Human Japanese Encephalitis Cases Research Articles

Potential for emergence of Japanese encephalitis in the European Union.

No autochthonous human cases of Japanese encephalitis (JE) have been reported to date in the European Union (EU). In this study, we assess the likelihood of Japanese encephalitis virus (JEV) introduction and transmission within the EU and propose outbreak response measures. Given the global geographical distribution of JEV, the probability of virus introduction into the EU is currently very low, with viremic bird migration being the most plausible pathway of introduction. However, this likelihood would significantly increase if the virus were to become established in the Middle East, Caucasus, Central Asia or Africa. Considering the environmental conditions that are expected to be conducive for virus circulation, there is a high likelihood of virus transmission within the EU after its introduction in environmentally suitable areas. The spread of the virus within the EU would likely occur through the movement of wild birds, pigs and mosquitoes. To mitigate or potentially contain the emergence of JE in the EU, early detection of both human and animal cases will be crucial.

Increasing seroprevalence of Japanese encephalitis virus in even-toed hoofed mammals (Artiodactyla species) associated with an upsurge of human cases in South Korea

The annual incidence of Japanese encephalitis (JE) has increased markedly in South Korea since 2010. We hypothesized that this increase was associated with higher frequencies of JE virus in animals. We analyzed 5201 serum samples collected from even-toed hoofed mammals (Artiodactyla species) across South Korea from 2008 to 2012 using a stratified two-stage probability approach. The highest annual incidence of human JE cases and deaths occurred in 2010. Cases increased from six (no deaths) in 2008-2009 to 26 cases (seven deaths) in 2010. The JE virus seroprevalence in deer and elk fawns increased from 2.4% in 2008 to 24.1% in 2009, and in wild boars, it increased from 19.3% to 55.0% in the same period, which preceded the surge of human cases. Furthermore, the seroprevalence in calves increased from 15.3% in 2008 to 35.8% in 2010, and that in lambs and goat kids, increased from 8.5% in 2009 to 26.2% in 2010, which coincided with the surge in humans. Our findings show that the increased incidence of human JE in South Korea was temporally associated with an increasing seroprevalence in the Artiodactyla species. Surveillance of sentinel animals may be useful to predict the emergence of JE in humans.

The Emergence of Japanese Encephalitis in Australia and the Implications for a Vaccination Strategy.

Japanese encephalitis (JE) is the leading cause of viral encephalitis in Asia. Until 2022, only six locally transmitted human JE cases had been reported in Australia; five in northern Queensland and one in the Northern Territory. Thus, JE was mainly considered to be a disease of travellers. On 4 March 2022, JE was declared a ‘Communicable Disease Incident of National Significance’ when a locally acquired human case was confirmed in southern Queensland. By 11 May 2022, 41 human JE cases had been notified in four states in Australia, in areas where JE has never been detected before. From this perspective, we discuss the potential reasons for the recent emergence of the JE virus in Australia in areas where JE has never been previously reported as well as the implications of and options for mass immunisation programs if the outbreak escalates in a JE virus-immunologically naïve population.

Re-Examining the Importance of Pigs in the Transmission of Japanese Encephalitis Virus.

Japanese encephalitis virus (JEV), a mosquito-borne flavivirus, is the leading cause of pediatric encephalitis in Southeast Asia. The enzootic transmission of JEV involves two types of amplifying hosts, swine and avian species. The involvement of pigs in the transmission cycle makes JEV a unique pathogen because human Japanese encephalitis cases are frequently linked to the epizootic spillover from pigs, which can not only develop viremia to sustain transmission but also signs of neurotropic and reproductive disease. The existing knowledge of the epidemiology of JEV largely suggests that viremic pigs are a source of infectious viruses for competent mosquito species, especially Culex tritaeniorhynchus in the endemic regions. However, several recently published studies that applied molecular detection techniques to the characterization of JEV pathogenesis in pigs described the shedding of JEV through multiple routes and persistent infection, both of which have not been reported in the past. These findings warrant a re-examination of the role that pigs are playing in the transmission and maintenance of JEV. In this review, we summarize discoveries on the shedding of JEV during the course of infection and analyze the available published evidence to discuss the possible role of the vector-free JEV transmission route among pigs in viral maintenance.

Environmental factors and spatiotemporal distribution of Japanese encephalitis after vaccination campaign in Guizhou Province, China (2004\u20132016)

BackgroundAlthough a vaccination campaign has been conducted since 2004, Japanese encephalitis (JE) is still a public health problem in Guizhou, one of the provinces with the highest incidence of JE in China. The aim of this study was to understand the spatiotemporal distribution of JE and its relationship with environmental factors in Guizhou Province in the post-vaccination era, 2004–2016.MethodsWe collected data on human JE cases in Guizhou Province from 2004 to 2016 from the national infectious disease reporting system. A Poisson regression model was used to analyze the relationship between JE occurrence and environmental factors amongst counties.ResultsOur results showed that the incidence and mortality of JE decreased after the initiation of vaccination. JE cases were mainly concentrated in preschool and school-age children and the number of cases in children over age 15 years was significantly decreased compared with the previous 10 years; the seasonality of JE before and after the use of vaccines was unchanged. JE incidence was positively associated with cultivated land and negatively associated with gross domestic product (GDP) per capita, vegetation coverage, and developed land. In areas with cultivated land coverage < 25%, vegetation coverage > 55%, and urban area coverage > 25%, the JE risk was lower. The highest JE incidence was among mid-level GDP areas and in moderately urbanized areas.ConclusionsThis study assessed the relationship between incidence of JE and environmental factors in Guizhou Province. Our results highlight that the highest risk of JE transmission in the post-vaccination era is in mid-level developed areas.

Detection of recent infection of Japanese encephalitis virus in swine population using IgM ELISA: A suitable sentinel to predict infection in humans

Japanese encephalitis (JE) is a mosquito-borne flaviviral zoonotic disease and is one of the major causes of encephalitis in children. Swine, being an amplifier host of Japanese encephalitis virus (JEV), play an important role in its epidemiology. Therefore, early detection of either JEV or antibodies against JEV in swine is a feasible alternative for initiating necessary measures to prevent the spread of infection to humans. Since IgM antibodies appear early in swine sera, recombinant NS1 protein based indirect IgM ELISA was developed in the present study with the objective to know the recent infection of swine population with JEV. The relative diagnostic sensitivity and specificity of the developed ELISA was 95.34% and 98.6%, respectively. The developed ELISA was found to have excellent reproducibility on inter-laboratory and inter-institutional validation studies. A total of 3,027 field swine sera samples were screened using the developed ELISA and 488 samples were found positive for IgM against JEV with an overall sero-positivity of 16.12% in swine population of India. The highest sero-positivity was observed in swine population of Eastern zone of India which coincided with the maximum number of human JE cases reported from this zone during the same period. Further, antibody kinetics study revealed that the IgM antibodies against NS1 protein of JEV started appearing in swine sera at day 5 and disappeared completely by day 40. The IgG antibodies started appearing at day 7, and remained for more than 365 days indicating the suitability of IgM ELISA to know the recent infection of JEV. The developed IgM ELISA can be readily incorporated into surveillance programs for detection of JEV activity in swine population so that outbreaks in humans can be prevented by taking suitable preventive measures.

Epidemic Changes and Spatio-Temporal Analysis of Japanese Encephalitis in Shaanxi Province, China, 2005-2018.

Japanese encephalitis (JE) is a mosquito-borne viral disease, which is the most serious viral encephalitis in China and other countries of the Asia-Pacific region. Since 2005, the epidemic patterns of JE have changed dramatically in China because of the vaccination of children younger than 15 years old, and JE is expanding geographically along with global warming. This retrospective epidemiological study analyzed dynamic environmental factors and the spatio-temporal distribution of human cases of JE in Shaanxi Province—one of the most severely affected areas of China—from 2005 to 2018. The results demonstrated that the high-risk population changed rapidly as the annual rate of JE cases increased by more than 40% in the age group >60 years during the study period, and endemic areas expanded northward in Shaanxi. Hotspot analysis detected four hotspots accounting for 52.38% the total cases, and the panel negative binomial regression model revealed that the spatio-temporal distribution of JE was significantly affected by temperature, relative humidity, wind velocity, El Niño-Southern Oscillation, coniferous forest coverage, and urban areas. These findings can provide useful information for improving current strategies and measures to reduce disease incidence.

Serological evidence of Japanese encephalitis virus infection in pigs in a low human incidence state, Goa, India

Japanese encephalitis (JE) is a mosquito-borne zoonosis caused by Japanese encephalitis virus (JEV). It is a leading cause of encephalitis in humans especially children in Asia. Aquatic wading birds are the reservoirs and pigs serve as amplifying hosts for JEV. Humans and horses are dead-end hosts. JE is endemic in several states of India. Goa, a small state on the west coast of India, had witnessed JE outbreaks in the past and as on date human JE cases are reported sporadically. Although human JE cases are well documented in Goa, the status of JEV exposure of pigs has not been well documented. Hence the present study was undertaken with an objective of identifying JEV exposure in the pig population of Goa state in the light of declining human JE cases. To achieve the objective, between January 2017 and May 2019, serum samples from 666 pigs were screened using enzyme-linked immunosorbent assay (ELISA) for the detection of anti-JEV IgG. The apparent prevalence of anti-JEV IgG in pigs was found to be 7.1 % (95 % confidence interval 5.3 %–9.3 %) and true prevalence was 4.6 % (95 % confidence interval 2.7 %–7.1 %). The seroprevalence of JE recorded in pigs of Goa state was low compared to other endemic states in India, which may also be one of the reasons for the lower prevalence of human JE cases in Goa state. Univariate analysis revealed that the age of the pigs and district did not significantly influence the JE seroprevalence in pigs of Goa state. However, in multivariable logistic regression, the North Goa district was found to significantly (p = 0.017) influence the JE seroprevalence in pigs. The study identified that JEV is still circulating in the Goan pig population and hence constant vigil is required to monitor the intensity of JEV circulation in pigs. Besides forewarning possible human outbreaks in the locality, evidence of JEV exposure in pig population provides valuable data on the magnitude and extent of geographical spread.

Mosquito abundance and pig seropositivity as a correlate of Japanese encephalitis in human population in Assam, India.

Assam is the most vulnerable state for Japanese encephalitis (JE) in India. The situation warrants characterization of epidemiological patterns of JE in vectors, pigs and human population. This investigation was aimed to determine the relative abundance of mosquito species and seroprevalence of JE in pigs in order to draw an epidemiological association with reported human JE cases in Assam. Pig sera and mosquitoes from selected farms in Sivasagar and Kamrup districts of Assam were collected fortnightly for one year during June 2015-May 2016. Pig sera were tested for JE antibodies by haemagglutination and virus neurtralization tests. Mosquito species were identified microscopically following the taxonomic keys. The results were analyzed with data on confirmed human JE cases in the selected districts. Culex gelidus (26.07%) and Cx. tritaeniorhynchus (24.07%) were the most abundant species in collected mosquitoes (n = 997). A total of 22.99% of pigs (n = 335) were JEV seropositive and 45.65% of human acute encephalitis syndrome cases (n = 230) were positive for JE virus (JEV) infection. Relative mosquito abundance, pig positivity and human cases were highest during monsoon (June-September) and least during winter (December-February). Rise in mosquito population was observed during pre-monsoon season (March-May) and concurrently higher number of human cases and pig seropositivity were recorded. A good correlation was observed between mosquito number and JEV positivity in pigs/human, and between pigs and human cases (p < 0.05). Human population in Sivasagar was at higher risk for JE infection (OR: 6.46, p < 0.0001) than in Kamrup rural district. This study indicates that a seasonal correlation exists between mosquito abundance and JEV seroconversion in pigs with concurrent human JEV outbreaks under field conditions in Sivasagar and Kamrup rural districts of Assam and that monitoring mosquito abundance/density and pig JEV seropositivity may help in predicting JEV outbreak in human population in the region.

How environmental conditions impact mosquito ecology and Japanese encephalitis: An eco-epidemiological approach

Japanese encephalitis (JE) is one of the major vector-borne diseases in Southeast Asia and the Western Pacific region, posing a threat to human health. In rural and suburban areas, traditional rice farming and intensive pig breeding provide an ideal environment for both mosquito development and the transmission of JEV among human beings. Combining surveillance data for mosquito vectors, human JE cases, and environmental conditions in Changsha, China, 2004–2009, generalized threshold models were constructed to project the mosquito and JE dynamics. Temperature and rainfall were found to be closely associated with mosquito density at 1, and 4month lag, respectively. The two thresholds, maximum temperature of 22–23°C for mosquito development and minimum temperature of 25–26°C for JEV transmission, play key roles in the ecology of JEV. The model predicts that, in the upper regime, a 1g/m3 increase in absolute humidity would on average increase human cases by 68–84%. A shift in mosquito species composition in 2007 was observed, and possibly caused by a drought. Effective predictive models could be used in risk management to provide early warnings for potential JE transmission.

The role of environmental factors in the spatial distribution of Japanese encephalitis in mainland China

Japanese encephalitis (JE) is the most common cause of viral encephalitis and an important public health concern in the Asia-Pacific region, particularly in China where 50% of global cases are notified. To explore the association between environmental factors and human JE cases and identify the high risk areas for JE transmission in China, we used annual notified data on JE cases at the center of administrative township and environmental variables with a pixel resolution of 1km×1km from 2005 to 2011 to construct models using ecological niche modeling (ENM) approaches based on maximum entropy. These models were then validated by overlaying reported human JE case localities from 2006 to 2012 onto each prediction map. ENMs had good discriminatory ability with the area under the curve (AUC) of the receiver operating curve (ROC) of 0.82–0.91, and low extrinsic omission rate of 5.44–7.42%. Resulting maps showed JE being presented extensively throughout southwestern and central China, with local spatial variations in probability influenced by minimum temperatures, human population density, mean temperatures, and elevation, with contribution of 17.94%–38.37%, 15.47%–21.82%, 3.86%–21.22%, and 12.05%–16.02%, respectively. Approximately 60% of JE cases occurred in predicted high risk areas, which covered less than 6% of areas in mainland China. Our findings will help inform optimal geographical allocation of the limited resources available for JE prevention and control in China, find hidden high-risk areas, and increase the effectiveness of public health interventions against JE transmission.

Isolation of Japanese encephalitis and Getah viruses from mosquitoes (Diptera: Culicidae) collected near Camp Greaves, Gyonggi Province, Republic of Korea, 2000.

As part of an evaluation of the ecology of arthropod-borne diseases in the Republic of Korea (ROK), we examined 8,765 mosquitoes captured in Paju County, Gyonggi Province, ROK, for the presence of viruses. Mosquitoes were captured in propane lantern/human-baited Shannon traps, Mosquito Magnet traps, or American Biophysics Corporation (East Greenwich, RI) miniature light traps with or without supplemental octenol bait and/or dry ice. Mosquitoes were identified to species, placed in pools of up to 40 mosquitoes each, and tested on Vero cells for the presence of virus. A total of 15 virus isolations were made from 293 pools of mosquitoes. Viruses were identified by reverse transcriptase-polymerase chain reaction and sequencing and consisted of 14 isolations of Japanese encephalitis (JE) virus and one isolation of Getah (GET) virus. All JE isolates were from Culex tritaeniorhynchus Giles, and the isolate of GET was from Aedes vexans (Meigen). The minimum field infection rate for JE in Cx. tritaeniorhynchus was 3.3 per 1,000, whereas the GET virus infection rate for Ae. vexans was 0.2 per 1,000. Isolation of JE and GET indicated that both viruses were actively circulating in northern Gyonggi Province, ROK. The lack of human cases of JE among the Korean population probably is because of an effective government-mandated vaccination program. The reason for no cases among >10,000 United States military and others that reside or train nearby is unknown, but may be related to personnel protection measures (permethrin-impregnated uniforms and use of deet repellent), adult mosquito control, mosquito selection of nonhuman hosts (unpublished data), and the low symptomatic to asymptomatic ratio of disease in adults.

Entomological investigations of an outbreak of Japanese encephalitis virus in the Torres Strait, Australia, in 1998.

Japanese encephalitis (JE) virus first appeared in Australia in 1995, when three clinical cases (two fatal) were diagnosed in residents on Badu Island in the Torres Strait, northern Queensland. More recently, two confirmed human JE cases were reported in the Torres Strait Islands and Cape York Peninsula, in northern Queensland in 1998. Shortly after JE virus activity was detected in humans and sentinel pigs on Badu Island in 1998, adult mosquitoes were collected using CO2 and octenol-baited CDC light traps; 43 isolates of JE virus were recovered. Although Culex sitiens group mosquitoes yielded the majority of JE isolates (42), one isolate was also obtained from Ochlerotatus vigilax (Skuse). Four isolates of Ross River virus and nine isolates of Sindbis (SIN) virus were also recovered from members of the Culex sitiens group collected on Badu Island in 1998. In addition, 3,240 mosquitoes were speciated and pooled after being anesthetized with triethylamine (TEA). There was no significant difference in the minimum infection rate of mosquitoes anesthetized with TEA compared with those sorted on refrigerated tables (2.8 and 1.6 per 1,000 mosquitoes, respectively). Nucleotide analysis of the premembrane region and an overlapping region of the fifth nonstructural protein and 3' untranslated regions of representative 1998 Badu Island isolates of JE virus reveled they were identical to each other. Between 99.1% and 100% identity was observed between 1995 and 1998 isolates of JE from Badu Island, as well as isolates of JE from mosquitoes collected in Papua New Guinea (PNG) in 1997 and 1998. This suggests that the New Guinea mainland is the likely source of incursions of JE virus in Australia.

大阪府における日本脳炎の生態学的研究 : 4. 日本脳炎患者数とコガタアカイエカの発生量に及ぼす気象条件の影響, 特に近年の低流行に関連して

大阪府における日本脳炎の生態学的研究 : 4. 日本脳炎患者数とコガタアカイエカの発生量に及ぼす気象条件の影響, 特に近年の低流行に関連して

Japanese Encephalitis on Saipan: a Survey of Suspected Mosquito Vectors

An outbreak of Japanese encephalitis (JE) occurred on Saipan, Commonwealth of Northern Mariana Islands, in October 1990. Adult and larval mosquitoes were collected during September-October 1991 to retrospectively determine the probable mosquito vector(s). Virus was not isolated from 119 mosquito pools composed of 7,250 adult specimens as follows: Aedes vexans nocturnis (14%), Culex tritaeniorhynchus (39%), Cx. sitiens group (11%), Culex (Culex) species (35%), and < 1% each of Ae. albopictus, Ae. oakleyi, Aedes saipanensis, Cx. annulirostris marianae, and Cx. fuscanus. Three additional species were collected only as larvae: Anopheles indefinitus, Ae. neopandani, and Cx. quinquefasciatus. Among the vectors of JE incriminated in other areas, Cx. tritaeniorhynchus was the predominant species in our collections and the principal species feeding on swine. This is the first published record of the occurrence of this species on Saipan. Culex tritaeniorhynchus is abundant and widely distributed on the southern half of Saipan where human JE cases occurred in 1990, and where swine seroconversions were detected. Although the identity of the mosquito vector(s) responsible for the 1990 outbreak cannot be established with certainty, our results suggest that Cx. tritaeniorhychus was probably involved.

大阪府における日本脳炎の生態学的研究 : 3. 豚へのワクチン接種によるコガタアカイエカの感染と患者の発生に対する効果

The effects of swine immunization during 1967-1973 as one of the precautionary measures against Japanese encephalitis (JE) were examined on the basis of the results of natural infection of Culex tritaeniorhynchus with JE virus and of incidence of human JE cases. The swine were immunized with live attenuated JE virus vaccine during this period except in 1967 when inactivated vaccine was used. From the point of view that JE viral infection rates vary depending upon mosquito abundance, it can be said that the infection rate of mosquitoes was lower in vaccinated areas than in unvaccinated areas in 1968-1970. However, in 1967 and 1969,8 and 2 human JE cases, respectively, were confirmed from vaccinated areas. This suggests that swine vaccination was not effective enough for control of JE among humans. Infection rate, the earliest date of isolation of JE virus from mosquitoes and the level of mosquito population tended to vary with the environmental condition of the collection sites. Therefore, comparison of the results of natural infection of mosquitoes with JE virus between the vaccinated years and unvaccinated years in areas which are favourable for the production of Cx. tritaeniorhynchus and infected mosquitoes, will reveal the effectiveness of swine vaccination.

Insecticidal resistance of Culex tritaeniorhynchus (Diptera: Culicidae) in Japan: a country-wide survey of resistance to insecticides.

Sixteen samples of Culex tritaeniorhynchus Giles collected in 14 prefectures in Japan in 1984 were assessed for resistance to insecticides. All of the samples were highly resistant to organophosphorus (OP) and carbamate insecticides, but none was resistant to a pyrethroid (permethrin). Resistance levels for each of the OP's and carbamates were similar among samples except for diazinon and temephos. Considerable variation in LC50's of temephos may have resulted from exposure to other OP's used for crop protection because temephos has not been used in ricefields in Japan. A uniform susceptibility to permethrin accorded with lack of a history of pyrethroids as agrochemicals. Insensitivity of acetylcholinesterases (AChE's) was the principal factor regulating resistance to OP's. Mosquitoes with such insensitive AChE's began to appear in ca. 1978 and rapidly replaced most of the susceptible mosquitoes within 2 or 3 yr. Since 1980 C. tritaeniorhynchus has become more abundant, and some resurgence in human cases of Japanese encephalitis has occurred at the same time. However, a recurrence of an epidemic of the magnitude of those experienced in the 1960s is implausible because of changes in agriculture and demography.