Orbiviruses are 1 of 9 genera in the family Reoviridae. Only 4 genera within the Reoviridae cause human disease: the orbiviruses, rotaviruses, orthoreoviruses, and coltiviruses. Coltiviruses cause Colorado tick fever. Orbiviruses are distinguished from the orthoreoviruses by their protein structure and arthropod transmission cycles.[1] The genus Orbivirus contains 19 species and at least 130 subspecies.
Orbiviruses are named for their doughnut-shaped capsomeres (orbi means ring in Latin). Structurally, each virion consists of an outer and inner capsid layer that surrounds a core genome of 10 nonenveloped double-stranded RNA segments. Type- and group-specific antigens include the outer VP2 and the core VP7 proteins, respectively. No lipid envelope is present. Overall, they are 70-80 nm in diameter.
The orbiviruses are primarily animal pathogens that cause bluetongue disease in sheep, cattle, goats, and wild ungulates; African horse sickness in horses, donkeys, and dogs; and epizootic hemorrhagic deer fever. Many other viruses in this genus infect animals, but the above are the most commonly recognized. Infections may affect fetal development and have been linked to congenital anomalies such as hydrocephalus and arthrogryposis. These are the best-studied orbiviral diseases. Only 7 per 100 orbiviruses are linked to human clinical disease, with only one, Oklahoma tick fever, causing disease within the United States.
Orbiviruses are vector-borne pathogens that are transmitted by ticks, mosquitoes, gnats, and midges. Studies on the pathophysiology of orbiviral infections specifically in humans have not been conducted. Data on the pathophysiology of orbiviral infections are derived mainly from studies of animal orbiviruses. According to Palacios et al, the ability to detect them has been hampered by their diversity. They developed a consensus reverse-transcription polymerase chain reaction (RT-PCR) method of targeting the polymerase gene for orbivirus recognition and characterization.[2]
In these cases, the virus enters the cell by endocytosis, the outer capsid is removed, and the core particle undergoes transcription. Viral proteins are synthesized 2-14 days after the infection and self-assemble within the cytoplasm. New virions are released and are then capable of infecting more cells, mainly within the lymphoreticular system. Many orbiviruses have a predilection for the vascular endothelial cells, which can lead to disruption in blood flow and subsequent ischemia. Orbiviruses also have a tropism for the nervous system, leading to encephalitis and, possibly, neuropathies.
United States
Within humans, Oklahoma tick fever is a tick-borne febrile illness that may be caused by an Orbivirus in the Kemerovo group. The exact frequency is unknown, but clinically recognized disease is uncommon. Two serologically diagnosed human cases have been reported in Oklahoma and Texas. These cases involved elevated levels of antibodies to Six Gun City and Lipovnik viruses, which are members of the Kemerovo serogroup. Viral isolation was not performed; therefore, the precise identity of the cases is not definitively known.
International
Internationally, only infrequent cases of clinical illness in humans have been reported in Russia, Eastern Europe, Africa, and South and Central America. To date, fewer than 50 cases have been described in the literature.
Deaths have not been attributed to orbiviral infections in humans. However, severe flulike illness, encephalitis, and polyradiculitis have occurred infrequently in patients with orbiviral infections. Patients with clinical orbiviral infections generally recover with no long-lasting effects.
Current reports do not demonstrate a racial predilection for orbiviral infections; however, no large epidemiologic trials or case series have been performed. Further clarification of this point requires more clinical cases with in-depth epidemiological investigations.
In the few human cases of orbiviral infections, incidence does not seem to be associated with sex.
All age groups may be infected with orbiviruses. However, seroprevalence studies suggest that most infections occur in childhood.
Worldwide, more than 100 orbiviruses affect animals. These diseases include bluetongue disease in sheep, cattle, goats, and wild ungulates; African horse sickness in horses, donkeys, and dogs[3] ; and epizootic hemorrhagic deer fever.
The patient may give a history of arthropod bites, including ticks, mosquitoes, gnats, and midges. In cases of Oklahoma tick fever or Kemerovo or Lipovnik virus infections, a tick transmits the virus. Orbiviral infections in Africa and South America may be spread via mosquito bites.
Although incubation time from exposure to clinical illness is unknown in humans, it has been estimated at 6-9 days in animals.
Based on serologic studies, orbiviral infections often are asymptomatic or present as a mild nonspecific febrile illness for which medical care is not sought. Patients who present for medical evaluation often report fever, myalgia, nausea, vomiting, diarrhea, and confusion. Seizures and, rarely, focal neurologic deficits may also develop.
History is significant for travel to a location that contains an orbiviral reservoir (ie, Russia, Eastern Europe, Africa, South America, Central America, the states of Texas and Oklahoma).
Russia and Eastern Europe
The Kemerovo antigenic complex includes the Kemerovo, Lipovnik, and Tribec viruses. These are tick-borne (specifically Ixodes ticks) orbiviruses that are found in Russia and Eastern Europe.
This group of viruses is the suspected cause of 12 cases of encephalitis in the Kemerovo region of Russia.[4] In addition, meningoencephalitis and, perhaps, polyradiculitis have been linked to the Lipovnik virus in the former Czechoslovakia.
Central and West Africa
Orungo virus is an Orbivirus found in parts of sub-Saharan Africa. This virus is thought to cause asymptomatic infection; however, it has been linked to acute illnesses characterized by fever, headache, and myalgia. This virus also is implicated in a case of encephalitis in a child.
A study has shown a high rate of co-infection with yellow fever and Orungo viruses, possibly due to their similar geographic distribution and their common use of Aedes mosquitoes as the principal vector.[5] Although the principal vector is Aedes, anopheline and Culex mosquitoes also are implicated in transmission.[6]
South Africa and Nigeria
Lebombo virus is also found in parts of Africa, specifically South Africa and Nigeria.
It has been isolated from Aedes and Mansonia mosquitoes and from rodents.
A single human case involving a Nigerian child (with fever) has been reported.[7]
South America
Changuinola virus is linked to a single documented case of an acute self-limited febrile illness in Panama. However, the seroprevalence of this disease is high in parts of South America; thus, the true extent or frequency of this infection currently is unknown.[8]
Transmission is most likely by Phlebotomus flies.
United States
Several cases of human disease have been reported in Oklahoma and Texas; the disease is now named Oklahoma tick fever. The disease is considered a new arboviral disease in the western United States that is related to the Kemerovo serogroup of orbiviruses.
Patients presented with prostrating grippes, nausea, abdominal pain, and fever. Several patients had concomitant cytopenia (transient thrombocytopenia, anemia, and/or leukopenia). Each patient recalled tick exposure; however, the specific causative tick is currently unknown.
Researchers observed a 4-fold rise in the immunofluorescent antibodies to Lipovnik and Six Gun City viruses and the absence of seroreactivity to Rocky Mountain spotted fever, Colorado tick fever, and Powassan virus. Because the causative virus was never isolated, the exact etiology remains unknown, although researchers suspect an Orbivirus. Consider orbiviruses within the differential of a suspected viral or rickettsial infection in the southwestern United States.
In the midwestern United States, Kemerovo-related viruses are known to cause infections in rabbits and large animals, but no human cases have been reported.
Physical findings vary depending on the specific Orbivirus involved; however, the most common physical finding is fever.
Other nonspecific symptoms have been reported, including headache, myalgia, and gastrointestinal problems.
Patients may be encephalopathic or may demonstrate focal neurologic findings.
Risk factors include travel to an area with known orbiviruses, particularly Texas and Oklahoma. Overseas travel to Russia, Eastern Europe, South America, Central America, and Africa may also lead to orbiviral exposure.
Outdoor activity is the best-known risk factor because disease transmission to humans is via arthropod vectors. The seasonality of the infection relates to the time of arthropod activity.
Aside from arthropod-borne transmission, 4 workers in South Africa were infected with lyophilized virus in a veterinarian's office (1989). The vaccine contained neurotropic attenuated strains of African horse sickness virus. Three developed frontotemporal encephalitis, and all 4 developed uveochorioretinitis. Cases were diagnosed serologically. No naturally occurring human infections have been reported with the African horse sickness viruses.
This test useful and may show thrombocytopenia, lymphopenia, and/or anemia. These findings may be transient.
In patients presenting with neurologic infection, collect cerebrospinal fluid (CSF) for cell count and differential, protein, glucose, bacterial culture, Gram stain, and viral culture.
In patients with the clinical signs of encephalitis or meningitis, obtain CSF to help establish a diagnosis, to rule out bacterial causes that may be life threatening if untreated, and to detect other viral causes.
In orbiviral infections, the protein and white blood cell count may be slightly elevated; however, little information on CSF findings is currently available in the literature. The CSF may be examined for evidence of an orbiviral infection with serology and/or viral isolation.
Testing specifically for orbiviral infection may be done via serological studies or viral isolation from the serum or CSF. The presence of viral-specific immunoglobin M (IgM) in the CSF suggests acute infection. Serologic studies may include complement fixation, enzyme immunoassay, and neutralizing antibodies. These tests are available at only a limited number of reference laboratories. Cases may be referred to the US Centers for Disease Control and Prevention at Fort Collins, Colorado or the US Army Medical Research Institute of Infectious Diseases in Fort Detrick, Md.
The serum may be used for viral isolation and for serology. Use the appropriate reference laboratory for these specimens.
The serologic diagnosis requires a 4-fold rise in acute and convalescent antibody titers. Viral isolation may be accomplished by the inoculation of suckling mice or by cell cultures (ie, Vero or BHK-21 cells). Only a limited number of reference laboratories test specifically for orbiviral infections.
In order to rule out other causes of encephalitis, one also must test for other etiologies, depending on the location of exposure.
In the western United States, test for Rocky Mountain spotted fever, Powassan virus, Colorado tick fever, western equine encephalitis virus, West Nile virus, and St. Louis encephalitis virus.
Seek other viral etiologies, including herpes viruses and enteroviruses.
No specific imaging studies are recommended to assist in the diagnosis of orbiviral infections.
In patients presenting with meningoencephalitis, the only procedure recommended in cases of suspected orbiviral infections is a lumbar puncture.
No known specific treatment exists for orbiviral infections. Supportive care is recommended.
Patients may return to their regular activities based on the resolution of their clinical symptoms.
Provide supportive care.
Assure normalization of test results after clinical illness has resolved.
Isolation of the patient is not necessary because the disease is transferred from arthropod vectors; no cases of human-to-human transmission have been reported.
Prevention entails avoiding tick and other arthropod vectors via insect repellants, wearing proper outdoor clothing, and, if possible, avoiding endemic areas.
While in endemic areas, search daily for ticks. When removing them, use a blunt forceps or tweezers to grasp the tick. Gently pull upwards with a steady, even pressure without twisting or jerking; this may cause mouth parts to be left in the wound. Avoid handling the tick with bare hands because infectious agents may enter via breaks in the skin. After removing the tick, thoroughly disinfect the bite with soap and water.
Complications in patients who present with meningoencephalitis may include seizures. One child presented with flaccid paralysis due to Orungo virus. Polyradiculoneuritis may be caused by orbiviral infections, and transient cytopenias occurred with Oklahoma tick fever.
Little is known regarding the prognosis of orbiviral infections because follow-up information is limited. Full recovery is expected in most, if not all, cases. Deaths secondary to orbiviral infections have not been reported.
Educate patients on how to avoid arthropod vectors, how to avoid tick exposure, how to conduct daily surveillance for ticks, and how to properly remove ticks.
For excellent patient education resources, see eMedicineHealth's patient education article Ticks.