Kyasanur forest disease: Unveiling the spread, consequences, and emerging risks

Introduction

Kyasanur Forest Disease (KFD) was first identified in 1956 in the forests of Shivamogga, Karnataka (Work and Trapido, 1957; Work et al., 1959; Lendzele, 2022) [31,32,33] . In March 1957, the virus was isolated from a black-faced Hanuman langur monkey (Semnopithecus entellus) in the Sorab taluk of Shivamogga (Work and Trapido, 1957; Work, 1958) [31,34] . Further serological studies showed that this novel illness was caused by a virus within the Russian spring-summer encephalitis (RSSE) complex, now recognized as part of the tick-borne encephalitis (TBE) flavivirus group. This finding led to speculation about a yellow fever-like incident in primates in India, though this theory was later disproven (Bhatt et al., 1966; Work and Trapido, 1957) [3,31] . The Virus Research Centre in Pune, alongside the Rockefeller Foundation and state health officials, collected ticks from various animals around the forested regions of Soraba and Sagara taluks in Shivamogga. The virus was subsequently isolated and identified as P9605 (Government of Karnataka, 2020) [7] . The Kyasanur Forest Disease Virus (KFDV) is classified as a high-risk pathogen, and its transmission cycle involves a wide array of vertebrates such as monkeys, bats, rodents, birds, and shrews, making it an unpredictable endemic infection (Carroll et al., 2010) [4] .

Genetic Evolutionary Analysis

Kyasanur Forest Disease virus (KFDV) shares its ancestry with Alkhurma hemorrhagic fever virus (AHFV), both of which belong to the tick-borne encephalitis virus serocomplex of flaviviruses, responsible for severe hemorrhagic fever in humans (Charrel et al., 2001; Simmonds et al., 2017; Work, 1958) [6,27,34] . In 1994, AHFV was identified in a butcher fatally infected in Makkah, Saudi Arabia. The clinical features of both KFD and AHFV are strikingly similar, presenting with sudden fever, muscle pain, encephalitis, and severe bleeding (Madani et al., 2010) [18] . Genetic comparison revealed over 92% homology, indicating divergent evolution over the last 700 years (Dodd et al., 2011) [8] . In 1989, a similar strain of KFD virus was isolated from Yunnan province, China, known as the "Nanjianyin virus" (Wang et al., 2009) [30] , with migratory birds identified as the primary vectors in the emergence of the virus (Ghosh et al., 1975; Venugopal et al., 1992) [10,29] . These birds, migrating from South India, carry infected ticks (Gong et al., 1989; Gong et al., 2001) [11,12] .

Transmission Pathways

KFDV, a member of the Flaviviridae family, has a genome composed of linear, positive-sense, single-stranded RNA of www.extensionjournal.com approximately 11 kb in length (Maclachlan et al., 2017) [17] . The virus is mainly transmitted through the bite of infected ticks (Haemaphysalis spinigera) to primates such as Semnopithecus entellus and Macaca radiata, and occasionally humans (Ajesh et al., 2017; Pattnaik, 2006; Work and Trapido, 1957) [1,24,31] . When an infected monkey dies, ticks detach from the carcass, potentially creating new hotspots (Sadanandane et al., 2017) [26] . Neutralizing antibodies have been identified in several animals, including cattle, buffaloes, porcupines, and birds (Pattnaik, 2016) [24] . Though direct transmission from rodents to humans is possible, person-to-person transmission has not been reported (Pattnaik, 2016) [24] . The tick lifecycle includes three stages-larvae, nymph, and adult-each facilitating virus transmission via bites (Mourya et al., 2014) [21] . Ajesh et al. (2017) [1] reported both transovarial and transstadial transmission in ticks. Co-feeding transmission, where virus exchange occurs between ticks without involving a host, is another efficient transmission method (Randolph, 2011; Mansfield et al., 2017) [25,19] . Additionally, unfed nymphs tend to transmit the infection primarily to humans (Pattnaik, 2006) [24] .

Spatial Distribution

KFD was first detected in the forests of Shivamogga district in Karnataka, a region within the Western Ghats of India. The disease has since spread to other areas of Karnataka, including Chikkamagalore, Uttara Kannada, Dakshina Kannada, and others. By 2013, KFDV was detected in monkey necropsies in Nilgiris district, Tamil Nadu. Over the years, reports of monkey deaths and human cases have emerged from neighboring states, including Kerala, Goa, and Maharashtra (Arunkumar et al., 2016; Mourya and Yadav, 2016) [2,20] . The disease's geographical spread is also reflected in serological studies, which show the presence of antibodies in individuals from regions as distant as Andaman and Nicobar Islands, Gujarat, and Rajasthan, suggesting the existence of potential silent infection foci (Chakraborty et al., 2017) [5] .

Disease Pattern Trends

From 1957 to 2017, approximately 9,594 KFD cases were documented along India's western coast. The first major outbreak in Shivamogga in 1957 saw around 500 cases, with annual cases generally dropping below 200, except for 1975 when 226 cases were reported. However, the outbreak in 1981 saw more than 500 cases in Shivamogga, and by 1982, the disease spread to Dakshina Kannada, with 1,984 cases in 1983. Over the years, KFD spread to additional regions, with the most significant recent outbreak occurring in 2017, reporting 462 cases (Chakraborty et al., 2017) [5] .

Recent Outbreaks

From 2018 to 2022, Shivamogga district recorded 609 KFD cases and 17 deaths, with Thirthahalli taluk accounting for 54% of cases and 35% of deaths. In 2022, Thirthahalli's share of cases rose to 86%. The correlation between human cases, tick pool positivity, and monkey carcass detection indicates the involvement of multiple transmission pathways. Middle-aged adults were at higher risk of infection and mortality, with only 37% of this group fully vaccinated (including boosters). The decline in reported cases from 2020 to 2021 may reflect underreporting due to COVID-19-induced staff shortages or an actual decrease in cases due to movement restrictions (Srividya et al., 2024) [28] . The first fatality of 2025 was reported in February, with 48 confirmed KFD cases across Shivamogga, North Kanara, and Chickkamagalur districts of Karnataka (Udayavani, 2025).

Ecological Influences on KFD Spread

Deforestation is a major driver of KFD transmission, with the virus spreading through human activities and animal movement (Jha et al., 2000) [14] . Outbreaks are more common from December to May, coinciding with peak nymph activity. Migratory birds and bats have also been implicated in introducing KFD to new areas such as Goa, Maharashtra, Kerala, and Tamil Nadu (Ajesh et al., 2017) [1] . Climate change, exacerbated by deforestation, also plays a role in KFD's spread, influencing tick populations and the geographic distribution of both hosts and vectors (Ogden et al., 2005) [23] . Global warming is likely to increase the prevalence of vector-borne diseases in India (Karunamoorthi, 2012) [15] .

Prevention Strategies

The current vaccine against KFDV is a formalin-inactivated version, with an effectiveness rate of 62.4% for individuals receiving two doses. Boosters increase efficacy to 83%, but vaccine coverage remains low in affected regions (Kasabi et al., 2013) [16] . Other prevention measures include personal protective strategies, landscape modifications, and the application of acaricides. Comprehensive actions, such as trimming vegetation and managing wildlife reservoirs, can also help reduce tick exposure (Eisen and Stafford, 2021) [9] .

Conclusion

The growing spread of KFD, combined with its zoonotic potential, presents significant challenges in disease control. The involvement of various wildlife species and vectors complicates efforts to manage outbreaks. Enhanced surveillance, increased vaccination efforts, and heightened public awareness are critical to addressing this ongoing threat. As the disease continues to spread beyond traditional regions, collaboration among public health authorities, researchers, and veterinarians is vital to combating this emerging health crisis.

References

1. Ajesh K, Nagaraja BK, Sreejith K. Kyasanur forest disease virus breaking the endemic barrier: An investigation into ecological effects on disease emergence and future outlook. Zoonoses Public Health. 2017;64(7):73-80.
2. Arunkumar G, Hossain SS, Santhosh D, Aswathyraj S, Sudheesh N, Jazeel A, et al. Redrawing the boundaries of Kyasanur Forest Disease (KFD) in India-Early result of GHSA -Supported acute febrile illness surveillance. Am J Trop Med Hyg. 2016;95(5):200-1.
3. Bhatt PN, Work TH, Varma MG, Trapido H, Murthy DP, Rodrigues FM. Kyasanur forest diseases. IV. Isolation of Kyasanur forest disease virus from infected humans and monkeys of Shimoga district, Mysore state. Indian J Med Sci. 1966;20:316-20.
4. Carroll SA, Bird BH, Rollin PE, Nichol ST. Ancient common ancestry of Crimean-Congo hemorrhagic fever virus. Mol Phylogenet Evol. 2010;55(3):1103-10.
5. Chakraborty S, Andrade FCD, Ghosh S, Uelmen J, Ruiz MO. Historical expansion of Kyasanur forest disease in India from 1957 to 2017: a retrospective analysis. GeoHealth. 2019;3(2):44-55.
6. Charrel RN, Zaki AM, Attoui H, Fakeeh M, Billoir F, Yousef AI, et al. Complete coding sequence of the Alkhurma virus, a tick-borne flavivirus causing severe hemorrhagic fever in humans in Saudi Arabia. Biochem Biophys Res Commun. 2001;287:455-61.
7. Director of Health and Family Welfare Services, Govt of Karnataka. Manual on Kyasanur Forest Disease. 2020. https://monkeyfeverrisk.ceh.ac.uk/sites/default/files/202 2-05/Operational-Manual-Kyasanur-Forest-DiseaseDHFWS-2020-compressed.pdf
8. Dodd KA, Bird BH, Khristova ML, Albarino CG, Carroll SA. Ancient ancestry of KFDV and AHFV revealed by complete genome analyses of viruses isolated from ticks and mammalian Hosts. PLoS Negl Trop Dis. 2011;5:13-52.
9. Eisen L, Stafford KC. Barriers to effective tick management and tick-bite prevention in the United States (Acari: Ixodidae). J Med Entomol. 2021;58:1588-600.
10. Ghosh SN, Rajagopalan PK, Singh GK, Bhat HR. Serological evidence of arbovirus activity in birds of KFD epizootic-epidemic area, Shimoga District, Karnataka, India. Indian J Med Res. 1975;63:1327-34.
11. Gong ZD, Hai BQ. Investigation of small animals in the Gaoli Mountain region [in Chinese]. J Vet Med. 1989;24:28-32.
12. Gong ZD, Zi DY, Feng XG. Composition and distribute of ticks in the Hengduan Mountain region of western Yunnan, China [in Chinese]. Chin J Pest Control. 2001;2:13-5.
13. Hoeve J, Joachim D, Addison E. Parasites of moose (Alces alces) from an agricultural area of eastern Ontario. J Wildl Dis. 1988;24(2):371-4.
14. Jha C, Dutt C, Bawa K. Deforestation and land use changes in Western Ghats, India. Curr Sci. 2000;79(2):231-8.
15. Karunamoorthi K. Impact of global warming on Vector-Borne Diseases: implications for integrated vector management. J Soc Sci. 2012;1(3):e113.
16. Kasabi GS, Murhekar MV, Sandhya VK, Raghunandan R, Kiran SK, Channabasappa GH, et al. Coverage and effectiveness of Kyasanur forest disease (KFD) vaccine in Karnataka, South India, 2005-10. PLoS Negl Trop Dis. 2013;7(1):e2025.
17. Maclachlan NJ, Dubovi EJ, Barthold SW, Swayne DE, Winton JR. Flaviviridae. In: Fenner's Veterinary Virology. 5th ed. 2017. p. 528-9.
18. Madani TA, Azhar EI, Abuelzein ET, Kao M, Al-Bar HM, Abu-Araki H, et akl. Alkhumra (Alkhurma) virus outbreak in Najran, Saudi Arabia: epidemiological, clinical, and laboratory characteristics. J Infect. 2011;62(1):67-76.
19. Mansfield KL, Jizhou L, Phipps LP, Johnson N. Emerging Tick-Borne Viruses in the twenty-first century. Front Cell Infect Microbiol. 2017;7:298.
20. Mourya DT, Yadav PD. Recent scenario of emergence of Kyasanur forest disease in India and public health importance. Trop Med Infect Dis. 2016;3(1):7-13.
21. Mourya DT, Yadav PD, Patil DY. Expediency of dengue illness classification: the Sri Lankan perspective Highly infectious tick-borne viral diseases: Kyasanur forest disease and Crimean-Congo haemorrhagic fever in India. WHO-SEAJPH. 2014;3:8-21.
22. Munivenkatappa A, Sahay RR, Yadav PD, Viswanathan R, Mourya DT. Clinical & epidemiological significance of Kyasanur forest disease. Indian J Med Res. 2018;148:145-50.
23. Ogden N, Bigras Poulin MO, Callaghan C, Barker I, Lindsay L, Maarouf A. A dynamic population model to investigate effects of climate on geographic range and seasonality of the tick Ixodes scapularis. Int J Parasitol. 2005;35(4):375-89.
24. Pattnaik P. Kyasanur forest disease: an epidemiological view in India. Rev Med Virol. 2006;16(3):151-65.
25. Randolph SE. Transmission of tick-borne pathogens between co-feeding ticks: Milan Labuda's enduring paradigm. Ticks Tick Borne Dis. 2011;2(4):179-82.
26. Sadanandane C, Elango A, Marja N, Sasidharan PV, Raju KHK, Jambulingam P. An outbreak of Kyasanur forest disease in the Wayanad and Malappuram districts of Kerala, India. Ticks Tick Borne Dis. 2017;8(1):2530.
27. Simmonds P, Becher P, Bukh J, Gould EA, Meyers G, Monath T, Muerho S, Pletnev A, Rico-Hesse R, Smith DB, et al. ICTV Virus Taxonomy Profile: Flaviviridae. J Gen Virol. 2017;98:2-3.
28. Srividya K, Bhavesh L, Choudhary S, Shewale A, Pallavi D, Padma M, Tiwari S. Descriptive Epidemiology of Kyasanur Forest Disease in Thirthahalli Taluk, Shivamogga. 2024. https://www.medrxiv.org/content/10.1101/2024.04.26.2 4306123v1.
29. Venugopal K, Buckley A, Reid HW, Gould EA. Nucleotide sequence of the envelope glycoprotein of Negishi virus show close homology to louping ill virus. Virol J. 1992;190:515-21.
30. Wang J, Zhang H, Fu S, Wang H, Ni D, Nasci R, Tang Q, Liang G. Isolation of Kyasanur forest disease virus from febrile patient, Yunnan, China. Emerg Infect Dis. 2009;15(2):326.
31. Work TH, Trapido H. Kyasanur Forest disease. A new virus disease in India. Summary of preliminary report of investigations of the Virus Research Centre on an epidemic disease affecting forest villagers and wild monkeys of Shimoga District. Indian J Med Res. 1957;11(5):341-2.
32. Work TH, Roderiguez FR, Bhatt PN. Virological epidemiology of the 1958 epidemic of Kyasanur Forest disease. Am J Public Health. 1959;49(7):869-74.
33. Lendzele SS, Koumba AA, Rodrigue MN, Mavoungou JF. Foot-and-mouth disease in Cameroon: A systematic review to support its progressive control. Int J Vet Sci Anim Husbandry. 2022;7(3):06-15. doi:10.22271/veterinary.2022.v7.i3a.416.
34. Work TH. Russian spring-summer virus in India: Kyasanur Forest disease. Prog Med Virol. 1958;1:24879.