Kyasanur Forest disease: an emerging arboviral threat

Kyasanur Forest disease is a neglected tick-borne viral haemorrhagic fever endemic to India's Western Ghats, caused by the Kyasanur Forest disease virus, a flavivirus transmitted by Haemaphysalis spinigera ticks. The virus circulates in a sylvatic cycle among monkeys, rodents, shrews, birds, and ixodid ticks, and is transmitted to humans incidentally via tick bites. Since its discovery in 1957 in Karnataka, Kyasanur Forest disease has spread to other Indian states, driven by deforestation, forest fragmentation, and increased human incursion into wildlife habitats. Clinically, the disease manifests in a biphasic pattern, with haemorrhagic and neurotropic presentations. Although a formalin-inactivated vaccine is available, its efficacy is not promising, and no antivirals have been approved to date. Field reports indicate that mortality in monkeys might serve as an early indicator of forthcoming human outbreaks. The transmission dynamics of Kyasanur Forest disease, diagnostic gap, and ecological complexities present substantial public health challenges. In this Review, we provide an update on Kyasanur Forest disease virus, covering its epidemiology, transmission dynamics, molecular virology, virus-host interactions, immunological responses, animal models, and potential antiviral therapies and vaccines.