Encephalitis In India Research Articles

Temporal Trends in Outbreaks of Chandipura Viral Infection in India: A Systematic Review.

Chandipura virus (CHPV) has emerged as a significant cause of acute encephalitis in India, especially affecting pediatric populations. This study aimed to analyze the temporal trends, clinical characteristics, and epidemiological features of CHPV infections reported in outbreaks across India. A comprehensive literature search on CHPV cases was conducted using Google Scholar, PubMed, and the Cochrane Library. Original research studies on laboratory-confirmed clinical cases of CHPV infections, available as full-text articles, were included. Data on outbreak characteristics, clinical presentations, diagnostics, and epidemiological factors were extracted and analyzed. Six studies met the inclusion criteria. The review revealed a geographical expansion of CHPV outbreaks across India over time, with a consistent seasonal pattern (May to September) coinciding with the monsoon season. CHPV predominantly affects children under 15 years of age, presenting with rapid-onset encephalitis characterized by high fever, altered consciousness, and seizures. Case fatality rates were alarmingly high, ranging from 28.6% to 78.3% within the first 48 hours of symptom onset. Diagnostic approaches evolved over the study period, with increasing use of molecular techniques. Entomological investigations consistently identified sandflies, particularly Phlebotomus argentipes, as potential vectors, though their precise role in transmission remains to be fully elucidated. CHPV is an emerging public health threat, especially for children under 15 years. Early diagnosis is crucial, as CHPV is associated with high mortality within the first 24-48 hours of symptom onset. Challenges include limited long-term follow-up data, potential underreporting of mild cases, and gaps in understanding transmission dynamics.

Understanding the Diagnosis of Viral Meningo-Encephalitis in India: A Systematic Review

Background and Objectives: Diagnosis of viral meningoencephalitis is very crucial for recognizing the occurrence of epidemics and for instituting appropriate treatment. The diagnostic capability of the country can be ascertained by studying the published reports of viral meningoencephalitis in our country from reputed scientific literature. Hence, we aimed to study the diagnostic methods used for viral meningo encephalitis from Indian studies indexed in PubMed database. Methods: The data was gathered from human studies of actual cases of viral meningitis, encephalitis or meningoencephalitis in India up to 8th August 2016 [earliest study found was from the year 1988] indexed in PubMed database. Results: A total of 186 articles were included from 1548 studies screened. Clinical diagnosis over arched all the methods of diagnosis of viral meningoencephalitis in all the studies. Only 23.1% studies reported definitive confirmation of the infectious agent by PCR. Only 34.3% studies reported any microbiological tests for viral etiology. SGPGI, NIV AND NIMHANS were the three major centers reporting molecular diagnosis. Over three decades PCR has superseded antibody testing for viral meningoencephalitis diagnosis. Interpretation and Conclusion: Our analysis shows that the diagnosis of viral meningo encephalitis in India is mainly based on clinical diagnosis. Definitive diagnosis by molecular diagnostic methods can be achieved with the establishment of a greater number of molecular viral diagnostic and research labs.

Japanese encephalitis in India: current situation and future needs.

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Anti-N-methyl D-aspartate Receptor Encephalitis in India: A Literature Review.

Anti N-methyl D-aspartate receptor encephalitis (NMDAR-E) though rare, is currently considered as the commonest antibody mediated encephalitis in the world. No review on perspectives of NMDAR-E from India is available. The aim of the study was to review all the cases of NMDAR-E reported from India until June 2021 in terms of clinical features, diagnosis, and treatment, and perform a comparison of adult and paediatric cases. A literature review of NMDAR-E case reports/case series published from India till June 2021 was done. Demography, clinical profile, triggers, electroencephalography (EEG), neuroimaging, treatment details and outcomes were analysed. Sixteen case series and 35 case reports with a total of 249 cases were analysed. 82% of cases were from paediatric age group. The female to male ratio was 3:1. Psychiatric deficits, movement disorders, seizures, and language abnormalities were the most common clinical features. MRI brain abnormalities were seen in 45% patients. Electroencephalographic abnormalities were seen in 85% of patients. Infective triggers (herpes simplex virus and various other agents) were reported in 11% of the cases. Pediatric patients as compared with adults had more encephalopathy, autonomic dysfunctions, and normal imaging whereas the latter had more cognitive dysfunctions and delta brush pattern in electroencephalography (p<0.005). Therefore, to conclude, this literature review suggests that overall, the clinical spectrum of Indian cases is like cases described from other parts of the world. However, most reported cases from India belonged to paediatric age group who had more encephalopathy, autonomic dysfunctions, and normal brain imaging compared to adults. A few novel infectious agents as triggers were described from India.

Central nervous system adverse events after ChAdOx1 vaccination.

IntroductionPost-ChAdOx1 vaccine (AZD1222) adverse events following immunization (AEFI) are uncommon. Recently described neurological events include thrombocytopenia with thrombosis syndrome (TTS) with cerebral venous thrombosis and Guillain-Barré syndrome. There are very few AEFI reports following COVID vaccination from India, because of underreporting or other factors. A few cases of acute transverse myelitis (ATM) and post-vaccinal encephalitis have also been reported.Materials and methodsOver 11 months, in 2 districts of Kerala, India, 8.19 million people were vaccinated with the ChAdOx1 vaccine.ResultsDuring this period, we encountered five cases of autoimmune central nervous system (CNS) AEFI following ChAdOX1 (Oxford/AstraZeneca, Covishield™) vaccination. These included three cases of acute disseminated encephalomyelitis (ADEM), one case of opsoclonus myoclonus ataxia syndrome (OMAS), and one case of limbic encephalitis. The calculated crude incidence of post-ChAdOX1 autoimmune CNS AEFI was approximately 0.24 cases per million for encephalitis and 0.36 per million for ADEM. This was compared to the crude annual incidence of community-acquired ADEM worldwide (3.2–4 per million) and the crude annual incidence of community-acquired encephalitis in India (8.35–10 per million).ConclusionThere was no increase in the incidence of post-vaccination CNS AEFI (ADEM or encephalitis) as compared to the community incidence of ADEM or encephalitis. While this emphasizes the safety of ChAdOX1 nCoV-19 vaccination for COVID-19, it is important to recognize these post-vaccination autoimmune syndromes early to initiate immunosuppressive therapy.

Changing Paradigm in the epidemiology of Japanese encephalitis in India.

Japanese encephalitis (JE) is a very serious public health problem in India and the conducive environment permit its emergence in non-endemic areas in the country. There are constant changes taking place in the pattern of current agricultural practices and vector breeding habitats which had far-reaching consequences on the epidemiology of JE and the severity of epidemic outbreaks today. Due to the continuous ecological changes taking place, vectors changed in their breeding dynamics, feeding, and resting behavior and started invading previously non-endemic areas. JE has recently spread to new territories due to land-use changes, including forest fragmentation and concentrated livestock production. Changes in the livestock population decreased the cattle pig ratio which enhanced the Japanese encephalitis virus (JEV) infection. This review brings forth the present widespread changes encountered that grossly impact the risk of infection in many places for the emergence of Japanese encephalitis and to address the implications for its control.

Cyclophilin A: a possible host modulator in Chandipura virus infection.

Chandipura virus (CHPV), belonging to the genus Vesiculovirus of the family Rhabdoviridae, has been identified as one of the causes of pediatric encephalitis in India. Currently, neither vaccines nor therapeutic drugs are available against this agent. Considering that the disease progresses very fast with a high mortality rate, working towards the development of potential therapeutics against it will have a public health impact. Although the use of viral inhibitors as antiviral agents is the most common way to curb virus replication, the mutation-prone nature of viruses results in the development of resistance to antiviral agents. The recent development of proteomic platforms for analysis of purified viral agents has allowed certain upregulated host proteins that are involved in the morphogenesis and replication of viruses to be identified. Thus, the alternative approach of inhibition of host proteins involved in the regulation of virus replication could be explored for their therapeutic effectiveness. In the current study, we have evaluated the effect of inhibition of cyclophilin A (CypA), an immunophilin with peptidyl-prolyl cis/trans-isomerase activity, on the replication of CHPV. Treatment with cyclosporin A, used in vitro for the inhibition of CypA, resulted in a 3-log reduction in CHPV titer and an undetectable level of CypA in comparison to an untreated control. An in silico analysis of the interaction of the CHPV nucleoprotein with the human CypA protein showed stable interaction in molecular docking and molecular dynamics simulations. Overall, the results of this study suggest a possible role of CypA in facilitating CHPV replication, thus making it one of the potential host factors to be explored in future antiviral studies.Supplementary informationThe online version contains supplementary material available at 10.1007/s00705-021-05237-1.

Effectiveness of Japanese encephalitis vaccine SA 14-14-2 and impact of immunization among adults in Assam, India

Background: Japanese encephalitis (JE) is the leading cause of viral encephalitis in India. Assam contributes 2.5% of the country's population, contributing to ∼36% of JE case-load. Vaccination is the only preventive measure available to combat the disease. Live attenuated JE vaccine, SA 14-14-2 is the most widely used JE vaccine in the Asian sub-continent. JE was earlier known as the disease of children. Thus, to combat the disease among the pediatric age-group, the Government of India (GoI) undertook a mass JE vaccination program in campaign mode during 2006 among children (1–15 years). Interestingly, a rising trend of JE among adults became conspicuous since 2007. In response, GoI undertook mass JE vaccination drive among adults in the worst JE affected district of Assam, Sivasagar, on a pilot basis in 2011. Another vaccination drive was carried out in 2014 to cover the missed out adult population. The present study aimed at evaluating vaccine effectiveness (VE) of a single dose of SA 14-14-2 up to seven years post-vaccination and understanding the impact of immunization among adults in Sivasagar. Methods and materials: During 2012–2018, a case-control study was conducted recruiting 261 JE cases and 522 age-sex matched healthy controls. VE was calculated based on the odds ratio. Incidence rate (IR) per 100,000 population during pre (2009–2011) and post-vaccination periods (2012–2018) were compared to assess the impact of immunization. Results: VE among adults was 90% in 2012; it gradually declined to 82% in 2013. Following the second round of vaccination in 2014, a marginal increase in VE was noted (84%). Subsequently (2015–2018), VE stabilized at ∼70%. IR during the pre-vaccination period was 11.5 that came down and maintained at ∼5 (post-vaccination). Vaccine coverage among controls was 39%. Conclusion: In Nepal, the same vaccine showed 96.2% VE among children (5 years’ post-vaccination) with coverage of above 70% that brought down IR <1. Therefore, high vaccine coverage (at least 70%) seems to be a prerequisite for achieving the desired results. As adults are highly mobile population, proper planning and sensitization prior to mass vaccination drive are of paramount importance to get a sizeable population covered.

Impact of SA 14-14-2 vaccination on the occurrence of Japanese encephalitis in India

ABSTRACT Japanese encephalitis virus is the major cause of encephalitis in India. To control the increasing incidence and fatal outbreaks, SA 14-14-2 vaccine was introduced initially in 104 endemic districts in phased manner from 2006 to 2011. As there is no data available before 2008 on the number of Japanese encephalitis (JE) cases excluding cases of Acute Encephalitis Syndrome (AES), a four year average of the number of JE vs. AES cases reported during 2008– 2011 was calculated and the value was used to determine the percentage of JE cases out of AES cases for the period 1994 to 2007. The analysis of data for the period 1994 to 2017 showed that there was a substantial increase of JE cases after the initiation of vaccination in 2006. Since the JE vaccination was given only in selected districts, comparing the vaccinated district with non vaccinated district would be more appropriate to determine the impact of vaccination. However, the data available on JE is only at the state wide. Hence, Tamil Nadu state where, district-wise JE data is available from 1993 onwards was used as a model state to determine the impact of vaccination. Even though the data for entire Tamil Nadu state showed an increasing trend, the analysis of data for vaccinated districts reveals that, the increase was due to increase of JE cases in non-vaccinated districts. It shows that, there was a reduction in JE case incidences in the vaccinated districts of Tamil Nadu in particular and India as a whole following the introduction of SA 14-14-2 vaccination.

Developing a transdisciplinary database for operationalization of One Health surveillance for Japanese Encephalitis in India

Developing a transdisciplinary database for operationalization of One Health surveillance for Japanese Encephalitis in India

Observations on the pupal productivity of Culex tritaeniorhynchus in rice fields of West Bengal, India: implications for vector management (Diptera: Culicidae)

The mosquito &lt;em&gt;Culex&lt;/em&gt; &lt;em&gt;tritaeniorhychus&lt;/em&gt; is an established vector of Japanese encephalitis in India and many Asian countries. Entomological monitoring enables estimation of the abundance of the vector mosquitoes and therefore aids in vector management and disease control. In compliance with this proposition, an assessment of the pupal productivity of the mosquito &lt;em&gt;C. tritaeniorhynchus&lt;/em&gt; was made from selected rice fields of West Bengal, India. The results are expected to provide the present status of mosquitoes in an endemic region of Japanese encephalitis. In course of sampling of the rice fields, the mosquito &lt;em&gt;C. tritaeniorhyhchus&lt;/em&gt; was found in abundance with other mosquitoes like &lt;em&gt;Culex&lt;/em&gt; &lt;em&gt;bitaeniorhynchus&lt;/em&gt;, &lt;em&gt;Anopheles subpictus, Anopheles vagus, Anopheles barbirostris&lt;/em&gt;. Application of multivariate analysis indicated that the plant height, water depth and temperature could explain the variations in the pupal productivity of&lt;em&gt; C. tritaeniorhynchus&lt;/em&gt; in rice fields. The correspondence of the immature abundance of &lt;em&gt;C. tritaeniorhynchus&lt;/em&gt; with plant height suggests persistence of the population throughout the paddy rice cultivation period. Using the plant height as an indicator, the abundance of the mosquito &lt;em&gt;C&lt;/em&gt;. &lt;em&gt;tritarniorhynchus&lt;/em&gt; can be predicted enabling application of appropriate strategies for population intervention and thus the possibility of the disease.

Rabies: the most common cause of fatal encephalitis in India

Rabies, a rapidly progressing encephalitis, is a substantial public health problem in India, responsible for more than 20 000 deaths every year. Although steps are being taken to contain the disease, India still carries over 35% of the global burden of rabies, due to inadequate post-exposure prophylaxis. Will India be able to control rabies? Sanjeet Bagcchi investigates.

Complete genome sequence of mumps viruses isolated from patients with parotitis, pancreatitis and encephalitis in India

Limited information is available regarding epidemiology of mumps in India. Mumps vaccine is not included in the Universal Immunization Program of India. The complete genome sequences of Indian mumps virus (MuV) isolates are not available, hence this study was performed. Five isolates from bilateral parotitis and pancreatitis patients from Maharashtra, a MuV isolate from unilateral parotitis patient from Tamil Nadu, and a MuV isolate from encephalitis patient from Uttar Pradesh were genotyped by the standard protocol of the World Health Organization and subsequently complete genomes were sequenced. Indian MuV genomes were compared with published MuV genomes, including reference genotypes and eight vaccine strains for the genetic differences. The SH gene analysis revealed that five MuV isolates belonged to genotype C and two belonged to genotype G strains. The percent nucleotide divergence (PND) was 1.1% amongst five MuV genotype C strains and 2.2% amongst two MuV genotype G strains. A comparison with widely used mumps Jeryl Lynn vaccine strain revealed that Indian mumps isolates had 54, 54, 53, 49, 49, 38, and 49 amino acid substitutions in Chennai-2012, Kushinagar-2013, Pune-2008, Osmanabad-2012a, Osmanabad-2012b, Pune-1986 and Pune-2012, respectively. This study reports the complete genome sequences of Indian MuV strains obtained in years 1986, 2008, 2012 and 2013 that may be useful for further studies in India and globally.

Vaccination Policy for Japanese Encephalitis in India: Tread with Caution!

Live attenuated SA-14-14-2 vaccine against Japanese encephalitis (JE) was introduced in the routine immunization under Universal Immunization Program in the 181 endemic districts of India. Recently, the Government of India has announced the introduction of one dose of JE vaccine for adults in endemic districts. The policy to mass vaccinate adults has raised several concerns that are discussed in this write-up. Apart from adult vaccination, the continuation of large scale JE vaccination program despite it being a very focal problem, and continued neglect of some other serious public health illnesses have also been highlighted. The issue of lack of authentic data on effectiveness of currently employed SA-14-14-2 JE vaccine has also been discussed.

Ocular Manifestations of Emerging Viral Diseases In India

Dengue fever is the most common arthropod borne disease of human in the tropical and subtropical regions.1 It is caused by the dengue virus, a Flavivirus, and is transmitted by the Aedes aegypti mosquito. It is an endemic disease in India and the latest outbreak occurred in 2012 during which a total of 47,029 cases of dengue fever was reported.2 According to a multinational study, the number of infections stood at 390 million a year and India had the highest burden, accounting for about a third of the world’s cases.3 Dengue has seen a global resurgence recently despite extensive control efforts. Ocular involvement in dengue fever has been reported in many studies. Subconjunctival petechial haemorrhage, secondary to marked thrombocytopenia, is the most common ocular involvement as reported in an East Indian population.4 However patients may present during recovery phase i.e. one week after the onset of fever with a sudden loss of vision or a central scotoma. These manifestations are due to involvement of the retinal and/or choroidal circulation, with a predilection for the macular area. The main findings of dengue maculopathy are retinal haemorrhage, venular sheathing, yellow subretinal dots, retinal pigment epithelium mottling, foveolitis, disc hyperaemia and disc oedema. Neurosensory retinal detachment is seen in 15% of eyes with retinal vascular leakage.1 Optic neuritis is another important ocular involvement in patients of dengue fever, which may be unilateral or bilateral.5 Japanese encephalitis (JE), a leading cause of viral encephalitis in Asia, is an endemo-epidemic disease in some regions in India. It is a vector-borne viral disease caused by Flavivirus. JE is the only virus so far confirmed to cause epidemics of encephalitis in India.6 It has a high mortality rates and usually affects children below 10 years of age. Ocular manifestations are not common. But cases have been reported with ocular palsy, papilloedema and ischaemic maculopathy during recovery stage. A case of optic neuritis has been reported three weeks after an attack of serologically positive JE.7

The host-range tdCE phenotype of Chandipura virus is determined by mutations in the polymerase gene

The emerging arbovirus Chandipura virus (CV) has been implicated in epidemics of acute encephalitis in India with high mortality rates. The isolation of temperature-dependent host-range (tdCE) mutants, which are impaired in growth at 39 °C in chick embryo (CE) cells but not in monkey cells, highlights a dependence on undetermined host factors. We have characterized three tdCE mutants, each containing one or more coding mutations in the RNA polymerase gene and two containing additional mutations in the attachment protein gene. Using reverse genetics, we showed that a single amino acid change in the virus polymerase of each mutant was responsible for the host-range specificity. In CE cells at the non-permissive temperature, the discrete cytoplasmic replication complexes seen in mammalian cells or at the permissive temperature in CE cells were absent with the tdCE mutants, consistent with the tdCE lesions causing disruption of the replication complexes in a host-dependent manner.

Japanese encephalitis in India: risk of an epidemic in the National Capital Region

Japanese encephalitis (JE) is a mosquitoborne viral disease that is the primary cause of acute encephalitis syndrome in India. This virus mainly infects the central nervous system and causes massive inflammation which, if left unchecked, may prove fatal. Survivors often suffer from mild to severe neuropsychiatric sequelae. JE is a major cause of death in many parts of India and there is a possibility of it spreading into the National Capital Region from highly endemic neighbouring states. Fourteen cases of JE were reported in Delhi in 2011 compared with none in the previous 4 years from 2007 to 2010. Unless immediate preventive measures are taken this trend could continue and the disease could spread with increasing prevalence.

Cloning and expression of an envelope gene of West Nile virus and evaluation of the protein for use in an IgM ELISA

West Nile virus (WNV) is a neurotropic flavivirus that has emerged globally as a significant cause of viral encephalitis. The early confirmatory diagnosis of WNV infections is important for timely clinical management and epidemiologic control in areas where multiple flaviviruses are endemic. The coexistence of WNV along with other members of flaviviruses like dengue and Japanese encephalitis in India has complicated the serodiagnosis due to cross-reactive antigens. In the present study, the development and evaluation of a highly sensitive and specific IgM enzyme-linked immunosorbent assay (ELISA) using the recombinant envelope protein (rWNV-Env) for rapid, early, and accurate diagnosis of WNV are reported. The gene coding for the envelope protein of WNV was cloned and expressed in pET 28a vector followed by purification of recombinant protein by affinity chromatography. An indirect IgM microplate ELISA using purified rWNV-Env protein was optimized having no cross reactivity with healthy human serum. Furthermore, the specificity of this assay was confirmed by cross checking with serum samples obtained from patients with dengue and Japanese encephalitis viruses. The comparative evaluation of this rWNV-Env protein–specific IgM ELISA with plaque reduction neutralization test assay using 105 acute phase of clinical samples revealed 95% concordance with sensitivity and specificity of 92% and 97%, respectively. The positive and negative predictive values of recombinant-based Env ELISA were 94% and 96%, respectively. The recombinant envelope protein–based WNV-specific ELISA reported in this study will be useful for rapid screening of large numbers of clinical samples in endemic areas during outbreaks.

An epidemic of encephalitis associated with human enterovirus B in Uttar Pradesh, India, 2008

Background Human enteroviruses (HEVs) are a rare cause of encephalitis, presenting in endemic or epidemic form. Objectives The aim of the study is to identify and characterise the causative agent of the encephalitis epidemic, which occurred in Uttar Pradesh, India during the summer of 2008. Study design A total of 90 cerebrospinal fluid (CSF) specimens were collected between June and October 2008 from children with symptoms of encephalitis admitted to Chhatrapati Shahuji Maharaj Medical University and Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow, Uttar Pradesh, India. Conventional and molecular methods were used to identify and characterise the viral agent associated with the epidemic. Results Enterovirus RNA was detected in 37 (41.11%) of 90 CSF samples by real-time polymerase chain reaction (PCR). Seroneutralisation, amplification and sequencing of the 3′-end of the VP1 region of EV isolates revealed coxsackievirus B5 (CBV) and echovirus 19 (ECV) as the main serotypes causing this epidemic. Phylogenetic analysis showed that sequence divergence among the same serotypes was 0–4% at the nucleotide level. Conclusions This is the first report suggesting that CBV 5 and ECV 19 may be responsible for an epidemic of encephalitis in India. These serotypes were variant and evolved within the studied area.

Molecular phylogenetic study of Culex quinquefasciatus mosquito from different geographical regions of India using 16S rRNA gene sequences

Culex quinquefasciatus is a major vector of filariasis and various encephalitis in India and worldwide. Vector control remains the most successful strategy for the suppression of mosquito borne diseases. The genetic structure of vector populations in terms of insecticide resistance and susceptibility or refractoriness to infection may possibly vary. To exploit the genetic variability in vector population could pave the path for the alternative strategies in vector management. The sequences of ribosomal RNA molecules have been widely used for such studies. Here, we examined the molecular phylogenetic relationship among the Cx. quinquefasciatus collected from different geographical regions of India, using 16S ribosomal RNA (16S rRNA) gene nucleotide sequences. The distances among the species were measured using Pearson correlation; the Neighbor-Joining (NJ) method was used for the clustering with appropriate bootstrap values using Data Analysis in Molecular Biology and Evolution (DAMBE) software. The results revealed that the populations are genetically diverse. Based on the distance values and the tree topology on the basis of 16S rRNA sequences reflected the clear biogeographical and geoclimatic pattern among the different geographical populations from India.