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Chandipura virus, encephalitis, and epidemic brain attack in India
Correspondence
Chandipura virus, encephalitis, and epidemic brain attack in India The report by B Rao and colleagues (Sept 4, p 869)1 details an outbreak of encephalitis associated with Chandipura virus in children in Andhra Pradesh, India, in June– September, 2003. However, in an analysis of the outbreak,2 I note the illness to be encephalopathy, not encephalitis. Typically, a rural child aged 2–15 years would go to bed normally, but wake up ill in the early hours of the next morning. Vomiting was followed by loss of consciousness that deteriorated to a deep coma and decerebrate posturing within several hours. Cerebrospinal fluid was clear, under pressure, and without pleocytosis. Many children died within 48–72 h of onset of symptoms. Early treatment with mannitol to reduce brain oedema was life saving. Also, in a report in the Journal of Pediatric Neurology,3 the epidemic is not reported as encephalitis nor is the role of Chandipura virus confirmed. The authors of both reports1,3 have done excellent work in their respective specialties—virology and neurology. The virological studies established Chandipura virus infection in some children, apparently leading to the conclusion that it caused the outbreak. A brain disease caused by viral infection ought to be called encephalitis, hence the outbreak was described as encephalitis. The detailed neurological findings and erudite argument by P N Rao and colleagues,3 however, convincingly establish the outbreak as one caused by an acute catastrophic event in the brain. The illness mimics Reye’s syndrome, with gross brain oedema, but there are important differences.3 The site of the lesion was the area supplied by the middle cerebral artery.3 There was no clinical evidence of invasion by a pathogen. The nature of the arterial www.thelancet.com Vol 364 December 18/25, 2004
pathology is likely to be spasm or transient obstruction due to vasculitis, rather than thromboembolism.3 That such a disease could arise as an epidemic is new information.4 If Chandipura virus is the cause, the disease is mediated via vasculitis, not encephalitis.3 Otherwise another infectious agent, probably viral, might be involved.3,4 Infection is invoked to explain an epidemic.3,4 Outbreaks of acute encephalopathy with high case fatality reminiscent of this outbreak have been reported repeatedly in several northern Indian towns and villages.1 To assume an illness is infectious just because it affects a group of people could be misleading. Sriramachari5 has suggested the clinical features of the recurrent encephalopathy outbreaks in northern India could be due to high environmental temperature, with or without secondary factors. He believes that the heat-related encephalopathy has all the brain features of Reye’s syndrome. B Rao and colleagues1 note that the summer temperature in the outbreak region was 36–49ºC. Both reports1,3 state that fever was a consistent feature. Some children indeed had hyperpyrexia.1 Cases were widely scattered. The subject is well worth further research. Outbreak investigations are incomplete without the basics of epidemiology. Case definition should be made and applied. Epidemiological links between cases should be ascertained, and risk factors explored. India is not short of competence in medicine and research, but epidemiology skills, training, and field application are inadequate.
T Jacob John [email protected] 439 Civil Supplies Godown Lane, Kamalakshipuram, Vellore, TN, 632 002, India 1
2
Rao BL, Basu A, Wairagkar NS, et al. A large outbreak of acute encephalitis with high fatality rate in children in Andhra Pradesh, India, in 2003, associated with Chandipura virus. Lancet 2004; 364: 869–74. John TJ. Outbreaks of killer brain disease: mystery or missed diagnosis? Indian Pediatr 2003; 40: 863–69.
3
4
5
Rao PN, Kumar PA, Rao TA, et al. Role of Chandipura virus in an “epidemic brain attack” in Andhra Pradesh, India. J Pediatr Neurol 2004; 2: 131–43. Ismail HIHM. Viruses and “epidemic brain attack”: new agents, new challenges. J Pediatr Neurol 2004; 2: 117–19. Sriramachari S. Heat hyperpyrexia: time to act. Indian J Med Res 2004; 119: vii–x.
Author’s reply T Jacob John concludes in his letter that the outbreak we describe is of acute encephalopathy—eg, Reye’s syndrome. However, minimum criteria set by the Centers for Disease Control and Prevention1 for this disorder are not met. 11 magnetic resonanace imaging scans of patients from Karimnagar, Andhra Pradesh, showed hypodensity indicative of damage in the cortical region and in the frontal and temporal lobes more frequently than in the parietal and occipital lobes. Young mice, infected with Chandipura virus intra-peritoneally, developed CNS lesions, with necrosis particularly affecting neurons and ependymal cells.2 In our experiments in animals (unpublished data), we also observed areas of mononucleocyte infiltration and accumulation of inflammatory cells in the brain after challenge with Chandipura virus. Furthermore, clinical and biochemical examination of patients indicated no liver dysfunction—eg, liver not palpable, and serum alanine aminotransferase, aspartate aminotransferase, and ammonia concentrations within the normal range. As stated in our article, there was a strong association between Chandipura virus and disease. All cases had acute onset of fever. P N Rao and colleagues3 have attempted to negate the role of Chandipura virus in the outbreak by analysing 55 cases in two groups— 28 individuals positive for Chandipura virus, and 27 negative. They note that clinical findings in the positive group were no different to those in the negative group, and conclude that the virus therefore had no role in encephalitis. However, when dealing with arboviral diseases laboratory confirmation of samples obtained during investigations
e-mail submissions to [email protected]
2175
Chandipura virus, encephalitis, and epidemic brain attack in India The report by B Rao and colleagues (Sept 4, p 869)1 details an outbreak of encephalitis associated with Chandipura virus in children in Andhra Pradesh, India, in June– September, 2003. However, in an analysis of the outbreak,2 I note the illness to be encephalopathy, not encephalitis. Typically, a rural child aged 2–15 years would go to bed normally, but wake up ill in the early hours of the next morning. Vomiting was followed by loss of consciousness that deteriorated to a deep coma and decerebrate posturing within several hours. Cerebrospinal fluid was clear, under pressure, and without pleocytosis. Many children died within 48–72 h of onset of symptoms. Early treatment with mannitol to reduce brain oedema was life saving. Also, in a report in the Journal of Pediatric Neurology,3 the epidemic is not reported as encephalitis nor is the role of Chandipura virus confirmed. The authors of both reports1,3 have done excellent work in their respective specialties—virology and neurology. The virological studies established Chandipura virus infection in some children, apparently leading to the conclusion that it caused the outbreak. A brain disease caused by viral infection ought to be called encephalitis, hence the outbreak was described as encephalitis. The detailed neurological findings and erudite argument by P N Rao and colleagues,3 however, convincingly establish the outbreak as one caused by an acute catastrophic event in the brain. The illness mimics Reye’s syndrome, with gross brain oedema, but there are important differences.3 The site of the lesion was the area supplied by the middle cerebral artery.3 There was no clinical evidence of invasion by a pathogen. The nature of the arterial www.thelancet.com Vol 364 December 18/25, 2004
pathology is likely to be spasm or transient obstruction due to vasculitis, rather than thromboembolism.3 That such a disease could arise as an epidemic is new information.4 If Chandipura virus is the cause, the disease is mediated via vasculitis, not encephalitis.3 Otherwise another infectious agent, probably viral, might be involved.3,4 Infection is invoked to explain an epidemic.3,4 Outbreaks of acute encephalopathy with high case fatality reminiscent of this outbreak have been reported repeatedly in several northern Indian towns and villages.1 To assume an illness is infectious just because it affects a group of people could be misleading. Sriramachari5 has suggested the clinical features of the recurrent encephalopathy outbreaks in northern India could be due to high environmental temperature, with or without secondary factors. He believes that the heat-related encephalopathy has all the brain features of Reye’s syndrome. B Rao and colleagues1 note that the summer temperature in the outbreak region was 36–49ºC. Both reports1,3 state that fever was a consistent feature. Some children indeed had hyperpyrexia.1 Cases were widely scattered. The subject is well worth further research. Outbreak investigations are incomplete without the basics of epidemiology. Case definition should be made and applied. Epidemiological links between cases should be ascertained, and risk factors explored. India is not short of competence in medicine and research, but epidemiology skills, training, and field application are inadequate.
T Jacob John [email protected] 439 Civil Supplies Godown Lane, Kamalakshipuram, Vellore, TN, 632 002, India 1
2
Rao BL, Basu A, Wairagkar NS, et al. A large outbreak of acute encephalitis with high fatality rate in children in Andhra Pradesh, India, in 2003, associated with Chandipura virus. Lancet 2004; 364: 869–74. John TJ. Outbreaks of killer brain disease: mystery or missed diagnosis? Indian Pediatr 2003; 40: 863–69.
3
4
5
Rao PN, Kumar PA, Rao TA, et al. Role of Chandipura virus in an “epidemic brain attack” in Andhra Pradesh, India. J Pediatr Neurol 2004; 2: 131–43. Ismail HIHM. Viruses and “epidemic brain attack”: new agents, new challenges. J Pediatr Neurol 2004; 2: 117–19. Sriramachari S. Heat hyperpyrexia: time to act. Indian J Med Res 2004; 119: vii–x.
Author’s reply T Jacob John concludes in his letter that the outbreak we describe is of acute encephalopathy—eg, Reye’s syndrome. However, minimum criteria set by the Centers for Disease Control and Prevention1 for this disorder are not met. 11 magnetic resonanace imaging scans of patients from Karimnagar, Andhra Pradesh, showed hypodensity indicative of damage in the cortical region and in the frontal and temporal lobes more frequently than in the parietal and occipital lobes. Young mice, infected with Chandipura virus intra-peritoneally, developed CNS lesions, with necrosis particularly affecting neurons and ependymal cells.2 In our experiments in animals (unpublished data), we also observed areas of mononucleocyte infiltration and accumulation of inflammatory cells in the brain after challenge with Chandipura virus. Furthermore, clinical and biochemical examination of patients indicated no liver dysfunction—eg, liver not palpable, and serum alanine aminotransferase, aspartate aminotransferase, and ammonia concentrations within the normal range. As stated in our article, there was a strong association between Chandipura virus and disease. All cases had acute onset of fever. P N Rao and colleagues3 have attempted to negate the role of Chandipura virus in the outbreak by analysing 55 cases in two groups— 28 individuals positive for Chandipura virus, and 27 negative. They note that clinical findings in the positive group were no different to those in the negative group, and conclude that the virus therefore had no role in encephalitis. However, when dealing with arboviral diseases laboratory confirmation of samples obtained during investigations
e-mail submissions to [email protected]
2175