Dengue virus

2021-08-15 10:30 PM

Dengue virus belongs to the family Flaviviridae, including 4 serotypes of Dengue virus that cause disease in humans, Dengue virus types 1, 2, 3 and 4

The Flaviviridae family includes many arboviruses (Arbovirus: Arthropod-borne viruses), which are viruses carried by blood-sucking insects such as mosquitoes or ticks and transmitted between vertebrates (including humans). Arboviruses that want to transmit disease from one vertebrate to another must have an intermediary insect (except in unusual cases). When the parasitic insect sucks the blood of an animal that is in the viremia stage, the virus will multiply in the insect's body for a few days (external incubation period), if the insect stings the cold animal. another animal will transmit the disease to that animal. These viruses multiply in the cells of parasitic insects (mosquitoes, ticks...) but do not cause disease.

Among the viruses of the Flaviviridae family that cause disease in Vietnam, the most common is the Japanese encephalitis virus and Dengue virus.

Dengue virus is the causative agent of classical dengue fever and dengue hemorrhagic fever. Dengue virus disease is found in many parts of the world.

Virological features

Dengue virus belongs to the family Flaviviridae, including 4 serotypes of dengue virus that cause disease in humans: Dengue virus type 1, Dengue virus type 2, Dengue virus type 3, and Dengue virus type 4.

Dengue virus contains a single-stranded, symmetric nucleocapsid with a nucleocapsid envelope. The complete virus particle is about 50 nm in diameter. The viral genome is about 11kb (kilobases) long, consisting of three genes encoding structural proteins, nucleocapsids or core proteins (C), membrane proteins (M) and envelope proteins (E), and seven genes encoding proteins. unstructured (NS). The order of coding for the proteins is as follows: 5'- C - prM(M) - E - NS1 - NS2A - NS2B - NS3 - NS4A - NS4B - NS5 - 3'.

Viruses are sensitive to ether and sodium desoxycholate. It is easily destroyed by heat, even at 4 0 C. Virus in patient serum kept at - 70 0 C or as lyophilized at 5 0 C can survive for 8-10 years. Viruses are destroyed by ultraviolet light within minutes. The virus is inactivated by formal and loses its immunogenic properties.

Organisms of adult Aedes aegypti or Toxorhynchites mosquitoes are most susceptible to the dengue virus because mosquitoes are natural hosts of the dengue virus. Currently, people have found many types of permanent cell cultures of mosquitoes with high susceptibility to Dengue virus such as C6/36, AP-61, TRA-284SF.

Dengue virus has complement-conjugated antigens and red blood cell agglutination antigens. These viruses cause agglutination of goose erythrocytes and erythrocytes of 1-day-old chicks.

Possibility to cause disease

Epidemiology

Dengue virus reservoirs are mainly humans, primates (monkeys, apes, chimpanzees), and Aedes mosquitoes. 

Insects are mediated by Aedes mosquitoes, mainly Aedes aegypti, which usually lay eggs in clear and clean water. Aedes mosquito can be infected with the virus when biting a patient in the viremia stage, the virus enters the digestive tract in the mosquito's body and resides in the salivary glands to spread to humans and animals. Depending on the outside temperature conditions, the duration of this external incubation is long and short (the incubation time outside is the time the virus multiplies in the mosquito's body). After sucking the patient's blood, if the outside temperature is 22 0 C, then after 9 days, the disease can be transmitted.

Thus, humans and some species of monkeys in some areas and mosquitoes merge into a viral infection ring, thanks to which the dengue virus persists in nature.

Dengue fever occupies an important place in epidemic infectious diseases in Southeast Asia. In Vietnam, the dengue epidemic occurs in many places, especially in densely populated areas in cities, plains, and coastal areas. The disease occurs year-round but thrives in hot, rainy months. The disease occurs at any age, but the target audience is mainly children.

Possibility to cause disease in humans

When a mosquito carrying the virus (which has had enough time to get sick outside) bites a normal person, the virus enters the body through the bite site. Viruses infect and multiply in cells of the mono-macrophage system, viruses circulate in the body in monocytes, macrophages... Viruses infect cells that cause cell degeneration in organizations of the body such as the liver, spleen, kidney, muscle, brain, connective tissue, intestinal mucosa, ...

Dengue virus can cause the following diseases in humans:

Classic Dengue Sauce

After an incubation period of 3-14 days, the disease begins suddenly with fever with chills, headache, pain in the eye socket when the eyeball moves, back pain, muscle, and joint pain. The fever rises rapidly to 40 0 C. Lymph nodes in the neck, muzzle above the pulley, and in the groin are often enlarged. After 48-96 hours of rapid fever reduction and profuse sweating, during the same period, a distinctive measles-like rash appeared, initially localized to the extremities, then spread to the whole body. Uncomplicated cases usually resolve. The recovery period lasts for several weeks.

Dengue hemorrhagic fever

The disease has a sudden onset with classic dengue-like symptoms. According to the World Health Organization, the criteria for the diagnosis of Dengue / Dengue hemorrhagic fever with shock syndrome (DSS) are high fever, manifestations of hemorrhage, hepatomegaly, and circulatory failure with accompanying circulatory failure. thrombocytopenia and hemoconcentration.

Pathophysiology:

Age, immune status, viral strain, and genetic status of the patient are considered to be the most important risk factors associated with severe dengue and mortality. Author SB Halstead proposed a pathogenesis hypothesis to explain Dengue/DSS hemorrhagic fever. According to SB Halstead, a risk factor for shock is that in the patient there are insufficient levels of Dengue antibodies to neutralize the virus, leading to a secondary infection due to "immunocompromised". Thus, only some people who are infected a second time with another type of Dengue will develop dengue/DSS. This theory suggests that monocytes are the site of the first development of the dengue virus. The level of heterozygous antibody below neutralization has been associated with the virus to increase the ability of phagocytosis, Once the virus enters the cell, the complex breaks down and causes the virus to multiply. The severity of the disease is related to the number of monocytes infected and secreted into the blood by mediators, which act on the vessel wall, causing plasma leakage through the capillaries and leading to shock syndrome in the blood. Dengue hemorrhagic fever/DSS.

Diagnosis of virology

Virus isolation

Specimens are the patient's blood, serum, plasma (taken at high fever) or liver, spleen, and brain tissue from the corpse. Dengue virus isolation by injection technique into the tissues of adult mosquitoes (injection into the chest or injection into the brain of Toxorhynchites mosquitoes), or inoculation into cell cultures derived from mosquitoes such as C6/36, AP- 61, TRA-284SF or animal cell cultures such as LLC-MK2, Vero. Then detect the presence of Dengue virus in the mosquito body and in cultured cells by direct fluorescent antibody technique. If the reaction is positive, continue to type the virus by indirect immunofluorescence with monoclonal antibodies Dengue 1, Dengue 2, Dengue 3, Dengue 4.

Detection of Dengue virus antigens

Dengue virus antigens can be detected in cadaver tissues, blood, and cerebrospinal fluid by immunohistochemistry, immunofluorescence, or enzyme immunoassay (ELISA).

Detection of RNA fragments of dengue virus

Dengue virus RNA fragments can be detected in blood and cerebrospinal fluid by gene amplification (RT-PCR: Reverse transcriptase - Polymerase chain reaction). This technique has a high sensitivity for rapid and early diagnosis of dengue hemorrhagic fever.

Serological diagnosis

Detection of anti-Dengue antibodies in patient's serum by erythrocyte agglutination inhibitor, complement conjugation reaction. Need to take the double serum, blood 1 is taken at the onset of the disease, blood 2 is taken 5 days to 2 weeks after blood 1 to find antibody dynamics.

Currently, MAC ELISA is commonly used to detect Dengue virus IgM antibodies that appear on day 5 of illness. The MAC ELISA reaction has the advantage that it is only necessary to draw blood once during the first week of illness (days 5-7).

Prevention and cure

Prevention

The most effective way to prevent the disease is to kill the Aedes aegypti mosquito by all possible methods. Because there is no vaccine to prevent the disease, monitoring and killing mosquitoes are the main way to prevent dengue today.

The dengue vaccine is being researched and tested.

To cure

There is no specific cure, only treating symptoms and improving resistance. For severe cases with shock, emergency treatment must be urgent, mainly by rapid replacement of circulating volume with fluids, preferably plasma, and when there is internal bleeding, blood transfusion.