West Nile Virus in North America: West Nile Virus in North America: An Update An Update Division of Vector Division of Vector - - Borne Infectious Diseases Borne Infectious Diseases Fort Collins, Colorado Fort Collins, Colorado Photo of Cx. quinquefasciatus courtesy of Dr. Stephen Higgs, UTMB/Galveston
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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
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.
•• 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
• 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
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*
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
•• 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
-- 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
•• 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
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
•• 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
•• 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 ++
•• 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
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
•• 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.