Emerging Infections of International Public Health Importance





Module 2:

Current Challenges in Infectious Diseases

LECTURE 4 Readings

West Nile Virus

Sharon G. Hopkins DVM, MPH

  Dr. Sharon Hopkins, DVM, MPH is a public health veterinarian at Seattle King County Public Health. She is also a clinical assistant professor in the Department of Epidemiology at the University of Washington’s School of Public Health and Community Medicine. Her research interests include communicable diseases and emerging infections.


  1. Be able to describe several examples of vector-borne disease
  2. Gain knowledge of global factors that facilitate emergence or re-emergence of such diseases
  3. Understand the epidemiology of West Nile Virus and its emergence in the United States
  4. Be able to describe the actions of a local public health agency in response to West Nile Virus


Vector Borne Diseases

Hundreds of disease-causing viruses, bacteria, and parasites require a hematophagous (blood-sucking) arthropod for transmission between vertebrate hosts. There are many arthropod vectors. The arthropod phylum includes insects (such as mosquitoes) and arachnids (such as ticks and mites). Arthropods are jointed body invertebrates with an exoskeleton.

Many of the vector-borne infections are zoonoses, diseases transmitted between animals and humans. Historically, vector-borne diseases were responsible for more human disease and death in the 17th through 20th centuries than any other cause.

[Figure:   Vector-borne diseases]

This slide shows four examples of arthropods that can spread disease.

  • Upper left: Ticks can transmit lyme disease
  • Upper right: Fleas can transmit plague
  • Lower left: mosquitoes can transmit malaria
  • Lower right: kissing bugs can transmit Chagas disease

There are three main disease classes for vector-borne diseases: bacterial, viral and parasitic. Examples of bacterial diseases are Lyme disease, tularemia, and plague. Viral diseases include West Nile, dengue, yellow fever, and tick-borne encephalitis. Examples of parasitic diseases include malaria and trypanosomiasis (African sleeping sickness, Chagas disease).


Global factors of emergence for vector borne disease

There are several factors that facilitate emergence or resurgence of vector borne diseases:

  • Population growth and crowding
  • Changing urban ecology and lifestyles
  • Migration of populations from rural to urban
  • Prolonged civil war or other disruption of society
  • Increased air travel
  • Importation and global movement of exotic species
  • Agricultural practices that reduce natural predator control of vectors or increase vector habitat
  • Pesticide resistance
  • Decline in public health infrastructure
  • Climate change/Global warming(?)


West Nile Virus (WNV)

West Nile Virus is part of the Japanese encephalitis serocomplex of viruses. This map shows the distribution worldwide of these different viruses which includes St. Louis encephalitis, West Nile, Japanese encephalitis, Murray Valley and others.

[Figure:   the Geographic Distribution of the Japanese Encephalatis Serocomplex of the Family Flaviridae, 2000]

The blue color indicates where West Nile is present. It arrived in the U.S in New York City in 1999 and 2000. Prior to that time it was present in parts of Africa, the Middle East and Europe. The black color indicates an area of overlap between Japanese encephalitis and West Nile Virus.

West Nile Virus is primarily a disease of birds.

[Figure:   West Nile Virus is primarily a disease of birds]

Human infections are considered ‘incidental’ infections and are not important in the actual lifecycle of this virus. Birds that are most susceptible are the raptors, such as owls, eagles, and hawks. They have a high mortality rate if they become infected. The other highly susceptible group is the corvids, which are the ravens, blue jays, and the crows. These birds also have a high mortality rate when they become infected with West Nile Virus. The flamingo was the first bird West Nile was recognized in when the virus first arrived in the U.S.

The transmission cycle of West Nile Virus occurs between the bird reservoir host and a mosquito vector.

[Figure:   West Nile virus transmission cycle]

During the course of a season, an increasing number of birds will become infected and infect an increasing number of mosquitoes and the cycle amplifies. At some point, it may spill over to humans, horses and other species. In the U.S., the reservoir bird hosts are not fully known yet. Crows and corvids that have a high death rate and may not be the primary reservoir of this disease. Researchers are looking at other species that may not become as ill or have as high a death rate as corvids or raptors. House sparrows or some other very common birds have been looked at and suggested as primary reserviors, but we really do not fully understand the ecology as yet.

In the U.S, West Nile has been found in more than 150 different species of birds. It has also been seen in deer, bear, wolf, skunk, harbor seal, alligator, bat, squirrel and chipmunk. The most severly affected of the domestic animal species affected are equines (horse, donkey, mule); domestic dogs and cats can get infected but they rarely show clinical illness.

This is a timeline for West Nile.

[Figure:   WNV Outbreak Timeline]

It was first recognized around the West Nile area of Uganda in 1937, hence the name. It was followed by outbreaks in the Middle East, France, and South Africa. There seemed to be some intensification in the 1990s with recent sporadic outbreaks. It is unclear whether the recent observations are due to surveillance or truly increased number of outbreaks.

This appeared recently in the CDC’s Emerging Infectious Disease online journal.

[Figure:   Historical Review: Alexander the Great and West Nile Virus Encephalitis]

This brief summary speculates that Alexander the Great may have died of West Nile Virus. He had a two-week febrile illness and ravens were exhibiting unusual behavior and dying at the same time. If true, the disease may have been present since 323 B.C.E.


West Nile Virus in the U.S.

What finally brought West Nile Virus to the U.S.?

  • Human transported bird, either legal or illegal
  • Human transported mosquitoes either in ship cargo holds or on airplanes
  • Storm transported birds who were blown off course from the Middle East
  • Intentional introduction such as bioterrorism (unlikely!)
  • Infected human traveler (unlikely since viral titer in humans is relatively low)

The bioterrorism and infected human traveler theories seem unlikely given the epidemiology of the disease in the United States.


Clinical Features of WNV in humans

  • Incubation period is 3-14 days
  • Majority of people (80%) with infection are asymptomatic
  • Sudden onset of fever occurs in 20% of people with West Nile
  • 50% of people with WNV fever sought medical attention
  • Less than 1 in 150 of those infected result in the severe neurologic form (encephalitis/meningoencephalitis, flaccid paralysis, or meningitis) of the disease
  • Symptoms can be mild such as rash or lymphadenopathy
  • More severe include weakness, neuropathy, ataxia, optic neuritis, or seizures
  • Of the seriously ill, 25% required the ICU and 10% required mechanical ventilation
  • Fatality rate is 3-15%

This is a graph of a series of 45 cases.

[Figure:   Number and rate of clinical WNV infections (n=45) by age group, NYC 1999]

You can see that there are low rates of clinical WNV at the younger ages but increases in an almost linear fashion beginning at age 50. There does not seem to be an increase at the younger age groups so it does not have a bi-modal age distribution.


Outcomes among people who are hospitalized with WNV:

  • 50% had not returned to previous functional level before illness
  • Only one-third were fully ambulatory
  • Two-thirds had persistent fatigue one year after illness
  • 50% had memory loss, difficulty walking or muscle weakness


Predictors of poor outcome for WNV:

  • Advancing age, with risk increasing with each decade over age 50
  • More severe disease with encephalitis and severe muscle weakness
  • Persons with diabetes mellitus or other immune-compromising disease


West Nile Virus in Domestic Animals

  • Horses significantly impacted
  • Clinical presentation is similar to humans
  • Over 15,000 equine cases were documented in 2002 in U.S.
  • Equine mortality rate was 30-40%
  • Clinical disease was rarely seen in dogs and cats--only 7 cases in 2002
  • Chickens are often infected but do not become ill
  • Commercial alligators are susceptible to this virus and had a high mortality rate of 50% in one outbreak

Because chickens can become infected with WNV but rarely become ill, they are used for sentinel surveillance for this disease. This technique is used in parts of eastern Washington. There is no evidence to suggest that WNV can be transmitted orally to humans by consuming food infected with the virus. It is a vector-borne disease, in this case by the mosquito. West Nile Virus amplifies in nature as mosquito season progresses. Mosquitoes are killed by freezes and only a few that have successfully wintered over hatch out in the spring. You need to have enough mosquitoes biting birds in a continuing cycle to amplify the virus.


WNV Transmission

Primary route is by the bite of an infected mosquito.

  • Only female mosquitoes bite
  • Mosquito must have fed on an infected animal to be infectious
  • Newly hatched mosquitoes cannot transmit WNV
  • Transovarial transmission in mosquitoes probably not a major factor
  • Even in epidemic situations, probably fewer than 1% of mosquitoes are carrying WNV
  • Peak of transmission seems to be late August and early September

This graph shows three different years of infection with the peak of disease seen in the last weeks of August and first weeks of September.

[Figure:   Date of WNV Symptom Onset US, 1999-2001]

Additional transmissions modes have been suggested.

  • Blood transfusion--In 2002, 23 persons were identified with WNV epidemiologically linked to blood transfusion. Blood screening for WNV began in July 2003.
  • Organ transplant--one case of WNV in a recipient of a contaminated donor
  • Breast feeding or intrauterine infection--one case described
  • Laboratory acquisition--reports from workers in an alligator farm when they did post-mortem examinations on alligators that had died.

This is a table of the WNV case summary for 1999-2003.

[Figure:   WNV Case Summary, 1999-2003]

In 1999, there were 62 cases and 7 deaths. In 2003, there were 9006 cases and 220 deaths. There were far more equine cases with higher death rates during these same time periods.

West Nile Virus sequentially moved through the United States. The following slides depict where the disease moved from 1999 through to 2003.

This map shows the distribution of WNV in the US in 1999.

[Figure:   Distribution of WNV as of November 1999]

You can see it is primarily concentrated in the New York region where the virus was first introduced.

This shows the distribution in 2000.

[Figure:   Distribution of WNV as of November 2000)

Distribution in 2001

[Figure:   Distribution of WNV as of November 2001]

Distribution in 2002:

[Figure:   Distribution of WNV as of November 2002]

This slide shows WNV in 2003 with the number of cases per state.

[Figure:   WNV in 2003: 9,006 cases, 220 deaths]

The following slides are from the US Geologic Survey, the first two are the human cases and the second two are the veterinary cases for the same years. The red dots represent the cases. The green dots indicate counties that submitted testing but had negative results. Both the human and veterinary cases show the westward progression of the virus.

WNV human cases 2002:

[Figure:   WNV human cases 2002]

WNV human cases 2003:

[Figure:   WNV human cases 2003]

WNV veterinary 2002:

[Figure:   WNV veterinary survey 2002]

WNV veterinary 2003:

[Figure:   WNV veterinary survey 2003]

Reasons for a decline in cases from one year to the next in a given geographic location are likely to be multifactorial. Mosquito control efforts were undertaken in many areas, which could reduce the mosquito burden. Populations of reservoir birds may have declined. Vaccination of horses may have reduced equine cases.

WNV is evolving epidemiologically. Reported human cases more than doubled in 2003 from 2002 with death rates remaining similar. Different states affected and were seeing more rural cases. Also as the disease moved westward, more recently affected states had higher rates than states affected the year before. Illinois had 884 cases in 2002 and 52 cases in 2003, Michigan was similar with 614 cases in 2002 and 15 cases in 2003. Colorado however had 14 cases in 2002 and 2477 cases in 2003.


Changing epidemic


  • Most intense in Central U.S. and Great Lakes region
  • Urban focus of cases
  • Largest arboviral epidemic in Western hemisphere
  • Completed transcontinental move with human case in Los Angeles, and equine case in Washington State


  • Most intense in Rocky Mountain States, especially Colorado
  • More rural focus, possibly different vector mosquito species associated with irrigation
  • Equine cases reduced, possibly affect of vaccination and natural immunity
  • Not yet established on West Coast, despite cases in 2002


Surveillance for WNV

With WNV, the first indicator in an area that there is a problem will be an increase in the dead bird sightings, usually most noticeable in crows. Following that there will be sentinel hosts, such as chickens that become infected. Afterwards, mosquitoes are collected and tested. Usually the next affected are the equines and finally the humans.

This graph demonstrates this surveillance concept based on disease activity and time.

[Figure:   Estimated sensitivity of WNV surveillance methods]


West Nile Virus in Washington State

We have not had a case of WNV in King County yet but have tested about 3000 dead birds. This map shows the counties where WNV cases have been identified in Washington State; three counties have been impacted.

[Figure:   Counties detecting WNV, 2002]

There have been two avian and two equine cases but no human cases to date.


WNV Response in King County

The Public Health Department of Seattle-King County has three components to its response plan:

  1. Surveillance
  2. Education
  3. Control.

This is a collaborative effort with the Public Health Department taking the lead and partnering with other agencies. There is a WNV Interagency Work Group is producing a phased response guideline. As part of the detection and control strategies we have also developed a WNV tabletop exercise.

Even with no WNV cases, King County has felt the impact of this disease in the following ways:

  • Half of the public health veterinarian’s time during WNV season is spent on this disease
  • Half of the public information officer’s time during WNV season is spent on WNV
  • Website and hotline set up
  • Hired a graduate student to coordinate education outreach
  • Hired a temporary employee to collect dead birds
  • Deluged with phone calls when a suspected case of WNV appeared, which later was determined not to be WNV


WNV Surveillance in King County

  • 17 human cases have met testing criteria in 2003
  • 3 had alternate diagnoses made
  • 6 were sent to the Dept of Health (DOH) laboratory for further testing
  • 1 came back positive but the exposure and infection was from Colorado
  • other 5 tested negative
  • 7 specimens were requested but never received
  • 1 lost to follow up

2689 dead bird reports

  • 159 birds submitted for WNV testing, all tested negative
  • 187 mosquito complaints
  • 95 mosquito pools sent to DOH for testing to determine species in area

4 horses tested, all negative

Here are pictures of mosquito surveillance techniques

[Figure:   Mosquito surveillance techniques]

The method on the left is a CO2 trap. It releases CO2 which mimics the respiration of a mammal and attracts the mosquitoes into the trap. A fan blows the mosquito into the net where it is trapped. The method on the right is to have a bucket with standing water and dip into it for mosquito larvae. The larvae are then placed in breeders and hatched. The purpose of these efforts has been to determine the species of mosquitoes found in King County; not all mosquito species are competent vectors of WNV

This is a list of the mosquito species we have found in King County; the names with a star next to them are the primary vectors for WNV

[Figure:   Mosquito species we have found in King County]


WNV Education Efforts

  • Outreach--via home care and residential service providers
  • Fact Sheets--sent to all providers of elderly
  • Radio Advertisements--targeting older adults
  • Community lectures--by Public Health staff
  • WNV information--sent to all King County residential care facilities
  • Senior Service Newsletter--article reached 70,000 persons
  • Website--video, hotline, brochures, and media events
  • Homeowner fact sheet--on prevention strategies


WNV Control Measures

Begin with public education by accurately communicating the risk and give personal responsibility for property and protection. Then do habitat reduction by reducing standing water—e.g., emptying cans and water troughs when not in use. The third phase is using pesticides, both larvicide (and adult mosquito sprays if indicated by the severity of the epidemic), to reduce the adult mosquito population.

This slide shows some typical mosquito habitats.

[Figure:   Typical mosquito habitats]

These are areas to watch for and take precautions. Removal of old tires and cans (where stagnant water can exist and larva can develop) and any other sources of standing water is important.

This slide shows the life cycle of the mosquito.

[Figure:   Life cycle]

The larval stage is the most susceptible; once they reach the pupa stage and hatch, they are no longer susceptible to most types of larvicides.

This slide shows some predators of the mosquito larva.

[Figure:   Predators--Larva]

These can go a long way toward controlling mosquitoes. The larva are a food source for many insects.

Larvicides kill the mosquito larvae. They help to reduce the adult mosquito population in nearby areas. Larvicides can include both microbes (bacillus) and pesticides.

In order to successfully do surveillance and control for this disease, the Public Health Department needs partner agencies. Liaisons with the Department of Natural Resources and Parks, Department of Roads, Department of Ecology, laboratories and others are essential for effective control.

Factors that need to be considered in developing a county-wide response plan:

  • What is the perceived or expected constituent response to the West Nile Virus?
  • State Department of Health response plan recommends proactive control and indicates control measures are beneficial
  • WNV is not a serious illness for most people, the elderly are at most risk
  • Mosquito control activities in other parts of the country may not have slowed the spread of the virus
  • Should private facilities be treated as well?
  • What is the cost of various response options?
  • What is being put off to deal with WNV?
  • Other agency issues or concerns with response options
  • Environmental concerns regarding control options, especially use of pesticides
  • Risk analysis of larvicides
  • Can control be focused on specific mosquito species?

These are possible response options from the Department of Natural Resources and Parks (DNRP)

  • Rely on education and media outreach. No planned control activities.
  • Respond to WNV outbreaks as they occur. Use localized control as specific problem areas are identified.
  • Limited proactive response near at risk populations with localized control as specific problem areas are identified.
  • Full proactive response at all facilities
  • Move population to mosquito free locations--not likely or feasible

The Water and Land Resource Division (WLRD) made the following recommendations:

  • DNRP to pursue a limited, proactive, targeted treatment program to include larvicide application at some, but not all, county maintained storm-water ponds in unincorporated King County
  • Proactive measures limited to facilities with primary vector species.

In practice, before treatment of storm-water ponds was undertaken, there needed to be a way of determining which ponds were to be selected. There needed to be water in the facility and mosquito larva present. The storm-water ponds needed to be near at-risk populations: those with a high density of >50 age groups, near nursing homes, and where morning or evening outdoor events (concerts, sporting events) took place. Also the proximity to mammalian or bird cases would be taken into account.

GIS systems were used to map the storm-water ponds and overlay this with the populations as determined in the first step. The results are seen on the following slides.

Population density of those age 50+ > 1000 per square mile:

[Figure:   Population density of those age 50+ > 1000 per square mile]

Population density of those 50+ where there are greater than 40 people per sq mi.

[Figure:   Population density of those age 50+ > 40 per square mile]

Storm-water services facilities:

[Figure:   Storm-water services facilities]

Overlay of storm water facilities with population density of age 50+ and incorporated areas:

[Figure:   Combined GIS map]

As you can see there is only a small area where there is the concentration needed to implement a treatment plan.

This map shows the potential larvicide facilities designated by the at risk populations:

[Figure:   Potential larvicide facilities by at risk populations]

These are marked in yellow and red. Nursing homes are the purple dots. We can see how the use of multiple technologies can be effective in proactively reducing the mosquito population.


Ongoing West Nile Virus issues from 2003 into the future

  • Be open to changing the control process
  • Manage expectations
  • Response is likely to change as the season progresses and there is a need for preparedness
  • Variable responses from partner agencies need to be managed. Some agencies worked well from guidelines, others needed very specific directives. Some were waiting for positive surveillance findings before acting. These differences need to be worked out for future response efforts.
  • Public Health and partner agencies face real issues of resources and need to weigh the cost vs benefit of any program
  • Need to continue to involve and prepare more cities and counties for response.


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