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Bilal Sami Al-Moshaigah
Neuropathogenic Viruses
Learning Objectives
Neuropathogenic Viruses
Eastern Equine Encephalitis virus
Western Equine Encephalitis virus
West Nile virus
Main properties Pathogenic mechanism Clinical significance Laboratory diagnosis
Introduction
Arbovirus Acronym for arthropod-borne virus and highlights the fact that these viruses are
transmitted by arthropods
Primarily mosquitoes and ticks
Blood-filled proboscis and the abdomen engorged with blood
It is a collective name for a large group of diverse viruses, more than 600
Important Properties
Most arboviruses are classified in three families, namely, Togaviruses,
Flaviviruses, and bunyaviruses
Important Properties
Togaviridae Flavivirdae
 Icosahedral nucleocapsid
 Enveloped
 Single-stranded
 Positive-polarity RNA genome
Alphaviruses
70 nm in diameter 40 to 50 nm in diameter
Flaviviruses
Family
Genus
West Nile virus
 EEEV
 WEEV
Transmission
Humans are dead-end hosts ?
Must be present in the bloodstream of the
vertebrate host (viremia) in sufficiently high titer
Extrinsic incubation period, must pass before
the virus has replicated sufficiently for the saliva
to contain enough virus
Only the female ?
Only she requires a blood meal in
order for progeny to be produced
Ranges from 7 to 14 days
Some are transmitted by vertical “transovarian”
passage from the mother tick to her offspring.
Value?
Pathogenic mechanism
On biting a host, the mosquito regurgitates virus-containing saliva
into the bloodstream
female
Circulates freely in the host’s plasma and Comes
into contact with susceptible target cell
Flulike symptoms
The virus gains access to the brain by infecting
the endothelial cells lining the small vessels of
the brain or the choroid plexus
Clinical significance
Most human arboviral infections are asymptomatic
A minority of infections cause neuroinvasive disease, such as encephalitis and meningitis
The clinical picture usually fits one of three categories
Encephalitis
Hemorrhagic fever
Fever with myalgias, arthralgias, and nonhemorrhagic rash
The pathogenesis of these diseases involves not only the cytocidal effect of the
virus, but also, in some, a prominent immunopathologic component
Eastern equine encephalitis virus
Western equine encephalitis virus
West Nile virus
Immunity following the
infection is lifelong
Eastern Equine Encephalitis Virus
Causes the most severe disease and is associated with the highest fatality rate (approximately 50%)
Encephalitis
Characterized by the sudden onset of :
 Severe headache
 Nausea and vomiting
 Fever
 Changes in mental status
 Rapidly progressive downhill course with nuchal rigidity
 Seizures
 Coma
The diagnosis is made by either isolating the virus or demonstrating a rise in antibody titer
Atlantic and Gulf states
If the patient survives, the central nervous system sequelae are usually severe occur in one third of survivors
The disease does not occur in the winter ?
Western Equine Encephalitis Virus
Causes disease more frequently than does EEE virus
The virus is transmitted primarily by Culex mosquitoes among the wild bird
The clinical picture of WEE virus infection is similar but less severe, the fatality rate is roughly 2%.
The diagnosis is made by isolating the virus or observing a rise in antibody titer
West of Mississippi
Sequelae are less common
Wild birds
West Nile Virus
The clinical picture is one of encephalitis with or without signs of meningitis, typically in a person over 60
years of age
Less than 1% of those infected have symptomatic disease, the mortality rate is roughly 12%.
The laboratory diagnosis can be made by either isolation of the virus from brain tissue, blood, or spinal
fluid or by detection of antibodies in spinal fluid or blood and PCR-based assays are also available.
Detection of IgM antibody is the most efficient diagnostic method
Endemic in Africa; Widespread in United States
The most common cause of neuroinvasive (encephalitis, meningitis) arboviral disease
Laboratory
diagnosis
Clinical significance
Main properties
Virus
isolating the virus
or demonstrating a
rise in antibody
titer
 The majority of infections are
subclinical
 May cause acute encephalitis
(most severe disease)
 Family Togaviridae
 Genus Alphavirus
 Enveloped, icosahedral viruses
 Positive sense
 Single-stranded RNA genome
 70 nm in diameter
 Transmitted to humans by mosquitoes
Eastern Equine
Encephalitis virus
 The majority of infections are
subclinical
 May cause acute encephalitis
(less severe disease)
Western Equine
Encephalitis virus
Isolation of the
virus from brain
tissue, blood, or
spinal fluid or by
detection of
antibodies in spinal
fluid or blood and
PCR-based assays
are also available
 Usually self-limited illness
 May result in aseptic meningitis or
meningoencephalitis, especially in
the elderly
 Family Flaviviridae
 Genus flavivirus
 Enveloped, icosahedral viruses
 Positive sense
 Single stranded RNA genome
 40 to 50 nm in diameter
 Transmitted to humans by mosquito
West Nile virus
Any Question
Reference
Warren E. Levinson (2014) Review of Medical Microbiology and Immunology, 13th edn., New
York, United States: McGraw-Hill Education - Europe.
Neal R. Chamberlain ( 2009) Medical Microbiology: The Big Picture, New York, United States:
McGraw-Hill Education - Europe.
Richard A. Harvey , Cynthia Nau Cornelissen (2012) Lippincott Illustrated Reviews:
Microbiology, Third edn., Philadelphia, United States: Lippincott Williams and Wilkins.
Neuropathogen

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Neuropathogen

  • 2. Learning Objectives Neuropathogenic Viruses Eastern Equine Encephalitis virus Western Equine Encephalitis virus West Nile virus Main properties Pathogenic mechanism Clinical significance Laboratory diagnosis
  • 3. Introduction Arbovirus Acronym for arthropod-borne virus and highlights the fact that these viruses are transmitted by arthropods Primarily mosquitoes and ticks Blood-filled proboscis and the abdomen engorged with blood It is a collective name for a large group of diverse viruses, more than 600 Important Properties Most arboviruses are classified in three families, namely, Togaviruses, Flaviviruses, and bunyaviruses
  • 4. Important Properties Togaviridae Flavivirdae  Icosahedral nucleocapsid  Enveloped  Single-stranded  Positive-polarity RNA genome Alphaviruses 70 nm in diameter 40 to 50 nm in diameter Flaviviruses Family Genus West Nile virus  EEEV  WEEV
  • 5. Transmission Humans are dead-end hosts ? Must be present in the bloodstream of the vertebrate host (viremia) in sufficiently high titer Extrinsic incubation period, must pass before the virus has replicated sufficiently for the saliva to contain enough virus Only the female ? Only she requires a blood meal in order for progeny to be produced Ranges from 7 to 14 days Some are transmitted by vertical “transovarian” passage from the mother tick to her offspring. Value?
  • 6. Pathogenic mechanism On biting a host, the mosquito regurgitates virus-containing saliva into the bloodstream female Circulates freely in the host’s plasma and Comes into contact with susceptible target cell Flulike symptoms The virus gains access to the brain by infecting the endothelial cells lining the small vessels of the brain or the choroid plexus
  • 7. Clinical significance Most human arboviral infections are asymptomatic A minority of infections cause neuroinvasive disease, such as encephalitis and meningitis The clinical picture usually fits one of three categories Encephalitis Hemorrhagic fever Fever with myalgias, arthralgias, and nonhemorrhagic rash The pathogenesis of these diseases involves not only the cytocidal effect of the virus, but also, in some, a prominent immunopathologic component Eastern equine encephalitis virus Western equine encephalitis virus West Nile virus Immunity following the infection is lifelong
  • 8. Eastern Equine Encephalitis Virus Causes the most severe disease and is associated with the highest fatality rate (approximately 50%) Encephalitis Characterized by the sudden onset of :  Severe headache  Nausea and vomiting  Fever  Changes in mental status  Rapidly progressive downhill course with nuchal rigidity  Seizures  Coma The diagnosis is made by either isolating the virus or demonstrating a rise in antibody titer Atlantic and Gulf states If the patient survives, the central nervous system sequelae are usually severe occur in one third of survivors The disease does not occur in the winter ?
  • 9. Western Equine Encephalitis Virus Causes disease more frequently than does EEE virus The virus is transmitted primarily by Culex mosquitoes among the wild bird The clinical picture of WEE virus infection is similar but less severe, the fatality rate is roughly 2%. The diagnosis is made by isolating the virus or observing a rise in antibody titer West of Mississippi Sequelae are less common Wild birds
  • 10. West Nile Virus The clinical picture is one of encephalitis with or without signs of meningitis, typically in a person over 60 years of age Less than 1% of those infected have symptomatic disease, the mortality rate is roughly 12%. The laboratory diagnosis can be made by either isolation of the virus from brain tissue, blood, or spinal fluid or by detection of antibodies in spinal fluid or blood and PCR-based assays are also available. Detection of IgM antibody is the most efficient diagnostic method Endemic in Africa; Widespread in United States The most common cause of neuroinvasive (encephalitis, meningitis) arboviral disease
  • 11. Laboratory diagnosis Clinical significance Main properties Virus isolating the virus or demonstrating a rise in antibody titer  The majority of infections are subclinical  May cause acute encephalitis (most severe disease)  Family Togaviridae  Genus Alphavirus  Enveloped, icosahedral viruses  Positive sense  Single-stranded RNA genome  70 nm in diameter  Transmitted to humans by mosquitoes Eastern Equine Encephalitis virus  The majority of infections are subclinical  May cause acute encephalitis (less severe disease) Western Equine Encephalitis virus Isolation of the virus from brain tissue, blood, or spinal fluid or by detection of antibodies in spinal fluid or blood and PCR-based assays are also available  Usually self-limited illness  May result in aseptic meningitis or meningoencephalitis, especially in the elderly  Family Flaviviridae  Genus flavivirus  Enveloped, icosahedral viruses  Positive sense  Single stranded RNA genome  40 to 50 nm in diameter  Transmitted to humans by mosquito West Nile virus
  • 13. Reference Warren E. Levinson (2014) Review of Medical Microbiology and Immunology, 13th edn., New York, United States: McGraw-Hill Education - Europe. Neal R. Chamberlain ( 2009) Medical Microbiology: The Big Picture, New York, United States: McGraw-Hill Education - Europe. Richard A. Harvey , Cynthia Nau Cornelissen (2012) Lippincott Illustrated Reviews: Microbiology, Third edn., Philadelphia, United States: Lippincott Williams and Wilkins.

Editor's Notes

  1. The life cycle of the arboviruses is based on the ability of these viruses to multiply in both the vertebrate host and the bloodsucking vector
  2. Most arboviruses maintain an enzootic (animal) cycle that does not involve human infection. After a bite from an infected mosquito, the virus replicates in dendritic cells and macrophages in local tissue and lymph nodes, resulting in a primary viremia that disseminates virus to end organs including the CNS. The ability of an arbovirus to invade the CNS (neuroinvasiveness) is determined by multiple viral and host factors.138 Proposed routes of arboviral CNS entry include penetration of the cerebral microvasculature after infection of endothelial cells, diapedesis of infected leukocytes, or penetration of the choroid plexus. When the virus has penetrated the blood-brain barrier, arboviruses can directly infect and cause death of neurons. Several studies have shown that apoptosis is an important mechanism of WNV neuron cell death and CNS injury.139-141 Immune responses also contribute to clearance of virus and immunopathologically mediated neuronal cell death.
  3. Clinicians should have a high index of suspicion in the summer months in the appropriate geographic areas. The disease does not occur in the winter because mosquitoes are not active. It is not known how the virus survives the winter—in birds, mosquitoes, or perhaps some other animal. No antiviral therapy is available. A killed vaccine is available to protect horses but not humans. The disease is too rare for production of a human vaccine to be economically feasible. Approximately 1 in 30 individuals exposed to eastern equine encephalitis virus develops disease
  4. The case-fatality rate is approximately 4% to 10% but is higher in infants and the elderly
  5. fever and headache without encephalitis occur in about 20%, and roughly 80% of infections are asymptomatic Mortality from WNV neuroinvasive disease is approximately 12%