Who japanese encephalitis virus

Safe and effective JEV vaccines are available, but unfortunately, their use remains low in most endemic countries where they are most needed. Increased surveillance and diagnosis of JE is required as climate change and social disruption are likely to facilitate further geographical expansion of Culex vectors and JE risk areas.

Japanese encephalitis virus JEV is one of the most important causes of human viral encephalitis in Asia [ 1 ]. JEV is a zoonotic, vector-borne virus, spread primarily by Culex mosquitoes. Various species of birds are the natural reservoir, while pigs are considered the main maintenance or amplifying host. However, these figures are widely regarded as an underestimate, with actual disease burden probably closer to , cases annually [ 4 , 5 ].

Humans are a dead-end host for JEV infection, because viraemia is insufficient to be infectious to the mosquito vector [ 6 ]. JEV circulates in a natural cycle involving a range of animal species including Culex mosquitoes, wild wading birds, and pigs [ 7 , 8 , 9 ] Figure 1. While birds are the natural reservoir for JEV, pigs act as amplifying hosts and are often associated with outbreaks amongst humans [ 10 ].

However, outbreaks do occur in the absence of pigs, which suggests that birds or other species may act as amplifying hosts in some instances [ 11 ].

JEV immunisation and eradication programs can practically eliminate human disease as evidenced in economically affluent Asian countries such as Japan, Korea, and Taiwan [ 12 ]. However, the geographical spread of JEV has continued to increase in Southeast Asia despite vaccination campaigns in some countries.

The increasing spread of mosquito vectors, compounded by poor knowledge on JEV transmission due to a lack of surveillance [ 13 , 14 , 15 ], constitutes a threat for the further expansion of the geographical range of JEV and greater impacts to human populations. Global climate change also presents an opportunity for increased distribution of mosquito vectors and JEV into previously non-endemic areas as mosquito habitats expand.

The JEV genome is approximately 11 kilobases in length and encodes a single open reading frame, which is translated into a large polyprotein that is proteolytically cleaved to form three structural proteins and seven non-structural proteins.

Virions are approximately 50 nm in diameter and are spherical in shape. JEV belongs to the Japanese encephalitis serocomplex, along with other important arboviruses with which it shares a close genetic and antigenic relationship, such as West Nile virus WNV , St. The JEV burden throughout Asia decreased during the late s following aggressive pesticide use and the introduction of JEV vaccines in economically affluent countries [ 12 , 18 ].

However, increases in population growth, pork production, and irrigated rice agriculture throughout Southeast Asia has led to further spread of JEV and increased the burden of JE in recent decades [ 15 , 19 , 20 ]. In the Torres Strait, a JEV outbreak in the mids led to the removal of pig populations from human habitats and a widespread vaccination campaign [ 26 , 27 ].

Although relocation of pigs did not eliminate the risk of JEV circulation [ 28 ], there have been no additional human JE cases reported in the Torres Straits.

However, ongoing mosquito and sentinel animal surveillance have demonstrated that the virus has continued to circulate in this region [ 29 , 30 ]. More recently, the first case of JE on the Tiwi Islands in the Northern Territory of Australia was reported in [ 31 ], raising concerns over future outbreaks in this region.

Moreover, the detection of an autochthonous case of JEV infection in Angola in [ 32 ] raises the troubling possibility that the virus could be emergent in the African continent. Despite the high JE disease burden, surveillance is still lacking throughout most of Southeast Asia. Many countries lack the diagnostic capabilities to confirm JEV infection, and JE is often misdiagnosed based on symptoms similar to other viral infections.

The virus is clearly endemic throughout the region, with high seroprevalence reported in wild and domestic animals and humans [ 33 ].

Health information is lacking in many countries that do not have the diagnostic capabilities to survey JEV burden. Clearly, transmission and infection rates of JEV are underestimated throughout the Asia-Pacific region. Increased surveillance and reporting of JEV infection need to be undertaken to realise the true burden of JE.

Most JEV infections in humans are asymptomatic or cause mild flu-like symptoms that last for 5—15 days [ 34 , 35 ]. However, some infections manifest as encephalitis characterised by headaches, fever, seizures, and abnormal behaviour 2—4 days following infection.

Haemorrhagic lesions develop in the brain, and the meninges become inflamed, characterised by neck stiffness. Paralysis, especially in the upper limbs, may follow. JEV remains the most common cause of childhood AME throughout Asia and therefore causes a significant morbidity and economic burden in affected countries [ 22 , 23 , 38 , 39 ].

Each genotype can be distinguished based on nucleotide sequence in the E-protein gene. However, all JEV strains belong to a single serotype, because neutralising antibodies are cross-reactive between genotypes [ 16 ]. GIII was the source of numerous JE outbreaks and was the most frequently isolated genotype throughout Asia until the s [ 42 , 43 ]. GI has been isolated during recent outbreaks in Japan [ 44 ], Korea [ 45 ], India [ 46 ], China [ 47 ], Taiwan [ 48 ], Vietnam [ 49 ], Thailand [ 50 ], Malaysia [ 51 ], and Cambodia [ 52 ].

In the Australasian region, although the first outbreak in was caused by a GII strain, since , only GI viruses have been detected [ 29 , 53 ]. Phylogeographic and phylodynamic analyses suggest that GI-a originated in Thailand in the s and GI-b in Vietnam in s. Historically, identification of positive selection in the genome of an emerging lineage would suggest a selective advantage.

Surprisingly, GIII was shown to have a greater selective advantage, because it was predicted to be shaped by positive selection, while GI was predicted to be neutral [ 42 ]. The lower diversity of GI strains was associated with a narrower vector range than GIII strains, suggesting enhanced transmission or more efficient replication cycle between Culex sp. GI isolates had more than an fold increase in titres compared to GIII isolates, which suggested GI had better replicative fitness in mosquitoes and therefore represent a greater risk of transmission [ 55 ].

In another study, oral challenge of Cx. However, a higher infection rate was found for the GIII isolate tested compared to the GI isolates [ 54 ], further confounding interpretations of the basis for the dominance of GI. Future in vivo challenge studies with the primary vector in Southeast Asia, Cx. Asia has had unprecedented population growth, increasing from 2. To support this population growth, Asia increased agricultural yield through expansion of rice and domestic swine production.

Swine are typically reared in open pens close to rural housing. These agricultural practices, combined with unprecedented population growth, may have contributed to JEV genotype replacement throughout Asia and the increasing burden of JE.

For example, increased vector mosquito habitats and pig populations may have provided an ecological advantage for GI strains, for which there is evidence of optimised transmission between Cx. JEV is maintained in a natural transmission cycle amongst mosquitoes and wading birds, while pigs act as an amplifying host Figure 1. Other domestic animals cows, dogs, chickens, goats, and horses and wildlife flying foxes, frogs, snakes, and ducks have been identified as dead-end hosts for JEV due to the low viraemia produced in these hosts, which is insufficient to infect the mosquito vector [ 33 ].

Host cell tropism is likely determined by JEV attachment and entry into host cells. Initial interaction of JEV to the host cell is thought to be through non-specific attachment of the virion, followed by highly specific binding of the envelope E protein to an unknown receptor [ 17 ]. Although much is understood about the viral processes involved in viral attachment and entry, little is known about the cellular aspects of this important process.

JEV is able to infect and replicate in a range of cell types from different animal species, including mammals, birds and insects. As such, there are probably numerous cell factors involved in viral attachment and entry. Further elucidation of the viral—host interactions is an important area of research for possible therapeutics against JEV infection [ 17 ].

At least 14 mosquito species have been confirmed as JEV vectors, and experimental vector competence has been demonstrated in a further 11 species reviewed in [ 59 ]. However, the major vectors of the virus are from the Culex vishnui subgroup, particularly Cx. Other Culex species including Cx. The distribution of Cx. It has also been found in Greece and Turkey [ 63 , 64 ], suggesting a possible continuum from Pakistan to Turkey via an unconfirmed presence in Iran.

Recent detection of Cx. Finally, Cx. The distribution of these vector species closely correlates to the distribution of JEV Figure 2 , showing the adaptability of JEV to increase its distribution area and a strong probability of extension towards the East.

These six species have conquered many different larval niches, including temporary, semi-permanent, and permanent ground water habitats. These habitats include pools, puddles, small streams, rice fields, and human water containers. Irrigated rice fields provide breeding grounds for Culex sp.

These urban environments provide access to human blood meals and increase the potential for JEV transmission. Blood meals isolated from Cx. Wild-collected mosquitoes fed on cows almost fold more frequently 39— Even when only one animal was present a single cow or pig , Cx. More recently, despite an apparent preference of Cx. However, feeding preferences in the wild are dependent on host abundance and time of feeding. As an example, dog blood was detected in four main Culex species in Cambodia [ 70 ].

In Australasia, where Cx. As such, the blood meals of the six major JEV vector Culex species will likely reflect the local domestic and wildlife populations where the mosquitoes are found, as they are known to be opportunistic and generalist feeders.

Wild ardeid waterbirds egrets and herons have been implicated as the main wildlife reservoir for JEV and are recognised as important transmission hosts. A variety of other bird species are susceptible to JEV infection but are considered to play a minor role as viral reservoirs compared to egrets, herons, and pigs.

JEV infection of ardeid birds is asymptomatic and leads to seroconversion [ 9 , 73 ]. Experimental infection has shown that egrets and herons with high viraemia are capable of transmitting JEV to mosquitoes [ 9 ]. The role of ardeid birds in JEV transmission has been supported by surveillance studies in villages near rice fields either with or without herons. The seasonal migratory movement of ardeid birds encompasses all continents except Antarctica with high population movement in south, east, central, and north Asia.

Thus, the migratory movement of ardeid birds potentially enhances JEV range and contributes to the transmission of the virus. Domesticated birds, adult ducks, and chickens are thought to play only minor roles in JEV ecology, because they develop low viraemia that is unlikely to result in transmission to feeding mosquitoes [ 75 ].

However, recent studies report that JEV viraemia is significantly higher in juvenile ducklings and chicks, which may lead to transmission to feeding mosquitoes [ 76 ]. Age-related viraemia was shown in ducklings and chicks experimentally infected with JEV between 2 and 42 days of age [ 76 ]. The authors noted JEV infection of chicks and ducklings was either subclinical or resulted in clinical signs similar to avian influenza infection, which may lead to outbreaks in poultry being mistakenly attributed to influenza or other poultry pathogens [ 76 ].

Considering that domesticated birds are housed in close proximity to humans throughout Asia, and live bird markets are commonly situated in densely populated cities, further field studies are needed to investigate the role of poultry in JEV transmission dynamics. Pigs serve as the principal amplifying hosts to JEV in epidemic areas and are maintenance hosts in endemic areas [ 7 , 10 , 77 ].

Concentrated pig farming in some regions of East and Southeast Asia results in pigs being the primary component of the domestic JEV transmission cycle [ 78 , 79 ]. Industrialisation of pig farming in Southeast Asia Vietnam, Thailand and Myanmar , with enhanced amplification of JEV within dense pig herds, has contributed to an increased risk of JEV transmission [ 80 ].

Therefore, the vicinity of pig populations is the main risk factor for JEV transmission into the human population. JEV infection of pigs generally remains asymptomatic or causes mild disease reviewed in [ 81 ] , which means that outbreaks in swine may go unnoticed [ 7 , 82 ].

However, sows exposed to JEV before pregnancy tend to have lower pregnancy abnormalities [ 84 ]. Infection of boars has also been associated with infertility [ 85 ]. Encephalitis has also been observed in piglets following experimental infection [ 81 , 86 ].

Infected Culex sp. Early evidence suggested that there are two viral amplification cycles in pigs. The second cycle involves infection of mosquitoes that have fed on viraemic pigs. Recent studies have confirmed vector-free transmission of JEV between pigs via direct contact with infected animals through the oronasal route [ 89 ]. JEV RNA and live virus persisted in pig tonsils for six weeks, which was likely the primary site of replication and transmission [ 89 ].

Vector-free transmission is a possible explanation for the rapid seroconversion of newborn piglets to JEV [ 85 ]. In a Cambodian study, seroconversion of piglets began within one month of weaning [ 90 ]. Amongst 29 piglets, 28 had seroconverted before the age of six months Despite the intensive circulation of JEV detected in pigs during this study, only one pool of Cx. The low prevalence of JEV positive mosquitoes in this study and others [ 91 ] suggests that vector-free transmission in pig populations could be an underappreciated factor in the epidemiology of JEV outbreaks.

JEV infection of pigs and the subsequent risk of outbreaks in humans can be reduced through vaccination of pig populations. Typically, JEV immunisation induces strong systemic IgM and IgG responses, which protect pigs against injected JEV challenge, with a resulting absence of transmission to feeding mosquitoes [ 92 ].

However, limitations to swine vaccination have led to low vaccination levels in piggeries. Because most pigs are slaughtered from 6—8 months of age, and commercial farms have high annual turnovers, vaccination is costly and impractical. Furthermore, maternal antibodies render the live-attenuated vaccine ineffective in pigs less than three months old [ 75 ], resulting in a narrow period of effective immunity in production pigs.

However, in areas where JEV is endemic and pigs live for longer than a few months, pig vaccination may be an effective means of reducing the risk of JE to humans and preventing reproductive losses in sows [ 93 ]. With JEV infection in pigs producing limited adverse events, impoverished pig farmers have little economic incentive to immunise swine, and thus the uptake of these vaccines is likely to remain low in developing countries where JE is endemic. Removal of pigs from areas of high human population density in JEV endemic regions has proven useful in reducing JE burden.

The reduction in JE incidence in Japan, Taiwan, and Korea may also be partially attributed to removal of piggeries from population centres [ 2 , 78 ]. Despite this, JEV was still detected in the community in a subsequent survey [ 28 ]. It was found that the piggery was located within the flight range of vector mosquitoes to the community; the presence of viraemic waterbirds nearby the community may also have been an alternative source of mosquito infection.

JEV transmission has been maintained in other areas where pig populations are low or where pigs have been removed. For instance, JEV remains endemic in Bangladesh despite the limited number of piggeries due to the diet of the predominantly Muslim population [ 38 , 93 ]. Singapore abolished pig farms in , which reduced JEV infection from 14 cases annually to 3 imported cases from to [ 11 ]. However, recent surveillance efforts have shown zoonotic transmission of JEV involving wild boars and a range of domestic and wild migratory birds including eagles, egrets, plovers and redshanks [ 11 , 95 ].

Thus, JEV amplification in ardeid birds egrets, herons may be important where domestic swine populations are absent, or numbers are low. Other domesticated cattle, horses, buffalo, and goats and wild marsupials animals are considered dead-end-hosts for JEV transmission.

These animals may be infected with JEV but develop low viraemia, incapable of transmitting to mosquitoes [ 25 , 33 , 96 , 97 , 98 , 99 , ]. In situations where dead-end hosts are present in sufficient numbers and are preferred sources of blood meals by vectors, they may act to dampen or suppress JEV activity by subverting vectors away from amplifying hosts. A recent study conducted in Cambodia observed that JEV may be circulating between multiple hosts including dogs and domestic birds chickens, ducks , with the presence of JEV neutralizing antibodies detected in a range of animals [ , ].

Most JEV infections in cattle and horses are subclinical. Although bovine JE is rare [ ], JE in horses is well recognised and outbreaks in horses parallel those in humans [ 99 ]. Unlike domesticated birds, very little is known about JEV viraemia in newborn calves or foals and whether higher viraemia could occur in these younger animals [ ]. However, maternal antibodies may protect calves and foals leading to low JEV infection until they have been weaned.

Due to relatively high levels of seropositivity, goats and cattle are considered suitable animals for surveillance purposes. In Sri Lanka, seroprevalence in cattle and goats was found to be a better predictor of the JE infection risk for humans than porcine seroprevalence [ ]. This is likely due to the vector feeding preference for these species over pigs.

JEV antibodies have also been detected from a large range of bat species in East Asia [ , ]. Experimental studies have mainly focussed on microbats, in which viremia has been found to last as long as 25—30 days at a level sufficiently high to infect mosquitoes [ ].

Transplacental virus transmission has also been demonstrated experimentally, and this may be a mechanism by which JEV can be maintained in nature [ ]. Experimental infections of a megabat species Pteropus alecto also demonstrated that animals infected by inoculation or via infected mosquitoes developed viraemia capable of infecting recipient mosquitoes [ ]. Bats have also been proposed to play a role in the over-wintering of JEV in the northern range of its distribution, via reactivation of viraemia in infected bats following hibernation [ ].

Further studies are needed to establish the role of bats in the natural cycle of JEV circulation. The changing climate, including an increase in global temperature and changes in precipitation and wind patterns, can have a profound effect on the distribution of the viral vectors, reservoir species, amplifying hosts, and even the genotypes of JEV.

In addition to increasing temperatures, potential regions where JEV can exist may experience longer and more intense periods of low rainfall or drought as well as periods of higher than usual rainfall and possibly an increase in the frequency and intensity of extreme weather events such as cyclones or hurricanes. The drivers of JEV ecology and epidemiology are complex, with contributions from hosts, vectors, viral genetics, and human behaviour, and these are influenced by a range of factors including climate [ 81 , , , , , , ].

Increases in temperature can have effects on the development time, immature survival, adult survival, mosquito size, blood feeding, and fecundity of Culex mosquitoes.

There may be changes in vector competence and the extrinsic incubation period [ , , ]. Fluctuating diurnal temperatures are an important aspect of field conditions, and these may have a greater effect than can be predicted solely from increases in mean temperature [ ].

Changes in temperature can also have some effect on the dispersal of aquatic birds such as herons, which may be infected with JEV without manifesting clinical signs.

Daytime and night-time temperatures can be an important component of the modelling for the distribution of the reservoir species [ ]. However, further studies are needed to establish these trends, as these associations may be due to bias introduced from sampling and sequence availability.

Further studies are needed to determine if genotype-defining substitutions can provide some insights into the molecular mechanisms responsible for this phenomenon [ ].

Prolonged dry periods can be associated with a reduction in natural breeding sites for mosquitoes and their reservoir species, resulting in reduced transmission of JEV.

The reduction in river flows can reduce the supply of irrigation water with a substantial reduction in rice fields contributing to a further reduction in transmission. Amplifying species such as pigs will be constantly replaced. Vaccination of pigs is rare, and when there is minimal transmission, the incentive for human vaccination may also be reduced.

This scenario can result in a substantial increase in the susceptible populations of both pigs and humans. When a heavy rain event occurs with resultant flooding, there can be long distance dispersal of JEV by aquatic birds and massive amplification by immunologically naive pigs [ , ], resulting in spillover into the susceptible human population.

Mosquitoes can be dispersed relatively long distances by wind [ , ]. The roles of cyclones and similar weather events in the dispersal of infected Culicoides and bluetongue outbreaks has been well documented [ , , , , , ], and there is also limited evidence that windblown mosquitoes can introduce JEV into new areas [ ].

The increased frequency and intensity of these events with global warming may introduce or enhance the distribution of JEV into areas that presently do not experience outbreaks.

Future trends in Asia will almost certainly include an expansion of the endemic and epidemic regions with very distinct seasonal variation [ ]. Inactivated vaccines derived from mouse brains or cell culture have proven to have high efficacy throughout Southeast Asia [ , ].

However, high production costs USD 3—5 per dose , poor induction of long-term immunity, multiple dose regimen, and reports of adverse events limited the use of this vaccine [ , ].

Inactivated vaccines have gradually been replaced with a live-attenuated SA; GIII strain vaccine, which is given in two to three doses during childhood and is inexpensive to make USD 0. The live-attenuated vaccine is immunogenic, induces long term immunity, and requires one or two doses in childhood [ ].

In China and Nepal, two dose regimens in children led to seroconversion in While initially only available in China, it is now the recommended vaccine for many endemic countries in Asia [ ].

However, some issues remain with these live attenuated vaccines. Serum from humans vaccinated with GIII inactivated vaccine was able to cross-neutralize viruses belonging to GI but with reduced levels of neutralisation [ , ]. Similar studies using animal antisera from GIII-vaccinates also showed limited cross-protection to local GI isolates [ , ]. JE vaccine strategies include campaigns, routine immunisation programs, or a combination of both.

From —, incidence of confirmed JEV following the campaign was 1. In , a JEV vaccine campaign was initiated in Myanmar with 14 million children 5—15 years targeted for immunisation followed by implementation of routine immunisation from [ ]. No data have yet been published for the effect this campaign has had on JEV circulation in Myanmar.

A comprehensive study on 14 endemic countries from the period of to estimated the outcomes of campaign and routine immunisation programs to result in a decrease of , JE cases, 43, deaths, and 77, cases with sequelae, thereby reducing 6,, disability-adjusted life years DALYs and saving USD19 million in AME cases [ ]. Thus, the implementation of JE vaccine programs in endemic countries are expected to be highly beneficial.

Vaccination programs are increasingly helping to control JEV, but better surveillance is needed to improve estimates of JEV burden. Underreporting is a key problem for understanding the local and global burden of JE and to help better identify areas at risk of disease. Japanese Encephalitis Minus Related Pages. For Healthcare Providers. Know before you travel. Geographic Distribution. Mosquitoes infected by pigs or wading birds spread JE….

Links with this icon indicate that you are leaving the CDC website. However, in the flavivirus group, serological data is not sufficient to distinguish the likely infecting flavivirus. No neurological manifestations or rashes were reported. Notably, there were no statistically significant differences found in clinical characteristics between confirmed and probable JE cases except for lowest hemoglobin level Furthermore, although our study plans did not include follow up assessment to determine long term outcome of the patients after discharge, all JE patients had resolved symptoms upon hospital discharge.

It is not clear from our data if there was any temporal distribution pattern of the JEV infection since our study was not conducted throughout the whole year and the limited number of identified JE cases prevented making such an analysis.

JEV was not previously considered a significant public health problem in Indonesia until nationwide studies in the early s based on syndromic surveillance and serologic assays suggested nationwide JEV endemicity [ 9 — 11 ]. From the thirteen JE patients diagnosed in this study, eleven were adults while only two were children. Further, the presence of pre-existing DENV antibodies in JEV-infected patients has recently been associated with better patient outcomes [ 39 ].

Hence, the absence of severe or encephalitic disease in these subjects could be partly attributed to pre-existing DENV immunity. Malaise, nausea, loss of appetite, myalgia, and headache were the major symptoms reported in the JEV cases here, similar to those reported previously [ 22 ]. However, these symptoms were also present in DENV-infected patients at similar frequency except for headache which was less observed in JE cases.

While this study suggests that thrombocytopenia, leukopenia, and lower hematocrit were less likely to be found in non-encephalitic JE compared with dengue cases, further studies are needed to confirm these findings. The role of other vector-borne viruses, including JEV, as causes of febrile illness or encephalitis has therefore likely been underestimated.

This study is limited by the number of non-encephalitic JE cases identified which does not allow for a sound stratified analysis of the results particularly regarding the clinical features. Furthermore, the higher prevalence of adults over children identified in the study might be due to lack of appropriate population denominator data.

The incidence of non-encephalitic JE might potentially be higher in children if the data from this study were adjusted by age stratified population denominator i. In summary, this work demonstrates JEV infection in non-encephalitic acute febrile illness patients identified using robust serological assays.

Hence, further JEV surveillance is required to fully reveal the epidemiology of JE disease in humans. This report on JEV as the cause of acute febrile illness in Bali is fundamental to characterizing JE epidemiology, identifying high-risk areas, and documenting the impact of prevention measures in Indonesia. The authors would like to thank the patients, physicians, and the management of Wangaya General Hospital, Denpasar, Bali for their support during the acute febrile illness study.

We thank Made Satya Dharmayanti of the Biomolecular Laboratory of Warmadewa University, for her help in diagnostic testing and specimen archiving.

The contents and conclusions of this report are those of the authors and do not necessarily represent the official position of the U. Abstract Although Japanese encephalitis virus JEV is considered endemic in Indonesia, there are only limited reports of JEV infection from a small number of geographic areas within the country with the majority of these being neuroinvasive disease cases. Data Availability: All relevant data are within the manuscript.

Introduction Japanese encephalitis JE is a vector-borne disease caused by JE virus JEV , a single-stranded RNA flavivirus that is transmitted through a zoonotic cycle between mosquitoes, pigs and water birds, with humans as dead-end hosts. Study site, patient recruitment, and sample collection Archived patient samples from a cross-sectional prospective study of dengue and acute febrile illness conducted in Wangaya General Hospital Rumah Sakit Umum Daerah Wangaya were analyzed.

Download: PPT. Table 1. Diagnostic interpretation of the serology testing results. Virus isolation Virus isolation was attempted by inoculating patient S1 serum onto African green monkey kidney Vero cells as previously described [ 24 ]. Statistical analysis Statistical analysis was performed using OpenEpi v3. Results During the study period, 3, patients with suspected dengue or acute febrile illness attended Wangaya Hospital and a total of patients were enrolled in the study Fig 1.

Fig 1. Patient enrollment, specimens collected, and molecular and serological test performed. Table 2. Table 3. Discussion JEV was not previously considered a significant public health problem in Indonesia until nationwide studies in the early s based on syndromic surveillance and serologic assays suggested nationwide JEV endemicity [ 9 — 11 ]. Acknowledgments The authors would like to thank the patients, physicians, and the management of Wangaya General Hospital, Denpasar, Bali for their support during the acute febrile illness study.

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