Kyasanur Forest Disease; A Review
Kyasanur Forest Disease (KFD) is a flavivirus infection caused by KFD virus which is transmitted by the bite of the tick (Haemaphysalis spinigera) or by close contact with infected monkeys. The infection is known since 1957 and was first seen around Shimoga district in the Indian State of Karnataka. Thereafter, it spread to other neighbouring states. KFD is mainly a zoonotic disease primarily causing infection in small rodents, birds and monkeys. Other animals may also get infected, but these animals play a little role in transmission of infection to man. Clinical manifestations may resemble other flavivirus infections causing haemorrhagic fevers. Incubation period is 3 – 8 days. Most cases resolve within 1-2 weeks, but 10-20% of patients may have complications. Diagnosis is based on molecular tests like real time PCR and ELISA test for IgM and IgG antibodies. Other blood parameters may provide supportive evidence for diagnosis. Formalin inactivated vaccine is available for prophylaxis, however, its efficacy is questionable as cases have been reported in some individuals despite vaccination.
Kyasanur Forest Disease, commonly known as ‘Monkey Fever’, is an arboviral infection, known since 1957. It is transmitted through the bite of nymph or tick Haemaphysalis spinigera. The causative agent, is Kyasanur Forest Disease virus, a RNA virus belonging to the Flavivirus family and is closely related to the virus responsible for Russian Spring-Summer Encephalitis.
KFD virus was first isolated in 1957 from a sick monkey from Kyasanur forest in Karnataka, hence the name KFD[1,2]. The disease was confined to regions around Kyasanur forest, mainly in Sagar Taluka, of Shimoga district, but subsequently spread to other areas of Uttar Kannada and further down south to Chikmaglur, Udupi and Mangalore. Later, the disease was reported from many neighbouring states including Tamil Nadu, Kerala, Maharashtra and Pali in Goa from 2011. In the recent times, outbreaks have been reported in Pali (Bicholim Taluka, Goa) in 2015 and Mauxi (Satari Taluka, Goa) in 2016. Centre for Disease Control (CDC) reports account for 400 to 500 cases and case fatality of 3% -5% every year, while other reports suggest 40-1000 cases with case fatality of 4 to 15%. The spread of KFD beyond Shimoga district was probably related to cutting down parts of the Shimoga forest and the infected monkeys migrating to other areas, thus spreading the infection. Hence, cutting down of the forest for cultivation or other purposes poses a great risk for the transmission of KFD.
A virus similar to KFD, Alkhurma Hemorrhagic Fever virus has been reported from Saudi Arabia. The relationship and link between these two viruses is yet to be established although they show 89% sequence homology[1,6].
Mode of transmission
Kyasanur Forest Disease is transmitted to man through the bite of infected hard ticks Haemaphysalis spinigera and their nymphs, or from close contact with infected animals. The infected ticks are highly anthropophilic and act as reservoirs of infection. The ticks drop from the infected animals after the death of these animals as their temperature comes down. In ticks, there is trans stadial transmission and once infected, they remain infected lifelong. However, transovarian transmission is not significant, although it is reported by some workers in other species of Haemaphysalis other than H. spinigera. KFD virus has been isolated from at least 16 different species of ticks, but Haemaphysalis spinigera is the major vector responsible for human transmission. The virus is known to infect small mammals, rodents, shrews, ground birds, ticks and monkeys. These monkeys later act as an amplifier host thereby spreading infection. People at risk of getting infected are hunters, campers, forest workers, animal attendants and farmers who venture into the forest and are accidentally bitten by ticks. Apart from small animals, other animals like goat, sheep and cow may also be infected but they do not play a role in human transmission. Unpasteurised milk from these animals is also not known to transmit infection.
Human infection leads to a dead end and no man to man transmission has been reported. There is also no evidence to suggest a nosocomial infection caused by KFD virus as this virus is not found in body fluids except blood.
Clinical manifestations of KFD are seen after an incubation period of 3-8 days. The patient presents with sudden onset of fever, chills, headache and severe muscle pain, which may be associated with vomiting, gastrointestinal symptoms and photophobia. Bleeding problems may be seen 3-4 days after initial symptoms. Patient may present with low blood pressure and decreased platelets, red blood cells and white blood cells. About 80-90% of patients may recover within 1-2 weeks of symptoms without any complications. However, in 10-20% of patients, the presentation is biphasic, with second phase of symptoms appearing in the beginning of third week. These symptoms include fever, severe headache, neurological manifestations, mental disturbances, tremors and vision defects. The case fatality is estimated to be 3 to 5% from KFD.
The clinical presentation may resemble haemorrhagic fever caused by other related arboviruses including dengue and etiological diagnosis may be the only means for confirmation.
Viral diagnostic laboratory was set up in Karnataka State for diagnosis of KFD in 1957 and was mainly based on isolation of the virus, serological tests like Haemagglutination Inhibition test (HI), Complement Fixation (CFT) and Neutralization test. Modern diagnostic tests developed by National Institute of Virology (NIV) in Pune, include Real time PCR, IgM and IgG Capture ELISA[3,8].
Other supportive laboratory findings include altered liver function tests, hypoalbuminemia, slightly raised levels of gamma globulins, moderately raised levels of alkaline phosphatase and bilirubin along with lymphopenia.
There is no specific treatment for Kyasanur Forest Disease, but early hospitalization with supportive care, maintenance of hydration and monitoring of bleeding disorders are found to be useful measures.
Formalin inactivated tissue culture vaccine which is available for control of KFD, was developed by the NIV in 1970. The technology is currently transferred to Karnataka Public Health Department for production of Vaccine. The vaccine gives rise to neutralizing antibodies in the 70% of vaccinated population. The vaccination strategy in Karnataka involves mass administration of vaccine during the months of August to November where KFD activity is reported based on laboratory evidence of infection in man or monkey within a radius of five kilometres. The dose schedule comprises of 2 doses given within the interval of one month for individuals within the age group of 7-65 years. Immunity is short lasting and booster doses are recommended for the subsequent five years[1,9].
Number of KFD cases in Karnataka has been increasing in the recent past, despite routine vaccination against KFD for high risk population and there are reports of KFD illness developing in vaccinated people, thereby suggesting insufficient efficacy of currently used vaccine and need for newer vaccine.
Other preventive measures against KFD include tick control with insecticide Lindane, which is highly effective in killing ticks. Tick repellents such as DEET, DMP and DBP provide 90-100% protection against tick bite. People visiting tick infested areas should wear appropriate protective garments.
Kyasunur Forest disease is one of the tick borne re-emerging viral infections in and around endemic areas where it was first reported. Although there is evidence that it is spreading beyond the known endemic areas on account of migration of monkeys, there is no satisfying argument for its occurrence in some localities not linked to endemic areas. Clinical suspicion should always be kept in mind especially in localities where monkey deaths are reported. Strict surveillance should be kept on the spread of disease and an etiological diagnosis should be made whenever possible using real time PCR and/ or Capture ELISA for IgM and IgG antibodies. Case management does not need any specific therapy, but supportive care should be provided all the time with stringent supervision. Further, people living in the vicinity of a forest should be on alert especially when monkey deaths are reported and should keep away from carcasses of dead monkeys. Such deaths should be brought to the notice of local health care authorities. Vaccination and preventive measures against ticks should be actively considered for high risk population. However low efficacy of vaccine and occurrence of KFD in some vaccinated population should act as a driving force for a new vaccine search.
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