic fever with renal syndrome( HFRS) is an acute infectious virus disease of zoonotic nature, characterized by systemic lesions of small vessels( arteries and veins), hemorrhagic diathesis, hemodynamic disorders and kidney damage with the development of acute renal failure( ARF).
Etiology. The causative agents of HFRS are arboviruses( hanta viruses) - Hantaan, Puumula, Seui, Dobrava. The most severe course is characteristic of the Hantaan virus, which is spread in the Far East of Russia. The Dobrava virus, found in Southeast Europe, is genetically close to Hantaan and also causes severe forms of the disease.
The Puumula virus causes an easier disease called "epidemic nephropathy", prevalent mainly in a number of Scandinavian countries. In 1993 there was an outbreak of hanta-viral pulmonary syndrome with a high mortality rate( more than 50%) in 4 US states. The disease was caused by Sin Nombre - a new serotype of hunt viruses. Then in the US and South America, a number of other similar viruses were identified.
Epidemiology. For the first time the clinical picture of HFRS was described in the early 30's.in the Far East. Later, its outbreaks were found in the Kaliningrad, Tula, Moscow regions and the Urals.
The reservoir and source of hunt virus transmission are various species of rodents( field and forest mice, rats) in which the infection is transmitted horizontally and vertically.
From human rodents, transmission of the HLGPS virus is performed by aspiration, alimentary and contact methods. In this case, the air-dust path is considered as the main one. The alimentary path of infection is caused by eating foods contaminated with rodents feces.
The peak incidence is closely related to infection and the number of rodents. There can be both epidemic outbreaks of the disease, and sporadic cases.
People with a predominantly young and middle-aged age who are engaged in agricultural work are affected by HFRS.Outbreaks among children are described.
Pathogenesis. The virus of HFRS, penetrating into the endothelium of the vessels, causes its damage. At the same time, biologically active substances that sharply alter the vascular permeability and promote the release of the liquid part of the blood beyond the vascular bed are allocated. Developing deficiency of the volume of circulating plasma is accompanied by a decrease in the level of blood pressure and the development of hypovolemic shock. Damage to the endothelium leads to the activation of Hageman's factor and the triggering of the coagulation system of blood, the formation of DIC syndrome, which exacerbates the lyorganic disorders in patients with HFRS.
Pathomorphology. Pathomorphological changes are characterized by pronounced involvement of blood vessels - focal dystrophic, edematous-destructive and necrobiotic changes develop in the walls of arterioles, capillaries and especially venules. In this case, pronounced inflammatory changes( vasculitis) in them are absent.
Vascular damage is accompanied by increased vascular permeability, hemorrhages and circulatory disorders in various organs. The most pronounced pathomorphological changes are found in the kidneys, pituitary and adrenal glands, right atrium and CNS.
On autopsy, the kidneys are enlarged in size, have a flabby consistency. On the cut, there is a sharp boundary between the pale cortical layer and the bright red, blood-filled brain substance. At a microscopic examination, morphological changes are regarded as acute tubulointerstitial nephritis.
Along with changes on the part of the kidneys, regular disturbances in the deceased are detected in the anterior pituitary gland( the posterior almost does not suffer), although in some cases necrosis and hemorrhage in both parts of the pituitary gland are noted.
In addition to the pituitary gland, changes are found in the adrenal glands, thyroid gland, insulin apparatus of the pancreas, CNS, myocardium, lungs, gastrointestinal tract.
Classification. In everyday practice it is possible to use the HLPS classification proposed by Z.V.Sirotina and V.F.Uchaykin( 1998):
Classification of HFRS in children
Diagnosis example:
Complications: acute renal failure, right-sided polysegmentary pneumonia, grade II diastolic.
Clinic. The incubation period for HFRS is an average of 2 to 4 weeks.
The disease begins acutely and is accompanied by a fever, chills, a headache, a pronounced general weakness, an aching all over the body. There are complaints of visual impairment( "fog" before the eyes), abdominal pain, especially in the lower back, nausea, agonizing hiccups, vomiting. Patients may note a decrease in urination.
The appearance of patients is characterized by a puffy, hyperemic face, scleritis, conjunctivitis.
After the third day, rarely from the first days of the disease, there may be a disorderly or strictly linear small-scale hemorrhagic rash on the skin of the lateral surfaces of the chest, the inner surface of the shoulders, in the supraclavicular and subclavian areas. There may be nasal bleeding, hemorrhage at the injection site, in the sclera.
In the event of cerebral hemorrhage, the adrenal glands die.
From the cardiovascular system in the midst of the disease, there are bradycardia, ventricular extrasystole, sometimes fibrillation of the atria, a decrease in blood pressure, up to a collapse or hypovolemic shock.
The development of arterial hypertension is accompanied by an increase in the level of urea, creatinine in the blood, a shift in the KHS towards acidosis, hyponatremia, an increase in the magnesium content in the blood serum. At the same time, the potassium content remains normal or slightly increased.
By the end of the second week of the disease, oliguria is replaced by polyuria. As the amount of diuresis is restored, the condition of the patients improves. The hyperemia of the skin disappears, small-dot hemorrhages on the skin, hemorrhages in the subcutaneous tissue dissolve, the blood pressure rises, the bradycardia disappears. Due to loss of fluid and increased catabolism, body weight decreases. In addition, uncorrectable losses of sodium and potassium in the urine can be clinically manifested by general and muscular weakness, nausea, abdominal pain, muscle twitching and paresthesia, tachycardia and hypotension.
The period of convalescence begins with a marked improvement in the general condition of patients, accompanied by the disappearance of azotemia. Recovery of kidney function occurs within 1-3 months, and sometimes much longer. Within a year after the disease, signs of asthenic syndrome, headaches, memory loss, vegetovascular disorders, focal neurological symptoms may appear in convalescents.
Changes in the general blood test in the first days of the disease are characterized by leukopenia, less frequent leukocytosis, the appearance of plasma cells, the presence of which has an important diagnostic value.
In the urine sediment, a small amount of fresh or leached red blood cells, a little protein and cells of the renal epithelium are found.
In severe forms of infection in the acute period, the level of urea and creatinine in the blood can increase.
Progression of the pathological process is accompanied by the appearance in the blood of neutrophilic leukocytosis, with a shift to the left to the stab, less often young forms and myelocytes. The increased content of plasma cells remains.
In the urine, hematuria, cylindruria, many renal epithelial cells are intensified, and moderate proteinuria is noted. In some patients, protein loss in the urine can be significant. In this case, flocculent fibrin is found in the urine, which sometimes causes renal colic.
The period of convalescence is characterized by a decrease in the level of urea and creatinine, the normalization of the number of leukocytes, erythrocytes and hemoglobin in the peripheral blood, the gradual disappearance of pathological changes in the general analysis of urine.
Differential diagnosis of .The presence of fever, hemorrhagic syndrome in HFRS requires the exclusion of such infectious diseases as:
Algorithm for differential diagnostics of diseases accompanied by the syndrome "Hemorrhagic exanthema"
Laboratory diagnostics. At present, the etiology of the disease in HFRS can be deciphered by the immunofluorescence( RIF) reaction. For diagnosis, paired sera taken at intervals of 5-7 days are used. In this case, an increase in the titre of antiviral antibodies by 4 or more times allows the diagnosis of HFRS.In the presence of an appropriate clinic, a definite diagnostic value may have a high initial titer, since specific antibodies to the virus appear only 3-4 days after the onset of the disease.
With the use of molecular cloning and expression of hantai-viral protein, another diagnostic system - EL1SA and IgG and IgM ELISA kits with recombinant antigens - was created, which allows early identification of viral subtypes.
Treatment of patients with HFRS is performed only in the hospital and should be:
An anodyne, specific immunoglobulin, hyperimmune plasma, interferon preparations and its inducers( amixin, etc.) can be used as etiotropic therapy.
The central place is taken by pathogenetic therapy aimed at combating intoxication, hemorrhagic manifestations( Table 10.2).At the same time, treatment is most effective in conditions of multi-purpose hospitals that provide not only specialized nephrological help, but also a resuscitation aid.
In connection with the threat of development of severe complications( collapse, bleeding, tearing or rupture of the cortical substance of the kidney), medical measures should be started at the pre-hospital stage, and transportation of patients to the hospital should be as gentle as possible.
An important place in the treatment of patients with HFRS is dietotherapy, which involves the appointment of easily digestible food containing all the necessary ingredients. Limit protein produced with pronounced azotemia.
To combat vomiting, subcutaneous injections of a 2.5% solution of aminazine, 2.5% solution of pipolpene, 0.1% solution of atropine, droperidol at age dosages can be used.
When expressed in the initial period of hypercoagulable disease, intravenous heparin is administered under the control of hemostatic parameters. It should be remembered that uncontrolled administration of this drug in HFRS can enhance the manifestation of hemorrhagic diathesis. In the phase of "consumption coagulopathy" frozen plasma is used. The positive effect in the treatment has intermittent selective plasmapheresis.
Treatment of arthritis in most patients is conservative, with strict control of water-electrolyte metabolism and CBS.
Tactics of complex therapy for HFRS
There is no consensus for stimulation of diuresis with large doses of diuretics. Some authors believe that with pronounced lesion of tubulointerstitial tissue of the kidneys, their tendency to spontaneous tearing and tearing of the cortex, the use of diuretics can lead to negative consequences.
Active tactics are required only in severe cases, where there is the greatest danger of exceeding adequate therapy. The emergence of spontaneous ruptures and tears in the cortical substance of the kidneys at the turn of the oliguric and polyuric periods serves as an indication for their prompt treatment.
In conditions of acute arterial hypertension, which is the basis of the entire HLPS clinic, and the reduced excretory capacity of the kidneys, even a slight excess of the volumes and doses of the drugs administered can cause iatrogenic disorders that are not related to the disease itself.
Outcomes. Most patients recover completely. Reliable cases of recurrent disease are not described.
The mortality from this disease is highest in Asian countries, where the infection is caused by the Hantaan virus. At present, in the Amur region, it has decreased from 10-15 to 7-8%.In the European regions of Russia, where HFRS proceeds less severely, the mortality rate ranges from 0.1 to 1%.
The main causes of death from HFRS are:
Most of the deaths due to these causes occur in the early period, no later than 10-12 days of the disease, and since they occur against the background of acute renal failure, this served as the basis for isolating HLRS patients and uremia as the cause of death.
In addition, in some patients, recovery may occur with residual phenomena in the form of chronic pyelonephritis, arterial hypertension, encephalopathy. The frequency and severity of residual phenomena depends on the severity of the HFRS.
Clinical examination. Clinical follow-up includes monitoring the restoration of kidney function, CNS, and other internal organs affected in the acute period. Observation should be carried out by a pediatrician and nephrologist.
The examination complex should include, in addition to clinical data, the study of blood and urine, bacteriological culture of urine, the determination of latent leukocyturia by Nechiporenko's method, the calculation of the daily amount of urine. Especially it is necessary to allocate ultrasound of kidneys and renoradiography, with the help of which it is possible to obtain very valuable information about the state of the kidneys.
The first examination is carried out a month after discharge from the hospital. Then the persons who have transferred an easy form of the disease, are examined every 3 months, and in the absence of pathology - once a year. Reconvalvesent of moderate and severe forms of HFRS visit the doctor once a month, and in the absence of deviations - 2 times a year.
Dispensary follow-up is discontinued after 3 years in the absence of violations from the kidneys and other organs.
Prevention. Specific prophylaxis involves the use of a vaccine against various serotypes of the Hantaan virus and the immunization of appropriate populations. Experience in this disease prevention has been accumulated in South Korea, North Korea and China.
Nonspecific prevention is to prevent people's contact with rodents, strict observance of personal hygiene measures, and sanitary education among the population living in areas where HFRS is spread.
Crimean haemorrhagic fever( CGL) is a natural focal arbovirus disease transmitted by ixodid mites and accompanied by fever, expressed symptoms of intoxication, hemorrhagic syndrome.
Etiology. The causative agent of CHF is an RNA-containing virus resistant to low temperatures, drying( stored for 2 years), but quickly dies by boiling. Increased pathogenicity of the virus is observed after passage through the human body.
Epidemiology. The main reservoir and source of infection are animals( cattle, hares, etc.) and birds from which they are infected and infected by parasitizing ticks. Transmission of the virus to humans occurs with a tick bite. From man to man, the disease is not transmitted. At the same time, nosocomial and family infections are possible in contact with the patient's blood. In this regard, during the bleeding period, patients present a particular danger to others.
KGL is naturally-focal in nature, more often sporadically, with a seasonal rise in the warm season.
Natural foci of infection exist in the western part of the Crimean peninsula, the Rostov region, Astrakhan. The emergence of infection is usually preceded by agricultural work in the field and tick bites.
Regardless of age, a person is highly susceptible to CHF.Mortality in this disease varies from 8 to 50%.
Pathogenesis. In the pathogenesis of CHL, the destruction of the walls of small blood vessels of the liver, kidneys, skin, and CNS is of primary importance, accompanied by an increase in their permeability.
The virus penetrates the human body when it bites an infected tick. The development of viremia coincides with the infectious-toxic manifestations of the initial period. The virus has vasotropy, which creates prerequisites for increasing the permeability of vascular walls, violations of the coagulation system, the development of DIC syndrome. In addition, the development of hemorrhagic syndrome helps suppress the growth of bone marrow cells and impaired liver function.
Pathomorphology. The section finds multiple hemorrhages in the mucous membrane of the stomach, intestines, the lungs, conjunctiva, skin.
Morphological examination reveals signs of edematous-destructive capillaritis in patients with severe generalized serous-hemorrhagic inflammation, extensive dystrophic changes, focal necrosis.
Classification. There is no generally accepted classification of CHF to date, therefore, when making a diagnosis, a classification based on the principles proposed by A.A.Koltypin and augmented by E.V.Leschinskaya( 1967)
Classification of CHL in children
Clinic. The incubation period lasts from 2 to 14 days and on average is 3-6 days.
For CHL is characterized by a rapid onset of the disease, accompanied by fever, hemorrhagic syndrome, which is absent only 7-9% of patients. The body temperature from the first hours of the disease rises to 39-40 ° C and is accompanied by chills.
The duration of the feverish period is 7-9 days, the temperature curve has a two-humped character with a "cut" on the 3-5 days. Clinically, the prehemorrhagic period, the period of hemorrhagic manifestations and convalescence are distinguished.
Typical for the prehemorrhagic period are complaints of headaches, joint and muscle pains, repeated vomiting, pain in the lower back and abdomen. Less common are indications of dizziness, thirst, dry mouth, nonsense, impaired consciousness, pain in the calf muscles.
At objective research there is hyperemia of the face, neck, upper chest, mucous oropharynx, conjunctiva. From the side of the cardiovascular system, there is a decrease in blood pressure, a relative bradycardia. The duration of this period is from several hours to 6-8 days.
With the appearance of hemorrhagic syndrome, body temperature decreases( the "cut-in" of the temperature curve), the general condition of patients deteriorates sharply due to bleeding that begins. Simultaneously, the skin appears petechial or larger hemorrhagic, often uninvolved, rash, which does not protrude above the surface of the skin, has a dark cherry color. Symptoms of "tourniquet" and "pinch" are positive. Exanthema is localized in the region of the shoulder girdle, on the back, hips, holds 5-8 days, then fades and disappears. Bleeding is possible from the nose, gums, pharynx, stomach, intestines, lungs, uterus. In many patients, bleeding occurs simultaneously from several organs. There are hemorrhages in the sclera, conjunctiva, injection site. In parallel with hemorrhagic syndrome, lethargy, drowsiness, deafness of cardiac tones, vomiting becomes more frequent, loss of consciousness is possible. Bradycardia is replaced by tachycardia, which indicates a severe course of the disease, lowering blood pressure. Some patients have a persistent bloating. The most dangerous for life profuse gastrointestinal bleeding with the development of hypovolemic shock and collapse. Hemorrhagic syndrome grows violently, lasts no more than a week, there are no recurrences.
During the course of the disease, moderate hepatomegaly, mild jaundice of the skin can be observed. The chair is often detained. Acute renal failure is not a permanent sign of CHF, but in some patients oliguria and hyperaemia may be recorded. The defeat of the central nervous system is manifested by drowsiness, delirium, progressive darkening of consciousness.
In the general analysis of blood, leukopenia occurs with a shift of the leukocyte formula to the left to young forms, thrombocytopenia, a decrease in the level of prothrombin. Part of the patients increase the activity of transaminases, there is albuminuria and hematuria.
Among the reasons for the unfavorable outcome in CHF, there is a collapse, pulmonary and brain edema, renal and hepatic insufficiency, cerebral hemorrhage, adrenal glands.
The period of convalescence is marked by a decrease in body temperature and cessation of bleeding. The general condition of patients is gradually improving. Long-term arterial hypotension, asthenoneurotic syndrome, the normal composition of peripheral blood is slowly restored. A part of children may have hearing loss, memory impairment. Complete recovery occurs at the 3-4 th week of the disease, sometimes later.
Laboratory diagnostics. Preliminary diagnosis is made on the basis of epidemiological history, characteristic clinical symptoms( rapid onset of the disease, fever, hemorrhagic manifestations), changes in the general blood test( leukopenia, thrombocytopenia).
Confirm the final diagnosis by isolating the virus from the blood of patients by intracerebral infection of white mice. Serological diagnostics can be used DSC, RIGA, RIF, delivered in dynamics, PCR
Program of laboratory examination of the patient CCHF
Differential diagnosis .Given the hemorrhagic syndrome, a differential diagnosis with CHF is performed with both infectious and non-infectious diseases.
Among the first require exceptions:
In addition, it should be remembered that the signs of DIC syndrome can accompany many infectious diseases that occur in severe or extremely severe forms. With regard to non-communicable diseases, the following should be excluded:
Treatment. If suspected of having CHF, patients are subject to mandatory hospitalization and treatment in the hospital. Patients with severe forms of the disease should be in intensive care units or intensive care units.
Ribavirin, interferon preparations or inducers may be used as etiotropic agents.
Pathogenetic therapy should be aimed at removing toxins from the body, fighting with DIC syndrome, metabolic disorders, respiratory and cardiovascular insufficiency.
Detoxication therapy involves the introduction of glucose-saline solutions with preparations of potassium, ascorbic acid, 5-10% albumin solution. As a haemostatic means, facilitating the relief of hemorrhagic syndrome, a 10% solution of calcium gluconate is prescribed;5% solution of ascorbic acid, freshly frozen plasma( all clotting factors, except platelets), cryoprecipitate( 8th coagulation factor, fibrinogen).The volume of infusion, dose and multiplicity of the introduction of pathogenetic therapy depends on the form of the disease. So, adults with severe forms are poured 600-800 ml of plasma, repeating the injections every 6-8 hours in a half dose. Cryoprecipitate is administered up to 10 times a day in a single dose of 25 ml. With gastrointestinal bleeding, androxone( adozone) is prescribed for 1-4 ml intramuscularly or intravenously 3 times a day, dicinone. The expressed thrombocytopenia serves as an indication for the use of thrombomass( intravenously drip, 1 therapeutic dose of the drug per 10 kg of the patient's body weight per day).
In addition to the listed medicines, protease inhibitors, antihistamines, glucocorticoids, broad-spectrum antibiotics( according to indications) are widely used.
Treatment of should be performed under daily control of the coagulogram and the number of peripheral blood platelets twice daily. In this case, unreasonable medical manipulations accompanied by traumatization of the skin and mucous membranes, creating an additional threat of bleeding, should be avoided. In this regard, it is advisable to use catheterization of the main vessels to ensure the introduction of drugs.
Tactics of complex therapy KGL
The discharge of reconvalescents is carried out on the basis of clinical recovery criteria: persistent normalization of temperature, coagulograms, platelet counts, absence of complications. The average discharge is not earlier than 21 days after the onset of the disease.
Clinical follow-up is conducted by a physician at the polyclinic in the course of the year with a quarterly follow-up( at 3, 6, 9, 12 months) with mandatory hemogram monitoring. Convalescents are obtained, if necessary, adaptogenes of plant origin, vitamins, diet, restrictive regime.
Prevention KGL is to combat the reclamation of domestic animals, the use of personal protective equipment against tick bites. In addition, a vaccine and a specific immunoglobulin against CHF have been developed.