Evolving Epidemiology of Japanese Encephalitis: Implications for Vaccination
Purpose of Review
We examine the present global burden of Japanese encephalitis (JE) in endemic populations, summarize published cases in travelers since 2009, examine current guidelines for vaccination for international travelers, and consider challenges in prevention of this vector-borne disease.
We identified 11 JE cases in travelers that were published in peer-reviewed literature since 2009. JE incidence in endemic countries appears to be declining but the number of JE cases reported to the World Health Organization (WHO) varied from estimates derived from other published reports based on serosurveys or sentinel surveillance. Current JE vaccines appear to be safe and are not associated with delayed hypersensitivity in contrast to the older mouse brain vaccine.
Given differences between WHO-reported cases and local surveillance data, future research on true incidence is needed. Regular assessment will inform JE risk in travelers. National and international guidelines on JE vaccination varied; we suggest areas for improvement.
KeywordsJapanese encephalitis Epidemiology Risk estimates Travelers Vaccination
The authors thank Dr. Susan Hills for her thoughtful review and suggestions.
Compliance with Ethical Standards
Conflict of Interest
JPC declares that he has no conflict of interest. LHC reports serving as advisor for Shoreland, Inc. and DSMB for Valneva (unrelated vaccine). DHH reports serving on advisory boards for Valneva and iJET.
Human and Animal Rights and Informed Consent
This article does not contain any studies with human or animal subjects performed by any of the authors.
Papers of particular interest, published recently, have been highlighted as • Of importance •• Of major importance
- 1.Solomon T. Japanese encephalitis. In: Magill A, editor. Hunter’s tropical medicine and emerging infectious disease, expert consult—online and print. 9th ed. Elsevier Health Sciences; 2013. p. 358–365.Google Scholar
- 2.Schuh AJ, Ward MJ, Leigh Brown AJ, Barrett ADT. Phylogeography of Japanese encephalitis virus: genotype is associated with climate. PLoS Negl Trop Dis. 2013;7(8) https://doi.org/10.1371/journal.pntd.0002411.
- 3.Zhang J, Zhao Q, Guo X, Zuo S, Cheng J, Jia N. Isolation and genetic characteristics of human genotype 1 Japanese Encephalitis Virus, China, 2009. PLoS One. 2011;6(1) https://doi.org/10.1371/journal.pone.0016418.
- 6.Nga PT, del Carmen Parquet M, Cuong VD, et al. Shift in Japanese encephalitis virus (JEV) genotype circulating in northern Vietnam: implications for frequent introductions of JEV from Southeast Asia to East Asia. J Gen Virol. 2004;85(6):1625–31. https://doi.org/10.1099/vir.0.79797-0.CrossRefPubMedGoogle Scholar
- 13.• Cao L, Fu S, Gao X, et al. Low protective efficacy of the current Japanese encephalitis vaccine against the emerging genotype 5 Japanese encephalitis virus. PLoS Negl Trop Dis. 2016;10(5):1–12. https://doi.org/10.1371/journal.pntd.0004686. Presents both in vivo and in vitro tests demonstrating poor protective efficacy of current genotype III-based inactivated and live-attenuated vaccines against genotype V . CrossRefGoogle Scholar
- 19.•• Cappelle J, Duong V, Pring L, Kong L, Yakovleff M, Prasetyo DB, et al. Intensive circulation of Japanese encephalitis virus in peri-urban sentinel pigs near Phnom. PLoS Negl Trop Dis. 2016;10(12):1–14. https://doi.org/10.1371/journal.pntd.0005149. Demonstrates a high prevalence of JE seropositivity in pigs in surveillance of piggeries in densely-populated outskirts of Phnom Penh, Cambodia CrossRefGoogle Scholar
- 21.• Ricklin ME, García-Nicolás O, Brechbühl D, Python S, Zumkehr B, Nougairede A, et al. Vector-free transmission and persistence of Japanese encephalitis virus in pigs. Nat Commun. 2016;7:10832. https://doi.org/10.1038/ncomms10832. Demonstrates under experimental conditions transmission of JEV between pigs via oronasal secretions; clinical and histological signs of infection did not differ between routes of transmission CrossRefPubMedPubMedCentralGoogle Scholar
- 25.Hills SL, Rabe IB, Fisher M. Chapter 3: infectious diseases related to travel, Japanese encephalitis. Centers for Disease Control Yellow Book. https://wwwnc.cdc.gov/travel/yellowbook/2018/infectious-diseases-related-to-travel/japanese-encephalitis. Published 2017.
- 27.Ravanini P, Huhtamo E, Ilaria V, Crobu M.G., Nicosia A.M., Servino L., Rivasi F., Allegrini S., Miglio U., Magri A., Minisini R., Vapalahti O., Boldorini R. Japanese encephalitis virus RNA detected in Culex pipiens mosquitoes in Italy. Euro Surveill. 2012;17(28).Google Scholar
- 30.Burke DS, Leake C. Japanese encephalitis. In: Monath T, editor. The arboviruses: epidemiology and ecology, vol. 3. Boca Raton: CRC Press; 1988.Google Scholar
- 32.•• Campbell G, Hills S, Fischer M, Jacobson J, Hoke C, Hombach J, et al. Estimated global incidence of Japanese encephalitis. Bull World Health Organ. 2011;89(10):766–74. https://doi.org/10.2471/BLT.10.085233. Most recent comprehensive assessment of global JE burden, estimating an annual incidence of 68,000 cases based on extrapolation of published sentinel surveillance studying CrossRefPubMedPubMedCentralGoogle Scholar
- 35.Testa G, Borghese L, Steinbeck JA, Bru O. Meeting report. Cell. 2007;153–156. https://doi.org/10.1016/j.stem.2007.07.006.
- 37.•• World Health Organization. WHO vaccine-preventable diseases: monitoring system. 2017 global summary. http://apps.who.int/immunization_monitoring/globalsummary/. Published 2017. Accessed 18 Dec 2017. Provides data on incidence and vaccination rates, as self-reported by individual countries.
- 39.Touch S, Hills S, Sokhal B, Samnang C, Sovann L, Khieu V, et al. Epidemiology and burden of disease from Japanese encephalitis in Cambodia: results from two years of sentinel surveillance. Tropical Med Int Health. 2009;14(11):1365–73. https://doi.org/10.1111/j.1365-3156.2009.02380.x.CrossRefGoogle Scholar
- 41.Lindahl J. Japanese encephalitis virus in pigs and vectors in the Mekong Delta with special reference to urban farming. 2012.Google Scholar
- 42.Yang Y, Liang N, Tan Y, Xie Z. Epidemiological trends and characteristics of Japanese encephalitis changed based on the vaccination program between 1960 and 2013 in Guangxi Zhuang Autonomous Region, southern China. Int J Infect Dis. 2016;45:135–8. https://doi.org/10.1016/j.ijid.2016.03.004.CrossRefPubMedGoogle Scholar
- 43.Huanyu W, Yixing L, Xiaofeng L, Guodong L. Japanese encephalitis in mainland China. Jpn J Infect Dis. 2009;62:331–6.Google Scholar
- 45.Directorate of National Vector Borne Disease Control Programme - Delhi. State wise number of AES/JE Cases and Deaths from 2010–2017. Dir Natl Vector Borne Dis Control Program. 2017:11651. http://nvbdcp.gov.in/Doc/je-aes.pdf.
- 46.Murhekar MV, Oak C, Ranjan P, Kanagasabai K, Shinde S, Pandey AK, et al. Coverage & missed opportunity for Japanese encephalitis vaccine, Gorakhpur division, Uttar Pradesh, India, 2015: implications for Japanese encephalitis control. Indian J Med Res. 2017;145(February):63–9. https://doi.org/10.4103/ijmr.IJMR.CrossRefPubMedPubMedCentralGoogle Scholar
- 50.World Health Organization. Japanese Encephalitis reported cases. http://apps.who.int/immunization_monitoring/globalsummary/timeseries/tsincidencejapenc.html. Published 2017. Accessed 1 Jan 2017.
- 51.Wagner H. Protecting the environment from the impact of the growing industrialization of livestock production in East Asia. In: 26th Session of Animal Production and Health Commission of Asia and the Pacific, Food and Agriculture Administration of United Nations. 2002. http://www.fao.org/docrep/005/ac801e/ac801e09.htm.
- 52.Vallée J, Dubot-Pérès A, Ounaphom P, Sayavong C, Bryant JE, Gonzalez JP. Spatial distribution and risk factors of dengue and Japanese encephalitis virus infection in urban settings: the case of Vientiane, Lao PDR. Tropical Med Int Health. 2009;14(9):1134–42. https://doi.org/10.1111/j.1365-3156.2009.02319.x.CrossRefGoogle Scholar
- 55.Oo PM, Hlaing T, Lwin S, Pittyawonganon C. A large outbreak of Japanese encephalitis in Rakhine State, Myanmar: implication for vaccine policy. Osir. 2016;9(2):8–15.Google Scholar
- 56.Ram ST, Neuberger A, Thapa LJ, Vir Singh RP, Shofty B, Schwartz E. Japanese encephalitis among patients with acute encephalitic syndrome admitted to a tertiary hospital in Chitwan, Nepal—a prospective observational study. PLoS One. 2014;9(6). https://doi.org/10.1371/journal.pone.0099999.
- 61.Sunwoo J, Jung K, Lee S, Lee SK, Chu K. Reemergence of Japanese encephalitis in South Korea, 2010-2015. 2016;22(10):1841–3. https://doi.org/10.3201/eid2210.160288.
- 66.Yen NT, Duffy MR, Hong NM, Hien NT, Fischer M, Hills SL. Surveillance for Japanese Encephalitis in Vietnam, 1998–2007. 2010;83(4):816–819. doi: https://doi.org/10.4269/ajtmh.2010.10-0262.
- 67.SAGE Working Group on Japanese encephalitis vaccines (World Health Organization). Background paper on Japanese encephalitis vaccines. 2016;(March):1–74.Google Scholar
- 69.Xufang Y, Huanyu W, Shihong F, Xiaoyan G, Shuye Z, Chunting L, et al. Etiological spectrum of clinically diagnosed Japanese encephalitis cases reported in Guizhou Province, China, in 2006. J Clin Microbiol. 2010;48(4):1343–9. https://doi.org/10.1128/JCM.01009-09.CrossRefPubMedPubMedCentralGoogle Scholar
- 74.Chen L et al. Japanese encephalitis in two children—United States, 2010. Morb Mortal Wkly Rep. 2011;60(9).Google Scholar
- 79.Doti P, Castro P, Martínez MJ, Zboromyrska Y, Aldasoro E, Inciarte A, et al. A case of Japanese encephalitis in a 20 year-old Spanish sportsman, February 2013. Eur Secur. 2013;18(35) https://doi.org/10.2807/1560-7917.ES2013.18.35.20573.
- 80.• Huang GKL, Tio SY, Caly L, et al. Prolonged detection of Japanese Encephalitis virus in urine and whole blood in a returned short-term traveler. Open Forum Infect Dis. 2017;ofx203. https://doi.org/10.1093/ofid/ofx203. Report of an Australian man with a fatal case of JE acquired during 8-day travel to Thailand, notable for isolation of JEV RNA from whole blood and culture of JEV from urine sample, findings which previously had not been reported.
- 82.Practices AC on I. Morbidity and mortality weekly report Japanese encephalitis vaccines recommendations of the Advisory Committee on Immunization Practices. Vol 59. 2010.Google Scholar
- 84.• Saito Y, Moi ML, Takeshita N, Lim CK, Shiba H, Hosono K, et al. Japanese encephalitis vaccine-facilitated dengue virus infection-enhancement antibody in adults. BMC Infect Dis. 2016;16(1):578. https://doi.org/10.1186/s12879-016-1873-8. Following a single dose of inactivated Vero cell-derived JE vaccine, Japanese adults demonstrated sub-neutralizing levels of cross-reactivity against dengue, implying a risk of more severe infection in the event of dengue infection following JE vaccination CrossRefPubMedPubMedCentralGoogle Scholar
- 86.Public Health Agency of Canada. An Advisory Committee Statement (ACS-4): statement on protection against Japanese Encephalitis. Vol 34; 2008.Google Scholar
- 87.European Centre for Disease Control andPrevention. Facts about Japanese encephalitis. https://ecdc.europa.eu/en/japanese-encephalitis/facts. Published 2017. Accessed 23 July 2017.
- 88.•• WHO. Japanese encephalitis vaccines: WHO position paper—February 2015. WHO Wkly Epidemiol Rec Relev épidémiologique Hebd. 2015;21(90):69–88. https://doi.org/10.1186/1750-9378-2-15.Voir. Provides most recent data on laboratory detection of JE and vaccine safety and immunogenecity; recommends vaccination in travelers to endemic areas during transmission season who have "extensive outdoor exposure" Google Scholar
- 89.National Health Service GB. Japanese encephalitis—prevention. NHS Choices. http://www.nhs.uk/Conditions/Japanese-encephalitis/Pages/Whileyoureaway.aspx. 2016. Accessed 20 July 2017.
- 90.Australian Government Department of Health. Japanese encephalitis. The Australian Immunisation Handbook, 10th ed. http://www.immunise.health.gov.au/internet/immunise/publishing.nsf/Content/Handbook10-home~handbook10part4~handbook10-4-8#4-8-7. 2017. Accessed 23 July 2017.
- 91.Himani D, Kumar HBC, Bhilegaonkar KN, Kumar A. Japanese encephalitis: a veterinary perspective. J Foodborne Zoonotic Dis. 2014;2(4):59–67.Google Scholar
- 95.Dubischar KL, Kadlecek V, Sablan B, et al. Safety of the inactivated Japanese encephalitis virus vaccine IXIARO® in children—an open-label, randomized, active-controlled, phase 3 study. 2017. https://doi.org/10.1097/INF.0000000000001623.
- 97.Integrated Disease Surveillance Program. National Centre for Disease Control, Directorate General of Health Services, Ministry of Health & Family Welfare, Government of India. http://idsp.nic.in. 2017.