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Fulltext The current burden of Japanese encephalitis and the estimated impacts of vaccination: Combining estimates of the spatial distribution and transmission intensity of a zoonotic pathogen

Moore SM

PLoS Negl Trop Dis, 2021 10;15(10):e0009385.
PMID: 34644296 DOI: 10.1371/journal.pntd.0009385

Japanese encephalitis virus (JEV) is a major cause of neurological disability in Asia and causes thousands of severe encephalitis cases and deaths each year. Although Japanese encephalitis (JE) is a WHO reportable disease, cases and deaths are significantly underreported and the true burden of the disease is not well understood in most endemic countries. Here, we first conducted a spatial analysis of the risk factors associated with JE to identify the areas suitable for sustained JEV transmission and the size of the population living in at-risk areas. We then estimated the force of infection (FOI) for JE-endemic countries from age-specific incidence data. Estimates of the susceptible population size and the current FOI were then used to estimate the JE burden from 2010 to 2019, as well as the impact of vaccination. Overall, 1,543.1 million (range: 1,292.6-2,019.9 million) people were estimated to live in areas suitable for endemic JEV transmission, which represents only 37.7% (range: 31.6-53.5%) of the over four billion people living in countries with endemic JEV transmission. Based on the baseline number of people at risk of infection, there were an estimated 56,847 (95% CI: 18,003-184,525) JE cases and 20,642 (95% CI: 2,252-77,204) deaths in 2019. Estimated incidence declined from 81,258 (95% CI: 25,437-273,640) cases and 29,520 (95% CI: 3,334-112,498) deaths in 2010, largely due to increases in vaccination coverage which have prevented an estimated 314,793 (95% CI: 94,566-1,049,645) cases and 114,946 (95% CI: 11,421-431,224) deaths over the past decade. India had the largest estimated JE burden in 2019, followed by Bangladesh and China. From 2010-2019, we estimate that vaccination had the largest absolute impact in China, with 204,734 (95% CI: 74,419-664,871) cases and 74,893 (95% CI: 8,989-286,239) deaths prevented, while Taiwan (91.2%) and Malaysia (80.1%) had the largest percent reductions in JE burden due to vaccination. Our estimates of the size of at-risk populations and current JE incidence highlight countries where increasing vaccination coverage could have the largest impact on reducing their JE burden.

Matched MeSH terms: Japanese Encephalitis Vaccines/administration & dosage*; Japanese Encephalitis Vaccines/immunology
Fulltext The effect of vaccination coverage and climate on Japanese encephalitis in Sarawak, Malaysia

Impoinvil DE, Ooi MH, Diggle PJ, Caminade C, Cardosa MJ, Morse AP, et al.

PLoS Negl Trop Dis, 2013;7(8):e2334.
PMID: 23951373 DOI: 10.1371/journal.pntd.0002334

BACKGROUND: Japanese encephalitis (JE) is the leading cause of viral encephalitis across Asia with approximately 70,000 cases a year and 10,000 to 15,000 deaths. Because JE incidence varies widely over time, partly due to inter-annual climate variability effects on mosquito vector abundance, it becomes more complex to assess the effects of a vaccination programme since more or less climatically favourable years could also contribute to a change in incidence post-vaccination. Therefore, the objective of this study was to quantify vaccination effect on confirmed Japanese encephalitis (JE) cases in Sarawak, Malaysia after controlling for climate variability to better understand temporal dynamics of JE virus transmission and control.
METHODOLOGY/PRINCIPAL FINDINGS: Monthly data on serologically confirmed JE cases were acquired from Sibu Hospital in Sarawak from 1997 to 2006. JE vaccine coverage (non-vaccine years vs. vaccine years) and meteorological predictor variables, including temperature, rainfall and the Southern Oscillation index (SOI) were tested for their association with JE cases using Poisson time series analysis and controlling for seasonality and long-term trend. Over the 10-years surveillance period, 133 confirmed JE cases were identified. There was an estimated 61% reduction in JE risk after the introduction of vaccination, when no account is taken of the effects of climate. This reduction is only approximately 45% when the effects of inter-annual variability in climate are controlled for in the model. The Poisson model indicated that rainfall (lag 1-month), minimum temperature (lag 6-months) and SOI (lag 6-months) were positively associated with JE cases.
CONCLUSIONS/SIGNIFICANCE: This study provides the first improved estimate of JE reduction through vaccination by taking account of climate inter-annual variability. Our analysis confirms that vaccination has substantially reduced JE risk in Sarawak but this benefit may be overestimated if climate effects are ignored.

Matched MeSH terms: Japanese Encephalitis Vaccines/administration & dosage*; Japanese Encephalitis Vaccines/immunology*
Fulltext Overview of Japanese encephalitis disease and its prevention. Focus on IC51 vaccine (IXIARO®)

Amicizia D, Zangrillo F, Lai PL, Iovine M, Panatto D

J Prev Med Hyg, 2018 Mar;59(1):E99-E107.
PMID: 29938245 DOI: 10.15167/2421-4248/jpmh2018.59.1.962

Japanese encephalitis (JE) is a vector-borne disease caused by the Japanese encephalitis virus (JEV). JEV is transmitted by mosquitoes to a wide range of vertebrate hosts, including birds and mammals. Domestic animals, especially pigs, are generally implicated as reservoirs of the virus, while humans are not part of the natural transmission cycle and cannot pass the virus to other hosts. Although JEV infection is very common in endemic areas (many countries in Asia), less than 1% of people affected develop clinical disease, and severe disease affects about 1 case per 250 JEV infections. Although rare, severe disease can be devastating; among the 30,000-50,000 global cases per year, approximately 20-30% of patients die and 30-50% of survivors develop significant neurological sequelae. JE is a significant public health problem for residents in endemic areas and may constitute a substantial risk for travelers to these areas. The epidemiology of JE and its risk to travelers have changed, and continue to evolve. The rapid economic growth of Asian countries has led to a surge in both inbound and outbound travel, making Asia the second most-visited region in the world after Europe, with 279 million international travelers in 2015. The top destination is China, followed by Thailand, Hong Kong, Malaysia and Japan, and the number of travelers is forecast to reach 535 million by 2030 (+ 4.9% per year). Because of the lack of treatment and the infeasibility of eliminating the vector, vaccination is recognized as the most efficacious means of preventing JE. The IC51 vaccine (IXIARO®) is a purified, inactivated, whole virus vaccine against JE. It is safe, well tolerated, efficacious and can be administered to children, adults and the elderly. The vaccination schedule involves administering 2 doses four weeks apart. For adults, a rapid schedule (0-7 days) is available, which could greatly enhance the feasibility of its use. Healthcare workers should inform both short- and long-term travelers of the risk of JE in each period of the year and recommend vaccination. Indeed, it has been shown that short-term travelers are also at risk, not only in rural environments, but also in cities and coastal towns, especially in tourist localities where excursions to country areas are organized.

Matched MeSH terms: Japanese Encephalitis Vaccines/administration & dosage*; Japanese Encephalitis Vaccines/adverse effects
A hospital-based surveillance for Japanese encephalitis in Bali, Indonesia

Kari K, Liu W, Gautama K, Mammen MP, Clemens JD, Nisalak A, et al.

BMC Med, 2006;4:8.
PMID: 16603053

Japanese encephalitis (JE) is presumed to be endemic throughout Asia, yet only a few cases have been reported in tropical Asian countries such as Indonesia, Malaysia and the Philippines. To estimate the true disease burden due to JE in this region, we conducted a prospective, hospital-based surveillance with a catchment population of 599,120 children less than 12 years of age in Bali, Indonesia, from July 2001 through December 2003.

Matched MeSH terms: Japanese Encephalitis Vaccines/therapeutic use
Fulltext Japanese encephalitis in Malaysia: An overview and timeline

Kumar K, Arshad SS, Selvarajah GT, Abu J, Toung OP, Abba Y, et al.

Acta Trop, 2018 Sep;185:219-229.
PMID: 29856986 DOI: 10.1016/j.actatropica.2018.05.017

Japanese encephalitis (JE) is a vector-borne zoonotic disease caused by the Japanese encephalitis virus (JEV). It causes encephalitis in human and horses, and may lead to reproductive failure in sows. The first human encephalitis case in Malaya (now Malaysia) was reported during World War II in a British prison in 1942. Later, encephalitis was observed among race horses in Singapore. In 1951, the first JEV was isolated from the brain of an encephalitis patient. The true storyline of JE exposure among humans and animals has not been documented in Malaysia. In some places such as Sarawak, JEV has been isolated from mosquitoes before an outbreak in 1992. JE is an epidemic in Malaysia except Sarawak. There are four major outbreaks reported in Pulau Langkawi (1974), Penang (1988), Perak and Negeri Sembilan (1998-1999), and Sarawak (1992). JE is considered endemic only in Sarawak. Initially, both adults and children were victims of JE in Malaysia, however, according to the current reports; JE infection is only lethal to children in Malaysia. This paper describes a timeline of JE cases (background of each case) from first detection to current status, vaccination programs against JE, diagnostic methods used in hospitals and factors which may contribute to the transmission of JE among humans and animals in Malaysia.

Matched MeSH terms: Japanese Encephalitis Vaccines/immunology
Fulltext A decade of Japanese encephalitis surveillance in Sarawak, Malaysia: 1997-2006

Wong SC, Ooi MH, Abdullah AR, Wong SY, Krishnan S, Tio PH, et al.

Trop Med Int Health, 2008 Jan;13(1):52-5.
PMID: 18291002 DOI: 10.1111/j.1365-3156.2007.01967.x

Japanese encephalitis virus (JEV) is an important encephalitis virus in Asia, but there are few data on Malaysia. A hospital-based surveillance system for Japanese encephalitis (JE) has been in operation in Sarawak, Malaysia, for the last 10 years. JEV is endemic in Sarawak, with cases occurring throughout the year and a seasonal peak in the last quarter (one-way anova, P < 0.0001). Ninety-two per cent of 133 cases were children aged 12 years or younger; the introduction of JE vaccination in July 2001 reduced the number of JE cases (84 in the four seasons prior to vs. 49 in the six seasons after, McNemar's test, P = 0.0001). After implementation of the programme, the mean age of infected children increased from 6.3 to 8.0 years (Student's t-test, P = 0.0037), suggesting the need for a catch-up programme.

Matched MeSH terms: Japanese Encephalitis Vaccines/administration & dosage
In vitro and in vivo characterization of chimeric duck Tembusu virus based on Japanese encephalitis live vaccine strain SA14-14-2

Wang HJ, Liu L, Li XF, Ye Q, Deng YQ, Qin ED, et al.

J Gen Virol, 2016 07;97(7):1551-1556.
PMID: 27100268 DOI: 10.1099/jgv.0.000486

Duck Tembusu virus (DTMUV), a newly identified flavivirus, has rapidly spread to China, Malaysia and Thailand. The potential threats to public health have been well-highlighted; however its virulence and pathogenesis remain largely unknown. Here, by using reverse genetics, a recombinant chimeric DTMUV based on Japanese encephalitis live vaccine strain SA14-14-2 was obtained by substituting the corresponding prM and E genes (named ChinDTMUV). In vitro characterization demonstrated that ChinDTMUV replicated efficiently in mammalian cells with small-plaque phenotype in comparison with its parental viruses. Mouse tests showed ChinDTMUV exhibited avirulent phenotype in terms of neuroinvasiveness, while it retained neurovirulence from its parental virus DTMUV. Furthermore, immunization with ChinDTMUV was evidenced to elicit robust IgG and neutralizing antibody responses in mice. Overall, we successfully developed a viable chimeric DTMUV, and these results provide a useful platform for further investigation of the pathogenesis of DTMUV and development of a live attenuated DTMUV vaccine candidate.

Matched MeSH terms: Japanese Encephalitis Vaccines/genetics*; Japanese Encephalitis Vaccines/immunology*
Fulltext Emergence of Japanese encephalitis virus genotype V in the Republic of Korea

Takhampunya R, Kim HC, Tippayachai B, Kengluecha A, Klein TA, Lee WJ, et al.

Virol J, 2011;8:449.
PMID: 21943222 DOI: 10.1186/1743-422X-8-449

Japanese encephalitis virus (JEV) genotype V reemerged in Asia (China) in 2009 after a 57-year hiatus from the continent, thereby emphasizing a need to increase regional surveillance efforts. Genotypic characterization was performed on 19 JEV-positive mosquito pools (18 pools of Culex tritaeniorhynchus and 1 pool of Cx. bitaeniorhynchus) from a total of 64 positive pools collected from geographically different locations throughout the Republic of Korea (ROK) during 2008 and 2010.

Matched MeSH terms: Japanese Encephalitis Vaccines