Dengue incubation period. Dengue fever: treatment

Dengue(synonyms: dengue-awn - German, French, Spanish; dangy - fever, breakbonefever - English; denguero - Italian, dengue fever, bonebreaker fever, joint fever, giraffe fever, five-day fever, seven-day fever, date disease) - spicy viral disease, occurring with fever, intoxication, myalgia and arthralgia, exanthema, lymphadenopathy, leukopenia. Some variants of dengue occur with hemorrhagic syndrome. Refers to vector-borne zoonoses.

The causative agents of dengue belong to viruses of the Togaviridae family of the Flavivirus genus (arboviruses of antigenic group B). They contain RNA, have a bilayer lipid shell of phospholipids and cholesterol, the virion size is 40-45 nm in diameter. Inactivated when treated with proteolytic enzymes and when heated above 60°C, under the influence ultraviolet irradiation. There are 4 known types of dengue virus, different antigenically. Dengue viruses are antigenically related to viruses yellow fever, Japanese and West Nile encephalitis. It multiplies on tissue cultures and kidney cells of monkeys, hamsters, KB, etc. In the blood serum of patients, the virus persists at room temperature for up to 2 months, and dried for up to 5 years.

Over the past 10-15 years, there has been a significant increase in incidence in various regions. Significant dengue outbreaks have been reported in China People's Republic, Vietnam, Indonesia, Thailand and Cuba. During an outbreak in Cuba in 1981, dengue fever affected nearly 350,000 people, about 10,000 of whom had the more severe hemorrhagic form, and 158 patients died (mortality rate 1.6%). In the People's Republic of China, during the 1980 epidemic, 437,468 people fell ill (54 died). During the epidemic outbreak of 1985-1986. 113,589 people fell ill (289 died). The reasons for the rise in incidence remain unclear, despite the great interest in the problem of dengue fever (during the period 1983-1988, 777 works were published in periodicals, in addition, the problem of dengue was discussed in 136 books).

Source of infection serve a sick person, monkeys and possibly bats.

Infection is transmitted in humans by Aedes aegypti mosquitoes and in monkeys by A. albopictus. The A. aegypti mosquito becomes infectious 8-12 days after feeding on the blood of a sick person. The mosquito remains infected for up to 3 months or more. The virus is able to develop in the body of a mosquito only at an air temperature of at least 22°C. In this regard, dengue is common in tropical and subtropical regions (from 42° north to 40° south latitude). Dengue is found in countries of South and Southeast Asia, Oceania, Africa, Caribbean. Mostly children, as well as newcomers to the endemic area, become ill.

Pathogenesis. The virus enters the body through the skin when a person is bitten by an infected mosquito. At the site of the infection gate, after 3-5 days, limited inflammation occurs, where the virus multiplies and accumulates. In the last 12 hours of the incubation period, penetration of the virus into the blood is noted. Viremia continues until the 3-5th day of the febrile period. Dengue can occur in classical and hemorrhagic forms. There is no strict relationship between the type of virus and the clinical picture. Dengue viruses of types 2, 3 and 4 were isolated from patients with the so-called Philippine hemorrhagic fever; in Singapore hemorrhagic fever, all 4 types were isolated; when assessing the etiology of Thai hemorrhagic fever, at one time they wrote about new types of dengue virus (5 and 6). The presence of these types of virus was not subsequently confirmed.

It has now been established that dengue hemorrhagic fever and dengue shock syndrome can be caused by all four serotypes of the dengue virus. In the pathogenesis of the disease, a particularly important role is played by the introduction of viruses of serotypes 1, 3 or 4 into the human body, followed a few years later by serotype 2. Immunological factors are of particular importance in the development of dengue hemorrhagic fever. Enhanced growth of dengue virus serotype 2 occurs in mononuclear phagocytes obtained from the peripheral blood of immunized donors or in cells from nonimmunized donors in the presence of subneutralizing concentrations of dengue virus or cross-heterotypic antibodies to flavoviruses. Virus-antibody complexes are attached to and then incorporated into mononuclear monocytes via Fc receptors. Active replication of the virus in these cells can lead to a series of secondary reactions (activation of complement, the kinin system, etc.) and the development of thrombohemorrhagic syndrome. Thus, hemorrhagic forms occur as a result of re-infection of local residents or primary infection of newborns who received antibodies from the mother. The interval between primary (sensitizing) and repeated (resolving) infection can range from 3 months to 5 years. Primary infection with any type of virus results in the classic form of dengue. New arrivals to the endemic focus only become ill with the classic form of dengue.

Hemorrhagic form develops only among local residents. In this form, predominantly small vessels are affected, where endothelial swelling, perivascular edema and mononuclear cell infiltration are detected. Increased vascular permeability leads to disruption of plasma volume, tissue anoxia, and metabolic acidosis. With vascular damage and disruption state of aggregation blood is associated with the development of common hemorrhagic phenomena. In more severe cases Multiple hemorrhages occur in the endo- and pericardium, pleura, peritoneum, gastric and intestinal mucosa, and in the brain.

The dengue virus also has toxic effect, which is associated with degenerative changes in the liver, kidneys, and myocardium. After an illness, immunity lasts about 2 years, but it is type-specific; repeated illnesses are possible in the same season (after 2-3 months) due to infection with a different type.

Symptoms and course. The incubation period lasts from 3 to 15 days (usually 5-7 days). The disease usually begins suddenly. Only in some patients, mildly expressed prodromal phenomena in the form of weakness and headache are observed within 6-10 hours. Usually among full health chills, pain in the back, sacrum, spine, joints (especially the knees) appear. Fever is observed in all patients, body temperature quickly rises to 39-40°C. Severe adynamia, anorexia, nausea, dizziness, insomnia are noted; in most patients - hyperemia and pastiness of the face, injection of scleral vessels, hyperemia of the pharynx.

By clinical course A distinction is made between the febrile form of dengue (classical) and hemorrhagic dengue fever.

Classic dengue fever has a benign course, although some patients (less than 1%) may develop coma with respiratory arrest. With classic dengue fever, the pulse dynamics are characteristic: at first it is rapid, then from the 2-3rd day bradycardia appears up to 40 beats/min. Significant leukopenia (1.5-109/l) with relative lymphocytosis and monocytosis, thrombocytopenia is observed. In most patients, peripheral lymph nodes are enlarged. Severe arthralgia, myalgia and muscle rigidity make it difficult for patients to move. By the end of 3 days, body temperature drops critically. Remission lasts 1-3 days, then the body temperature rises again and the main symptoms of the disease appear. After 2-3 days, body temperature drops. The total duration of fever is 2-9 days. Characteristic symptom dengue - exanthema. It can sometimes appear during the first febrile wave, more often during the second increase in body temperature, and sometimes during the period of apyrexia after the second wave, on the 6-7th day of illness. However, in many patients, dengue can occur without a rash. Exanthema is characterized by polymorphism. More often it is small-papular (measles-like), but can be petechial, scarlet-like, or urticarial. The rash is profuse, itchy, first appears on the torso, then spreads to the limbs, leaving behind peeling. Elements of the rash persist for 3-7 days. Hemorrhagic phenomena are rare (in 1-2% of patients). During the convalescence period, asthenia, weakness, decreased appetite, insomnia, muscle and joint pain remain for a long time (up to 4-8 weeks).

Dengue hemorrhagic fever (Philippine hemorrhagic fever, Thai hemorrhagic fever, Singapore hemorrhagic fever) is more severe. The disease begins suddenly, the initial period is characterized by fever, cough, anorexia, nausea, vomiting, abdominal pain, sometimes very severe. The initial period lasts 2-4 days. In contrast to the classic form of dengue, myalgia, arthralgia and bone pain are rare. During the examination, an increase in body temperature to 39-40°C and above is noted, the mucous membrane of the tonsils and back wall the pharynx is hyperemic, enlarged lymph nodes are palpable, the liver is enlarged. During the peak period, the patient's condition quickly deteriorates and weakness increases. To assess the severity of the process, WHO proposed clinical classification dengue hemorrhagic fever. There are 4 degrees, which are characterized by the following clinical symptoms.

Degree I. Fever, symptoms of general intoxication, the appearance of hemorrhages in the elbow when a cuff or tourniquet is applied ("tourniquet test"), in the blood - thrombocytopenia and blood thickening.

Degree II. There are all the manifestations characteristic of grade I + spontaneous bleeding (intradermal, from the gums, gastrointestinal), when examining blood - more pronounced hemoconcentration and thrombocytopenia.

Grade III. See Grade II + circulatory insufficiency, agitation. Laboratory: hemoconcentration and thrombocytopenia.

Grade IV. See Grade III + deep shock (blood pressure 0). Laboratory - hemoconcentration and thrombocytopenia.

Degrees III and IV are characterized as dengue shock syndrome. When examining a patient during the height of the disease, the patient’s anxiety is noted, his limbs are cold and sticky, and his torso is warm. There is pallor of the face, cyanosis of the lips, in half of the patients petechiae are detected, most often localized on the forehead and on the distal parts of the extremities. Less commonly, macular or maculopapular exanthema appears. Blood pressure decreases, pulse pressure decreases, tachycardia, cyanosis of the extremities appear, and pathological reflexes appear. Death often occurs on the 4th-5th day of illness. Hematemesis, coma, or shock are poor prognostic signs. Widespread cyanosis and seizures are the terminal manifestations of the disease. Patients who survive the critical period of the disease (the height of the disease) quickly begin to recover. There are no relapses of the disease. Dengue hemorrhagic fever is more common in children. The mortality rate for this form is about 5%.

Complications- encephalitis, meningitis, psychosis, polyneuritis, pneumonia, mumps, otitis media.

Diagnosis and differential diagnosis. When recognizing, epidemiological prerequisites are taken into account (stay in an endemic area, morbidity level, etc.). During epidemic outbreaks clinical diagnosis is not difficult and is based on characteristic clinical manifestations (double-wave fever, exanthema, myalgia, arthralgia, lymphadenopathy).

Diagnosis of dengue hemorrhagic fever is based on criteria developed by WHO. These include:

Fever - acute onset, high, persistent, lasting from 2 to 7 days;

Hemorrhagic manifestations, including at least a positive tourniquet test and any of the following criteria: petechiae, purpura, ecchymosis, epistaxis, gingival bleeding, bloody vomiting or melena;

Enlarged liver; thrombocytopenia not more than 100x10 9 /l, hemoconcentration, increase in hematocrit by not less than 20%.

Criteria for diagnosing dengue shock syndrome - fast, weak pulse with decreasing pulse pressure(no more than 20 mm Hg), hypotension, cold, clammy skin, anxiety. The WHO classification includes the previously described four degrees of severity. With classic dengue fever, mild symptoms may occur. hemorrhagic symptoms not meeting WHO criteria for the diagnosis of dengue hemorrhagic fever. These cases should be considered dengue fever with hemorrhagic syndrome, but not dengue hemorrhagic fever.

Laboratory diagnosis is confirmed by the isolation of the virus from the blood (in the first 2-3 days of illness), as well as by an increase in antibody titer in paired sera (RSC, RTGA, neutralization reaction).

Differentiate from malaria, chikungunya fever, pappataci, yellow fever, other hemorrhagic fevers, infectious-toxic shock with bacterial diseases(sepsis, meningococcemia, etc.).

In addition, information can be obtained here:

Dengue is an acute arboviral disease of hot countries, characterized by two-wave fever, arthralgia and myalgia, exanthema, polyadenitis, leukopenia and often hemorrhagic syndrome. Dengue fever is transmitted by mosquitoes. Distributed in the tropics and subtropics, especially in the countries of the southwestern Pacific. Severe forms Dengue fever has been reported in cities in Southeast Asia. Visitors rarely get sick.

Etiology

The causative agent of dengue is an RNA virus. There are 6 known serotypes. The virus is heat labile and sensitive to disinfectants, in human blood serum at - 70 °C and in dried form persists for up to 8-10 years. Strains adapted to mice are non-pathogenic to humans.

Pathogenesis

The pathogen enters the body when bitten by an infected mosquito. At the site of the bite, the virus multiplies and accumulates in the cells of the reticulohistiocytic system. Viremia lasts from last hours incubation until the 3-5th day of the febrile period. With the blood, the virus is introduced into the liver, kidneys, muscles, brain, connective tissue, etc. Cells affected by the virus undergo cytolysis with the re-release of the virus into the blood. During primary infection, dengue manifests itself only in the classical form; the hemorrhagic version of the disease occurs as a result of repeated infection.

Epidemiology

The source of infection is a sick person and monkeys, in which the infection can be latent. The patient is contagious during the period of viremia. The pathogen is transmitted by mosquitoes, which become infectious after 8-14 days and remain infectious for life. The virus develops in the body of a mosquito at an air temperature of at least 22 °C. This causes the disease to spread in hot countries between 42° north and 40° south latitude. Not found in the CIS.

Clinic

The disease occurs in two forms: classical dengue fever and dengue hemorrhagic fever. The incubation period lasts 3-15 days (usually 5-8). The disease begins acutely with chills and a rise in temperature to 39-41 °C.

From the 1st day, algic syndrome is expressed, especially strong retroorbital headache, as well as pain in muscles and joints (gait without bending the legs - “dandy”, “dandy”). There may be swelling and redness of small joints, nausea and vomiting.

Hyperemia and puffiness of the face, injection of scleral vessels, general erythema (“red fever”) and skin hyperesthesia are distinct. Peripheral lymph nodes are enlarged.

Tachycardia is noted, and from the 2-3rd day of illness - bradycardia. Leukopenia and thrombocytopenia are detected in the blood.

The internal organs are not significantly changed. By the 3-4th day the temperature drops, which is accompanied by heavy sweat.

The condition improves, but myalgia, arthralgia, typical gait, severe weakness (“lead cape on the shoulders”) persist. After 1-4 days, the temperature rises again, the main symptoms of the disease intensify. The second wave is easier and lasts 2-3 days.

In 80-90% of patients, during the second wave or immediately after a drop in temperature, a profuse maculopapular (“flying measles”), urticarial or scarlet-like (“rheumatic scarlet fever”) rash appears, accompanied by itching and leaving pityriasis-like peeling. The total duration of the disease is 6-10 days.

Convalescence lasts for 3-8 weeks (asthenia, pain in joints and muscles). The hemorrhagic form is more severe.

In addition to the described clinic, during the first febrile wave, more severe intoxication is observed. In most patients, the size of the liver increases.

From the 2nd day of illness to varying degrees expressed hemorrhagic syndrome: petechial rash, hemorrhagic purpura, extensive ecchymoses, bleeding gums, nasal, pulmonary, gastrointestinal bleeding. In 20-40% of patients, infectious-toxic shock develops with symptoms of depression of the central nervous system, cardiovascular failure, blood thickening, hypoproteinemia, oligo- or anuria.

The mortality rate for classic dengue fever does not exceed 0.1-0.5%, for hemorrhagic fever it reaches 5%, and among children - 15-20%.

Differential diagnosis

When conducting differential diagnosis nosogeography and the characteristic symptom complex of the disease should be taken into account - two-wave fever, arthralgia, myalgia, appearance and gait of patients, exanthema, lymphadenopathy. During epidemic outbreaks, diagnosis is not difficult. Difficulties arise with sporadic diseases. Pappataci fever is similar to dengue: the onset of the disease, the presence of headache and muscle pain, seasonality, and place of spread. Classic dengue fever is distinguished from pappataci by the second febrile wave, the presence of changes in the joints, exanthema, altered gait, and lymphadenopathy.

In addition, pappataci differs from dengue by Taussig's symptom and the always present injection of scleral vessels in the form of a triangle at the outer corners of the eyes (Pick's symptom). The initial symptoms of malaria are chills, rapid rise fever, headache and muscle pain, leukopenia - may resemble the symptom pathology of the first dengue fever wave. However, malaria is characterized by an early increase in the size of the spleen and liver, subsequent periodicity of characteristic febrile attacks (3- and 4-day malaria), and a long duration of the disease. Dengue is also distinguished from malaria by a profuse rash, polyadenitis, a typical gait, and a change from tachycardia to bradycardia.

The last two symptoms and the absence of jaundice are the main ones distinctive features hemorrhagic forms of dengue. The diagnosis is sometimes determined through laboratory tests. Dengue fever differs from influenza in its seasonality associated with the flight of mosquitoes, the absence of catarrhal symptoms, and appearance and the gait of patients, the presence of rash, polyadenitis. The presence of a rash with dengue makes it necessary to differentiate it from measles, scarlet fever, and rubella.

Dengue is distinguished from these diseases by severe headache, retro-orbital pain, muscle and joint pain, and a characteristic gait. In addition, unlike measles, dengue fever does not have pronounced catarrhal symptoms of the upper respiratory tract(cough, runny nose) Velsky - Filatov - Koplik spots, clear phasing (day by day) of rashes. The measles rash is not accompanied by itching. Dengue differs from scarlet fever by the absence of a bright sore throat, severe pain when swallowing, a pale nasolabial triangle, and a “crimson” tongue.

With scarlet fever, the fever does not have a two-wave character; there is leukocytosis in the blood, not leukopenia. Leptospirosis from dengue help to distinguish the duration of the disease, symptoms of liver and kidney damage, an increase in the size of the spleen, the appearance of jaundice, typical “scleritis”, leukocytosis in the blood, the presence of leptospira in the blood and urine.

Prevention

Prevention - protection from bites of disease carriers.

Diagnostics

The diagnosis of dengue fever is confirmed by the isolation of the virus from the blood of newborn white mice (in the first 48 hours of the disease) and an increase in the antibody titer in paired sera in the RTGA, RTPGA, RSK and in the neutralization reaction.

Attention! The described treatment does not guarantee positive result. For more reliable information, ALWAYS consult a specialist.

Dengue fever, or joint fever, is a natural focal infectious diseases and is caused by a group of arboviruses (a type of virus carried by arthropods). Depending on the form, it occurs like the flu with a rash on the body, myalgia and joint pain, or is accompanied by hemorrhagic syndrome, spontaneous bleeding, shock, collapse, and often leads to death. The disease is caused by the dengue virus, which is transmitted by tropical mosquitoes. There are no etiotropic drugs that affect it, so therapy is based on eliminating symptoms and the use of hemostatic and anti-shock measures.

Features of the disease

Dengue fever is a vector-borne disease caused by the virus of the same name, found in tropical and subtropical climate zones. Cases of mass infection have been identified in 110 countries, Australia, Africa and Oceania, on the South American continent, southeast Asia, and the Mediterranean coast.

Outbreaks of epidemics depend on the seasons and are observed during the rainy season. In endemic areas, usually in cities, up to several hundred thousand people become infected per year; precedents are recorded outside the hotspots during the migration of already infected people or the importation of carrier mosquitoes.

Fever manifests itself in two independent forms, differing in symptoms and consequences of infection:

• Classic. Accompanied febrile state, pain in the joints and muscles, the development of lymphadenitis (inflammation of the lymph nodes) and leukopenia (decreased white blood cells).
• Hemorrhagic. The disease is severe and is characterized by impaired vascular permeability. Hemorrhagic diarrhea develops due to a decrease in the number of platelets in the blood (thrombocytopenia) and a clotting defect. A decrease in circulating blood, proteins and electrolytes causes disturbances in organ function, which leads to shock, becoming the main cause of high mortality rates from the disease (in some areas - up to 50%).

There are cases of atypical and asymptomatic course of the disease, which is associated with the characteristics of the genes of individual individuals.

Reasons

Dengue virus

Fever develops as a result of invasion of the human body by an arbovirus from the family Togaviridae, genus Flavivirus. Science knows the virion serotypes from DEN-1-2-3-4, the fifth was established recently, in 2013. All of them differ in antigenic structure, differentiation occurs by the neutralization reaction and HRT titers.

Each strain causes similar symptoms of disease and can provoke both types of fever. Types 2 and 3 have the greatest cytopathic effect.

After the illness, immunity to the pathogen is developed for 2 years and resistance to other types for 2 months.

It has been noted that the hemorrhagic form often develops in people who have previously been ill when they are re-infected with a different serotype of the virus. Disorders of hemostasis, activation of complement and other parts of the system are most likely associated with the immune response and its damaging effects.

The shape of the dengue virus is spherical, the diameter is approximately 40-45 nm. It has an additional lipid bilayer with surface projections and single-stranded unsegmented RNA. Close relatives of the virion are the encephalitis, yellow fever, West Nile, and Zika viruses. All of these species are transmitted by arthropods and are therefore called arboviruses.

Extracellular agents are unstable to heat and die at a temperature of about 60 °C, but when dried or frozen to -70 °C they remain active for up to 10 years. They are sensitive to formaldehyde, ether, and are destroyed by proteolytic enzymes.

Transmission routes

Scheme of human infection

The source of infection is a sick person, primates and bats. The virus is transmitted by yellow fever mosquitoes of the genus Aedes, mainly Aedes aegypti, but also Aedes albopictus, Aedes scutellaris, Aedes polynesiensis.

Having penetrated the body of a blood-sucking insect with the patient’s blood, the pathogen develops in its intestines at a temperature of at least 22 °C, and after 8-14 days it spreads to other parts of the body. The mosquito becomes infectious by excreting the virus in its saliva throughout its life. Mosquitoes are active and reproduce at a temperature of 28 °C - during this period, the maturation time of the virus is reduced to a minimum.

A person is sensitive to the pathogen, so one insect bite is enough for infection. A person bitten becomes infectious the day before symptoms appear and spreads the infection for 5 days after the onset of the disease.

In countries where mosquito vectors live, endemic foci have formed, and outbreaks of epidemics occur periodically. Major pandemics occur when a new serotype of the virus is introduced into an area. The classic form is observed among the local population (mainly children) and visitors. Hemorrhagic fever primarily affects babies under one year of age who have passive immunity to another type of virus - they form a primary immune response. This group includes children who have previously had the disease and who develop a secondary type of reaction to the new serotype immune system. The virus is also dangerous for elderly and frail people with asthma and diabetes.

Symptoms

After a mosquito bite, the virus multiplies in the cells of the lymph nodes and endothelium lining the cavity blood vessels, destroying them. After 5 days, primary replication ends, and the particles enter the bloodstream - they enter the brain, heart, liver and other organs, causing fever and signs of intoxication.

The virus actively multiplies in monocyte cells and tissue macrophages. As a result, the affected particles produce enzymes that affect inflammatory proteins, change the permeability of the vascular walls and the blood coagulation system. These factors influence the development of the form of the disease and its clinical manifestations.

Classic shape

In the classic course of the disease, from the introduction of infection to the appearance of symptoms of the disease, on average, it takes from 3 days to two weeks, more often - 5-7 days. The short-term prodromal period is characterized by decreased appetite and weakness, conjunctivitis and rhinitis.

Often the disease manifests itself acutely, the following are observed:

• dizziness and intense headache concentrated behind the eyes;
• nausea with vomiting;
• chills and sharp increase temperatures up to 39°, often up to 41°;
• hyperemia and puffiness of the face, scleral injection, in 80% of patients the next day there is general erythema (redness skin caused by dilation of capillaries);
• enlargement of peripheral lymph nodes;
• severe pain in the vertebral and thigh muscles, in the joints (usually in the knees), sometimes noticeable swelling appears;
• rapid heartbeat (on the 2nd or 3rd day, tachycardia turns into relative bradycardia);
• coated tongue and redness on the palate.

Myalgia and arthralgia cause difficulty in movement, which is expressed in a change in gait - it becomes mannered and unnatural. This symptom formed the basis for the name of the disease: dengue - a distorted English word dandy (dandy). A decrease in leukocytes (leukopenia) and platelets (thrombocytopenia) is detected in the patient’s blood, and the presence of protein is detected in the urine.

After 3 or 4 days sharp decline temperature accompanied profuse sweating. The person’s well-being improves, but pain in the muscles and joints remains. The next wave of exacerbation provokes a repeated increase in temperature over 2-3 days, but with more low performance, which is associated with the penetration of pathogenic agents into organs.

During the period of apyrexia (between attacks) or during a new exacerbation (approximately on the 6th - 7th day of the disease), the erythema transforms into a multimorphic profuse rash in the form of urticaria or maculopapular formations, which are accompanied by pityriasis-like peeling.

The duration of the disease is up to 9 days until a sufficient amount of antibodies accumulates in the blood. Full recovery even with mild flow occurs after 3-4 weeks, in some cases it lasts up to two months, while signs of weakness, pain in muscles and joints remain.

Hemorrhagic form

Petechial rash

The duration of incubation of the hemorrhagic form is 4-10 days. The disease is manifested by a sharp increase in temperature, signs of intoxication, and cephalgia. Myalgia and arthralgia are often absent. The condition is accompanied by:

• conjunctivitis;
• nausea and vomiting;
• disturbance of consciousness (prostration);
• enlarged liver, abdominal pain;
• the appearance of a petechial rash on the skin after 2 or 3 days - the formation of hemorrhagic purpura and extensive areas of hemorrhage (ecchymosis) is possible.

Mainly small vessels are affected. Deterioration of blood aggregation in severe cases is manifested by bleeding gums and nosebleeds, hemorrhages in the internal organs: Gastrointestinal tract, lungs, myocardium.

Damage is indicated by bloody vomiting, black semi-liquid feces (melena), and blood in the urine (hematuria).

On the 3rd - 7th day, 40% of patients develop shock syndrome. It is believed to be caused by autoimmune processes. The condition is characterized by increased permeability of the vascular walls, which leads to plasma leakage, thickening of the blood and a decrease in protein in it (hypoproteinemia). Due to internal bleeding The patient's blood pressure drops, tachycardia develops, and intravascular coagulation accelerates with the formation of blood clots. Due to lack of blood, internal organs and the brain suffer, cyanosis, loss of consciousness, and sometimes convulsions are observed.

To determine the severity of disorders in the hemorrhagic course of Dengue fever and determine the prognosis, a classification has been created that divides the disease into stages:

Careful monitoring of patients is important. Urgently needed medical care when signs appear state of shock: weakening and increased heart rate, cold extremities, blue discoloration around the mouth (cyanosis), decreased blood pressure and a sharp increase in hematocrit. Excessive agitation or lethargy may be evidence of shock.

Complications

The virus is carried by blood into the liver, bone marrow, connective tissues, muscles, subjects them to cytolysis, also penetrates the nervous system, so complications may develop after the disease, which manifest themselves:

• otitis;
• thrombophlebitis;
• polyneuritis;
• psychosis;
• encephalitis or meningitis;
• cerebral edema;
• mumps, and in men - orchitis.

In pregnant women, the infection can cause miscarriage or fetal death.

Diagnostics

Making a diagnosis with the classic picture of the disease is not difficult and is based on typical manifestations Dengue fever:

• muscle and joint soreness;
• change in gait;
• two-wave flow;
• exanthema and enlarged lymph nodes.

Errors are possible with an atypical course of infection, when the high temperature remains at the same level and there are no rashes.

At hemorrhagic form preliminary diagnosis is established based on signs of intoxication and identification hemorrhagic diathesis. During examination, a “tourniquet test” helps confirm the assumption: positive reaction It is noted when, after applying a bandage or pneumatic cuff to measure pressure for 5 minutes, new spots of intradermal hemorrhage appear at the site of exposure. The presence of disease outbreaks, mosquito bites, and visits to endemic areas must be taken into account.

Early laboratory tests blood:

• confirm the presence of a virus in the body PCR method or through intracerebral infection of newborn young white mice;
• show the dynamics of the increase in antibodies to the type of virus introduced and its related species using serological studies of RPHA or RSK, enzyme immunoassay testing;
• reveal a decrease in the number of whites blood cells and platelet mass, metabolic disorders towards a decrease in pH (metabolic acidosis);
• show a moderate increase in the enzyme transaminase in the liver, which is associated with leukopenia and thrombocytopenia.

Severe fever leads to plasma leakage and blood thickening, so examination reveals an increase in hematocrit (red blood cells) and a decrease in albumin concentration (hypoalbuminemia), which indicates movement of exudate from the vascular space. If there is a noticeable accumulation of fluid in abdominal cavity and pleural effusion, pathology is detected during physical examination. The beginning of the process is difficult to detect, so ultrasound examination is used.

The classic version of Dengue fever is differentiated from influenza, yellow fever and pappataci fever, and in children - from measles and rubella. Hemorrhagic form - from hemorrhagic diathesis of non-infectious nature and other types of viral invasions, similar in clinical manifestations - chikungunya, Crimean and Omsk, yellow hemorrhagic fever, etc.

Treatment

Polyion solution

Etiotropic therapy for dengue fever is not carried out, since methods to combat the virus do not yet exist. Measures are being taken to relieve symptoms of the disease:

• For severe joint pain, painkillers are used.
• For insomnia, delirium and agitation, barbiturates, bromides or tranquilizers are prescribed.
• When dehydration develops due to high temperature and vomiting, frequent drinking is recommended. Pronounced violation acid-base balance towards a decrease in pH (acidosis) and an increase in hematocrit (red blood cells) requires infusion therapy: intravenous infusion of glucose, alkaline and electrolyte solutions of sodium chloride and bicarbonate, Hemodez.
• For severe pain and intoxication, the use of Prednisolone is indicated.
• When a secondary infection occurs, antibiotics are used.

In case of shock, oxygen therapy is indicated - the use of oxygen, cardiac medications. Plasma or plasma substitutes are administered intravenously until recovery is achieved. normal indicators body temperature, respiration and pulse. Polyionic solutions are used until the hematocrit level decreases to 40%.

Prognosis and prevention

In sporadic cases of dengue fever, the prognosis is usually favorable. During extensive epidemics, 0.5% of deaths were recorded; during periods of individual outbreaks, mortality reached 2 and even 5%, mainly in children. With the hemorrhagic form, about 40% of patients die.

Disease prevention in epidemic areas includes the following measures:

• extermination of mosquitoes and treatment of areas where offspring live;
• the use of fumigators, repellents and nets to block access to the premises;
• wearing long sleeves to protect against bites;
• compliance sanitary standards and storing water in closed containers;
• isolation of patients and avoidance of contact with the carrier until the period of illness is over.

It is possible to prevent the spread of infection from endemic areas through quarantine measures.

Currently, the only vaccine against dengue fever is CYD-TDV, which is based on weakened strains of 4 serotypes of the virus. It is approved for use after 9 years, but its final qualification has not yet been carried out. Research results have shown that the effectiveness of vaccination in treating infection remains at the level of 60-79%. Controversy arises due to cases of severe disease development due to the use of the vaccine in children, therefore, further testing and new developments are required due to the discovery of a new fifth virion.

– a natural focal infection caused by arboviruses of the same name and occurring with a flu-like syndrome or hemorrhagic manifestations. Classic dengue fever is characterized by a two-wave rise in temperature, myalgia, arthralgia, lymphadenitis, exanthema, hemorrhagic - spontaneous bleeding. When diagnosing dengue fever, epidemiological and clinical data, the results of virological and serological tests are taken into account. Specific therapy and immunization have not been developed, so treatment of dengue fever is predominantly symptomatic.

General information

Dengue fever (bone disease, joint fever) – transmissible viral infection, occurring in two clinical forms - classical and hemorrhagic. Dengue fever is common in regions with tropical and subtropical climates: Southeast Asia, South America, Australia and Oceania, Mediterranean Sea etc. Every year, hundreds of thousands of cases of dengue fever are registered in endemic areas. Outside the area of ​​infection, imported cases of dengue fever occur, due to both the migration of infected individuals and the importation of infected mosquitoes. The classic form of dengue fever has a benign course, but the hemorrhagic form is characterized by high mortality.

Causes of dengue fever

Dengue virus (Dengue-virus) belongs to the arboviruses of antigenic group B, belonging to the genus Flavivirus, family Togaviridae. There are 4 known serovars of the pathogen (DEN-1, DEN-2, DEN-3, DEN-4), each of which is capable of causing both classical and hemorrhagic forms of dengue fever. After infection with one or another serotype of the virus, lifelong type-specific immunity remains, but this does not exclude the possibility of future infection with another serotype of the virus. Dengue-virus has single-stranded RNA, a bilayer lipid envelope, and the virion diameter is 40-45 nm. In its antigenic structure, the dengue virus is close to the viruses of yellow fever, West Nile and Japanese mosquito encephalitis. The dengue virus is resistant to freezing and drying, but is labile to heat, ultraviolet radiation, and proteolytic enzymes.

Reservoirs and sources of infection are sick people, monkeys, bats, and carriers of the virus are mosquitoes of the genus Aedes (A. albopictus and A. Aegypti, A. Polinesiensis, A. Cutellaris). Mosquitoes become infectious 8-12 days after blood-sucking and retain a lifelong ability to transmit the virus. Healthy people contract dengue fever through the bites of infected mosquitoes. IN to a greater extent Children under 2 years of age, elderly and frail people, as well as visitors, including tourists, are susceptible to dengue fever. Local residents of endemic areas and visitors fall ill mainly with classic dengue fever. Children who have previously had classic dengue, caused by types 1, 3 or 4 viruses, are more likely to become infected with severe dengue hemorrhagic fever when infected with the second type of virus.

After a mosquito bite, the virus multiplies within 3-5 days in regional lymph nodes and vascular endothelium. After the period of primary replication, viral particles penetrate into the blood, causing the development of viremia, which is clinically manifested by feverish intoxication syndrome. The second wave of fever is associated with the penetration of viruses into organs and tissues. Cupping clinical symptoms occurs as virus-neutralizing and complement-binding antibodies accumulate in the blood. In the hemorrhagic form of dengue fever, damage occurs mainly to small vessels, a violation of the aggregative state of the blood with the development of multiple hemorrhages in the membranes of the heart, pleura, gastrointestinal mucosa, and brain.

Dengue fever symptoms

Dengue fever can occur in two clinical variants: classic and hemorrhagic (without shock syndrome or with dengue shock syndrome). After the incubation period (from 3 to 15 days after a mosquito bite), a short-term prodromal period begins, during which malaise, headache, signs of rhinitis and conjunctivitis are noted. Sometimes acute manifestations occur against the background of complete well-being without previous symptoms.

In the classic form of dengue fever, chills develop and a rapid increase in body temperature to 39-41°C. During this period, patients experience nausea, anorexia, arthralgia, ossalgia and myalgia, which impede movement. Typical objective signs are bradycardia, lymphadenitis, hyperemia of the pharynx, injection of scleral vessels. After 3-4 days, body temperature drops sharply, and a short period of apyrexia occurs, lasting 1-3 days. Then a second wave of fever develops, accompanied by the same symptoms.

A typical symptom of classic dengue fever is exanthema, which appears during the first or second febrile wave. The rash is polymorphic, more often morbilliform, sometimes urticarial, scarlatiniform or petechial. Skin rashes abundant, localized on the trunk and limbs, accompanied by itching and peeling of the skin. Total duration acute period classic dengue fever is 7-9 days. The period of convalescence extends to 4-8 weeks, during which asthenia, insomnia, joint and muscle pain persist.

The hemorrhagic form of dengue fever, also known as Philippine, Singapore, and Thai hemorrhagic fever, has more severe course. In the initial period, just like in the classical form, there is an increase in temperature and intoxication. Pain in the joints and muscles occurs rarely, but severe abdominal pain and liver enlargement are common. On days 2-3, a petechial rash appears on the skin; in severe cases, spontaneous nasal, gingival, uterine, and gastrointestinal bleeding, hemorrhages in internal organs, and hematuria develop. On days 3-5 from the onset of fever, dengue shock syndrome may develop, accompanied by tachycardia, arterial hypotension, oligoanuria, disseminated intravascular coagulation syndrome, cyanosis and convulsions.

To determine the severity clinical manifestations and prognosis assessments distinguish 4 degrees of dengue hemorrhagic fever:

• I degree: clinical signs- feverish-intoxication syndrome and “positive tourniquet test”; laboratory tests - thrombocytopenia and hemoconcentration.
• II degree: clinical signs (optional) – bleeding (ecchymosis, from the nose, gums, genital tract, hematemesis, melena); laboratory signs– increase in thrombocytopenia and hemoconcentration.
• III degree: clinically – signs of circulatory failure, development of dengue shock; laboratory – increased thrombocytopenia and hemoconcentration.
• IV degree: dengue deep shock syndrome.

With dengue hemorrhagic fever, deaths are recorded in 5-20% of cases, mainly among children. In surviving patients, complications are possible in the form of polyneuritis, pneumonia, encephalitis, meningitis, mumps, otitis media, orchitis, thrombophlebitis, etc.

Diagnosis and treatment of dengue fever

The criteria developed by WHO allow one to suspect dengue fever in the event of the development of: a febrile syndrome that lasts 2-7 days; thrombohemorrhagic syndrome; thrombocytopenia (less than 100x109/l) and an increase in Ht by 20%; hepatomegaly and shock syndrome. The presence of epidemiological prerequisites (visits to endemic regions, mosquito bites, outbreaks of infection) and typical clinical symptoms (two-wave fever, arthralgia, myalgia, exanthema) are also taken into account. An additional criterion can be a positive “tourniquet test” (intradermal hemorrhage after applying a tourniquet or cuff in the elbow area).

Laboratory confirmation of dengue fever is carried out by isolating the virus from the patient’s blood using PCR and determining the increase in titer specific antibodies in paired sera over time using RSK, RNIF, RN, RTGA. Dengue fever should be differentiated from pappatachi and chikungunya fever, yellow fever, malaria, meningococcal infection, sepsis; in children - from measles, scarlet fever, rubella.

There is no etiotropic therapy for dengue fever, therefore therapeutic measures are mainly symptomatic in nature (taking antipyretics, antihistamines, detoxification). For the hemorrhagic form of dengue fever, hemostatic and anti-shock therapy, correction of disseminated intravascular coagulation syndrome, transfusion of red blood cells and platelets, and blood plasma are carried out. There is information about the effectiveness of parenteral administration of interferon in the early stages of the disease.

Prognosis and prevention of dengue fever

The classic form of dengue fever usually progresses favorably and ends with recovery. In the hemorrhagic form, the prognosis is serious, largely depending on the patient’s age, virus serotype, and timing of initiation of therapy. The highest mortality rate is observed among young children.

Experimental vaccines for dengue fever are currently in different stages clinical trials, therefore we can only talk about nonspecific prevention. To prevent infection in regions where dengue fever is endemic, it is necessary to use mosquito repellents, fumigators, and mosquito nets. Of particular relevance is the destruction of mosquitoes that carry the dengue virus, the use of insecticides, the fight against waterlogging and contamination of the territory, and the storage of water supplies in closed containers.

Dengue fever – viral disease, which until the middle of the 20th century was called bone or joint fever, after the name of its main symptoms: muscle and joint pain. The causative agent of the disease is a virus that has 4 serotypes, all of which can equally cause fever, which, fortunately, in most cases has a benign course and ends with recovery. After recovery, the patient develops stable immunity only to the serotype of the virus that caused this particular case of the disease, that is, the risk of re-infection with another type of this virus remains.

It is extremely important for travelers and tourists to know the symptoms of this disease in order not to miss the necessary start of treatment. Prevention can prevent illness, so read about its basic principles in this article.

How is dengue fever transmitted?

Prevalence of Dengue fever.

Currently, the incidence of dengue fever has increased throughout the world, although 50 years ago outbreaks were observed only in some African countries, South America, East (China) and Southeast Asia (Singapore, Philippines, Thailand). According to WHO, today imported cases of the disease are registered in almost all countries of the world, including in Europe, and outbreaks of dengue fever often occur, in which the number of sick people amounts to several thousand people.

The main carriers of the infection are Aedes aegypti; transmission of the virus occurs through the bites of female mosquitoes. Infected people, the main carriers of viruses, are a source of infection for uninfected mosquitoes. Patients can transmit the infection within 5-12 days after they first show signs of illness.

The high prevalence of the disease is due to the fact that this type of mosquito lives and breeds in urban environments, in artificial containers (this also explains the migration of disease carriers between countries and continents). An infected female mosquito can infect people throughout its life. Temperature environment, favorable for the development of the virus in the body of a mosquito, should be at least 22 degrees C, this explains the prevalence of the disease in the tropics and subtropics.

There is another species of mosquito that can also carry the virus that causes dengue fever: Aedes albopictus. It is this species of mosquito that spread to North America and Europe as a result of the movement of goods. These mosquitoes easily adapt to colder conditions, which determines their survival.

Human susceptibility to the virus is high; most often the disease is diagnosed in children (even infancy) and tourists visiting endemic areas.

Dengue fever symptoms

There are no clear differences in the clinical picture when infected with different types of the virus.

The incubation period of the disease averages 5-7 days, after which symptoms of fever suddenly appear.

Only in some people can a prodromal period be distinguished: 6-12 hours before the appearance of the main signs of the disease, they experience headache, weakness, chills, joint pain, which is very similar to the symptoms.

Depending on the clinical picture, there are two variants of the course of fever: classical and hemorrhagic.

Classic (benign) form of dengue fever

All patients experience a sharp increase in body temperature to 39-40 degrees C, severe tachycardia, and hyperemia and swelling of the face and hyperemia of the pharynx. Patients complain about sharp pain in the joints and muscles, due to which they are forced to limit themselves in movement.

By the end of 3 days of illness, body temperature drops sharply and tachycardia is replaced by up to 40 beats/min. The condition of the patients improves, but after 1-3 days the body temperature rises again to its previous values, and the patients develop the main symptoms of dengue fever.

One of the main signs of the disease is a rash (exanthema), in some cases it appears in the first wave of fever, but more often in the second.

The rash is polymorphic, the rash elements can be red spots of various sizes (as with), pinpoint hemorrhages, small papules (nodules). First it appears on the torso, then spreads to the limbs, patients complain of severe pain.

Within 3-7 days, the rashes disappear, leaving peeling in their place.

A few days after the second rise, the body temperature returns to normal and the recovery period begins.

Thus, fever lasts on average up to 9 days.

During the period of convalescence (which lasts 1-2 months), patients continue to experience weakness, sleep disturbances, myalgia, arthralgia, and decreased appetite.

Hemorrhagic form of dengue fever

This form of the disease is more severe than the classic one, and the mortality rate is correspondingly higher (up to 5%). It most often occurs in people with increased susceptibility to the causative agent of fever or when infected with two types of virus at once.

The disease also begins suddenly with a sharp rise in body temperature to 39-40 degrees C, and signs of general intoxication rapidly increase (weakness, lack of appetite, nausea, headache, dizziness). On the 2-3rd day of illness, a rash appears in the form of petechiae: pinpoint hemorrhages in the skin and mucous membranes. Upon examination, attention is drawn to hyperemia of the pharynx, tonsils, and lymph nodes.

In severe cases, hemorrhagic syndrome occurs: hemorrhagic purpura (multiple subcutaneous hemorrhages), nasal, gastric, and uterine bleeding are possible. On days 3-5 of illness, shock or coma may develop, which is an unfavorable prognostic sign; it is during this period that the most large number fatalities.

The duration of the febrile period is 4-8 days. As a rule, there is no second wave of rise in body temperature in the hemorrhagic form of the disease. Also, unlike the classic form of dengue fever, patients are not bothered by muscle and joint pain. After graduation critical period illness, the patients' condition quickly improves and they recover.

Treatment

The vaccine is under development.

Specific treatment There is no vaccine for this disease, according to WHO, vaccines are currently being developed. On early stage diseases (in the first hours), interferon-based drugs are effective, but it should be remembered that the later the drug is taken, the lower its effectiveness.

To alleviate the condition of patients, they are used symptomatic remedies(painkillers, antihistamines, antipyretics, etc.), patients require detoxification therapy, control of water and electrolyte balance, and, if necessary, antibiotics are prescribed (if complications develop).

Today, in order to prevent dengue fever infection, mosquitoes that transmit the disease are being combated. In areas where it is registered high level incidence of dengue fever, it is necessary to exclude access of mosquitoes to places where they can lay eggs, namely to artificial reservoirs with water.

Proper storage conditions should be provided for water supplies (closed containers that need to be emptied and washed at least once a week). When storing water for technical purposes in containers outdoors, you must use approved insecticides.