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PurposePurpose(You may click to go to the specific section or proceed through (You may click to go to the specific section or proceed through the presentation)the presentation)
Briefly review Briefly review West Nile virus (WNV) ecology West Nile virus (WNV) ecology and epidemiologyand epidemiology
Update of Update of WNV in CaliforniaWNV in California Highlight Highlight current clinical informationcurrent clinical information Address diagnostic Address diagnostic testing and reporting issuestesting and reporting issues
When to suspect and test for WNVWhen to suspect and test for WNV How to testHow to test
Review effective Review effective prevention of WNVprevention of WNV Provide realProvide real--life illustrative life illustrative case studiescase studies
WNV Ecology and WNV Ecology and EpidemiologyEpidemiology
What is West Nile virus? What is West Nile virus?
First identified in Uganda, First identified in Uganda, 19371937
A virus in the A virus in the FlaviviridaeFlaviviridaefamily, related to:family, related to: Yellow feverYellow fever Dengue Dengue St. Louis encephalitis (SLE)St. Louis encephalitis (SLE)
VirologyVirology Spherical, enveloped Spherical, enveloped capsidcapsid SingleSingle--stranded, positivestranded, positive--sense sense
RNARNA
Transmission electron micrograph of WNV particles. Source: CDC
Transmission CycleTransmission CycleWest Nile virus is maintained in nature in a
mosquito-bird cycleMigratory birds expand the endemic region of WNV
Bird reservoir host
Primary Transmission Cycle
Mosquito vector (Culex spp. mostly )
Transmission CycleTransmission Cycle
Incidental Infection
Humans Other mammals
Incidental infections occur when infected Incidental infections occur when infected mosquitoes feed on humans or other animals.mosquitoes feed on humans or other animals. Incidental hosts cannot infect mosquitoes (Incidental hosts cannot infect mosquitoes (““deaddead--endend””) hosts) hosts
Incidental Infection
Bird reservoir host
Primary Transmission Cycle
Mosquito vector
Other Modes of TransmissionOther Modes of Transmission Blood transfusion (over 2,000 infected Blood transfusion (over 2,000 infected
donors identified since 1999)donors identified since 1999)
Less common other Less common other modes:modes: Organ transplant (at least Organ transplant (at least
2 implicated donors)2 implicated donors) LaboratoryLaboratory--acquired (2 acquired (2
reported)reported) TransplacentalTransplacental (1 possible)(1 possible) Breast milk (1 probable)Breast milk (1 probable)
WNV in the United StatesWNV in the United States The most widespread The most widespread flavivirusflavivirus in the U.S.in the U.S. Human toll in the U.S., 1999Human toll in the U.S., 1999--20102010
30,70230,702 total symptomatic casestotal symptomatic cases 12,755 (42%)12,755 (42%) neuroinvasiveneuroinvasive disease (WNND) casesdisease (WNND) cases 1,220 (4%)1,220 (4%) fatal casesfatal cases
Economic tollEconomic toll Louisiana 2002: estimated total epidemic costs Louisiana 2002: estimated total epidemic costs
(medical and mosquito control) were $20.14 million for (medical and mosquito control) were $20.14 million for 329 cases 329 cases ((ZohrabianZohrabian A, et al., A, et al., EmergEmerg Infect Dis. 2004)Infect Dis. 2004)
Sacramento County 2005: $2.98 million for 163 cases Sacramento County 2005: $2.98 million for 163 cases ($2.28 million medical costs, $700,000 mosquito ($2.28 million medical costs, $700,000 mosquito control). control). (Barber LM et al. (Barber LM et al. EmergEmerg Infect Dis. 2010)Infect Dis. 2010)
WNV in CaliforniaWNV in California
WNV cases and clinical classification 2004 - 2010. Total = 2,985 (101 Fatal)
0
100
200
300
400
500
600
700
800
900
2004
2005
2006
2007
2008
2009
2010
Num
ber c
ases
FatalitiesNeuroinvasive diseaseFever, Other
•Incidence of WNV has decreased since 2004, but WNV remains endemic to California
•Future change in incidence will depend on weather, host immunity, mosquito control, personal protective measures and case detection.
•Neuroinvasive cases make up an increasing proportion of detected West Nile virus cases, likely because less ill cases do not seek medical care or are not tested.
Reported incidence of West Nile virus, by county of residence, California 2004 - 2010
> 5.0
2.1 – 4.9
0.60 - 2.0
0.21 - 0.50
0.01 – 0.2
0
Reported cases per 100,000 person years
Incidence of WNV tends to be higher in the Central and San Joaquin Valley areas of California where prolonged high summer temperatures increase the rate and amount of viral replication within the natural cycle.
Human West Nile Virus Cases by Week of Onset, California, 2004-2009
* Onset dates known for 2,518 (88%) cases
SEPT
0
20
40
60
80
100
120
140
160
19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51
Week of onset* (CDC disease week)
Num
ber o
f cas
es
200420052006200720082009
JUL AUG SEP
WNV is a disease of summer: most cases occur between July and September
West Nile Virus Clinical InformationWest Nile Virus Clinical Information
““WeWe’’re pretty sure itre pretty sure it’’s the West Nile virus...s the West Nile virus...””
© 2008 The New Yorker Collection from cartoonbank.com. All Rights Reserved.
Three General Clinical Categories of WNV Disease
~80%Asymptomatic
20%- 30%“West Nile Fever”
<1%CNS
disease
Neuroinvasive Disease (WNND)• Meningitis, encephalitis,
poliomyelitis
West Nile Fever (WNF)• Fever, headache, rash, fatigue
Asymptomatic Infection• Generation of life-long
immunity (presumed)
~10% of WNND are fatal(<0.1% of total infections)
Incubation period of 2 – 15 days
Risk for severe illness and deathRisk for severe illness and death Established risk factors for severe illnessEstablished risk factors for severe illness
Advanced age, Advanced age, immunosuppressionimmunosuppression a,ba,b
Conditions significantly associated with Conditions significantly associated with severe illness:severe illness: Hypertension, cardiovascular disease, and Hypertension, cardiovascular disease, and
diabetesdiabetesb,cb,c
Possible risk factors for serious diseasePossible risk factors for serious disease Alcohol and drug abuseAlcohol and drug abusedd
ChemokineChemokine receptor CCR5 receptor CCR5 genegeneee
a Nash et al., NEJM, 2001b Murray et al., EID, 2006c Jean et al., EID, 2007
d Bode et al., CID, 2006e Lim et al., JID, 2010
LongLong--term complications of WNV diseaseterm complications of WNV disease
Suggestion of persistent symptoms or new complications of WNV disease, regardless of initial disease presentation, e.g.
Slow return to pre-morbid condition (> 6 months) On-going fatigue New-onset depression
Loeb et al, Ann Int Med 2008; Voelker et al JAMA 2008; Carson et al CID 2006; Watson et al, Ann Int Med 2004
Long-term neurocognitive impairmentSejvar J, J Neuropsychol 2008
Persistent limb weakness or paralysis Persistent movement disorders
Sejvar J, CID, 2007
LongLong--term complications of WNV diseaseterm complications of WNV disease
PersistentPersistent infection suggested by polymerase chain infection suggested by polymerase chain reaction detection of WNV in one study of WN reaction detection of WNV in one study of WN encephalitis patients with chronic symptomsencephalitis patients with chronic symptomsMurray et al, J Inf Disease, 2010
TreatmentTreatment
No specific treatment is currently availableNo specific treatment is currently available Primarily supportive care: hospitalization, Primarily supportive care: hospitalization,
respiratory support, etc.respiratory support, etc. One treatment trial evaluating the efficacy One treatment trial evaluating the efficacy
of a monoclonal antibody for WNV of a monoclonal antibody for WNV neuroneuro--invasive disease invasive disease (not currently accepting (not currently accepting participants) participants) ((http://clinicaltrials.gov/ct2/show/NCT00927953http://clinicaltrials.gov/ct2/show/NCT00927953) )
Testing and Testing and Reporting WNVReporting WNV
When to suspect West Nile virusWhen to suspect West Nile virus
West Nile virus should be considered in West Nile virus should be considered in patients with compatible clinical patients with compatible clinical presentationpresentation Unexplained encephalitis or meningitis in Unexplained encephalitis or meningitis in
persons of all agespersons of all ages Local presence of activity or casesLocal presence of activity or cases Recent travel to area with WNV activityRecent travel to area with WNV activity Onset during West Nile virus Onset during West Nile virus ““seasonseason””
In California, ~July through SeptemberIn California, ~July through September
Study reviewed hospital records from 2009 and 2010 West Nile Virus season (April 1, 2011-October 31)
Study population: •At least one hospital from each study county likely to see WNV cases, as recommended by county infection control
o Sacramento – Suttero Yolo – Woodlando Riverside – Corona (and Eisenhower)o Kern – Mercy
Are Patients with WNVAre Patients with WNV--Compatible Compatible NeuroinvasiveNeuroinvasive Disease Being Tested? Disease Being Tested? Completeness of Reporting Study: 2009Completeness of Reporting Study: 2009--2010 2010
ICD9/Testing ReviewICD9/Testing Review
Data collection:
Who should have been tested? •“query to identify patients that were discharged with neuroinvasive ICD-9 codes* as one of their first three diagnoses”
Who was tested?•“identify all WNV test requests submitted during the same time period”
Are Patients with WNVAre Patients with WNV--Compatible Compatible NeuroinvasiveNeuroinvasive Disease Being Tested? Disease Being Tested? Completeness of Reporting Study: 2009Completeness of Reporting Study: 2009--2010 2010
ICD9/Testing ReviewICD9/Testing Review
Are Patients with WNVAre Patients with WNV--Compatible Compatible NeuroinvasiveNeuroinvasive Disease Being Tested? Disease Being Tested?
Conclusions:•From April 1-Oct 31, 2010, 80% of patients with a neuroinvasive diagnosis were not tested for WNV.
•From April 1-Oct 31, 2010, only 20% of all encephalitis cases were tested for WNV. This is a decrease from 2009 (27%).
Recommendation:•WNV should be considered in patients with compatible clinical presentation
Completeness of Reporting Study: 2009Completeness of Reporting Study: 2009--2010 2010 ICD9/Testing ReviewICD9/Testing Review
Why test if there is no treatment?
Testing will differentiate WNV from other conditions (enterovirus, other arboviral diseases).
Testing offers anticipatory guidance—with potential lingering symptoms associated with WNV infection, knowing the underlying etiology is helpful for the patient and family members.
Mosquito control and public health agencies can institute proper control measures to prevent further cases
WNV Diagnostic TestingWNV Diagnostic Testing WN WN IgMIgM antibodyantibody
Enzyme immunoassay (EIA) 99% samples positive for 99% samples positive for IgMIgM at 5 days of onset for at 5 days of onset for
neuroinvasiveneuroinvasive diseasedisease
Plaque reduction neutralization test (PRNT) Plaque reduction neutralization test (PRNT) considered confirmatory, but is not often used as considered confirmatory, but is not often used as default testdefault test Only a few labs perform itOnly a few labs perform it Longer turnaround timeLonger turnaround time Not as helpful for Not as helpful for IgGIgG--negative specimensnegative specimens
How to test for WNVHow to test for WNV
Contact your local health department for details Generally an acute serum specimen ( ≥ 2cc) and, if
lumbar puncture performed, 1-2 cc cerebrospinal fluid are required for testing. Many public health laboratories offer free testing, check
with your local health department.
How to test for WNVHow to test for WNV If West Nile virus is highly suspected and acute
serum is negative or inconclusive, a 2nd serum sample may be requested 3-5 days after acute serum Paired acute and convalescent serum specimens can
demonstrate sero-conversion to WNV. A single acute serum may provide evidence of recent
WNV infection, a negative acute serum does not necessarily rule out infection.
Occasionally, a specimen may be collected too soon to show antibody related to a current illness (e.g. with immuno- compromised individuals).
InfectionInfectionIllness onsetIllness onset
D4 D4 –– D6 illnessD6 illness 1Y after illness1Y after illness
ViremiaViremia
Serum & CSF Serum & CSF IgMIgM AbAb
IgGIgG & & NtNt AbAb
D14 D14 –– D21 illnessD21 illness
Con
cent
ratio
nC
once
ntra
tion
WNVWNV--CNS tissueCNS tissue
Incubation: 2Incubation: 2--15 days15 days
Typical antibody response profile to WNV in serum and CSF
Test Results InterpretationIgMIgG
NegativeNegative
Antibody not detected
IgMIgG
NegativePositive
Infection at undetermined time
IgMIgG
PositiveNegative
Possible evidence of recent of current infection; further testing necessary*
IgMIgG
PositivePositive
Evidence of recent or current infection**
IgMIgG
IndeterminateNegative
Inconclusive- request convalescent serum***
Interpretation of WNV antibody resultsInterpretation of WNV antibody resultsResults should be interpreted along with clinical and epidemiological information
***
***
Note the possibility of a false-positive IgM resultNote that some individuals may have persisting antibodies from the previous WNV seasonPaired acute and convalescent serum samples may help demonstrate seroconversion
WNV is a reportable diseaseWNV is a reportable disease
Contact your local health department if you suspect Contact your local health department if you suspect West Nile virusWest Nile virus
Laboratories required to report positive Laboratories required to report positive test resultstest results
Public Health preventive measures Public Health preventive measures (mosquito control, education) can be (mosquito control, education) can be implemented quickly when human implemented quickly when human cases are reported in a timely fashioncases are reported in a timely fashion
Prevention of WNVPrevention of WNV
Vaccine DevelopmentVaccine Development No human vaccine currently availableNo human vaccine currently available Vaccines undergoing clinical trials include:Vaccines undergoing clinical trials include:
ChimeriVaxChimeriVax--WN02. A live, attenuated recombinant WN02. A live, attenuated recombinant vaccine based on infectious clones of yellow fever and vaccine based on infectious clones of yellow fever and West Nile virus. Phase I complete, Phase II in West Nile virus. Phase I complete, Phase II in process. (process. (SanofiSanofi--Aventis)Aventis)
Recombinant DNA Plasmid Vaccine. Phase I complete Recombinant DNA Plasmid Vaccine. Phase I complete (Sponsored by NIAD (Sponsored by NIAD --National Institute of Allergy and National Institute of Allergy and Infectious Diseases) Infectious Diseases)
Live attenuated Live attenuated chimericchimeric virus, derived from the DEN4 virus, derived from the DEN4 dengue virus and wilddengue virus and wild--type WN serotypes. In Phase I type WN serotypes. In Phase I (Sponsored by NIAD and Johns Hopkins School of (Sponsored by NIAD and Johns Hopkins School of Public Health)Public Health)
Prevention:Prevention:Personal Protection: The 3 DPersonal Protection: The 3 D’’ss
DRAIN:DRAIN: Mosquitoes lay their eggs on standing water. Young mosquitoes grow in the water. Get rid of standing water around the home. Empty water out of buckets, old tires, flower pots, and toys.
DEFEND:DEFEND: Use an EPA-registered insect repellent with DEET, picaridin, IR3535 or oil of lemon eucalyptus in it. Put the repellent on your skin that is not covered by clothes. Follow the directions carefully.
DUSK and DAWN:DUSK and DAWN: Mosquitoes that transmit West Nile virus bite in the early morning and early evening hours, and sometimes throughout the night. When outside in the early morning or evening hours, wear long pants and a long sleeved shirt.
Habitat
modification
Chemical BiologicalMosquito fish
Chemical, Biological
Mosquito Control
Local mosquito and vector control agencies use multiple approaches to control mosquitoes following the California Mosquito-borne Virus Surveillance and Response Plan
West Nile Virus ResourcesWest Nile Virus Resources
Case studiesCase studies
Case study #1:Case study #1:Clinical presentation is not the whole storyClinical presentation is not the whole story
7878--yearyear--old male presenting in January old male presenting in January with fever, altered consciousness, with fever, altered consciousness, encephalopathyencephalopathy
HospitalizedHospitalized No lumbar puncture performedNo lumbar puncture performed Day 1 Day 1 –– serum collectedserum collected
WNV EIA WNV EIA IgMIgM(+), (+), IgGIgG(+)(+) IgMIgM weakly positiveweakly positive
Case study #1, continuedCase study #1, continued Epidemiologic data Epidemiologic data -- one positive dead bird; no one positive dead bird; no
other activityother activity No history of travel or other exposuresNo history of travel or other exposures Day 26 Day 26 –– convalescent serum collectedconvalescent serum collected
No change in titersNo change in titers
Ultimately, determined to be likely an old Ultimately, determined to be likely an old infection; patient was not reported as an acute infection; patient was not reported as an acute case. Cause for clinical presentation case. Cause for clinical presentation undeterminedundetermined
Case study #2Case study #2Travel adds wrinkle to diagnosisTravel adds wrinkle to diagnosis
3939--yearyear--old male presenting with fever, old male presenting with fever, headache, muscle weakness, diarrhea, headache, muscle weakness, diarrhea, chillschills
Day 8 Day 8 –– serum sample collectedserum sample collected WNV EIA WNV EIA IgMIgM(+) and (+) and IgGIgG(+)(+)
County health department submitted West County health department submitted West Nile virus case report form to CDPHNile virus case report form to CDPH
Case study #2, continuedCase study #2, continued Case report form noted travel to Guatemala in Case report form noted travel to Guatemala in
OctoberOctober Additional testing on serumAdditional testing on serum
Dengue IFA Dengue IFA IgMIgM(+) and (+) and IgGIgG(+)(+) Dengue PRNT = 1:320Dengue PRNT = 1:320 WNV PRNT = 1:20WNV PRNT = 1:20
Patient had dengue infection. Check history for Patient had dengue infection. Check history for travel to areas with other travel to areas with other flavivirusflavivirus activityactivity
Case study #3Case study #3Some cases we may never knowSome cases we may never know
5858--yearyear--old male presenting with febrile old male presenting with febrile illnessillness
History of dengue fever, malariaHistory of dengue fever, malaria Received yellow fever vaccineReceived yellow fever vaccine No recent travel, but lived in various parts No recent travel, but lived in various parts
of Africa, Haiti, and Australia, from 1980s of Africa, Haiti, and Australia, from 1980s through 2000through 2000
Epidemiologic data Epidemiologic data -- very little WNV very little WNV activity in county of residenceactivity in county of residence
Case study #3, continuedCase study #3, continued
Received serum samples collected Day 3, Received serum samples collected Day 3, Day 7, Day 20, Day 75Day 7, Day 20, Day 75
All WNV and dengue results for all All WNV and dengue results for all samples positivesamples positive
Not confirmable if WNV, dengue or both. Not confirmable if WNV, dengue or both. Cases with prior Cases with prior flavivirusflavivirus infection and/or infection and/or vaccination can be difficult to diagnosevaccination can be difficult to diagnose
Thank you for your attentionThank you for your attention
For more information:For more information: Visit: Visit: www.westnile.ca.govwww.westnile.ca.gov Call Cynthia Yen, MPH: (510) 620Call Cynthia Yen, MPH: (510) 620--39873987
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