West Nile Virus


Article Author:
Michael Clark


Article Editor:
Timothy Schaefer


Editors In Chief:
David Wood
Andrew Wilt
Hajira Basit


Managing Editors:
Avais Raja
Orawan Chaigasame
Khalid Alsayouri
Kyle Blair
Radia Jamil
Erin Hughes
Patrick Le
Anoosh Zafar Gondal
Saad Nazir
William Gossman
Hassam Zulfiqar
Navid Mahabadi
Hussain Sajjad
Steve Bhimji
Muhammad Hashmi
John Shell
Matthew Varacallo
Heba Mahdy
Ahmad Malik
Sarosh Vaqar
Mark Pellegrini
James Hughes
Beenish Sohail
Hajira Basit
Phillip Hynes
Sandeep Sekhon


Updated:
6/30/2019 7:32:23 AM

Introduction

West Nile virus is an enveloped, single-stranded RNA virus and member of the Flaviviridae family. It is an arbovirus transmitted to humans by the bite of a mosquito.

It is known to cause disease in humans with a wide array of presentations. These range from the asymptomatic infected patient to fever and malaise to florid neurological deficits secondary to encephalitis. However, most people infected with West Nile virus are asymptomatic. Approximately 1 in 4 patients experience fever with symptoms of a viral syndrome, while around 1 in 200 develops neuroinvasive disease.[1][2]

Originally seen in Africa, West Nile virus began showing up throughout Europe, Asia, and North America in the 1990s. It is now present throughout much of the world.

Etiology

The West Nile virus infects humans following a mosquito bite. The Culex species of mosquito is the most common vector. Besides humans, the West Nile virus can infect birds, horses, dogs, and many other mammals. Wild birds may be the optimal hosts for harboring and enabling amplification of the virus. Humans are considered accidental dead-end hosts due to the low and transient viral levels in the bloodstream. Additional and rare means of transmission include infected donor blood, organs, breast milk, or transplacental infection.[3]

Epidemiology

The first reports of West Nile virus were in Uganda in 1937. It resurfaced in 1999 when there were reports of seven deaths and 62 cases of encephalitis in New York; this was the first presentation of the virus in the western hemisphere. As of today, the West Nile virus is found in Africa, Europe, Asia, North America, Australia, and the Middle East.[4]

The original outbreaks of the virus showed a typically self-limited and minor illness. In the mid-1990s West Nile virus became correlated with severe neurologic disease. Based on a comprehensive literature review in 2013, meningitis and encephalitis (neuroinvasive disease) were present in less than one percent of infected patients with a mortality of 10 percent. West Nile fever is present in 25% of those infected; the remaining 75% show few to no symptoms. This fact leads to the likely vast underreporting of West Nile virus infections. Outbreaks tend to be associated late summer and fall due to the mosquito vector’s life cycle and the amplification from the bird-mosquito-bird cycle. In warmer climates, cases can occur throughout the year.[1]

In the US from 1999 to 2015, there have been almost 44000 confirmed and probable cases of West Nile virus with over 20000 cases of neuroinvasive disease. The number of neuroinvasive cases varies heavily year to year, ranging from 386 to 2946. Serologic surveys and blood donor screening data shows a rate of neuroinvasive disease of around 0.5% of infected patients and an infection rate of 10% in areas of outbreak. This data extrapolates to an estimated 3 to 5 million cases of infection.[5]

Pathophysiology

The virus is transmitted when the mosquito feeds, passing infected saliva into the host.  The early phase following transmission includes viral replication in dermal dendritic cells and keratinocytes. This phase is followed by the visceral-organ dissemination phase, which includes viral replication in draining lymph nodes, viremia, and spread to the visceral organs. The third and final phase spreads to the central nervous system (CNS).

The mechanism for viral CNS entry is unclear but may include a direct crossing of the blood-brain barrier, passive transport through the endothelium, infected macrophages crossing the blood-brain barrier or direct axonal retrograde transport. Once in the CNS the virus primarily induces inflammation and a subsequent loss of neurons within the spinal cord and brainstem gray matter.[6][7]

History and Physical

The clinical presentation of West Nile virus in most cases is mild myalgias, malaise, and a low-grade fever. Other associated symptoms include headache, eye pain, vomiting, anorexia, and up to 50% may have a maculopapular rash on the trunk appearing upon defervescence. However, in rare cases, the virus can cause neurologic symptoms, including severe muscle weakness, changes in mental status, seizures, or flaccid paralysis. These patients initially present with features of encephalitis and/or meningitis that progresses rapidly, and they require ICU care. Even with aggressive supportive treatment, the mortality rate following a case of neuroinvasive West Nile infection is high.

Most people infected with West Nile virus have a history of travel to an area where the virus is endemic during the summer or fall. However, this includes areas on most continents, as listed in the epidemiology section. The West Nile virus incubation period is two to 14 days. The typical infection includes a fever for five days, headache for 10 days and fatigue for around a month.[8]

Evaluation

Routine labs may reveal leukocytosis and other non-specific findings secondary to the viral infection. The diagnosis is via serologic detection of West Nile virus using an enzyme-linked immunosorbent assay (ELISA) for the IgM antibody in blood or CSF samples. A plaque reduction neutralization test (PRNT) can distinguish serologic cross-reactions.

Neuroinvasive West Nile virus will typically have findings consistent with viral meningitis on lumbar puncture. Analysis of CSF shows elevated protein and leucocyte levels, with a possible predominance of neutrophils early, transitioning to a lymphocytic predominance accompanied by normal glucose levels. For neuroinvasive disease, the CSF should also be tested using the ELISA test. In patients with a high suspicion of viral infection and an initial negative test, a repeat should be performed 10 days later as IgM levels may take time to elevate to the levels necessary to be detectable.

Imaging: CT of the brain will typically not show any acute findings of the disease. MRI may show abnormalities after several weeks of acute neuroinvasive disease.

Treatment / Management

Treatment of West Nile virus is primarily supportive care. Researchers have tried everal agents; including interferon, ribavirin, and intravenous immunoglobulin. No clear efficacy data exists as only one controlled study has been performed to date.[9]

Once the clinician has made a diagnosis of West Nile virus, individuals with milder cases can be managed symptomatically as outpatients and tend to have an excellent prognosis. However, toxic patients with neurologic symptoms usually require long-term ICU care. These patients will typically require long-term physical and occupational therapy at rehabilitation centers. After the infection, neurologic injury from the West Nile virus may include gross motor, cognitive, and fine motor abnormalities. Many patients have residual neurologic deficits, which can take a long time to recover, and some deficits may be permanent.

Differential Diagnosis

The differential for the West Nile virus is extensive, and investigation should include a careful travel history[10]:

  • Bacterial meningitis
  • Varicella-zoster virus
  • Herpes simplex type 1 virus
  • St. Louis encephalitis – confirmatory testing required may cross-react
  • Enteroviruses
  • Dengue virus
  • Japanese encephalitis

The differential also includes tickborne illnesses:

  • Lyme disease
  • Ehrlichiosis
  • Anaplasmosis
  • Rocky Mountain spotted fever
  • Powassan virus

Prognosis

The prognosis for the vast majority of patients with West Nile virus (WNV) is excellent.  Most infected patients are asymptomatic. Those who develop West Nile fever tend to have symptoms of a viral syndrome. It is a self-limited illness with most symptoms lasting up to 10 days. However, the rare and most serious clinical manifestation, neuroinvasive disease, has a mortality of approximately 10 percent. The geriatric population has the highest risk for neuroinvasive WNV. The neuroinvasive disease includes a wide spectrum of neurologic deficits, and some of these may persist for years or even become permanent.[11][12]

Complications

  • Neurologic symptoms
    • Meningitis, encephalitis, weakness, neuropathy, acute flaccid paralysis, seizures, coma
  • Ocular manifestations
    • Vvitreitis, chorioretinitis, retinal hemorrhages
  • Myocarditis
  • Pancreatitis
  • Rhabdomyolysis
  • Central diabetes insipidus
  • Death

Deterrence and Patient Education

Since WNV is transmitted almost exclusively through a mosquito vector, avoiding mosquito bites is the primary method of prevention.

Current methods of deterrence consist of two main components, personal protective measures and mosquito control. Insect repellants containing DEET or picaridin, permethrin-treated clothing, and avoiding exposure to endemic or high-risk areas with mosquitoes are the mainstays of personal protection. Mosquito control programs may also help decrease exposure along with reducing high-risk conditions, such as standing water around the home.[13]

Pearls and Other Issues

The prognosis after severe neuroinvasive WNV infection is often guarded. Most individuals require long-term rehabilitation, and some neurologic deficits may be permanent. There is no clear evidence for effective treatment beyond supportive care at this time.

Enhancing Healthcare Team Outcomes

WNV infection is challenging to diagnose and can quickly progress to neurologically devastating and even fatal disease. This condition is best managed by an interprofessional team that includes an emergency medicine physician, an internist for inpatient management, a critical care physician if needing ICU management, an infectious disease physician, along with pharmacy and nursing support. The care is primarily supportive, and the diagnosis is often difficult to make due to the variable presentation and overall rarity of the disease. The patient’s primary care doctor, physician assistant, or nurse practitioner should dispense preventative education; this includes protecting exposed skin, the use of insect repellants, and avoiding high-risk areas.

To summarize, West Nile virus infection requires an interprofessional team approach, including physicians, specialists, specialty-trained nurses, and pharmacists, all collaborating across disciplines to achieve optimal patient results. [Level V]


Interested in Participating?

We are looking for contributors to author, edit, and peer review our vast library of review articles and multiple choice questions. In as little as 2-3 hours you can make a significant contribution to your specialty. In return for a small amount of your time, you will receive free access to all content and you will be published as an author or editor in eBooks, apps, online CME/CE activities, and an online Learning Management System for students, teachers, and program directors that allows access to review materials in over 500 specialties.

Improve Content - Become an Author or Editor

This is an academic project designed to provide inexpensive peer-reviewed Apps, eBooks, and very soon an online CME/CE system to help students identify weaknesses and improve knowledge. We would like you to consider being an author or editor. Please click here to learn more. Thank you for you for your interest, the StatPearls Publishing Editorial Team.

West Nile Virus - Questions

Take a quiz of the questions on this article.

Take Quiz
A 35-year-old male was found down at home with altered mental status yesterday. After the initial workup in the emergency department, he was admitted to the ICU. Vital signs are notable for a fever of 101 F, and physical exam shows a confused male, oriented only to self, with 4/5 strength in his upper extremities. His workup was notable for increased protein and leukocytes with normal glucose on the lumbar puncture, a raised WBC count on CBC, a negative head CT, negative drug screen and toxicology labs, and a positive ELISA test for an ssRNA arbovirus found throughout most of the world that is known to cause neuroinvasive disease. Given its primary mode of transmission, which of the following is correct?

(Move Mouse on Image to Enlarge)
  • Image 248 Not availableImage 248 Not available
    Contributed Illustration by Bryan Parker
Attributed To: Contributed Illustration by Bryan Parker



Click Your Answer Below


Would you like to access teaching points and more information on this topic?

Improve Content - Become an Author or Editor and get free access to the entire database, free eBooks, as well as free CME/CE as it becomes available. If interested, please click on "Sign Up" to register.

Purchase- Want immediate access to questions, answers, and teaching points? They can be purchased above at Apps and eBooks.


Sign Up
A 27-year-old man comes into the clinic with one week of fever, headache, generalized body aches and fatigue and extremity weakness onset today. He works outside as a camp counselor and lifeguard at the local lake. Vital signs are notable for a fever of 102 F. Physical exam is notable for extremity strength 4/5, sensation intact and insect bites over both arms. After that initial lab work comes back he is diagnosed with the neuroinvasive form of an enveloped, single-stranded RNA flavivirus that has become recently endemic to the US. Which of the following serious complications may occur?



Click Your Answer Below


Would you like to access teaching points and more information on this topic?

Improve Content - Become an Author or Editor and get free access to the entire database, free eBooks, as well as free CME/CE as it becomes available. If interested, please click on "Sign Up" to register.

Purchase- Want immediate access to questions, answers, and teaching points? They can be purchased above at Apps and eBooks.


Sign Up
A 23-year-old female presents with headache, myalgias, and right arm weakness for the last three days. Her friend states she has been getting confused today and the other symptoms seem to be worsening. Vital signs show a temperature of 100.6 F, heart rate of 86/min, respiratory rate of 20/min, oxygen saturation of 99%, and blood pressure of 122/74. The initial workup shows leukocytosis, unremarkable metabolic panel, mildly elevated lactate, and the CT head is unremarkable. A lumbar puncture was performed immediately and cerebrospinal fluid (CSF) analysis revealed a white blood cell (WBC) count of 0, a red blood cell (RBC) count of, a protein level of 18 mg/dL, and a glucose level of 59mg/dL (the synchronous serum value was 115mg/dL). Repeat examination shows small, healing insect bites on the extremities and the patient's friend states they returned from a summer camping trip in upstate New York two days ago. The patient is admitted to the ICU, blood cultures are sent, broad-spectrum antibiotics and antivirals are started, and the ELISA test returns showing infection with a single-stranded RNA virus. Given the most likely diagnosis, what is the most common presentation of this disease?



Click Your Answer Below


Would you like to access teaching points and more information on this topic?

Improve Content - Become an Author or Editor and get free access to the entire database, free eBooks, as well as free CME/CE as it becomes available. If interested, please click on "Sign Up" to register.

Purchase- Want immediate access to questions, answers, and teaching points? They can be purchased above at Apps and eBooks.


Sign Up
A 65-year-old female patient comes to the emergency department complaining of losing control over her legs, headache, neck stiffness, malaise, body aches, and several days of fever. Vital signs are notable for a temperature of 38.1 C. Physical exam shows an uncomfortable woman with tacky mucous membranes, hyperreflexia of the extremities along with flaccid paralysis and small insect bites on her extremities. She states that she went camping last week and was bitten by numerous mosquitoes. A lumbar puncture is done, and it shows increased lymphocytes, normal protein, and normal glucose levels. Which of the following is the most appropriate next step in the management of this patient?



Click Your Answer Below


Would you like to access teaching points and more information on this topic?

Improve Content - Become an Author or Editor and get free access to the entire database, free eBooks, as well as free CME/CE as it becomes available. If interested, please click on "Sign Up" to register.

Purchase- Want immediate access to questions, answers, and teaching points? They can be purchased above at Apps and eBooks.


Sign Up
Which of these infections is not acquired through the bite of an Ixodes scapularis tick?



Click Your Answer Below


Would you like to access teaching points and more information on this topic?

Improve Content - Become an Author or Editor and get free access to the entire database, free eBooks, as well as free CME/CE as it becomes available. If interested, please click on "Sign Up" to register.

Purchase- Want immediate access to questions, answers, and teaching points? They can be purchased above at Apps and eBooks.


Sign Up
A young male recently returned from a business trip to Asia. His high fever and body aches motivate him to seek care in the emergency department. Due to the recent travel history and associated symptoms, West Nile viral infection is on the differential diagnosis. What additional symptoms would be concerning for severe disease? Select all that apply.



Click Your Answer Below


Would you like to access teaching points and more information on this topic?

Improve Content - Become an Author or Editor and get free access to the entire database, free eBooks, as well as free CME/CE as it becomes available. If interested, please click on "Sign Up" to register.

Purchase- Want immediate access to questions, answers, and teaching points? They can be purchased above at Apps and eBooks.


Sign Up
A client diagnosed with West Nile encephalitis is transferred to your floor. Nursing considerations that will guide your plan of care include which of the following? Select all that apply.



Click Your Answer Below


Would you like to access teaching points and more information on this topic?

Improve Content - Become an Author or Editor and get free access to the entire database, free eBooks, as well as free CME/CE as it becomes available. If interested, please click on "Sign Up" to register.

Purchase- Want immediate access to questions, answers, and teaching points? They can be purchased above at Apps and eBooks.


Sign Up
A 28-year-old female presents to the office for her annual checkup. She has been planning a trip to North Texas for the last several months and will be outdoors on her friend’s ranch. She remembers hearing about the big West Nile outbreak in Dallas several years ago and expresses concern. Given how the virus is transmitted, which of the following is most helpful in the prevention of infection with West Nile virus?



Click Your Answer Below


Would you like to access teaching points and more information on this topic?

Improve Content - Become an Author or Editor and get free access to the entire database, free eBooks, as well as free CME/CE as it becomes available. If interested, please click on "Sign Up" to register.

Purchase- Want immediate access to questions, answers, and teaching points? They can be purchased above at Apps and eBooks.


Sign Up
A 42-year-male comes into the emergency department via EMS after five days of fever with altered mental status. The physical exam is notable for a diffuse maculopapular rash on the trunk, small erythematous insect bites on his arms, generalized extremity weakness and a GCS of 13. His family states he was camping recently and had body aches and a headache prior to presentation when they found him confused in bed, unable to get up. Initial lab testing shows leukocytosis. Lumbar puncture shows no organisms on gram stain with a high protein and mild leukocytosis. CT head is unremarkable. The patient is admitted, and further workup is sent. Over the next two days, results are notable for negative blood cultures, no growth on the CSF culture, positive ELISA for West Nile, negative blood smears, and worsening clinical status. Which of the following is most concerning for the patient’s probable diagnosis?



Click Your Answer Below


Would you like to access teaching points and more information on this topic?

Improve Content - Become an Author or Editor and get free access to the entire database, free eBooks, as well as free CME/CE as it becomes available. If interested, please click on "Sign Up" to register.

Purchase- Want immediate access to questions, answers, and teaching points? They can be purchased above at Apps and eBooks.


Sign Up
A 67-year-old male is intubated and sedated in the ICU secondary to flaccid paralysis. On the third day of his hospital stay, confirmatory testing comes back and he is diagnosed with acute onset paralysis secondary to neuroinvasive West Nile virus. What is detected with the most common initial testing for West Nile virus?



Click Your Answer Below


Would you like to access teaching points and more information on this topic?

Improve Content - Become an Author or Editor and get free access to the entire database, free eBooks, as well as free CME/CE as it becomes available. If interested, please click on "Sign Up" to register.

Purchase- Want immediate access to questions, answers, and teaching points? They can be purchased above at Apps and eBooks.


Sign Up
A 37-year-old male is brought to the emergency department with fever and altered mental status. The physical exam is notable for generalized extremity weakness, a maculopapular rash on his back and a GCS of 13. His family states he was camping last week and was complaining of body aches and a headache the day before. Today he was found confused in bed, unable to get up. Initial labs show a leukocytosis. Lumbar puncture gram stain shows no organisms with a high protein count and mild leukocytosis. Additional results are notable for negative blood cultures, no growth at 48 hours on the CSF cultures, positive ELISA for West Nile, and negative blood smears. Given the most likely diagnosis, what is the most likely route the patient was infected?



Click Your Answer Below


Would you like to access teaching points and more information on this topic?

Improve Content - Become an Author or Editor and get free access to the entire database, free eBooks, as well as free CME/CE as it becomes available. If interested, please click on "Sign Up" to register.

Purchase- Want immediate access to questions, answers, and teaching points? They can be purchased above at Apps and eBooks.


Sign Up
A patient is infected with the severe neuroinvasive form of a single-stranded RNA flavivirus. This arbovirus is found throughout much of the world and became endemic to North America in the 1990s. Which of the following diseases or infectious agents is most likely to present in a similar way?



Click Your Answer Below


Would you like to access teaching points and more information on this topic?

Improve Content - Become an Author or Editor and get free access to the entire database, free eBooks, as well as free CME/CE as it becomes available. If interested, please click on "Sign Up" to register.

Purchase- Want immediate access to questions, answers, and teaching points? They can be purchased above at Apps and eBooks.


Sign Up

West Nile Virus - References

References

[Tropical ophthalmology : Intraocular inflammation caused by "new" infectious pathogens and travel-related infections]., Pleyer U,Klauß V,Wilking H,Nentwich MM,, Der Ophthalmologe : Zeitschrift der Deutschen Ophthalmologischen Gesellschaft, 2015 Dec 9     [PubMed]
Petersen LR,Brault AC,Nasci RS, West Nile virus: review of the literature. JAMA. 2013 Jul 17;     [PubMed]
Zou S,Foster GA,Dodd RY,Petersen LR,Stramer SL, West Nile fever characteristics among viremic persons identified through blood donor screening. The Journal of infectious diseases. 2010 Nov 1;     [PubMed]
O'Leary DR,Kuhn S,Kniss KL,Hinckley AF,Rasmussen SA,Pape WJ,Kightlinger LK,Beecham BD,Miller TK,Neitzel DF,Michaels SR,Campbell GL,Lanciotti RS,Hayes EB, Birth outcomes following West Nile Virus infection of pregnant women in the United States: 2003-2004. Pediatrics. 2006 Mar;     [PubMed]
Nash D,Mostashari F,Fine A,Miller J,O'Leary D,Murray K,Huang A,Rosenberg A,Greenberg A,Sherman M,Wong S,Layton M, The outbreak of West Nile virus infection in the New York City area in 1999. The New England journal of medicine. 2001 Jun 14;     [PubMed]
Williamson PC,Custer B,Biggerstaff BJ,Lanciotti RS,Sayers MH,Eason SJ,Dixon MR,Winkelman V,Lanteri MC,Petersen LR,Busch MP, Incidence of West Nile virus infection in the Dallas-Fort Worth metropolitan area during the 2012 epidemic. Epidemiology and infection. 2017 Sep;     [PubMed]
Guarner J,Shieh WJ,Hunter S,Paddock CD,Morken T,Campbell GL,Marfin AA,Zaki SR, Clinicopathologic study and laboratory diagnosis of 23 cases with West Nile virus encephalomyelitis. Human pathology. 2004 Aug;     [PubMed]
Potokar M,Jorgačevski J,Zorec R, Astrocytes in Flavivirus Infections. International journal of molecular sciences. 2019 Feb 6;     [PubMed]
Watson JT,Pertel PE,Jones RC,Siston AM,Paul WS,Austin CC,Gerber SI, Clinical characteristics and functional outcomes of West Nile Fever. Annals of internal medicine. 2004 Sep 7;     [PubMed]
Hart J Jr,Tillman G,Kraut MA,Chiang HS,Strain JF,Li Y,Agrawal AG,Jester P,Gnann JW Jr,Whitley RJ, West Nile virus neuroinvasive disease: neurological manifestations and prospective longitudinal outcomes. BMC infectious diseases. 2014 May 9;     [PubMed]
Chowers MY,Lang R,Nassar F,Ben-David D,Giladi M,Rubinshtein E,Itzhaki A,Mishal J,Siegman-Igra Y,Kitzes R,Pick N,Landau Z,Wolf D,Bin H,Mendelson E,Pitlik SD,Weinberger M, Clinical characteristics of the West Nile fever outbreak, Israel, 2000. Emerging infectious diseases. 2001 Jul-Aug;     [PubMed]
Petersen LR,Marfin AA, West Nile virus: a primer for the clinician. Annals of internal medicine. 2002 Aug 6;     [PubMed]
Fradin MS, Mosquitoes and mosquito repellents: a clinician's guide. Annals of internal medicine. 1998 Jun 1;     [PubMed]

Disclaimer

The intent of StatPearls is to provide practice questions and explanations to assist you in identifying and resolving knowledge deficits. These questions and explanations are not intended to be a source of the knowledge base of all of medicine, nor is it intended to be a board or certification review of Pediatrics-Medical Student. The authors or editors do not warrant the information is complete or accurate. The reader is encouraged to verify each answer and explanation in several references. All drug indications and dosages should be verified before administration.

StatPearls offers the most comprehensive database of free multiple-choice questions with explanations and short review chapters ever developed. This system helps physicians, medical students, dentists, nurses, pharmacists, and allied health professionals identify education deficits and learn new concepts. StatPearls is not a board or certification review system for Pediatrics-Medical Student, it is a learning system that you can use to help improve your knowledge base of medicine for life-long learning. StatPearls will help you identify your weaknesses so that when you are ready to study for a board or certification exam in Pediatrics-Medical Student, you will already be prepared.

Our content is updated continuously through a multi-step peer review process that will help you be prepared and review for a thorough knowledge of Pediatrics-Medical Student. When it is time for the Pediatrics-Medical Student board and certification exam, you will already be ready. Besides online study quizzes, we also publish our peer-reviewed content in eBooks and mobile Apps. We also offer inexpensive CME/CE, so our content can be used to attain education credits while you study Pediatrics-Medical Student.