eMedicine Specialties > Infectious Diseases > Viral Infections

Orbivirus

Updated: Mar 27, 2008

Introduction

Background

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. 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.

Pathophysiology

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.

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.

Frequency

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.

Mortality/Morbidity

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.

Race

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.

Sex

In the few human cases of orbiviral infections, incidence does not seem to be associated with sex.

Age

All age groups may be infected with orbiviruses. However, seroprevalence studies suggest that most infections occur in childhood.

Breed

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; and epizootic hemorrhagic deer fever.

Clinical

History

Bites

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.¹ 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.² Although the principal vector is Aedes, anopheline and Culex mosquitoes also are implicated in transmission.

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.³

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.
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

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.

Causes

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.

Differential Diagnoses

Eastern Equine Encephalitis
Rocky Mountain Spotted Fever
St. Louis Encephalitis
Western Equine Encephalitis

Workup

Laboratory Studies

Complete blood count: This test useful and may show thrombocytopenia, lymphopenia, and/or anemia. These findings may be transient.
Cerebrospinal fluid
- 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.
Serological testing
- 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.
Other
- 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.

Imaging Studies

No specific imaging studies are recommended to assist in the diagnosis of orbiviral infections.

Procedures

In patients presenting with meningoencephalitis, the only procedure recommended in cases of suspected orbiviral infections is a lumbar puncture.

Treatment

Medical Care

No known specific treatment exists for orbiviral infections. Supportive care is recommended.

Activity

Patients may return to their regular activities based on the resolution of their clinical symptoms.

Medication

No medications are used to treat these infections.

Follow-up

Further Outpatient Care

Provide supportive care.
Assure normalization of test results after clinical illness has resolved.

Transfer

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.

Deterrence/Prevention

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

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.

Prognosis

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.

Patient Education

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, visit eMedicine's Bites and Stings Center. Also, see eMedicine's patient education article Ticks.

Miscellaneous

Medicolegal Pitfalls

Thoroughly evaluate all patients presenting with neurologic involvement. In particular, ensure that all potentially treatable causes (eg, bacterial causes, herpes simplex) are excluded.

Special Concerns

Orbiviruses primarily are diseases of animals and may profoundly affect livestock populations. Animal diseases include bluetongue disease in sheep, cattle, goats, and wild ungulates; African horse sickness in horses, donkeys, and dogs; and epizootic hemorrhagic deer fever. Animal infections may result in gastrointestinal illness characterized by vomiting, abortions, fetal abnormalities, hydrocephalus, and arthrogryposis.

References

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Moore DL, Causey OR, Carey DE, et al. Arthropod-borne viral infections of man in Nigeria, 1964-1970. Ann Trop Med Parasitol. Mar 1975;69(1):49-64.
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Keywords

Orbivirus, orbiviruses, orbiviral infection, Kemerovo virus, Lipovnik virus, Tribec virus, Orungo virus, Lebombo virus, Changuinola virus, Oklahoma tick fever virus, bluetongue disease, African horse sickness, epizootic hemorrhagic deer fever, hydrocephalus, arthrogryposis, polyradiculitis, Ixodes ticks, meningoencephalitis, Aedes mosquitoes, anopheline mosquitoes, Culex mosquitoes, Mansonia mosquitoes, Phlebotomus flies

Contributor Information and Disclosures

Author

Nancy F Crum-Cianflone, MD, Consulting Staff, Department of Internal Medicine, Division of Infectious Diseases, Naval Medical Center at San Diego; HIV Research Physician, Infectious Disease Clinical Research Program, Uniformed Services University of the Health Sciences
Nancy F Crum-Cianflone, MD is a member of the following medical societies: American College of Physicians and Infectious Diseases Society of America
Disclosure: Nothing to disclose.

Medical Editor

Thomas J Marrie, MD, Chair, Professor, Department of Medicine, Division of Infectious Diseases, University of Alberta College of Medicine
Thomas J Marrie, MD is a member of the following medical societies: Alpha Omega Alpha, American College of Physicians, American Society for Microbiology, Canadian Infectious Disease Society, and Royal College of Physicians and Surgeons of Canada
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Managing Editor

Charles V Sanders, MD, Edgar Hull Professor and Chairman, Department of Internal Medicine, Professor of Microbiology, Immunology and Parasitology, Louisiana State University School of Medicine at New Orleans; Medical Director, Medicine Hospital Center, Charity Hospital and Medical Center of Louisiana at New Orleans; Consulting Staff, Ochsner Medical Center
Charles V Sanders, MD is a member of the following medical societies: Alliance for the Prudent Use of Antibiotics, Alpha Omega Alpha, American Association for the Advancement of Science, American Association of University Professors, American Clinical and Climatological Association, American College of Physician Executives, American College of Physicians, American Federation for Medical Research, American Foundation for AIDS Research, American Geriatrics Society, American Lung Association, American Medical Association, American Society for Microbiology, American Thoracic Society, American Venereal Disease Association, Association for Professionals in Infection Control and Epidemiology, Association of American Medical Colleges, Association of American Physicians, Association of Professors of Medicine, Infectious Disease Society for Obstetrics and Gynecology, Infectious Diseases Society of America, Louisiana State Medical Society, Orleans Parish Medical Society, Royal Society of Medicine, Sigma Xi, Society of General Internal Medicine, Southeastern Clinical Club, Southern Medical Association, Southern Society for Clinical Investigation, and Southwestern Association of Clinical Microbiology
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CME Editor

Eleftherios Mylonakis, MD, Clinical and Research Fellow, Department of Internal Medicine, Division of Infectious Diseases, Massachusetts General Hospital
Eleftherios Mylonakis, MD is a member of the following medical societies: American Association for the Advancement of Science, American College of Physicians, American Society for Microbiology, and Infectious Diseases Society of America
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Chief Editor

Burke A Cunha, MD, Professor of Medicine, State University of New York School of Medicine at Stony Brook; Chief, Infectious Disease Division, Winthrop-University Hospital
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Further Reading