Japanese encephalitis: Epidemiology, diagnosis, treatment, and prevention
- Susan L Hills, MBBS, MTH
Susan L Hills, MBBS, MTH
- Medical Epidemiologist
- Centers for Disease Control and Prevention
- Marc Fischer, MD, MPH
Marc Fischer, MD, MPH
- Medical Epidemiologist
- Centers for Disease Control and Prevention
- Tom Solomon, FRCP, PhD
Tom Solomon, FRCP, PhD
- Professor of Neurological Science
- University of Liverpool
Japanese encephalitis virus (JEV), a mosquito-borne flavivirus, is the most important cause of viral encephalitis in Asia based on its frequency and severity. With the near eradication of poliomyelitis, JEV is now the leading cause of childhood viral neurological infection and disability in Asia . JEV is closely related to West Nile, St. Louis encephalitis, and Murray Valley encephalitis viruses .
About 68,000 cases of Japanese encephalitis (JE) are estimated to occur each year. JEV is endemic throughout most of Asia and parts of the western Pacific, but local transmission has not been observed in Africa, Europe, or the Americas. For travelers to Asia, the risk of JE is very low but varies based on season, destination, duration, and activities . The estimated incidence of JE among travelers to Asia from nonendemic countries is <1 case per 1 million travelers. Risk is likely to be higher for expatriates or travelers with longer duration of travel or whose plans include extensive outdoor activities in rural areas . Since 1973, only 56 cases of JE among travelers from nonendemic countries have been reported ; since a JE vaccine was licensed in the United States in 1992, only four cases of JE were reported among United States travelers between 1992 and 2008 .
Most human JEV infections are asymptomatic or cause a nonspecific febrile illness. Less than 1 percent of JEV infections results in symptomatic neuroinvasive disease . However, when neurological disease does occur, it is usually very severe with a high case fatality rate; among survivors, neurological sequelae are common. All travelers to JEV-endemic countries should be given advice on measures to prevent JE, and JE should be considered among the differential diagnoses for patients with suspected neurological infection who have returned from recent travel in a JEV-endemic country in Asia or the Western Pacific region.
Japanese encephalitis (JE) is endemic throughout most of Asia and parts of the Western Pacific region (figure 1). Within the JE-endemic region, there are two typical patterns of transmission:
●In areas with temperate climates (including China, Japan, South Korea, Nepal, northern Vietnam, and northern India), most cases occur over a period of several months when the weather is warmest, usually after the monsoons begin or associated with heavy rainfall [2,7,8]. The peak months of transmission and the length of the season vary from place to place. There are sometimes large, explosive outbreaks.
- Halstead SB, Jacobson J. Japanese encephalitis. Adv Virus Res 2003; 61:103.
- Mackenzie JS, Williams DT, Smith DW. Japanese encephalitis virus: The geographic distribution, incidence, and spread of a virus with a propensity to emerge in new areas. In: Emerging Viruses in Human Populations, Tabor E (Ed), Elsevier, 2007.
- Fischer M, Lindsey N, Staples JE, et al. Japanese encephalitis vaccines: recommendations of the Advisory Committee on Immunization Practices (ACIP). MMWR Recomm Rep 2010; 59:1.
- Hills SL, Griggs AC, Fischer M. Japanese encephalitis in travelers from non-endemic countries, 1973-2008. Am J Trop Med Hyg 2010; 82:930.
- Centers for Disease Control and Prevention (CDC). Japanese encephalitis in two children--United States, 2010. MMWR Morb Mortal Wkly Rep 2011; 60:276.
- Halstead S, Jacobson J. Japanese encephalitis vaccines. In: Vaccines, 5th ed, Plotkin S, Orenstein W, Offit P (Eds), Saunders Elsevier, 2008.
- Endy TP, Nisalak A. Japanese encephalitis virus: ecology and epidemiology. Curr Top Microbiol Immunol 2002; 267:11.
- Arai S, Matsunaga Y, Takasaki T, et al. Japanese encephalitis: surveillance and elimination effort in Japan from 1982 to 2004. Jpn J Infect Dis 2008; 61:333.
- Vaughn DW, Hoke CH Jr. The epidemiology of Japanese encephalitis: prospects for prevention. Epidemiol Rev 1992; 14:197.
- Ompusunggu S, Hills SL, Maha MS, et al. Confirmation of Japanese encephalitis as an endemic human disease through sentinel surveillance in Indonesia. Am J Trop Med Hyg 2008; 79:963.
- Tsai TF. New initiatives for the control of Japanese encephalitis by vaccination: minutes of a WHO/CVI meeting, Bangkok, Thailand, 13-15 October 1998. Vaccine 2000; 18 Suppl 2:1.
- Wu YC, Huang YS, Chien LJ, et al. The epidemiology of Japanese encephalitis on Taiwan during 1966-1997. Am J Trop Med Hyg 1999; 61:78.
- Centers for Disease Control and Prevention. CDC Heath Information for International Travel 2012. US Department of Health and Human Services, Public Health Service, Atlanta, GA 2011.
- van den Hurk AF, Ritchie SA, Mackenzie JS. Ecology and geographical expansion of Japanese encephalitis virus. Annu Rev Entomol 2009; 54:17.
- Ooi MH, Lewthwaite P, Lai BF, et al. The epidemiology, clinical features, and long-term prognosis of Japanese encephalitis in central sarawak, malaysia, 1997-2005. Clin Infect Dis 2008; 47:458.
- Solomon T, Dung NM, Kneen R, et al. Japanese encephalitis. J Neurol Neurosurg Psychiatry 2000; 68:405.
- LINCOLN AF, SIVERTSON SE. Acute phase of Japanese B encephalitis; two hundred and one cases in American soldiers, Korea, 1950. J Am Med Assoc 1952; 150:268.
- Solomon T, Dung NM, Kneen R, et al. Seizures and raised intracranial pressure in Vietnamese patients with Japanese encephalitis. Brain 2002; 125:1084.
- Solomon T, Kneen R, Dung NM, et al. Poliomyelitis-like illness due to Japanese encephalitis virus. Lancet 1998; 351:1094.
- Chung CC, Lee SS, Chen YS, et al. Acute flaccid paralysis as an unusual presenting symptom of Japanese encephalitis: a case report and review of the literature. Infection 2007; 35:30.
- Solomon T. Flavivirus encephalitis. N Engl J Med 2004; 351:370.
- Maschke M, Kastrup O, Forsting M, Diener HC. Update on neuroimaging in infectious central nervous system disease. Curr Opin Neurol 2004; 17:475.
- Wang HS. Comparison of magnetic resonance imaging abnormalities in Japanese encephalitis and acute necrotizing encephalopathy of childhood. Arch Neurol 2004; 61:1149.
- Dung NM, Turtle L, Chong WK, et al. An evaluation of the usefulness of neuroimaging for the diagnosis of Japanese encephalitis. J Neurol 2009; 256:2052.
- Solomon T, Thao TT, Lewthwaite P, et al. A cohort study to assess the new WHO Japanese encephalitis surveillance standards. Bull World Health Organ 2008; 86:178.
- Kari K, Liu W, Gautama K, et al. A hospital-based surveillance for Japanese encephalitis in Bali, Indonesia. BMC Med 2006; 4:8.
- Burke DS, Lorsomrudee W, Leake CJ, et al. Fatal outcome in Japanese encephalitis. Am J Trop Med Hyg 1985; 34:1203.
- Chanama S, Sukprasert W, Sa-ngasang A, et al. Detection of Japanese encephalitis (JE) virus-specific IgM in cerebrospinal fluid and serum samples from JE patients. Jpn J Infect Dis 2005; 58:294.
- Swami R, Ratho RK, Mishra B, Singh MP. Usefulness of RT-PCR for the diagnosis of Japanese encephalitis in clinical samples. Scand J Infect Dis 2008; 40:815.
- Kuwayama M, Ito M, Takao S, et al. Japanese encephalitis virus in meningitis patients, Japan. Emerg Infect Dis 2005; 11:471.
- Solomon T, Hart IJ, Beeching NJ. Viral encephalitis: a clinician's guide. Pract Neurol 2007; 7:288.
- Reimann CA, Hayes EB, DiGuiseppi C, et al. Epidemiology of neuroinvasive arboviral disease in the United States, 1999-2007. Am J Trop Med Hyg 2008; 79:974.
- Tiroumourougane SV, Raghava P, Srinivasan S. Japanese viral encephalitis. Postgrad Med J 2002; 78:205.
- Kumar R, Tripathi P, Baranwal M, et al. Randomized, controlled trial of oral ribavirin for Japanese encephalitis in children in Uttar Pradesh, India. Clin Infect Dis 2009; 48:400.
- Hoke CH Jr, Vaughn DW, Nisalak A, et al. Effect of high-dose dexamethasone on the outcome of acute encephalitis due to Japanese encephalitis virus. J Infect Dis 1992; 165:631.
- Solomon T, Dung NM, Wills B, et al. Interferon alfa-2a in Japanese encephalitis: a randomised double-blind placebo-controlled trial. Lancet 2003; 361:821.
- Gould EA, Solomon T, Mackenzie JS. Does antiviral therapy have a role in the control of Japanese encephalitis? Antiviral Res 2008; 78:140.
- Caramello P, Canta F, Balbiano R, et al. Role of intravenous immunoglobulin administration in Japanese encephalitis. Clin Infect Dis 2006; 43:1620.
- Chaturvedi UC, Mathur A, Chandra A, et al. Transplacental infection with Japanese encephalitis virus. J Infect Dis 1980; 141:712.
- Mathur A, Tandon HO, Mathur KR, et al. Japanese encephalitis virus infection during pregnancy. Indian J Med Res 1985; 81:9.
- Centers for Disease Control and Prevention. Vaccine Recommendations of the ACIP. http://www.cdc.gov/vaccines/hcp/acip-recs/vacc-specific/index.html (Accessed on November 12, 2014).
- Tauber E, Kollaritsch H, Korinek M, et al. Safety and immunogenicity of a Vero-cell-derived, inactivated Japanese encephalitis vaccine: a non-inferiority, phase III, randomised controlled trial. Lancet 2007; 370:1847.
- Japanese Encephalitis Vaccine, Inactivated, Adsorbed (IXIARO). Package insert (commercial). http://www.fda.gov/BiologicsBloodVaccines/Vaccines/ApprovedProducts/ucm179132.htm (Accessed on May 19, 2011).
- Tauber E, Kollaritsch H, von Sonnenburg F, et al. Randomized, double-blind, placebo-controlled phase 3 trial of the safety and tolerability of IC51, an inactivated Japanese encephalitis vaccine. J Infect Dis 2008; 198:493.
- Rabe IB, Miller ER, Fischer M, Hills SL. Adverse events following vaccination with an inactivated, Vero cell culture-derived Japanese encephalitis vaccine in the United States, 2009-2012. Vaccine 2015; 33:708.
- Dubischar-Kastner K. Pediatric data for Ixiaro: Japanese encephalitis vaccine, inactivated, adsorbed. Presentation to the Advisory Committee on Immunization Practices, Atlanta, GA, June 19, 2013. http://www.cdc.gov/vaccines/acip/meetings/downloads/slides-jun-2013/02-JE-Dubischar-Kastner.pdf (Accessed on November 19, 2013).
- Food and Drug Administration. Clinical review: Ixiaro. Silver Spring, MD: Food and Drug Administration; 2013. http://www.fda.gov/downloads/biologicsbloodvaccines/vaccines/approvedproducts/ucm354012.pdf (Accessed on November 19, 2013).
- Centers for Disease Control and Prevention (CDC). Use of Japanese encephalitis vaccine in children: recommendations of the advisory committee on immunization practices, 2013. MMWR Morb Mortal Wkly Rep 2013; 62:898.
- Kaltenböck A, Dubischar-Kastner K, Schuller E, et al. Immunogenicity and safety of IXIARO (IC51) in a Phase II study in healthy Indian children between 1 and 3 years of age. Vaccine 2010; 28:834.
- Centers for Disease Control and Prevention (CDC). Recommendations for use of a booster dose of inactivated vero cell culture-derived Japanese encephalitis vaccine: advisory committee on immunization practices, 2011. MMWR Morb Mortal Wkly Rep 2011; 60:661.
- Jelinek T, Burchard GD, Dieckmann S, et al. Immunogenicity and safety of an accelerated dosing regimen of Japanese Encephalitis inactivated absorbed vaccine for travelers: A phase III randomized study in healthy adults. Abstract. 5th Northern European Conference on Travel Medicine. June 5-8, 2014.
- FDA. Product approval information [package insert]. Ixiaro (Japanese encephalitis virus vaccine inactivated). Intercell Biomedical, Livingston, United Kingdom. http://www.fda.gov/cber/label/ixiarocommercialLB.pdf (Accessed on July 31, 2009).
- Erra EO, Askling HH, Rombo L, et al. A single dose of vero cell-derived Japanese encephalitis (JE) vaccine (Ixiaro) effectively boosts immunity in travelers primed with mouse brain-derived JE vaccines. Clin Infect Dis 2012; 55:825.
- Woolpert T, Staples JE, Faix DJ, et al. Immunogenicity of one dose of Vero cell culture-derived Japanese encephalitis (JE) vaccine in adults previously vaccinated with mouse brain-derived JE vaccine. Vaccine 2012; 30:3090.
- Erra EO, Askling HH, Yoksan S, et al. Cross-protection elicited by primary and booster vaccinations against Japanese encephalitis: a two-year follow-up study. Vaccine 2013; 32:119.
- CLINICAL MANIFESTATIONS
- Laboratory findings
- Diagnostic testing
- Differential diagnosis
- Personal protective measures
- - Whom to vaccinate
- - Immunogenicity and safety
- - Dose and administration