Ronan Kelly
Retired 2020
Re: Whose failure? Encephalitis kills 50,000 in 30 years
Brazilian Journal of Infectious Diseases
Print version ISSN 1413-8670
Braz J Infect Dis vol.16 no.6 Salvador Nov./Dec. 2012
http://dx.doi.org/10.1590/S1413-86702012000600011
Japanese encephalitis: a review of the Indian perspective
Sarika Tiwari; Rishi Kumar Singh; Ruchi Tiwari; Tapan N. Dhole*
Department of Microbiology, Sanjay Gandhi Post Graduate Institute of Medical Sciences, Uttar Pradesh, India
ABSTRACT
Japanese encephalitis virus (JEV) causes Japanese encephalitis, which is a leading form of viral encephalitis in Asia, with around 50,000 cases and 10,000 deaths per year in children below 15 years of age. The JEV has shown a tendency to extend to other geographic regions. Case fatality averages 30% and a high percentage of the survivors are left with permanent neuropsychiatric sequelae. Currently, there is no cure for JEV, and treatment is mainly supportive. Patients are not infectious, but should avoid further mosquito bites. A number of antiviral agents have been investigated; however, none of these have convincingly been shown to improve the outcome of JEV. In this review, the current knowledge of the epidemiology and the pathogenesis of this deadly disease have been summarized.
Introduction
Japanese encephalitis (JE) is a common mosquito borne flaviviral encephalitis. It is one of the leading forms of viral encephalitis worldwide, mostly prevalent in eastern and southern Asia, covering a region with a population of over three billion.1 Most infections of JE are asymptomatic, but if clinical illness develops, it causes significant morbidity and mortality. Though underreported, JE causes an estimated 50,000 cases and 15,000 deaths annually.2 JE is a disease of public health importance because of its epidemic potential and high fatality rate. In endemic areas, the highest age-specific attack rates occur in children of 3 to 6 years of age.3,4 Approximately one third of patients die, and half of the survivors suffer severe neuropsychiatric sequelae from the disease.5
Japanese encephalitis virus (JEV) belongs to the family flaviviridae and genus Flavivirus.6 It is a single stranded, positive-sense polarity RNA genome of approximately 11 kb in length. The virion of JEV contains three structural proteins - nucleocapsid or core protein (C), non-glycosylated membrane protein (M), and glycosylated envelope protein (E), as well as seven non-structural (NS) proteins - NS1, NS2A, NS2B, NS3, NS4A, NS4B, and NS.7 J EV exists in a zoonotic cycle between mosquitoes and pigs and/or water birds. This study reviewed JEV literature from 2000 to 2010, outlining the Indian scenario, clinical depictions, diagnosis, and the prevention of this deadly disease.
Historical perspective
The first outbreak of encephalitis attributed to JEV was reported in Japan in 1871. Major epidemics have been reported about every ten years; in 1924, over 6,000 cases were documented in a severe epidemic in Japan.8 In 1935, the prototype Nakayama strain was isolated from the brain of a patient suffering from encephalitis. Thereafter, the virus had been classified with other flaviviruses as a group B arbovirus in the family Togaviridae, Originally the term "type B" encephalitis was used to distinguish this summer epidemic from von Economo's lethargica/sleepy sickness, commonly known as type A encephalitis,5 which occurs in winter with a different clinical presentation. Later on, the designation "type B" was abandoned, and in 1985, JEV was designated under a separate family Flaviviridae, as a member of genus Flavivirus.9 The genus Flavivirus has been named after the prototype yellow fever virus (from the Latin word flavi,), and is comprised of 70 small, enveloped viruses with single stranded positive-sense RNA.5
Epidemiological features
Global outlook
Japanese encephalitis is one of the most important forms of epidemic and sporadic encephalitis in the tropical regions of Asia, including Japan, China, Taiwan, Korea, Philippines, all of Southeastern Asia, and India; however, related neurotropic viruses are spread across the globe.10 Countries with proven epidemics of JE include India, Pakistan, Nepal, Sri Lanka, Burma, Laos, Vietnam, Malaysia, Singapore, Philippines, Indonesia, China, maritime Siberia, Korea, and Japan.11 In the past 50 years, the geographic areas affected by JEV have expanded (Fig. 1). Epidemic activity in Northern India, Central India, and Nepal has increased since the early 1970s. In the 1990s, the virus continued to spread in Pakistan,12 in the Kath mandu valley of Nepal,13 and also in continental Australia.14 JE is primarily found in Southeast Asian countries. Three epidemiological regions can be distinguished. First, the endemic region composed of Southern India, Southern Vietnam, Southern Thailand, the Philippines, Malaysia, and Indonesia. Secondly, the intermediary subtropical region, which includes Northern India, Nepal, North and Central Burma, Northern Thailand, Northern Vietnam, Southern China, and Bangladesh. Thirdly, the temperate epidemic region, spanning Northern China, Korea, Japan, Taiwan, and the southern extremities of Russia. Transmission is variable, and is coupled with environmental temperature. During winter, mosquitoes are inactive, but huge epidemics can happen during summer and autumn. The geographical area of this disease is showing a trend towards expansion. Postulated explanations are bird migration, certain irrigation projects, animal smuggling, and global warming. Development of rice plantations is theoretically foreseeable in other regions (Pakistan, Afghanistan, Nile Valley, Madagascar, and Oriental Africa), creating a favorable environment for further vector proliferation.15
Problem in India
In India, epidemics of JE are reported from many parts of the country, and it is considered a major pediatric problem. The first recognition of JE based on serological surveys was in 1955, in Tamil Nadu, India.16 A total of approximately 65 cases were reported between 1955 and 1966 in Southern India.17 Subsequent surveys carried out by the National Institute of Virology of Pune indicated that approximately half of the population in Southern India has neutralizing antibodies to the virus. Since 1955, many major outbreaks in different parts of the country have been reported. A major outbreak resulting in a 42.6% fatality rate was reported in the Bankura District of West Bengal in 1973. Subsequently, the disease spread to other states and caused a series of outbreaks in different parts of the country. In 1978, cases were reported from 21 states and union territories.15 In Uttar Pradesh, the first major JE epidemic occurred in Gorakhpur in 1978, with 1,002 cases and 297 deaths reported. Many outbreaks were reported in Gorakhpur after the 1978 JE outbreak, with varying intensity and magnitude. Since 1978 to 2005, this encephalitis has taken more than 10,000 lives in the state.18 The 2005 epidemic surpassed all previous reported outbreaks in the country. In that year, Uttar Pradesh faced a devastating outbreak of JE, mostly confined to Gorakhpur, with 6,061 cases and 1,500 deaths; another outbreak occurred in 2006, with 2,320 cases and 528 deaths. Similarly, JE cases in Uttar Pradesh were confined predominantly to Gorakhpur during 2007, with 3,024 cases and 645 deaths,18 and then onwards till 2007 there have been 103,389 reported cases in India, and 33,729 deaths.19 Approximately 597,542,000 people in India live in JE-endemic regions, and 1,500 to 4,000 cases are reported every year.20 These figures are based on total reported cases; it is possible that many cases are unreported and hence the actual magnitude of the threat of JE may be considerably higher, both in the Indian and in the global context. JE incidence during the past few years is given in Table 1.21 The trend of JE suggests that the problem in Northern India is escalating, and larger epidemics may occur in the future.22
Vector and transmission
The JEV is transmitted to vertebrates by mosquitoes. Mosquito transmission was suspected during the early 1930s; in 1938, Mitamura et al. reported isolation from Culex tritaeniorynchus.23 The ecology of JEV has come from various studies carried out in Japan by Scherer et al.,24 and JEV ecology has been the subject of several reviews.11,25,26 Many species of Culex mosquitoes can transmit JE. For Southern Asia, Eastern Asia, and Southeastern Asia, the main vector of JE is C. tritaeniorhynchus. For Northern Australia, the main vector is C. annulirostris. However, various other secondary vectors may be important. Indian studies in particular have revealed a number of secondary vectors, including Mansonia indiana, C. pseudovishnui, C. whitmorei, C. gelidus, C. epidesmus, Anopheles subpictus, A. peditaeniatus, and M. uniform.27 The natural cycle of JE virus in Asia involves water birds and Culex mosquitoes. However, unlike many other mosquito-borne diseases, an amplifying host is important in the epidemiology of human JE. In Asia, pigs are considered to be the most important amplifying host, providing a link to humans through their proximity to housing.28 The life cycle of the virus is illustrated in Fig. 2. There are two epidemiological patterns of transmission: an endemic pattern in tropical areas with viral circulation in most months of the year, but with a broad seasonal peak, probably resulting from irrigation practices; and an epidemic pattern in more temperate areas with clear summer seasonality.11,29
Mortality and morbidity
JE's mortality rate is approximately 25% to 30%.1,29 Although intensive care support can reduce the mortality rate, patients often suffer significant long-term morbidity. Some effects, such as learning difficulties and behavioral problems, can be subtle and may remain undetected for several years.30,31 50% of those who recover suffer from neurological deficit.32 Over the past 60 years, it has been estimated that JEV has infected more than ten million people, of whom three million died and four million suffered long-term disabilities.29
...
continues in full at; http://www.scielo.br/scielo.php?scr...1413-86702012000600011&lng=en&nrm=iso&tlng=en
Brazilian Journal of Infectious Diseases
Print version ISSN 1413-8670
Braz J Infect Dis vol.16 no.6 Salvador Nov./Dec. 2012
http://dx.doi.org/10.1590/S1413-86702012000600011
Japanese encephalitis: a review of the Indian perspective
Sarika Tiwari; Rishi Kumar Singh; Ruchi Tiwari; Tapan N. Dhole*
Department of Microbiology, Sanjay Gandhi Post Graduate Institute of Medical Sciences, Uttar Pradesh, India
ABSTRACT
Japanese encephalitis virus (JEV) causes Japanese encephalitis, which is a leading form of viral encephalitis in Asia, with around 50,000 cases and 10,000 deaths per year in children below 15 years of age. The JEV has shown a tendency to extend to other geographic regions. Case fatality averages 30% and a high percentage of the survivors are left with permanent neuropsychiatric sequelae. Currently, there is no cure for JEV, and treatment is mainly supportive. Patients are not infectious, but should avoid further mosquito bites. A number of antiviral agents have been investigated; however, none of these have convincingly been shown to improve the outcome of JEV. In this review, the current knowledge of the epidemiology and the pathogenesis of this deadly disease have been summarized.
Introduction
Japanese encephalitis (JE) is a common mosquito borne flaviviral encephalitis. It is one of the leading forms of viral encephalitis worldwide, mostly prevalent in eastern and southern Asia, covering a region with a population of over three billion.1 Most infections of JE are asymptomatic, but if clinical illness develops, it causes significant morbidity and mortality. Though underreported, JE causes an estimated 50,000 cases and 15,000 deaths annually.2 JE is a disease of public health importance because of its epidemic potential and high fatality rate. In endemic areas, the highest age-specific attack rates occur in children of 3 to 6 years of age.3,4 Approximately one third of patients die, and half of the survivors suffer severe neuropsychiatric sequelae from the disease.5
Japanese encephalitis virus (JEV) belongs to the family flaviviridae and genus Flavivirus.6 It is a single stranded, positive-sense polarity RNA genome of approximately 11 kb in length. The virion of JEV contains three structural proteins - nucleocapsid or core protein (C), non-glycosylated membrane protein (M), and glycosylated envelope protein (E), as well as seven non-structural (NS) proteins - NS1, NS2A, NS2B, NS3, NS4A, NS4B, and NS.7 J EV exists in a zoonotic cycle between mosquitoes and pigs and/or water birds. This study reviewed JEV literature from 2000 to 2010, outlining the Indian scenario, clinical depictions, diagnosis, and the prevention of this deadly disease.
Historical perspective
The first outbreak of encephalitis attributed to JEV was reported in Japan in 1871. Major epidemics have been reported about every ten years; in 1924, over 6,000 cases were documented in a severe epidemic in Japan.8 In 1935, the prototype Nakayama strain was isolated from the brain of a patient suffering from encephalitis. Thereafter, the virus had been classified with other flaviviruses as a group B arbovirus in the family Togaviridae, Originally the term "type B" encephalitis was used to distinguish this summer epidemic from von Economo's lethargica/sleepy sickness, commonly known as type A encephalitis,5 which occurs in winter with a different clinical presentation. Later on, the designation "type B" was abandoned, and in 1985, JEV was designated under a separate family Flaviviridae, as a member of genus Flavivirus.9 The genus Flavivirus has been named after the prototype yellow fever virus (from the Latin word flavi,), and is comprised of 70 small, enveloped viruses with single stranded positive-sense RNA.5
Epidemiological features
Global outlook
Japanese encephalitis is one of the most important forms of epidemic and sporadic encephalitis in the tropical regions of Asia, including Japan, China, Taiwan, Korea, Philippines, all of Southeastern Asia, and India; however, related neurotropic viruses are spread across the globe.10 Countries with proven epidemics of JE include India, Pakistan, Nepal, Sri Lanka, Burma, Laos, Vietnam, Malaysia, Singapore, Philippines, Indonesia, China, maritime Siberia, Korea, and Japan.11 In the past 50 years, the geographic areas affected by JEV have expanded (Fig. 1). Epidemic activity in Northern India, Central India, and Nepal has increased since the early 1970s. In the 1990s, the virus continued to spread in Pakistan,12 in the Kath mandu valley of Nepal,13 and also in continental Australia.14 JE is primarily found in Southeast Asian countries. Three epidemiological regions can be distinguished. First, the endemic region composed of Southern India, Southern Vietnam, Southern Thailand, the Philippines, Malaysia, and Indonesia. Secondly, the intermediary subtropical region, which includes Northern India, Nepal, North and Central Burma, Northern Thailand, Northern Vietnam, Southern China, and Bangladesh. Thirdly, the temperate epidemic region, spanning Northern China, Korea, Japan, Taiwan, and the southern extremities of Russia. Transmission is variable, and is coupled with environmental temperature. During winter, mosquitoes are inactive, but huge epidemics can happen during summer and autumn. The geographical area of this disease is showing a trend towards expansion. Postulated explanations are bird migration, certain irrigation projects, animal smuggling, and global warming. Development of rice plantations is theoretically foreseeable in other regions (Pakistan, Afghanistan, Nile Valley, Madagascar, and Oriental Africa), creating a favorable environment for further vector proliferation.15
Problem in India
In India, epidemics of JE are reported from many parts of the country, and it is considered a major pediatric problem. The first recognition of JE based on serological surveys was in 1955, in Tamil Nadu, India.16 A total of approximately 65 cases were reported between 1955 and 1966 in Southern India.17 Subsequent surveys carried out by the National Institute of Virology of Pune indicated that approximately half of the population in Southern India has neutralizing antibodies to the virus. Since 1955, many major outbreaks in different parts of the country have been reported. A major outbreak resulting in a 42.6% fatality rate was reported in the Bankura District of West Bengal in 1973. Subsequently, the disease spread to other states and caused a series of outbreaks in different parts of the country. In 1978, cases were reported from 21 states and union territories.15 In Uttar Pradesh, the first major JE epidemic occurred in Gorakhpur in 1978, with 1,002 cases and 297 deaths reported. Many outbreaks were reported in Gorakhpur after the 1978 JE outbreak, with varying intensity and magnitude. Since 1978 to 2005, this encephalitis has taken more than 10,000 lives in the state.18 The 2005 epidemic surpassed all previous reported outbreaks in the country. In that year, Uttar Pradesh faced a devastating outbreak of JE, mostly confined to Gorakhpur, with 6,061 cases and 1,500 deaths; another outbreak occurred in 2006, with 2,320 cases and 528 deaths. Similarly, JE cases in Uttar Pradesh were confined predominantly to Gorakhpur during 2007, with 3,024 cases and 645 deaths,18 and then onwards till 2007 there have been 103,389 reported cases in India, and 33,729 deaths.19 Approximately 597,542,000 people in India live in JE-endemic regions, and 1,500 to 4,000 cases are reported every year.20 These figures are based on total reported cases; it is possible that many cases are unreported and hence the actual magnitude of the threat of JE may be considerably higher, both in the Indian and in the global context. JE incidence during the past few years is given in Table 1.21 The trend of JE suggests that the problem in Northern India is escalating, and larger epidemics may occur in the future.22
Vector and transmission
The JEV is transmitted to vertebrates by mosquitoes. Mosquito transmission was suspected during the early 1930s; in 1938, Mitamura et al. reported isolation from Culex tritaeniorynchus.23 The ecology of JEV has come from various studies carried out in Japan by Scherer et al.,24 and JEV ecology has been the subject of several reviews.11,25,26 Many species of Culex mosquitoes can transmit JE. For Southern Asia, Eastern Asia, and Southeastern Asia, the main vector of JE is C. tritaeniorhynchus. For Northern Australia, the main vector is C. annulirostris. However, various other secondary vectors may be important. Indian studies in particular have revealed a number of secondary vectors, including Mansonia indiana, C. pseudovishnui, C. whitmorei, C. gelidus, C. epidesmus, Anopheles subpictus, A. peditaeniatus, and M. uniform.27 The natural cycle of JE virus in Asia involves water birds and Culex mosquitoes. However, unlike many other mosquito-borne diseases, an amplifying host is important in the epidemiology of human JE. In Asia, pigs are considered to be the most important amplifying host, providing a link to humans through their proximity to housing.28 The life cycle of the virus is illustrated in Fig. 2. There are two epidemiological patterns of transmission: an endemic pattern in tropical areas with viral circulation in most months of the year, but with a broad seasonal peak, probably resulting from irrigation practices; and an epidemic pattern in more temperate areas with clear summer seasonality.11,29
Mortality and morbidity
JE's mortality rate is approximately 25% to 30%.1,29 Although intensive care support can reduce the mortality rate, patients often suffer significant long-term morbidity. Some effects, such as learning difficulties and behavioral problems, can be subtle and may remain undetected for several years.30,31 50% of those who recover suffer from neurological deficit.32 Over the past 60 years, it has been estimated that JEV has infected more than ten million people, of whom three million died and four million suffered long-term disabilities.29
...
continues in full at; http://www.scielo.br/scielo.php?scr...1413-86702012000600011&lng=en&nrm=iso&tlng=en
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