Kyasanurus forest disease

Kyasanur forest disease (KFD) is an acute viral zoonotic infection of humans, which occurs with severe intoxication, often with biphasic fever, and is accompanied by severe hemorrhagic syndrome and prolonged asthenic manifestations.

Kyasanur forest disease was first identified as a separate nosological entity in 1957 after an outbreak of the disease with high mortality in the state of Mysore (now Kartanaka) in the village of Kyasanur in India. The symptoms of Kyasanur forest disease (hemorrhagic syndrome, liver damage) were initially associated with a new variant (Asian) of yellow fever, but the virus isolated from dead monkeys and ticks belonged to a pathogen different from the yellow fever virus but also to the Flavivitidae family. In its antigenic properties, the Kyasanur forest disease virus is similar to the Omsk hemorrhagic fever virus.

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Epidemiology of Kyasanur forest disease

Outbreaks of Kyasanur forest disease are registered only in the state of Kartanaka, several dozen cases annually. At the same time, in recent years, the presence of specific antibodies to Kyasanur forest disease has been established in wild animals and people in the northwestern region of India, remote from the state of Kartanaka (outbreaks of Kyasanur forest disease have not been registered there). Endemic foci are located in the area of tropical forests on mountain slopes and valleys with lush vegetation and a large distribution of ticks, mainly Haemaphysalis spinigera (up to 90% of all cases of the disease), among wild mammals (monkeys, pigs, porcupines), birds, forest rodents (squirrels, rats). Ticks do not transmit the virus transovarially. Humans are mainly infected through tick nymphs. The virus can persist for a long time (in the dry season) in the tick's body. Domestic cattle do not play a significant role in the spread of the infection.

Human infection occurs through transmission during human activities (hunters, farmers, etc.) in the forests of the endemic region; mainly men become ill.

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Causes of Kyasanur forest disease

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Family Flaviviridae

The name of the Flaviviridae family comes from the Latin flavus - yellow, after the name of the disease "yellow fever", which is caused by the virus of this family. The family unites three genera, two of which are pathogenic for humans: the Flavivirus genus, which includes many pathogens of arbovirus infections, and the Hepacivints genus, which includes the hepatitis C virus (HCV) and G (HGV).

The type representative of the Flaviviridae family is the yellow fever virus, strain Asibi, belonging to the genus Flavivirus.

Characteristics of hemorrhagic fevers of the Flaviviridae family

Name of GL	Genus of virus	Carrier	Spread of GL
Yellow fever	Flavivirus Yellow Fever	Mosquitoes (Aedes aegypti)	Tropical Africa, South America
Dengue	Flavored Dengue	Mosquitoes (Aedes aegypti, less commonly A. albopjctus, A. polynesiensis)	Asia, South America, Africa
Kmasanur forest disease	Flaviviras Kyasanur Forest	Ticks (Haemaphysalis spinigera)	India (Karnataka)
Omsk hemorrhagic fever	Flavors Omsk	Ticks (Dermacentor pictus and D. marginatus)	Russia (Siberia)

Kyasanur forest disease is caused by complex RNA-genomic viruses of spherical shape. They are smaller than alpha viruses (their diameter is up to 60 nm), have a cubic type of symmetry. The genome of the viruses consists of a linear single-stranded plus-RNA. The nucleocapsid contains protein V2, the surface of the supercapsid contains glycoprotein V3, and on its inner side - structural protein VI.

During reproduction, viruses penetrate the cell by receptor endocytosis. The viral replicative complex is associated with the nuclear membrane. Reproduction of flaviviruses is slower (more than 12 hours) than that of alphaviruses. A polyprotein is translated from viral RNA, which breaks down into several (up to 8) nonstructural proteins, including protease and RNA-dependent RNA polymerase (replicase), capsid and supercapsid proteins. Unlike alphaviruses, only one type of mRNA (45S) of flaviviruses is formed in the cell. Maturation occurs by budding through the membranes of the endoplasmic reticulum. In the cavity of vacuoles, viral proteins form crystals. Flaviviruses are more pathogenic than alphaviruses.

Glycoprotein V3 has diagnostic significance: it contains genus-, species- and complex-specific antigen determinants, is a protective antigen and hemagglutinin. Hemagglutinating properties of flaviviruses are manifested in a narrow pH range.

Flaviviruses are grouped into complexes based on antigenic relatedness: the complex of tick-borne encephalitis viruses, Japanese encephalitis, yellow fever, dengue fever, etc.

A universal model for isolating flaviviruses is intracerebral infection of newborn white mice and their sucklings, which develop paralysis. Infection of monkeys and chicken embryos is possible in the chorioallantoic membrane and yolk sac. Mosquitoes are a highly sensitive model for dengue fever viruses. Many cell cultures of humans and warm-blooded animals are sensitive to flaviviruses, where they cause CPE. CPE has not been observed in arthropod cell cultures.

Flaviviruses are unstable in the environment. They are sensitive to ether, detergents, chlorine-containing disinfectants, formalin, UV, and heating above 56 °C. They remain contagious when frozen and dried.

Flaviviruses are widespread in nature and cause natural focal diseases with a transmissible mechanism of infection. The main reservoir of flaviviruses in nature is blood-sucking arthropods, which are also carriers. Transphase and transovarial transmission of flaviviruses has been proven for arthropods. The vast majority of flaviviruses are spread by mosquitoes (dengue fever viruses, yellow fever virus), some are transmitted by ticks (Kiassanur forest disease virus, etc.). Mosquito-borne flavivirus infections are distributed mainly near the equatorial zone - from 15 ° N to 15 ° S. Tick-borne infections, on the contrary, are found everywhere. An important role in maintaining the population of flaviviruses in nature is played by their hosts - warm-blooded vertebrates (rodents, birds, bats, primates, etc.). Humans are a random, "dead-end" link in the ecology of flaviviruses. However, for dengue fever and urban yellow fever, a sick person can also be a reservoir and source of the virus.

Flavivirus infection can occur through contact, airborne and foodborne routes. Humans are highly susceptible to these viruses.

Immunity after past illnesses is strong, and recurrent illnesses are not observed.

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Pathogenesis of Kyasanur forest disease

The pathogenesis of Kyasanur forest disease is similar to that of many hemorrhagic fevers, and has been poorly studied in humans. Experimental models have shown prolonged circulation of the virus from day 1-2 of illness to day 12-14 with a peak between days 4 and 7 of illness. Generalized dissemination of the virus is observed, with damage to various organs: liver (areas of predominantly central lobule necrosis), kidneys (damage with necrosis of the glomerular and tubular sections). Apoptosis of various cells of the erythrocyte and leukocyte sprouts is significantly increased. Significant foci of damage to the endothelium of various organs (intestines, liver, kidneys, brain, lungs) are noted. Interstitial inflammation of the peribronchial tree with a hemorrhagic component may develop in the lungs. Inflammatory processes are noted in the sinuses of the spleen with increased lysis of erythrocytes (erythrophagocytosis). The development of myocarditis and encephalitis similar to Omsk hemorrhagic fever and Rift Valley hemorrhagic fever is possible.

Symptoms of Kyasanur forest disease

The incubation period of Kyasanur forest disease lasts from 3 to 8 days. Kyasanur forest disease begins acutely - with high temperature, chills, headache, severe myalgia, leading to exhaustion of patients. Symptoms of Kyasanur forest disease may include pain in the eyes, vomiting, diarrhea, abdominal pain, hyperesthesia. During examination, facial hyperemia, conjunctivitis are noted, and generalized lymphadenopathy is often present (an increase in the lymph nodes of the head and neck only is possible).

In more than 50% of cases, Kyasanur forest disease is accompanied by pneumonia with a mortality rate of 10 to 33% of cases. Hemorrhagic syndrome is accompanied by the development of bleeding from the mucous membranes of the oral cavity (gums), nose, gastrointestinal tract. In 50% of cases, an enlarged liver is noted, jaundice rarely develops. A slow pulse (AV block) is often determined. Meningism and meningitis (moderate monocytic pleocytosis) may be observed. The development of convulsive syndrome, often accompanied by the development of hemorrhagic pulmonary edema, is an unfavorable prognosis. Sometimes signs of encephalitis can be observed.

In 15% of cases, the temperature returns to normal after a few days, but rises again after 7-21 days, and all signs of the disease return. The risk of complications with repeated temperature rise is significantly higher, and the prognosis is unfavorable.

The recovery period can last from several weeks to months - patients experience weakness, adynamia, and headache.

Diagnosis of Kyasanur forest disease

Leukopenia, thrombocytopenia, and anemia are detected in the peripheral blood. Increased ALT and AST may be observed. Paired sera in ELISA and RPGA demonstrate a 4-fold increase in titer; antibody neutralization reaction and RSK are also used in diagnostics. Cross-reactions with other viruses from this group are possible. Virological diagnostics of Kyasanur forest disease is used; PCR diagnostics have been developed.

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Treatment of Kyasanur forest disease

There is no specific treatment for Kyasanur forest disease. Pathogenetic treatment is used (as with other hemorrhagic fevers).

How to prevent Kyasanur forest disease?

A specific vaccine (inactivated with formalin) has been developed to prevent Kyasanur forest disease, but its use is limited.