Dengue fever

Dengue fever is an acute zoonotic arbovirus infectious disease with a transmissible mechanism of pathogen transmission, common in tropical and subtropical countries.

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Epidemiology

The source of the infectious agent is a sick person and monkeys, in which the 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. The carriers are mosquitoes of the genus Aedes (A. aegypti, A. albopictus, A. cutellaris, A. polinesiensis), and it is possible that mosquitoes of the genera Anopheles and Cilex play a certain role.

Mosquitoes of the genus Aedes become infectious after bloodsucking in 8-12 days, depending on temperature conditions. Their ability to infect remains throughout life, i.e. 1-3 months, however, at air temperatures below 22 °C, the virus does not reproduce in the mosquito's body, so the range of dengue is smaller than the range of mosquito carriers and is limited to 42° north and 40° south longitude.

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

The main carrier of the pathogen in the human population is the mosquito A. aeguti, which lives in human dwellings. The female mosquito bites a person during the day. The mosquito is most active at a temperature of 25-28 °C, at the same temperature its numbers reach a maximum, and the period of infectivity after bloodsucking is minimal. Humans are highly susceptible to dengue fever. Infection occurs even with a single mosquito bite. In humans, each of the four types of the virus is capable of causing the classic form of dengue fever and dengue hemorrhagic fever. Immunity after the disease is short-term, lasts for several years, type-specific, therefore after the disease a person remains susceptible to other serotypes of the virus. Large epidemics are always associated with the introduction of a virus type that is not characteristic of a given region or to regions (countries) where there is no endemic incidence. Classic dengue fever and dengue hemorrhagic fever differ significantly. Classical dengue is observed among local residents, mainly children and visitors of any age, and dengue hemorrhagic fever mainly affects children. The peak incidence occurs in two age groups: under 1 year old, who have passive immunity against another type of virus, and 3-year-old children who have had classical dengue. In the first group, an immune response is formed according to the primary type, in the second - according to the secondary type. Severe dengue hemorrhagic fever - dengue shock syndrome most often develops when infected with the second type of virus when children who have previously had dengue caused by viruses of type I, III or IV are infected. Thus, during the epidemic in Cuba in 1981, it was found that in more than 98% of patients, severe course of the disease and dengue shock syndrome were associated with infection with the type II virus in the presence of antibodies to the type I virus.

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Causes dengue fevers

Dengue fever is caused by an arbovirus belonging to the Flavivirus genus, Feaviviridae family. The genome is represented by single-stranded RNA. The virion size is 40-45 nm. It has an additional supercapsid membrane, which is associated with antigenic and hemagglutinating properties. Its stability in the environment is average, it is well preserved at low temperatures (-70 °C) and in a dried state: it is sensitive to formalin and ether, it is inactivated when treated with proteolytic enzymes and when heated to 60 °C. There are four known 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. No pronounced dependence of the clinical picture on the serotype of the virus has been established. The virus has weak cytopathic activity. Its replication occurs in the cytoplasm of affected cells. In monkeys, it causes asymptomatic infection with the formation of strong immunity. The virus is pathogenic for newborn white mice when infected in the brain or intraperitoneally. The virus multiplies in tissue cultures of monkey kidneys, hamsters, monkey testicles, as well as on HeLa, KB cell lines and human skin.

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Pathogenesis

Infection occurs through the bite of 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 a repeated wave of fever is associated. Recovery is associated with the accumulation of complement-binding and virus-neutralizing antibodies in the blood, which persist for several years.

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

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Symptoms dengue fevers

Symptoms of dengue fever may be absent or may 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. A distinction is made between classical, atypical hemorrhagic dengue fever (without dengue shock syndrome and accompanied by it).

Classic dengue fever begins with a short prodromal period. During it, malaise, conjunctivitis and rhinitis are noted. However, more often the prodromal period is absent. Symptoms of dengue fever begin with chills, a rapid increase in temperature to 38-41 C, which persists 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 with any movement, immobilizes the patient (the name of the disease comes from the English "dandy" - a medical stretcher). In severe cases of the disease, along with a severe headache, vomiting, delirium, loss of consciousness are possible. Sleep is disturbed, appetite worsens, bitterness appears in the mouth, weakness and general malaise are pronounced.

From the first day of the disease, the patient's appearance changes: the face is brightly hyperemic, there is pronounced injection of the scleral vessels, hyperemia of the conjunctiva. Enanthema often appears on the soft palate. The tongue is coated. The eyes are closed due to photophobia. An enlarged liver is noted, but jaundice is not observed. Enlargement of the peripheral lymph nodes is characteristic. By the end of the 3rd day or on the 4th day, the temperature critically drops to normal. The period of apyrexia usually lasts 1-3 days, then the temperature rises again to high numbers. In some patients, the period of apyrexia at the height of the disease is not observed. A characteristic symptom is exanthema. The rash usually appears on the 5th-6th day of the disease, sometimes earlier, first on the chest, the inner surface of the shoulders, then spreads to the trunk and limbs. A maculopapular rash is characteristic, which is often accompanied by itching, leaves behind peeling.

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

In atypical dengue fever, fever, anorexia, headache, myalgia, ephemeral rash are observed, polyadenopathy is absent. The duration of the disease does not exceed 3 days.

Dengue hemorrhagic fever has typical symptoms, of which there are 4 main ones: high temperature, hemorrhages, hepatomegaly and circulatory failure.

Dengue hemorrhagic fever begins with a sudden increase in body temperature to 39-40 C, severe chills, headache, cough, and pharyngitis. Unlike classical dengue, myalgia and arthralgia are rare. In severe cases, prostration develops rapidly. Characteristic features include marked hyperemia and puffiness of the face, shiny eyes, and hyperemia of all visible membranes. Scarlet fever-like redness of the entire body is often noted, against which a punctate rash appears, mainly on the extensor surfaces of the elbow and knee joints. In the next 3-5 days of the disease, a measles-like maculopapular or scarlet fever-like rash appears on the trunk, and then on the limbs and face. Pain in the epigastric region or throughout the abdomen is noted, accompanied by repeated vomiting. The liver is painful and enlarged.

After 2-7 days, body temperature often drops to normal or low levels, dengue fever symptoms may regress, and recovery occurs. In severe cases, the patient's condition worsens. The most common hemorrhagic sign is a positive tourniquet test (most patients develop bruises at injection sites). Petechiae, subcutaneous hemorrhages, and bleeding appear on the skin. The number of platelets decreases significantly, the hematocrit increases by 20% or more. Hypovolemic shock is typical.

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Stages

Degree			Clinical signs
Gld		I	Fever accompanied by non-specific symptoms, the only manifestation of hemorrhage is a positive result of the tourniquet test (tourniquet test)
		II	Symptoms of grade III + spontaneous bleeding (intradermal, from gums, gastrointestinal)
	Dengue shock syndrome	III	Symptoms of stage II + circulatory failure, expressed by frequent and weak pulse, decreased pulse pressure or hypotension, cold and clammy skin and agitation
		IV	Symptoms of stage III + deep shock, in which it is impossible to determine blood pressure (BP - 0),

In severe cases, after several days of high temperature, the patient's condition suddenly worsens. During the temperature drop (between the 3rd and 7th day of illness), signs of circulatory disorders appear: the skin becomes cold, puffy, covered with spots, cyanosis of the skin around the mouth and increased pulse rate are often noted.

The pulse is rapid, the patients are restless, complain of abdominal pain. Some patients are inhibited, but then they become agitated, after which the critical stage of shock occurs. The condition progressively worsens. A petechial rash appears on the forehead and distal extremities, arterial pressure drops sharply, its amplitude decreases, the pulse is threadlike, tachycardia and dyspnea increase. The skin is cold, damp, cyanosis increases. On the 5th-6th day, bloody vomiting, melena, and convulsions occur. The duration of shock is short. The patient may die within 12-24 hours or quickly recover after appropriate anti-shock measures. Recovery from dengue hemorrhagic fever with or without shock occurs quickly and proceeds without complications. A favorable prognostic sign is the restoration of appetite.

Blood tests reveal thrombocytopenia, high hematocrit, prolongation of prothrombin time (in one third of patients) and thromboplastin time (in half of patients), hemofibrinogenemia, the appearance of fibrin degradation products in the blood, and metabolic acidosis. Hemoconcentration (indicating loss of plasma) is almost always noted, even in patients without shock. The number of leukocytes varies from leukopenia to slight leukocytosis. Lymphocytosis with atypical lymphocytes is often detected.

Some patients experience symptoms of dengue fever such as damage to the central nervous system, namely: convulsions, spasms and prolonged (more than 8 hours) impairment of consciousness.

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

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Forms

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

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

Dengue hemorrhagic fever (ferbis hemorragka dengue, synonym - dengue shock syndrome) is characterized by the development of thrombohemorrhagic syndrome, shock and high mortality.

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Diagnostics dengue fevers

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, hemorrhages, bleeding):
• enlarged liver;
• thrombocytopenia (less than 100x10 ⁹ /l), increase in hematocrit by 20% or more;
• development of shock.

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

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

Diagnosis of dengue fever (classical form) is based on the presence of characteristic symptoms: pain in the joints and muscles, two-wave fever, rash, lymphadenopathy, periorbital and headache.

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

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

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Differential diagnosis

Differential diagnostics of dengue fever (classical form) is carried out with influenza, measles, and phlebotomy fever.

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

Indications for consultation with other specialists

In case of shock development - consultation with a resuscitator, in case of neurological complications (disorders of consciousness, seizures) - consultation with a neurologist.

Treatment dengue fevers

There is no etiotropic treatment for dengue fever. High temperature and vomiting cause thirst and dehydration, so patients should drink as much fluid as possible. In hemorrhagic dengue fever without shock, rehydration therapy is administered, primarily oral. Patients should be closely monitored for early signs of shock.

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

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

Increased hematocrit and development of acidosis are indications for parenteral administration of alkaline and polyionic solutions. In shock, administration of plasma or plasma substitutes is indicated. In most cases, it is necessary to administer no more than 20-30 ml of plasma per 1 kg of body weight. Fluid administration should be continued at a constant rate (10-20 ml/kg per hour) until breathing, pulse, and temperature clearly improve. Dextran 40 is an effective plasma substitute. Oxygen therapy is indicated. The effectiveness of glucocorticoids and heparin is questionable. Replacement therapy for dengue fever is stopped when the hematocrit decreases to 40%. Blood transfusion is not indicated. Antibiotics are prescribed in case of bacterial complications. Under favorable conditions, complete recovery occurs.

Approximate periods of incapacity for work

It is determined individually depending on the clinical picture and the presence of complications.

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Clinical examination

Dengue fever does not require medical observation of those who have recovered from the disease.

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Prevention

Dengue fever is prevented by measures that include the destruction of mosquitoes and the neutralization of their breeding grounds. Use personal protective equipment against mosquitoes. Screening of window and door openings. Emergency prevention of dengue fever consists of the use of specific immunoglobulin or immunoglobulin from the plasma of donors living in endemic areas.

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Forecast

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

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