Kyasanur Forest disease

Kyasanur Forest disease (KFD) is a tick-borne viral hemorrhagic fever endemic to South Asia.^[1] The disease is caused by a virus belonging to the family Flaviviridae, which also includes yellow fever and dengue fever.

History

The disease was first reported from Kyasanur Forest of Karnataka in India in March 1957. The disease first manifested as an epizootic outbreak among monkeys killing several of them in the year 1957. Hence the disease is also locally known as Monkey Disease or Monkey Fever.^[2] The similarity with Russian Spring-summer encephalitis was noted and the possibility of migratory birds carrying the disease was raised.^[3] Studies began to look for the possible species that acted as reservoirs for the virus and the agents responsible for transmission. Subsequent studies failed to find any involvement of migratory birds although the possibility of their role in initial establishment was not ruled out. The virus was found to be quite distinctive and not closely related to the Russian virus strains. Antigenic relatedness is however close to many other strains including the Omsk hemorrhagic fever (OHF) and birds from Siberia have been found to show an antigenic response to KFD virus. Sequence based studies however note the distinctivenss of OHF.^[4] Early studies in India were conducted in collaboration with the US Army Medical Research Unit and this led to controversy and conspiracy theories.^[5][6]

Subsequent studies based on sequencing found that the Alkhurma virus, found in Saudi Arabia is closely related.^[7] In 1989 a patient in Nanjianin, China was found with fever symptoms and in 2009 its viral gene sequence was found to exactly match with that of the KFD reference virus of 1957. This has however been questioned since the Indian virus shows variations in sequence over time and the exact match with the virus sequence of 1957 and the Chinese virus of 1989 is not expected. This study also found using immune response tests that birds and humans in the region appeared to have been exposed to the virus.^[8] Another study has suggested that the virus is recent in origin dating the nearest common ancestor of it and related viruses to around 1942, based on the estimated rate of sequence substitutions. The study also raises the possibility of bird involvement in long-distance transfer.^[9] It appears that these viruses diverged 700 years ago.^[10]

Distribution

The disease was first noted at Kyasanur village near Sagar in Shivamogga district of Karnataka. The virus has been detected in monkeys in parts of Bandipur National Park (Chamarajnagar) and parts of the Nilgiris. Human infection occurred in Bandipur through handling of dead monkeys that were infected. A human carrier was also detected in Wayanad (Kerala).^[11]

Transmission

There are a variety of animals thought to be reservoir hosts for the disease, including porcupines, rats, squirrels, mice and shrews.^[12] The vector for disease transmission is Haemaphysalis spinigera, a forest tick.^[13] Humans contract infection from the bite of nymphs of the tick.

Epidemiology

The disease has a fatality rate of 3-10%, and it affects 400-500 people annually.^{[14] [15]}

Symptoms

The symptoms of the disease include a high fever with frontal headaches, followed by haemorrhagic symptoms, such as bleeding from the nasal cavity, throat, and gums, as well as gastrointestinal bleeding.^[12] Other symptoms include vomiting, muscle stiffness, tremors, absent reflexes, and mental disturbances. ^{[16] [17]}

An affected person may recover in two weeks time, but the convalescent period is typically very long, lasting for several months. There will be muscle aches and weakness during this period and the affected person is unable to engage in physical activities.

Genetics

The genome of KFDV consists of 10,774 nucleotides of single-stranded positive sense RNA.^[18] Its genome was discovered to only code for one polyprotein: C-prM-E-NS1-NS2A-NS2B-NS3-NS4A-NS4B-NS5.^{[19] [20]} The genome of KFDV is very similar (>92% homologous) to that of Alkhurma Hemorrhagic Fever Virus which is primarily found in Saudi Arabia. These two species both belong to the family Flaviviridae and diverged over 700 years ago and have thus remained geographically separated.^[21]

Pathology

The pathogenesis of KFDV is not completely understood, but studies have been undertaken that have given insight to the pathology that was previously unknown. Research using mice models found that KFDV primarily replicated in the brain.^[22] Other research has expanded on this by described neurological changes that occurred within infected organisms. This experiment was completed by using KFDV-infected mice and discovered that KFDV caused gliosis, inflammation, and cell death in the brain. Within their discussion, the authors presented the idea that KFDV could be primarily a neuropathic disease and other symptoms are due to this pathogenesis.^[23]

Diagnosis

Previous methods of diagnosis included HI, complement fixation, neutralization tests, and injecting the serum of infected individuals into mice. However, new research has introduced more efficient methods to diagnose KFDV. These methods include: nested RT-PCR, TaqMan-based real-time RT-PCR, and immunoglobin M antibodies detection by ELISA. The two methods involving PCR are able to function by attaching a primer to the NS-5 gene which is highly conserved among the genus to which KFDV belongs. The last method allows for the detections of anti-KFDV antibodies in patients.^[24]

Prevention and treatment

Prophylaxis by vaccination, as well as preventive measures like protective clothing, tick control, and mosquito control are advised. The vaccine for KFDV consists of formalin-inactivated KFDV. The vaccine has a 62.4% effectiveness rate for individuals who receive two doses. For individuals who receive an additonal dose, the effectiveness increases to 82.9%.^[25] Specific treatments are not available.

References