| Kyasanur forest disease | |
|---|---|
| Other names | Monkey disease, monkey fever |
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| Virus ecology | |
| Specialty | Infectious disease |
Kyasanur forest disease (KFD) is a tick-borne viral haemorrhagic fever endemic to South-western part of India. [1] The disease is caused by a virus belonging to the family Flaviviridae. KFDV is transmitted to humans through the bite of infected hard ticks ( Haemaphysalis spinigera ) which act as a reservoir of KFDV.
The symptoms of the disease include a high fever with frontal headaches, chills, severe muscle pain, vomiting, and other gastrointestinal symptoms. Bleeding problems may occur 3–4 days after initial symptom onset. Patients may experience abnormally low blood pressure, and low platelet, red blood cell, and white blood cell count. After 1–2 weeks of symptoms, some patients recover without complication. However, the illness is biphasic for a subset of patients (10–20%) who experience a second wave of symptoms at the beginning of the third week. These symptoms include fever and signs of neurological manifestations, such as severe headache, mental disturbances, tremors, and vision deficits. [2] [3] [4] The convalescent period is typically very long, lasting several months. Muscle aches and weakness also occur during this period, and the patient is unable to engage in physical activities.
| Kyasanur Forest disease virus | |
|---|---|
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| Flavivirus structure and genome | |
Virus classification  | |
| (unranked): | Virus |
| Realm: | Riboviria |
| Kingdom: | Orthornavirae |
| Phylum: | Kitrinoviricota |
| Class: | Flasuviricetes |
| Order: | Amarillovirales |
| Family: | Flaviviridae |
| Genus: | Flavivirus |
| Species: | Kyasanur Forest disease virus |
| Synonyms [5] | |
Kyasanur Forest virus | |
The KFD virus is a typical flavivirus measuring about 40–60 nm in diameter. The genome of KFDV consists of 10,774 nucleotides of single-stranded, positive-sense RNA encoding a single polyprotein that is cleaved post-translationally into three structural (C, prM/M and E) and seven non-structural (NS1, NS2a, NS2b, NS3, NS4a, NS4b and NS5) proteins. [6] [7] [8] 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. [9]
A variety of animals are thought to be reservoir hosts for the disease, including porcupines, rats, squirrels, mice, and shrews. [2] Monkeys are the main amplifying hosts for KFD virus and they are also affected by the virus. The surili Presbytis entellus and the bonnet macaque are very susceptible to the KFD virus. They develop tremendous viremia and infect the ticks. The vector for disease transmission is Haemaphysalis spinigera , a forest tick. [10] Humans contract infection from the bite of nymphs of the tick. Man is a terminal host and there no human-to-human transmission because the human domestic environment does not sustain the ticks.
The pathogenesis of KFDV is not completely understood. Research using mice models found that KFDV primarily replicated in the brain. [11] 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. They posited that KFDV could be primarily a neuropathic disease and other symptoms are due to this pathogenesis. [12]
In earlier days suspected case were confirmed in a laboratory by serum inoculation into suckling mice (Swiss Albino mice) and subsequent death of mice was leveled as KFD Positive case. Other methods of diagnosis included hemagglutination inhibition (HI), complement fixation, neutralization tests. [13] However, new research has introduced more efficient molecular based methods to diagnose KFDV. These methods include: RT-PCR, nested RT-PCR, TaqMan-based real-time RT-PCR, Immunoglobin M antibodies and Immunoglobin G detection by ELISA. The two methods involving RT-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. PCR positivity is limited to 8–10 days from the onset of symptoms. The ELISA based methods allows for the detections of anti-KFDV antibodies in patients typically from 5th day of onset of symptoms up to 3 months. [14]
Prevention is by vaccination, as well as preventive measures such as protective clothing and tick population control. 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 additional dose, the effectiveness increases to 82.9%. [15] Specific antiviral treatments are not available as of 2022. [16]
Kyassanur forest disease spreads in places where humans interact with wildlife, especially villages adjoining forest areas and inter-state borders. [17] People who frequently visit the forest areas of the Western Ghats and who refuse the KFD vaccination have a high risk of acquiring KFD infection.
The disease was first reported from Kattinakere village forest which is in the Kyasanur forest range of Karnataka in India in March 1957. When the officials visited the Kattinakere forest and discovered the diseases they noticed a sign board informing that this was the Kyasanur forest range. Hence the name. 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". [18] The similarity with Russian spring-summer encephalitis was noted by the British neurovirologist Hubert Webb and the possibility of migratory birds carrying the disease was raised. [19] 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 note the distinctiveness of OHF. [20] Early studies in India were conducted in collaboration with the US Army Medical Research Unit and this led to controversy and conspiracy theories. [21] [22]
Subsequent studies based on sequencing found that the Alkhurma virus found in Saudi Arabia is closely related. [23] 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 been questioned, though, 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. [24] 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. [25] It appears that these viruses diverged 700 years ago. [26]
A recent outbreak in 2020, claimed two lives in Siddapura, Karnataka. The peak season for this disease in Malnad is from March till May but has been observed to peak earlier in the year as well. There were a total of 55 reported cases in Shivamogga district, Karntaka. [27] [28]
The disease initially reported from Shimoga district of Karnataka which is a primitive sylvan territory in Western Ghats of India. The disease spread out to other districts of Karnataka involving districts of Chikkamagalore, Uttara Kannada, Dakshina Kannada, Udupi, Chamarajanagar (2012), Belagavi (2016). In 2013, KFDV was detected in monkey autopsies from Nilgiris district of Tamil Nadu state. Monkey deaths and human cases have now been reported from three neighbouring states bordering Karnataka, i.e., Wayanad (2013) and Malappuram districts of Kerala (2014), North Goa district of Goa state (2015), and Sindhudurg district of Maharashtra (2016). [29]
There are reported serological evidence for KFD detected in humans in other parts of India, namely Kutch and Saurashtra regions of Gujarat state, Kingaon and Parbatpur of West Bengal state. [30] A seroprevalence study in Andaman and Nicobar islands in 2002 revealed a high prevalence of hemagglutination inhibition (HI) antibodies against KFDV. [31]
The disease has a fatality rate of 3-10%, and it affects 400-500 people annually. [10] [14]
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). [32] The disease has shown its presence in the adjacent states of Karnataka including Kerala, Maharashtra, Goa, Tamil Nadu and Gujarat. [33] [34] [35]
Marburg virus disease (MVD), formerly Marburg hemorrhagic fever (MHF) is a viral hemorrhagic fever in human and non-human primates caused by either of the two Marburgviruses: Marburg virus (MARV) and Ravn virus (RAVV). Its clinical symptoms are very similar to those of Ebola virus disease (EVD).
Chikungunya is an infection caused by the Chikungunya virus (CHIKV). The disease was first identified in 1952 in Tanzania and named based on the Kimakonde words for "to become contorted".
Flavivirus, renamed Orthoflavivirus in 2023, is a genus of positive-strand RNA viruses in the family Flaviviridae. The genus includes the West Nile virus, dengue virus, tick-borne encephalitis virus, yellow fever virus, Zika virus and several other viruses which may cause encephalitis, as well as insect-specific flaviviruses (ISFs) such as cell fusing agent virus (CFAV), Palm Creek virus (PCV), and Parramatta River virus (PaRV). While dual-host flaviviruses can infect vertebrates as well as arthropods, insect-specific flaviviruses are restricted to their competent arthropods. The means by which flaviviruses establish persistent infection in their competent vectors and cause disease in humans depends upon several virus-host interactions, including the intricate interplay between flavivirus-encoded immune antagonists and the host antiviral innate immune effector molecules.
Arbovirus is an informal name for any virus that is transmitted by arthropod vectors. The term arbovirus is a portmanteau word. Tibovirus is sometimes used to more specifically describe viruses transmitted by ticks, a superorder within the arthropods. Arboviruses can affect both animals and plants. In humans, symptoms of arbovirus infection generally occur 3–15 days after exposure to the virus and last three or four days. The most common clinical features of infection are fever, headache, and malaise, but encephalitis and viral hemorrhagic fever may also occur.
Tick-borne diseases, which afflict humans and other animals, are caused by infectious agents transmitted by tick bites. They are caused by infection with a variety of pathogens, including rickettsia and other types of bacteria, viruses, and protozoa. The economic impact of tick-borne diseases is considered to be substantial in humans, and tick-borne diseases are estimated to affect ~80 % of cattle worldwide. Most of these pathogens require passage through vertebrate hosts as part of their life cycle. Tick-borne infections in humans, farm animals, and companion animals are primarily associated with wildlife animal reservoirs. Many tick-borne infections in humans involve a complex cycle between wildlife animal reservoirs and tick vectors. The survival and transmission of these tick-borne viruses are closely linked to their interactions with tick vectors and host cells. These viruses are classified into different families, including Asfarviridae, Reoviridae, Rhabdoviridae, Orthomyxoviridae, Bunyaviridae, and Flaviviridae.
Bunyavirales is an order of segmented negative-strand RNA viruses with mainly tripartite genomes. Member viruses infect arthropods, plants, protozoans, and vertebrates. It is the only order in the class Ellioviricetes. The name Bunyavirales derives from Bunyamwera, where the original type species Bunyamwera orthobunyavirus was first discovered. Ellioviricetes is named in honor of late virologist Richard M. Elliott for his early work on bunyaviruses.
Viral hemorrhagic fevers (VHFs) are a diverse group of animal and human illnesses. VHFs may be caused by five distinct families of RNA viruses: the families Filoviridae, Flaviviridae, Rhabdoviridae, and several member families of the Bunyavirales order such as Arenaviridae, and Hantaviridae. All types of VHF are characterized by fever and bleeding disorders and all can progress to high fever, shock and death in many cases. Some of the VHF agents cause relatively mild illnesses, such as the Scandinavian nephropathia epidemica, while others, such as Ebola virus, can cause severe, life-threatening disease.
Tick-borne encephalitis (TBE) is a viral infectious disease involving the central nervous system. The disease most often manifests as meningitis, encephalitis or meningoencephalitis. Myelitis and spinal paralysis also occurs. In about one third of cases sequelae, predominantly cognitive dysfunction, persist for a year or more.
Crimean–Congo hemorrhagic fever (CCHF) is a viral disease. Symptoms of CCHF may include fever, muscle pains, headache, vomiting, diarrhea, and bleeding into the skin. Onset of symptoms is less than two weeks following exposure. Complications may include liver failure. Survivors generally recover around two weeks after onset.
Thogotovirus is a genus of enveloped RNA viruses, one of seven genera in the virus family Orthomyxoviridae. Their single-stranded, negative-sense RNA genome has six or seven segments. Thogotoviruses are distinguished from most other orthomyxoviruses by being arboviruses – viruses that are transmitted by arthropods, in this case usually ticks. Thogotoviruses can replicate in both tick cells and vertebrate cells; one subtype has also been isolated from mosquitoes. A consequence of being transmitted by blood-sucking vectors is that the virus must spread systemically in the vertebrate host – unlike influenza viruses, which are transmitted by respiratory droplets and are usually confined to the respiratory system.
An emerging infectious disease (EID) is an infectious disease whose incidence has increased recently, and could increase in the near future. The minority that are capable of developing efficient transmission between humans can become major public and global concerns as potential causes of epidemics or pandemics. Their many impacts can be economic and societal, as well as clinical. EIDs have been increasing steadily since at least 1940.
Alkhurma virus (ALKV) is a zoonotic virus of the Flaviviridae virus family. ALKV causes Alkhurma hemorrhagic fever (AHF), or alternatively termed as Alkhurma hemorrhagic fever virus, and is mainly based in Saudi Arabia.
The National Institute of Virology in Pune, India is an Indian virology research institute and part of the Indian Council of Medical Research (ICMR). It was previously known as 'Virus Research Centre' and was founded in collaboration with the Rockefeller Foundation. It has been designated as a WHO H5 reference laboratory for SE Asia region.
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Langat virus (LGTV) is a virus of the genus Flavivirus. The virus was first isolated in Malaysia in 1956 from a hard tick of the Ixodes genus. This virus is antigenically related to Omsk hemorrhagic fever virus, Kyasanur forest disease virus, Alkhurma virus, Louping ill virus and other viruses of the tick-borne encephalitis virus (TBEV) complex. The Langat virus does not pose a significant epidemiological threat in comparison with TBEV. There are no known cases of human diseases associated with LGTV. The Malaysian strain is naturally attenuated and induces neutralizing antibodies to tick-borne encephalitis virus (TBEV) and protection against other TBEV complex viruses in animals.
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