Kyasanur forest disease

Kiasanur Forest Disease (KLB) is an acute viral zoonotic infection of a person that occurs with severe intoxication, often with a two-phase fever, accompanied by severe hemorrhagic syndrome, prolonged asthenic manifestations.

The Kiasanur forest disease was first isolated into a separate nosological form in 1957 after an outbreak of a very lethal disease in the state of Mysore (now Kartanaka) in the village of Kiasanur in India. Symptoms of the kyasanur forest disease (hemorrhagic syndrome, liver damage) were originally associated with a new variant of the (Asian) course of yellow fever, but the isolated virus from the dead monkeys and from the ticks belonged to a pathogen other than the yellow fever virus but also to the Flavivitidae family. According to its antigenic properties, the virus of the Kiasanur forest disease is similar to the Omsk hemorrhagic fever virus.

[1], [2], [3], [4], [5]

Epidemiology of kyasanur forest disease

Outbreaks of Kiasanur forest disease are registered only in the state of Cartanac for several dozen cases annually. At the same time, in recent years, the presence of specific antibodies to the Kiasanur forest disease in wild animals and humans in the remote North Kartanaki region of northwestern India has been established (there are no outbreaks of Kiasanur forest disease there). Endemic foci are located in the area of tropical forests on mountain slopes and valleys with lush vegetation and a large spread of mites, mainly Haemaphysalis spinigera (up to 90% of all cases), wild mammals (monkeys, pigs, porcupines), birds, forest rodents (protein, rats). There is no transovarial transmission of the virus in ticks. The person is mainly infected through the nymph of the tick. The virus can persist for a long time (in the dry season) in the mite. Livestock does not play a significant role in spreading the infection.

The infection of a person occurs by a transmissible way during human activities (hunters, farmers, etc.) in the forests of the endemic area; mostly men fall ill.

[6], [7], [8]

Causes of Kiasanur Forest Disease

[9]

Family Flaviviridae

The family name Flaviviridae comes from the Latin. Flavus - yellow, by the name of the disease "yellow fever", which causes the virus of this family. The family consists of three genuses, two of which are pathogenic to humans: the Flavivirus genus, which includes a variety of pathogens for arbovirus infections and the genus Hepacivints, which includes the hepatitis C virus (HCV) and G (HGV).

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

Characteristics of hemorrhagic fevers of the Flaviviridae family

Name of GL	The genus of the virus	The transporter	Distribution of GL
Yellow fever	Flavivirus Yellow fever	Mosquitoes (Aedes aegypti)	Tropical Africa, South America
Dengue	Flaviviras Dengue	Mosquitoes (Aedes aegypti, less often A. Albopjctus, A. Polynesiensis)	Asia, South America, Africa
Kmasanur Forest disease	Flaviviras Kyasanur Forest	Ticks (Haemaphysalis spinigera)	India (Karnataka State)
Omsk hemorrhagic fever	Flaviviras Omsk	Ticks (Dermacentor pictus and D. Marginatus)	Russia Siberia)

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

During reproduction, viruses enter the cell through receptor endocytosis. The viral replicative complex is associated with a nuclear membrane. Flavivirus reproduction is slower (more than 12 hours) than in alpha viruses. The polyprotein is translated with viral RNA, which decomposes into several (up to 8) non-structural proteins, including protease and RNA-dependent RNA polymerase (replicase), capsid and supercapsid proteins. Unlike alpha viruses, 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 alpha viruses.

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

Flaviviruses on antigenic relationship are grouped in complexes: a complex of viruses of tick-borne encephalitis, Japanese encephalitis, yellow fever, dengue fever, etc.

A universal model for the isolation of flaviviruses is the intracerebral infection of newborn white mice and their suckers, in whom paralysis develops. It is possible to infect monkeys and chick embryos on the chorioallantoic membrane and into the yolk sac. For the viruses of dengue fever, mosquitoes are a highly sensitive model. Flaviviruses are sensitive to many cultures of human cells and warm-blooded animals, where they cause CPD. In cultures of arthropods cells, the CPD was not observed.

Flaviviruses are not very stable in the environment. They are sensitive to the action of ether, detergents, chlorine-containing disinfectants, formalin, UV, heating above 56 ° C. Preserve contagiosity 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 vectors. For arthropods, transfacial and transovarial transmission of flaviviruses has been demonstrated. The vast majority of flaviviruses are spread by mosquitoes (dengue fever viruses, yellow fever virus), some are transmitted by mites (Kiasanur Forest disease virus, etc.). Mosquito flavivirus infections are prevalent mainly near the equatorial zone - from 15 ° N. Up to 15 ° S Tick infections, on the other hand, are found everywhere. Their feeders-warm-blooded vertebrates (rodents, birds, bats, primates, etc.) play an important role in maintaining the flavivirus population in nature. Man - an accidental, "deadlock" link in the ecology of flaviviruses. However, for a dengue fever and urban yellow fever, the sick person can also be a reservoir and source of the virus.

Infection with flaviviruses can occur by contact, aerogenic and food pathways. A person is highly susceptible to these viruses.

Immunity after the transferred diseases is intense, repeated diseases are not observed.

[10], [11],

Pathogenesis of the Kiasanur Forest Disease

The pathogenesis of the Kiasanur forest disease is similar to the pathogenesis of many hemorrhagic fevers, and has been little studied in humans. In the experimental models it was found that a prolonged circulation of the virus is observed in the 1-2 days of the disease to 12-14 days with a peak between the 4th and 7th days of the disease. There is generalized dissemination of the virus, the defeat of various organs: the liver (areas of predominantly central necrosis of the lobes), kidneys (lesions with glomerular and tubular necrosis). Significantly increased apoptosis of various cells of erythrocyte and leukocyte sprouts. There are significant foci of endothelial damage of various organs (intestine, liver, kidneys, brain of the lungs). In the lungs, interstitial inflammation of the peribronchial tree with a hemorrhagic component can develop. Inflammatory processes in the sinuses of the spleen with increased erythrocyte lysis (erythrophagocytosis) are noted. Perhaps the development of myocarditis, encephalitis, similar to Omsk hemorrhagic fever and haemorrhagic fever in the Rift Valley.

Symptoms of Kiasanur Forest Disease

The incubation period of the Kiasanur forest disease lasts from 3 to 8 days. Kiasanur forest disease begins acutely - with high fever, chills, headache, pronounced myalgias, leading to exhaustion of the patients. There may be symptoms of kyasanur forest disease, such as eye pain, vomiting, diarrhea, abdominal pain, hyperesthesia. On examination, there is hyperemia of the face, conjunctivitis, often there is generalized lymphadenopathy (probably enlargement of the lymph nodes only of the head and neck).

In more than 50% of cases, the Kiasanur Forest disease is accompanied by a clinic of pneumonia with a lethality of 10 to 33% of cases. Hemorrhagic syndrome is accompanied by the development of bleeding from the mucous cavity of the mouth (gums), nose, gastrointestinal tract. In 50% of cases, there is an increase in the liver, rarely jaundice. A slow heart rate (AV block) is often determined. Meningism and meningitis can be observed (moderately expressed monocytic pleocytosis). The development of convulsive syndrome, often accompanied by the development of hemorrhagic pulmonary edema, is an unfavorable prognosis. Sometimes there may be signs of encephalitis.

In 15% of cases a few days later the temperature normalizes, and after 7-21 days it rises again, and all signs of the disease return. The risk of complications with a repeated increase in temperature is much higher, and the prognosis is unfavorable.

The period of convalescence can last from several weeks to months - the patients have weakness, adynamia, headache.

Diagnosis of Kiasanur Forest Disease

In the peripheral blood, leukopenia, thrombocytopenia, anemia are detected. There may be an increase in ALT and ACT. Paired sera in ELISA and RPGA demonstrate an increase in titer by 4 times, also in the diagnosis using the neutralization of antibodies and RSK. Cross-reactions with other viruses from this group are possible. Virological diagnostics of the Kiasanur forest disease is used, PCR diagnostics is developed.

[12], [13], [14]

Treatment of Kiasanur Forest Disease

Specific treatment of Kiasanur forest disease is absent. Pathogenetic treatment is performed (as in other hemorrhagic fevers).

How is kyasanur forest disease prevented?

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