Crimean hemorrhagic fever symptoms, prevention, first signs. Congo Crimean hemorrhagic fever - Symptoms, Diagnosis, Treatment. Material for research

What is Crimean hemorrhagic fever

Crimean-Congo hemorrhagic fever(lat. febris haemorrhagica crimiana, synonym: Crimean hemorrhagic fever, Congo-Crimean hemorrhagic fever, Central Asian hemorrhagic fever) is an acute infectious human disease transmitted through tick bites, characterized by fever, severe intoxication and hemorrhages on the skin and internal organs. It was first identified in 1944 in Crimea. The pathogen was identified in 1945. In 1956, a similar disease was identified in the Congo. Studies of the virus have established its complete identity with the virus discovered in Crimea.

What causes Crimean hemorrhagic fever

The causative agent of Crimean hemorrhagic fever is a virus from the family Bunyaviridae, genus Nairovirus. Belongs to arboviruses (Arboviridae). Discovered in 1945 by M.P. Chumakov in the Crimea, while studying the blood of sick soldiers and settlers who fell ill while working on hay harvesting. In 1956, a virus with a similar antigenic composition was isolated from the blood of a sick boy in the Congo. The causative agent is called the Congo virus. Virions are spherical, 92-96 nm in diameter, surrounded by a lipid-containing envelope. The most sensitive to the virus are embryonic kidney cell cultures from pigs, Syrian hamsters and monkeys. Poorly stable in the environment. When boiled, the virus dies instantly, at 37 `C - after 20 hours, at 45 `C - after 2 hours. When dried, the virus remains viable for over 2 years. In affected cells it is localized mainly in the cytoplasm.

Natural reservoir of the pathogen- rodents, large and small livestock, birds, wild species of mammals, as well as ticks themselves, which are capable of transmitting the virus to offspring through eggs and are virus carriers for life. The source of the pathogen is a sick person or an infected animal. The virus is transmitted through a tick bite or through medical procedures involving injections or blood sampling. The main carriers are ticks Hyalomma marginatus, Dermacentor marginatus, Ixodes ricinus. Outbreaks of the disease in Russia occur annually in the Krasnodar and Stavropol territories, Astrakhan, Volgograd and Rostov regions, in the republics of Dagestan, Kalmykia and Karachay-Cherkessia. The disease also occurs in southern Ukraine and Crimea, Central Asia, China, Bulgaria, Yugoslavia, Pakistan, Central, Eastern and Southern Africa (Congo, Kenya, Uganda, Nigeria, etc.). In 80% of cases, people aged 20 to 60 years get sick.

Pathogenesis (what happens?) during Crimean hemorrhagic fever

At the core pathogenesis of hemorrhagic Crimean fever there is an increase in the permeability of the vascular wall. Increasing viremia causes the development of severe toxicosis, up to infectious-toxic shock with disseminated intravascular coagulation, inhibition of hematopoiesis, which aggravates the manifestations of hemorrhagic syndrome.

The gateway to infection is the skin at the site of a tick bite or minor injuries upon contact with the blood of sick people (in case of nosocomial infection). No pronounced changes are observed at the site of the infection gate. The virus enters the blood and accumulates in the cells of the reticuloendothelial system. With secondary, more massive viremia, signs of general intoxication appear, damage to the vascular endothelium and thrombohemorrhagic syndrome develops of varying severity. Pathological changes are characterized by multiple hemorrhages in the mucous membranes of the stomach and intestines, the presence of blood in the lumen, but there are no inflammatory changes. The brain and its membranes are hyperemic, hemorrhages with a diameter of 1-1.5 cm with destruction of the brain matter are found in them. Small hemorrhages are detected throughout the brain. Hemorrhages are also observed in the lungs, kidneys, etc. Many issues of the pathogenesis of Crimean-Congo fever remain unexplored.

At autopsy, multiple hemorrhages are found in the mucous membranes of the gastrointestinal tract, blood in its lumen, but there are no inflammatory changes. The brain and its membranes are hyperemic, hemorrhages with a diameter of 1-1.5 cm with destruction of the brain matter are found in them. Small hemorrhages are detected throughout the brain. Hemorrhages are also observed in the lungs, kidneys, liver, etc.

Symptoms of Crimean hemorrhagic fever

Incubation period from one to 14 days. Most often 3-5 days. There is no prodromal period. The disease develops acutely.

In the initial (prehemorrhagic) period There are only signs of general intoxication, characteristic of many infectious diseases. The initial period usually lasts 3-4 days (from 1 to 7 days). During this period, against the background of high fever, weakness, weakness, headache, aches throughout the body, severe headache, pain in muscles and joints are noted.

More rare manifestations of the initial period include dizziness, impaired consciousness, severe pain in the calf muscles, and signs of inflammation of the upper respiratory tract. Only some patients, even before the development of the hemorrhagic period, develop symptoms characteristic of this disease.
symptoms - repeated vomiting not associated with food intake, lower back pain, abdominal pain, mainly in the epigastric region.

A constant symptom is fever, which lasts on average 7-8 days, the temperature curve is especially typical for Crimean hemorrhagic fever. In particular, when hemorrhagic syndrome appears, there is a decrease in body temperature to subfebrile, after 1-2 days the body temperature rises again, which causes the “double-humped” temperature curve characteristic of this disease.

Hemorrhagic period corresponds to the peak period of the disease. The severity of thrombohemorrhagic syndrome determines the severity and outcome of the disease. In most patients, on the 2-4th day of illness (less often on the 5-7th day), a hemorrhagic rash appears on the skin and mucous membranes, hematomas at the injection sites, and there may be bleeding (stomach, intestinal, etc.). The patient's condition deteriorates sharply. Facial hyperemia gives way to pallor, the face becomes puffy, cyanosis of the lips and acrocyanosis appear. The skin rash is initially petechial, at this time enanthema appears on the mucous membranes of the oropharynx, and there may be larger hemorrhages into the skin. Nasal and uterine bleeding, hemoptysis, bleeding of the gums, tongue, and conjunctiva are possible. The prognosis is unfavorable for the appearance of massive gastric and intestinal bleeding. The condition of the patients becomes even more severe, and disturbances of consciousness are noted. Characterized by abdominal pain, vomiting, diarrhea; the liver is enlarged, painful on palpation, Pasternatsky's sign is positive. Bradycardia gives way to tachycardia, blood pressure is reduced. Some patients experience oliguria and residual nitrogen increases. In peripheral blood - leukopenia, hypochromic anemia, thrombocytopenia, ESR without significant changes. Fever lasts 10-12 days. Normalization of body temperature and cessation of bleeding characterizes the transition to the recovery period. Asthenia persists for a long time (up to 1-2 months). Some patients may have mild forms of the disease that occur without pronounced thrombohemorrhagic syndrome, but they, as a rule, remain undetected.

Sepsis, pulmonary edema, focal pneumonia, acute renal failure, otitis media, thrombophlebitis can be observed as complications. Mortality ranges from 2 to 50%.

Diagnosis of Crimean hemorrhagic fever

Diagnosis of Crimean hemorrhagic fever is based on the clinical picture, epidemiological history data (stay in the area of ​​natural foci, tick attacks, contact with patients with Crimean hemorrhagic fever), and the results of laboratory tests. There is a reduced number of red blood cells in the blood, leukopenia (up to 1x109-2x109/l), neutropenia, thrombocytopenia. To confirm the diagnosis, virus isolation from the patient’s blood is used; from the 6-10th day of illness, an increase in antibody titer is determined in repeated samples of the patient’s blood serum in the RSC, diffuse precipitation reactions in agar, and passive hemagglutination reactions.

Differential diagnosis is carried out with other viral diseases manifested by hemorrhagic syndrome, especially if the patient in the last days before the development of clinical manifestations of the disease was in countries with tropical and subtropical climates, with leptospirosis, hemorrhagic fever with renal syndrome, hemorrhagic vasculitis, sepsis, etc.

Treatment of Crimean hemorrhagic fever

Patients must be isolated in the infectious diseases department of the hospital. Treatment is symptomatic and etiotropic. Anti-inflammatory drugs and diuretics are prescribed. Avoid the use of drugs that increase kidney damage, such as sulfonamides. Antiviral drugs (ribavirin, reaferon) are also prescribed. In the first 3 days, heterogeneous specific equine immunoglobulin, immune serum, plasma or specific immunoglobulin obtained from the blood serum of recovered or vaccinated individuals is administered. Specific immunoglobulin is used for emergency prophylaxis in persons in contact with the patient’s blood.

Prevention of Crimean hemorrhagic fever

To prevent infection, the main efforts are directed towards combating the vector of the disease. They carry out disinfestation of premises for keeping livestock, and prevent grazing on pastures located on the territory of a natural outbreak. Individuals should wear protective clothing. Treat clothing, sleeping bags and tents with repellents. If you are bitten by a tick in your habitat, immediately contact a medical facility for help. For persons who are planning to enter the territory of the South of Russia, preventive vaccination is recommended. In medical institutions, the high contagiousness of the virus, as well as its high concentration in the blood of patients, should be taken into account. Therefore, patients must be placed in a separate box, and care must be provided only to specially trained personnel.

Which doctors should you contact if you have Crimean hemorrhagic fever?

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20.02.2019

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• Crimean-Congo hemorrhagic fever virus (CCHFV) causes a number of viral hemorrhagic fever outbreaks.
• The case fatality rate during CCHF outbreaks reaches 40%.
• The virus is transmitted to people mainly from ticks and livestock. Person-to-person transmission can occur through close contact with the blood, secretions, organs, or other body fluids of infected people.
• CCHF is endemic in Africa, the Balkans, the Middle East and Asia, in countries south of the 50th parallel north latitude.
• There is no vaccine for humans or animals.

Crimean-Congo hemorrhagic fever (CCHF) is a widespread disease caused by a tick-borne virus (Nairovirus) of the Bunyaviridae family. CCHF virus causes outbreaks of severe viral hemorrhagic fever with a case fatality rate of 10-40%.

CCHF is endemic in Africa, the Balkans, the Middle East and Asian countries south of the 50th parallel north latitude, the geographic limit of the tick's primary vector.

Crimean-Congo hemorrhagic fever virus in animals and ticks

CCHF virus vectors include a wide range of wild and domestic animals such as cattle, sheep and goats. Many birds are resistant to the infection, but ostriches are susceptible and may have high infection rates in endemic areas where they are a source of infection in human cases. For example, one past outbreak of the disease occurred at an ostrich slaughterhouse in South Africa. There are no obvious signs of disease in these animals.

Animals are infected by the bite of an infected tick, and the virus remains in their bloodstream for approximately one week after infection, allowing subsequent tick bites to continue the tick-animal-tick cycle. Although several species of ticks can be infected with the CCHF virus, the main carriers are Hyalomma ticks.

Transmission of infection

CCHF virus is transmitted to humans either through tick bites or through contact with infected blood or tissues of animals during and immediately after slaughter. Most cases of infection occur in people involved in factory farming, such as farm workers, slaughterhouse workers and veterinarians.

Person-to-person transmission can occur through close contact with the blood, secretions, organs, or other body fluids of infected people. Hospital-acquired infections may also occur as a result of improper sterilization of medical equipment, reuse of needles, and contamination of medical supplies.

Signs and symptoms

The length of the incubation period depends on the method of infection with the virus. After infection through a tick bite, the incubation period usually lasts one to three days, with a maximum duration of nine days. The incubation period after exposure to infected blood or tissue typically lasts five to six days, with a documented maximum period of 13 days.

Symptoms appear suddenly with fever, myalgia (muscle pain), dizziness, neck pain and stiffness, back or lower back pain, headache, eye inflammation and photophobia (sensitivity to light). Nausea, vomiting, diarrhea, abdominal pain and sore throat may occur, followed by mood swings and confusion. After two to four days, agitation may give way to drowsiness, depression and fatigue, and abdominal pain may be localized to the upper right with detectable hepatomegaly (enlarged liver).

Other clinical signs include tachycardia (rapid heartbeat), lymphadenopathy (enlarged lymph nodes), and petechial rash (a rash caused by bleeding into the skin) on the inner surface of mucous membranes, such as the mouth and throat, and on the skin. Petechial rashes can develop into larger rashes called ecchymoses and other hemorrhagic phenomena. Signs of hepatitis are common, and after the fifth day of illness, severely ill patients may experience rapid deterioration of kidney function and sudden liver or pulmonary failure.

The mortality rate for CCHF is approximately 30%, with death occurring in the second week of illness. In recovering patients, improvement usually begins on the ninth or tenth day after the onset of the disease.

Diagnostics

CCHF virus infection can be diagnosed by several different laboratory tests:

• enzyme immunoassay (ELISA);
• identification of antigens;
• serum neutralization;
• reverse transcriptase polymerase chain reaction (RT-PCR);
• virus isolation in cell cultures.

Terminally ill patients and those in the first few days of illness usually do not produce measurable antibodies, so diagnosis in these patients is made by detecting virus or RNA in blood or tissue samples.

Testing of patient samples poses an extremely high biological risk and should only be carried out under maximum biosafety conditions. However, if samples are inactivated (eg by virucides, gamma radiation, formaldehyde, exposure to high temperatures, etc.), they can be handled under basic biosafety conditions.

Treatment

The main approach to the management of CCHF in humans is usual supportive care with symptomatic treatment.

The antiviral drug ribavirin leads to clear positive results in the treatment of CCHF infection. Both oral and intravenous dosage forms are effective.

Disease prevention and control

Control of CCHF in animals and ticks

Robert Swanepoel/NICD South Africa

Prevention and control of CCHF infection in animals and ticks is difficult because the tick-animal-tick cycle is usually silent and infection in domestic animals usually occurs without obvious signs. In addition, ticks that transmit the disease are numerous and widespread, so the only practical option for properly managed livestock production operations is to control ticks with acaricides (chemicals designed to kill ticks). For example, following an outbreak of this disease at an ostrich slaughterhouse in South Africa (mentioned above), measures were taken to ensure that ostriches remained tick-free in the quarantine facility for 14 days before slaughter. This measure helped reduce the risk that the animal was infected at the time of slaughter and prevented infection of people who had contact with the animals.

There are no vaccines for use in animals.

Reducing the risk of human infection

Although an inactivated vaccine derived from mouse brain tissue has been developed against CCHF and used on a small scale in Eastern Europe, there is currently no safe and effective vaccine for widespread use in humans.

In the absence of a vaccine, the only way to reduce the number of infections among people is to increase awareness of risk factors and educate people about measures they can take to limit exposure to the virus.

• Reducing the risk of tick-to-human transmission of the virus:
• wear protective clothing (long sleeves, long trousers);
• wear light-colored clothing that makes it easy to spot ticks on clothing;
• use approved acaricides (chemicals intended to kill ticks) on clothing;
• use approved repellents for skin and clothing;
• regularly inspect clothing and skin to detect ticks; if found, remove them using safe methods;
• strive to prevent animals from being affected by ticks or carry out tick control in animal housing;
• Avoid staying in areas where there are large numbers of ticks and during the seasons when they are most active.
• Reducing the risk of transmission of the virus from animals to humans:
• wear gloves and other protective clothing when handling animals or their tissues in endemic areas, especially during slaughter, dressing and culling in slaughterhouses or at home;
• Quarantining animals before entering slaughterhouses or routinely treating animals with pesticides two weeks before slaughter.
• Reducing the risk of person-to-person transmission in selected communities:
• avoid close physical contact with people infected with CCHF;
• wear gloves and protective clothing when caring for sick people;
• Wash your hands regularly after caring for or visiting sick people.

Infection control in health care settings

Health care workers caring for patients with suspected or confirmed CCHF or handling specimens collected from them should follow standard infection control precautions. These include basic hand hygiene, use of personal protective equipment, safe injection practices and safe disposal practices.

As a precaution, healthcare workers caring for patients directly outside the CCHF outbreak area should also follow standard infection control measures.

Specimens from people with suspected CCHF should be handled by trained staff working in appropriately equipped laboratories.

Recommendations for infection control during the care of patients with suspected or confirmed Crimean-Congo hemorrhagic fever should be consistent with WHO recommendations developed for Ebola and Marburg hemorrhagic fevers.

WHO activities

WHO is working with partners to support CCHF surveillance, diagnostic capacity and outbreak response in Europe, the Middle East, Asia and Africa.

WHO also provides documentation to support research and control of the disease and has developed an advisory note on standard precautions in health care settings, which is intended to reduce the risk of transmission of bloodborne and other pathogens.

The content of the article

Crimean hemorrhagic fever(disease synonyms: Acute infectious capillary toxicosis, Crimean-Congo hemorrhagic fever) is an acute natural focal infectious disease, which is caused by a virus, transmitted by ticks, characterized by high, often two-wave fever with severe hemorrhagic syndrome, thrombocytopenia.

Historical data of hemorrhagic fever

The first cases of Crimean hemorrhagic fever were identified in the steppe regions of the Crimean region in the summer of 1944 among the population engaged in haymaking and harvesting. For the first time, the clinical and epidemiology of the disease was studied in detail by A. A. Kolachov, Y. K. Gimelfarb, 1. R. Drobinsky, V. M. Domracheva. The disease was tentatively named “acute infectious capillary toxicosis.” Expedition led by Academician M.P. Chumakov in 1944-1945 pp. established the viral etiology of the disease.

Etiology of hemorrhagic fever

The causative agent of CHF-virus belongs to the genus Najarovirus, family Bunyaviridae, and contains RNA. Virions have two glycoproteins on the surface of the envelope and a nucleocapsid protein, as well as a large protein that probably has transcriptase activity. Glycoproteins determine high pathogenic properties.

Epidemiology of hemorrhagic fever

The source of infection for CHH are wild and domestic animals - cows, sheep, goats, hares, African hedgehogs, etc. The reservoir and carrier of the virus are about 20 species of ticks with transovarial transmission of the pathogen. A typical carrier of the pathogen is ixodid ticks. In Crimea it is Hyalomma plumbeum.
The mechanism of infection is transmissible through the bite of an infected tick. Infection is possible through contact with infected blood of sick people (nosocomial, family) and animals, and in laboratory conditions also through aerogenic means. Mostly livestock breeders, shepherds, milkmaids, veterinarians, etc. get sick. After an illness, viscospedic immunity remains. In endemic areas, the incidence is seasonal - March - September (the period of tick activity) and increases during the period of agricultural work (July - August). CHH is observed in the steppe regions of Crimea; isolated cases occur in the Odessa and Kherson regions of Ukraine. According to some scientists (M.P. Chumakov), hemorrhagic fevers of Central Asia are identical to CHH.

Pathogenesis and pathomorphology of hemorrhagic fever

The virus enters the body through the skin when bitten by an infected tick. This leads to viremia, which lasts throughout the incubation period and the first 3-5 days of the febrile period. Viremia is associated with infectious-toxic manifestations of the initial period, damage to the autonomic nervous system, especially vascular nerves. The CHG virus directly affects the vascular wall, increasing its permeability. Disturbances occur in the blood coagulation system, and DIC syndrome develops. Viremia also leads to damage to the bone marrow (thrombocytopenia and other signs) and liver. At autopsy, numerous hemorrhages and serous-hemorrhagic impregnation are found in almost all organs. The liver, kidneys and autonomic ganglia also show degenerative changes.

Hemorrhagic fever clinic

The incubation period lasts 2-14, on average 3-7 days. At the site of the tick bite, a feeling of heat appears, and subsequently itching. The disease begins acutely, with chills, body temperature rises to 39-40 ° C, headache is observed, as well as pain in the muscles, joints, abdomen and lumbar region, and sometimes vomiting. Patients are apathetic, some may experience psychomotor agitation. The skin of the face, neck, and upper chest turns red; at the same time, hyperemia of the conjunctiva and pharyngeal mucosa appears. It turns out there is arterial hypertension, relative bradycardia. On the 3-6th day of illness, often after a short, for 1-2 days, decrease in body temperature (two-wave temperature curve), most patients experience symptoms of hemorrhagic diathesis. A hemorrhagic rash appears on the skin, which is most significant on the lateral surfaces of the torso, abdomen, limbs, axillary and groin areas, as well as at injection sites (hematomas). In severe cases, hemorrhagic purpura and ecchymoses are found on the skin.
If the course is mild, the rash is sometimes non-hemorrhagic in nature and resembles erythema macular or roseola. The Konchalovsky-Rumpel-Leede (tourniquet) and Hecht-Moser (pinch) signs are not always present. 1-2 days before the rash appears, a small enanthema often appears on the mucous membrane of the soft palate, sometimes hemorrhagic.
In cases of severe disease, bleeding of the mucous membrane of the gums, mouth, tongue, conjunctiva, nosebleeds, hemoptysis, metrorrhagia, and gross hematuria appears. A severe prognostic sign is massive gastrointestinal bleeding. Changes in the central nervous system quickly appear - drowsiness, lethargy, meningeal symptoms, and sometimes loss of consciousness. Arterial hypotension increases, bradycardia can change into tachycardia, and sometimes a collaptoid state develops. The liver enlarges. In complicated cases, acute renal failure with anuria and azotemia may develop.
The febrile period usually lasts 1.5-2 weeks. From the 7-9th day, a gradual, stepwise decrease in body temperature begins. The course of the convalescence period is very slow, patients experience weakness, apathy, and dizziness for a long time (up to 4-8 weeks).
Possible course of CHH without hemorrhagic syndrome (abortive forms), when the disease is diagnosed only using specific research methods.
Forecast in severe hemorrhagic syndrome, the mortality rate reaches 10-30%.
Complicated ong>. Most often, these are massive hemorrhages into internal organs and cavities. Possible acute renal failure, pneumonia, pulmonary edema, thrombophlebitis, myocarditis, infectious-toxic shock.

Diagnosis of hemorrhagic fever

The main symptoms of the clinical diagnosis of CHH are the acute onset of the disease, a two-wave nature of body temperature, hyperemia of the face, neck (lapel symptom), conjunctiva in the initial period, severe hemorrhagic syndrome during the height of the disease, leukopenia, thrombocytopenia. Epidemiological history (tick bites, stay in an endemic area) is important.

Specific diagnosis of hemorrhagic fever

There are methods for isolating the virus from the blood during viremia. In clinical practice, serological reactions are used - RSK, RGNGA, RNIF, RDPA, which are carried out in the dynamics of the disease (paired serum method). To isolate the virus, newborn white mice are infected with the blood of patients.

Differential diagnosis of hemorrhagic fever

CHH should be differentiated from hemorrhagic fevers of other etiologies, meningococcal disease, influenza, leptospirosis, typhus, thrombocytopenic purpura (Werlhof's disease), hemorrhagic vasculitis (Henoch-Henoch disease), sepsis, yellow fever.

Treatment of hemorrhagic fever

Patients are isolated in separate boxes with special personnel and equipment. Prescribe pathogenetic and symptomatic treatment, hemostatic drugs, if necessary, replaceable blood transfusions, red blood cells and platelets, use glycocorticosteroids, and antibiotics if indicated. A positive effect is achieved by using convalescent immune serum of 60-100 ml (proposed by M.P. Chumakov in 1944) and hyper-unified immunoglobulin.
Prevention. The cells take a set of measures to destroy ticks and provide personal protection against tick bites. According to epidemiological indications, they are vaccinated with a specific vaccine and immunoglobulin against CHG is administered.

Crimea-Congo hemorrhagic fever (febris haemorrhagica Crimeae-Congo) is a natural focal bunyavirus disease spread by ticks in the subtropical and tropical regions of Asia, Africa and Europe, occurring in the form of a two-phase acute febrile disease with massive hemorrhagic syndrome and multiple organ lesions.
The disease, called “Crimean hemorrhagic fever,” was first described in 1944 - 1945 in Crimea by M.P. Chumakov and co-workers, who isolated the causative agent of the disease and established its transmission by ticks. In 1956, a virus was isolated from a patient with hemorrhagic fever in the Congo, which later turned out to be similar to the Crimean hemorrhagic fever virus, so the disease received a double name in 1969. In subsequent years, similar diseases were identified in the southern regions of the former USSR, southern Europe, East and West Africa, and South and Central Asia. Since 2012, in the southern regions of the Russian Federation, relatively forgotten diseases of Crimea-Congo fever began to be recorded again, often with fatal outcomes.
ETIOLOGY. The pathogen belongs to the family Bunyaviridae, genus Nairovirus. The virion genome is represented by single-stranded RNA. Virions are spherical in shape, 92 - 96 nm in diameter. The virus is inactivated within 2 hours when heated to 45°C and instantly dies when boiled, but is resistant to lyophilization. Sucking mice are sensitive to infection, but the virus is better cultivated on the kidney cells of embryos of pigs, monkeys and Syrian hamsters. The virus is localized predominantly in the cytoplasm. In a lyophilized state, it retains its activity for more than 2 years.
EPIDEMIOLOGY. Crimean hemorrhagic fever is a natural focal bunyavirus infection. Natural reservoir of the virus- wild (wood mouse, small gopher, hares, African hedgehogs, etc.) and domestic (cows, sheep, goats) animals, And ticks more than 20 species in which transovarial transmission of viruses occurs.
The natural mechanism of human infection is blood-borne, is realized through the suction of infected ticks Hyalomma plumbeum (in Crimea), Hyalomma anatolicum (in Central Asia and Africa), as well as Dermacentor spp. and Rhipicephalus spp. Possible bloodborne infection in contact with blood, tissues and blood-containing excreta of infected animals, as well as nosocomial infection through contact with blood and blood-containing material from sick people and sometimes aerosol contamination (in laboratory conditions).
Fig.1. Hyalomma mite.
In endemic areas, the incidence is seasonal and increases in the summer during agricultural work (May - August), often becoming local outbreaks. Susceptibility is high, and those at high risk of infection are rural residents caring for animals, veterinarians, as well as visitors to the endemic focus (non-immune persons).
Endemic foci of CCHF are located in Crimea, the southern regions of the European part of Russia (Astrakhan and Rostov regions, Krasnodar and Stavropol territories), Ukraine, southern Western Europe, the countries of the Middle East, Central Asia, China, and Africa. In 80% of cases, people aged 20 to 60 years get sick.

Pathogenesis and pathological anatomy.

The entry point for infection is damaged skin. at the site of a tick bite or contact with the blood of a patient (human or animal) containing the virus during the height of the disease. After inoculation of the virus, its replication occurs in the cells of the reticulohistiocytic system, followed by massive secondary viremia and multiorgan dissemination. This causes the development of a nonspecific general toxic syndrome, signs of damage to internal organs and increased permeability of the capillary wall with the occurrence of thrombohemorrhagic syndrome of varying severity.
As a result of damage to endothelial cells, damage to the bone marrow with inhibition of leukopoiesis and platelet formation, as well as due to the development
thrombohemorrhagic syndrome, multiple extensive hemorrhages occur in the skin, mucous membranes, lungs and other internal organs.
During pathomorphological examination, multiple hemorrhages are found in the mucous membranes of the stomach and intestines, as well as in the brain and its membranes, where hemorrhages reach 1.0 - 1.5 cm, damaging the medulla (small hemorrhages throughout the brain). Hemorrhages are also found in other organs (lungs, kidneys, etc.). Dystrophic and necrotic changes in the myocardium, hepatocytes, and nephrocytes are characteristic. Not only the meninges, but also brain tissue can be affected.
Convalescents develop immunity.
CLINICAL MANIFESTATIONS AND COURSE.
Incubation period with transmissible infection it lasts 1 - 3 days (up to 9), and with blood-contact infection - 5 - 6 days (up to 14).
Initial period (feverish) lasts 3 - 6 days (up to 7). There are no prodromal phenomena. The disease begins suddenly with an increase in body temperature to 39 - 40 ° C (sometimes with stunning chills), the pulse lags behind the temperature, slow (bradycardia up to 40 beats). Patients are usually excited, the face, mucous membranes, neck and upper chest are hyperemic, the lips are dry, and herpes labialis is often noted. Against the background of high fever, patients complain of headache, fatigue, weakness, pain in the epigastrium, muscles and joints, photophobia. Sometimes there are mild catarrhal symptoms from the upper respiratory tract. Dry mouth and repeated vomiting are very characteristic, debilitating the patient and not associated with food intake, which makes one think about damage to the stomach and the autonomic nervous system of the solar plexus; Abdominal pain is common and diarrhea is possible. This is due to a nonspecific general toxic response to viremia. A number of patients experience pain in the lower back and when tapping the lumbar region. Hematological changes during this period are manifested by leukopenia with a neutrophilic shift in the leukocyte formula to the left, thrombocytopenia, and an increase in ESR.
Many patients experience generalized enlargement of the lymph nodes. A constant symptom of CCHF is fever, which lasts on average 7 - 8 days (up to 10 - 12 days). The temperature curve is especially typical for this hemorrhagic fever. In particular, when hemorrhagic syndrome appears, there is a decrease in body temperature to subfebrile, after 1 - 2 days the body temperature rises again, which causes the “double-humped” temperature curve characteristic of this disease. That is, the disease is characterized by a two-phase course with the development of erased, mild, moderate and severe forms of the disease.
Heightened period (hemorrhagic) often develops after a short-term, within 1 - 2 days, decrease in temperature, followed by an increase and the appearance of a hemorrhagic rash. At this stage of the disease, a pronounced hemorrhagic syndrome is detected in the form of a petechial rash on the lateral areas of the body, in the area of ​​​​large folds and limbs. At the beginning, the rash appears in the armpits, elbows, and on the inner thighs, and then spreads to the entire skin and mucous membranes (enanthems, hemorrhages in the conjunctiva). The face becomes pale, puffy, acrocyanosis, cyanosis, and large hemorrhages in the skin appear. In severe forms of CCHF, purpura, ecchymoses are observed, bleeding from the gums, nose, stomach, uterus, intestines, lungs (hemoptysis), and hemorrhages at injection sites are typical. Bradycardia gives way to tachycardia, blood pressure decreases, and oliguria appears.
Rice. 2. Multiple hemorrhages on the arm.
Patients are depressed, pale, the face becomes puffy, acrocyanosis, tachycardia and severe arterial hypotension are detected. The prognosis is unfavorable for the appearance of massive gastric and intestinal bleeding. The condition of the patients becomes even more severe, and disturbances of consciousness are noted. In 10 - 25% of cases, meningeal symptoms are observed, delirium and agitation of patients, convulsions with subsequent development of coma are possible.
The liver is often enlarged and painful on palpation, jaundice and hyperfermentemia are possible. In severe forms of the disease, oliguria, albuminuria, microhematuria, hyposthenuria, azotemia, and a positive Pasternatsky sign often develop.
The hemogram of patients during this period is characterized by anemia, leukopenia (less often leukocytosis), severe thrombocytopenia (up to 40,000 per μl). ESR is unchanged, prothrombin is reduced. At the same time, an increase in hematocrit, residual nitrogen, aminotransferase activity and signs of metabolic acidosis are often detected. Significant thrombocytopenia and high hematocrit values ​​may indicate a poor prognosis. In the urine - erythrocyturia, proteinuria.
Main complications:■ pneumonia; ■ pulmonary edema; ■ thrombophlebitis; ■ decreased urinary function, often without acute renal failure; ■ profuse bleeding; ■ shock, ■ sepsis.
Death may occur in the 2nd week of the disease as a result of the development of shock, renal-hepatic and respiratory failure. The duration of the febrile period is 4 - 12 days.
Convalescence period long-lasting, up to 1-3 months, it is characterized by an asthenic symptom complex. In some patients, performance is restored within 1 to 2 years.
Abortive forms of CCHF without hemorrhagic syndrome, but with a temperature curve typical of CCHF (two-humped) are often observed in endemic areas.
Forecast. The disease is characterized by a severe course. Mortality ranges from 1 - 5 to 10 - 15%, and with blood-contact infection it reaches 60 - 90%.
DIAGNOSTICS.
CCHF can be assumed with the development of an acute febrile illness followed by the emergence (after temperature remission) of a progressive
hemorrhagic syndrome in individuals at high risk of infection or in patients who have had contact with blood-containing material from patients from endemic foci. Clinical diagnosis is often based on endemic data. An important basis for the diagnosis are epigastric pain, bradycardia in the initial period of the disease, and repeated vomiting. Characteristic changes in peripheral blood: leukopenia with a shift to the left, thrombocytopenia, normal ROE.
For specific diagnosis, virological and serological methods are used. Isolation of the virus from the blood of patients in the initial period of the disease (1st week) is carried out using cell lines of animal embryos in laboratories with level IV safety. It is possible to detect virus antigens in the tissues of dead people using immunohistochemical methods. Detection of virus RNA in the blood of patients using PCR has been developed.
Serodiagnosis in the early stages of the disease (after 5-6 days) is based on the determination of specific IgM class antibodies in the blood serum of patients using ELISA; in the later stages of the disease, an increase in antibody titer is detected in RSC, RTGA, RSC and MFA. The IF method, radioimmune and PCR methods are promising. When assessing the results of serological studies, it is necessary to take into account that antiviral IgM can persist for 4 months, and anti-IgG for 5 years after CCHF.
Differential diagnosis carried out with other hemorrhagic fevers, leptospirosis, viral encephalitis, meningococcemia, typhus, sepsis. Mortality in different regions of the Russian Federation ranges from 1 - 5% to 60 - 80%.
TREATMENT.
Patients with CCHF should be treated in an infectious diseases hospital, and in severe cases of the disease - in an intensive care unit, observing the prevention of blood-contact infection.
Treatment of CCHF must be comprehensive. Detoxification and anti-shock therapy are carried out, and transfusions of fresh frozen blood plasma are prescribed. The positive effect of the use of specific serotherapy by administering the blood serum of those who have recovered from CCHF, taken 20 to 45 days after the onset of the disease, has been proven: the serum is administered 20 ml intramuscularly for 3 days in a row (Chumakov M.P., 1944). The method is effective even in severe forms with massive intestinal bleeding, but is limited due to the difficulty of finding such donors. A high therapeutic effect from intravenous use has been established ribavirin.
In the initial stage detoxification therapy is used with a 5% glucose solution, polyionic solutions up to 1.5 liters per day; ascorbic acid is introduced up to 10 ml of a 5% solution, rutin. Plasma transfusion and hemodesa 100 - 200 ml per day are indicated. To reduce vascular permeability and intoxication, prednisolone is administered intravenously up to 100-120 mg per day, and symptomatic medications are prescribed.
During the period of bleeding administration of aminocaproic acid and fibrinogen is indicated (under the control of a coagulogram). With the onset of bleeding, transfusion of up to 500 - 700 ml of fresh citrated whole blood is mandatory; subsequently, taking into account the hemogram, separate administration of erythrocyte, leukocyte and platelet masses is used. Calculation of the volume of injected blood and its fractions is carried out taking into account the total blood loss and the deficiency of its individual components. Direct blood transfusions from a donor (close relative or volunteer) have not become widespread due to the risk of infection of the donor during the procedure.
During the period of convalescence General strengthening therapy and a complex of vitamins are indicated. Convalescents must remain on a gentle regimen for a long time. Those who have had mild forms of the disease receive exemption from work for 10 - 20 days, moderate forms - 1 - 1.5 months, severe forms - up to 2 months.
The prognosis improves somewhat with adequate treatment started early. In case of complications, they are treated depending on the type of complications. Patients with pneumonia and other focal infections are treated with antibiotics. In uncomplicated cases it is not indicated.
Prevention.
In CCHF outbreaks, a set of measures should be carried out to combat ticks and protect people from their attacks using repellents (lubricating the skin with diethylmethyltuluamide - DEET, impregnating clothing with permethrin). To prevent blood-contact infection from animals or sick people, barrier methods of protection (rubber gloves) are used. In laboratories, measures are taken to prevent airborne contamination of personnel; material containing blood from patients is disinfected before biochemical or microscopic examination. In Russia, an inactivated vaccine was developed from the brains of infected white suckling mice or rats, which was used for epidemiological indications. Clinical examination of those who have recovered from the disease is established for 1 - 3 years. Work associated with overheating and hypothermia should be avoided. Persons traveling to CCHF-endemic regions must strictly follow the specified rules for personal prevention of this serious disease.
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Crimean hemorrhagic fever (CCHF, Crimean-Congo fever) is an acute pathology of viral etiology, which is characterized by natural focality, a transmissible route of infection, a serious condition of the patient and thrombocytopenia in the blood. The disease manifests itself as high fever, pain in muscles and joints, hemorrhages on the skin, internal and external bleeding.

CCHF was first diagnosed in people who cut hay and harvested crops in Crimea. Initially, the disease was called “infectious capillary toxicosis.” In 1945, Academician Chumakov and his expedition established the viral etiology of the disease. The infection has another name - Crimea-Congo fever. This is due to the identification of a similar case in the Congo in 1956. A virus with a similar antigenic structure was found in the blood of a sick child. The microbe caused an outbreak of infection among local residents. Scientists have determined that it is completely identical to the virus identified in Crimea.

Crimean fever is a zoonotic infection transmitted by blood-sucking insects - ticks. This is a very dangerous disease with a high mortality rate, reaching 40% of the total number of sick people. The infection is most common in the steppe, forest-steppe and semi-desert zones. Most cases of CCHF were registered in countries with warm climates: in Crimea, the North Caucasus, China, Kazakhstan, the southern republics of the former USSR, in all countries of Central Asia and in African territories.

The infection begins acutely, develops rapidly and occurs with two febrile periods. The disease manifests itself as cephalgia, myalgia, arthralgia, hemorrhagic skin rash, hemorrhages and bleeding. Diagnosis of pathology is based on epidemiological data, clinical signs, and laboratory test results. Treatment of CCHF includes detoxification, immunotherapy, antiviral and hemostatic effects. After an illness, species-specific immunity remains.

Timely diagnosis and correct treatment largely determine the outcome of the pathology. In advanced cases, serious consequences develop: blood circulation is disrupted and multiple bleeding occurs. If medical assistance is not provided in time, the patient will die.

Etiology

Crimea-Congo hemorrhagic fever virus

The causative agent of CCHF is a microorganism from the arbovirus family, transmitted by ticks. It is spherical in shape and contains an RNA molecule. On the outside, the microbial cell is covered with a shell of fat-containing compounds, on the surface of which there is a nucleocapsid protein and two glycoproteins that determine the virulence and pathogenicity of the virus. After introduction into the body, it penetrates the cytoplasm of cells, where it begins to actively multiply and exert its pathogenic effect.

Arbovirus reproduces in two temperature ranges – 22-25°C and 36-38°C. Thanks to this feature, it is able to live in the body of insects, animals and humans.

The virus is resistant to some environmental factors. It remains viable for a long time when frozen and dried. The microbe is inactivated by solutions of disinfectants and fat solvents and instantly dies when boiled.

In laboratory conditions, the virus is cultivated in the cells of the kidney tissue of monkeys, hamsters, white mice and pigs.

Epidemiological features

The natural reservoir of infection is rodents, hares, hedgehogs, gophers, jerboas, foxes, cows, goats, horses, birds, dogs, and the carriers of the pathogen are ixodid ticks Hyalomma marginatus. They are lifelong carriers of the infection and are able to transmit it to their offspring at the egg stage.

life cycle of the tick virus and transmission routes of the Crimean-Congo hemorrhagic fever virus

Tick ​​vectors usually live in steppes and forest-steppe zones. But they often penetrate into personal plots or outbuildings.

The spread of infection occurs:

• Transmissible - during a tick bite,
• By contact - when crushing an infected tick during its removal from animals,
• By aspiration - when shearing sheep and inhaling infected air.

Hospital-acquired infections are known to be caused by the use of poorly sterilized medical instruments. Isolated cases of infection due to consumption of infected milk have been recorded. The patient's full clinical picture developed within a few hours.

Susceptibility to CCHF is very high. The disease mainly affects agricultural workers who care for animals and prepare hay, livestock breeders, shepherds, milkmaids, veterinarians, hunters, housewives, pensioners and employees who have cattle on their farm, as well as doctors who come into contact with patients with this infection. Men 20-50 years old are most often infected. In children, the disease occurs extremely rarely and is very severe. This is due to the functional weakness of the not yet fully formed immune system.

The peak incidence occurs in the spring-summer season, namely in the months from March to September, when tick activity increases and the period of agricultural work begins.

Pathogenesis

Pathomorphological changes in CCHF correspond to the signs of vasculitis of infectious etiology and are accompanied by dystrophic processes in the internal organs and the formation of necrotic foci.

Pathogenetic links of infection:

1. Introduction of a pathogenic agent into the human body through a transmissible route,
2. Accumulation of microbes in tissue macrophages,
3. Reproduction of viruses inside cells,
4. Release of microorganisms into the systemic circulation,
5. Viremia,
6. Toxinemia,
7. Development of intoxication syndrome,
8. Damage to vascular endothelial cells,
9. Increased endothelial permeability,
10. Leakage of red blood cells into tissues
11. Hemorrhages,
12. Internal and external bleeding,
13. Intravascular thrombosis,
14. Development of disseminated intravascular coagulation syndrome,
15. Dysfunction of organs and systems,
16. Hemorrhages in the liver, kidneys, lungs, brain, under the skin.

Pathoanatomical changes found at autopsy include: multiple hemorrhages in the mucous membranes of parenchymal organs, the gastrointestinal tract, and the brain without signs of inflammation, as well as hyperemia of the meninges with foci of hemorrhage and tissue destruction.

Clinical picture

CHF has an acute onset and severe course. The pathology clinic includes signs of intoxication and hemorrhagic syndromes.

The length of the incubation period depends on the method of infection. If a person is bitten by a tick, incubation is three days. If there is a contact route of infection, the first symptoms will appear only by the 7th day of the disease. With weak immunity, the incubation period can be reduced to 1 day.

In patients, the body temperature rises sharply to febrile levels, cephalgia, shaking chills, hyperemia of the face, pharynx and conjunctiva, severe weakness, dizziness, myalgia, arthralgia, epigastric pain, dyspepsia, bradycardia, photophobia, agitation and aggressiveness, followed by apathy and fatigue occur. , drowsiness. In more rare cases, the initial stage of CHF is manifested by paresthesia and pain in the legs, catarrhal symptoms - runny nose, sore throat, as well as confusion.

After a couple of days, the body temperature returns to normal or remains subfebrile, and then a second wave of fever occurs, accompanied by manifestation hemorrhagic manifestations. Patients experience bleeding and hemorrhage. Bruises, petechiae, hemorrhages, purpura, and ecchymoses appear on the skin and mucous membranes. Hemorrhagic rashes on the skin are called exanthema, and on the mucous membrane - enanthema. The rashes are localized mainly on the lateral surfaces of the torso, abdomen, limbs, in the axillary and inguinal folds. Then the gums and injection sites begin to bleed, bleeding from the nose, uterus, and intestines occurs.

Patients complain of hemoptysis, abdominal and lumbar pain, heaviness in the right hypochondrium, diarrhea, dry mouth, and vomiting. Later, jaundice, oliguria, and lethargy develop. Patients experience increased heart rate and decreased blood pressure. The hyperemic face begins to turn pale. Signs of acrocyanosis appear on it - blue lips, nose, ears and fingers. In patients, the lymph nodes and liver become enlarged, meningeal and convulsive syndromes, confusion, and coma occur.

Fever usually lasts 10-12 days. When the body temperature returns to normal and bleeding stops, recovery occurs. At the same time, patients remain exhausted and weakened for several months. Asthenic syndrome persists for 1-2 years. All this time, those who have recovered from the disease suffer from occasional dizziness, low blood pressure, and tachycardia.

The disease occurs in one of three forms - mild, moderate and severe. This depends on the severity of the manifestations of hemorrhagic syndrome. In some patients, its symptoms may be completely absent. In such cases, the clinical picture of a febrile illness consists of manifestations of intoxication syndrome. Characteristic changes are detected in the blood of patients - thrombocytopenia and leukopenia. It is these data that are important when making a diagnosis.

If the outcome of the disease is unfavorable, deadly complications develop. These include:

• Septic conditions,
• Edema of the lung and brain tissue,
• Pneumonia,
• Acute hepatic-renal dysfunction,
• Thrombosis and inflammation of veins,
• Myocarditis,
• Massive bleeding and excessive blood loss,
• State of shock.

Diagnostic measures

Diagnosis of Congo-Crimean hemorrhagic fever consists of examining the patient, listening to complaints and collecting an epidemiological history. Specialists need to establish the fact of a tick bite and the patient’s stay in an endemic area in the spring and summer.

To confirm or refute the suspected diagnosis, a number of laboratory tests are carried out.

1. Hemogram- signs of anemia, thrombocytopenia, leukopenia, neutropenia, elevated ESR.
2. Clinical urine analysis– proteinuria, oliguria, hyposthenuria and hematuria.
3. Blood test for biochemical markers of the liver - an increase in transaminase levels.
4. Coagulogram- a significant decrease in coagulation factors, platelet and coagulation components of hemostasis, fibrinogen and prothrombin levels.
5. Immunogram– determination of IgM and IgG titers to the CCHF virus by performing an enzyme-linked immunosorbent assay.
6. PCR- determination of virus RNA in biomaterial from a patient.
7. Serological reactions– complement fixation, indirect hemagglutination and indirect immunofluorescence in the dynamics of the disease using the method of paired sera. A serological test allows you to determine the amount of antibodies to the pathogen.
8. Virological research- bioassay on white mice, hamsters or guinea pigs. The virus isolated from the patient is introduced into the body of laboratory animals for the purpose of subsequent observation.

Treatment

All patients with suspected CCHF are hospitalized in the infectious diseases department and isolated in a closed box. Hospital staff undergo special training to care for such patients. Doctors prescribe them strict bed rest, diet and complete exclusion of physical activity.

Treatment of CCHF is detoxification, antiviral, immunomodulatory and hemostatic. Diet therapy involves eating easily digestible foods. Patients are recommended low-fat broths and soups, water-based porridges, fruit and vegetable purees. When the patient’s condition has stabilized, boiled meat, fish, and fermented milk products are introduced into the diet.

Patients are prescribed:

Video: diagnosis and treatment of Congo-Crimean hemorrhagic fever

Prevention and prognosis

To prevent infection and the development of pathology, it is necessary to fight the vectors - ticks. To do this, disinfestation measures are carried out: premises where livestock are kept, as well as pastures located on the territory of a natural outbreak, are treated with acaricides. The destruction of ticks that transmit infection is an ineffective measure.

If a tick bites a person, you should immediately go to the hospital. Employees of the infectious diseases department where the patient is located must carefully perform invasive procedures, use only disposable needles and syringes, and observe safety precautions when working with patient biomaterial. Emergency prophylaxis for persons in contact with contaminated blood is carried out by administering immunoglobulin synthesized from convalescent serum.

For preventive purposes, Rospotrebnadzor employees constantly monitor the condition of natural foci of infection and conduct sanitary education among the population. Specific prevention consists of vaccination, which is indicated for residents of endemic regions for CCHF and tourists planning to visit them.

The prognosis of CCHF is ambiguous. It is determined by the time of hospitalization, treatment tactics, and the quality of patient care. The rapid progression and severe course of the pathology leads to the early development of life-threatening complications. If treatment and diagnostic measures are delayed and the patient begins to bleed, death may occur. To save the patient's life, it is necessary to start treatment on time.

CCHF is a dangerous disease that requires immediate hospitalization and therapy. If you miss time, you can lose the patient. Serious complications leading to death develop rapidly. To avoid progression of the disease, it is necessary to consult a doctor at the first symptoms. Recently, the incidence of CCHF in our country has increased significantly. This is due to poor quality anti-epidemic measures and the lack of proper treatment of livestock against ticks.