Dave Warshauer PhD DABMM Deputy Director Communicable Diseases Wisconsin State Laboratory of Hygiene WISCONSIN STATE LABORATORY OF HYGIENE UNIVERSITY OF WISCONSIN 2 Describe the arboviruses that cause disease in the US and Wisconsin ID: 775239
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Slide2Arboviruses: Update and Review
Dave Warshauer, PhD, D(ABMM)
Deputy Director, Communicable DiseasesWisconsin State Laboratory of Hygiene
WISCONSIN STATE LABORATORY OF HYGIENE - UNIVERSITY OF WISCONSIN 2
Slide3Describe the arboviruses that cause disease in the US and WisconsinDescribe the epidemiology of the arbovirusesDescribe arbovirus laboratory diagnosisDescribe the arbovirus surveillance activities in Wisconsin
Objectives
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Slide4Medically Important Arboviruses in the United States
Family/GenusPathogensTogaviridae/AlphavirusEastern equine encephalitisss + RNA +; 70 nm particleWestern equine encephalitisVenezuelan equine encephalitisFlaviviridae/FlavivirusSt. Louis encephalitisss + RNA; 40-60 nm particlePowassanWest Nile DengueBunyaviridae/Bunyavirus California serogroupCalifornia encephalitisss -RNA; 3 segment genomeLa Crosse encephalitisJamestown CanyonSnowshoe hareCache Valley (bunyamwera)Reoviridae/ColtivirusColorado tick feverds RNA
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Slide7WeatherTemp and precipitationZoonotic host and vector abundanceHuman behaviorRepellent use, outdoor activitiesUse of air conditioning or screens
Factors that Affect Arbovirus Incidence
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Slide82-15 day incubationUsually mild and nonspecificHeadache, Fever,FatigueMuscle achesSwollen lymph nodesNeuroinvasive diseaseFlaccid paralysisEncephalitisMeningitis
Clinical Manifestations
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Slide10WNV80% experience no symptoms20% relatively mild illness (WNV fever)<1% (approx 1:150) seriously illNeuroinvasive diseaseHigh feverNeck stiffnessExtreme muscle weaknessDisorientationTremors, convulsions, disorientation10% mortality
Clinical Manifestations
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Slide11Previous WNV Outbreaks/Isolations
1937 West Nile, Uganda1951-54, 57 Israel1962 France1974 South Africa1996 Romania1999 Russia1999-2000 USA, Israel 2002 Canada
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Slide121999
2000
2001
2002
Spread of WN Virus in the US
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Slide13West Nile Virus In Wisconsin
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Slide14WNV Neuroinvasive Disease, 2013
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Slide15West Nile Virus – Transmission Cycle
Incidental infections
Mosquito vector
Reservoir
hosts
Transmission Cycle
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Slide16West Nile Virus-Human InfectionsNovel Modes of Transmission
TransplantationTransfusionBreastfeeding Transplacental transmissionOccupational exposure
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Slide17West Nile Virus In Wisconsin
WNV Dead Bird SurveillanceSensitive indicator of viral activity in the environmentMonitor the spread of the virusCrudely estimates intensity of epizooticDoes not predict human risk
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Slide18SurveillanceCrows Ideal Sentinels
Widely distributedFound in multiple settingsHighly susceptibleMortality > 90%Virus titers in tissues high enough to permit delayed testing
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Slide19Avian Surveillance
Crows:Reported by residentsCollected by LHDTested at WVDL
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Slide20West Nile Virus - Mosquitoes
175 mosquito species found in the U.S. Over 50 species of mosquitoes in WisconsinNot all of them bite people Only female mosquitoes seek blood mealsVery few mosquitoes are infected with virus Typically <1% mosquitoes of any species found with virus
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Slide21CDC Tests for WNV
Specimen1st ChoiceOtherCommentsHuman serum/CSFIgM, IgG ELISAPlaque Reduction NeutralizationNAATVirus IsolationNAAT (57%) for acute CSF; <10% serumHuman tissueNAATVirus IsolationIHCFatal WN cases: NAAT positive ~ 100%Non-Human1st Choice2nd ChoiceAvian tissueNAATVirus isolationVecTest Ag. Cap. ELISAAg.-based tests require1000 pfuMosquito poolNAATVirus isolationVecTestAg. Cap. ELISA
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Slide22DAYS POST ONSET
1 2 3 4 5 6 7 8 9 10
-5 -4 -3 -2 -1 0
IgM
IgG
ELISA
P/N
#
pfu
/ml
WN
viremia
150
illness
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Slide23HRP
HRP
Coat With Goat anti-Human IgM
4
° Overnight
Add Patient Serum @ 1:400
37
° 1 Hour
Add West Nile Recombinant Antigen
4
° Overnight
Add HRP anti-Flavivirus McAb
37
° 1 Hour
IgM Capture ELISA
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Slide24P/N: O.D. patient serum/O.D. negative control serum.P/N > 3 = positiveP/N < 2 = negativeP/N 2-3 = equivocalELISA Assay must be standardized in each lab
Interpretation of Results
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Slide26Plaque-reduction neutralization assay (PRNT)Microsphere immmunoassay (MIA)SLE/WNVBioPlex instrument
Additional/Confirmatory Testing
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Slide27WN Serological Data
Typical Human WN Case
In primary flavivirus infections ;
Martin et al 2002
: IgM P/N to WN is 3-5X greater than SLE. 2002 data: Use 2X criteria WN to SLE ratio: only 1 exception in 417 WN confirmed cases.
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Slide28Longevity of Human WN Virus-Reactive IgM in Serum
5.0
(3.1-6.9)
6 (60)
2
5 (42)
12
500
4.0 (31.-6.5)
11 (52)
2
9 (43)
21
300-400
6.0 (3.0-10.8)
17 (77)
4
13 (60)
22
200
Ave. P/N (Range)
Total (%)
Equivocal
Positive (%)
N
Days P.I.
Positive MAC-ELISA
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Slide29CDC IgM ELISA Assay
Good
Points Sensitive Relatively Specific (WN & SLE P/N ratio) Technology Transferable
Bad Points Cross-reactivity among flaviviruses Limited utility in secondary infections Two day testTechnically complex IgM persistence
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Slide30Serological Testing Algorithmfor West Nile Virus
human serum/csf
IgM ELISA WN & SLE
POS
NEG
Plaque reduction
Neutralization test (PRNT) with:SLE, WN, (other flaviviruses)
STOP
National Case Definition
Confirmed:
IgM pos csf
IgM pos serum + PRNT
>4-fold increase PRNT titer
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Slide31IgM Detectable in serum & csf by onset (99%)6 exceptions------ serum from 800 cases10 exceptions----- csf from 800 IgG Positive by day 7 Post-OnsetP/N 3-5X Higher to WN than SLEIgM Persistence > 1 YearSecondary Flavivirus Infections are Problematic
WN Human Serological Data
Lessons Learned 1999-2002
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Slide32WNV-TO DO LIST
Effective therapiesVaccine developmentMethods of vector controlBasic research on the virusDevelopment of commercial diagnostic tests that can be used in the clinical laboratoryFocus Laboratories FDA approved IgM IgGOther commercial lab LDT assays
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Slide33POWASSAN
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Slide34Two typesLineage 1 POWAssociated with Ixodes cookei or I. marxiLineage 2 (Deer Tick Virus) POWAssociated with I. scapularisBoth linked to human disease
Powassan Virus
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I.
cookei
Slide35Maintained in a cycle between ticks and small-to-medium-sized rodentsI. cookei-----woodchucksI. marxi-----squirrels
Powassan Virus Transmission
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Slide36Ixodes scapularis(Blacklegged Tick)
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Slide37Incubation period 1-4 weeksMany people asymptomaticFever, headache, vomiting, weakness, confusion, loss of coordination, speech difficulties, and seizuresEncephalitis and meningitis50% with permanent neurological symptoms10% fatality rate
Powassan Clinical Manifestations
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Slide38Powassan virus neuroinvasive disease cases reported 2004-2013
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Slide40Powassan Virus 2014
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Pos
Tests
Mass 4
NJ 1
NY
1
WI 2
Slide41Clinical features, activities, epidemiologic history of the location where infection likely occurredLaboratory Diagnosis—in fatal casesNucleic acid amplificationHistopathology w/ immunohistochemistryVirus CultureRoutine testingIgM capture ELISA or MIAIgG ELISA
Powassan Diagnosis
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Slide42CSF findingsLymphocytic pleocytosis Usually <500 WBCs/mm3Granulocytes can predominate early in diseaseProtein normal and mildly elevatedGlucose normalMRI brain scanChanges consistent with microvascular ischemia or demyelinating disease in the parietal or temporal lobes
Powassan Diagnosis
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Slide43La Crosse 2014
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Slide44EEE Virus 2014
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Slide45California serogroupWide distribution in North AmericaInitially described in the early 1970s to cause mild human febrile diseaseAffects adults and more likely to cause meningitisSeroprevalence of up to 12% in NY and CTRetrospective studies shows JCV under-diagnosed1971-1981----41/53 patients had antibody to JCVReports are rareBecame reportable in US in 2004Circulates primarily between deer and mosquiotoes
Jamestown Canyon Virus
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Slide46Bird surveillanceCorvids---crow, blue jays, and ravensReport all sick and dead corvids for WNV testingDead-bird hotline 800-433-1610Equine WNV surveillanceWVDL reports positive results to DPH
Arbovirus Surveillance in Wisconsin
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Slide47Human Surveillance Diagnostic testing at WSLHPanel—LAC, EEE, WNV, SLE, POW, JC to CDC when requested by DPHAlso, consider Enterovirus Fee-exempt testing for patients who meet criteriaConfirmatory testing of positive results from other labsPatient >65 yr with CNS disease with no other DxDiagnosis of Guillain-Barre and no other lab Dx.Request of LHDFee-for-service available for patients who do not meet criteriahttps://www.dhs.wisconsin.gov/arboviral/westnilevirus.htm
Arbovirus Surveillance in Wisconsin
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Slide48Thank You
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