West Nile Virus

West Nile Virus

Emily Zielinski-Gutierrez, DrPH Lisa Lundgren, RN, MSN, FNP-C Division of Vector Borne Infectious Diseases (DVBID) National Center for Infectious Diseases Centers for Disease Control and Prevention Fort Collins, Colorado

West Nile Virus (WNV) before 1996 • First discovered in 1937 in the West Nile district of Uganda • Mild feverish illness • Severe illness, like meningitis or encephalitis, was rare • Wide distribution in Asia, Eastern Europe, Africa

WNV is an Arthropod-Borne virus • •

Transmitted by mosquitoes Can infect people and other animals

• Similar to some other viruses (a Flavivirus, in the Japanese Encephalitis Antigenic Complex – e.g. similar family to Yellow Fever, St. Louis encephalitis virus)

West Nile virus: Approximate geographic range as of 1998

WNV: Basic Transmission Cycle Most important cycle is from mosquito to bird to mosquito

“Incidental” infections: unlikely amplifying hosts

Amplifying hosts

1999

2000

2001

2002

2003

2003

WNND County Level Incidence per Million, United States, 2003*

Incidence per million .01-9.99 10-99.99 >=100

WNND: West Nile Neuroinvasive Disease

*Reported as of 4/9/2004

Transmission • The MOST IMPORTANT route of infection is bite of infectious mosquito • 2002 revealed novel modes of transmission • Blood Transfusion • Organ Transplantation • Intrauterine • Percutaneous exposure (occ. exposure) • Breastmilk (probable)

Screening of Blood Supply • As of July 2003, all blood donated in US is being screened for WNV (nucleic acid amplification testing rather than antibody screening) • Testing being conducted under IND • Minipool vs. individual testing • Presumptive viremic donors important for surveillance • Will be updated in MMWRs/website • Risk through transfusion very, very low

Mosquito Vectors • Nearly 50 species of mosquitoes capable (at least in the lab) of transmitting WNV Culex tarsalis feeding

• Important vectors vary by geography, e.g. •Culex tarsalis (western states) •Culex pipiens (Midwest, and elsewhere) •Culex quinquefasciatus (south) • Different behaviors – some fly very long distances • Feeding habits, infection rates, breeding areas all important

West Nile Virus—Clinical Disease Prior to 1996:

Since 1996:

* Mild illness with fever

* More severe illness, more of the sick dying

* Young adults in Africa, Middle East

* Older adults, people who have immune system problems

* Outbreaks infrequent

* More frequent outbreaks

* Rare involvement of the brain, spinal cord or nerves

* Increased reporting of meningitis and encephalitis

WNV Human Infection “Iceberg” For every case of illness involving the brain or spinal cord, ~150 total infections

<1% CNS disease ~20% “West Nile Fever”

~80% Asymptomatic

~10% fatal (<0.1% of total infections) Very crude estimates

WNV Fever • Most people who get sick from WNV infection have WNV fever • Time from exposure (usually by mosquito bite): 3-14 days • Fever, chills, headache, fatigue • Can be severe • Nausea, vomiting (can be severe) • Rash, usually not itchy, lasting a few days, mainly on chest, back, abdomen, and/or arms • Usually better within a week, though persistent headache, fatigue common -- reports of weeks, even longer among otherwise healthy persons

WNV Meningitis • Similar to other meningitis from viruses • Fever, headache, meningismus (neck stiffness, light bothering eyes) • White blood cells in the cerebrospinal fluid • Headache may be quite severe • Most people improve, though persistent headache, fatigue common

WNV Encephalitis • Severity ranges from mild confusion to coma and death • People who are older (over 50) and/or who have chronic medical problems are usually the ones to have WNV encephalitis

WNV Encephalitis • There are a number of other problems that people with WNV encephalitis may suffer: • Tremor • Myoclonus • Quick, uncontrolled muscle jerking • Problems with balance • Dizziness

WNV-Associated Flaccid Paralysis • Seen more frequently over the last 2 years • Unclear how often it is happening: • May be present in almost 15% of people with severe illness • Affects relatively young people who are often healthy otherwise • May not have fever or headache before paralysis

WNV-Associated “Poliomyelitis-like illness” • Most cases of WNV-associated weakness that is persistent • Clinical hallmarks: • Onset early in infection • Weakness can often be in only one limb • Absence of numbness; pain sometimes present

Diagnosis of WNV Infection (1) • Based on high index of clinical suspicion and obtaining specific laboratory tests • Consider WNV, or other arboviral diseases such as St. Louis encephalitis, (esp. in adults >50 years) w/ unexplained encephalitis or meningitis (esp. in summer or early fall). • The local presence of WNV enzootic (bird, mosquito, vet) activity or other human cases should further raise suspicion. • Recent travel history also important.

Diagnosis (2) • Testing obtained through local or state health departments and increasingly through private labs • Public health laboratories usually perform an IgM antibody capture enzyme-linked immunosorbent assay (MAC-ELISA). • W/ this test virus-specific IgM can be detected in nearly all CSF and serum specimens from WNV-infected patients at time of clinical presentation • Serum IgM antibody may persist for + 1 yr., so physicians must determine whether the antibody is result of a previous WNV infection and unrelated to the current clinical presentation.

Diagnosis (3) • Most conclusive to identify person w/CNS infection is WNV-specific IgM in CSF using MAC-ELISA. Strongly suggests acute CNS infection. • If no CSF and using serum samples, paired acute and convalescent-phase samples should be acquired. • Acute at initial presentation, convalescent 7-14 days later. • If no convalescent sample, acute specimen should be tested w/ MAC-ELISA. If IgM neg, acute WNV infection unlikely. If IgM pos and clinically compatible may be recent WNV infection (see note about other flavivirus infections).

Diagnosis (4) • Ideally MAC-ELISA should be performed using WNV and SLE viruses • If WNV and SLE results similar – necessary to use PRNT to confirm. • Recent vaccination (e.g. yellow fever) or related flavivirus infection may (e.g. dengue) may result in positive WNV MAC-ELISA. • See: http://www.cdc.gov/ncidod/dvbid/westnile/reso urces/fact_sheet_clinician.htm

Reporting • Reporting procedures vary by state – refer to state coordinators/state websites • Neuroinvasive disease is nationally notifiable, fever is not. States differ in their reporting of these.

WNV: Illness Outcomes • Current information limited • Fatality rates • 10-20% with severe disease die • Fatalities primarily among elderly, immunosuppressed • Unknown why some people do not get sick and some get extremely sick

WNV—Long-term problems: “When will I get better?” • Fatigue • Headache • Difficulty with concentration or memory • However—most people eventually DO get better (based on limited observations to date) • May take many months

WNV-Long-term outcomes • WNV Poliomyelitis-like illness • Outcomes vary • Some people from 2002 and 2003 have had dramatic, almost complete recovery; others have had continued weakness • We do not know why some people improve and some do not BUT • Those with less severe initial weakness tend to have a better prognosis

WNV--Treatment • As is true for most viruses that cause human illness, there is no specific treatment for WNV • Studies of: • Antisense WNV-RNA • Interferon-α • WNV-specific immune globulin (“IVIG”) • Results are only preliminary now • Basic problem—drug has to be given very early, almost before the person is very sick

Q: Once someone gets infected with WNV, can they get sick with WNV again? • A: If someone was sick with WNV last summer, they are probably immune. We think that this immunity lasts a long time (many years). However, mosquitoes can carry other viruses that can make people sick, so they should still take care to avoid mosquito bites!

Q: When a person tests positive for WNV, does that mean that the virus is still in them?

A: By the time someone gets sick, the virus is long-gone. The test measures the body’s reaction to the virus, to determine if the virus was present in the body recently or in the more distant past.

Q: What is the status of a human vaccine for WNV? A: Several agencies and companies are working on a vaccine for humans, and one is planned for testing next year.

WNV Prevention • Treatment is symptomatic – therefore prevention of illness is crucial • Preventive measures • Personal • Household • Community / environmental

WNV—Personal Protection • Use mosquito repellent • DEET (skin or clothing) • Up to 50% concentration • Permethrin (clothing) • Wear long sleeves, pants • Emphasize protection at times of high mosquito activity (dawn/dusk) or stay indoors • Protect your house and yard • Use/ fix screens • Air-conditioning • Empty water (breeding sites)

• After getting sick, recovery can take a long time, but most people do improve • Avoiding getting bitten by mosquitoes is the only way to prevent WNV • There is no treatment, but people are working very hard to develop one