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  • Some encephalitis links

    Some JE links

    Japanese encephalitis: a review of the Indian perspective
    Equates AES & JE to a certain extent. Covers India 2004 - 2010 - Ro

    India 2008 - July 2014 AES and JE separated
    I suspect that if a third of cases are testing positive for JE, then most of the cases are probably JE

    Laboratory-based Japanese Encephalitis Surveillance in Nepal and the Implications for a National Immunization Strategy
    Period covered May 2004-April 2006 - 4,652 patients; 3,198 tested, 32% JE positive

    Confirmation of Japanese Encephalitis as an Endemic Human Disease Through
    Sentinel Surveillance in Indonesia
    period covered 2005-2006; 1,496 AES cases, 82 JE pos, probably a low estimate due to testing issues, not all CSF, not all 9 days or later, some samples sat for 5 months

    Japanese Encephalitis Surveillance and Immunization ? Asia and the Western Pacific, 2012
    10,426 reported cases in Asia & WP 2011, but 67,900 estimated cases

    The incidence of acute encephalitis syndrome in Western industrialised and tropical countries
    various countries, various timeframes published 2008

    by age 30 almost 100% of pop had JEV antibodies indicating large nos of asymptomatic cases - similar to Tamil Nadu, India
    Twitter: @RonanKelly13
    The views expressed are mine alone and do not represent the views of my employer or any other person or organization.

  • #2
    Re: Some JE links

    But what about the cases where few if any test positive for JE -

    Cassia occidentalis toxicity causes recurrent outbreaks of brain disease
    in children in Saharanpur (Uttar Pradesh)

    Acute encephalitis syndrome in children in Muzaffarpur: hypothesis
    of toxic origin (Bihar)

    Recurring Epidemics of Acute Encephalopathy in Children in Muzaffarpur, Bihar
    suggests heat stress as cause

    The recurring epidemic of heat stroke in children in Muzaffarpur, Bihar, India;aulast=Sahni

    Possible factors causing Acute Encephalits Syndrome outbreak in Bihar,India

    Enteroviruses in Patients with Acute Encephalitis, Uttar Pradesh, India

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

    Severe enterovirus 76-associated acute encephalitis syndrome complicated by myocarditis and successfully treated with intravenous immunoglobulins;aulast=Bhatt

    Enterovirus 75 encephalitis in children, southern India.
    Recent outbreaks of enterovirus in Southeast Asia emphasize difficulties in diagnosis of this infection. To address this issue, we report 5 (4.7%) children infected with enterovirus 75 among 106 children with acute encephalitis syndrome during 2005-2007 in southern India. Throat swab specimens may be useful for diagnosis of enterovirus 75 infection.

    West Nile encephalitis outbreak in Kerala, India, 2011
    Twitter: @RonanKelly13
    The views expressed are mine alone and do not represent the views of my employer or any other person or organization.


    • #3
      Re: Some encephalitis links


      Acute encephalopathy in children in Nagpur (Maharashtra): similarity to Reye's syndrome
      Twitter: @RonanKelly13
      The views expressed are mine alone and do not represent the views of my employer or any other person or organization.


      • #4
        Re: Some encephalitis links

        Estimating the Burden of Japanese Encephalitis Virus and Other Encephalitides in Countries of the Mekong Region
        Arnaud Tarantola,1,* Flavie Goutard,1,2 Paul Newton,3 Xavier de Lamballerie,4 Olivier Lortholary,5 Julien Cappelle,1,2 and Philippe Buchy1
        Darren J. Gray, Editor
        Author information ► Article notes ► Copyright and License information ►
        This article has been cited by other articles in PMC.
        Go to:
        Diverse aetiologies of viral and bacterial encephalitis are widely recognized as significant yet neglected public health issues in the Mekong region. A robust analysis of the corresponding health burden is lacking. We retrieved 75 articles on encephalitis in the region published in English or in French from 1965 through 2011. Review of available data demonstrated that they are sparse and often derived from hospital-based studies with significant recruitment bias. Almost half (35 of 75) of articles were on Japanese encephalitis virus (JEV) alone or associated with dengue. In the Western Pacific region the WHO reported 30,000?50,000 annual JEV cases (15,000 deaths) between 1966 and 1996 and 4,633 cases (200 deaths) in 2008, a decline likely related to the introduction of JEV vaccination in China, Vietnam, or Thailand since the 1980s. Data on dengue, scrub typhus and rabies encephalitis, among other aetiologies, are also reviewed and discussed.

        Countries of the Mekong region are undergoing profound demographic, economic and ecological change. As the epidemiological aspects of Japanese encephalitis (JE) are transformed by vaccination in some countries, highly integrated expert collaborative research and objective data are needed to identify and prioritize the human health, animal health and economic burden due to JE and other pathogens associated with encephalitides.
        Twitter: @RonanKelly13
        The views expressed are mine alone and do not represent the views of my employer or any other person or organization.


        • #5
          Re: Some encephalitis links

          Pediatric Infectious Disease Journal:
          October 2014 - Volume 33 - Issue 10 - p 1077-1082
          doi: 10.1097/INF.0000000000000368
          Pathogenesis and Host Response

          Association of CPT II Gene With Risk of Acute Encephalitis in Chinese Children
          Hu, Jianxia MD*; Chen, Zongbo MD†; Liu, Xiaoyi MD‡; Chen, Zhihong MD†; Xin, Dandan MD†; Liu, Peipei MD†


          Mutations of the CPT II gene cause CPT II deficiency, an inborn metabolic error affecting mitochondrial fatty acid β-oxidation. Associations and mechanisms of CPT II gene with acute encephalitis need to be elucidated. We aimed to investigate the associations of CPT II gene variants and CPT II activity with development of acute encephalitis.


          A total of 440 blood-unrelated Chinese children with acute encephalitis and 229 healthy controls were enrolled in this case control study. Sequencing of 5 exons of the CPT II gene was carried out to look for the variants associated with acute encephalitis. CPT II activity and blood adenosine triphosphate concentration were examined during high fever and convalescent phase to confirm the hypothesis.


          Polymorphism of rs2229291 in CPT II gene was significantly associated with an increased risk of acute encephalitis (P = 0.031), where as rs1799821 displayed a decrease risk (P = 0.018). Positive association was found between rs2229291 and patients with fever at onset of seizure and degree of pathogenetic condition (P = 0.018 and P = 0.023), but not for rs1799821. CPT II activity of patients with rs2229291 reduced greatly during high fever compared with the convalescent phase.


          rs2229291 and rs1799821 variants in CPT II gene might be 1 of the predisposing factors of acute encephalitis.

          Findings From Qingdao University Broaden Understanding Of Acute Encephalitis (Association Of CPT II Gene With Risk Of Acute Encephalitis In Chinese Children)
          2014 Oct 25 — By a News Reporter-Staff News Editor at Pediatrics Week -- Investigators publish new report on Acute Encephalitis. According to news reporting originating from Qingdao, People’s Republic of China, by VerticalNews correspondents, research stated, “Mutations of the CPT II gene cause CPT II deficiency, an inborn metabolic error affecting mitochondrial fatty acid beta-oxidation. Associations and mechanisms of CPT II gene with acute encephalitis need to be elucidated.”

          Twitter: @RonanKelly13
          The views expressed are mine alone and do not represent the views of my employer or any other person or organization.


          • #6
            Re: Some encephalitis links

            Viral aetiology and clinico-epidemiological features of acute encephalitis syndrome in eastern India

            S. K. RATHOREa1a2, B. DWIBEDIa1 c1, S. K. KARa1, S. DIXITa1, J. SABATa1 and M. PANDAa1
            a1 Regional Medical Research Centre (ICMR), Bhubaneswar, Odisha, India
            a2 School of Biotechnology, KIIT University, Bhubaneswar, Odisha, India

            This study reports clinico-epidemiological features and viral agents causing acute encephalitis syndrome (AES) in the eastern Indian region through hospital-based case enrolment during April 2011 to July 2012. Blood and CSF samples of 526 AES cases were investigated by serology and/or PCR. Viral aetiology was identified in 91 (17?2%) cases. Herpes simplex virus (HSV; types I or II) was most common (16?1%), followed by measles (2?6%), Japanese encephalitis virus (1?5%), dengue virus (0?57%), varicella zoster virus (0?38%) and enteroviruses (0?19%). Rash, paresis and cranial nerve palsies were significantly higher (P < 0?05) with viral AES. Case-fatality rates were 10?9% and 6?2% in AES cases with and without viral aetiology, respectively. Simultaneous infection of HSV I and measles was observed in seven cases. This report provides the first evidence on viral aetiology of AES viruses from eastern India showing dominance of HSV that will be useful in informing the public health system.

            (Received May 24 2013)
            (Revised November 28 2013)
            (Accepted December 11 2013)
            (Online publication January 23 2014)

            Key words
            Acute encephalitis syndrome; acyclovir; herpes simplex virus

            c1 Author for correspondence: Dr B. Dwibedi, Regional Medical Research Centre (ICMR), Chandrasekharpur, Bhubaneswar-23, Odisha, India. (Email:

            Twitter: @RonanKelly13
            The views expressed are mine alone and do not represent the views of my employer or any other person or organization.


            • #7
              Jundishapur J Microbiol. 2014 Sep;7(9):e11821. doi: 10.5812/jjm.11821. Epub 2013 Sep 1.
              Detection of human herpesvirus 6 in cerebrospinal fluid of children with possible encephalitis.

              Yavarian J1, Gavvami N1, Mamishi S2.
              Author information



              Encephalitis is swelling and inflammation of brain, usually due to viral infection. Viral encephalitis symptoms could be fever, headache, altered level of consciousness, and seizures.

              The aim of this study was detection of human herpesvirus-6 (HHV-6) DNA in cerebrospinal fluid (CSF) of patients with symptoms of possible acute encephalitis and without typical signs or symptoms of roseola infantum, using real-time polymerase chain reaction (PCR).

              We studied children two years old or younger, admitted to the pediatric emergency ward with encephalitis-like symptoms. Our evaluation included detection of HHV-6 in CSF of these patients. After DNA extraction, real-time PCR was performed with primers and a probe specific for the U22 open reading frame of both HHV-6A and B.

              From a total of 114 patients, HHV-6 was detected in 10 (8.8%), 90% of which were boys with mean age 7.7 months and median of 7.5 months. No significant differences were found in clinical presentations and laboratory findings between the patients positive and negative for HHV-6. All the children had complete recovery without neurological deficit or death.

              According to this research and prevalence of HHV-6 in children, evaluation of CSF (detecting the HHV-6 DNA by PCR) is recommended in patients younger than 13 months with possible encephalitis.


              Cerebrospinal Fluid; Encephalitis; Human Herpesvirus6; Real-Time Polymerase Chain Reaction


              Twitter: @RonanKelly13
              The views expressed are mine alone and do not represent the views of my employer or any other person or organization.


              • #8
                Outbreaks of Unexplained Neurologic Illness — - Muzaffarpur, India, 2013–-2014


                January 30, 2015 / 64(03);49-53
                Aakash Shrivastava, MD1, Padmini Srikantiah, MD2,3, Anil Kumar, MD1, Gyan Bhushan, MD4, Kapil Goel, MD5, Satish Kumar, MD5, Tripurari Kumar, MBBS5, Raju Mohankumar, MBBS5, Rajesh Pandey, MBBS5, Parvez Pathan, MBBS5, Yogita Tulsian, MBBS5, Mohan Pappanna, MD6, Achhelal Pasi, MD6, Arghya Pradhan, MBBS6,Pankaj Singh, MBBS6, D. Somashekar, MD6, Anoop Velayudhan, MBBS6, Rajesh Yadav, MBBS6, Mala Chhabra, MD1, Veena Mittal, MD1, Shashi Khare, MD1, James J Sejvar, MD7, Mayank Dwivedi, MD2, Kayla Laserson, ScD2,3, Kenneth C. Earhart, MD2,3, P. Sivaperumal, PhD8, A. Ramesh Kumar, PhD8, Amit Chakrabarti, MD8,Jerry Thomas, MD9, Joshua Schier, MD9, Ram Singh, PhD1, Ravi Shankar Singh, MD1, A.C. Dhariwal, MD10, L.S. Chauhan, MD1 (Author affiliations at end of text)
                Outbreaks of an unexplained acute neurologic illness affecting young children and associated with high case-fatality rates have been reported in the Muzaffarpur district of Bihar state in India since 1995. The outbreaks generally peak in June and decline weeks later with the onset of monsoon rains. There have been multiple epidemiologic and laboratory investigations of this syndrome, leading to a wide spectrum of proposed causes for the illness, including infectious encephalitis and exposure to pesticides. An association between illness and litchi fruit has been postulated because Muzaffarpur is a litchi fruit–producing region (Figure 1). To better characterize clinical and epidemiologic features of the illness that might suggest its cause and how it can be prevented, the Indian National Centre for Disease Control (NCDC) and CDC investigated outbreaks in 2013 and 2014. Clinical and laboratory findings in 2013 suggested a noninflammatory encephalopathy, possibly caused by a toxin. A common laboratory finding was low blood glucose (<70 mg/dL) on admission, a finding associated with a poorer outcome; 44% of all cases were fatal. An ongoing 2014 investigation has found no evidence of any infectious etiology and supports the possibility that exposure to a toxin might be the cause. The outbreak period coincides with the month-long litchi harvesting season in Muzaffarpur. Although a specific etiology has not yet been determined, the 2014 investigation has identified the illness as a hypoglycemic encephalopathy and confirmed the importance of ongoing laboratory evaluation of environmental toxins to identify a potential causative agent, including markers for methylenecyclopropylglycine (MCPG), a compound found in litchi seeds known to cause hypoglycemia in animal studies (1–3). Current public health recommendations are focused on reducing mortality by urging affected families to seek prompt medical care, and ensuring rapid assessment and correction of hypoglycemia in ill children.
                2013 Outbreak Investigation

                During May 17–July 22, 2013, a total of 133 children were admitted to the two main referral hospitals in Muzaffarpur with illnesses that met the investigation case definition of acute onset seizures or altered mental status within 7 days of admission in a child aged <15 years. Of these, 94 (71%) patients were from Muzaffarpur; other patients were from six neighboring districts. Among the 133 patients, 71% were aged 1–5 years, 94% had generalized seizures, and 93% had altered mental status. Most (61%) were afebrile at admission; the case fatality rate was 44%. Among 56 patients with cerebrospinal fluid (CSF) examined, 31 (55%) had normal cytology (white blood cell [WBC] count = <5/mm3); 48 of 59 (81%) had CSF normal protein (<45 mg/dL), and 46 of 61 (75%) had normal CSF glucose (>45 mg/dL) levels. At admission, 20 (21%) of 94 patients had hypoglycemia (blood glucose <70 mg/dL).
                CSF samples were tested at NCDC for selected infectious pathogens known to cause encephalitis in the region. Of 60 CSF specimens tested for Japanese encephalitis virus by immunoglobulin M (IgM) capture enzyme-linked immunosorbent assay, 33 by polymerase chain reaction, and 33 by virus isolation, all were negative. Sixteen convalescent serum specimens, collected 14 days after illness onset, also were negative for Japanese encephalitis virus by IgM assay. Thirty CSF specimens examined by reverse transcription–polymerase chain reaction for flaviviruses and 13 examined more specifically for West Nile virus also were negative, as were 23 evaluated for Chandipura virus. Fourteen CSF specimens evaluated by polymerase chain reaction and virus isolation for enteroviruses did not demonstrate evidence of infection.
                Analysis of risk factors for death among 94 affected children showed that low blood glucose at admission was more common among those who died (odds ratio = 2.6; 95% confidence interval [CI] = 1.0–7.2). A case-control study enrolled 101 case-patients and 202 age-matched controls, 101 from the hospital and 101 from the community. Ill children had spent a greater amount of time in agricultural fields or orchards (matched odds ratio = 2.6; CI = 1.2–5.2) than controls. Anthropometric data on 24 patents suggested that younger patients (those aged <5 years) were more likely to have wasting (>2 standard deviations below the median weight for height of the reference population) than controls in the same age group (p = 0.03).
                Data collected during the 2013 investigation suggested that the illness was more likely to be a noninflammatory encephalopathy than an infectious encephalitis, and raised concern for the possibility of a toxin-mediated illness. Although the 2013 investigation did not identify a specific etiology, key recommendations shared with state and district health officials focused on reduction of mortality, including provision of glucometers for hospitals and peripheral health facilities and rapid assessment and treatment of hypoglycemia in children with suspected illness.
                2014 Outbreak Investigation

                Building on the 2013 findings, NCDC and CDC again investigated this syndrome in 2014, using 1) facility-based clinical surveillance, 2) epidemiologic case-control and environmental studies to examine risk factors for illness, including toxin exposures and nutritional indices, and 3) comprehensive laboratory evaluation of patient specimens and environmental samples to search for infectious pathogens as well as selected pesticides, heavy metals, and naturally occurring plant or fruit toxins. Suspected patients were promptly tested for hypoglycemia on arrival at the hospital, before being given any treatment. Patients admitted with the suspected outbreak illness were recommended to receive immediate intravenous dextrose therapy.
                During May 26–July 17, 2014, a total of 390 patients admitted to the two referral hospitals in Muzaffarpur with illnesses that met the same case definition used in 2013 were evaluated by the NCDC/CDC investigation team. Among the patients, 213 (55%) were male, the median age was 4 years (range = 6 months–14 years), and 280 (72%) were aged 1–5 years. Most patients were from Muzaffarpur district (70%), although patients also were reported from six surrounding districts. As in previous years, clustering of cases was not observed; the illness of each affected child appeared to be an isolated case in various villages (approximate population per village = 1,000). The outbreak peaked in mid-June, with 147 cases reported during June 8–14, 2014. The number of cases declined significantly after the onset of monsoon rains on June 21, 2014 (Figure 2).
                Caregivers reported that affected children were previously healthy and experienced an acute onset of convulsions, often between 4:00 a.m. and 8:00 a.m., frequently followed by a decreased level of consciousness. Of 345 patients with recorded data, 324 (94%) had seizures on admission, and 267 (77%) had altered mental status.Of 357 patients with body temperature measured on admission, 219 (61%) were afebrile (≤99.5?F [≤37.5?C]).The case-fatality rate was 31%.
                Detailed clinical evaluation of 52 patients within 12 hours of admission elicited a history of generalized tonic or tonic-clonic seizures in 100%. Upper motor neuron findings of generalized hypertonia and Babinksi's sign were observed in approximately one third of patients; focal neurologic deficits were rare. Brain magnetic resonance imaging of 16 patients selected at random revealed no focal abnormalities or changes suggestive of inflammation; eight patients (50%) showed mild to moderate cerebral edema. Electroencephalography in 30 cases demonstrated findings consistent with generalized encephalopathy in 22 (73%); seven demonstrated epileptiform discharges. Overall, neurologic findings suggested a diffuse encephalopathy with seizures and cerebral edema.
                Of 62 patients with CSF collected for analysis, 52 (84%) had normal WBC counts, 58 (94%) had normal protein, and 49 (79%) had normal glucose levels. Of 327 patients with blood glucose measurement on admission, the median blood glucose level was 48 mg/dL, and 171 (52%) and 204 (62%) patients had glucose levels of ≤50 mg/dL and ≤70 mg/dL, respectively. Laboratory diagnostic testing of 17 CSF specimens for Japanese encephalitis virus and West Nile virus by polymerase chain reaction was negative. Additionally, evaluation of 12 CSF specimens with a multiplex polymerase chain reaction platform assay with the capacity to detect 11 viruses* also was negative.

                The 2013 and 2014 Muzaffarpur investigations indicate that this outbreak illness is an acute noninflammatory encephalopathy. This is supported by clinical and laboratory findings, inclusive of negative diagnostic results for the most common pathogens that cause infectious encephalitis in this region. Laboratory data indicate that significant hypoglycemia is an important presenting feature of illness. Furthermore, the implementation of the 2013 recommendations for rapid assessment and correction of hypoglycemia might, in part, have helped to reduce mortality (44% in 2013 versus 31% in 2014).
                Although the underlying cause of this illness remains unknown, initial clinical and laboratory results of the 2014 investigation confirm the importance of systematically evaluating toxins and agents with the potential to cause acute encephalopathy. Furthermore, the consistent finding of hypoglycemia among affected children underscores the importance of examining the possible role of compounds that might acutely result in low blood sugar, seizures, and encephalopathy, including the possible role of MCPG in litchis. Outbreaks of similar acute neurologic illnesses occurring in litchi-growing regions of Bangladesh and Vietnam have been reported (4,5) raising further interest in a possible association between litchis and this illness. The investigation in Bangladesh focused primarily on the possibility that pesticides used seasonally in litchi orchards might be involved, but no specific pesticide was implicated. The investigation in Vietnam focused primarily on possible infectious agents that might be present seasonally near litchi fruit plantations but found none to explain the outbreak. In Muzaffarpur, MCPG is hypothesized to cause acute hypoglycemia and illness through a similar mechanism to hypoglycin A, a toxin that has been reported to cause acute encephalopathy in the West Indies and West Africa after consumption of unripe ackee, a fruit in the same botanical family as litchi (6–9).
                As part of the collaborative investigation, blood and urine specimens of affected children are being systematically assayed by the Indian National Institute for Occupational Health and CDC for pesticide metabolites, heavy metals, and markers for MCPG and its metabolites. Litchi fruits collected from orchards that border the homes of affected children are being examined for MCPG markers, and environmental samples (local vegetation, food grains, and water) collected from homes of patients and controls are being evaluated for pesticide residues. Additionally, analysis of epidemiologic data collected in the 2014 case-control study, including detailed histories regarding consumption of litchis or exposure to pesticides, might elucidate potential risk factors for illness among these children.
                Analysis of nutritional indices and other host factors is planned to search for an explanation for the lack of clustering of cases in these outbreaks. Until an etiology for this illness is identified, current public health and clinical recommendations are focused on reducing mortality by ensuring families with affected children rapidly access medical attention, and health care providers promptly assess for and correct hypoglycemia.
                1National Centre for Disease Control, Directorate General of Health Services, Ministry of Health and Family Welfare, Government of India, New Delhi, India; 2Global Disease Detection Program, CDC, New Delhi, India; 3Division of Global Health Protection, Center for Global Health, CDC; 4Muzaffarpur District Health Department, Government of Bihar, Muzaffarpur, India; 5India Epidemic Intelligence Service Cohort 1, National Centre for Disease Control, New Delhi, India, 6India Epidemic Intelligence Service Cohort 2, National Centre for Disease Control, New Delhi, India; 7National Center for Enteric and Zoonotic Diseases, CDC; 8National Institute of Occupational Health, Indian Council of Medical Research, Ahmedabad, India; 9National Center for Environmental Health, CDC; 10National Vector Borne Disease Control Programme, Directorate General of Health Services, Ministry of Health and Family Welfare, Government of India, New Delhi, India (Corresponding authors: Padmini Srikantiah,, +91-11-2419-8876, Aakash Shrivastava,, +91-11-23909242)

                P.K. Sen, MD, R. Jaiswal, MD, and other officials of the National Vector Borne Disease Control Programme, India. B. Mohan, MD, A. Kumar, MD, G.S. Sahni, MD, Rajiva Kumar MD, and other pediatricians at participating hospitals.
                1. Gray DO, Fowden L. alpha-(methylenecyclopropyl)glycine from litchi seeds. Biochem J 1962;82:385–9.
                2. Melde K, Jackson S, Bartlett K, Sherratt HS, Ghisla S. Metabolic consequences of methylenecyclopropylglycine poisoning in rats. Biochem J 1991;274:395–400.
                3. Melde K, Buettner H, Boschert W, Wolf HP, Ghisla S. Mechanism of hypoglycaemic action of methylenecyclopropylglycine. Biochem J 1989;259:921–4.
                4. Paireau J, Tuan NH, Lefrancois R, et al. Litchi-associated acute encephalitis in children, Northern Vietnam, 2004–2009. Emerg Infect Dis 2012;18:1817–24.
                5. Biswas SK. Outbreak of illness and deaths among children living near lychee orchards in northern Bangladesh. International Centre for Diarrhoeal Diseases Research, Bangladesh ICDDRB Health Sci Bull 2012;10:15–22.
                6. Gaillard Y, Carlier J, Berscht M, et al. Fatal intoxication due to ackee (Blighia sapida) in Suriname and French Guyana. GC-MS detection and quantification of hypoglycin-A. Forensic Sci Int 2011;206:e103–7.
                7. CDC. Toxic hypoglycemic syndrome—Jamaica, 1989-1991. MMWR Morb Mortal Wkly Rep 1992;41:53–5.
                8. Joskow R, Belson M, Vesper H, Backer L, Rubin C. Ackee fruit poisoning: an outbreak investigation in Haiti 2000-2001, and review of the literature. Clin Toxicol (Phila) 2006;44:267–73.
                9. Meda HA, Diallo B, Buchet JP, et al. Epidemic of fatal encephalopathy in preschool children in Burkina Faso and consumption of unripe ackee (Blighia sapida) fruit. Lancet 1999;353:536–40.
                * Herpes simplex viruses 1 and 2, human herpes viruses 6 and 7, cytomegalovirus, varicella zoster virus, Epstein-Barr virus, parechovirus, adenovirus, enteroviruses, and parvovirus B19.

                What is already known on this topic?
                Seasonal outbreaks of an unexplained acute neurologic illness affecting young children and associated with high case fatality have been reported from Muzaffarpur, India, since 1995. Multiple potential etiologies have been proposed, including infectious encephalitis and pesticide exposure, but not systematically assessed.
                What is added by this report?
                Outbreak investigations in 2013 and 2014 helped to classify this illness as a noninflammatory encephalopathy. Approximately 60% of patients had low blood glucose (<70 mg/dL) on admission, which was associated with poorer outcomes and prompted recommendations for rapid assessment and treatment of low blood glucose. The low blood glucose raised the possibility that exposure to a toxin could result in low blood glucose, seizures, and encephalopathy. One specific hypothesis was that exposure to MCPG, a toxin in litchis, might cause acute hypoglycemia and encephalopathy in some children. Laboratory investigations to assess this possibility and understand why only some children are affected are ongoing.
                What are the implications for public health practice?
                A collaborative, multidisciplinary systematic investigation of this outbreak has been essential to correctly classify this illness and focus analytic efforts on evaluation of testable data-driven hypotheses to identify a potential etiology. The implementation of the 2013 recommendations for rapid assessment and correction of hypoglycemia might, in part, have helped to reduce mortality (44% in 2013 compared with 31% in 2014). Public health recommendations are focused on advising affected families to seek prompt medical attention, and advising healthcare providers to rapidly assess and correct hypoglycemia in ill children.

                FIGURE 1. Litchi fruit orchards have been a focus of the investigation into outbreaks of unexplained neurologic illness among children — Muzaffarpur, India, 2013–2014

                Alternate Text: The figure above is a photograph of litchi fruit in Muzaffarpur, India. An association between unexplained neurologic illness and litchi fruit has been postulated because Muzaffarpur is a litchi fruit-producing region.

                FIGURE 2. Number of patients admitted to two referral hospitals with unexplained acute neurologic illness, by date of admission — Muzaffarpur, India, May 26–July 17, 2014

                Alternate Text: The figure above is an epidemiologic curve showing the number of patients admitted to two referral hospitals with unexplained acute neurologic illness, by date of admission, in Muzaffarpur, India during May 26-July 17 2014.

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                • #9
                  Infectious Causes of Encephalitis and Meningoencephalitis in Thailand, 2003?2005
                  Twitter: @RonanKelly13
                  The views expressed are mine alone and do not represent the views of my employer or any other person or organization.


                  • #10
                    A child-killing toxin emerges from shadows
                    Priyanka Pulla*
                    As the heat builds before the monsoon rains in the north Indian state of Bihar, hundreds of young children come down with an illness that kills many victims and leaves others brain damaged. Now, scientists believe they have unmasked the mystery culprit: a toxin in the lychee fruit. After a 2-year investigation, researchers suggest in the 30 January issue of Morbidity and Mortality Weekly Report that the illness results from crashing blood sugar levels likely due to a lychee toxin known to cause hypoglycemia in rats. Two other groups finger the toxin in Current Science and in the May issue of Emerging Infectious Diseases. The mechanism underscores the threat of similar toxins present in related fruits in West Africa and the Caribbean, as well as in a mushroom in China.
                    Volume 21, Number 5?May 2015


                    Probable Toxic Cause for Suspected Lychee-Linked Viral Encephalitis

                    On This Page


                    Suggested citation for this article
                    To the Editor: Paireau et al. (1) reported a spatiotemporal association between unexplained outbreaks of suspected acute encephalitis in children in northern Vietnam and the harvesting of lychee (litchi) fruit. The clinical, biologic, and immunologic characteristics of the patients suggested a viral etiology (1). However, the lychee-associated acute brain disorder, which has also been reported in Bangladesh and India (Bihar and West Bengal), could also result from ingestion of phytotoxins present in lychee fruit, specifically α-(methylenecyclopropyl)glycine (2), the lower homologue of the neurotoxic L-amino acid hypoglycine (3,4).
                    As previously described (5), ingestion of the hypoglycine-rich fruit of ackee, a relative of lychee, can induce a dose-dependent toxic hypoglycemic encephalopathy in poorly nourished children. The syndrome is best known from Jamaica, where ackee is widely eaten, and occurs most frequently in 2- to 10-year-old children, who develop severe hypoglycemia and metabolic acidosis. Clinical manifestations of Jamaican vomiting sickness include headache, thirst, sweating, vomiting, lethargy, seizures, coma, and death over a span of hours to days. Patients may be mildly to moderately febrile, and emesis may not be present in all cases. Heavy ingestion of the immature fruit of ackee (Blighia sapida) or other members of the soapberry family (Sapindaceae), including lychee (Litchi sinensis), rambutan (Nephelium lappaceum), and longan (Dimocarpus longan), by an undernourished child with low glycogen/glucose stores probably has the potential to result in toxic hypoglycemic syndrome.
                    Assessment of finger-prick blood glucose levels, which may be markedly depressed in children with severe Sapindaceae fruit poisoning, provides a rapid and convenient screening tool to identify suspected cases. Intravenous administration of glucose is the first line of treatment, along with serial monitoring of glucose, serum aminotransferase, and serum creatinine levels. Restoration of body fluid, electrolytes, glucose, and pH balance is the goal of supportive treatment.
                    Note added in proof. Subsequent to the submission of this letter, a description was published of recent outbreaks of unexplained acute hypoglycemic encephalopathy in young children in Muzaffarpur, Bihar, coinciding with local lychee harvests (6).

                    Peter S. Spencer , Valerie S. Palmer, and Rajarshi Mazumder
                    Author affiliations: Oregon Health & Science University, Portland, Oregon, USA (P.S. Spencer, V.S. Palmer); Legacy Health, Portland (R. Mazumder)

                    • Paireau J, Tuan NH, Lefran?ois R, Buckwalter MR, Nghia ND, Hien NT, Litchi-associated acute encephalitis in children, northern Vietnam, 2004?2009. Emerg Infect Dis. 2012;18:1817?24. DOIPubMed
                    • Gray DO, Fowden L. α-(Methylenecyclopropyl)glycine from Litchi seeds. Biochem J. 1962;82:385?9.PubMed
                    • Spencer PS. Hypoglycine. In: Spencer PS, Schaumburg HH, editors. Experimental and clinical neurotoxicology. 2nd ed. Oxford (NY); 2000. p. 669?72.
                    • John TJ, Das M. Acute encephalitis syndrome in children in Muzaffarpur: hypothesis of toxic origin. Curr Sci. 2014;106:1184?5.
                    • Centers for Disease Control and Prevention. Toxic hypoglycemic syndrome?Jamaica, 1989?1991. MMWR Morb Mortal Wkly Rep.1992;41:53?5.PubMed
                    • Shrivastava A, Srikantiah P, Kumar A, Bhushan G, Goel K, Kumar S, Outbreaks of unexplained neurologic illness?Muzaffarpur, India, 2013?2014.MMWR Morb Mortal Wkly Rep. 2015;64:49?53.PubMed
                    Suggested citation for this article: Spencer PS, Palmer VS, Mazumder R. Probable toxic cause for suspected lychee-linked viral encephalitis [letter]. Emerg Infect Dis. 2015 May [date cited].
                    DOI: 10.3201/eid2105.141650
                    Twitter: @RonanKelly13
                    The views expressed are mine alone and do not represent the views of my employer or any other person or organization.


                    • #11
                      Characterization of Japanese encephalitis virus (JEV) genotype III clinical isolates in northeast India

                      +Author Affiliations
                      • Arbovirology group, Entomology and Filariasis Division, Regional Medical Research Centre, ICMR, Northeast Region, P.O. Box 105, Dibrugarh-786001, Assam, India
                      • 1 Present address: Department of Biotechnology, Tocklai Tea Research Institute, TRA, Jorhat-785008, Assam, India
                      • Received March 20, 2015.
                      • Revision received May 19, 2015.
                      • Accepted May 19, 2015.


                      Background Japanese encephalitis virus (JEV) is one of the major etiological agents responsible for causing large numbers of acute encephalitis syndrome (AES) cases in the northeastern region of India. This study was carried out to establish and characterize the circulating strain of JEV in the region in order to understand the disease epidemiology.
                      Methods Virus isolation was attempted from 121 patients that presented with AES. Phylogenetic analysis was done using the Kimura-2-Parameter model based on envelope and pre-membrane gene sequence. A pathogenecity study was done in the Swiss albino mice model and assessed by Kaplan-Meier survival analysis.
                      Results The phylogenetic analysis of the two JEV isolates obtained placed them within genotype (G)III, where they form a subclade within the Vellore group of Indian JEV strains. Neutralization assays suggested similarity between the study isolates and prototype Vellore JEV strain P20778. Pathogenesis in mice suggested that the circulating GIII JEV strains were neuroinvasive.
                      Conclusions This study showed that a pathogenic GIII JEV strain was circulating in the northeastern region of India. This finding is important as it is contrary to the belief that GI is gradually replacing GIII as the dominant genotype in Asia. GenBank accession numbers: HQ270470, JQ434468, HQ246155,JX018170.


                      Twitter: @RonanKelly13
                      The views expressed are mine alone and do not represent the views of my employer or any other person or organization.


                      • #12
                        Epidemiological Investigation of an Outbreak of Acute Encephalitis Syndrome (AES) in Malda District of West Bengal, India

                        Background: An unusual outbreak of acute encephalitis syndrome (AES) with high case fatality was reported
                        from Kaliachak- I, II and III Blocks of Malda District of West Bengal in the month of June 2014 affecting 72 children
                        with 34 deaths. The purpose of this study was to investigate the outbreak in the light of epidemiological as well as
                        etiological determinants.

                        Methods: The investigating team collected clinical and epidemiological data from the cases admitted at Malda
                        Medical College and at the Kaliachak BPHC. Different clinical samples, (serum, CSF etc) collected from cases as
                        well as control population were screened for different pathological, biochemical and microbiological parameters.
                        Additionally, the CSF specimens were also processed for the isolation of viruses by inoculating in the chorio-allantoic
                        membrane (CAM) of embryonated chick eggs and intracerebral inoculation of suckling mice. Statistical methods
                        included calculation of proportions (percentages), different test of significance (t-test, chi square etc).

                        Results: All children were from age group of 9 months to 10 years (median=3, mean=3.73, SD=1.98) and
                        belonged to low socioeconomic background of litchi growing belt of Malda. Most of the cases were male (65%
                        approx). Case Fatality Rate was 47.2%. The main presenting features were sudden onset of convulsions (100%) in
                        the early hours of dawn followed by rapid progression to unconsciousness (100%) and decerebrate rigidity (47%).
                        Fever was present in around one third of cases. Hypoglycaemia and leucocytosis were two predominant features.
                        Clinical samples subjected to molecular and serological testing, were all found negative for known viruses causing
                        acute encephalitis. 3 out of 4 CSF samples produced demonstrable pocks in Chorio allantoic membrane of the
                        embryonated eggs although the pock count varied from 4- 22 per CAM. Significantly low blood glucose level was
                        found in the controls from litchi belt areas as compared to the controls of non-litchi belt areas of Malda.

                        Conclusion: The evidence gathered so far pointed towards a viral etiology although the causative virus
                        remained unidentified. Hypoglycaemia probably induced by litchi fruit might have aggravated the encephalitis rather
                        than actually causing it.


                        A Descriptive Study of Japanese Encephalitis in West Bengal, India, Based on Surveillance Data: Changing Pattern Observed in Recent Years
                        Dr. Debjit Chakraborty1
                        , Dr. Surajita Banerjee2
                        , Dr. Dipankar Maji3
                        , Dr. Tushar Kanti Dey4
                        Mr. Palash Mondal5
                        , Dr. Mausumi Basu*

                        Abstract: Japanese encephalitis (JE), commonly affects children and is a major cause of acute childhood
                        encephalopathy. Growth of population, intensified rice farming, pig rearing and lack of surveillance are the key factors
                        for transmission of the disease. Although various hospital and laboratory based studies have been conducted on
                        epidemiology of JE in various parts of India including West Bengal, still the need for further research to have a much
                        clear understanding of this disease epidemiology is beyond any question. The present study aimed at determining the
                        Sample Positivity Rate (SPR) and distribution (Time, Place, Person) of JE cases in West Bengal. This descriptive study
                        was conducted over 9 months periods (June 2012 – February 2013), based on surveillance data corresponding to years
                        2011& 2012, collected from different JE screening Sentinel Laboratories of West Bengal. Confirmation of JE was done
                        by IgM ELISA method. SPR was significantly higher for older age groups. Mean age of JE cases were significantly
                        higher in 2012. Cases were also found consistently in 2011-12 in districts of North Bengal such as Jalpaiguri, Dakshin
                        Dinajpur, Coochbehar etc. Two different peaks were observed in Epi Curve i.e. for northern part, during July - August
                        and for southern part, during October – November. JE has been found to be significantly affecting older age groups as
                        well as people of North Bengal districts of West Bengal in recent years. Also different seasonal pattern has been playing
                        role in transmission of JE in different parts of West Bengal.
                        Twitter: @RonanKelly13
                        The views expressed are mine alone and do not represent the views of my employer or any other person or organization.


                        • #13
                          Japanese Encephalitis - Global Status - Gideon
                          Twitter: @RonanKelly13
                          The views expressed are mine alone and do not represent the views of my employer or any other person or organization.


                          • #14
                            Arch Virol. 2015 Sep 11. [Epub ahead of print]
                            Phylogeographic analysis of Japanese encephalitis virus in India (1956-2012).
                            Cherian SS1, Walimbe AM2.
                            Author information
                            Japanese encephalitis virus (JEV) isolates from India phylogenetically belong to two genotypes, III and I. We used envelope gene sequences from GenBank, representing different states of India and other countries, to study the spatiotemporal transmission histories of these two JEV genotypes separately. Genotype III was found to have been successively introduced in the 1930s, 1950s and 1960s, followed by genotype I twice around 2003-2006. Changes in JEV disease patterns in India over the last five decades could thus be attributed to multiple introductions of JEV strains from neighboring Asian countries along with increased transmission potential due to altered ecological settings.
                            PMID: 26362532 [PubMed - as supplied by publisher]
                            Twitter: @RonanKelly13
                            The views expressed are mine alone and do not represent the views of my employer or any other person or organization.


                            • #15
                              Public Health Laboratory Surveillance and Diagnosis of Japanese
                              Encephalitis: Time to Revisit

                              From #Public Health Foundation of India, New Delhi; *Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow, Uttar
                              Pradesh; and University College of Medical Sciences, Dilshad Garden, Delhi; India.

                              Objective: We assessed detection of recent Japanese encephalitis virus infection using
                              recommended strategy.
                              Methods: Cross-sectional community-based study conducted in 12 villages in Kushinagar,
                              Uttar-Pradesh, India in 2012-13. Recent infection with Japanese encephalitis virus in 239
                              healthy children aged 1-15 year was detected using a combination of serology and
                              molecular methods.
                              Results: 24 (10%) children showed recent infection; 2 by serology and 22 by molecular
                              method. Symptomatic cases were estimated as 626 in Kushinagar against reported 139 in all
                              age groups across the state.

                              Conclusion: Lower positivity using recommended serology suggests major gap in existing
                              surveillance and diagnostic protocols and estimation of burden of Japanese encephalitis.
                              Keywords: Japanese encephalitis, Laboratory diagnosis, Surveillance.

                              Correspondence to: Dr Manish Kakkar, Public Health Foundation of India, Plot 47, Sector 44, Institutional Area, Gurgaon 122 002, Haryana, India. Received: April 23, 2015; Initial review: June 01, 2015; Accepted: November 09, 2015

                              We estimated 626 symptomatic JE cases in
                              Kushinagar in 2012, while the state of UP reported 139
                              confirmed cases during the same transmission season.
                              Nationally, number of confirmed JE cases (reported)
                              stood at 745 [15]. This extrapolation needs further
                              validation through wider studies. It highlights potentially
                              large undiagnosed and/or unreported burden of JE,
                              questioning the recently reported declining trend of JE as
                              a cause of AES in Gorakhpur region [4,5].

                              Findings from the study highlight the possibility of a
                              large gap in estimation and understanding of JE burden in
                              Northern India. The inadequately sensitive diagnostics
                              currently in use needs urgent attention, along with
                              revisiting of recommended laboratory diagnosis and
                              surveillance strategy. In the absence of true estimates and
                              presence of alternate etiology narratives, public health
                              programs run the risk of being sub-optimally informed, or
                              at times, misinformed.

                              Twitter: @RonanKelly13
                              The views expressed are mine alone and do not represent the views of my employer or any other person or organization.