# Presentation: 236087

## West Nile Virus UpdateAugust 23, 2007

- Carolyn Reimann, MD
- Emily Zielinski-Gutierrez, DrPH
- Division of Vector Borne Infectious Diseases (DVBID)
- National Center for Infectious Diseases
- Centers for Disease Control and Prevention
- Fort Collins, Colorado

## WNV is an Arthropod-Borne virus

- First discovered in 1937 in the West Nile district of Uganda
- Until 1999 only found in Asia, Southern Europe, Africa
- Flavivirus, in the Japanese Encephalitis Antigenic Complex –similar family to Yellow Fever, St. Louis encephalitis virus
- Transmitted by mosquitoes

## WNV: Basic Transmission Cycle

- Most important cycle is from mosquito to bird to mosquito

- Amplifying hosts

- “Incidental” infections: unlikely amplifying hosts

## Transmission

- The most common route of infection is bite of infectious mosquito
- 2002 revealed other modes
- Blood Transfusion
- Organ Transplantation
- Intrauterine
- Percutaneous exposure (occ. exposure)
- Breastmilk (probable)

## Screening of Blood Supply

- Since July 2003, all blood donated in US is screened for WNV using nucleic acid amplification testing (NAT)
- Platform under Investigational New Drug protocol
- Use of NAT continues to be refined
- Transfusion-associated risk very, very low
- In 2006, 361 Presumptively Viremic Donors (PVDs) identified
- Seasonal algorithms for use of single- or multiple-donor testing still under exploration

## Presumptively Viremic Blood Donors, 2006

## Presumptively Viremic Blood Donors, 2007

- As of Aug 14, 2007

## WNV and Pregnancy

- One confirmed intrauterine WNV infection (2002)
- 2003-2004 study of 72 infants born to WNV-infected mothers (O’Leary, 2006)
- No confirmed cases of transplacental WNV transmission detected based on cord blood IgM
- However, 3 cases of neonatal WNV infection were detected (2 neuroinvasive, 1 rash)
- Suspected to be transplacentally transmitted, but cord blood negative for IgM

## WNV and Pregnancy

- 7 major birth defects were detected among 66 infants with physical exam data (10.6% of live births)
- Only 3 of these defects could have been caused by maternal WNV infection based on timing.
- None had any conclusive evidence of WNV etiology.
- ONGOING -- Cohort study of pregnant women with and without WNV infection through Tulane, enrollment through 2007
- Study coordinator Scott McRae
- westnilepregnancy.net

## WNV Human Infection “Iceberg” 

**~80****%**
**Asymptomatic**

**~****20%**
**“****West Nile Fever”**

**<1%**
**CNS**
**disease**

**~****10% of CNS disease is fatal**
**(<0.1% of total infections)**

**WNV Human Infection “Iceberg” **

**For every case of illness**
**involving the brain or spinal**
**cord,**
**~140 total infections**

## West Nile Fever

- Most who get sick from WNV infection have WNV fever
- Time from mosquito bite to illness ranges from 3-14 days
- Fever, chills, headache, fatigue can be severe
- Nausea, vomiting
- Rash, usually not itchy, lasting a few days, mainly on chest, back, abdomen,  and/or arms
- Persistent fatigue common -- may continue for months, even among otherwise healthy persons
- In one study, “~96% of patients with WNF ...described post-illness fatigue that lasted a median of 36 days” (Sejvar, 2007)

## WNV Meningitis

- More likely than encephalitis to have myalgias, arthralgias, nausea, vomiting, rash, and back pain (Bode, 2006)
- White blood cells in the cerebrospinal fluid
- Headache may be quite severe
- Most people improve, though persistent symptoms may include fatigue, weakness, and memory and concentration problems (Sejvar, 2007)

## WNV Encephalitis

- Encephalitis patients more likely than meningitis patients to have memory problems, dysarthria, dysphagia, and focal motor abnormalities incl. cranial nerve palsies (Bode, 2006)
- Severity ranges from mild confusion to coma and death

## WNV-Associated Flaccid Paralysis

- Recognized more frequently in the last 2 years
- Affects relatively healthy young people
- May not have fever or headache before paralysis
- Clinical hallmarks:
- Onset early in infection
- Weakness can often be in only one limb
- Absence of numbness; pain sometimes present

## Risk for Severe Disease 

- Advanced age and HTN are risk factors for developing encephalitis
- After adjusting for age, the following are risk factors for death: black race, chronic renal disease, hepatitis C virus, and immunosuppression (Murray, 2006)
- Solid organ transplant recipients are at ~40 times greater risk for ND than overall population (Kumar, 2004)

## Human WNV Disease Incidence, by Age Group and Clinical Category, United States, 2006*

**Human WNV Disease Incidence, by Age Group and Clinical Category, United States, 2006***

*** Reported as of 5/6/2007**

*** *Entire US population**

## West Nile virus neuroinvasive disease cases by age group and gender, 1999-2006*

- Reported as of 5/2/2007

## Diagnosis of WNV Infection

- Suspect in meningitis, encephalitis, or flaccid paralysis from summer through fall, or December in the South
- Consider other arboviral diseases such as St. Louis encephalitis, La Crosse encephalitis (esp in children)
- Local WNV enzootic activity or other human cases should raise suspicion
- Recent travel history also important
- State labs can help with diagnostic testing of serum or CSF for WNV IgM and/or IgG
- Testing also available from many commercial labs

## WNV Treatment

- No specific treatment for WNV disease
- 2 IRB-approved, double-blinded, placebo-controlled clinical trials available testing safety and efficacy of alpha interferon. More information:
- http://www.cdc.gov/ncidod/dvbid/westnile/clinicalTrials.htm

## WNV Outcomes

- For all WNV syndromes, younger age is more predictive of full recovery than is initial illness severity (Sejvar, 2007)
- WN encephalitis patients more likely than WN meningitis patients to develop respiratory failure -- 34% vs. 2% in one study (Bode, 2006)
- WN meningitis mortality almost none, while WN encephalitis mortality 15-25% (Campbell, 2002)
- WNV flaccid paralysis
- Some people with almost complete recovery; others with continued weakness
- Those with less severe initial weakness tend to have a better prognosis

## Reporting

- Reporting procedures vary by state – Check with state coordinators/state websites
- All human WNV illness is reportable as of 2004
- WN Fever is greatly underreported
- ND cases should be used for temporal and geographic comparisons

## WNND County Level Incidence per Million, United States, 2006

## WNND County Level Incidence per Million, United States, 2007

- As of Aug. 14, 2007

## 2006 WNV Activity

## 2007 WNV Activity as of Aug 14, 2007

**(available : **_[http://www.cdc.gov/ncidod/dvbid/westnile/surv&control04Maps.htm](http://www.cdc.gov/ncidod/dvbid/westnile/surv&control04Maps.htm)__)_

## WNV Prevention

- Personal Prevention-emphasis at times of high mosquito activity (dawn/dusk) or stay indoors
- Use mosquito repellent
- Wear long sleeves, pants
- Household
- Use/ fix screens
- Air-conditioning
- Empty standing water
- Community / environmental
- Community-based mosquito management

## Repellent Guidance 

- Skin
- DEET still “gold standard”
- Higher concentrations (20-50%) provide longest protection times
- Picaridin
- Roughly equivalent to DEET at same concentration
- Only low concentration products (<15%) currently sold in US
- Oil of lemon eucalyptus
- Plant based
- 30% product similar to low concentration DEET
- Not for kids <3 years old
- Clothing
- Permethrin, effective through multiple washings

## Info Online

**General/Updates statistics: www.cdc.gov/westnile **
**West Nile Virus: Information and Guidance for Clinicians**
- http://www.cdc.gov/ncidod/dvbid/westnile/clinicians/
**Diagnosis section **http://www.cdc.gov/ncidod/dvbid/westnile/resources/fact_sheet_clinician.htm

## References

- Bode AV et al. West Nile Virus Disease: A Descriptive Study of 228 Patients Hospitalized in a 4-County Region of Colorado in 2003. Clin Infect Dis 2006;42:1234-40.
- Campbell GL et al. West Nile Virus. Lancet Infect Dis 2002;2:519-29.
- Kumar D et al. A Seroprevalence Study of West Nile Virus Infection in Solid Organ Transplant Recipients. Am J Transplantation 2004;4:1883-88.
- O’Leary DR et al. Birth Outcomes Following West Nile Virus Infection of Pregnant Women in the United States: 2003-2004. Pediatrics 2006;117:e537-e545.
- Sejvar JJ. The Long-Term Outcomes of Human West Nile Virus Infection. Clin Infect Dis 2007;44:1617-24.