Dengue Fever

What is Dengue Fever?

Dengue fever (synonyms: dengue-awn – it is German., French, Spanish; dangy – a man, breakbonefever – English; denguero – ital, a dengue fever, bone marrow fever, articular fever, giraffe fever, five days old fever, a day fever, a joint fever, articular fever, giraffe fever, five days’ fever disease) – an acute viral disease that occurs with fever, intoxication, myalgia and arthralgia, exanthema, lymphadenopathy, leukopenia. Some variants of dengue occur with hemorrhagic syndrome. Refers to the transmissible zoonoses.

The disease is known for a long time. In accordance with the main symptom complex, the disease was called bone fever. The concept of hemorrhagic fever dengue was established only in 1954 after describing the clinical picture of the disease in children in the Philippines, and then in other countries of Southeast Asia. By this time, evidence had already been obtained of the viral etiology of the disease.

Causes of Dengue Fever

Dengue pathogens are viruses of the Togaviridae family of the genus Flavivirus (arboviruses of the antigen group B). They contain RNA, have a bilayer lipid shell of phospholipids and cholesterol, the size of the virion 40-45 nm in diameter. Inactivated by processing with proteolytic enzymes and by heating above 60 ° C, under the influence of ultraviolet radiation. There are 4 known types of dengue virus, different in antigenic terms. Dengue viruses are antigenically related to yellow fever viruses, Japanese and West Nile encephalitis. It reproduces in tissue cultures and in kidney cells of monkeys, hamsters, KB, etc. In the 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 the incidence in various regions. Significant dengue outbreaks have been reported in the People’s Republic of China, Viet Nam, Indonesia, Thailand and Cuba. During an outbreak in Cuba in 1981, dengue fever was observed in almost 350,000 people, about 10,000 of them suffered from a more severe hemorrhagic form, 158 patients died (1.6% mortality). In the People’s Republic of China during the 1980 epidemic, 437,468 people fell ill (54 died). During the 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 (for the period 1983-1988, 777 works were published in periodicals, in addition, the problem of dengue was examined in 136 books).

The source of infection is a sick person, monkeys, and possibly bats.

Transmission of infection in humans is carried out by Aedes aegypti mosquitoes, in monkeys – A. albopictus. The mosquito A. aegypti becomes infectious 8-12 days after feeding on the blood of a sick person. Mosquito remains infected for 3 months or more. The virus can develop in the body of a mosquito only when the air temperature is not lower than 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, the Caribbean. Children are predominantly ill, as well as newly arrived individuals in an endemic area.

The natural susceptibility of people is high, children and people who come to endemic areas are sick more often. Post-infectious immunity is type-specific, persistent, and lasts for several years. Repeated diseases are possible after this time or when infected with a virus of another type.

Pathogenesis during Dengue Fever

The virus enters the body through the skin when a person is bitten by an infected mosquito. At the site of the gate of infection after 3-5 days, limited inflammation occurs, where reproduction and accumulation of the virus occurs. In the last 12 hours of the incubation period, the virus has entered the bloodstream. 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. From the patients of the so-called Philippine hemorrhagic fever, dengue viruses of 2, 3, and 4 types were isolated, with Singapore hemorrhagic fever – all 4 types, while evaluating the etiology of Thai hemorrhagic fever, one time wrote about new types of dengue virus (5 and 6). Further, the presence of these types of virus has not been confirmed.

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

Hemorrhagic form develops only in local residents. In this form, mainly small vessels are affected, where swelling of the endothelium, perivascular edema and infiltration with mononuclear cells are detected. Increased vascular permeability leads to disruption of plasma volume, tissue anoxia, metabolic acidosis. The development of common hemorrhagic phenomena is associated with damage to the blood vessels and violation of the aggregative state of the blood. In more severe cases, multiple hemorrhages occur in the endocardium and pericardium, pleura, peritoneum, the mucous membrane of the stomach and intestines, and in the brain.

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

Symptoms of Dengue Fever

The incubation period lasts from 3 to 15 days (usually 5-7 days). The disease usually begins suddenly. Only in some patients for 6-10 h are marked mild prodromal phenomena in the form of fatigue and headache. Usually, chills, pains in the back, sacrum, spine, joints (especially knees) appear among full health. Fever is observed in all patients, the body temperature quickly rises to 39-40 ° C. There are severe adynamia, anorexia, nausea, dizziness, insomnia; in most patients – hyperemia and pastoznost face, vascular injection of the sclera, hyperemia of the pharynx.

According to the clinical course, there is a febrile form of dengue (classical) and dengue hemorrhagic fever.

Classical dengue fever is favorable, although some patients (less than 1%) may develop a comatose state with respiratory arrest. In the case of classical dengue, the dynamics of the pulse is characteristic: at first it is speeded up, then from the 2-3rd day bradycardia appears up to 40 beats / min. There is a significant leukopenia (1.5-10 9 / l) with relative lympho- and monocytosis, thrombocytopenia. In most patients, peripheral lymph nodes are enlarged. Pronounced arthralgia, myalgia and muscle rigidity make it difficult for patients to move. By the end of 3 days, body temperature drops critically. Remission lasts for 1-3 days, then body temperature rises again and the main symptoms of the disease appear. After 2-3 days the body temperature drops. The total duration of fever is 2-9 days. The characteristic symptom of dengue is rash. It can sometimes appear during the first febrile wave, more often with the second increase in body temperature, and sometimes in 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. The exanthema is distinguished by polymorphism. More often it is not very papular (core like), but it can be petechial, scarlet-like, urtikarnoy. The rash is profuse, itchy, first appears on the body, then spreads to the extremities, leaving behind a peeling. Elements of the rash persist for 3-7 days. Hemorrhagic events are rarely observed (in 1-2% of patients). In the period of recovery, for a long time (up to 4-8 weeks) asthenia, weakness, loss of appetite, insomnia, muscle and joint pain remain.

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, pain in the abdomen, sometimes very strong. The initial period lasts 2-4 days. Unlike the classic form of dengue myalgia, arthralgia and bone pain are rare. The examination showed an increase in body temperature up to 39-40 ° C and higher, the mucous membrane of the tonsils and the posterior pharyngeal wall was hyperemic, enlarged lymph nodes were palpable, and the liver was enlarged. During the height of the patient’s condition deteriorates rapidly, weakness increases.

To assess the severity of the process, WHO proposed a clinical classification of dengue haemorrhagic fever. There are 4 degrees, which are characterized by the following clinical symptoms.

Grade I. Fever, symptoms of general intoxication, the appearance of hemorrhages in the elbow when the cuff or the tourniquet is applied (“test of the harness”), thrombocytopenia and thickening of blood in the blood.

Grade II. There are all manifestations characteristic of degree I + spontaneous bleeding (intracutaneous, from the gums, gastrointestinal), in the study of blood – more pronounced hemoconcentration and thrombocytopenia.

Grade III. See Grade II + circulatory failure, arousal. Laboratory: hemoconcentration and thrombocytopenia.

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

Grades III and IV are characterized as dengue shock. When examining the patient during the height of the disease, the patient is worried, his limbs are cold and sticky, the body is warm. Pallor of the face, cyanosis of the lips is noted, in half of the patients petechiae are detected, localized more often on the forehead and distal parts of the extremities. Less commonly, spotted or maculopapular rash appears. Blood pressure decreases, pulse pressure decreases, tachycardia, limbs cyanosis appear, and pathological reflexes appear. Death more often occurs on the 4-5th day of the disease. Bloody vomiting, coma or shock are prognostically unfavorable signs. Common cyanosis and seizures are the terminal manifestations of the disease. Patients who have experienced a critical period of illness (peak), quickly begin to recover. Relapse of the disease does not happen. Dengue haemorrhagic fever is more common in children. Mortality in this form is about 5%.

Complications – encephalitis, meningitis, psychosis, polyneuritis, pneumonia, parotitis, otitis.

Diagnosis of Dengue Fever

In recognition, epidemiological prerequisites are taken into account (stay in an endemic area, incidence rate, etc.). During epidemic outbreaks, clinical diagnosis is not difficult and is based on characteristic clinical manifestations (two-wave fever, exanthema, myalgia, arthralgia, lymphadenopathy).

The 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 test of the tourniquet and any of the following criteria: petechiae, purpura, ecchymosis, nasal bleeding, bleeding from the gums, bloody vomiting or melena;
– enlarged liver; thrombocytopenia not more than 100×109 / l, hemoconcentration, hematocrit increase not less than 20%.

Criteria for the diagnosis of dengue shock syndrome – fast, weak pulse with a decrease in pulse pressure (no more than 20 mmHg), hypotension, cold, clammy skin, anxiety. The WHO classification includes the four degrees of severity described previously. In classical dengue fever, mild hemorrhagic symptoms may occur that do not meet the WHO criteria for the diagnosis of dengue hemorrhagic fever. These cases should be considered as dengue fever with hemorrhagic syndrome, but not as dengue hemorrhagic fever.

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

Differentiate from malaria, chikungunya fever, pappatachi, yellow fever, other hemorrhagic fevers, and infectious toxic shock in bacterial diseases (sepsis, meningococcemia, etc.).

Dengue Fever Treatment

There is no specific treatment for conventional dengue forms. Hemorrhagic fever and shock syndrome use corticosteroids and antibiotics, but their effectiveness has not been proven. In cases of shock syndrome, measures are recommended to maintain the body’s water balance and the use of means to increase plasma volume.

The prognosis is favorable for the classical and serious for the hemorrhagic form of the disease (the mortality rate for the latter is 30-50%).

Dengue Fever Prevention

To date, there are no licensed vaccines against dengue. Development of vaccines against dengue disease (both mild and severe forms) is difficult due to the fact that it can be caused by any of the four dengue viruses, and therefore, the vaccine must protect against all four viruses, that is, it must be tetravalent. In addition, the absence of suitable animal models and a limited understanding of the pathology of the disease and the immune responses responsible for protection further complicate the development and clinical evaluation of candidate dengue vaccines. However, progress has been made in developing vaccines that can protect against all four dengue viruses. Two candidate vaccines are in clinical evaluation in endemic countries, and a number of other candidate vaccines are in earlier stages of development. The WHO Vaccine Research Initiative supports the development and evaluation of dengue vaccines by providing technical advice and guidance in areas such as measuring immunity of vaccine origin and testing vaccines in areas that are endemic to the disease.

Currently, the only way to control or prevent the transmission of dengue virus is to combat mosquito vectors.

In Asia and America, Aedes aegypti reproduces mainly in man-made containers such as clay vessels, metal barrels and concrete tanks used to store household water supplies, as well as discarded plastic food containers, old car tires and other items, in which rainwater accumulates. In Africa, mosquitoes also breed widely in their natural environment — in tree hollows and on leaves, forming “cups” in which water is collected.

In recent years, Aedes albopictus, a secondary carrier of dengue in Asia, has spread to the United States of America, several countries in Latin America and the Caribbean, and parts of Europe and Africa. The rapid geographical spread of this species occurred, largely due to the international trade in old tires, which are the breeding ground of mosquitoes.

Vector control of infection is carried out on the basis of environmental management and the use of chemical methods. Proper disposal of solid waste and improved water storage practices, including in lockable containers that prevent the access of egg-laying female mosquitoes, are among the methods recommended in community-based programs. The use of proper insecticides in places where larvae accumulate and, especially, in households, for example, in water storage vessels, prevents mosquitoes from reproducing for several weeks, and then such treatment must be repeated periodically. Small fish and tiny crustaceans that feed on mosquitoes are also used with some success.

During disease outbreaks, extreme vector control measures may also include extensive use of insecticides sprayed from hand-held or truck-mounted devices or even from aircraft. However, the effectiveness of such measures for the destruction of mosquitoes is temporary and depends on whether aerosol droplets have penetrated inside the premises where individual adult individuals can remain. In addition, these are costly and difficult to implement activities. To choose the right chemicals, it is necessary to regularly monitor vector sensitivity to commonly used insecticides. To determine the effectiveness of programs, along with vector control measures, it is necessary to conduct active monitoring and surveillance of natural populations of mosquitoes.

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