Orthobunyaviruses

Boston University
Research Occupational Health Program (ROHP)
617-358-7647

Agent

Orthobunyaviruses (over 170 species, including Batai virus, Ngari virus, Inkoo virus, Jamestown Canyon virus, Tahyna virus, Keystone virus, Bunyamwera virus) are a genus of single-stranded, tri-segmented negative-sense RNA viruses that belong to the family Peribunyaviridiae. Orthobunyaviruses are endemic to many areas of the world, including Africa, Europe, Asia, and North America. All viruses are of zoonotic origin and are transmitted primarily by contact with infected mosquitoes. Clinical manifestations caused by infections of these pathogens are limited primarily to a mild flu-like illness, rash, and rarely meningoencephalitis. Some strains have been associated with the development of hemorrhagic fever (Oropouche virus).

Disease/Infection

Batai virus
Bunyamwera virus (Bunyamwera fever)
Inkoo virus
Jamestown Canyon virus
Keystone virus
Oropouche virus
Tahyna virus

Pathogenicity

Most patients improve after 1-2 weeks, but some may develop chronic neurologic infection or severe hemorrhagic fever. There have been case reports of severe sepsis and thrombocytopenia. Approximately half of all patients can exhibit recurrence of symptoms 1 to 10 days after initial recovery.

• Special Populations at Risk
  There have been case reports of children and immunocompromised patients who have increased susceptibility to chronic neurologic infections. Orthobunyaviridiae have been associated with abortions and congenital defects (microcephaly and hydrocephalus) in cattle, sheep, and goats.

Biosafety Information

Risk Group/BSL
Risk Group 2
Biosafety level 2

Modes of Transmission

The only documented transmission of orthobunyaviruses have been through zoonotic means (mosquito bites, tick bites, Culicoid flies).

Oropouche virus is suspected to be infectious by aerosol, as based on reported laboratory infections.

Host Range/Reservoir
Mosquitoes.  Humans are accidental hosts. Other mammals, including hares, rabbits, hedgehogs, rodents, and seals may serve as accidental or amplifying hosts.

Symptoms
This genus of virus is associated primarily with mild, febrile flu-like illnesses. Occasionally, those exposed to the virus may experience rash, joint pain, and rarely meningoencephalitis. Subclinical disease may also be present in humans. High viremia is essential for neuroinvasion.

Batai virus – Associated with encephalitis in harbor seals.
La Crosse virus – pediatric encephalitis
Bunyamwera virus – May cause acute febrile illness in humans. Isolated from humans in Uganda, Nigeria, and South Africa. Several other serogroups found in the Americas are infrequently reported to cause acute febrile illness.
Inkoo virus – It causes a mild febrile illness in humans with rare encephalitis cases. Seroprevalence of nearly 50% in endemic areas (Finland and Sweden).
Jamestown Canyon virus – Causes acute febrile illness in humans, including meningoencephalitis in 35% of cases from a review in Midwest US.
Keystone virus – May cause a mild febrile illness with a rash that resolves in a few days. Seroprevalence up to 20% in endemic areas (Chesapeake Bay, Florida, and Texas).
Oropouche virus – febrile illness
Tahyna virus – May cause flu-like illness, including acute-onset joint pain and meningoencephalitis. Seroprevalence up to 60-80% in endemic areas (Tibet, China, Eastern and Western Europe).

Incubation Period
The incubation period is approximately 3 to 7 days. Most cases report sudden onset of fever, stiff neck, lethargy, headache, nausea, vomiting. Symptoms usually end within 7 days.

Mosquitoes begin to become infectious approximately 1-2 weeks after ingestion of the virus (extrinsic incubation period).

Viability
Treatment with lipid solvents or nonionic detergents removes the viral envelope and results in loss of infectivity for arthropods and mammals.

Survival Outside Host
Unknown

Information for Lab Workers

Laboratory PPE

Appropriate attire should be worn, including lab coats and gloves. Eye protection and face shields can also be worn, as needed. All procedures that can cause infection from aerosols or splashes should be performed within a biological safety cabinet (BSC).

Containment

All work with infections virus must be performed in BSL-2/ABSL-2 containment.

In Case of Exposure/Disease

• For injuries in the lab which are major medical emergencies (heart attacks, seizures, etc…).
  • Medical Campus: call or have a coworker call the Control Center at 617-414–4144.
  • Charles River Campus: call or have a coworker call campus security at 617-353-2121.
    You will be referred to or transported to the appropriate health care location by the emergency response team.
• For lab exposures (needle sticks, bite, cut, scratch, splash, etc…) involving animals or infectious agents, or for unexplained symptoms or illness call the ROHP 24/7 hour number (1-617-358-ROHP (7647); or, 8-ROHP (7647) if calling from an on-campus location) to be connected with the BU Research Occupational Health Program (ROHP) medical officer. ROHP will refer you to the appropriate health care location.
• Under any of these scenarios, always inform the physician of your work in the laboratory and the agent(s) that you work with.
• Provide the wallet-size agent ID card to the physician.

Vaccination

There is no approved vaccine for use in humans or animals. Several inactivated vaccines are being developed, though further study is necessary.

Information for First Responders/Medical Personnel

Public Health Issues

Transmission is primarily through mosquito bites. Disease has not been documented to show transmission from human to human. If working in an endemic area or near mosquitoes that may be infected with Orthobunyaviruses, be sure to minimize skin exposure and use personal protectants containing N, N-diethyl-meta-toluamide (DEET).

Diagnosis/Surveillance

Diagnosis relies primarily on serologic methods, as the virus is generally absent from blood or secretions during CNS disease. Hemagluttinin inhibition testing is sensitive for these viruses, though neutralization and RT-PCR with nucleotide genome sequencing are needed to confirm the diagnosis. ELISA may also be used, but has not been widely studied.

First Aid/Post Exposure Prophylaxis

 Perform one of the following actions:

Treatment

There is no proven antiviral treatment for orthobunyavirus infections. Ribavirin treatment has been studied in humans, though was not proven to reduce either viral load or mortality. Management is mainly supportive. If severe enough, blood product transfusion may be necessary. Data is insufficient regarding the use of steroids, intravenous immunoglobulin, or plasma exchange. However, some advocate the use of IVIG from patients endemic to the area of infection, as there is a higher probability of antibodies against the virus.

References

Calisher, C. H. “Orthobunyaviruses.” Encyclopedia of Virology, 3^rd Edition. Academic Press: 2008. 479-483.

Dutuze MF, Nzayirambaho M, Mores CN, Christofferson RC. A Review of Bunyamwera, Batai, and Ngari Viruses: Understudied Orthobunyaviruses With Potential One Health Implications. Front Vet Sci. 2018;5:69. Published 2018 Apr 12. doi:10.3389/fvets.2018.00069

Elliott, Richard M. and Connie Schmaljohn. “Bunyaviridiae.” Fields Virology, 6^th Edition. Lippincott Williams & Wilkins. Philadelphia, PA: 2013.

Jo WK, Pfankuche VM, Lehmbecker A, Martina B, Rubio-Garcia A, Becker S, Kruppa J, Jung K, Klotz D, Metzger J, Ludlow M, Baumgärtner W, van der Vries E, Osterhaus A. Association of Batai Virus Infection and Encephalitis in Harbor Seals, Germany, 2016. Emerg Infect Dis. 2018 Sep;24(9):1691-1695. doi: 10.3201/eid2409.171829. PubMed PMID: 30124416; PubMed Central PMCID: PMC6106443.

Kim, K.; Oh, M. (2014). “Severe Fever with Thrombocytopenia Syndrome”. Korean Journal of Medicine. 86 (3): 271–276. doi:10.3904/kjm.2014.86.3.271

Pinheiro FP, Travassos da Rosa AP, Travassos da Rosa JF, et al. Oropouche virus. I. A review of clinical, epidemiological, and ecological findings. Am J Trop Med Hyg 1981;30:149–160.