Omsk Hemorrhagic Fever Virus

Introduction

Omsk hemorrhagic fever is an acute disease caused by the Omsk hemorrhagic fever virus (OHFV) and is prevalent in some areas of western Siberia. OHFV is one of the tickborne flaviviruses that is known to cause hemorrhagic fever, in league with Kyasanur forest disease virus (KFDV) in southern India and the Alkhurma hemorrhagic fever virus (AHFV) variant subset of KFDV in Saudi Arabia, as well as with some strains of the Far-Eastern subtype of tickborne encephalitis virus (FE-TBEV) in the Novosibirsk region of Russia. OHFV is closely related to FE-TBEV, having a similar morphology and mode of replication. OHFV differs from the other tickborne encephalitis serocomplex viruses, however, in that Dermacentor reticulatus hard ticks are its primary vector. D. reticulatus is a member of the family Ixodidae that is found in wooded areas of Europe and western Asia. The other members of the tickborne encephalitis viral complex use Ixodes species ticks. While many studies have been carried out on both OHFV and TBEV, many of the findings about OHFV were published in Russian-language journals and proceedings, leading to a relative dearth of information about OHFV in English-language reviews.

History

Sporadic cases of a novel, acute hemorrhagic fever disease were first reported in 1941 in the northern lake-steppe and forest-steppe and marsh areas of the Omsk region of Siberia in Russia. The causative virus, OHFV, was isolated in 1947. The Novosibirsk region has over 3000 lakes found at altitudes of 150–200 m above sea level. It has a continental climate with a long winter and a short, hot, wet summer in which most of rainfall occurs. Two types of natural OHFV “pseudofoci” are present in western Siberia. In the first, active area, seroprevalence in humans is about 35% and includes children, while in the other potential area, it is less than 15% and does not appear to include anyone under the age of 14 years.

Following its discovery, more than 1000 cases of Omsk hemorrhagic fever were diagnosed between 1946 and 1958, followed by a temporary decrease in the number of human infections. After 1988, however, the disease reemerged and disease incidence in humans has increased in endemic areas, which remain within four Russian provinces. The importation and release of 4000 North American muskrats into the region appears to have precipitated the initial disease outbreaks in Siberia. These economically valuable animals are highly susceptible to OHFV infection. People coming into close contact with muskrats or muskrat hides are at high risk of infection by the virus.

The Disease

Many OHFV infections are mild and may be unreported or misdiagnosed. These cases have no fever or hematological features. During a disease outbreak in 1988–1989, over 80% of the patients had a mild form of the disease. The highest incidence of reported disease is found in people between the ages of 20 and 40 years, although one-third of the infections are reported in children under the age of 15 years.

Omsk hemorrhagic fever is biphasic, with patients being viremic during the first, but not the second, phase. Symptoms include moderately severe hemorrhagic disease with a fever of 39–40°C and abundant bleeding from the nose, mouth, lungs, and uterus, as well as hemorrhagic rash and hemorrhaging of the skin. Other symptoms include dehydration, headache, nausea, severe pain in the calf muscles and regional joints, and cough. The fever usually is accompanied by chills that last for 8–15 days. Clinical signs early during the course of the disease include an enlarged liver; arterial hypotension and bradycardia; hyperemia of the face, neck, and breasts; a brightly colored mouth and throat; scleral injection; dryness of the tongue; a foul odor emanating from the mouth; and puffiness of the face. These symptoms are then followed by increased amounts of bleeding, including gastrointestinal and pulmonary bleeding in serious cases.

After 1–2 weeks, 50%–70% of the patients completely recover. The remaining patients then enter into the second phase of illness, which lasts a further 5–14 days. This phase includes some of the initial symptoms, as well as spread of the disease to additional anatomical sites. Pathological changes involve several organ systems. Changes in the blood cells include high hemoglobin concentrations at disease onset, leukopenia and neutrophilia with left shifts, monocytosis, thrombocytopenia, and reduced complement levels. The cardiovascular system manifestations include diffuse or focal dystrophic degenerative changes of the myocardium, severe arterial hypotonia, hyperemia of the face and upper trunk, exanthema, a small degree of petechial rash, and hemorrhaging from the nasal, pulmonary, gastrointestinal, and uterine areas. The pulmonary manifestations include bronchitis and atypical pneumonia. Renal manifestations include moderate albuminuria and intermittent hematuria. Nervous system manifestations are also present, such as headache, muscle pain, Kernig’s sign, occipital rigidity, Lasegne’s sign, loss of taste, and decreased hearing, together with behavioral and psychological changes. One-third of the patients develop pneumonia, nephrosis, or meningitis.

Despite the severity of illness, disease prognosis is typically favorable with most of the patients having a complete recovery after a long convalescent period. Infrequently, permanent complications are seen, including weakness, hearing and hair loss, and behavioral and psychological problems, including poor memory and difficulty concentrating or working. Mortality rates are low (0.4%–2.5%) and death occurs after a rapid onset of hemorrhagic symptoms or later, from septic complications.