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Japanese Complex mediated amplification assay (Procleix, Novartis). The same patient was negative when tested with the Cobas Taqscreen Disease Agent: (Roche) WNV PCR assay.

• virus (JEV) and Common Human Exposure Routes: (USUV) • Vector-borne ( mosquitoes) Disease Agent Characteristics: Likelihood of Secondary : • Family: ; Genus: • Virion morphology and size: Enveloped, icosahedral nucleo- • For JEV, absent except for rare intrauterine transmission symmetry, spherical particles, 40 to 60 nm in recorded diameter • Undocumented for USUV • Nucleic acid: Linear, positive-sense, single-stranded RNA At-Risk Populations: genome, ~11.0 kb in length • Physicochemical properties: Infectivity inactivated and • Widely distributed in destroyed by heating for 10 minutes at >56°C; half life of 7 • Affects all ages, but especially children and the elderly hours at 37°C; sensitive to treatment with lipid solvents, Vector and Reservoir Involved: detergents, ether, trypsin, chloroform, , heat and b-propiolactone; infectivity reduced after exposure to • Main epidemic JEV vectors are mosquitoes of the Culex irradiation and inactivated at pH 1-3 species, especially C. tritaeniorhynchus, which is an evening- and nighttime-biting that feeds preferentially on Disease Name: pigs and birds and infrequently on humans. Culicine mos- • Japanese encephalitis quitos are also the vectors for USUV. • In temperate regions, pigs and birds (principally ardeid Priority Level: species, such as egrets and black-crowned night herons, and • Scientific/Epidemiologic evidence regarding blood safety: possibly ducks) are effective amplifying hosts for JEV. USUV Theoretical; because of the similarity to circulates in birds. (WNV), transfusion risk during JEV outbreaks may occur. Blood Phase: • Public perception and/or regulatory concern regarding blood safety: Absent • Virus can be isolated from the blood infrequently after the • Public concern regarding disease agent: Absent appearance of symptoms. It is unknown whether a biologi- cally relevant viremic phase occurs during asymptomatic Background: infections. • Recognized in horses and humans in 1871; severe epidemic Survival/Persistence in Blood Products: occurred in in 1924; isolated from human in 1935 • Unknown • Increasing in , , and South East Asia while declin- Transmission by Blood Transfusion: ing in Japan, S. Korea, , and since 1970 because of widespread vaccination programs and other preventive • No cases documented; however, because of similarity to measures. Most recently detected in . WNV (i.e., mosquito-borne flavivirus that results in com- • 35,000-50,000 cases and 10,000 deaths occur annually in munity epidemics), transfusion transmission is plausible Asia, but the disease is greatly underreported. during JEV and USUV outbreaks. • A closely related member of the JEV complex, USUV, was Cases/Frequency in Population: implicated in the development of neuroinvasive disease in two immunosuppressed patients in northern Italy; one who • JEV is widely distributed in Asia; infection rates may exceed was viremic immediately prior to orthotopic liver trans- 1% during periods of peak transmission, which usually plantation and the other who became infected following occurs from June to November chemotherapy. Virus-specific RNA was detected by RT-PCR • Where vaccination programs are not in place, nearly all in the plasma of both patients and virus was isolated from persons in endemic areas have been infected (- the blood in one patient and CSF in the other patient; in positive) by young adulthood. both cases, sequencing revealed 98% identity with known • JEV is not endemic in the US but imported by travelers USUV isolates. Transmission in both cases occurred while returning from endemic areas with an estimated risk of one USUV was circulating in the area; prior to these two case per million travelers; risk increases with a prolonged cases, USUV had not been associated with neurological stay in a rural area where active JEV transmission is occur- disease in humans. In one of the cases, the patient was ring. From 1973-2008, 55 cases of travel-associated JE identified due to low-level reactivity in a WNV transcription- were reported from 17 countries (15 from the US). ,

December 2010: update to TRANSFUSION 2009;49(Suppl):116-117S.  Indonesia and China were where the disease was most com- Agent-specific Screening Question(s): monly acquired. • No specific question is in use. • USUV is found in sub-Saharan Africa, central and southern • No sensitive or specific question is feasible. Europe. Laboratory Test(s) Available: : • No FDA-licensed blood donor screening tests exist. • 6-16 days from exposure to onset of symptoms • Virus can occasionally be isolated in from the Likelihood of Clinical Disease: blood of symptomatic cases. Isolation possibilities are better from the CSF (up to one-third of cases). • Inapparent-to-apparent infection rate ranges from 200-300 • Serology on paired serum samples showing fourfold rise in to 1 titer by neutralization, CF or HI is diagnostic. • An IgM-capture EIA test is helpful in diagnosing JEV by Primary Disease Symptoms: detection of serum and intrathecal antibody. • JEV • PCR and viral sequencing are used for both JEV and USUV  Febrile headache syndrome  Aseptic meningitis Currently Recommended Donor Deferral Period:  Encephalitis characterized by rapid onset with a 2- to • No FDA Guidance or AABB Standard exists. 4-day prodrome of headache, fever, chills, nausea, • Prudent practice would be to defer for 1 year after resolution vomiting, dizziness, and drowsiness followed by nuchal of symptoms based on limited data regarding persistence in rigidity, photophobia, altered states of consciousness, PBMC. , hyperexcitability, and focal neurologic signs of CNS involvement. Impact on Blood Availability:

 Acute flaccid paralysis similar to poliomyelitis can • Agent-specific screening question(s): Not applicable occur • Laboratory test(s) available: Not applicable • USUV  Clinical illness is unusual and described only in case Impact on Blood Safety: reports. In immunocompromised hosts, it appears • Agent-specific screening question(s): Not applicable capable of causing neuroinvasive disease broadly • Laboratory test(s) available: Not applicable similar to JEV. Leukoreduction Efficacy: Severity of Clinical Disease: • Unknown, but PBMC isolation study mentioned previously • Severe manifestations of the disease can occur with accom- suggests that leukoreduction might lower a theoretical risk panying mortality. from JEV • Neuropsychiatric sequelae are frequent (45%-70% of JEV sur- vivors) often with thalamic or other lesions on MRI. These Pathogen Reduction Efficacy for Plasma Derivatives: include a Parkinsonian syndrome, convulsive disorders, • Multiple pathogen reduction steps used in the fractionation paralysis, mental retardation, and psychiatric disorders. process have been shown to be robust in removal of envel- Mortality: oped .

• Children and the elderly are at the highest risk for JEV mor- Other Prevention Measures: tality, which ranges from 5%-40% (2%-11% reported in US • Formalin-inactivated for humans have an efficacy military personnel) with the highest frequency usually of 91%; a live attenuated is in use in China yielding associated with poor medical care. seroconversion in 95% after one dose. Genetically engi- Chronic Carriage: neered vaccines are in development. • • Evidence for persistent/latent infection in humans is based on recovery of JEV from PBMC of asymptomatic children 9 Suggested Reading: months after acute JEV as well as in children developing 1. Berenson MW, Top FH Jr, Gresso W, Ames CW, Altstatt LB. recurrent disease. JEV was also recovered from CSF 4 months The virulence to man of Japanese encephalitis virus in Thai- after onset of symptoms. The relevance of these data remains land. Am J Trop Med Hyg 1975;24:974-80. to be elucidated. 2. Centers for Disease Control and Prevention. Japanese encephalitis virus. Recommendations of the Advisory Com- Treatment Available/Efficacious: mittee on Immunization Practices (ACIP). Morb Mortal Wkly • Supportive treatment Rep MMWR 2010;59:1-27.

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