# Presentation: 858819

## Update on West Nile Virus – United States, 1999-2006

**Eileen C. Farnon, MD**
**Arboviral Diseases Branch**
**Division of Vector-Borne Infectious Diseases**
**Centers for Disease Control and Prevention**
**Fort Collins, Colorado**

**Blood Products Advisory Committee**
**89****th**** Meeting**
**April 27, 2007**

**Notes:**
Good afternoon.  I will be presenting an update on West Nile virus epidemiology in the United States from 1999 to 2006.

## WNV Transmission Cycle

**Enzootic (Maintenance/Amplification)**

**Amplifying hosts**

**Notes:**
WNV is a flavivirus that is transmitted by mosquitoes.  The virus is transmitted in an enzootic cycle between birds and mosquitoes, and causes epizootics in which birds and mammals are infected via “bridge” mosquitoes.  Horses and humans are considered dead-end hosts because they don’t develop high enough viremia to infect mosquitoes and thereby perpetuate the cycle.

## Slide 3

**Notes:**
This map shows the approximate global distribution of WNV.  Prior to 1999, WNV was found in Africa, parts of Asia, and Europe, with the closely related Kunjin virus occurring in Australia.  In 1999, WNV was introduced into North America, and has since been found in parts of Central and South America.  Human disease has been detected in the Cayman Islands, Mexico, El Salvador, and Argentina.

## ArboNET

**Arboviral national electronic surveillance system**
**Humans **
**Ecologic**
**Mosquitoes**
**Birds**
**Animals**
**WNV, SLE, EEE, WEE, LAC, DEN, VEE**
**All data current as of April 12, 2007**

**Notes:**
CDC developed ArboNET, the U.S. arboviral national electronic surveillance system, in 2000, in response to the detection of WNV in the U.S. in 1999.  
ArboNET is a passive surveillance system that collects data on WNV and other arboviral infections in humans, as well as ecologic data regarding infected mosquitoes, birds, and other animals.
The information that I’ll cover today is based on reports to ArboNET.  All the data are current as of April 12, 2007

## Human WNV Syndromes Reported to ArboNET

**WN fever (WNF)**
**WN neuroinvasive disease (WNND)**
**Meningitis**
**Encephalitis**
**Acute flaccid paralysis**
**Other **
**Unspecified illness**

**Notes:**
The human WNV syndromes reported to ArboNET include WN fever, WNND, including meningitis, encephalitis, and acute flaccid paralysis, other clinical syndromes, and unspecified illness.

## WNV Neuroinvasive Disease Incidence, by County, US, 1999

**WNV Neuroinvasive Disease Incidence, by County, US, 1999**

- N=59

**Notes:**
This series of maps shows WNND incidence by county in the US from 1999-2006.  Neuroinvasive disease incidence is thought to reflect the burden of human WNV disease more accurately than total case counts, since WN fever reporting varies widely from state to state.  Counties highlighted in green had ecologic activity in mosquitoes, birds, or mammals, and the dots represent incidence per million of WNND in humans. 
In 1999, WNV was first recognized in the US in the outbreak in NYC.
 In 2000, there were cases in neighboring states.
 In 2001, WNND incidence increased in the NE and spread to the SE.
 In 2002, high WNND incidence was seen in central and south-central states.
 In 2003, there was a large epidemic, with the highest incidence in the western plains states.
 The incidence in 2004 was lower overall, but continued to be high in the south-central, central, and western states, and increased in the southwest and along the west coast.
 In 2005, incidence increased in the south-central, central and western states.
 And, in 2006, incidence increased again and remained highest in the south-central, central, and western states.

## WNV Neuroinvasive Disease Incidence, by County, US, 2000

**WNV Neuroinvasive Disease Incidence, by County, US, 2000**

- N=19

**Notes:**
In 2000, there were cases in neighboring states.

## WNV Neuroinvasive Disease Incidence, by County, US, 2001

**WNV Neuroinvasive Disease Incidence, by County, US, 2001**

- N=64

**Notes:**
In 2001, WNND incidence increased in the NE and spread to the SE.

## WNV Neuroinvasive Disease Incidence, by County, US, 2002

**WNV Neuroinvasive Disease Incidence, by County, US, 2002**

- N=2,946

**Notes:**
In 2002, high WNND incidence was seen in central and south-central states.

## WNV Neuroinvasive Disease Incidence, by County, US, 2003

**WNV Neuroinvasive Disease Incidence, by County, US, 2003**

- N=2,866

**Notes:**
In 2003, there was a large epidemic, with the highest incidence in the western plains states.

## WNV Neuroinvasive Disease Incidence, by County, US, 2004

**WNV Neuroinvasive Disease Incidence, by County, US, 2004**

- N=1,148

**Notes:**
 The incidence in 2004 was lower overall, but continued to be high in the south-central, central, and western states, and increased in the southwest and along the west coast.

## WNV Neuroinvasive Disease Incidence, by County, US, 2005

**WNV Neuroinvasive Disease Incidence, by County, US, 2005**

- N=1,309

**Notes:**
In 2005, incidence increased in the south-central, central, and western states.

## WNV Neuroinvasive Disease Incidence, by County, US, 2006

**WNV Neuroinvasive Disease Incidence, by County, US, 2006**

- N=1,491

***Reported as of 4/12/2007**

**Notes:**
And, in 2006, incidence increased again and remained highest in the south-central, central, and western states.

## Slide 14

**Notes:**
This map shows the cumulative WNV activity and human cases by county, from the years 1999 to 2006.  Counties with ecologic WNV activity are depicted in blue, and counties with human cases are depicted in red.  All of the lower 48 states have had evidence of ecologic WNV activity, and only ME, HI and AK remain free of human cases.  
Since 1999, almost all counties in the lower 48 states have reported some WNV activity, sparing only a few counties, which are mostly in the northwest.

## Onset of Human WNV Disease,

**United States 1999-2006***

***Reported as of 4/12/2006**

**Notes:**
The onset of human WNV disease cases in the US has changed from 1999-2006. 
The WNV season has steadily lengthened, and in 2005 and 2006 the dates of onset of human cases spanned almost the entire year, from early January until mid-December, with states in the south having the longest human WNV season.

## Cumulative WNND Incidence, by County, US, 2002-2006

**Cumulative WNND Incidence, by County, US, 2002-2006**

***Reported as of 11/14/06**
**Lindsey N, et al, in press**

**Notes:**
We wanted to see whether some states have had persistently high incidence of WNND over the past five years, to see whether there might be hotspots of WNV activity in humans.  This map shows the cumulative incidence of WNND by county in the US from 2002 to 2006, with the red counties having the highest cumulative incidence and the lighter colored counties having the lowest cumulative incidence.  Harding County, South Dakota, has the highest cumulative incidence of 241 per 100,000.  25 counties in 6 Western states have a cumulative WNND incidence over 100 per 100,000.  Nicole Lindsey in our group at CDC recently examined how many of the counties with high cumulative WNND incidence have had consistently high annual rates of WNND incidence and therefore might be hotspots where WNV activity may continue to be high in the future.  

## Median Annual WNND Incidence Rank versus 

**Median Annual WNND Incidence Rank versus **
**Cumulative WNND Incidence Rank by County, 2002-2006 **

***Reported as of 11/14/06**
**Lindsey N, et al, in press**

**Notes:**
This scatter plot compares the median annual WNND incidence rank for each county with its cumulative WNND incidence from 2002-2006, in order to determine whether counties with high cumulative incidence had persistently high annual incidence in the five years from 2002-2006.  Since some counties have very few WNND cases and small populations, Nicole limited the analysis of county incidence to 447 counties where the lower limit of the 95% confidence interval for the cumulative incidence rate was more than zero.  The plot shows that most counties did not have consistently high annual incidence over the five year period from 2002-2006.  There were only a few counties that were hotspots, shown in red, orange, and light blue, with high cumulative incidence and persistently high annual incidence.  Most counties with high cumulative incidence had only one or two years with high annual incidence (POINT TO END OF X-AXIS).  The analysis also indicates that counties that have had low incidence of WNV transmission, in dark blue, tend to maintain low transmission rates.  

## Counties with Persistently High WNND Incidence, 2002-2006

**Counties with Persistently High WNND Incidence, 2002-2006**

**Notes:**
Looked at geographically, this map shows the hotspot counties that had persistently high WNND incidence from 2002-2006.  The counties in the top 5% of both cumulative and median annual incidence for WNND are shown in red, the ones in the top 10% in orange, and those in the top 20% in light blue.  These hotspot counties cluster in the Western plains states and at the eastern edge of the Rocky Mountains, with a few in the south-central states.

## Reported WNV Disease Cases in Humans – United States, 1999-2006*

| Year | Total | WNND | WNF/other | Deaths |
| --- | --- | --- | --- | --- |
| 1999-2001 | 149 | 142 | 7 | 18 |
| 2002 | 4,156 | 2,946 | 1,210 | 284 |
| 2003 | 9,862 | 2,866 | 6,996 | 264 |
| 2004 | 2,539 | 1,148 | 1,391 | 100 |
| 2005 | 3,000 | 1,309 | 1,691 | 119 |
| 2006 | 4,261 | 1,491 | 2,770 | 176 |
| Total | 23,967 | 9,902 | 14,065 | 961 |

***Reported as of 4/12/2007**

**Notes:**
This chart summarizes the total reported WNV disease cases in humans in the US from 1999-2006.
The columns show the total number of cases, WNND cases, WNF or other cases, and deaths; and the rows show the year.
The number of human cases peaked in 2003, declined by almost a fourth in 2004, and have been increasing again, for a total of 4,261 human cases in 2006 reported to ArboNET, and almost 24,000 cases to date since 1999.

## WNV Blood Screening

**2002 – 23 cases of transfusion-associated transmission (TAT)**
**2003 – Nucleic acid amplification tests (NAT)**
**MP-NAT (6-16 units) ******** ID-NAT**
**Blood banks report presumptively viremic donors (PVDs) to local public health department**
**Remove infectious blood products from circulation**
**Public health departments report to ArboNET**
**Perform clinical follow-up**
**Perform trace-back investigations**

**Notes:**
The need for blood screening for WNV became apparent in 2002, when 23 cases of WNV transfusion-associated transmission, or “TAT,” were documented.  In 2003, FDA initiated screening of the blood supply with nucleic acid amplification tests, or NAT.  Minipool NAT, or MP-NAT, is done on pools of samples of 6-16 units, and units from positive pools are then tested individually by individual NAT, or ID-NAT.  Blood banks report presumptively viremic donors, or PVDs, to the local public health department, and remove infectious blood products from circulation. Public health departments then report these cases to ArboNET, and perform clinical followup of the cases, including trace-back investigations along with partners including blood banks, tissue banks, organ procurement organizations, and FDA as appropriate, in order to identify other potential cases infected by the same donors.  

## WNV PVDs by Year*

| Year | PVDs |
| --- | --- |
| 2003 | 818 |
| 2004 | 224 |
| 2005 | 417 |
| 2006 | 361 |
| Total | 1820 |

***Reported as of 4/12/2007**

**Notes:**
This chart shows the number of WNV presumptively viremic donors by year.  In 2003, after screening of the blood supply for WNV began, 818 donors were identified, followed by 224 in 2004, 417 in 2005, and 361 in 2006.  A total of 1820 PVDs have been identified by this system over the past 4 years.

** **

**West Nile Viremic Blood Donors, **
**by State of Residence, 2006***

***Reported as of 4/12/2007**

**Notes:**
This map shows the number of presumptively viremic blood donors by state of residence in 2006.  These numbers correlate fairly well with the states that had the highest incidence of neuroinvasive disease cases in 2006.

## PVDs Reported to ArboNET*, 2006

**Over 8 million donations screened**
**361 PVDs reported to ArboNET**
**84 (23%) WNF**
**4 (0.1%) WNND**
**2 (0.1%) other**
**118 (33%) reported from 3 states: NE, ID, TX**

***Reported as of 4/12/2007**

**Notes:**
Over 8 million blood donations were screened in 2006.
Of the 361 PVDs reported to ArboNET in 2006, 23% developed WNF, 0.1% developed WNND, and 0.1% developed other unspecified illness from WNV infection.  These percentages are similar to those seen in WNV serosurveys.
33% of the PVDs reported in 2006 were from 3 states – NE, ID, and TX.

## WNV Transfusion-associated Transmission, 2006 – Case 1

**82 y male resident of SD recently post-kidney transplant**
**4d post-transplant:  2U PRBC**
**21d post-transplant: encephalitis**
**WNV IgM detected in serum and CSF**
**Organ donor tested negative for WNV**
**Blood donor tested positive for WNV IgM**
**negative MP-NAT**

**MMWR 2/2/07**

**Notes:**
2 suspect cases of transfusion-associated transmission that were investigated in 2006 were found to originate from a donor whose MP-NAT screen was negative.  The blood bank testing his donation had not yet reached their trigger for ID-NAT, although other blood banks had also found PVDs around that time from the same region.
The first case was an 82 year old male resident of SD who had recently received a kidney transplant.  He had received 2 U PRBC four days post-tx.  At 21d post-tx, he developed encephalitis; WNV IgM was detected in serum and CSF.
Premortem serum from the organ donor was negative for WNV by serology and PCR.  The recipient of the organ donor’s other kidney was asymptomatic, and his serum post-transplant tested negative for WNV infection.  The case-patient had received blood products from 6 different donors before he developed encephalitis, and all 6 donors were tested for WNV infection.  One of the blood donors tested positive for WNV IgM.  He was from rural South Dakota, and had been asymptomatic before and after donating blood.

## WNV Transfusion-associated Transmission, 2006 – Case 2

**60 y male resident of IA 5y post-kidney transplant**
**Spinal fracture repair in SD:  15 blood products**
**6U FFP from blood donor**
**11d post-operatively:  encephalomyelitis**
**WNV IgM detected in CSF**

**MMWR 2/2/07**

**Notes:**
A trace-back investigation of this blood donor revealed that a second immunocompromised patient had also likely been infected by a donation from the same donor.   Fresh frozen plasma from his donation had been transfused into a 60 year old male resident of IA who was 5y post-kid tx.  He had undergone surgery to repair a spinal fracture in SD and received 15 blood products, including the 6U of FFP from the WNV-infected blood donor.  11d post-op, he developed encephalomyelitis, and WNV IgM was detected in his CSF. 
Both of these cases are considered to be suspect cases of WNV transfusion-associated transmission; both had been hospitalized for at least 2 weeks before the onset of WNND, and were unlikely to have acquired the disease via mosquito bite.  These cases were described in an MMWR article that was published in February, which discussed the issue of how ID-NAT triggering mechanisms differ across the U.S.  The occurrence of these cases indicates that despite enormous successes screening the blood supply for WNV, it may be possible to improve on current triggering mechanisms.  This could be approached by examining how different triggering methods would have worked using either existing surveillance data or using theoretical models of WNV outbreaks.

## Summary

**WNV occurs throughout the continental U.S. **
**Western plains have highest incidence of WNND**
**Dates of onset for WNV disease span the year**
**2 cases of transfusion-associated transmission despite MP-NAT testing**
**New approaches to triggering ID-NAT considered**

**Notes:**
In summary, WNV transmission now occurs throughout the continental United States.  States and counties in the western plains and eastern edge of the Rocky Mountains seem to have the highest risk of WNND.  The dates of onset for human WNV disease now span almost the entire year.  Two cases of transfusion-associated transmission occurred despite MP-NAT testing in a region where PVDs were diagnosed simultaneously by separate labs. 
Because of these cases, new approaches to triggering ID-NAT are being considered in order to further lower the risk of transmitting WNV through the blood supply.

## Acknowledgements

**The findings and conclusions in this presentation are those of the authors and do not necessarily represent the views of the Centers for Disease Control and Prevention.**

**Jennifer Lehman**
**Nicole Lindsey**
**Stephanie Kuhn**
**Margaret Collins**
**Kate Ellingson**
**Matt Kuehnert**
**Mark Duffy**
**Marc Fischer**
**Edward Hayes**
**John Jones**
**Nicholas Komar**

**Roger Nasci**
**John Roehrig**
**Janet McAllister **
**Harry Savage**
**James Sejvar**
**Theresa Smith**
**Grant Campbell**
**Brad Biggerstaff**
**Lyle Petersen**
**All reporting states, jurisdictions, and local health departments**

**Notes:**
I would like to thank the individuals and organizations who assisted with this investigation.  Thank you.

## Photo: Meggan Gould

**Photo: Meggan Gould**

## Cumulative Incidence of WNND by State – United States, 2002-2006*

**Cumulative Incidence of WNND by State – ****United States, 2002-2006***

***Reported as of 11/14/06**

**Notes:**
This map shows the cumulative incidence of WNND cases by state, from 2002-2006. The cumulative incidence ranges from 32.2 per 100,000 in SD to 0.2 per 100,000 in NH.  Again, the states with the highest incidence over the past four years are in the central and western US.  However, the incidence has changed from year to year in any given state and county, and these results do not necessarily indicate areas that will have a high incidence of WNND in the future.