West Nile Virus in North America: West Nile Virus in North America: An UpdateAn Update

Division of VectorDivision of Vector--Borne Infectious DiseasesBorne Infectious DiseasesFort Collins, ColoradoFort Collins, Colorado

Photo of Cx. quinquefasciatuscourtesy of Dr. Stephen Higgs, UTMB/Galveston

West Nile Virus before 1996West Nile Virus before 1996

•• Isolation in 1937, West Nile district of UgandaIsolation in 1937, West Nile district of Uganda•• Mild dengueMild dengue--like illnesslike illness•• CNS involvement rareCNS involvement rare•• Wide distribution in Asia, Eastern Europe, Africa Wide distribution in Asia, Eastern Europe, Africa

West Nile Virus Since 1996West Nile Virus Since 1996

•• More frequent outbreaksMore frequent outbreaks•• Apparent increased severity of human illnessApparent increased severity of human illness

•• Encephalitis/meningitisEncephalitis/meningitis•• Weakness and/or flaccid paralysis: Weakness and/or flaccid paralysis:

poliomyelitis syndrome poliomyelitis syndrome •• Avian mortalityAvian mortality•• Virus introduced into North America (NYC)Virus introduced into North America (NYC)

WNV: Introduction to U.S.WNV: Introduction to U.S.

•• Labor Day, 1999Labor Day, 1999•• Four elderly patients w/ encephalopathy & feverFour elderly patients w/ encephalopathy & fever

•• GBSGBS•• Acute flaccid paralysisAcute flaccid paralysis•• Global weaknessGlobal weakness•• Aseptic meningitisAseptic meningitis

•• Bronx Zoo: Chilean flamingo dieBronx Zoo: Chilean flamingo die--offoff•• Queens/Bronx/Brooklyn: Crow dieQueens/Bronx/Brooklyn: Crow die--off off

WNV: Introduction to U.SWNV: Introduction to U.S

•• Initially, St. Louis encephalitis (SLE) virusInitially, St. Louis encephalitis (SLE) virus•• BUTBUT

•• Never occurred in NYCNever occurred in NYC•• Doesn’t kill birdsDoesn’t kill birds

•• Combined efforts of many …. West Nile virusCombined efforts of many …. West Nile virus•• Since 1996, West Nile meningoencephalitis (WNME) in Since 1996, West Nile meningoencephalitis (WNME) in

Russia, Romania, IsraelRussia, Romania, Israel•• Virus identical to 1998 Israel isolate Virus identical to 1998 Israel isolate

Madagascar

Uganda 1937

Central African Republic2

Egypt 1951France 1962 South Africa 1974

NE United StatesIsrael 98/99/2000

India

Kunjin

Romania 1996Italy 1998Volgograd 1999

1

LINEAGEClade

Eg 101

U.S./Israel

Europe/Russia

India

Kunjin

Phylogenetic Tree of West Nile

Viruses

Israel 2000

West Nile Virus:Approximate Geographic Range

West Nile Fever: Classical Clinical Description

• Mild dengue-like illness of sudden onset

• Duration 3-6 days

• Fever, lymphadenopathy, headache, abdominal pain, vomiting, rash, conjunctivitis, eye pain, anorexia

• Symptoms of West Nile fever in contemporary outbreaks not fully studied

EpidemiologyEpidemiology

•• Human IR Human IR ∝∝ CulexCulex mosquito IRmosquito IR•• Infection Infection roughlyroughly equal across age groupsequal across age groups•• Low human IR:Low human IR:

•• Queens (NYC) 1999 Queens (NYC) 1999 –– 2.6%2.6%•• Staten Island (NYC) 2000 Staten Island (NYC) 2000 –– 0.4%0.4%•• Suffolk County (NY) 2000 Suffolk County (NY) 2000 –– 0.1%0.1%•• Greenwich/Stamford (CT) 2000 Greenwich/Stamford (CT) 2000 –– 0% 0% •• St. Tammany Parish (LA) 2002 St. Tammany Parish (LA) 2002 -- ? ?

Clinical EpidemiologyClinical Epidemiology

•• Incubation period 2Incubation period 2--14 days14 days•• Advanced age primary risk factor for severe Advanced age primary risk factor for severe

neurological disease and deathneurological disease and death•• Immunosuppressive drugs and hematological Immunosuppressive drugs and hematological

malignancies probable risk factors for severe malignancies probable risk factors for severe disease and deathdisease and death

•• Approximately 10 Approximately 10 -- 20% mortality among persons 20% mortality among persons with meningoencephalitiswith meningoencephalitis

•• LongLong--term morbidity commonterm morbidity common

~80%Asymptomatic

~20%“West Nile Fever”

<1%CNS

disease

~10% fatal(<0.1% of total infections)

WNV Human Infection “Iceberg”

1 CNS disease case=

~150 total infectionsVery crude estimates

19991999--2002 Verified WNV Surveillance Results 2002 Verified WNV Surveillance Results Reported to ArboNetReported to ArboNet

7317319199197332733266/966/927+DC27+DC20012001

43 + DC43 + DC

11 + DC11 + DC

44

StatesStates

1102511025

6363

2525

HorsesHorses

5934593414411144113873/2463873/2462002 2002

5155154305430521/221/220002000

1616??62/662/619991999

MosquitoMosquitoPoolsPoolsBirdsBirdsHumans/Humans/

FatalitiesFatalitiesYearYear

As of December 31

Avian surveillance

U.S. counties reporting any -infectedbirdsbirds in 19991999 (N = 28 counties)

U.S. counties reporting any -infectedbirdsbirds from Jan Jan -- Dec 2000Dec 2000 (N = 136 counties)

U.S. counties reporting any -infectedbirdsbirds from Jan Jan -- Dec 2001Dec 2001 (N = 328 counties)

* Reported as of 11/30/2002

U.S.counties reporting WNV-positive dead birds, 2002*

14,122 birds1,719 counties42 states & D.C.

WNV surveillance, United States, 2002*:WNV surveillance, United States, 2002*:Summary of dead bird dataSummary of dead bird data

•• 94,919 dead birds reported94,919 dead birds reported•• 26,168 tested (27%)26,168 tested (27%)•• 14,122 WNV14,122 WNV--positive (54%)positive (54%)

•• 7,719 crows (55%)7,719 crows (55%)•• 4,948 blue jays (35%)4,948 blue jays (35%)•• 1,455 other 1,455 other sppspp.** (10%).** (10%)

•• 10,036 tested crows 10,036 tested crows -- 7,719 (77%) infected7,719 (77%) infected•• 16,132 other bird species 16,132 other bird species -- 6,403 (40%) infected6,403 (40%) infected•• 19991999--2002: 146 2002: 146 sppspp. WNV. WNV--positive bird speciespositive bird species

* Reported as of 11/30/2002** Representing 93 species

DCDC

9,7879,787

8,4848,484

3,2363,236

AreaArea(hundred mi(hundred mi22))

0.10.1947947WestWest

0.80.86,6986,698CentralCentral

4.94.915,86915,869EastEast

RatioRatio# dead birds# dead birdstestedtested

RegionRegion

* Reported as of 11/01/2002

WNV surveillance, regional differences, 2002*WNV surveillance, regional differences, 2002*

Non-human mammal surveillance

Reported WNV-infected non-human mammals, United States, 1999-2002*

??11Little Brown BatLittle Brown Bat

??33OtherOther

??33CanineCanine

11

11

11

77

11

11

ThousandsThousands

# Infected# Infected

??

??

??

??

??

??

YesYes

DiseaseDiseaseSpeciesSpecies

Big Brown BatBig Brown Bat

Striped SkunkStriped Skunk

Eastern ChipmunkEastern Chipmunk

SquirrelSquirrel

Domestic rabbitDomestic rabbit

CatCat

EquineEquine

* Reported as of 11/01/2002

U.S. counties reporting U.S. counties reporting equineequine WNVWNV illnessesillnesses19991999 (N = 2 counties)(N = 2 counties)

U.S. counties reporting U.S. counties reporting equineequine WNV illnessesWNV illnesses20002000 (N = 26 counties)(N = 26 counties)

U.S. counties reporting U.S. counties reporting equineequine WNV illnessesWNV illnesses20012001 (N = 125 counties)(N = 125 counties)

U.S. counties reporting equine WNV disease cases, 2002*

* Reported as of 11/30/2002

9,144 cases1,374 counties38 states

Equine illnesses, by week of onset, Equine illnesses, by week of onset, northern vs. southern United States, Junnorthern vs. southern United States, Jun--Oct 2002*Oct 2002*

0

200

400

600

800

1000

1200

15-J

un29

-Jun

13-J

ul27

-Jul

10-A

ug24

-Aug

7-Se

p21

-Sep

5-Oc

t19

-Oct

Week ending

# ca

ses

NorthSouth

* Reported as of 11/01/2002

Mosquito surveillance

•• 1.3M mosquitoes tested1.3M mosquitoes tested•• 4,943 WNV4,943 WNV--positive poolspositive pools•• 639 counties test mosquitoes; 315 (49%) report 639 counties test mosquitoes; 315 (49%) report

positive poolspositive pools•• 27 positive species in 200227 positive species in 2002•• 8 first8 first--time time sppspp. includes . includes AeAe. aegypti. aegypti and and Cx. tarsalisCx. tarsalis•• 19991999--2002, 37 WNV2002, 37 WNV--infected speciesinfected species•• Earliest: 22 MAY, Earliest: 22 MAY, Cx. restuansCx. restuans, Monmouth Co., NJ, Monmouth Co., NJ•• Latest: 15 OCT, Latest: 15 OCT, AeAe. albopictus. albopictus, Tulsa Co., OK; , Tulsa Co., OK; Cx. Cx.

tarsalistarsalis, Tillman Co., OK (3 pools), Tillman Co., OK (3 pools)

WNV surveillance, United States, 2002*:WNV surveillance, United States, 2002*:Summary of mosquito dataSummary of mosquito data

* Reported as of 11/30/2002

U.S. counties reporting WNV-positive mosquitoes, 2002*

* Reported as of 11/30/2002

4,943 pools27 species315 counties28 states & D.C.

111111113366

77171722223838

% % totaltotal

11,32911,3295050AeAe. albopictus . albopictus 103,188103,1884646AeAe. vexans . vexans

147,867147,8671,0701,070Cx. pipiensCx. pipiens

58586868

134134278278

321321810810

1,7981,798

PositivePositivepoolspools

33,44633,446129,154129,154103,911103,911151,490151,490

12,81612,81629,90129,901

7,7127,712

IndividualsIndividualstestedtestedSpeciesSpecies

OcOc. triseriatus. triseriatusCx. salinariusCx. salinariusCx. tarsalisCx. tarsalisCx. restuansCx. restuans

Cx. quinquefasciatusCx. quinquefasciatusCx. pipiens / restuansCx. pipiens / restuans

Cx. Cx. sp.sp.

“Top 10” WNV-positive mosquito species reported, United States, 2002*

* Reported as of 11/01/2002

* Reported as of 11/01/2002 – 37 species

WNVWNV--positive mosquito species reported,positive mosquito species reported,United States, 1999United States, 1999--2002*2002*

OrthopodomyiaOrthopodomyia signiferasigniferatriseriatustriseriatuserraticuserraticus

UranotaeniaUranotaenia sapphirinasapphirinatrivittatustrivittatusterritansterritans

Ps. Ps. feroxferoxtaeniorhynchustaeniorhynchusabominatorabominator

Ps. ciliataPs. ciliatawalkeriwalkerisollicitanssollicitansnigripalpusnigripalpus

Ps. columbiaePs. columbiaequadrimacquadrimac..japonicusjaponicussalinariussalinarius

DeinoceritesDeinocerites cancercancerpuncitpennispuncitpenniscantatorcantatorvexansvexansrestuansrestuansCqCq. perturbans. perturbanscrucianscrucianscanadensiscanadensiscinereuscinereustarsalistarsalis

Cs. inornataCs. inornatabarberibarberiatropalpusatropalpusaegyptiaegyptiquinqquinq..Cs. melanuraCs. melanuraatroposatroposatlanticusatlanticusalbopictusalbopictuspipienspipiensOtherOtherAnophelesAnophelesOchlerotatusOchlerotatusAedesAedesCulexCulex

Sentinel animals

*Reported as of 11/01/2002

WNV surveillance: Sentinel chickens, 2002*

No WNV sentinel activity or human cases

WNV sentinel activity preceded human cases

Human cases preceded WNV sentinel activity

Human surveillance

Surveillance Case DefinitionsSurveillance Case Definitions

•• West Nile meningoencephalitisWest Nile meningoencephalitis (WNME): (WNME): •• FeverFever•• NeurologicNeurologic S&S (e.g., encephalopathy, meningitis, S&S (e.g., encephalopathy, meningitis,

acute flaccid paralysis [polio], stroke, GBS, severe acute flaccid paralysis [polio], stroke, GBS, severe headache)headache)

•• Evidence of recent WNV infection:Evidence of recent WNV infection:•• WNVWNV--specific IgM in CSFspecific IgM in CSF•• WNVWNV--specific IgM in serum & 4specific IgM in serum & 4--fold change in fold change in

neutneut antibody titer (acuteantibody titer (acute-- & convalescent& convalescent--phase phase serum samples)serum samples)

•• WNV antigen, RNA or virus in tissue, CSF, or WNV antigen, RNA or virus in tissue, CSF, or serumserum

•• West Nile feverWest Nile fever (WNF): Fever, musculoskeletal pain, (WNF): Fever, musculoskeletal pain, rash; same serologic criteriarash; same serologic criteria

U.S. counties reporting humanhuman WNV illness19991999 (N = 6 counties)

U.S. counties reporting humanhuman WNV illness20002000 (N = 10 counties)

U.S. counties reporting humanhuman WNV illnessJan Jan -- Dec 2001Dec 2001 (N = 39 counties)

U.S. counties reporting human WNV illnesses, 2002*

* Reported as of 11/30/2002

3,389 cases619 counties37 states & D.C.

Reported WNV illness in humans,Reported WNV illness in humans,United States, 1999United States, 1999--2002*2002*

* Reported as of 11/30/2002

13 JUL 13 JUL –– 7 DEC7 DEC39391010666620012001

6 JUN 6 JUN –– 4 NOV4 NOV61961937**37**3,3893,38920022002

20 JUL 20 JUL –– 27 SEP27 SEP101033212120002000

2 AUG 2 AUG –– 24 SEP24 SEP6611626219991999

Onset Date RangeOnset Date Range# Counties# Counties# States# States# Cases# CasesYearYear

** Plus D.C.

05

101520253035404550

Jul Aug Sep Oct Nov Dec Jul Aug Sep Oct Nov Dec Jul Aug Sep Oct Nov Dec

Num

b er o

f ca s

e s

1999 2000 2001

Human WNV Disease Cases, by month of onset, Human WNV Disease Cases, by month of onset, United States, 1999United States, 1999--20012001

Human WNV illnesses, by onset week, Human WNV illnesses, by onset week, northern vs. southern United States, 2002*northern vs. southern United States, 2002*

0

100

200

300

400

500

15-J

un

29-J

un

13-J

ul

27-J

ul10

-Aug

24-A

ug

7-Se

p

21-S

ep

5-Oc

t

19-O

ct

Week ending

# ca

ses

NorthSouth

* Reported as of 11/01/2002

* Reported as of 11/30/2002

WNV illnesses, demographics & mortality, United States, 1999-2002*

44%44%44 44 –– 9090

7575

100%100%

1818

19991999--01 01 (Fatal)(Fatal)

6%**6%**54%54%

<1 <1 –– 99995555

10%10%

21%21%

69%69%

3,3893,389

2002 2002 (All)*(All)*

60%60%24 24 –– 9999

7878

1%1%

99%99%

201201

2002 2002 (Fatal)*(Fatal)*

ClinicalClinical

5%5%WN FeverWN Fever

UnknownUnknown

95%95%WN MEWN ME

59%59%MalesMales

12%12%MortalityMortality

5 5 –– 9090rangerange6666medianmedian

Age (yr)Age (yr)

149149nn

19991999--01 01 (All)(All)

**8.5% of WNME cases

0

10

20

30

0-910-19

20-2930-39

40-4950-59

60-6970-79

80-8990-99

Age Group (yr)

Prop

ortio

n of

Tot

al (%

)

WNME (n=2354)WNF (n=704)

Age distribution of all human WNV illnesses,by clinical category, United States, 2002*

* Reported as of 11/30/2002

* Reported as of 11/01/2002

Age distribution of fatal human WNME cases (n = 199),United States, 2002*

0

10

20

30

40

50

0-910-1

920-2

930-3

940-4

950-5

960-6

970-7

980-8

990-9

9

Age Group (yr)

Prop

ortio

n of

Tot

al (%

)

A Season of SurprisesA Season of Surprises

•• Largest arbovirus meningoencephalitis outbreak Largest arbovirus meningoencephalitis outbreak epidemic ever documented in western epidemic ever documented in western hemispherehemisphere

•• Largest WNME epidemic ever documentedLargest WNME epidemic ever documented•• Geographic spread to the Pacific CoastGeographic spread to the Pacific Coast•• AFP was not AFP was not GuillianGuillian--BarreBarre syndromesyndrome•• High frequency of cogwheel rigidity, tremor, High frequency of cogwheel rigidity, tremor,

myoclonusmyoclonus in acute patientsin acute patients•• New modes of transmissionNew modes of transmission

Novel Modes of West Nile Virus Novel Modes of West Nile Virus Transmission, 2002Transmission, 2002

•• Transplanted organsTransplanted organs•• Transfused bloodTransfused blood•• Breast milkBreast milk•• TransplacentalTransplacental transmission transmission •• PercutaneousPercutaneous, occupational exposure, occupational exposure

West Nile Virus Infection in an Organ Donor West Nile Virus Infection in an Organ Donor and Four Transplant Recipientsand Four Transplant Recipients

August 2002August 2002

Organ Donor

WNV PCR –IgM –

Organ Donor

WNV PCR +

Culture +IgM –

Kidney recipientWNME (fatal)

Kidney recipientWNME

Liver recipientWNF

Heart recipientWNME

Blood Blood components components

from 63 donorsfrom 63 donors

TransfusionTransfusion--associated West Nile virus infectionassociated West Nile virus infection

BackgroundBackground•• Potential transmissionPotential transmission

-- Transient viremiaTransient viremia-- Most infections asymptomaticMost infections asymptomatic

•• “Small but not zero” risk“Small but not zero” risk-- No chronic carriersNo chronic carriers-- No cases reported in prior years or fromNo cases reported in prior years or from

endemic countriesendemic countries

•• Estimated risk: Estimated risk: 1.81.8--2.7/10,000 donations in 2.7/10,000 donations in 1999 Queens (NYC) epidemic1999 Queens (NYC) epidemic

West Nile virus infections in blood transfusion West Nile virus infections in blood transfusion recipientsrecipients

•• 58 possible cases reported Aug 28 58 possible cases reported Aug 28 –– Nov 26, 2002Nov 26, 2002

•• 19 19 notnot transfusiontransfusion--associated WNVassociated WNV

•• 9 9 -- No WNV infectionNo WNV infection•• 3 3 -- Received transfusions Received transfusions afterafter symptom onsetsymptom onset•• 2 2 -- Symptom onset >28 days after transfusionSymptom onset >28 days after transfusion•• 5 5 -- WNV infection but all donors WNV IgMWNV infection but all donors WNV IgM--negativenegative

•• 39 under investigation:39 under investigation:•• At least 1600 donations (>40 donations/case)At least 1600 donations (>40 donations/case)•• 13 confirmed cases of transfusion13 confirmed cases of transfusion--associated associated

transmissiontransmission•• 26 still working26 still working

Confirmed cases of transfusionConfirmed cases of transfusion--related WNV infectionrelated WNV infection

CasesCasesPatient 1 Patient 1 Patient 2 Patient 2 Patient 3Patient 3Patient 4 Patient 4 Patient 5 Patient 5 Patient 6Patient 6Patient 7 Patient 7 Patient 8Patient 8Patient 9Patient 9Patient 10Patient 10Patient 11Patient 11Patient 12Patient 12Patient 13Patient 13Patient 14Patient 14

Underlying Underlying conditioncondition

Post partumPost partumLiver transplantLiver transplant

Post partumPost partumAMLAML

CancerCancerCancerCancer

AMLAMLPendingPending

BMTBMTCancerCancerSepsisSepsisCABGCABGCABGCABG

AML/BMTAML/BMT

OutcomeOutcomeAliveAliveAliveAliveAliveAliveAliveAliveFatalFatalAliveAliveFatalFatalAliveAliveAliveAliveAliveAliveAliveAliveFatalFatalAliveAliveFatalFatal

MosquitoMosquitoExposureExposure

YesYesPossiblePossible

YesYesNoNo

UnlikelyUnlikelyPossiblePossiblePossiblePossibleUnlikelyUnlikelyPossiblePossiblePossiblePossiblePossiblePossiblePossiblePossiblePossiblePossibleUnlikelyUnlikely

*

*

*

*

TransfusionTransfusion--associated WNV Infectionassociated WNV InfectionPatients 2 (s/p Liver Transplant) and 3 (PostPatients 2 (s/p Liver Transplant) and 3 (Post--partum)partum)

9/29/2 9/59/5

IllnessIllnessonsetonset

CSFIgM +

8/208/208/158/15 10/710/78/178/17

Serum Serum IgM +IgM +

DONOR

PATIENT 2 (39 donors)

PRBC PRBC transfusedtransfused

9/39/3 9/139/13

Illness Illness onsetonset

PATIENT 3 (2 donors)

9/189/18

CSFCSFIgM +IgM +

DonationDonation

DONORFever; weakness 8/19Fever; weakness 8/19

rash 8/20rash 8/20

PLTS transfused

Fourteen confirmed cases of transfusionFourteen confirmed cases of transfusion--associated West Nile virus infection: Summaryassociated West Nile virus infection: Summary

•• Illness onset: August 1 Illness onset: August 1 –– October 23October 23

•• 3 recipients without illness onset3 recipients without illness onset

•• Days from transfusion to illness onset (N=11)Days from transfusion to illness onset (N=11)•• Range: 4 Range: 4 –– 23 days23 days•• Median: 11 daysMedian: 11 days

•• Implicated componentsImplicated components•• 7 units red blood cells7 units red blood cells•• 5 units platelets5 units platelets•• 2 units plasma2 units plasma

•• Duration of PCRDuration of PCR--positivitypositivity: at least 17 days after : at least 17 days after symptom onset for 1 patientsymptom onset for 1 patient

Ten implicated donors or infectious units: SummaryTen implicated donors or infectious units: Summary

•• Dates of Donation: Jul 22 Dates of Donation: Jul 22 –– Sep 20Sep 20•• All donors IgM negative at time of donationAll donors IgM negative at time of donation•• WNV RNA at low concentration (< 20 WNV RNA at low concentration (< 20 pfu/mLpfu/mL))•• WNV isolated from one of two recovered plasma WNV isolated from one of two recovered plasma

samplessamples

•• Illness onsets:Illness onsets:•• 2 donors symptoms before donation2 donors symptoms before donation•• 6 donors symptoms post donation6 donors symptoms post donation•• 2 donors asymptomatic2 donors asymptomatic

•• Maximum interval from donation to transfusion Maximum interval from donation to transfusion •• PLT 5 days; RBC 33 days; FFP 44 daysPLT 5 days; RBC 33 days; FFP 44 days

Prevention of TransfusionPrevention of Transfusion--Related InfectionRelated Infection

•• FDA encouraging development of nucleic acidFDA encouraging development of nucleic acid--based based screening testsscreening tests•• Will pooled nucleic acid testing have high enough Will pooled nucleic acid testing have high enough

sensitivity?sensitivity?•• Can these tests, if developed, be implemented in Can these tests, if developed, be implemented in

time for the 2003 season?time for the 2003 season?•• Market Market withdrawlwithdrawl of fresh frozen plasma collected of fresh frozen plasma collected

during 2002 epidemic periodduring 2002 epidemic period•• Identification of possible transfusionIdentification of possible transfusion--related cases: related cases:

market market withdrawlwithdrawl of all inof all in--date products from donors date products from donors of units given to these casesof units given to these cases

TransfusionTransfusion--associated West Nile virus infection associated West Nile virus infection Unanswered questionsUnanswered questions

•• Better definition of clinical course of WNV Better definition of clinical course of WNV infection and viremiainfection and viremia

•• Define scope and magnitude of transfusion Define scope and magnitude of transfusion transmissiontransmission

•• Prevalence of viremia in donorsPrevalence of viremia in donors

•• Rate of transmission from viremic donors Rate of transmission from viremic donors and associated risk factorsand associated risk factors

•• SeroprevalenceSeroprevalence in frequently transfused in frequently transfused personspersons

•• Transmission of other flaviviruses (SLE, Transmission of other flaviviruses (SLE, dengue)?dengue)?

Breast MilkBreast Milk--Associated WNV InfectionAssociated WNV Infection

1212 151500 11 1818 2525

Breastfeedingbegins

Infectedblood transfusion

Symptomonset

AdmitWNME

Breastfeeding

stopped

Breast milkPCR +

IgM and IgG +

1616

Breast milkPCR -; IgM +Infant serum

IgM +

Days After DeliveryInfant asymptomatic

Breast Milk TransmissionBreast Milk Transmission

•• Animal modelAnimal model•• High rate of transmission to suckling hamsters High rate of transmission to suckling hamsters

from lactationfrom lactation•• Case 2Case 2

•• WNV in mother from postWNV in mother from post--partum transfusionpartum transfusion•• Mother developed prolonged febrile illness and Mother developed prolonged febrile illness and

mild meningitis, but breast fed continuouslymild meningitis, but breast fed continuously•• Breast milk not testedBreast milk not tested•• Infant IgM negativeInfant IgM negative

Intrauterine TransmissionIntrauterine Transmission

•• Mother developed WNME and flaccid paralysis around 27Mother developed WNME and flaccid paralysis around 27thth

week of pregnancyweek of pregnancy•• Term delivery (38 weeks)Term delivery (38 weeks)•• Infant: bilateral Infant: bilateral chorioretinitischorioretinitis; MRI severe bilateral white ; MRI severe bilateral white

matter loss in temporal and occipital lobesmatter loss in temporal and occipital lobes•• Heel stick, cord blood, and infant CSF IgM +Heel stick, cord blood, and infant CSF IgM +•• Placenta and umbilical cord PCR +, cultures Placenta and umbilical cord PCR +, cultures ––•• Infant CSF: PCR negative for WNV, EV, HSVInfant CSF: PCR negative for WNV, EV, HSV•• Infant serum: negative for CMV IgM and Infant serum: negative for CMV IgM and lymphocyticlymphocytic

choriomeningitischoriomeningitis virusvirus

LaboratoryLaboratory--Acquired WNV InfectionAcquired WNV Infection

•• Case 1Case 1•• Day 0: Lacerated thumb while removing a bird Day 0: Lacerated thumb while removing a bird

brain from infected birdbrain from infected bird•• Day 4: Onset WN feverDay 4: Onset WN fever•• Day 7: WNV IgM and neutralizing Day 7: WNV IgM and neutralizing AbAb negativenegative•• Day 17: WNV IgM +Day 17: WNV IgM +•• Day 21: WNV IgM + and neutralizing Day 21: WNV IgM + and neutralizing AbAb ++

LaboratoryLaboratory--Acquired WNV InfectionAcquired WNV Infection

•• Case 2Case 2•• Previous history of dengue fever and received JE and Previous history of dengue fever and received JE and

YF vaccinesYF vaccines•• Day 0: Punctured finger with contaminated needle while Day 0: Punctured finger with contaminated needle while

harvesting mouse brainsharvesting mouse brains•• Day 1: Serum: WNV IgM negativeDay 1: Serum: WNV IgM negative•• Day 3: Onset URIDay 3: Onset URI--like symptomslike symptoms•• Day 4: Low grade feverDay 4: Low grade fever•• Day 6: Serum: WNV IgM negativeDay 6: Serum: WNV IgM negative•• Day 7: WNV IgM and neutralizing Day 7: WNV IgM and neutralizing AbAb negativenegative•• Day 10: WNV IgM + and neutralizing Day 10: WNV IgM + and neutralizing AbAb ++

Surveillance summarySurveillance summary

Epidemic West Nile meningoencephalitis, Epidemic West Nile meningoencephalitis, United States, 2002United States, 2002

•• Unofficial Unofficial U.S. human totals*:U.S. human totals*:•• 2,354 WNME cases2,354 WNME cases•• 704 WNF cases704 WNF cases•• 201 deaths201 deaths•• 37 states & D.C.37 states & D.C.

•• Largest arbovirus meningoencephalitis Largest arbovirus meningoencephalitis epidemic ever documented in western epidemic ever documented in western hemispherehemisphere

•• LargestLargest WNMEWNME epidemic ever documentedepidemic ever documented

* As of 11/30/2002

Humans200120001999

2002

States Reporting WNV Activity, 1999-2002*

* Reported as of 11/01/2002

So, what will happen in 2003?So, what will happen in 2003?

Comparison with other West Nile and St. Comparison with other West Nile and St. Louis encephalitis virus epidemicsLouis encephalitis virus epidemics

280280170170171740403333

199199

Deaths Deaths (approx.)(approx.)

8%8%2,0002,000SLESLEU.S.U.S.197519755%5%350350WNWNRomaniaRomania19961996

SLESLE

WNWNWNWNWNWN

VirusVirus

U.S.U.S.

RussiaRussiaIsraelIsraelU.S.U.S.

LocationLocation

10%10%40040019991999

20%20%1,4001,40019331933

14%14%240240200020009%9%2,4002,4002002*2002*

CFR CFR (approx.)(approx.)

ME cases ME cases (approx.)(approx.)

YearYear

Epidemic WNME, United States, 2002Epidemic WNME, United States, 2002Comparison with other largeComparison with other large

WNME or SLE epidemicsWNME or SLE epidemics

* As of 11/30/2002

DCDC

SLE 1975

DCDC

WNME 2002*

>=10

1 – 9.9

0 – 0.9

Incidence per 106

Reported Incidence in Humans:SLE 1975

vs. WNME 2002

* Reported as of 11/01/2002

0

500

1000

1500

2000

2500

1932 1942 1952 1962 1972 1982 1992 2002

Reported and estimated number of St. Louisencephalitis cases, U.S., 1932-2002

0

500

1000

1500

2000

2500

1932 1942 1952 1962 1972 1982 1992 2002

Reported number of West Nile meningoencephalitis cases, U.S., 1932-2002

WNV: Where are we going?WNV: Where are we going?SLE vs. JE patternSLE vs. JE pattern

•• SLE SLE –– Sporadic epidemics / thousands of casesSporadic epidemics / thousands of cases•• JE JE –– Annual Annual hyperendemichyperendemic/epidemic patterns/epidemic patterns•• Worrisome:Worrisome:

•• 20012001--2002: Wide2002: Wide--spread urban, suburban, and spread urban, suburban, and rural activityrural activity

•• Persistent virus activity in some area for 4 yearsPersistent virus activity in some area for 4 years•• Large number of infected bird speciesLarge number of infected bird species•• Large number of infected mosquito speciesLarge number of infected mosquito species•• Large number of Large number of peridomesticperidomestic CulexCulex, , AedesAedes, and , and

OchlerotatusOchlerotatus speciesspecies

Too early to predict the epidemiologic pattern Too early to predict the epidemiologic pattern that will be established in the Americasthat will be established in the Americas

West Nile virus, 2002:West Nile virus, 2002:Emerging issuesEmerging issues

•• ““Early season” avian mortalityEarly season” avian mortality•• New modes of transmissionNew modes of transmission

•• Transfusion / transplantation Transfusion / transplantation •• Breast milkBreast milk•• TransplacentalTransplacental

•• Emerging clinical syndromesEmerging clinical syndromes•• WN feverWN fever•• WNME / acute flaccid paralysis / brachial WNME / acute flaccid paralysis / brachial

plexopathyplexopathy•• WNME / WNME / rhabdomyolysisrhabdomyolysis

•• LongLong--term outcome studiesterm outcome studies•• LaboratoryLaboratory-- and occupationallyand occupationally--acquired acquired

infectionsinfections

AcknowledgementsAcknowledgements

•• ArboNET: ArboNET: Scores of partners in state/local Scores of partners in state/local health departmentshealth departments

•• CDC:CDC:Aaron Aaron KippKipp Duane GublerDuane GublerNick Nick KomarKomar Peggy CollinsPeggy CollinsJohn Roehrig John Roehrig Veronica ElkoVeronica ElkoKeith OlsenKeith Olsen Roger NasciRoger NasciJennifer LehmanJennifer Lehman Lyle Petersen Lyle Petersen John JonesJohn Jones Catherine ChowCatherine ChowSusan MontgomerySusan Montgomery

This paper was produced for a meeting organized by Health & Consumer Protection DG and represents the views of its author on the subject. These views have not been adopted or in any way approved by the Commission and should not be relied upon as a statement of the Commission's or Health & Consumer Protection DG's views. The European Commission does not guarantee the accuracy of the data included in this paper, nor does it accept responsibility for any use made thereof.