Viral Encephalitis

Viral Viral EncephalitisEncephalitis

Dan Karlin, Jenny Richmond, Chiemi Dan Karlin, Jenny Richmond, Chiemi SuzukiSuzuki

BIO 4158: Microbiology and BioterrorismBIO 4158: Microbiology and BioterrorismDr. ZubayDr. Zubay

April 20, 2004April 20, 2004

RoadmapRoadmap

IntroductionIntroduction History and epidemiologyHistory and epidemiology Molecular biologyMolecular biology WeaponizationWeaponization Clinical manifestationsClinical manifestations Preparednes and continued Preparednes and continued

surveillancesurveillance

IntroductionIntroduction Encephalitis is an acute inflammatory process Encephalitis is an acute inflammatory process

affecting the brainaffecting the brain Viral infection is the most common and important Viral infection is the most common and important

cause, with over 100 viruses implicated worldwidecause, with over 100 viruses implicated worldwide Symptoms Symptoms

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

Causes of Viral Causes of Viral EncephalitisEncephalitis

Herpes viruses – HSV-1, HSV-2, varicella zoster virus, Herpes viruses – HSV-1, HSV-2, varicella zoster virus, cytomegalovirus, Epstein-Barr virus, human herpes virus 6 cytomegalovirus, Epstein-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 Arboviruses – examples: Japanese encephalitis; St. Louis

encephalitis virus; West Nile encephalitis virus; Eastern, encephalitis virus; West Nile encephalitis virus; Eastern, Western and Venzuelan equine encephalitis virus; tick Western and Venzuelan equine encephalitis virus; tick borne encephalitis virusborne encephalitis virus

Bunyaviruses – examples: La Crosse strain of California Bunyaviruses – examples: La Crosse strain of California virusvirus

Reoviruses – example: Colorado tick fever virusReoviruses – example: Colorado tick fever virus Arenaviruses – example: lymphocytic choriomeningitis Arenaviruses – example: lymphocytic choriomeningitis

virus virus

What Is An Arbovirus?What Is An Arbovirus?

Arboviruses = arthropod-borne viruses Arboviruses = arthropod-borne viruses Arboviruses are maintained in nature Arboviruses are maintained in nature

through biological transmission through biological transmission between susceptible vertebrate hosts between susceptible vertebrate hosts by blood-feeding arthropodsby blood-feeding arthropods

Vertebrate infection occurs when the Vertebrate infection occurs when the infected arthropod takes a blood mealinfected arthropod takes a blood meal

http://www.cdc.gov/ncidod/dvbid/arbor/schemat.pdf

Major Arboviruses That Major Arboviruses That Cause EncephalitisCause Encephalitis

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

http://www.cdc.gov/ncidod/dvbid/arbor/worldist.pdf

West Nile VirusWest Nile Virus

West Nile VirusWest Nile Virus FlavivirusFlavivirus Primary host – wild Primary host – wild

birdsbirds Principal arthropod Principal arthropod

vector – mosquitoesvector – mosquitoes Geographic Geographic

distribution - Africa, distribution - Africa, Middle East, Western Middle East, Western Asia, Europe, Asia, Europe, Australia, North Australia, North America, Central America, Central AmericaAmerica

http://www.walgreens.com/images/library/healthtips/july02/westnilea.jpg

History of West Nile History of West Nile VirusVirus

1937 - West Nile virus isolated from woman 1937 - West Nile virus isolated from woman in Ugandain Uganda

1950s – First recorded epidemics in Israel 1950s – First recorded epidemics in Israel (1951-1954, 1957)(1951-1954, 1957)

1962 – Epidemic in France1962 – Epidemic in France 1974 – Epidemic in South Africa. Largest 1974 – Epidemic in South Africa. Largest

ever West Nile epidemic.ever West Nile epidemic. 1996 – Romanian epidemic with features 1996 – Romanian epidemic with features

similar to those of the North American similar to those of the North American outbreak. 500 cases and 50 deaths.outbreak. 500 cases and 50 deaths.

1999 – Russian outbreak. 40 deaths. 1999 – Russian outbreak. 40 deaths.

West Nile Virus: 1999 New West Nile Virus: 1999 New York OutbreakYork Outbreak

Crows dying in and around Crows dying in and around Queens in late summerQueens in late summer

27 deaths among captive 27 deaths among captive birds in the Queens and birds in the Queens and Bronx zoosBronx zoos

Concomitant human infection Concomitant human infection of apparent encephalitis in of apparent encephalitis in the same areathe same area

Outbreak was first attributed Outbreak was first attributed to St. Louis encephalitis, but to St. Louis encephalitis, but tissue samples from dead tissue samples from dead crows confirmed that it was crows confirmed that it was West Nile virusWest Nile virus

59 human cases requiring 59 human cases requiring hospitalization, including 7 hospitalization, including 7 deathsdeaths

Spread of West Nile Virus Spread of West Nile Virus in the USin the US

2000 – spread throughout 2000 – spread throughout New England and Mid-New England and Mid-Atlantic regions.Atlantic regions. 18 new human cases reported18 new human cases reported

2001 – spread throughout the 2001 – spread throughout the entire eastern half of the USentire eastern half of the US 64 cases reported, with NY, 64 cases reported, with NY,

FL and NJ accounting for FL and NJ accounting for 60%60%

2002 – spread westward 2002 – spread westward across Great Plains into across Great Plains into Western US. Reached Western US. Reached California by Labor Day.California by Labor Day. By end of 2002 cumulative By end of 2002 cumulative

human cases > 3900, with > human cases > 3900, with > 250 deaths250 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 including 262 deaths in 45 states and D.C.states and D.C.

West Nile Activity in the US West Nile Activity in the US – Reports as of April 7, – Reports as of April 7,

20042004

West Nile Activity in the US West Nile Activity in the US – Counties Reporting Cases – Counties Reporting Cases

as of March 24, 2004as of March 24, 2004

West Nile Virus 2004:West Nile Virus 2004:BREAKING NEWSBREAKING NEWS

April 13, 2004 – Ohio may have first 2004 West April 13, 2004 – Ohio may have first 2004 West Nile CaseNile Case 79 year old man from Scioto County, OH was admitted 79 year old man from Scioto County, OH was admitted

April 1 with viral meningitis and encephalitis which April 1 with viral meningitis and encephalitis which rapidly progressed to coma over 2 days.rapidly progressed to coma over 2 days.

Initial IgM antibody titers were positive for West Nile virus Initial IgM antibody titers were positive for West Nile virus and he complained of itching from insect bites upon and he complained of itching from insect bites upon admissionadmission

Has been treated with blood-pressure drugs to control Has been treated with blood-pressure drugs to control over-response by the immune system to West Nile virus, over-response by the immune system to West Nile virus, causing brain inflammation.causing brain inflammation.

Previously unresponsive and paralyzed.Previously unresponsive and paralyzed. Can now open his eyes and shake his head in response to Can now open his eyes and shake his head in response to

questions, but still cannot talk.questions, but still cannot talk.

St. Louis St. Louis EncephalitisEncephalitis

St. Louis EncephalitisSt. Louis Encephalitis

FlavivirusFlavivirus Most common Most common

mosquito-mosquito-transmitted human transmitted human pathogen in the USpathogen in the US

Leading cause of Leading cause of epidemic flaviviral epidemic flaviviral encephalitisencephalitis

History of St. Louis History of St. Louis EncephalitisEncephalitis

1933 – virus isolated during St. Louis and 1933 – virus isolated during St. Louis and Kansas City, MO epidemicKansas City, MO 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 1974-1977 – last major epidemic. Over 2,500

cases in 35 states.cases in 35 states. 1990-1991 – South Florida epidemic. 226 1990-1991 – South Florida epidemic. 226

cases and 11 deaths.cases and 11 deaths. 1999 – New Orleans outbreak. 20 reported 1999 – New Orleans outbreak. 20 reported

cases.cases.

St. Louis EncephalitisSt. Louis Encephalitis

Japanese Japanese EncephalitisEncephalitis

Japanese EncephalitisJapanese Encephalitis Flavivirus related to St. Louis Flavivirus related to St. Louis

encephalitisencephalitis Most important cause of Most important cause of

arboviral encephalitis arboviral encephalitis worldwide, with over 45,000 worldwide, with over 45,000 cases reported annuallycases reported annually

Transmitted by culex Transmitted by culex mosquito, which breeds in mosquito, which breeds in rice fieldsrice fields Mosquitoes become infected Mosquitoes become infected

by feeding on domestic pigs by feeding on domestic pigs and wild birds infected with and wild birds infected with Japanese encephalitis virus. Japanese encephalitis virus. Infected mosquitoes transmit Infected mosquitoes transmit virus to humans and animals virus to humans and animals during the feeding process.during the feeding process.

History of Japanese History of Japanese EncephalitisEncephalitis

1800s – recognized in Japan1800s – recognized in Japan 1924 – Japan epidemic. 6125 cases, 3797 1924 – Japan epidemic. 6125 cases, 3797

deathsdeaths 1935 – virus isolated in brain of Japanese 1935 – virus isolated in brain of Japanese

patient who died of encephalitispatient who died of encephalitis 1938 – virus isolated from Culex mosquitoes in 1938 – virus isolated from Culex mosquitoes in

JapanJapan 1948 – Japan outbreak1948 – Japan outbreak 1949 – Korea outbreak1949 – Korea outbreak 1966 – China outbreak1966 – China outbreak Today – extremely prevalent in South East Today – extremely prevalent in South East

Asia. 30,000-50,000 cases reported each year. Asia. 30,000-50,000 cases reported each year.

Distribution of Japanese Distribution of Japanese Encephalitis in Asia, 1970-Encephalitis in Asia, 1970-

19981998

Eastern Equine Eastern Equine EncephalitisEncephalitis

Eastern Equine Eastern Equine EncephalitisEncephalitis

TogavirusTogavirus Caused by a virus transmitted Caused by a virus transmitted

to humans and horses by the to humans and horses by the bite of an infected mosquito.bite of an infected mosquito.

200 confirmed cases in the US 200 confirmed cases in the US 1964-present1964-present

Average of 4 cases per yearAverage of 4 cases per year States with largest number of States with largest number of

cases – Florida, Georgia, cases – Florida, Georgia, Massachusetts, and New Massachusetts, and New Jersey. Jersey.

Human cases occur relatively Human cases occur relatively infrequently, largely because infrequently, largely because the primary transmission the primary transmission cycle takes place in swamp cycle takes place in swamp areas where populations tend areas where populations tend to be limited. to be limited.

History of Eastern Equine History of Eastern Equine EncephalitisEncephalitis

1831 – First recognized as a disease in horses. 1831 – First recognized as a disease in horses. Over 75 horses died in 3 counties in Over 75 horses died in 3 counties in Massachusetts.Massachusetts.

1845-1912 – epizootics in Northeast and Mid-1845-1912 – epizootics in Northeast and Mid-Atlantic regionsAtlantic regions

1933 – virus isolated from horse brains1933 – virus isolated from horse brains 1938 – association of human disease with 1938 – association of human disease with

epizootics. 30 cases of fatal encephalitis in epizootics. 30 cases of fatal encephalitis in children living in same area as equine cases.children living in same area as equine cases.

1947 – largest recorded outbreak in Louisiana 1947 – largest recorded outbreak in Louisiana and Texas. 13,344 cases and 11,722 horse and Texas. 13,344 cases and 11,722 horse deathsdeaths

Western Equine Western Equine EncephalitisEncephalitis

Western Equine Western Equine EncephalitisEncephalitis

TogavirusTogavirus Mosquito-borneMosquito-borne 639 confirmed cases 639 confirmed cases

in the US since 1964 in the US since 1964 Important cause of Important cause of

encephalitis in encephalitis in horses and humans horses and humans in North America, in North America, mainly in the mainly in the Western parts of the Western parts of the US and CanadaUS and Canada

History of Western Equine History of Western Equine EncephalitisEncephalitis

Early 1900’s – epizootics of viral Early 1900’s – epizootics of viral encephalitis in horses described in encephalitis in horses described in ArgentinaArgentina

1912 – 25,000 horses died in Central 1912 – 25,000 horses died in Central Plains of USPlains of US

1930 – San Joaquin Valley, CA outbreak. 1930 – San Joaquin Valley, CA outbreak. 6000 cases in horses. Virus isolated from 6000 cases in horses. Virus isolated from horse brainshorse brains

1938 – virus isolated from brain of a child1938 – virus isolated from brain of a child

La Crosse La Crosse EncephalitisEncephalitis

La Crosse EncephalitisLa Crosse Encephalitis BunyavirusBunyavirus On average 75 cases per year On average 75 cases per year

reported to the CDCreported to the CDC Most cases occur in children Most cases occur in children

under 16 years oldunder 16 years old Zoonotic pathogen that cycles Zoonotic pathogen that cycles

between the daytime biting between the daytime biting treehole mosquito, and treehole mosquito, and vertebrate amplifier hosts vertebrate amplifier hosts (chipmunk, tree squirrel) in (chipmunk, tree squirrel) in deciduous forest habitatsdeciduous forest habitats

Most cases occur in the upper Most cases occur in the upper Midwestern state, but Midwestern state, but recently cases have been recently cases have been reported in the Mid-Atlantic reported in the Mid-Atlantic region and the Southeastregion and the Southeast

1963 – isolated in La Crosse, 1963 – isolated in La Crosse, WI from the brain of a child WI from the brain of a child who died from encephalitiswho died from encephalitis

Summary – Confirmed and Summary – Confirmed and Probable Human Cases in Probable Human Cases in

the USthe USVirusVirus YearsYears Total casesTotal cases

Eastern Eastern EquineEquine

1964-20001964-2000 182182

Western Western EquineEquine

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

Molecular Biology Molecular Biology of Viruses that can of Viruses that can

Cause Viral Cause Viral EncephalitisEncephalitis• Flaviviridae: Flaviviridae: West Nile VirusWest Nile Virus• Togaviridae: Togaviridae: Eastern and Eastern and Western Western Equine Equine

EncephalitisEncephalitis• Bunyaviridae: Bunyaviridae: La Crosse VirusLa Crosse Virus

FlavivirusFlavivirus• Japanese Encephalitis Japanese Encephalitis

VirusVirus• St. Louis encephalitis St. Louis encephalitis

virusvirus• West Nile VirusWest Nile Virus

Flavivirus: Virus Flavivirus: Virus ClassificationClassification

Family FlaviviridaeFamily Flaviviridae 3 Genera 3 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 Includes West Nile Virus (WNV), St. Louis

Encephalitis, and othersEncephalitis, and others

Scanned images of West Nile virus isolated from brain tissue from a

crow found in New York.

Viral Replication CycleViral Replication Cycle

Genome StructureGenome Structure

Viral GenomeViral Genome Positive Strand RNA GenomePositive Strand RNA Genome 1 ORF – Genome encodes single 1 ORF – Genome encodes single

polyprotein which is subsequently cleavedpolyprotein which is subsequently 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 Genome also includes 5’ and 3’ noncoding regions which have functional importanceregions which have functional importance

Secondary structure Secondary structure loopsloops

3’ Stem Loop of Plus 3’ Stem Loop of Plus StrandStrand

Tertiary interactions of 3’ non-coding region Tertiary interactions of 3’ non-coding region serve to stabilize and compact the 3’ region serve to stabilize and compact the 3’ region of the genome and may also create binding of the genome and may also create binding sites for cellular and/or viral proteinssites for cellular and/or viral proteins

Pseudoknots – Formed by interactions Pseudoknots – Formed by interactions between 3’ stem loop and adjacent between 3’ stem loop and adjacent nucleotidesnucleotides PK1 May be important for minus strand PK1 May be important for minus strand

replicationreplication Interacts with cellular proteinsInteracts with cellular proteins

P104, EF-1P104, EF-1αα, and p84, and p84

Conserved SecondaryConserved Secondary and and Tertiary Terminal RNA Tertiary Terminal RNA

Structures in Minus StrandStructures in Minus Strand Stem loop structures at 5’ and 3’ ends are Stem loop structures at 5’ and 3’ ends are

conserved across flavivirus species conserved across flavivirus species suggesting a functional importance for suggesting a functional importance for these groups.these groups.

Minus strand stem loops may play a role Minus strand stem loops may play a role in facilitating the formation of replication in facilitating the formation of replication complexes and in releasing newly complexes and in releasing newly synthesized minus strands from plus synthesized minus strands from plus strands.strands.

In addition, its interaction with cellular In addition, its interaction with cellular proteins is important for replication.proteins is important for replication.

Viral Proteins: Structural Viral Proteins: Structural and Non-Structuraland Non-Structural

Structural ProteinsStructural Proteins Capsid (C), Membrane (M), Envelope (E)Capsid (C), Membrane (M), Envelope (E)

The envelope - receptor binding The envelope - receptor binding Dimers of E protein arrange their β sheets in a Dimers of E protein arrange their β sheets in a

head to tail formation which lie flat on top of head to tail formation which lie flat on top of the lipid bilayer. The distal portions of these the lipid bilayer. The distal portions of these proteins are anchored in the membraneproteins 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 Many functions of non-structural proteins have yet to be determinedhave yet to be determined

Viral Non-Structural Viral Non-Structural ProteinsProteins

NS1- may play a role in flavivirus RNA synthesis; it has NS1- may play a role in flavivirus RNA synthesis; it has been shown to be essential for negative strand synthesisbeen shown to be essential for negative strand synthesis

NS2A, NS2B, NS4A, NS4B - may facilitate the assembly of NS2A, NS2B, NS4A, NS4B - may facilitate the assembly of viral replication complexes by an unknown mechanismviral replication complexes 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 RNA triphosphatase function thought to be important

for the synthesis of the 5’ cap structurefor the synthesis of the 5’ cap structure Helicase and NTPase activityHelicase and NTPase activity Its activity may be upregulated through interaction with Its activity may be upregulated through interaction with

phosphorylated NS5phosphorylated NS5 NS5NS5

RNA dependent RNA polymeraseRNA dependent RNA polymerase Methyltransferase domain thought to be required for Methyltransferase domain thought to be required for

formation of the 5’ capformation of the 5’ cap

Model for Closed-Loop Model for Closed-Loop Complex Formation in Complex Formation in

FlavivirusesFlaviviruses

TogavirusTogavirus

• Eastern Equine Encephalitis Eastern Equine Encephalitis VirusVirus

• Western Equine Encephalitis Western Equine Encephalitis VirusVirus

• Venezuelan Equine Encephalitis Venezuelan Equine Encephalitis VirusVirus

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 5’ end: Unknown number of non-structural

proteins probably involved in replicationproteins probably involved in replication Genome has an opposite orientation from Genome has an opposite orientation from

the Flaviviruses the Flaviviruses

Alphavirus StructureAlphavirus Structure

http://www.cdc.gov/ncidod/dvbid/arbor/alphavir.htm

Alphaviruses: Protein Alphaviruses: Protein FunctionFunction

E1and E2 glycoprotein heterodimers form trimers E1and E2 glycoprotein heterodimers form trimers that appear as knobs on the surface of the virionthat appear as knobs on the surface of the virion E1 – transmembrane glycoprotein with 2 to 3 N-linked E1 – transmembrane glycoprotein with 2 to 3 N-linked

glycosylation sitesglycosylation sites E2 - glycoprotein with 1 to 2 N-linked glycosylation E2 - glycoprotein with 1 to 2 N-linked glycosylation

sites, contains short intracytoplasmic tail and sites, contains short intracytoplasmic tail and hydrophobic stretch of amino acids that serves as the hydrophobic stretch of amino acids that serves as the fusion peptide for viral entryfusion peptide for viral entry

Capsid protein has a conserved N-terminal region Capsid protein has a conserved N-terminal region which binds RNA and a C-terminal region which which binds RNA and a C-terminal region which interacts with the cytoplasmic tail of E2 as well interacts with the cytoplasmic tail of E2 as well as capsid proteinsas capsid proteins

E3 and 6K proteins are signal sequences for E2 E3 and 6K proteins are signal sequences for E2 and E1, respectively, and are largely cleaved off and E1, respectively, and are largely cleaved off from the mature virionfrom the mature virion

Replication CycleReplication Cycle Proposed Model: E1 glycoprotein interacts with Proposed Model: E1 glycoprotein interacts with

proteins on the cell surface. E2 binds to cellular proteins on the cell surface. E2 binds to cellular proteins and receptor-mediated endocytosis takes proteins and receptor-mediated endocytosis takes place.place.

In acidified endosomal compartment, glycoproteins In acidified endosomal compartment, glycoproteins fuse with membrane and the nucleocapsid is released.fuse with membrane and the nucleocapsid is released.

Virion RNA serves as mRNA, translation of non-Virion RNA serves as mRNA, translation of non-structural proteins beginsstructural proteins 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 E2 At cellular membrane regions containing E1 and E2

heterodimers interact with nucleocapsids and viral heterodimers interact with nucleocapsids and viral particles bud from the cell surfaceparticles bud from the cell surface

BunyaviridaeBunyaviridae

La Crosse VirusLa Crosse Virus

La Crosse VirusLa Crosse Virus

http://www.virology.net/Big_Virology/BVRNAbunya.html

BunyavirusesBunyaviruses

Genome - single strand of negative sense Genome - single strand of negative sense RNARNA

Four structural proteinsFour structural proteins Two external proteinsTwo external proteins Two associated with RNA to form Two associated with RNA to form

nucleocapsidnucleocapsid Matrix proteins absent from Matrix proteins absent from

Bunyaviruses, therefore capsid proteins Bunyaviruses, therefore capsid proteins and envelope glycoproteins directly and envelope glycoproteins directly interact prior to buddinginteract prior to budding

http://www.cdc.gov/ncidod/dvbid/arbor/index.htm

BioweaponizationBioweaponization

West Nile virus

Mosquito vector

Bird reservoir hosts

Transmission Cycle is Transmission Cycle is Key to WeaponizationKey to Weaponization

Incidental infections

Incidental infections

http://www.cdc.gov/ncidod/dvbid/westnile/conf/February_2003.htm

BioweaponizationBioweaponization Vector, Vector, VectorVector, Vector, Vector

In areas around NYC mosquitoes are In areas around NYC mosquitoes are extremely ubiquitous during the summer extremely ubiquitous during the summer monthsmonths

Mosquitoes are already virulent, further Mosquitoes are already virulent, further genetic engineering is unnecessarygenetic engineering 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 Widespread Panic would be generated

as the outbreak progressesas the outbreak progresses

The Iraq ConnectionThe Iraq Connection

The US shipped various pathogens, The US shipped various pathogens, including WNV, to Iraq in the 1980sincluding WNV, to Iraq in the 1980s

In 1999 following the West Nile In 1999 following the West Nile Virus outbreak in NYC there were Virus outbreak in NYC there were fears that Iraqi bioterrorism was fears that Iraqi bioterrorism was involvedinvolved

Investigations by the CDC and the Investigations by the CDC and the CIA found no evidence of CIA found no evidence of bioterrorism in the 1999 outbreakbioterrorism in the 1999 outbreak

WNV as a low-tech WNV as a low-tech Bioweapon:Bioweapon:

Possible Connection to Possible Connection to 1999 outbreak1999 outbreak Gather mosquitoes in an endemic areaGather mosquitoes in an endemic area

Incubate mosquitoes with a food Incubate mosquitoes with a food sourcesource

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 Take bus from airport; Release

mosquitoes from bus windowmosquitoes from bus window Wait for outbreakWait for outbreak Source: Dr. Ilya Trakht

Clinical Clinical ConsiderationsConsiderations

Case StudyCase StudyIn August 2002, a 91 year old male from Northern In August 2002, a 91 year old male from Northern Staten Island who presented initially with sudden onset Staten Island who presented initially with sudden onset of fever, left lower extremity weakness, inability to of fever, left lower extremity weakness, inability to walk, and possibly some transient and mild AMS, was walk, and possibly some transient and mild AMS, was admitted to a Staten Island hospital. admitted to a Staten Island hospital.

He was not considered to have aseptic meningitis or He was not considered to have aseptic meningitis or encephalitis and WN virus infection was not considered encephalitis and WN virus infection was not considered at that time. After being discharged, he was evaluated at that time. After being discharged, he was evaluated by a neurologist for persistent left leg weakness and by a neurologist for persistent left leg weakness and inability to walk. inability to walk.

In April 2003, the neurologist reported this case to the In April 2003, the neurologist reported this case to the DOHMH as a possible polio case. Serological DOHMH as a possible polio case. Serological specimens were forwarded to the NYSDOH where they specimens were forwarded to the NYSDOH where they tested positive for WN virus.tested positive for WN virus.


DiagnosisDiagnosis

Patient HistoryPatient History Detailed history critical to determine the likely cause of Detailed history critical to determine the likely cause of

encephalitis. encephalitis. Prodromal illness, recent vaccination, development of few Prodromal illness, recent vaccination, development of few

days → Acute Disseminated Encephalomyelitis (ADEM) .days → Acute Disseminated Encephalomyelitis (ADEM) . Biphasic onset: systemic illness then CNS disease → Biphasic onset: systemic illness then CNS disease →

Enterovirus encephalitis. 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.

History cont.History cont. SeasonSeason

Japanese encephalitis is more common during the rainy Japanese encephalitis is more common during the rainy season.season.

Arbovirus infections are more frequent during summer Arbovirus infections are more frequent during summer and fall. and fall.

Predisposing factors:Predisposing factors: Immunosuppression caused by disease and/or drug Immunosuppression caused by disease and/or drug

treatment. 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 abuse Drug ingestion and/or abuse TraumaTrauma

Initial SignsInitial Signs

HeadacheHeadache Malaise Malaise Anorexia Anorexia Nausea and VomitingNausea and Vomiting Abdominal painAbdominal pain

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 change personality change behavioral disorders behavioral disorders occasionally frank psychosisoccasionally frank psychosis

Focal or general seizures in >50% severe Focal or general seizures in >50% severe cases.cases.

Severe focused neurologic deficits.Severe focused neurologic deficits.

Neurologic SignsNeurologic Signs

Virtually every possible focal neurological Virtually every possible focal neurological disturbance has been reported.disturbance has been reported.

Most CommonMost Common AphasiaAphasia Ataxia Ataxia Hemiparesis with hyperactive tendon reflexesHemiparesis with hyperactive tendon reflexes Involuntary movementsInvoluntary movements Cranial nerve deficits (ocular palsies, facial Cranial nerve deficits (ocular palsies, facial

weakness)weakness)

Other Causes of Other Causes of EncephalopathyEncephalopathy

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 Mitochondrial cytopathy (Reye’s and MELAS

syndromes)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)

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 (2) Parameningeal infections or partially treated bacterial

meningitismeningitis (3) Nonviral infectious meningitides where cultures may be (3) Nonviral infectious meningitides where cultures may be

negative (e.g., fungal, tuberculous, parasitic, or syphilitic negative (e.g., fungal, tuberculous, parasitic, or syphilitic disease)disease)

(5) Meningitis secondary to noninfectious inflammatory diseases(5) Meningitis secondary to noninfectious inflammatory diseases MRIMRI

Can exclude subdural bleeds, tumor, and sinus thrombosis Can exclude subdural bleeds, tumor, and sinus thrombosis Biopsy Biopsy

Reserved for patients who are worsening, have an undiagnosed Reserved for patients who are worsening, have an undiagnosed lesion after scan, or a poor response to acyclovir.lesion after scan, or a poor response to acyclovir.

Clinical signs cannot distinguish different viral Clinical signs cannot distinguish different viral encephalitidesencephalitides

Differential Diagnosis Differential Diagnosis cont.cont.

EncephalopathyEncephalopathy EncephalitisEncephalitisFeverFever Uncommon Uncommon CommonCommonHeadache Headache UncommonUncommon CommonCommonAMS AMS Steady deterioration May fluctuateSteady deterioration May fluctuateFocal Neurologic Signs Focal Neurologic Signs Uncommon Uncommon CommonCommonTypes of seizures Types of seizures GeneralizedGeneralized BothBothBlood: Leukocytosis Blood: Leukocytosis UncommonUncommon CommonCommonCSF: Pleocytosis CSF: Pleocytosis UncommonUncommon CommonCommonEEG: Diffuse slowingEEG: Diffuse slowing CommonCommon +Focal+FocalMRI MRI Often normal Often normal Focal Abn.Focal Abn.


RadiologyRadiology

MRIMRI

MRIMRI


Laboratory DiagnosisLaboratory Diagnosis

Laboratory DiagnosisLaboratory Diagnosis

Diagnosis is usually based on CSF Diagnosis is usually based on CSF Normal glucoseNormal glucose Absence of bacteria on culture. Absence of bacteria on culture. Viruses occasionally isolated directly Viruses occasionally isolated directly

from CSFfrom CSF Less than half are identifiedLess than half are identified

Polymerase Chain Reaction Polymerase Chain Reaction techniquestechniques Detect specific viral DNA in CSFDetect specific viral DNA in CSF

NYSDOH PCRNYSDOH PCRNEW YORK STATE DEPARTMENT OF HEALTH (NYSDOH)NEW YORK STATE DEPARTMENT OF HEALTH (NYSDOH)

Viral Encephalitis Letter of Agreement forViral Encephalitis Letter of Agreement forPhysician 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 NYSDOH's Wadsworth Center offers the following tests on CSF for viral encephalitis:encephalitis:

PCR testing for a panel of viruses, including: herpes simplex, varicella zoster, PCR testing for a panel of viruses, including: herpes simplex, varicella zoster, cytomegalovirus, Epstein-Barr virus, enteroviruses, St. Louis encephalitis cytomegalovirus, Epstein-Barr virus, enteroviruses, St. Louis encephalitis (SLE), eastern equine encephalitis (EEE), California encephalitis (including (SLE), eastern equine encephalitis (EEE), California encephalitis (including LaCrosse and Jamestown Canyon viruses), Powassan and West Nile (WN) LaCrosse and Jamestown Canyon viruses), Powassan and West Nile (WN) viruses, andviruses, andEnzyme-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 If 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 ELISA and PCR for WN virus, please consider the following in determining which test is most appropriate for your patient:which test is most appropriate for your patient:ELISA is more sensitive than PCR for WN viral testing and should be ELISA is more sensitive than PCR for WN viral testing and should be considered when there is stronger suspicion of WN virus than other viruses. considered when there is stronger suspicion of WN virus than other viruses. PCR is less sensitive for WN virus, but tests for a wide range of viruses. PCR PCR 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. should be considered if viruses other than WN virus are suspected.

Please note your testing priority below or on the viral Please note your testing priority below or on the viral encephalitis/meningitis case report form. If PCR testing is desired, encephalitis/meningitis case report form. If PCR testing is desired, the agreement below must be completed.the agreement below must be completed.

Viral Encephalitis PCR PanelViral Encephalitis PCR Panel West Nile Virus ELISA Antibody Testing West Nile Virus ELISA Antibody Testing


Disease ProgressionDisease Progression

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 Loss of tissue fluid may be equally

important.important. Homeostatic failureHomeostatic failure Decreased respiratory driveDecreased respiratory drive


TreatmentTreatment

TreatmentTreatment

When HSE cannot be ruled out, When HSE cannot be ruled out, Acyclovir must be started promptly Acyclovir must be started promptly (before the patient lapses into coma) (before the patient lapses into coma) and continued at least 10 days for and continued at least 10 days for maximal therapeutic benefit. maximal therapeutic benefit.

Rocky Mountain spotted fever Rocky Mountain spotted fever should also be considered, and should also be considered, and empiric treatment with Doxycycline empiric treatment with Doxycycline is indicated.is indicated.

Suspected HSE Suspected HSE Treatment PlanTreatment Plan

AcyclovirAcyclovir

Acyclovir is a synthetic purine Acyclovir is a synthetic purine nucleoside analogue with inhibitory nucleoside analogue with inhibitory activity against HSV-1 and HSV-2, activity against HSV-1 and HSV-2, varicella-zoster virus (VZV), Epstein-varicella-zoster virus (VZV), Epstein-Barr virus (EBV) and Barr virus (EBV) and cytomegalovirus (CMV)cytomegalovirus (CMV) In order of decreasing effectivenessIn order of decreasing effectiveness

Highly selectiveHighly selective

Acyclovir ActionAcyclovir Action Thymidine Kinase (TK) of uninfected cells does not use Thymidine Kinase (TK) of uninfected cells does not use

acyclovir as a substrate.acyclovir as a substrate. TK encoded by HSV, VZV and EBV2 converts acyclovir into TK encoded by HSV, VZV and EBV2 converts acyclovir into

acyclovir monophosphate. acyclovir monophosphate. The monophosphate is further converted into diphosphate by The monophosphate is further converted into diphosphate by

cellular guanylate kinase and into triphosphate by a number cellular guanylate kinase and into triphosphate by a number of cellular enzymes.of cellular enzymes.

Acyclovir triphosphate interferes with Herpes simplex virus Acyclovir triphosphate interferes with Herpes simplex virus DNA polymerase and inhibits viral DNA replication. DNA polymerase and inhibits viral DNA replication.

Acyclovir triphosphate incorporated into growing chains of Acyclovir triphosphate incorporated into growing chains of DNA by viral DNA polymerase.DNA by viral 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 Acyclovir is preferentially taken up and selectively converted

to the active triphosphate form by HSV-infected cells. to the active triphosphate form by HSV-infected cells. Thus, acyclovir is much less toxic Thus, acyclovir is much less toxic in vitroin vitro for normal for normal

uninfected cells because: 1) less is taken up; 2) less is uninfected cells because: 1) less is taken up; 2) less is converted to the active form.converted to the active form.

Supportive TherapySupportive Therapy Fever, dehydration, electrolyte imbalances, and Fever, dehydration, electrolyte imbalances, and

convulsions require treatment.convulsions require treatment. For cerebral edema severe enough to produce herniation, For cerebral edema severe enough to produce herniation,

controlled hyperventilation, mannitol, and dexamethasone.controlled 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 If these measures are used, monitoring ICP should be

considered. considered. If there is evidence of ventricular enlargement, If there is evidence of ventricular enlargement,

intracranial pressure may be monitored in conjunction intracranial pressure may be monitored in conjunction with CSF drainage.with CSF drainage. Outcome is usually poor.Outcome is usually poor. For infants with subdural effusion, repeated daily subdural For infants with subdural effusion, repeated daily subdural

taps through the sutures usually helps. taps through the sutures usually helps. No more than 20 mL/day of CSF should be removed from one No more than 20 mL/day of CSF should be removed from one

sideside to prevent sudden shifts in intracranial contents. to prevent sudden shifts in intracranial contents. If the effusion persists after 3 to 4 weeks of taps, surgical If the effusion persists after 3 to 4 weeks of taps, surgical

exploration for possible excision of a subdural membrane is exploration for possible excision of a subdural membrane is indicated.indicated.

DexamethasoneDexamethasone

Synthetic adrenocortical steroid Synthetic adrenocortical steroid Potent anti-inflammatory effectsPotent anti-inflammatory effects Dexamethasone injection is Dexamethasone injection is

generally administered initially via generally administered initially via IV then IMIV then IM

Side effects: convulsions; increased Side effects: convulsions; increased ICP after treatment; vertigo; ICP after treatment; vertigo; headache; psychic disturbances headache; psychic disturbances


Patient PrognosisPatient Prognosis

PrognosisPrognosis The mortality rate varies with etiology, and epidemics The mortality rate varies with etiology, and epidemics

due to the same virus vary in severity in different years. due to the same virus vary in severity in different years. Bad: Eastern equine encephalitis virus infection, nearly 80% of Bad: Eastern equine encephalitis virus infection, nearly 80% of

survivors have severe neurological sequelae. survivors have severe neurological sequelae. Not so Bad: EBV, California encephalitis virus, and Venezuelan Not so Bad: EBV, California encephalitis virus, and Venezuelan

equine encephalitis virus, severe sequelae are unusual. equine encephalitis virus, severe sequelae are unusual. Approximately 5 to 15% of children infected with LaCrosse Approximately 5 to 15% of children infected with LaCrosse

virus have a residual seizure disorder, and 1% have persistent virus have a residual seizure disorder, and 1% have persistent hemiparesis. hemiparesis.

Permanent cerebral sequelae are more likely to occur in Permanent cerebral sequelae are more likely to occur in infants, but young children improve for a longer time infants, but young children improve for a longer time than adults with similar infections. than adults with similar infections. Intellectual impairment, learning disabilities, hearing loss, and Intellectual impairment, learning disabilities, hearing loss, and

other lasting sequelae have been reported in some studies. other lasting sequelae have been reported in some studies.

Prognosis w/ TreatmentPrognosis w/ Treatment Considerable variation in the incidence and severity of Considerable variation in the incidence and severity of

sequelae.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 incidence and severity of sequelae were directly related to

the age of the patient and the level of consciousness at the time the age of the patient and the level of consciousness at the time of initiation of therapy. of initiation of therapy.

Patients with severe neurological impairment (Glasgow coma Patients with severe neurological impairment (Glasgow coma score 6) at initiation of therapy either died or survived with score 6) at initiation of therapy either died or survived with severe sequelae. severe sequelae.

Young patients (<30 years) with good neurological function at Young patients (<30 years) with good neurological function at initiation of therapy did substantially better (100% survival, initiation of therapy did substantially better (100% survival, 62% with no or mild sequelae) compared with their older 62% with no or mild sequelae) compared with their older counterparts (>30 years); (64% survival, 57% no or mild counterparts (>30 years); (64% survival, 57% no or mild sequelae). sequelae).

Recent studies using quantitative CSF PCR tests for HSV Recent studies using quantitative CSF PCR tests for HSV indicate that clinical outcome following treatment also indicate that clinical outcome following treatment also correlates with the amount of HSV DNA present in CSF at correlates with the amount of HSV DNA present in CSF at the time of presentation. the time of presentation.

Glasgow Coma ScaleGlasgow Coma Scale TestTest ResponseResponse ____Score ____Score Eye Eye NoneNone 11 OpeningOpening To painTo pain 22 To verbal stimuliTo verbal stimuli 33 Spontaneously Spontaneously 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


VaccinationVaccination

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 There is no JE-specific therapy other than supportive

care care Live-attenuated vaccine developed and tested in Live-attenuated vaccine developed and tested in

China China Appears to be safe and effectiveAppears to be safe and effective Chinese immunization programs involving millions of Chinese immunization programs involving millions of

children children Vero cell-derived inactivated vaccines have been Vero cell-derived inactivated vaccines have been

developed in Chinadeveloped in China 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

Public Health Public Health ConsiderationsConsiderations

Endemic PreventionEndemic Prevention

Infection ControlInfection Control

CDC’s “Three Ways to Reduce CDC’s “Three Ways to Reduce your West Nile Virus Risk”your West Nile Virus Risk” Avoid mosquito bitesAvoid mosquito bites Mosquito-proof your homeMosquito-proof your home Help your communityHelp your community

Avoid Mosquito BitesAvoid Mosquito Bites

Apply Insect Repellent Containing Apply Insect Repellent Containing DEETDEET

Clothing Can Help Reduce Clothing Can Help Reduce Mosquito BitesMosquito Bites Cover upCover up

Be Aware of Peak Mosquito HoursBe Aware of Peak Mosquito Hours Dusk to dawn are peak mosquito biting Dusk to dawn are peak mosquito biting

times for many species.times for many species.

Mosquito-Proof Home Mosquito-Proof Home

Drain Standing WaterDrain Standing Water Install or Repair ScreensInstall or Repair Screens

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

Blood SupplyBlood Supply NYC Policy Statement reflecting FDA policy:NYC Policy Statement reflecting FDA policy:

““To reduce WN transmission through blood To reduce WN transmission through blood components…. Blood donations will be components…. Blood donations will be screened for WN virus RNA… using nucleic screened for WN virus RNA… using nucleic acid amplification tests (NAT). In the event of acid amplification tests (NAT). In the event of a NAT-reactive donation, blood centers will a NAT-reactive donation, blood centers will remove and quarantine all blood components remove and quarantine all blood components associated with the donation and notify the associated with the donation and notify the state or local health department. In addition, state or local health department. In addition, blood testing centers have added screening blood testing centers have added screening questions to identify and exclude persons with questions to identify and exclude persons with fever and headache in the week prior to fever and headache in the week prior to donation.”donation.”

Mosquito Control Mosquito Control ProgramsPrograms

NYC DOHMH Statement:NYC DOHMH Statement:

““ We hope that spraying of adulticides We hope that spraying of adulticides will not be required this summer. will not be required this summer. However, if there is a threat of an However, if there is a threat of an outbreak of human illness and spraying outbreak of human illness and spraying is deemed necessary, targeted adult is deemed necessary, targeted adult mosquito control measures (via ground mosquito control measures (via ground or aerial spraying of pesticides) may be or aerial spraying of pesticides) may be required.”required.”

Mosquito ControlMosquito Control

But wait, there’s more:But wait, there’s more: Same Memo:Same Memo:

Confirmed or suspected cases of Confirmed or suspected cases of pesticide poisoning must be reported pesticide poisoning must be reported to the New York State Department of to the New York State Department of Health’s Pesticide Poisoning Registry Health’s Pesticide Poisoning Registry at (800)-322-6850, and to the New at (800)-322-6850, and to the New York City Poison Control Center at York City Poison Control Center at (212)-764-7667.(212)-764-7667.

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 toxic Although pyrethroids are among the least toxic

insecticides, they are nerve poisons, and act upon insecticides, they are nerve poisons, and act upon the sodium ion channels in nerve cell membranes.the sodium ion channels in nerve cell membranes.

Inhaling pyrethroid insecticides can cause Inhaling pyrethroid insecticides can cause coughing, wheezing, shortness of breath, runny coughing, wheezing, shortness of breath, runny or stuffy nose, chest pain, or difficulty breathing. or stuffy nose, 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 Sumithrin is not very toxic to mammals, but it is

highly toxic to bees and fish.highly toxic to bees and fish.

Crop-Dusting NYC?Crop-Dusting NYC?

Aerosolized liquids sprayed over Aerosolized liquids sprayed over large areas of the city.large areas of the city.

Terrorism concern?Terrorism concern? New vector for urban area.New vector for urban area.

Public Health Public Health ConsiderationsConsiderations

SurveillanceSurveillance

SurveillanceSurveillance

““Since 2000, the NYC DOHMH has conducted Since 2000, the NYC DOHMH has conducted comprehensive arthropod-borne disease comprehensive arthropod-borne disease surveillance and control. In 2003, efforts will surveillance and control. In 2003, efforts will again focus on mosquito control through again focus on mosquito control through reduction of breeding sites and application of reduction of breeding sites and application of larvicides. In addition, comprehensive mosquito, larvicides. In addition, comprehensive mosquito, avian and human data collected during the 2000-avian and human data collected during the 2000-2002 seasons have allowed NYC DOHMH to 2002 seasons have allowed NYC DOHMH to develop more sensitive surveillance criteria for develop more sensitive surveillance criteria for determining the level of WN viral activity in birds determining the level of WN viral activity in birds and mosquitoes that may indicate a significant and mosquitoes that may indicate a significant risk for a human outbreak. These indicators will risk for a human outbreak. These indicators will be monitored citywide to identify areas at risk for be monitored citywide to identify areas at risk for human transmission.”human transmission.”

Standing Water Standing Water ReportingReporting

The Department of Health & Mental The Department of Health & Mental Hygiene is now accepting reports of Hygiene is now accepting reports of standing water. However, we will standing water. However, we will not be able to visit and treat all not be able to visit and treat all reported nuisances. Therefore we reported nuisances. Therefore we are encouraging City residents and are encouraging City residents and business owners to take immediate business owners to take immediate action to eliminate standing water action to eliminate standing water on their property. on their property.

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 The Department of Health & Mental Hygiene is now accepting reports of dead birds. Only a is now accepting reports of dead birds. Only a sample of dead birds that meet specific criteria sample of dead birds that meet specific criteria will be picked up and tested for the West Nile will be picked up and tested for the West Nile virus. However, your report of a dead bird is virus. However, your report of a dead bird is extremely important to us because dead bird extremely important to us because dead bird reports may indicate the presence of West Nile reports may indicate the presence of West Nile virus. If you do not receive a call back from the virus. If you do not receive a call back from the Department of Health within two business Department of Health within two business days of making your report, please dispose of days of making your report, please dispose of the bird.the bird.

Mosquito TestingMosquito Testing

““Five pools of mosquitoes collected in New York City Five pools of mosquitoes collected in New York City have tested positive for West Nile (WN) virus. These have tested positive for West Nile (WN) virus. These include a pool of include a pool of Culex salinariusCulex salinarius, a human biting , a human biting mosquito, collected on July 15, in the Willowbrook mosquito, collected on July 15, in the Willowbrook Park area of Staten Island, a pool Park area of Staten Island, a pool of Culex restuansof Culex restuans, , primarily a bird-biting mosquito, collected from primarily a bird-biting mosquito, collected from Brookville Park, Queens on July 17, a pool of Brookville Park, Queens on July 17, a pool of Culex Culex pipienspipiens, a mosquito that bites both birds and humans, , a mosquito that bites both birds and humans, collected from the Hunts Point area of the Bronx on collected from the Hunts Point area of the Bronx on July 18, a pool of July 18, a pool of CulexCulex species collected from species collected from Jamaica Bay, Queens on July 16, and a pool of Jamaica Bay, Queens on July 16, and a pool of Culex Culex salinariussalinarius collected from Greenwood Cemetery, collected from Greenwood Cemetery, Brooklyn on July 21. These positive pools are the first Brooklyn on July 21. These positive pools are the first evidence of West Nile (WN) virus in New York City in evidence of West Nile (WN) virus in New York City in 2003” 2003”

Disease ReportingDisease Reporting

““The New York City Department of Health The New York City Department of Health and Mental Hygiene (NYC DOHMH) is and Mental Hygiene (NYC DOHMH) is again requesting that during the peak again requesting that during the peak adult mosquito season, from June 1 – adult mosquito season, from June 1 – October 31, 2003, all suspected cases of October 31, 2003, all suspected cases of viral encephalitis viral encephalitis (all ages)(all ages) and viral and viral meningitis meningitis (adults only)(adults only) be reported be reported immediately by telephone or facsimile and immediately by telephone or facsimile and that appropriate laboratory specimens that appropriate laboratory specimens (cerebrospinal fluid and sera)(cerebrospinal fluid and sera) be submitted be submitted promptly for testing for West Nile (WN) promptly for testing for West Nile (WN) virus.”virus.”

Documents

Viral Encephalitis