APPENDIX 2 Borna Disease Virus At-Risk Populations: • Unknown Disease Agent: Vector and Reservoir Involved: • Borna disease virus (BDV) • Sporadic enzootic disease of horses and sheep Disease Agent Characteristics: although host range is wide; however, mode of trans- • Family: Bornaviridae; Genus: Bornavirus mission and reservoir is unknown. • Virion morphology and size: Enveloped, helical • Neonatal rats experimentally infected with BDV nucleocapsid symmetry, spherical, 90-100 nm or develop viral persistence, so rodents are a theoretical larger in diameter reservoir and vector, although naturally infected • Nucleic acid: Linear, nonsegmented, negative-sense, rodents have not been found. single-stranded RNA, 8.9 kb in size • Physicochemical properties: Cell-free virion infectiv- Blood Phase: ity is inactivated by heating at 56°C for 0.5-3 hours but • Unknown, but transcripts and proteins detected more stable in tissues or in the presence of serum; in PBMC from patients with acute or chronic under in vitro conditions, virions are relatively stable psychiatric disease; cross-contamination not ruled when stored at 37°C, with minimal loss of infectivity out after 24 hours in the presence of serum; stable after drying and for at least 3 months at 4°C; tolerant of Survival/Persistence in Blood Products: alkaline pH but inactivated below pH 4; virions are • Unknown sensitive to treatment with organic solvents and detergents, and infectivity is reduced after exposure Transmission by Blood Transfusion: to ultraviolet light and irradiation. • Never reported Disease Name: Cases/Frequency in Population: • Borna disease • Worldwide natural infection of domestic animals Priority Level: • High seroprevalence (6%-37%) in hospitalized • Scientific/Epidemiologic evidence regarding blood patients with psychiatric, neurologic, and/or immu- safety: Theoretical nologic disorders, i.e., major depression and • Public perception and/or regulatory concern regard- schizophrenia ing blood safety: Absent • Low seroprevalence (1%-2%) found in healthy • Public concern regarding disease agent: Absent volunteers • BDV RNA detected in 4.7% healthy Japanese blood Background: donors • BDV RNA present in monocytes from acute or chronic • 1766: Borna disease first described in European sheep psychiatric patients at a frequency of up to 50% and horses • BDV naturally infects ostriches, horses, cattle, sheep, Incubation Period: dogs, cats, and foxes; experimentally transmitted to nonhuman primates. • Approximately 1-3 months for horses and sheep • 1996: BDV isolated from patients with mood disorders • Unknown human incubation period • BDV’s role as a potential human pathogen has not Likelihood of Clinical Disease: been established and is currently controversial. Only infrequently has viral nucleic acid been found in • Theoretical human blood or tissue specimens. • More research is needed to associate BDV infection with human neuropsychiatric disease, and much Common Human Exposure Routes: work is required to demonstrate transfusion • Unknown, but contact with infected domestic transmission. animals, such as horses, sheep, and cats, has been Primary Disease Symptoms: proposed. However, no research is available to prove transmission from domestic animals to humans. • Causes severe, frequently fatal neurological disease in horses and sheep Likelihood of Secondary Transmission: • Potential cause of human psychiatric and neurologic • Unknown disorders Volume 49, August 2009 Supplement TRANSFUSION 57S APPENDIX 2 • Patients with acute major depression exhibit serocon- Leukoreduction Efficacy: version to BDV, but the etiologic significance is • Unknown speculative. Pathogen Reduction Efficacy for Plasma Derivatives: Severity of Clinical Disease: • Multiple pathogen reduction steps used in the frac- • Unknown tionation process have been shown to be robust in the removal of enveloped viruses. Mortality: Other Prevention Methods: • Unknown, but acute BD in animals results in high • None mortality (75%-95%) Suggested Readings: Chronic Carriage: 1. Bode L. Human infections with Borna disease virus • Unknown in humans and potential pathogenic implications. Curr Top • Horses: Lifelong persistence with short periods of Microbiol Immunol 1995;190:103-30. activation and long periods of inactivity 2. Bode L, Ludwig H. Borna disease virus infection, a human mental-health risk. Clin Microbiol Rev 2003; Treatment Available/Efficacious: 16:534-45. • No consensus 3. de la Torre JC. Bornavirus and the brain. J Infect Dis 2002;186 Suppl 2:S241-7. Agent-Specific Screening Question(s): 4. Hatalski CG, Lewis AJ, Lipkin WI. Borna disease. EID 1997;3:129-35. [cited 2009 June]. Available from: • No specific question is in use. http://www.cdc.gov/ncidod/EID/vol3no2/hatalski/ • Not indicated because transfusion transmission has htm not been demonstrated 5. Kishi M, Nakaya T, Nakamura Y, Kakinuma M, Taka- • No sensitive or specific question is feasible. hashi TA, Sekiguchi S, Uchikawa M, Tadokoro K, Ikeda Laboratory Test(s) Available: K, Ikuta K. Prevalence of Borna disease virus RNA in peripheral blood mononuclear cells from blood • No FDA-licensed blood donor screening test donors. Med Microbiol Immunol 1995;184:135-8. exists. 6. Lipkin WI, Briese T. Bornaviridae. In: Knipe DM, • Generally accepted standards for diagnosis of human Howley PM, editors. Fields virology, 5th ed. BDV infection not established. Philadelphia: Lippincott Williams & Wilkins; 2007. p. • Options for laboratory testing include immunofluo- 1829-51. rescence, immunoprecipitation, and western blot 7. Planz O, Rentzsch C, Batra A, Rziha HJ, Stitz L. Persis- (specific antibodies in serum and CSF), flow cytom- tence of Borna disease virus-specific nucleic acid in etry (BDV nucleic acid and antigens in PBMC), tissue blood of psychiatric patient. Lancet 1998; 352:623. culture (BDV in CSF), and RT-PCR (saliva, nasal or 8. Richt JA, Vande-Woude S, Zink MC, Clements JE, conjunctival fluid). Herzog S, Stitz L, Rott R, Narayan O. Infection with Currently Recommended Donor Deferral Period: Borna disease virus: molecular and immunobiologi- cal characterization of the agent. Clin Infect Dis 1992; • No FDA Guidance or AABB Standard exists. 14:1240-50. Impact on Availability: 9. Salvatore M, Morzunov S, Schwemmle M, Lipkin WI. The Borna Virus Study Group Borna disease virus in • Agent-specific screening question(s): Not applicable brains of North American and European people with • Laboratory test(s) available: Not applicable schizophrenia and bipolar disorder. Lancet 1997; 349: 1813-4. Impact on Blood Safety: 10. Schwemmie M. Borna disease virus infection in psy- • Agent-specific screening question(s): Not applicable chiatric patients: are we on the right track? Lancet • Laboratory test(s)available: Not applicable Infect Dis 2001;1:46-52. 58S TRANSFUSION Volume 49, August 2009 Supplement.