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Viral encephalitis

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  • Have icosahedral geometry: twenty equal sides/ faces
  • Serotype:1 : a group of intimately related microorganisms distinguished by a common set of antigens2 : the set of antigens characteristic of a serotype
  • Non-structural proteins all have diverse functions, not all of which have actually been determined.
  • Many of these functions were detemined by when something did not occur in mutants
  • Only structural proteins described as polyprotein, unlike flavivirus where only ORF and whole genome is transcribed as polyprotein
    Here cellular membrane becomes viral membrane, as opposed to flavivirus where packaged in golgi and exocytosed from cell
  • Transcript

    • 1. Viral EncephalitisViral Encephalitis Dan Karlin, Jenny Richmond, Chiemi SuzukiDan Karlin, Jenny Richmond, Chiemi Suzuki BIO 4158: Microbiology and BioterrorismBIO 4158: Microbiology and Bioterrorism Dr. ZubayDr. Zubay April 20, 2004April 20, 2004
    • 2. RoadmapRoadmap  IntroductionIntroduction  History and epidemiologyHistory and epidemiology  Molecular biologyMolecular biology  WeaponizationWeaponization  Clinical manifestationsClinical manifestations  Preparednes and continued surveillancePreparednes and continued surveillance
    • 3. IntroductionIntroduction  Encephalitis is an acute inflammatory process affecting the brainEncephalitis is an acute inflammatory process affecting the brain  Viral infection is the most common and important cause, withViral infection is the most common and important cause, with over 100 viruses implicated worldwideover 100 viruses implicated worldwide  SymptomsSymptoms  FeverFever  HeadacheHeadache  Behavioral changesBehavioral changes  Altered level of consciousnessAltered level of consciousness  Focal neurologic deficitsFocal neurologic deficits  SeizuresSeizures  Incidence of 3.5-7.4 per 100,000 persons per yearIncidence of 3.5-7.4 per 100,000 persons per year
    • 4. Causes of Viral EncephalitisCauses of Viral Encephalitis  Herpes viruses – HSV-1, HSV-2, varicella zoster virus, cytomegalovirus,Herpes viruses – HSV-1, HSV-2, varicella zoster virus, cytomegalovirus, Epstein-Barr virus, human herpes virus 6Epstein-Barr virus, human herpes virus 6  AdenovirusesAdenoviruses  Influenza AInfluenza A  Enteroviruses, poliovirusEnteroviruses, poliovirus  Measles, mumps, and rubella virusesMeasles, mumps, and rubella viruses  RabiesRabies  Arboviruses – examples: Japanese encephalitis; St. Louis encephalitis virus;Arboviruses – examples: Japanese encephalitis; St. Louis encephalitis virus; West Nile encephalitis virus; Eastern, Western and Venzuelan equineWest Nile encephalitis virus; Eastern, Western and Venzuelan equine encephalitis virus; tick borne encephalitis virusencephalitis virus; tick borne encephalitis virus  Bunyaviruses – examples: La Crosse strain of California virusBunyaviruses – examples: La Crosse strain of California virus  Reoviruses – example: Colorado tick fever virusReoviruses – example: Colorado tick fever virus  Arenaviruses – example: lymphocytic choriomeningitis virusArenaviruses – example: lymphocytic choriomeningitis virus
    • 5. What Is An Arbovirus?What Is An Arbovirus?  Arboviruses = arthropod-borne virusesArboviruses = arthropod-borne viruses  Arboviruses are maintained in nature throughArboviruses are maintained in nature through biological transmission between susceptiblebiological transmission between susceptible vertebrate hosts by blood-feeding arthropodsvertebrate hosts by blood-feeding arthropods  Vertebrate infection occurs when the infectedVertebrate infection occurs when the infected arthropod takes a blood mealarthropod takes a blood meal
    • 6. http://www.cdc.gov/ncidod/dvbid/arbor/schemat.pdf
    • 7. Major Arboviruses That CauseMajor Arboviruses That Cause EncephalitisEncephalitis  FlaviviridaeFlaviviridae  Japanese encephalitisJapanese encephalitis  St. Louis encephalitisSt. Louis encephalitis  West NileWest Nile  TogaviridaeTogaviridae  Eastern equine encephalitisEastern equine encephalitis  Western equine encephalitisWestern equine encephalitis  BunyaviridaeBunyaviridae  La Crosse encephalitisLa Crosse encephalitis
    • 8. West Nile VirusWest Nile Virus
    • 9. West Nile VirusWest Nile Virus  FlavivirusFlavivirus  Primary host – wild birdsPrimary host – wild birds  Principal arthropodPrincipal arthropod vector – mosquitoesvector – mosquitoes  Geographic distribution -Geographic distribution - Africa, Middle East,Africa, Middle East, Western Asia, Europe,Western Asia, Europe, Australia, NorthAustralia, North America, CentralAmerica, Central AmericaAmerica http://www.walgreens.com/images/library/healthtips/july02/westnilea.jpg
    • 10. History of West Nile VirusHistory of West Nile Virus  1937 - West Nile virus isolated from woman in Uganda1937 - West Nile virus isolated from woman in Uganda  1950s – First recorded epidemics in Israel (1951-1954,1950s – First recorded epidemics in Israel (1951-1954, 1957)1957)  1962 – Epidemic in France1962 – Epidemic in France  1974 – Epidemic in South Africa. Largest ever West1974 – Epidemic in South Africa. Largest ever West Nile epidemic.Nile epidemic.  1996 – Romanian epidemic with features similar to1996 – Romanian epidemic with features similar to those of the North American outbreak. 500 cases andthose of the North American outbreak. 500 cases and 50 deaths.50 deaths.  1999 – Russian outbreak. 40 deaths.1999 – Russian outbreak. 40 deaths.
    • 11. West Nile Virus: 1999 New YorkWest Nile Virus: 1999 New York OutbreakOutbreak  Crows dying in and around QueensCrows dying in and around Queens in late summerin late summer  27 deaths among captive birds in27 deaths among captive birds in the Queens and Bronx zoosthe Queens and Bronx zoos  Concomitant human infection ofConcomitant human infection of apparent encephalitis in the sameapparent encephalitis in the same areaarea  Outbreak was first attributed to St.Outbreak was first attributed to St. Louis encephalitis, but tissueLouis encephalitis, but tissue samples from dead crowssamples from dead crows confirmed that it was West Nileconfirmed that it was West Nile virusvirus  59 human cases requiring59 human cases requiring hospitalization, including 7 deathshospitalization, including 7 deaths
    • 12. Spread of West Nile Virus in the USSpread of West Nile Virus in the US  2000 – spread throughout New2000 – spread throughout New England and Mid-Atlantic regions.England and Mid-Atlantic regions.  18 new human cases reported18 new human cases reported  2001 – spread throughout the2001 – spread throughout the entire eastern half of the USentire eastern half of the US  64 cases reported, with NY, FL64 cases reported, with NY, FL and NJ accounting for 60%and NJ accounting for 60%  2002 – spread westward across2002 – spread westward across Great Plains into Western US.Great Plains into Western US. Reached California by Labor Day.Reached California by Labor Day.  By end of 2002 cumulative humanBy end of 2002 cumulative human cases > 3900, with > 250 deathscases > 3900, with > 250 deaths  2003 – US, Canada, Mexico2003 – US, Canada, Mexico  9,858 cases reported to CDC,9,858 cases reported to CDC, including 262 deaths in 45 statesincluding 262 deaths in 45 states and D.C.and D.C.
    • 13. West Nile Activity in the US –West Nile Activity in the US – Reports as of April 7, 2004Reports as of April 7, 2004
    • 14. West Nile Activity in the US –West Nile Activity in the US – Counties Reporting Cases as ofCounties Reporting Cases as of March 24, 2004March 24, 2004
    • 15. West Nile Virus 2004:West Nile Virus 2004: BREAKING NEWSBREAKING NEWS  April 13, 2004 – Ohio may have first 2004 West Nile CaseApril 13, 2004 – Ohio may have first 2004 West Nile Case  79 year old man from Scioto County, OH was admitted April 1 with viral79 year old man from Scioto County, OH was admitted April 1 with viral meningitis and encephalitis which rapidly progressed to coma over 2 days.meningitis and encephalitis which rapidly progressed to coma over 2 days.  Initial IgM antibody titers were positive for West Nile virus and heInitial IgM antibody titers were positive for West Nile virus and he complained of itching from insect bites upon admissioncomplained of itching from insect bites upon admission  Has been treated with blood-pressure drugs to control over-response byHas been treated with blood-pressure drugs to control over-response by the immune system to West Nile virus, causing brain inflammation.the immune system to West Nile virus, causing brain inflammation.  Previously unresponsive and paralyzed.Previously unresponsive and paralyzed.  Can now open his eyes and shake his head in response to questions, but stillCan now open his eyes and shake his head in response to questions, but still cannot talk.cannot talk.
    • 16. St. Louis EncephalitisSt. Louis Encephalitis
    • 17. St. Louis EncephalitisSt. Louis Encephalitis  FlavivirusFlavivirus  Most commonMost common mosquito-transmittedmosquito-transmitted human pathogen in thehuman pathogen in the USUS  Leading cause ofLeading cause of epidemic flaviviralepidemic flaviviral encephalitisencephalitis
    • 18. History of St. Louis EncephalitisHistory of St. Louis Encephalitis  1933 – virus isolated during St. Louis and Kansas City,1933 – virus isolated during St. Louis and Kansas City, MO epidemicMO epidemic  1940’s – virus spread to Pacific Coast1940’s – virus spread to Pacific Coast  1959-1971 – virus spread to Southern Florida1959-1971 – virus spread to Southern Florida  1974-1977 – last major epidemic. Over 2,500 cases in1974-1977 – last major epidemic. Over 2,500 cases in 35 states.35 states.  1990-1991 – South Florida epidemic. 226 cases and 111990-1991 – South Florida epidemic. 226 cases and 11 deaths.deaths.  1999 – New Orleans outbreak. 20 reported cases.1999 – New Orleans outbreak. 20 reported cases.
    • 19. St. Louis EncephalitisSt. Louis Encephalitis
    • 20. Japanese EncephalitisJapanese Encephalitis
    • 21. Japanese EncephalitisJapanese Encephalitis  Flavivirus related to St. LouisFlavivirus related to St. Louis encephalitisencephalitis  Most important cause of arboviralMost important cause of arboviral encephalitis worldwide, with overencephalitis worldwide, with over 45,000 cases reported annually45,000 cases reported annually  Transmitted by culex mosquito,Transmitted by culex mosquito, which breeds in rice fieldswhich breeds in rice fields  Mosquitoes become infected byMosquitoes become infected by feeding on domestic pigs and wildfeeding on domestic pigs and wild birds infected with Japanesebirds infected with Japanese encephalitis virus. Infectedencephalitis virus. Infected mosquitoes transmit virus tomosquitoes transmit virus to humans and animals during thehumans and animals during the feeding process.feeding process.
    • 22. History of Japanese EncephalitisHistory of Japanese Encephalitis  1800s – recognized in Japan1800s – recognized in Japan  1924 – Japan epidemic. 6125 cases, 3797 deaths1924 – Japan epidemic. 6125 cases, 3797 deaths  1935 – virus isolated in brain of Japanese patient who1935 – virus isolated in brain of Japanese patient who died of encephalitisdied of encephalitis  1938 – virus isolated from Culex mosquitoes in Japan1938 – virus isolated from Culex mosquitoes in Japan  1948 – Japan outbreak1948 – Japan outbreak  1949 – Korea outbreak1949 – Korea outbreak  1966 – China outbreak1966 – China outbreak  Today – extremely prevalent in South East Asia.Today – extremely prevalent in South East Asia. 30,000-50,000 cases reported each year.30,000-50,000 cases reported each year.
    • 23. Distribution of JapaneseDistribution of Japanese Encephalitis in Asia, 1970-1998Encephalitis in Asia, 1970-1998
    • 24. Eastern EquineEastern Equine EncephalitisEncephalitis
    • 25. Eastern Equine EncephalitisEastern Equine Encephalitis  TogavirusTogavirus  Caused by a virus transmitted toCaused by a virus transmitted to humans and horses by the bite ofhumans and horses by the bite of an infected mosquito.an infected mosquito.  200 confirmed cases in the US200 confirmed cases in the US 1964-present1964-present  Average of 4 cases per yearAverage of 4 cases per year  States with largest number of casesStates with largest number of cases – Florida, Georgia, Massachusetts,– Florida, Georgia, Massachusetts, and New Jersey.and New Jersey.  Human cases occur relativelyHuman cases occur relatively infrequently, largely because theinfrequently, largely because the primary transmission cycle takesprimary transmission cycle takes place in swamp areas whereplace in swamp areas where populations tend to be limited.populations tend to be limited.
    • 26. History of Eastern EquineHistory of Eastern Equine EncephalitisEncephalitis  1831 – First recognized as a disease in horses. Over 751831 – First recognized as a disease in horses. Over 75 horses died in 3 counties in Massachusetts.horses died in 3 counties in Massachusetts.  1845-1912 – epizootics in Northeast and Mid-Atlantic1845-1912 – epizootics in Northeast and Mid-Atlantic regionsregions  1933 – virus isolated from horse brains1933 – virus isolated from horse brains  1938 – association of human disease with epizootics.1938 – association of human disease with epizootics. 30 cases of fatal encephalitis in children living in same30 cases of fatal encephalitis in children living in same area as equine cases.area as equine cases.  1947 – largest recorded outbreak in Louisiana and1947 – largest recorded outbreak in Louisiana and Texas. 13,344 cases and 11,722 horse deathsTexas. 13,344 cases and 11,722 horse deaths
    • 27. Western EquineWestern Equine EncephalitisEncephalitis
    • 28. Western Equine EncephalitisWestern Equine Encephalitis  TogavirusTogavirus  Mosquito-borneMosquito-borne  639 confirmed cases in639 confirmed cases in the US since 1964the US since 1964  Important cause ofImportant cause of encephalitis in horsesencephalitis in horses and humans in Northand humans in North America, mainly in theAmerica, mainly in the Western parts of the USWestern parts of the US and Canadaand Canada
    • 29. History of Western EquineHistory of Western Equine EncephalitisEncephalitis  Early 1900’s – epizootics of viral encephalitis inEarly 1900’s – epizootics of viral encephalitis in horses described in Argentinahorses described in Argentina  1912 – 25,000 horses died in Central Plains of1912 – 25,000 horses died in Central Plains of USUS  1930 – San Joaquin Valley, CA outbreak. 60001930 – San Joaquin Valley, CA outbreak. 6000 cases in horses. Virus isolated from horse brainscases in horses. Virus isolated from horse brains  1938 – virus isolated from brain of a child1938 – virus isolated from brain of a child
    • 30. La Crosse EncephalitisLa Crosse Encephalitis
    • 31. La Crosse EncephalitisLa Crosse Encephalitis  BunyavirusBunyavirus  On average 75 cases per year reportedOn average 75 cases per year reported to the CDCto the CDC  Most cases occur in children under 16Most cases occur in children under 16 years oldyears old  Zoonotic pathogen that cycles betweenZoonotic pathogen that cycles between the daytime biting treehole mosquito,the daytime biting treehole mosquito, and vertebrate amplifier hostsand vertebrate amplifier hosts (chipmunk, tree squirrel) in deciduous(chipmunk, tree squirrel) in deciduous forest habitatsforest habitats  Most cases occur in the upperMost cases occur in the upper Midwestern state, but recently casesMidwestern state, but recently cases have been reported in the Mid-Atlantichave been reported in the Mid-Atlantic region and the Southeastregion and the Southeast  1963 – isolated in La Crosse, WI from1963 – isolated in La Crosse, WI from the brain of a child who died fromthe brain of a child who died from encephalitisencephalitis
    • 32. Summary – Confirmed and ProbableSummary – Confirmed and Probable Human Cases in the USHuman Cases in the US VirusVirus YearsYears Total casesTotal cases Eastern EquineEastern Equine 1964-20001964-2000 182182 Western EquineWestern Equine 1964-20001964-2000 649649 La CrosseLa Crosse 1964-20001964-2000 2,7762,776 St. LouisSt. Louis 1964-20001964-2000 4,4824,482 West NileWest Nile 1999-present1999-present > 9,800> 9,800
    • 33. Molecular Biology ofMolecular Biology of Viruses that can CauseViruses that can Cause Viral EncephalitisViral Encephalitis• Flaviviridae:Flaviviridae: West Nile VirusWest Nile Virus • Togaviridae:Togaviridae: Eastern and WesternEastern and Western Equine EncephalitisEquine Encephalitis • Bunyaviridae:Bunyaviridae: La Crosse VirusLa Crosse Virus
    • 34. FlavivirusFlavivirus • Japanese Encephalitis VirusJapanese Encephalitis Virus • St. Louis encephalitis virusSt. Louis encephalitis virus • West Nile VirusWest Nile Virus
    • 35. Flavivirus: Virus ClassificationFlavivirus: Virus Classification  Family FlaviviridaeFamily Flaviviridae  3 Genera3 Genera  Flavivirus, Pestivirus, HepacivirusFlavivirus, Pestivirus, Hepacivirus  Flavivirus - 12 SerogroupsFlavivirus - 12 Serogroups  Japanese encephalitis virus serogroupJapanese encephalitis virus serogroup  Includes West Nile Virus (WNV), St. Louis Encephalitis,Includes West Nile Virus (WNV), St. Louis Encephalitis, and othersand others
    • 36. Scanned images of West Nile virus isolated from brain tissue from a crow found in New York.
    • 37. Viral Replication CycleViral Replication Cycle
    • 38. Genome StructureGenome Structure
    • 39. Viral GenomeViral Genome  Positive Strand RNA GenomePositive Strand RNA Genome  1 ORF – Genome encodes single polyprotein which is1 ORF – Genome encodes single polyprotein which is subsequently cleavedsubsequently cleaved  5’ portion5’ portion  3 structural proteins3 structural proteins  3’ portion3’ portion  7 non-structural proteins7 non-structural proteins  Genome also includes 5’ and 3’ noncoding regionsGenome also includes 5’ and 3’ noncoding regions which have functional importancewhich have functional importance
    • 40. Secondary structure loopsSecondary structure loops
    • 41. 3’ Stem Loop of Plus Strand3’ Stem Loop of Plus Strand  Tertiary interactions of 3’ non-coding region serve toTertiary interactions of 3’ non-coding region serve to stabilize and compact the 3’ region of the genome andstabilize and compact the 3’ region of the genome and may also create binding sites for cellular and/or viralmay also create binding sites for cellular and/or viral proteinsproteins  Pseudoknots – Formed by interactions between 3’ stemPseudoknots – Formed by interactions between 3’ stem loop and adjacent nucleotidesloop and adjacent nucleotides  PK1 May be important for minus strand replicationPK1 May be important for minus strand replication  Interacts with cellular proteinsInteracts with cellular proteins  P104, EF-1P104, EF-1αα, and p84, and p84
    • 42. Conserved SecondaryConserved Secondary and Tertiaryand Tertiary Terminal RNA Structures in MinusTerminal RNA Structures in Minus StrandStrand  Stem loop structures at 5’ and 3’ ends are conservedStem loop structures at 5’ and 3’ ends are conserved across flavivirus species suggesting a functionalacross flavivirus species suggesting a functional importance for these groups.importance for these groups.  Minus strand stem loops may play a role in facilitatingMinus strand stem loops may play a role in facilitating the formation of replication complexes and in releasingthe formation of replication complexes and in releasing newly synthesized minus strands from plus strands.newly synthesized minus strands from plus strands.  In addition, its interaction with cellular proteins isIn addition, its interaction with cellular proteins is important for replication.important for replication.
    • 43. Viral Proteins: Structural andViral Proteins: Structural and Non-StructuralNon-Structural  Structural ProteinsStructural Proteins  Capsid (C), Membrane (M), Envelope (E)Capsid (C), Membrane (M), Envelope (E)  The envelope - receptor bindingThe envelope - receptor binding  Dimers of E protein arrange their β sheets in a head to tailDimers of E protein arrange their β sheets in a head to tail formation which lie flat on top of the lipid bilayer. The distalformation which lie flat on top of the lipid bilayer. The distal portions of these proteins are anchored in the membraneportions of these proteins are anchored in the membrane  Non-Structural Multifunctional ProteinsNon-Structural Multifunctional Proteins  NS1, NS2A, NS2B, NS3, NS4A, NS4B, NS5NS1, NS2A, NS2B, NS3, NS4A, NS4B, NS5  Many functions of non-structural proteins have yet toMany functions of non-structural proteins have yet to be determinedbe determined
    • 44. Viral Non-Structural ProteinsViral Non-Structural Proteins  NS1- may play a role in flavivirus RNA synthesis; it has been shown to beNS1- may play a role in flavivirus RNA synthesis; it has been shown to be essential for negative strand synthesisessential for negative strand synthesis  NS2A, NS2B, NS4A, NS4B - may facilitate the assembly of viral replicationNS2A, NS2B, NS4A, NS4B - may facilitate the assembly of viral replication complexes by an unknown mechanismcomplexes by an unknown mechanism  NS3: MultifunctionalNS3: Multifunctional  Proteolytic function upon association with NS2BProteolytic function upon association with NS2B  RNA triphosphatase function thought to be important for the synthesisRNA triphosphatase function thought to be important for the synthesis of the 5’ cap structureof the 5’ cap structure  Helicase and NTPase activityHelicase and NTPase activity  Its activity may be upregulated through interaction with phosphorylatedIts activity may be upregulated through interaction with phosphorylated NS5NS5  NS5NS5  RNA dependent RNA polymeraseRNA dependent RNA polymerase  Methyltransferase domain thought to be required for formation of the 5’ capMethyltransferase domain thought to be required for formation of the 5’ cap
    • 45. Model for Closed-Loop ComplexModel for Closed-Loop Complex Formation in FlavivirusesFormation in Flaviviruses
    • 46. TogavirusTogavirus • Eastern Equine Encephalitis VirusEastern Equine Encephalitis Virus • Western Equine Encephalitis VirusWestern Equine Encephalitis Virus • Venezuelan Equine Encephalitis VirusVenezuelan Equine Encephalitis Virus
    • 47. TogavirusTogavirus  Family: TogaviridaeFamily: Togaviridae  Genus: AlphavirusGenus: Alphavirus  49S Single Stranded Genome49S Single Stranded Genome  ~11700 Nucleotides~11700 Nucleotides  3’ end: Five potential structural proteins3’ end: Five potential structural proteins  C, E3, E2, 6K, and E1C, E3, E2, 6K, and E1  5’ end: Unknown number of non-structural proteins5’ end: Unknown number of non-structural proteins probably involved in replicationprobably involved in replication  Genome has an opposite orientation from theGenome has an opposite orientation from the FlavivirusesFlaviviruses
    • 48. Alphavirus StructureAlphavirus Structure http://www.cdc.gov/ncidod/dvbid/arbor/alphavir.htm
    • 49. Alphaviruses: Protein FunctionAlphaviruses: Protein Function  E1and E2 glycoprotein heterodimers form trimers that appear asE1and E2 glycoprotein heterodimers form trimers that appear as knobs on the surface of the virionknobs on the surface of the virion  E1 – transmembrane glycoprotein with 2 to 3 N-linked glycosylation sitesE1 – transmembrane glycoprotein with 2 to 3 N-linked glycosylation sites  E2 - glycoprotein with 1 to 2 N-linked glycosylation sites, contains shortE2 - glycoprotein with 1 to 2 N-linked glycosylation sites, contains short intracytoplasmic tail and hydrophobic stretch of amino acids that servesintracytoplasmic tail and hydrophobic stretch of amino acids that serves as the fusion peptide for viral entryas the fusion peptide for viral entry  Capsid protein has a conserved N-terminal region which bindsCapsid protein has a conserved N-terminal region which binds RNA and a C-terminal region which interacts with theRNA and a C-terminal region which interacts with the cytoplasmic tail of E2 as well as capsid proteinscytoplasmic tail of E2 as well as capsid proteins  E3 and 6K proteins are signal sequences for E2 and E1,E3 and 6K proteins are signal sequences for E2 and E1, respectively, and are largely cleaved off from the mature virionrespectively, and are largely cleaved off from the mature virion
    • 50. Replication CycleReplication Cycle  Proposed Model: E1 glycoprotein interacts with proteins on theProposed Model: E1 glycoprotein interacts with proteins on the cell surface. E2 binds to cellular proteins and receptor-mediatedcell surface. E2 binds to cellular proteins and receptor-mediated endocytosis takes place.endocytosis takes place.  In acidified endosomal compartment, glycoproteins fuse withIn acidified endosomal compartment, glycoproteins fuse with membrane and the nucleocapsid is released.membrane and the nucleocapsid is released.  Virion RNA serves as mRNA, translation of non-structuralVirion RNA serves as mRNA, translation of non-structural proteins beginsproteins begins  Structural proteins are transcribed as polyproteinStructural proteins are transcribed as polyprotein  E2 and E1 travel from ER to the GolgiE2 and E1 travel from ER to the Golgi  At cellular membrane regions containing E1 and E2At cellular membrane regions containing E1 and E2 heterodimers interact with nucleocapsids and viral particles budheterodimers interact with nucleocapsids and viral particles bud from the cell surfacefrom the cell surface
    • 51. BunyaviridaeBunyaviridae La Crosse VirusLa Crosse Virus
    • 52. La Crosse VirusLa Crosse Virus http://www.virology.net/Big_Virology/BVRNAbunya.html
    • 53. BunyavirusesBunyaviruses  Genome - single strand of negative sense RNAGenome - single strand of negative sense RNA  Four structural proteinsFour structural proteins  Two external proteinsTwo external proteins  Two associated with RNA to form nucleocapsidTwo associated with RNA to form nucleocapsid  Matrix proteins absent from Bunyaviruses, thereforeMatrix proteins absent from Bunyaviruses, therefore capsid proteins and envelope glycoproteins directlycapsid proteins and envelope glycoproteins directly interact prior to buddinginteract prior to budding
    • 54. http://www.cdc.gov/ncidod/dvbid/arbor/index.htm BioweaponizationBioweaponization
    • 55. West Nile virus Mosquito vector Bird reservoir hosts Transmission Cycle is Key toTransmission Cycle is Key to WeaponizationWeaponization Incidental infections Incidental infections http://www.cdc.gov/ncidod/dvbid/westnile/conf/February_2003.htm
    • 56. BioweaponizationBioweaponization  Vector, Vector, VectorVector, Vector, Vector  In areas around NYC mosquitoes are extremelyIn areas around NYC mosquitoes are extremely ubiquitous during the summer monthsubiquitous during the summer months  Mosquitoes are already virulent, further geneticMosquitoes are already virulent, further genetic engineering is unnecessaryengineering is unnecessary  A fully effective cure is not availableA fully effective cure is not available  Diagnosis is difficultDiagnosis is difficult  Widespread Panic would be generated as theWidespread Panic would be generated as the outbreak progressesoutbreak progresses
    • 57. The Iraq ConnectionThe Iraq Connection  The US shipped various pathogens, includingThe US shipped various pathogens, including WNV, to Iraq in the 1980sWNV, to Iraq in the 1980s  In 1999 following the West Nile Virus outbreakIn 1999 following the West Nile Virus outbreak in NYC there were fears that Iraqi bioterrorismin NYC there were fears that Iraqi bioterrorism was involvedwas involved  Investigations by the CDC and the CIA foundInvestigations by the CDC and the CIA found no evidence of bioterrorism in the 1999no evidence of bioterrorism in the 1999 outbreakoutbreak
    • 58. WNV as a low-tech Bioweapon:WNV as a low-tech Bioweapon: Possible Connection to 1999 outbreakPossible Connection to 1999 outbreak  Gather mosquitoes in an endemic areaGather mosquitoes in an endemic area  Incubate mosquitoes with a food sourceIncubate mosquitoes with a food source  Put them to sleepPut them to sleep  Place mosquitoes in a matchboxPlace mosquitoes in a matchbox  Board plane to USBoard plane to US  Take bus from airport; Release mosquitoes fromTake bus from airport; Release mosquitoes from bus windowbus window  Wait for outbreakWait for outbreak Source: Dr. Ilya Trakht
    • 59. Clinical ConsiderationsClinical Considerations
    • 60. Case StudyCase Study In August 2002, a 91 year old male from Northern Staten IslandIn August 2002, a 91 year old male from Northern Staten Island who presented initially with sudden onset of fever, left lowerwho presented initially with sudden onset of fever, left lower extremity weakness, inability to walk, and possibly some transientextremity weakness, inability to walk, and possibly some transient and mild AMS, was admitted to a Staten Island hospital.and mild AMS, was admitted to a Staten Island hospital. He was not considered to have aseptic meningitis or encephalitisHe was not considered to have aseptic meningitis or encephalitis and WN virus infection was not considered at that time. Afterand WN virus infection was not considered at that time. After being discharged, he was evaluated by a neurologist for persistentbeing discharged, he was evaluated by a neurologist for persistent left leg weakness and inability to walk.left leg weakness and inability to walk. In April 2003, the neurologist reported this case to the DOHMHIn April 2003, the neurologist reported this case to the DOHMH as a possible polio case. Serological specimens were forwardedas a possible polio case. Serological specimens were forwarded to the NYSDOH where they tested positive for WN virus.to the NYSDOH where they tested positive for WN virus.
    • 61. Clinical ConsiderationsClinical Considerations DiagnosisDiagnosis
    • 62. Patient HistoryPatient History  Detailed history critical to determine the likely cause of encephalitis.Detailed history critical to determine the likely cause of encephalitis.  Prodromal illness, recent vaccination, development of few days → AcuteProdromal illness, recent vaccination, development of few days → Acute Disseminated Encephalomyelitis (ADEM) .Disseminated Encephalomyelitis (ADEM) .  Biphasic onset: systemic illness then CNS disease → Enterovirus encephalitis.Biphasic onset: systemic illness then CNS disease → Enterovirus encephalitis.  Abrupt onset, rapid progression over few days → HSE.Abrupt onset, rapid progression over few days → HSE.  Recent travel and the geographical context:Recent travel and the geographical context:  Africa → Cerebral malariaAfrica → Cerebral malaria  Asia → Japanese encephalitisAsia → Japanese encephalitis  High risk regions of Europe and USA → Lyme diseaseHigh risk regions of Europe and USA → Lyme disease  Recent animal bites → Tick borne encephalitis or Rabies.Recent animal bites → Tick borne encephalitis or Rabies.  OccupationOccupation  Forest worker, exposed to tick bitesForest worker, exposed to tick bites  Medical personnel, possible exposure to infectious diseases.Medical personnel, possible exposure to infectious diseases.
    • 63. History cont.History cont.  SeasonSeason  Japanese encephalitis is more common during the rainy season.Japanese encephalitis is more common during the rainy season.  Arbovirus infections are more frequent during summer and fall.Arbovirus infections are more frequent during summer and fall.  Predisposing factors:Predisposing factors:  Immunosuppression caused by disease and/or drug treatment.Immunosuppression caused by disease and/or drug treatment.  Organ transplant → Opportunistic infectionsOrgan transplant → Opportunistic infections  HIV → CNS infectionsHIV → CNS infections  HSV-2 encephalitis and Cytomegalovirus infection (CMV)HSV-2 encephalitis and Cytomegalovirus infection (CMV)  Drug ingestion and/or abuseDrug ingestion and/or abuse  TraumaTrauma
    • 64. Initial SignsInitial Signs  HeadacheHeadache  MalaiseMalaise  AnorexiaAnorexia  Nausea and VomitingNausea and Vomiting  Abdominal painAbdominal pain
    • 65. Developing SignsDeveloping Signs  Altered LOC – mild lethargy to deep coma.Altered LOC – mild lethargy to deep coma.  AMS – confused, delirious, disoriented.AMS – confused, delirious, disoriented.  Mental aberrations:Mental aberrations:  hallucinationshallucinations  agitationagitation  personality changepersonality change  behavioral disordersbehavioral disorders  occasionally frank psychosisoccasionally frank psychosis  Focal or general seizures in >50% severe cases.Focal or general seizures in >50% severe cases.  Severe focused neurologic deficits.Severe focused neurologic deficits.
    • 66. Neurologic SignsNeurologic Signs  Virtually every possible focal neurologicalVirtually every possible focal neurological disturbance has been reported.disturbance has been reported.  Most CommonMost Common  AphasiaAphasia  AtaxiaAtaxia  Hemiparesis with hyperactive tendon reflexesHemiparesis with hyperactive tendon reflexes  Involuntary movementsInvoluntary movements  Cranial nerve deficits (ocular palsies, facial weakness)Cranial nerve deficits (ocular palsies, facial weakness)
    • 67. Other Causes of EncephalopathyOther Causes of Encephalopathy  Anoxic/Ischemic conditionsAnoxic/Ischemic conditions  Metabolic disordersMetabolic disorders  Nutritional deficiencyNutritional deficiency  Toxic (Accidental & Intentional)Toxic (Accidental & Intentional)  Systemic infectionsSystemic infections  Critical illnessCritical illness  Malignant hypertensionMalignant hypertension  Mitochondrial cytopathy (Reye’s and MELAS syndromes)Mitochondrial cytopathy (Reye’s and MELAS syndromes)  Hashimoto’s encephalopathyHashimoto’s encephalopathy  Traumatic brain injuryTraumatic brain injury  Epileptic (non-convulsive status)Epileptic (non-convulsive status)  CJD (Mad Cow)CJD (Mad Cow)
    • 68. Differential DiagnosisDifferential Diagnosis  Distinguish EtiologyDistinguish Etiology  (1) Bacterial infection and other infectious conditions(1) Bacterial infection and other infectious conditions  (2) Parameningeal infections or partially treated bacterial meningitis(2) Parameningeal infections or partially treated bacterial meningitis  (3) Nonviral infectious meningitides where cultures may be negative (e.g.,(3) Nonviral infectious meningitides where cultures may be negative (e.g., fungal, tuberculous, parasitic, or syphilitic disease)fungal, tuberculous, parasitic, or syphilitic disease)  (5) Meningitis secondary to noninfectious inflammatory diseases(5) Meningitis secondary to noninfectious inflammatory diseases  MRIMRI  Can exclude subdural bleeds, tumor, and sinus thrombosisCan exclude subdural bleeds, tumor, and sinus thrombosis  BiopsyBiopsy  Reserved for patients who are worsening, have an undiagnosed lesionReserved for patients who are worsening, have an undiagnosed lesion after scan, or a poor response to acyclovir.after scan, or a poor response to acyclovir.  Clinical signs cannot distinguish different viral encephalitidesClinical signs cannot distinguish different viral encephalitides
    • 69. Differential Diagnosis cont.Differential Diagnosis cont. EncephalopathyEncephalopathy EncephalitisEncephalitis FeverFever UncommonUncommon CommonCommon HeadacheHeadache UncommonUncommon CommonCommon AMSAMS Steady deterioration May fluctuateSteady deterioration May fluctuate Focal Neurologic SignsFocal Neurologic Signs UncommonUncommon CommonCommon Types of seizuresTypes of seizures GeneralizedGeneralized BothBoth Blood: LeukocytosisBlood: Leukocytosis UncommonUncommon CommonCommon CSF: PleocytosisCSF: Pleocytosis UncommonUncommon CommonCommon EEG: Diffuse slowingEEG: Diffuse slowing CommonCommon +Focal+Focal MRIMRI Often normalOften normal Focal Abn.Focal Abn.
    • 70. Clinical ConsiderationsClinical Considerations RadiologyRadiology
    • 71. MRIMRI
    • 72. MRIMRI
    • 73. Clinical ConsiderationsClinical Considerations Laboratory DiagnosisLaboratory Diagnosis
    • 74. Laboratory DiagnosisLaboratory Diagnosis  Diagnosis is usually based on CSFDiagnosis is usually based on CSF  Normal glucoseNormal glucose  Absence of bacteria on culture.Absence of bacteria on culture.  Viruses occasionally isolated directly from CSFViruses occasionally isolated directly from CSF  Less than half are identifiedLess than half are identified  Polymerase Chain Reaction techniquesPolymerase Chain Reaction techniques  Detect specific viral DNA in CSFDetect specific viral DNA in CSF
    • 75. NYSDOH PCRNYSDOH PCR NEW YORK STATE DEPARTMENT OF HEALTH (NYSDOH)NEW YORK STATE DEPARTMENT OF HEALTH (NYSDOH) Viral Encephalitis Letter of Agreement forViral Encephalitis Letter of Agreement for Physician Ordered Testing by Polymerase Chain Reaction (PCR)Physician Ordered Testing by Polymerase Chain Reaction (PCR) NYSDOH's Wadsworth Center offers the following tests on CSF for viral encephalitis:NYSDOH's Wadsworth Center offers the following tests on CSF for viral encephalitis: PCR testing for a panel of viruses, including: herpes simplex, varicella zoster, cytomegalovirus,PCR testing for a panel of viruses, including: herpes simplex, varicella zoster, cytomegalovirus, Epstein-Barr virus, enteroviruses, St. Louis encephalitis (SLE), eastern equine encephalitis (EEE),Epstein-Barr virus, enteroviruses, St. Louis encephalitis (SLE), eastern equine encephalitis (EEE), California encephalitis (including LaCrosse and Jamestown Canyon viruses), Powassan and WestCalifornia encephalitis (including LaCrosse and Jamestown Canyon viruses), Powassan and West Nile (WN) viruses, andNile (WN) viruses, and Enzyme-linked immunoassay (ELISA) for WN virus.Enzyme-linked immunoassay (ELISA) for WN virus. If there is insufficient quantity of CSF (less than 1.0 ml) to conduct both ELISA and PCR forIf there is insufficient quantity of CSF (less than 1.0 ml) to conduct both ELISA and PCR for WN virus, please consider the following in determining which test is most appropriate for yourWN virus, please consider the following in determining which test is most appropriate for your patient:patient: ELISA is more sensitive than PCR for WN viral testing and should be considered when there isELISA is more sensitive than PCR for WN viral testing and should be considered when there is stronger suspicion of WN virus than other viruses.stronger suspicion of WN virus than other viruses. PCR is less sensitive for WN virus, but tests for a wide range of viruses. PCR should bePCR is less sensitive for WN virus, but tests for a wide range of viruses. PCR should be considered if viruses other than WN virus are suspected.considered if viruses other than WN virus are suspected. Please note your testing priority below or on the viral encephalitis/meningitis case reportPlease note your testing priority below or on the viral encephalitis/meningitis case report form. If PCR testing is desired, the agreement below must be completed.form. If PCR testing is desired, the agreement below must be completed. Viral Encephalitis PCR PanelViral Encephalitis PCR Panel West Nile Virus ELISA Antibody TestingWest Nile Virus ELISA Antibody Testing
    • 76. Clinical ConsiderationsClinical Considerations Disease ProgressionDisease Progression
    • 77. Disease ProgressionDisease Progression  Worsening neurologic symptomsWorsening neurologic symptoms  Vascular collapse and shockVascular collapse and shock  May be due to adrenal insufficiency.May be due to adrenal insufficiency.  Loss of tissue fluid may be equally important.Loss of tissue fluid may be equally important.  Homeostatic failureHomeostatic failure  Decreased respiratory driveDecreased respiratory drive
    • 78. Clinical ConsiderationsClinical Considerations TreatmentTreatment
    • 79. TreatmentTreatment  When HSE cannot be ruled out, Acyclovir mustWhen HSE cannot be ruled out, Acyclovir must be started promptly (before the patient lapsesbe started promptly (before the patient lapses into coma) and continued at least 10 days forinto coma) and continued at least 10 days for maximal therapeutic benefit.maximal therapeutic benefit.  Rocky Mountain spotted fever should also beRocky Mountain spotted fever should also be considered, and empiric treatment withconsidered, and empiric treatment with Doxycycline is indicated.Doxycycline is indicated.
    • 80. Suspected HSE Treatment PlanSuspected HSE Treatment Plan
    • 81. AcyclovirAcyclovir  Acyclovir is a synthetic purine nucleosideAcyclovir is a synthetic purine nucleoside analogue with inhibitory activity against HSV-1analogue with inhibitory activity against HSV-1 and HSV-2, varicella-zoster virus (VZV),and HSV-2, varicella-zoster virus (VZV), Epstein-Barr virus (EBV) and cytomegalovirusEpstein-Barr virus (EBV) and cytomegalovirus (CMV)(CMV)  In order of decreasing effectivenessIn order of decreasing effectiveness  Highly selectiveHighly selective
    • 82. Acyclovir ActionAcyclovir Action  Thymidine Kinase (TK) of uninfected cells does not use acyclovir as aThymidine Kinase (TK) of uninfected cells does not use acyclovir as a substrate.substrate.  TK encoded by HSV, VZV and EBV2 converts acyclovir into acyclovirTK encoded by HSV, VZV and EBV2 converts acyclovir into acyclovir monophosphate.monophosphate.  The monophosphate is further converted into diphosphate by cellularThe monophosphate is further converted into diphosphate by cellular guanylate kinase and into triphosphate by a number of cellular enzymes.guanylate kinase and into triphosphate by a number of cellular enzymes.  Acyclovir triphosphate interferes with Herpes simplex virus DNA polymeraseAcyclovir triphosphate interferes with Herpes simplex virus DNA polymerase and inhibits viral DNA replication.and inhibits viral DNA replication.  Acyclovir triphosphate incorporated into growing chains of DNA by viralAcyclovir triphosphate incorporated into growing chains of DNA by viral DNA polymerase.DNA polymerase.  When incorporation occurs, the DNA chain is terminated.When incorporation occurs, the DNA chain is terminated.  Acyclovir is preferentially taken up and selectively converted to the activeAcyclovir is preferentially taken up and selectively converted to the active triphosphate form by HSV-infected cells.triphosphate form by HSV-infected cells.  Thus, acyclovir is much less toxicThus, acyclovir is much less toxic in vitroin vitro for normal uninfected cells because:for normal uninfected cells because: 1) less is taken up; 2) less is converted to the active form.1) less is taken up; 2) less is converted to the active form.
    • 83. Supportive TherapySupportive Therapy  Fever, dehydration, electrolyte imbalances, and convulsions require treatment.Fever, dehydration, electrolyte imbalances, and convulsions require treatment.  For cerebral edema severe enough to produce herniation, controlledFor cerebral edema severe enough to produce herniation, controlled hyperventilation, mannitol, and dexamethasone.hyperventilation, mannitol, and dexamethasone.  Patients with cerebral edema must not be overhydrated.Patients with cerebral edema must not be overhydrated.  If these measures are used, monitoring ICP should be considered.If these measures are used, monitoring ICP should be considered.  If there is evidence of ventricular enlargement, intracranial pressure may beIf there is evidence of ventricular enlargement, intracranial pressure may be monitored in conjunction with CSF drainage.monitored in conjunction with CSF drainage.  Outcome is usually poor.Outcome is usually poor.  For infants with subdural effusion, repeated daily subdural taps through theFor infants with subdural effusion, repeated daily subdural taps through the sutures usually helps.sutures usually helps.  No more than 20 mL/day of CSF should be removed from one sideNo more than 20 mL/day of CSF should be removed from one side to prevent suddento prevent sudden shifts in intracranial contents.shifts in intracranial contents.  If the effusion persists after 3 to 4 weeks of taps, surgical exploration for possibleIf the effusion persists after 3 to 4 weeks of taps, surgical exploration for possible excision of a subdural membrane is indicated.excision of a subdural membrane is indicated.
    • 84. DexamethasoneDexamethasone  Synthetic adrenocortical steroidSynthetic adrenocortical steroid  Potent anti-inflammatory effectsPotent anti-inflammatory effects  Dexamethasone injection is generallyDexamethasone injection is generally administered initially via IV then IMadministered initially via IV then IM  Side effects: convulsions; increased ICP afterSide effects: convulsions; increased ICP after treatment; vertigo; headache; psychictreatment; vertigo; headache; psychic disturbancesdisturbances
    • 85. Clinical ConsiderationsClinical Considerations Patient PrognosisPatient Prognosis
    • 86. PrognosisPrognosis  The mortality rate varies with etiology, and epidemics due to theThe mortality rate varies with etiology, and epidemics due to the same virus vary in severity in different years.same virus vary in severity in different years.  Bad: Eastern equine encephalitis virus infection, nearly 80% of survivorsBad: Eastern equine encephalitis virus infection, nearly 80% of survivors have severe neurological sequelae.have severe neurological sequelae.  Not so Bad: EBV, California encephalitis virus, and Venezuelan equineNot so Bad: EBV, California encephalitis virus, and Venezuelan equine encephalitis virus, severe sequelae are unusual.encephalitis virus, severe sequelae are unusual.  Approximately 5 to 15% of children infected with LaCrosse virus have aApproximately 5 to 15% of children infected with LaCrosse virus have a residual seizure disorder, and 1% have persistent hemiparesis.residual seizure disorder, and 1% have persistent hemiparesis.  Permanent cerebral sequelae are more likely to occur in infants,Permanent cerebral sequelae are more likely to occur in infants, but young children improve for a longer time than adults withbut young children improve for a longer time than adults with similar infections.similar infections.  Intellectual impairment, learning disabilities, hearing loss, and otherIntellectual impairment, learning disabilities, hearing loss, and other lasting sequelae have been reported in some studies.lasting sequelae have been reported in some studies.
    • 87. Prognosis w/ TreatmentPrognosis w/ Treatment  Considerable variation in the incidence and severity of sequelae.Considerable variation in the incidence and severity of sequelae.  Hard to assess effects of treatment.Hard to assess effects of treatment.  NIAID-CASG trials:NIAID-CASG trials:  The incidence and severity of sequelae were directly related to the age of theThe incidence and severity of sequelae were directly related to the age of the patient and the level of consciousness at the time of initiation of therapy.patient and the level of consciousness at the time of initiation of therapy.  Patients with severe neurological impairment (Glasgow coma score 6) at initiationPatients with severe neurological impairment (Glasgow coma score 6) at initiation of therapy either died or survived with severe sequelae.of therapy either died or survived with severe sequelae.  Young patients (<30 years) with good neurological function at initiation ofYoung patients (<30 years) with good neurological function at initiation of therapy did substantially better (100% survival, 62% with no or mild sequelae)therapy did substantially better (100% survival, 62% with no or mild sequelae) compared with their older counterparts (>30 years); (64% survival, 57% no orcompared with their older counterparts (>30 years); (64% survival, 57% no or mild sequelae).mild sequelae).  Recent studies using quantitative CSF PCR tests for HSV indicate that clinicalRecent studies using quantitative CSF PCR tests for HSV indicate that clinical outcome following treatment also correlates with the amount of HSV DNAoutcome following treatment also correlates with the amount of HSV DNA present in CSF at the time of presentation.present in CSF at the time of presentation.
    • 88. Glasgow Coma ScaleGlasgow Coma Scale  TestTest ResponseResponse ____Score____Score  EyeEye NoneNone 11  OpeningOpening To painTo pain 22  To verbal stimuliTo verbal stimuli 33  SpontaneouslySpontaneously 44  BestBest NoneNone 11  VerbalVerbal Incomprehensible wordsIncomprehensible words 22  ResponseResponse Inappropriate wordsInappropriate words 33  Disoriented conversationDisoriented conversation 44  Oriented conversationOriented conversation 55  BestBest NoneNone 11  MotorMotor Abnormal extensionAbnormal extension 22  ResponseResponse Abnormal flexionAbnormal flexion 33  Flexion withdrawalFlexion withdrawal 44  Localizes painLocalizes pain 55  ____________________________Obeys commandsObeys commands _________6 __________6 _  Total scoreTotal score 3-153-15
    • 89. Clinical ConsiderationsClinical Considerations VaccinationVaccination
    • 90. VaccinationVaccination  None for most EncephalitidesNone for most Encephalitides  JEJE  Appears to be 91% effectiveAppears to be 91% effective  There is no JE-specific therapy other than supportive careThere is no JE-specific therapy other than supportive care  Live-attenuated vaccine developed and tested in ChinaLive-attenuated vaccine developed and tested in China  Appears to be safe and effectiveAppears to be safe and effective  Chinese immunization programs involving millions of childrenChinese immunization programs involving millions of children  Vero cell-derived inactivated vaccines have been developed inVero cell-derived inactivated vaccines have been developed in ChinaChina  2 millions doses are produced annually in China and Japan2 millions doses are produced annually in China and Japan  Several other JE vaccines under developmentSeveral other JE vaccines under development
    • 91. Public HealthPublic Health ConsiderationsConsiderations Endemic PreventionEndemic Prevention
    • 92. Infection ControlInfection Control  CDC’s “Three Ways to Reduce your WestCDC’s “Three Ways to Reduce your West Nile Virus Risk”Nile Virus Risk”  Avoid mosquito bitesAvoid mosquito bites  Mosquito-proof your homeMosquito-proof your home  Help your communityHelp your community
    • 93. Avoid Mosquito BitesAvoid Mosquito Bites  Apply Insect Repellent Containing DEETApply Insect Repellent Containing DEET  Clothing Can Help Reduce Mosquito BitesClothing Can Help Reduce Mosquito Bites  Cover upCover up  Be Aware of Peak Mosquito HoursBe Aware of Peak Mosquito Hours  Dusk to dawn are peak mosquito biting times forDusk to dawn are peak mosquito biting times for many species.many species.
    • 94. Mosquito-Proof HomeMosquito-Proof Home  Drain Standing WaterDrain Standing Water  Install or Repair ScreensInstall or Repair Screens
    • 95. Community-Wide EffortsCommunity-Wide Efforts  Clean Up Breeding GroundsClean Up Breeding Grounds  Ensure Safe Blood SupplyEnsure Safe Blood Supply  Mosquito Control ProgramsMosquito Control Programs  ControversialControversial  SurveillanceSurveillance
    • 96. Blood SupplyBlood Supply  NYC Policy Statement reflecting FDA policy:NYC Policy Statement reflecting FDA policy: ““To reduce WN transmission through bloodTo reduce WN transmission through blood components…. Blood donations will be screened forcomponents…. Blood donations will be screened for WN virus RNA… using nucleic acid amplification testsWN virus RNA… using nucleic acid amplification tests (NAT). In the event of a NAT-reactive donation,(NAT). In the event of a NAT-reactive donation, blood centers will remove and quarantine all bloodblood centers will remove and quarantine all blood components associated with the donation and notifycomponents associated with the donation and notify the state or local health department. In addition, bloodthe state or local health department. In addition, blood testing centers have added screening questions totesting centers have added screening questions to identify and exclude persons with fever and headache inidentify and exclude persons with fever and headache in the week prior to donation.”the week prior to donation.”
    • 97. Mosquito Control ProgramsMosquito Control Programs NYC DOHMH Statement:NYC DOHMH Statement: ““ We hope that spraying of adulticides will not beWe hope that spraying of adulticides will not be required this summer. However, if there is arequired this summer. However, if there is a threat of an outbreak of human illness andthreat of an outbreak of human illness and spraying is deemed necessary, targeted adultspraying is deemed necessary, targeted adult mosquito control measures (via ground or aerialmosquito control measures (via ground or aerial spraying of pesticides) may be required.”spraying of pesticides) may be required.”
    • 98. Mosquito ControlMosquito Control  But wait, there’s more:But wait, there’s more:  Same Memo:Same Memo: Confirmed or suspected cases of pesticideConfirmed or suspected cases of pesticide poisoning must be reported to the New Yorkpoisoning must be reported to the New York State Department of Health’s PesticideState Department of Health’s Pesticide Poisoning Registry at (800)-322-6850, and to thePoisoning Registry at (800)-322-6850, and to the New York City Poison Control Center at (212)-New York City Poison Control Center at (212)- 764-7667.764-7667.
    • 99. What’s Being SprayedWhat’s Being Sprayed  The adulticides used during the last three seasons in New York City is Sumithrin, a pyrethroid.  Although pyrethroids are among the least toxicAlthough pyrethroids are among the least toxic insecticides, they are nerve poisons, and act upon theinsecticides, they are nerve poisons, and act upon the sodium ion channels in nerve cell membranes.sodium ion channels in nerve cell membranes.  Inhaling pyrethroid insecticides can cause coughing,Inhaling pyrethroid insecticides can cause coughing, wheezing, shortness of breath, runny or stuffy nose,wheezing, shortness of breath, runny or stuffy nose, chest pain, or difficulty breathing.chest pain, or difficulty breathing.  Skin contact can cause a rash, itching, or blisters.Skin contact can cause a rash, itching, or blisters.  Sumithrin is not very toxic to mammals, but it is highlySumithrin is not very toxic to mammals, but it is highly toxic to bees and fish.toxic to bees and fish.
    • 100. Crop-Dusting NYC?Crop-Dusting NYC?  Aerosolized liquids sprayed over large areas ofAerosolized liquids sprayed over large areas of the city.the city.  Terrorism concern?Terrorism concern?  New vector for urban area.New vector for urban area.
    • 101. Public HealthPublic Health ConsiderationsConsiderations SurveillanceSurveillance
    • 102. SurveillanceSurveillance ““Since 2000, the NYC DOHMH has conducted comprehensiveSince 2000, the NYC DOHMH has conducted comprehensive arthropod-borne disease surveillance and control. In 2003,arthropod-borne disease surveillance and control. In 2003, efforts will again focus on mosquito control through reductionefforts will again focus on mosquito control through reduction of breeding sites and application of larvicides. In addition,of breeding sites and application of larvicides. In addition, comprehensive mosquito, avian and human data collected duringcomprehensive mosquito, avian and human data collected during the 2000-2002 seasons have allowed NYC DOHMH to developthe 2000-2002 seasons have allowed NYC DOHMH to develop more sensitive surveillance criteria for determining the level ofmore sensitive surveillance criteria for determining the level of WN viral activity in birds and mosquitoes that may indicate aWN viral activity in birds and mosquitoes that may indicate a significant risk for a human outbreak. These indicators will besignificant risk for a human outbreak. These indicators will be monitored citywide to identify areas at risk for humanmonitored citywide to identify areas at risk for human transmission.”transmission.”
    • 103. Standing Water ReportingStanding Water Reporting The Department of Health & Mental Hygiene isThe Department of Health & Mental Hygiene is now accepting reports of standing water.now accepting reports of standing water. However, we will not be able to visit and treat allHowever, we will not be able to visit and treat all reported nuisances. Therefore we arereported nuisances. Therefore we are encouraging City residents and business ownersencouraging City residents and business owners to take immediate action to eliminate standingto take immediate action to eliminate standing water on their property.water on their property.
    • 104. Dead-Bird ReportingDead-Bird Reporting  Online formOnline form  http://www.nyc.gov/html/doh/html/wnv/wnvbird.htmlhttp://www.nyc.gov/html/doh/html/wnv/wnvbird.html  The Department of Health & Mental Hygiene is nowThe Department of Health & Mental Hygiene is now accepting reports of dead birds. Only a sample of deadaccepting reports of dead birds. Only a sample of dead birds that meet specific criteria will be picked up andbirds that meet specific criteria will be picked up and tested for the West Nile virus. However, your report oftested for the West Nile virus. However, your report of a dead bird is extremely important to us because deada dead bird is extremely important to us because dead bird reports may indicate the presence of West Nilebird reports may indicate the presence of West Nile virus. If you do not receive a call back from thevirus. If you do not receive a call back from the Department of Health within two business days ofDepartment of Health within two business days of making your report, please dispose of the bird.making your report, please dispose of the bird.
    • 105. Mosquito TestingMosquito Testing ““Five pools of mosquitoes collected in New York City haveFive pools of mosquitoes collected in New York City have tested positive for West Nile (WN) virus. These include a pooltested positive for West Nile (WN) virus. These include a pool ofof Culex salinariusCulex salinarius, a human biting mosquito, collected on July 15,, a human biting mosquito, collected on July 15, in the Willowbrook Park area of Staten Island, a poolin the Willowbrook Park area of Staten Island, a pool of Culexof Culex restuansrestuans, primarily a bird-biting mosquito, collected from, primarily a bird-biting mosquito, collected from Brookville Park, Queens on July 17, a pool ofBrookville Park, Queens on July 17, a pool of Culex pipiensCulex pipiens, a, a mosquito that bites both birds and humans, collected from themosquito that bites both birds and humans, collected from the Hunts Point area of the Bronx on July 18, a pool ofHunts Point area of the Bronx on July 18, a pool of CulexCulex speciesspecies collected from Jamaica Bay, Queens on July 16, and a pool ofcollected from Jamaica Bay, Queens on July 16, and a pool of Culex salinariusCulex salinarius collected from Greenwood Cemetery, Brooklyncollected from Greenwood Cemetery, Brooklyn on July 21. These positive pools are the first evidence of Weston July 21. These positive pools are the first evidence of West Nile (WN) virus in New York City in 2003”Nile (WN) virus in New York City in 2003”
    • 106. Disease ReportingDisease Reporting ““The New York City Department of Health andThe New York City Department of Health and Mental Hygiene (NYC DOHMH) is againMental Hygiene (NYC DOHMH) is again requesting that during the peak adult mosquitorequesting that during the peak adult mosquito season, from June 1 – October 31, 2003, allseason, from June 1 – October 31, 2003, all suspected cases of viral encephalitissuspected cases of viral encephalitis (all ages)(all ages) andand viral meningitisviral meningitis (adults only)(adults only) be reportedbe reported immediately by telephone or facsimile and thatimmediately by telephone or facsimile and that appropriate laboratory specimensappropriate laboratory specimens (cerebrospinal(cerebrospinal fluid and sera)fluid and sera) be submitted promptly for testingbe submitted promptly for testing for West Nile (WN) virus.”for West Nile (WN) virus.”