Omsk Hemorrhagic Fever Virus: A Comprehensive Review from Epidemiology to Diagnosis and Treatment

Abstract

Omsk hemorrhagic fever virus (OHFV) is the etiological agent of a poorly studied acute viral disease, causing several epidemic waves observed in the western Siberia regions of Omsk, Kurgan, Novosibirsk, and Tyumen. OHFV is a flavivirus and shares structural and morphological features with tick-borne encephalitis (TBE) complex viruses. The disease's symptoms show high variability, from flu-like symptoms, hyperesthesia, and petechial rush in the upper body to high fever and hemorrhagic manifestations, with a fatality rate of about 1%. The real number of OHFV-infected people is still unknown due to the difficulties in diagnosis and the presence of asymptomatic patients that lead to an underestimation of the total cases. Little is known about the viral infection dynamics at the molecular and cellular levels, the viral involvement in immune escape, cellular pathways alteration, or metabolic influence. It is noteworthy that no clinical trials have currently been performed for effective and specific drug treatments. In this review, we will give an overview of OHFV interactions with humans and animals, diagnostic tools, and drug treatments. We aim to highlight the importance of a frequently undiagnosed or misdiagnosed viral infection that might also even cause severe clinical manifestations such as meningitis and hemorrhage, in order to point out the need to develop new research studies, new diagnostic tools, and new treatments for OHFV.

Keywords: Omsk hemorrhagic fever virus; TBEV; flaviviridae; hemorrhagic fever; tick-borne encephalitis complex.

Figure 1

The structure of the flaviviridae virion with specific features of OHFV. Due to the lack of a schematic representation of the OHFV external structure, we added specific OHFV features to a common Flaviviridae virion scheme. Image modified by ViralZone, SIB Swiss Institute of Bioinformatics (https://viralzone.expasy.org/ accessed on 6 February 2025).

Figure 2

Schematic representation of OHFV viral genome organization.

Figure 3

OHFV ML phylogenetic tree obtained with MAFFT v7, IQ–TREE software version 2.4.0 and visualized with Tree Viewer v2.2.0 of 46 viral complete sequences of different strains of OHFV. Branches in blue are classified as genotype 1, branch in red as genotype 2, branches in green as genotype 3; branches unclassified in the literature are shown in gray [13]. In the same color shading are the strains that can be classified to that specific genotype. Dots of different colors represent the source of isolation: red for strains isolated from human blood, yellow for strains isolated from mosquitoes, green for strains isolated from O. zibethicus, light blue for strains isolated from M. oeconomus, and brown for strains isolated from D. marginatus. Boxes of different colors represent the region of isolation: in green, the strain isolated in the Novosibirsk region; in blue, the strain isolated in the Kurgan region; in red, the strains isolated in the Omsk region; and in gray, the strains of the unknown region of isolation.

Figure 4

Geographical distribution of Omsk hemorrhagic fever. Endemic administrative regions of Russia. This graph was modified from the CDC guideline website [16] and created with MapChart (http://www.MapChart.net, accessed on 6 February 2025).

Figure 5

Transmission route of the ecological cycle of OHFV. In the graphic, the principal hosts and vectors involved in OHF infection are shown. OHFV is primarily found in rodents and is spread by the bite of an infected tick (non-transmissive cycle). Similarly, humans can contract the disease following an infected tick bite or by contact with biological material from an infected, sick, or deceased animal (transmissive cycle). Hunting and trapping are examples of recreational and occupational activities that may raise the risk of infection in humans. Human-to-human transmission has not been reported to date. Created with bioRender.com (http://www.biorender.com, accessed on 6 February 2025).

Figure 6

Cumulative seasonal variability in the morbidity of OHFV in the 1988–1992 outbreaks reported in the Novosibirsk region. Most of the cases (83.3%) were reported between September and October, corresponding to the muskrat hunting season (figure modified from Ruzek and coworkers [32]).