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      Encephalitis outbreaks in India: A cluttered landscape

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          Abstract

          Acute encephalitis is widely prevalent in India and its sub-continent. They cause great burden on morbidity and mortality among pediatric population of the country, yet there are no authentic nationally representative data on exact incidence rate of the illness. The etiology of the illness is diverse, and the currently employed terminology, Acute Encephalitis Syndrome (AES), which has rendered a specific entity to a constellation of diverse neurological diseases, some even non-infectious in nature, seems misnomer. Admittedly, the purpose is to capture all neurological diseases presenting in outbreak forms with special focus on surveillance of Japanese Encephalitis (JE). 1 1 Burden in India: Do we have reliable estimate? One way to find burden of AES in India is through the website maintained by Directorate of National Vector Borne Disease Control Programme (NVBDCP), Delhi. 2 However, here again the focus is JE, and all non-JE cases are clubbed under one head. No details are provided on different etiological causes of AES. As per the latest data, this year till October 31, 7201 cases and 989 deaths of AES are reported from all over the country. 2 Then there are sporadic reports mainly from the different medical institutions on incidence of AES or acute viral encephalitis, mainly among hospitalized children.3, 4, 5, 6, 7 There is paucity of population-based studies, as well as incidence rate of a particular viral encephalitis. Most of the population-based studies have focused on outbreak investigations and surveillance of AES. A recent review provides an overview of these studies in some details. 8 2 Outbreak investigations: Another Achilles’ heel? There is no ‘early warning’ or ‘alert system’ available in the country on any outbreak of known or unknown entity. Most of the times, the media ‘break’ the news regarding appearance of an outbreak. Here, the focus seems on ‘sensationalization’ with hidden motive to harass health officials or institutions. These news items lack specificity and details. The response of the health department and investigating agencies is also equally shoddy and clumsy. The usual ‘knee-jerk reaction’ is to dub all these outbreaks as viral encephalitis or JE. There is hardly any effort made to define a case properly, a correct case definition is often lacking, teams work with a rigid mindset and complete the ritual of collecting few samples. Lack of adequate research laboratories for virological workup is lacking in the vicinity of most outbreaks, the delay in collecting, transporting and processing the samples further make the entire process a redundant exercise. Autopsies and detailed histopathological studies of viscera have almost become extinct now. 9 Another big flaw is to differentiate various outbreaks of AES on the basis of ‘primary’ versus the ‘secondary’ brain diseases. Here comes the significance of segregating the latter from the former. A primary brain infection must be distinguished from a secondary involvement of brain. Or in other words, ‘encephalitis’ from the ‘encephalopathy’. It is of paramount importance not only to reach at a correct diagnosis, but also to launch preventive measures at community level. There are instances in the past, when an entirely a non-infectious entity was targeted for control with large scale vaccination drive! Many outbreak investigations are terminated before reaching to their conclusive ends. For example, investigations of outbreaks of acute brain diseases with high mortality in Jamshedpur 10 and Nagpur 11 in 50s are still inconclusive. Whether these outbreaks were indeed caused by some viruses or were entirely non-infectious in nature is still undetermined. 12 There is a tendency to dub every outbreak involving fever with altered sensorium as acute encephalitis or AES. Certainly, there are some ‘clues’ or ‘pointers’ that hint to a diagnosis other than the acute encephalitis if followed judiciously. 13 WHO has also not provided any proper algorithm for outbreak investigations to those engaged in the field. The major contributors to the broad group of AES should be identified and compartmentalized. 3 Has JE lost its pre-eminence as a leading viral encephalitis in India? Till quite recently, JE has been the center of all investigations pertaining to acute encephalitis in India. In fact, as stated above, the term ‘AES’ was coined to facilitate JE surveillance. However, in last decade or so, there is a shift in the spectrum of causative organisms responsible for acute encephalitis in India. 8 Most studies have now reported non-JE etiology for AES in India; accordingly, enteroviruses, rhabdoviruses, herpesviruses, paramyxoviruses, etc. are getting larger share.4, 5, 8 If one analyzes the data provided by NVBDCP, the JE constitutes from a meager 8.9% of all reported AES in 2012 to 19.2% in 2015 till October, 2015 2 (Fig. 1 ). It means non-JE viruses and some non-encephalitic illness, i.e. encephalopathies are contributing chiefly to overall burden of AES in India. It seems that JE has now acquired a regional status; its outbreaks are more circumscribed, and confined to a limited geographical area, but are now mainly reported from a few states such as Assam, West Bengal, Uttar Pradesh, and Jharkhand. 2 Of late, people have started questioning the prudence of continuing large scale JE vaccination program in view of its focal nature, low burden, and uncertain effectiveness of currently employed JE vaccine. 14 The vast group of illnesses contained in the non-JE group needs to be defined, if we need to reduce the burden of AES in India. Mere relying on vector control and JE-vaccination may not yield the desired results. Fig. 1 Cases and deaths due to AES and JE in India, 2009–15. Data from Directorate of National Vector Borne Disease Control Programme – Delhi. 4 Is existing surveillance competent enough to detect any new agent? In recent times, many new viruses are detected from different regions of the world that include Ebola, Crimean-Congo Hemorrhagic Fever, Middle East Respiratory Syndrome Coronavirus (MERS-CoV), Zika virus, etc. Is our existing surveillance competent enough to suspect and diagnose transmission of these novel agents? There are many instances in recent past, when our investigating agencies and surveillance systems did very sloppy investigations. Take the case of a lethal outbreak in Siliguri, which created havoc among public and heath experts way back in January–February 2001. Several agencies had investigated this peculiar outbreak and came out with their own interpretations and results. Initially, it was reported to be caused by unidentified vial agent, later atypical-Measles virus and Hantavirus infection were blamed, and ultimately, CDC, Atlanta concluded that the outbreak was caused by Nipah/Hendra or closely related virus! 15 There are instances when even premiere investigating agencies had failed to differentiate a non-infectious entity with viral encephalitis. Investigations performed in Saharanpur and adjoining districts of western UP and Uttarakhand, and Muzaffarpur, Bihar are the most recent examples. These illustrations highlight the significance of establishing a competent surveillance system, which is well supported by sophisticated investigational facilities, capable of handling and diagnosing new pathogens. A precious time is lost to institute appropriate education, preventive and control measures. A timely intervention is the key to prevent or minimize human losses. On global level, the success to curb an evolving pandemic of SARS and more recently, successfully containing emerging Ebola outbreak in Africa are shining examples of extraordinary swift and coordinated actions taken by global health sectors, governments, and agencies. 5 What is needed? Currently, we do not have a composite picture of overall burden of AES, or more precisely, viral encephalitis in India. Merely clubbing all related illnesses under one head is not sufficient. The time has come to move beyond, but presuming every case (or an outbreak) of AES is yet another instance of acute viral encephalitis that in turn is caused by JE virus may not serve the purpose. We need to invest heavily in building a well performing AES surveillance system backed by state-of-the-art laboratory network. Laboratories that perform routine testing for known pathogens responsible for viral encephalitis should be established in every district's health headquarter. Routine surveillance should be augmented and outbreak investigations must be bolstered. We need a well coordinated, thorough systematic outbreak investigation approach with correct methodology to investigate all the recurring outbreaks of unknown etiology rather than clubbing them under one head of viral encephalitis and resorting to empiric preventive measures like mass JE vaccination programs. There must be an official ‘early warning’ or ‘disease alert’ system so that our reliance on media reporting and media based investigations is curtailed. Our inability to deal with emerging pathogens or even denying the existence of a problem or censoring the news of any new disease appearance is not going to be rewarding in this era of information revolution. On the contrary, it would bring bad name and erode our reputation among international health community. Conflicts of interest The author has none to declare.

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          Most cited references13

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          Nipah/Hendra virus outbreak in Siliguri, West Bengal, India in 2001.

          The viral encephalitides caused by animal or human viruses are characterized by sudden outbreaks of neurological disease in both tropical and temperate regions. An outbreak of acute encephalitis occurred in Siliguri (West Bengal) town of India between January 31 and February 23, 2001. This outbreak was investigated by a team of scientists from four major institutions, and the findings are presented here. Detailed information about the outbreak was collected with the help of local health authorities. Limited entomological investigations were also done. Samples collected from cases and contacts were sent for analysis. A total of 66 probable cases and 45 deaths were reported. Epidemiological linkages between cases point towards person-to-person transmission and incubation period of around 10 days. There was neither any concurrent illness in animals nor was there any exposure of cases to animals. Centres for Disease Control and Prevention, Atlanta, USA concluded on the basis of tests carried out on serum specimen from four cases and two contacts that the causative pathogen appears to be Nipah/ Hendra or closely related virus. This outbreak highlights the importance and urgency of establishing a strong surveillance system supported by a network of state-of-the-art laboratories equipped to handle and diagnose new pathogens and including patient isolation techniques, use of personal protective equipment, barrier nursing and safe disposal of potentially infected material in the prevention and control measures for Nipah/Hendra virus infection.
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            Etiology and clinico-epidemiological profile of acute viral encephalitis in children of western Uttar Pradesh, India.

            To study the etiology of viral encephalitis (VE) in the children of western Uttar Pradesh, India and to assess the clinico-epidemiological profile of these children in relation to VE. Both cerebrospinal fluid and serum samples were collected from pediatric patients suffering from encephalitis hospitalized at Jawaharlal Nehru Medical College, Aligarh from July 2004 to November 2006. Viral isolation was done on RD cells, HEp-2 cells, and Vero cells from the cerebrospinal fluid samples of children with suspected VE. A microneutralization test was performed for enterovirus 71. An enzyme immunoassay for IgM antibodies was performed for measles virus, mumps virus, varicella zoster virus, herpes simplex virus 1, and Japanese encephalitis virus. Eighty-seven patients were enrolled in the study. The most common etiology of VE was enterovirus 71 (42.1%), followed by measles (21.1%), varicella zoster virus (15.8%), herpes simplex virus (10.5%), and mumps (10.5%). Japanese encephalitis virus was not found in any case. Enterovirus 71 infection caused significant morbidity in children; mortality occurred in 50%. A preponderance of cases occurred in December. In our study generalized convulsions along with altered sensorium were the significant findings in patients with VE. Enterovirus 71, the major etiology of VE in our study, was associated with significant mortality and morbidity. Such studies should be conducted frequently to assess the role of emerging VE in different regions. Copyright 2010. Published by Elsevier Ltd.
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              Epidemiology and etiology of acute encephalitis syndrome in North India.

              Acute encephalitis syndrome (AES) is a major public health problem in eastern Uttar Pradesh, claiming thousands of lives every year. Here we report the common viral etiologic agents of AES and its epidemiology in the vicinity of Lucknow in Uttar Pradesh, North India. Cerebrospinal fluid (CSF) samples collected from patients with AES, who were referred to a viral diagnostic laboratory from January 2011 to December 2012, were tested for IgM antibodies against Japanese encephalitis virus (JEV), dengue virus (DV), herpes simplex virus (HSV), measles virus, mumps virus, varicella zoster virus (VZV), and enterovirus using commercial enzyme immuno-assays. Of the 1,578 enrolled patients, JEV was the most commonly detected (16.2%), followed by DV (10.8%), HSV (9.3%), measles virus (8.9%), mumps virus (8.7%), VZV (4.4%), and enterovirus (0%). Co-positivity with more than 1 virus was observed in 12 patients. The demographic distribution of patients pertaining to age, sex, and geographic and seasonal variation is discussed. Maximum mortality was caused by JEV infection, while patients with HSV infection had maximum residual neuro-psychiatric disability. JEV and DV are the chief causative agents of AES in North India, although other viruses should also be considered in a differential diagnosis.
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                Author and article information

                Contributors
                Journal
                Pediatric Infectious Disease
                Indian Academy of Paediatrics. Published by Elsevier, a division of Reed Elsevier India, Pvt. Ltd.
                2212-8328
                2212-8336
                2 December 2015
                October-December 2015
                2 December 2015
                : 7
                : 4
                : 89-91
                Affiliations
                [0005]Consultant Pediatrician, Mangla Hospital and Research Center, Shakti Chowk, Bijnor, UP 246 701, India
                Article
                S2212-8328(15)00067-3
                10.1016/j.pid.2015.11.008
                7148934
                b742b702-775b-4e13-877f-b7f89e4e2b1a
                Copyright © 2015 Indian Academy of Paediatrics. Published by Elsevier, a division of Reed Elsevier India, Pvt. Ltd. All rights reserved.

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