Dengue fever

Dengue fever is an acute zooanthroponotic arbovirus infectious disease with a transmissible mechanism of transmission of the pathogen, prevalent in countries of the tropical and subtropical belt.

[1], [2], [3]

Epidemiology

The source of the causative agent of infection is a sick person and monkeys, whose disease can be latent.

In endemic regions, there are natural foci of the disease in which the virus circulates between monkeys, lemurs, squirrels, bats, and possibly other mammals. Carriers - mosquitoes of the genus Aedes (A. Aegypti, A. Albopictus, A. Cutellaris, A. Polinesiensis), probably, a certain role belongs to the mosquitoes of the genera Anopheles and Cilex.

Mosquitoes of the genus Aedes after bloodsucking become infectious in 8-12 days, depending on the temperature conditions. Their ability to infect is maintained throughout life, i.e. 1-3 months, but at an air temperature below 22 ° C the virus does not multiply in the mosquito, so the dengue is smaller than the range of mosquito vectors and is limited to 42 ° N and 40 ° S.

Infection of a person in endemic regions led to the formation of persistent anthropurgic foci of infection, regardless of natural conditions. In these outbreaks, the source of the pathogen is a sick person who becomes infectious almost a day before the onset of the disease and remains infectious during the first 3-5 days of the illness.

The main carrier of the pathogen in the human population is the mosquito A. Aeguti, which lives in the human dwelling. A female mosquito bites a person in the afternoon. The mosquito is most active at a temperature of 25-28 ° C, at the same temperature its abundance reaches a maximum, and the timing of infectivity after the bloodsucking is minimal. A person is highly sensitive to dengue fever. Infection occurs even with a single mosquito bite. In humans, each of the four types of the virus can cause the classic form of dengue and dengue hemorrhagic fever. Immunity after the transferred illness is short-term, lasts for several years, type-specific, so after the transferred illness the person remains susceptible to other serotypes of the virus. Large epidemics are always associated with a drift of a type of virus that is not characteristic of this region or in regions (countries) where there is no endemic morbidity. Classical dengue fever and Dengue hemorrhagic fever are significantly different. Classical dengue is observed among local residents, mostly children and visitors of any age, and Dengue hemorrhagic fever is mainly caused by children. Peaks of morbidity fall on two age groups: up to 1 year old, having passive immunity against another type of virus, and children of 3 years old who have recovered from classical dengue. In the first group the immune response is formed by the type of the primary one, in the second group by the type of the secondary one. Dengue hemorrhagic fever in severe form - dengue shock syndrome most often develops when a second type of virus is infected with infecting children who have suffered in the past dengue, caused by type I, III or IV viruses. Thus, during the epidemic in Cuba in 1981 it was found that in more than 98% of patients, severe disease and shock dengue syndrome were associated with infection with type II virus in the presence of antibodies to type I virus.

[4], [5], [6], [7]

Causes of the dengue fever

The cause of dengue fever is arbovirus, which belongs to the genus Flavivirus, the family Feaviviridae. The genome is represented by single-stranded RNA. The size of the virion is 40-45 nm. Has an additional super capsid shell, which is associated with antigenic and hemagglutinating properties. The environmental stability is medium, well maintained at low temperatures (-70 ° C) and in the dried state: sensitive to formalin and ether, inactivated when treated with proteolytic enzymes and heated to 60 ° C. There are four antigenic serotypes of the dengue virus: DEN I, DEN II, DEN III, DEN IV. The dengue virus is transmitted to humans through mosquito bites and therefore belongs to the ecological group of arboviruses. The pronounced dependence of the clinical picture on the serotype of the virus is not established. The virus has a weak cytopathic activity. Its replication occurs in the cytoplasm of the affected cells. In monkeys, it causes an asymptomatic infection with the formation of lasting immunity. The virus is pathogenic to newborn white mice when infected in the brain or intraperitoneally. The virus multiplies in cultures of kidney tissues of monkeys, hamsters, testicles of monkeys, and also on the lines of cells HeLa, KB and human skin.

[8], [9], [10], [11]

Pathogenesis

Infection occurs when bitten by an infected mosquito. Primary replication of the virus occurs in regional lymph nodes and vascular endothelial cells. At the end of the incubation period, viremia develops, accompanied by fever and intoxication. As a result of viremia, various organs and tissues are affected. It is with organ damage that the repeated wave of fever is associated. Recovery is associated with the accumulation in the blood of complement-binding and viral neutralizing antibodies, which persist for several years.

A similar pattern of pathogenesis is characteristic of classical dengue, which develops in the absence of previous active or passive immunity.

[12], [13], [14], [15], [16], [17]

Symptoms of the dengue fever

Symptoms of dengue fever may be absent or occur as undifferentiated fever, dengue fever, or Dengue hemorrhagic fever.

In clinically expressed cases, the incubation period of dengue fever lasts from 3 to 15 days, more often 5-8 days. There are classical, atypical hemorrhagic fever of Dengue (without the shock syndrome of dengue and accompanying it).

Classical dengue fever begins with a brief prodromal period. During it, note malaise, conjunctivitis and rhinitis. However, more often the prodromal period is absent. Symptoms of dengue fever start with a chill, a rapid increase in temperature to 38-41 C, persisting for 3-4 days (the initial period of the disease). Patients complain of severe headache, pain in the eyeballs, especially when moving, muscles, large joints, spine, lower limbs. This leads to difficulty in any movement, immobilizes the patient (the name of the disease comes from the English "dandy" - medical stretcher). In severe disease, along with a severe headache, vomiting, nonsense, and loss of consciousness are possible. Sleep is disturbed, appetite worsens, bitterness appears in the mouth, weakness and general malaise are pronounced.

Already from the first day of the illness, the appearance of the patient changes: the face is clearly hyperemic, the injection of vessels of the sclera, hyperemia of the conjunctiva is expressed. Often on the soft palate appears enanthema. The language is imposed. The eyes are covered because of photophobia. The liver is enlarged, but jaundice is not observed. Characteristic increase in peripheral lymph nodes. By the end of 3 days or on the 4th day the temperature drops to normal. The period of apyrexia lasts usually 1-3 days, then the temperature rises again to high figures. In some patients, apyrexia is not observed at the height of the disease. A characteristic symptom is exanthema. The rash usually appears on the 5th-6th day of the illness, sometimes earlier, first on the chest, the inner surface of the shoulders, then spreads to the trunk and limbs. Characteristic spotted-papular rash, which is often accompanied by itching, leaves after itself peeling.

The total duration of fever is 5-9 days. In the hemogram in the initial period - moderate leukocytosis and neutrophilia. Later - leukopenia, lymphocytosis. Possible proteinuria.

With an atypical fever, dengue is observed fever, anorexia. Headache, myalgia, ephemeral rash, polyadenopathy is absent. The duration of the disease does not exceed 3 days.

Dengue hemorrhagic fever has typical symptoms, of which 4 main symptoms are distinguished: high fever, hemorrhages, hepatomegaly and circulatory insufficiency.

Hemorrhagic fever of dengue begins with a sudden increase in body temperature to 39-40 C, severe chills, headache, cough, pharyngitis. Unlike classical dengue, myalgia and arthralgia are rarely observed. In severe cases prostration develops rapidly. Characterized by severe hyperemia and puffiness of the face, glitter of eyes, hyperemia of all visible membranes. Often, scarlatine-like reddening of the whole body is noted, against which there is a punctual rash, mainly on the extensor surfaces of the elbows and knee joints. In the next 3-5 days of the disease appears korepodobnaya patchy-papular or scarlet-like rash on the body, and then - on the limbs and face. Mark pain in the epigastric region or throughout the abdomen, accompanied by repeated vomiting. The liver is painful, enlarged.

After 2-7 days, body temperature often decreases to normal or low levels, symptoms of dengue fever can regress, recovery comes. In severe conditions, the patient's condition worsens. The most frequent hemorrhagic sign is a positive test with a tourniquet (most patients have bruises at the injection sites). On the skin there are petechiae, subcutaneous hemorrhage, bleeding. Significantly reduced the number of platelets, the hematocrit increases by 20% or more. Characteristic development of hypovolemic shock.

[18], [19], [20],

Stages

Power			Clinical signs
Geld		I	Fever, accompanied by nonspecific symptoms, The only manifestation of hemorrhage is a positive test result with a tourniquet (turnstile test)
		II	Symptoms of grade III + spontaneous bleeding (intradermal, gum, gastrointestinal)
	Shock Dengue Syndrome	III	Symptoms of 2nd degree + circulatory insufficiency expressed by frequent and weak pulse, decrease in pulse pressure or hypotension, cold and damp skin and excitation
		IV	Symptoms of III degree + deep shock, in which it is impossible to determine blood pressure (AD - 0),

In severe cases, after several days of high fever, the patient's condition suddenly deteriorates. During the temperature drop (between the 3rd and the 7th day of the disease), signs of circulatory disturbance appear: the skin becomes cold, puffy, stained, often marked by cyanosis of the skin around the mouth and increased heart rate.

The pulse is frequent, the patients are restless, complain of pain in the abdomen. Some patients are inhibited, but then they develop excitement, after which the critical stage of shock comes. The condition progressively worsens. In the forehead and distal parts of the limbs, a petechial rash appears, the blood pressure drops sharply, its amplitude decreases, the pulse becomes thready, tachycardia and dyspnea become worse. The skin is cold, moist, cyanosis is growing. On the 5th-6th day there is bloody vomiting, melena, convulsions. The duration of the shock is not great. The patient may die within 12-24 hours or recover quickly after the corresponding anti-shock measures. Recovery with hemorrhagic fever Dengue with a shock or without shock comes quickly and proceeds without complications. A favorable prognostic sign is restoration of appetite.

Blood test reveals thrombocytopenia, high hematocrit, prolonged prothrombin (one-third of patients) and thromboplastin time (in half of patients), hemofibrinogenemia, the appearance of fibrin degradation products in the blood, metabolic acidosis. Almost always, hemoconcentration is noted (indicating a loss of plasma), even in patients without shock. The number of leukocytes varies from leukopenia to a small leukocytosis. Often there is lymphocytosis with atypical lymphocytes.

Some patients observe symptoms of dengue fever, such as CNS damage, namely: convulsions, spasms and prolonged (more than 8 hours) impairment of consciousness.

Dengue fever can be complicated by shock, pneumonia, encephalitis, meningitis, psychosis, polyneuritis.

[21], [22]

Forms

There are two clinical forms of the disease: classical and hemorrhagic (shock syndrome dengue).

Classical dengue fever (synonyms - dengue, costal fever) is characterized by a two-wave fever, arthralgia, myalgia, exanthema. Polyadenitis, leukopenia and benign course of the disease.

Hemorrhagic dengue fever ( ferbis hemorragka dengue, synonymous with dengue shock syndrome) is characterized by the development of thrombohemorrhagic syndrome, shock and high lethality.

[23], [24], [25], [26], [27], [28]

Diagnostics of the dengue fever

Diagnosis of dengue fever according to WHO criteria is based on the following symptoms:

• rapid increase in temperature to 39-40 ° C, persisting for 2-7 days;
• the appearance of signs of thrombohemorrhagic syndrome (petechiae, purpura, hemorrhage, bleeding):
• enlargement of the liver;
• thrombocytopenia (less than 100х10 ⁹ / l), increase of hematocrit by 20% and more;
• development of shock.

The first two clinical criteria in combination with thrombocytopenia and hemoconcentration or elevated hematocrit are sufficient to diagnose dengue hemorrhagic fever.

It is also necessary to take into account the epidemiological history (stay in the endemic area).

Diagnosis of dengue fever (the classic form) is based on the presence of characteristic symptoms: joint and muscle pain, two-wave fever, rash, lymphadenopathy, near-orbital and headache.

With classical dengue fever, mild manifestations of hemorrhagic diathesis may not occur that do not meet WHO criteria. In these cases, dengue fever with hemorrhagic syndrome is diagnosed, but not dengue hemorrhagic fever.

Diagnosis of dengue fever is based on virological and serological studies. There are two main methods for diagnosing dengue fever: virus isolation and detection of an increase in the titer of antibodies to the dengue virus (in paired blood sera in RSK, RTGA, PH-viruses). Isolation of the virus gives more accurate results, but for this type of research requires a specially equipped laboratory. Serological tests are much simpler, and they take less time to set. However, cross-reactions with other viruses are possible. This can be the cause of false-positive results.

[29], [30], [31], [32],

Differential diagnosis

Differential diagnosis of dengue fever (classic form) is carried out with influenza, measles, phlebotomal fever.

Dengue fever (hemorrhagic form) differentiates from meningococcemia, sepsis, tropical malaria, Chikungunya fever and other hemorrhagic fevers.

Indications for consultation of other specialists

With the development of shock - consultation resuscitator, neurological complications (disorders of consciousness, convulsions) - a neurologist.

Treatment of the dengue fever

There is no etiotropic treatment for dengue fever. High fever and vomiting cause thirst and dehydration, so patients should drink as much fluids as possible. With hemorrhagic fever Dengue without shock, rehydration therapy, mainly oral, is performed. Patients should be carefully monitored to identify early signs of shock.

Patients should immediately be hospitalized if any of the following signs and symptoms of shock are present:

• excitement or inhibition;
• cold extremities and cyanosis around the mouth;
• fasted weak pulse;
• decreased pulse pressure or hypotension;
• a sharp increase in hematocrit.

Increased hematocrit, the development of acidosis - an indication for parenteral administration of alkaline and polyionic solutions. In shock, injection of plasma or plasma substitutes is indicated. In most cases, it is necessary to inject no more than 20-30 ml of plasma per 1 kg of body weight. The introduction of the liquid should continue at a constant rate (10-20 ml / kg / h) until there is an obvious improvement in respiration, pulse and temperature. As a substitute for plasma, dextran 40 is effective. Oxygenotherapy is indicated. The effectiveness of glucocorticoids, heparin is questionable. The substitution treatment for dengue fever is stopped when the hematocrit is reduced to 40%. Blood transfusion is not indicated. Antibiotics are prescribed in case of attachment of bacterial complications. Under favorable conditions, a full recovery occurs.

Approximate terms of incapacity for work

Determine individually depending on the clinical picture, the presence of complications.

[33], [34],

Clinical examination

Dengue fever does not require dispensary follow-up.

[35], [36], [37], [38], [39]

Prevention

Dengue fever is prevented with the help of activities that include the destruction of mosquitoes and the neutralization of localization sites for their offspring. Use individual means of protection against mosquitoes. Window and door openings. Emergency prevention of dengue fever is implicated in the use of a specific immunoglobulin or immunoglobulin from the plasma of donors living in endemic areas.

[40], [41], [42],

Forecast

Classical dengue fever usually has a favorable prognosis, lethality with hemorrhagic fever Dengue - up to 40%, with adequate therapy - 5-10%. The highest mortality in children under 1 year.

[43], [44], [45], [46], [47]