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Journal of Epidemiology and Global... Jun 2023We estimated the incidence of Japanese encephalitis (JE) and acute encephalitis syndrome (AES) following routine immunization with the live-attenuated SA 14-14-2 JE...
BACKGROUND
We estimated the incidence of Japanese encephalitis (JE) and acute encephalitis syndrome (AES) following routine immunization with the live-attenuated SA 14-14-2 JE vaccine.
METHODS
We implemented enhanced surveillance of AES and JE hospitalizations in endemic districts in Maharashtra and Telangana States during 2015-2016 and 2018-2020. We estimated incidence and compared differences in the incidence of JE and AES between two states, and vaccinated and unvaccinated districts during two study periods. We also considered secondary data from public health services to understand long-term trends from 2007 to 2020.
RESULTS
The annual AES incidence rate of 2.25 cases per 100,000 children in Maharashtra during 2018-2020 was significantly lower than 3.36 cases per 100,000 children during 2015-2016. The six JE-vaccinated districts in Maharashtra had significantly lower incidence rates during 2018-2020 (2.03, 95% CI 1.73-2.37) than in 2015-16 (3.26, 2.86-3.70). In addition, the incidence of both JE and AES in two unvaccinated districts was higher than in the vaccinated districts in Maharashtra. Telangana had a lower incidence of both JE and AES than Maharashtra. The AES incidence rate of 0.95 (0.77-1.17) during 2018-2020 in Telangana was significantly lower than 1.67 (1.41-1.97) during 2015-2016.
CONCLUSIONS
The annual incidence rate of Japanese encephalitis was < 1 case per 100,000 children. It indicated accelerated control of Japanese encephalitis after routine immunization. However, the annual incidence of acute encephalitis syndrome was still > 1 case per 100,000 children. It highlights the need for improving surveillance and evaluating the impacts of vaccination.
Topics: Child; Humans; Encephalitis, Japanese; Incidence; Acute Febrile Encephalopathy; India; Hospitalization
PubMed: 37162636
DOI: 10.1007/s44197-023-00110-7 -
Journal of Virology Sep 2019Accumulated evidence demonstrates that Japanese encephalitis virus (JEV) infection triggers endoplasmic reticulum (ER) stress and neuron apoptosis. ER stress sensor...
Accumulated evidence demonstrates that Japanese encephalitis virus (JEV) infection triggers endoplasmic reticulum (ER) stress and neuron apoptosis. ER stress sensor protein kinase R-like endoplasmic reticulum kinase (PERK) has been reported to induce apoptosis under acute or prolonged ER stress. However, the precise role of PERK in JEV-induced apoptosis and encephalitis remains unknown. Here, we report that JEV infection activates the PERK-ATF4-CHOP apoptosis pathway both and PERK activation also promotes the formation of stress granule, which in turn represses JEV-induced apoptosis. However, PERK inhibitor reduces apoptosis, indicating that JEV-activated PERK predominantly induces apoptosis via the PERK-ATF4-CHOP apoptosis pathway. Among JEV proteins that have been reported to induce ER stress, only JEV NS4B can induce PERK activation. PERK has been reported to form an active molecule by dimerization. The coimmunoprecipitation assay shows that NS4B interacts with PERK. Moreover, glycerol gradient centrifugation shows that NS4B induces PERK dimerization. Both the LIG-FHA and the LIG-WD40 domains within NS4B are required to induce PERK dimerization, suggesting that JEV NS4B pulls two PERK molecules together by simultaneously interacting with them via different motifs. PERK deactivation reduces brain cell damage and encephalitis during JEV infection. Furthermore, expression of JEV NS4B is sufficient to induce encephalitis via PERK in mice, indicating that JEV activates PERK primarily via its NS4B to cause encephalitis. Taken together, our findings provide a novel insight into JEV-caused encephalitis. Japanese encephalitis virus (JEV) infection triggers endoplasmic reticulum (ER) stress and neuron apoptosis. ER stress sensor protein kinase R-like endoplasmic reticulum kinase (PERK) has been reported to induce apoptosis under acute or prolonged ER stress. However, whether the PERK pathway of ER stress response plays important roles in JEV-induced apoptosis and encephalitis remains unknown. Here, we found that JEV infection activates ER stress sensor PERK in neuronal cells and mouse brains. PERK activation induces apoptosis via the PERK-ATF4-CHOP apoptosis pathway upon JEV infection. Among the JEV proteins prM, E, NS1, NS2A, NS2B, and NS4B, only NS4B activates PERK. Moreover, activated PERK participates in apoptosis and encephalitis induced by JEV and NS4B. These findings provide a novel therapeutic approach for JEV-caused encephalitis.
Topics: Activating Transcription Factor 4; Adenine; Animals; Apoptosis; Binding Sites; Cell Line; Disease Models, Animal; Encephalitis Virus, Japanese; Encephalitis, Japanese; Endoplasmic Reticulum Stress; Eukaryotic Initiation Factor-2; Indoles; Mice; Neurons; Protein Multimerization; Signal Transduction; Transcription Factor CHOP; Viral Nonstructural Proteins; eIF-2 Kinase
PubMed: 31189710
DOI: 10.1128/JVI.00887-19 -
PLoS Neglected Tropical Diseases Jul 2022Japanese encephalitis (JE) is a vector-borne zoonosis and the leading cause of human viral encephalitis in Asia. Its transmission cycle is usually described as involving...
Japanese encephalitis (JE) is a vector-borne zoonosis and the leading cause of human viral encephalitis in Asia. Its transmission cycle is usually described as involving wild birds as reservoirs and pigs as amplifying hosts. JE is endemic in Cambodia, where it circulates in areas with low pig densities (<70 pigs per km2), and could be maintained in a multi-host system composed of pigs, but also poultry as competent hosts, and dogs, cattle and humans as non-competent hosts. We used a mathematical model representing Japanese encephalitis virus (JEV) transmission in a traditional Cambodian village that we calibrated with field data collected in 3 districts of Kandal province, Cambodia. First, R0 calculations allowed us to assess the capacity of the epidemiological system to be invaded by JEV and sustain virus transmission in villages in the 3 districts, and we predicted human exposure at the epidemiological equilibrium, based on simulations. Changes in spatial density of livestock, in agricultural practices, and epizootics (e.g., African swine fever), can profoundly alter the composition of host communities, which could affect JEV transmission and its impact on human health. In a second step, we then used the model to analyse how host community composition affected R0 and the predicted human exposure. Lastly, we evaluated the potential use of dog JE seroprevalence as an indicator of human exposure to JEV. In the modeled villages, the calculated R0 ranged from 1.07 to 1.38. Once the equilibrium reached, predicted annual probability of human exposure ranged from 9% to 47%, and predicted average age at infection was low, between 2 and 11 years old, highlighting the risk of severe forms of JEV infection and the need to intensify child immunization. According to the model, increasing the proportion of competent hosts induced a decrease in age at infection. The simulations also showed that JEV could invade a multi-host system with no pigs, reinforcing the assumption of poultry acting as reservoirs. Finally, the annual human exposure probability appeared linearly correlated with dog seroprevalence, suggesting that in our specific study area, dog seroprevalence would be a good proxy for human exposure.
Topics: African Swine Fever; Animals; Asian People; Cattle; Child; Child, Preschool; Dogs; Encephalitis Virus, Japanese; Encephalitis, Japanese; Humans; Seroepidemiologic Studies; Swine
PubMed: 35816555
DOI: 10.1371/journal.pntd.0010572 -
Virologica Sinica Aug 2021Japanese encephalitis virus (JEV) is a mosquito-borne flavivirus, which causes the most commonly diagnosed viral encephalitis named Japanese encephalitis (JE) in the...
Japanese encephalitis virus (JEV) is a mosquito-borne flavivirus, which causes the most commonly diagnosed viral encephalitis named Japanese encephalitis (JE) in the world with an unclear pathogenesis. Axl, a receptor tyrosine kinase from TAM family, plays crucial role in many inflammatory diseases. We have previously discovered that Axl deficiency resulted in more severe body weight loss in mice during JEV infection, which we speculate is due to the anti-inflammatory effect of Axl during JE. Currently, the role of Axl in regulating the neuroinflammation and brain damage during JE has not been investigated yet. In this study, by using Axl deficient and heterozygous control mice, we discovered that Axl deficient mice displayed accelerated JE progression and exacerbated brain damage characterized by increased neural cell death, extended infiltration of inflammatory cells, and enhanced production of pro-inflammatory cytokines, in comparison to control mice. Additionally, consistent with our previous report, Axl deficiency had no impact on the infection and target cell tropism of JEV in brain. Taken together, our results suggest that Axl plays an anti-inflammatory and neuroprotective role during the pathogenesis of JE.
Topics: Animals; Brain; Cytokines; Disease Models, Animal; Encephalitis Virus, Japanese; Encephalitis, Japanese; Mice
PubMed: 33534086
DOI: 10.1007/s12250-020-00342-y -
Frontiers in Bioscience (Landmark... Jun 2020Japanese Encephalitis Virus (JEV) is the most common Flavivirus based mosquito borne viral encephalitis in the world, especially in countries of South-East Asia. The... (Review)
Review
Japanese Encephalitis Virus (JEV) is the most common Flavivirus based mosquito borne viral encephalitis in the world, especially in countries of South-East Asia. The conventional methods such as Enzyme-Linked Immunosorbent Assays (ELISA), Reverse Transcriptase Polymerase Chain Reaction (RT-PCR), Plaque Reduction Neutralization Test and virus isolation are still in use today but new advances are being made to develop more efficient, inexpensive, quicker, sensitive and time-saving techniques to detect JEV. Some of these include the use of immunosensors, both lateral flow based assays and electrochemical, as well as the incorporation of nanotechnology into biosensors to develop highly sensitive detection tools. This review focuses on the recent advances that have been made to diagnose Japanese Encephalitis Virus which are critical in breaking the link to zoonotic transmission into the human population where humans are dead-end hosts.
Topics: Animals; Antibodies, Viral; Biosensing Techniques; Encephalitis Virus, Japanese; Encephalitis, Japanese; Enzyme-Linked Immunosorbent Assay; Humans; RNA, Viral; Reverse Transcriptase Polymerase Chain Reaction; Viral Zoonoses
PubMed: 32472762
DOI: 10.2741/4882 -
Brain & Development Feb 2020A hospital-based prospective study was performed to determine: 1) whether Japanese encephalitis (JE) normally triggers anti-N-methyl-d-aspartate receptor (NMDAR)...
OBJECTIVES
A hospital-based prospective study was performed to determine: 1) whether Japanese encephalitis (JE) normally triggers anti-N-methyl-d-aspartate receptor (NMDAR) immunoglobulin G (IgG) synthesis, especially in monophasic JE patients; and 2) the incidence of JE-induced anti-NMDAR encephalitis in pediatric patients with JE.
METHODS
We detected the level of anti-NMDAR IgG in the serum and cerebral spinal fluid (CSF) of JE patients within one week of onset. If patients relapsed during the convalescence phase, we detected JE virus RNA in the CSF and anti-NMDAR IgG in both the serum and CSF. For patients who did not relapse during the convalescence phase, serum was collected and anti-NMDAR IgG was detected during the 30-60-day course of the disease.
RESULTS
We enrolled 65 JE patients, who were negative for anti-NMDAR IgG in the serum and CSF during the acute phase, of which 63 patients were successfully followed up. Five patients relapsed during the convalescence phase, for whom JE virus RNA in the CSF was negative and excluded latent JE reactivation. The distinctive symptoms of four younger patients were choreoathetosis, whereas the psychiatric and behavioral manifestations were the distinctive symptoms experienced by the teenager. Anti-NMDAR IgG in the CSF of three patients was positive and they were diagnosed with anti-NMDAR encephalitis. The other two patients were negative for anti-NMDAR IgG in both the serum and CSF. For the 58 patients who did not relapse during the convalescence phase, anti-NMDAR IgG was negative in the serum of all patients at 30-60 days during the course of the disease.
CONCLUSIONS
JE does not typically trigger anti-NMDAR IgG synthesis. Besides anti-NMDAR IgG, other unknown autoantibodies can also cause autoimmune encephalitis in the convalescence phase of JE. The incidence of JE-induced autoimmune encephalitis in pediatric patients with JE was 7.9%, and the incidence of JE-induced anti-NMDAR encephalitis was 4.7%.
Topics: Adolescent; Anti-N-Methyl-D-Aspartate Receptor Encephalitis; Child; Child, Preschool; Encephalitis, Japanese; Female; Follow-Up Studies; Hospitals, Pediatric; Humans; Incidence; Male; Prospective Studies
PubMed: 31563418
DOI: 10.1016/j.braindev.2019.09.003 -
Acta Neurologica Taiwanica Sep 2022Here we present a case of Japanese encephalitis with an interesting MRI image. The patient is a previously healthy 27 years old male living around a hog farm. Initially,...
Here we present a case of Japanese encephalitis with an interesting MRI image. The patient is a previously healthy 27 years old male living around a hog farm. Initially, he went to a local hospital and was treated with Levofloxacin as a pneumonia infection. He presented with fever and headache for two days before he sought medical assistance. For two days, his symptoms didn't improve, and progressive consciousness declining was noted. Hence the family decided to transfer to our hospital for further evaluation. On examination, his consciousness was stupor, cannot obey orders, and febrile. The pupils were equal with preserved light reflex. His muscle powers were symmetric bilaterally near his baseline. CSF examination showed normal opening pressure, elevated WBC count with 196 nucleated cells/mm3, normal glucose, and elevated protein level. Brain MRI showed left medial thalamic hyperintensity on T2WI and DWI (Figure 1). Finally, the patient was diagnosed with Japanese encephalitis based on the positive result of the Nucleic acid amplification test. The patient received supportive care with a gradual recovery of his consciousness and became able to obey commands. However, subtle learning problems persisted after one week. Based on the literature review, the MRI or CT finding on thalamic lesions on imaging has high specificity, which could be an assistance tool diagnosis of Japanese encephalitis.[1] The typical Japanese MRI feature consists of hyperintense lesions on T2WI or DWI, and the thalamus was the most commonly involved region. [2][3][4] Although the majority of Japanese encephalitis had bilateral thalamic lesions, the unilateral lesion is uncommon. [4][5] Thus the case presented here provides a rare image of reference for Japanese encephalitis with a unilateral thalamic lesion Reference 1. Dung NM, et al. An evaluation of the usefulness of neuroimaging for the diagnosis of Japanese encephalitis. J Neurol. 2009;256(12): 2052-60. 2. Maschke M, et al. Update on neuroimaging in infectious central nervous system disease. Curr Opin Neurol. 2004;17(4):475-80. 3. Sunwoo, J.-S., et al., Clinical Characteristics of Severe Japanese Encephalitis: A Case Series from South Korea. The American journal of tropical medicine and hygiene, 2017. 97(2): p. 369-375. 4. Phukan, P., et al., MRI Spectrum of Japanese Encephalitis in Northeast India: A Cross-Sectional Study. Journal of neurosciences in rural practice, 2021. 12(2): p. 281-289. 5. Yakushiji, Y., et al., [A case of Japanese encephalitis presenting with unilateral lesions in diffusion-weighted MRI]. Rinsho Shinkeigaku, 2001. 41(9): p. 602-5.
PubMed: 35040109
DOI: No ID Found -
Journal of Virology May 2023Japanese encephalitis virus (JEV), with neurotoxic and neuroinvasive properties, is the major cause of human viral encephalitis in Asia. Although Guillain-Barré...
Japanese encephalitis virus (JEV), with neurotoxic and neuroinvasive properties, is the major cause of human viral encephalitis in Asia. Although Guillain-Barré syndrome caused by JEV infections is not frequent, a few cases have been reported in recent years. To date, no existing animal model for JEV-induced peripheral nerve injury (PNI) has been established, and thus the pathogenic mechanism is not clarified. Therefore, an animal model is urgently required to clarify the correlation between JEV infection and PNI. In the present study, we used JEV GIb strain of NX1889 to establish a mouse model of JEV infection. The general neurological signs emerged on day 3 of modeling. The motor function continued to deteriorate, reaching a maximum at 8 to 13 days postinfection (dpi) and gradually recovered after 16 dpi. The injuries of 10 PFU and 10 PFU groups were the most severe. Transmission electron microscopy and immunofluorescence staining showed varying degrees of demyelination and axonal degeneration in the sciatic nerves. The electrophysiological recordings demonstrated the presence of demyelinating peripheral neuropathy with reduced nerve conduction velocity. The decreased amplitudes and the prolonged end latency revealed axonal-type motor neuropathy. Demyelination is predominant in the early stage, followed by axonal injury. The expression level of JEV-E protein and viral RNA was elevated in the injured sciatic nerves, suggesting that it may cause PNI at the early stage. Inflammatory cell infiltration and increased inflammatory cytokines indicated that neuroinflammation is involved in JEV-induced PNI. JEV is a neurotropic flavivirus belonging to the family and causes high mortality and disability rates. It invades the central nervous system and induces acute inflammatory injury and neuronal death. Thus, JEV infection is a major global public health concern. Previously, motor dysfunction was mainly attributed to central nervous system damage. Our knowledge regarding JEV-induced PNI is vague and neglected. Therefore, a laboratory animal model is essential. Herein, we showed that C57BL/6 mice can be used to study JEV-induced PNI through multiple approaches. We also demonstrated that viral loads might be positively correlated with lesion severity. Therefore, inflammation and direct virus infection may be the putative mechanisms underlying JEV-induced PNI. The results of this study laid the foundation for further elucidation of the pathogenesis mechanisms of PNI caused by JEV.
Topics: Animals; Humans; Mice; Demyelinating Diseases; Encephalitis Virus, Japanese; Encephalitis, Japanese; Mice, Inbred C57BL; Peripheral Nerve Injuries; Disease Models, Animal
PubMed: 37071015
DOI: 10.1128/jvi.01658-22 -
Pediatrics and Neonatology Feb 2020Japanese encephalitis (JE) is a mosquito-borne viral infection which is prevalent in Taiwan. The virus circulates in an enzootic cycle in pigs which serve as amplifying... (Review)
Review
Japanese encephalitis (JE) is a mosquito-borne viral infection which is prevalent in Taiwan. The virus circulates in an enzootic cycle in pigs which serve as amplifying hosts. Outbreaks typically occur during summer. A universal vaccination program using 4-shot mouse brain-derived inactivated vaccine has successfully controlled JE epidemics in Taiwan since 1968. More than 90% of JE cases in recent years were older than 20 years in Taiwan. Because of several drawbacks, mouse brain-derived vaccine has been replaced by newer generation JE vaccines, including inactivated Vero cell-derived vaccine and live chimeric vaccine. The present article describes the recommendations in Taiwan for the use of new JE vaccines and the schedules for shifting between different JE vaccines.
Topics: Encephalitis, Japanese; Humans; Japanese Encephalitis Vaccines; Taiwan; Vaccination; Vaccines, Inactivated
PubMed: 31870559
DOI: 10.1016/j.pedneo.2019.11.009 -
Cell Reports May 2023Upon recognizing danger signals produced by virally infected neurons, macrophages in the central nervous system (CNS) secrete multiple inflammatory cytokines to...
Upon recognizing danger signals produced by virally infected neurons, macrophages in the central nervous system (CNS) secrete multiple inflammatory cytokines to accelerate neuron apoptosis. The understanding is limited about which key effectors regulate macrophage-neuron crosstalk upon infection. We have used neurotropic-virus-infected murine models to identify that vascular endothelial growth factor receptor 3 (VEGFR-3) is upregulated in the CNS macrophages and that virally infected neurons secrete the ligand VEGF-C. When cultured with VEGF-C-containing supernatants from virally infected neurons, VEGFR-3 macrophages suppress tumor necrosis factor α (TNF-α) secretion to reduce neuron apoptosis. Vegfr-3 (deletion of ligand-binding domain in myeloid cells) mice or mice treated with the VEGFR-3 kinase inhibitor exacerbate the severity of encephalitis, TNF-α production, and neuron apoptosis post Japanese encephalitis virus (JEV) infection. Activating VEGFR-3 or blocking TNF-α can reduce encephalitis and neuronal damage upon JEV infection. Altogether, we show that the inducible VEGF-C/VEGFR-3 module generates protective crosstalk between neurons and macrophages to alleviate CNS viral infection.
Topics: Mice; Animals; Tumor Necrosis Factor-alpha; Vascular Endothelial Growth Factor Receptor-3; Vascular Endothelial Growth Factor C; Ligands; Vascular Endothelial Growth Factor A; Encephalitis, Japanese; Encephalitis Virus, Japanese; Neurons; Macrophages
PubMed: 37167063
DOI: 10.1016/j.celrep.2023.112489