WEST NILE VIRUS: CLINICAL ASPECTS

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WEST NILE VIRUS CLINICAL ASPECTS

• Patrick F. Luedtke MD, MPH
• Deputy State Epidemiologist
• Utah Department of Health
• University of Utah
• pluedtke_at_utah.gov

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A TALE OF TWO PATIENTS

• On May 29 Alex, a 32 year old Caucasian male,
  developed a fever. Over the next 13 days he had
  sustained fever, excessive thirst and
  diaphoresis, abdominal pain, weak-
• ness, delirium, flaccid paralysis,
  encephalopathy and finally, death on June 10th.
  (1)

• On July 15th, Julie, a 48 year old female,
  presented to the emergency room because of
  progressive unilateral leg weakness following a
  mild upper respiratory syndrome. Her URI
  resolved but seven months after discharge her
  leg weakness persists.

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What is West Nile Virus (WNV)

• WNV Family---Flaviviridae
• Genus----Flavivirus
• First isolated from a febrile woman in the West
  Nile district of Uganda in 1937
• Single-stranded RNA virus within the Japanese
  Encephalitis Virus antigenic complex which
  includes JEV, SLEV, MVEV, Kunjin virus (2)

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History of WNV

• Largely confined to Africa, Asia, Middle East and
  Europe until the early 1990s
• Eight outbreaks in Israel between 1941 and 2000
  No deaths in 1941 outbreak 1957
  outbreak---single encephalitis case in 2000 a
  country-wide outbreak occurred with a case
  fatality rate of 8.4 and 58 of hospitalized
  human cases having encephalitis (3)
• Old world WNV verses New world WNV

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CLINICAL EPIDEMIOLOGY I

• 1. Incubation period variable (2-14 days)
• 2. Patterns of infectivity (NYC experience)
• a.) 80 of infections not clinically
  apparent
• b.) 20 develop West Nile fever (or
  worse)
• 1.) One half (10) of these see
  physician
• 2.) If hospitalized, 4-18 Case
  Fatality rate
• 3.) Approximately 0.7 develop
  meningitis
• or encephalitis (or 1 in 150
  infections)

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CLINICAL EPIDEMIOLOGY II

• 3. Advanced age (gt75) is by far the greatest
  risk factor for severe neurological disease,
  long-term morbidity and death. (3)
• 4. Clinical clues to WNV infection onset of
  meningitis or encephalitis in late summer or
  early fall profound muscle weakness

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CLINICAL PRESENTATIONS I

• WNV Clinical Syndromes
• West Nile Fever (WNF)
• West Nile Meningitis (WNM)
• West Nile Encephalitis (WNE)
• West Nile Virus Associated-Acute Flaccid
  Paralysis (AFP)

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CLINICAL PRESENTATIONS II

• 1. West Nile Fever (20 of NYC infections?)
• a.) Mild illness lasting 3-6 days.
• b.) Sudden onset of malaise, anorexia,
• nausea, vomiting, eye pain, headache,
• myalgia, rash
• c.) May include fever, URI symptoms and
• non-specific rash

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CLINICAL PRESENTATIONS III

• West Nile Meningitis(0.2 of NYC infx?)
• a.) Fever present in gt 90 (Tgt37.8)
• b.) Weakness, nausea, vomiting in
  approx. 50
• c.) Meningismus
• fever, headache and nuchal ridigity
  clinically indistinguishable from other
  non-WNV viral meningitis cases

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CLINICAL PRESENTATIONS IV

• West Nile Encephalitis(0.4 of NYC infx?)
• a.) Fever present in gt 90
• b.) GI tract symptoms, headache and severe
  weakness common
• c.) Encephalitic changes
• (altered level of consciousness, abnormal
  mental state, focal or diffuse neurological
  signs---cranial nerves, deep tendon
  reflexes,
• seizures)

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CLINICAL PRESENTATIONS V

• Acute Flaccid Paralysis (? of NYC infections)
• a.) Asymmetric weakness affecting upper or
  lower limbs
• b.) Can occur without menigoencephalitis!
• c.) Concomitant bowel/bladder dysfunction
• and sensory deficits common
• d.) Polio-like destruction of anterior horn
  cells of spinal cord also axonal or
  de-myelinating neuropathy described

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MAKING THE DIAGNOSIS

• Clinical suspicion consistent presentation
  during appropriate time of year
• Lab testing CSF or serum MAC-ELISA (IgM
  antibody capture-ELISA). IgM serum and IgG
  testing requires acute and convalescent sera!
  (CSF?, Case definition probable/confirmed)
• Beware recent YF/JEV vaccinees or SLEV infx
• Nucleic Acid Amplification (PCR) available at
  Utah State Laboratory

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WNV TESTING I

• 1. Who to test?
• a.) Encephalitis cases of unknown etiology
• b.) Non-enteroviral meningitis cases
• c.) Patients with flaccid paralysis or
  neurological symptoms following a febrile
  illness
• d.) Pregnant women
• ---If compatible febrile syndrome with
• exposure history
• ---No indication to screen asymptomatic
• women

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WNV TESTING II

• 2. What to Test?
• a.) Serum CSF
• ---IgM ELISA
• 4 commercial labs, state labs
• ---IgG not useful acutely
• 3. When to test?
• a.) Clinically compatible cases during
  transmission season
• ---June to September with highest risk August to
  mid September

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WNV TREATMENT

• In general treatment is supportive
• No controlled studies have assessed the efficacy
  of ribavirin, interferon, gamma-globulin,
  steroids, anticonvulsants or osmotic agents---but
  research continues!
• Vaccine no human vaccine exists an equine
  vaccine is in use

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DIFFERENTIAL DIAGNOSES

• JEV group (JEV, SLEV, MVEV, Kunjin virus)
• Other viral infections e.g., Herpes,
  enteroviruses, VEE, WEE, etc.
• Bacterial infections e.g., N. meningitidis
• Presentation dependent (e.g., Polio for the acute
  flaccid paralysis patient Guillain-Barre---viral/
  Campylobacter)

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CLINICAL OUTCOMES (4-7)
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SYNDROME PROGNOSES (8)

• WNF infected persons in New World appear to
  fully recover to pre-morbid functioning following
  a short illness.
• WNM nearly everyone has full recovery (in
  Louisiana follow-up study, 5/5 had full recovery
  and no discernable neurological deficit after 8
  months)

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SYNDROME PROGNOSES II

• 3. WNE 6/8 returned to pre-morbid level of
  functioning at 6 months (2 required initial
  discharge to LTC, 1 ultimately died) 5/8 had
  postural and/or kinetic tremor at 8 months (one
  severe) most had persistent fatigue and myalgias
• 4. AFP 3/3 had no resolution of limb weakness
  after one year all had persistent fatigue and
  myalgias bladder symptoms resolved.

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RISK FACTORS (9)

• 1. For severe disease (WNE AFP)
• a.) Age gt 75 (RR2.7 95CI1.3-5.8)
• b.) Diabetes mellitus (age adjusted
  RR5.1 95CI1.5-17.3)
• c.) Anemia?
• d.) Immunosuppression? (malignancy,
  chemotherapy, other medications)

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TRANSMISSION ISSUES (9)

• a.) Blood transfusion (peak lt21/10,000
  donations in severely affected cities)
• b.) Organ transplantation from infected
  donor
• c.) Bone marrow/stem cell transplants
• d.) Maternal-fetal intrauterine? breast
• feeding?

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A tale of two patients---revisited

• On May 29 Alex, a 32 year old Caucasian male,
  developed a fever. Over the next 13 days he had
  sustained fever, excessive thirst and
  diaphoresis, abdominal pain, weak-
• ness, delirium, flaccid paralysis,
  encephalopathy and finally, death on June 10th.
  (1)

• On July 15th, Julie, a 48 year old female,
  presented to the emergency room because of
  progressive unilateral leg weakness following a
  mild upper respiratory syndrome. Her URI
  resolved but seven months after discharge her
  leg weakness persists.

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A tale of two patients---revisited

• Alexander the Great
• Died June 10, 323 BC in Babylon (90 km south of
  Bagdhad)
• West Nile Encephalitis?!

• Intermountain West Pt.
• MRI normal brain and spinal cord CE
• CSF IgM
• Acute Flaccid Paralysis!

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ITS COMING BACK!
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Bibliography

• Marr J, Calisher C. Alexander the Great and West
  Nile Virus Encephalitis. Emerg Infect Dis.
  200391599-1603.
• Petersen L, Marfin A. West Nile Virus.
• JAMA. 2003290524-528.
• 3. Petersen L, Marfin A. West Nile Virus A
  Primer for the Clinician. Ann Intern Med.
  2002137173-179.

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Bibliography II

• Tsai T, Popovici F. West Nile encephalitis
  epidemic in southeastern Romania.Lancet.
  1998352767-771.
• Platonov A, Shipulin G. Outbreak of West Nile
  Virus Infection in Volgograd Region, Russia,
  1999. Emerg Infect Dis. 20017128-132.

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Bibliography III

• Weiss D, Carr, D. Clinical Findings of WNV
  Infection in Hospitalized Patients, NY and NJ,
  2000. Emerg Infect Dis. 2001
• 7654-658.
• Chowers M, Lang R. Clinical Characteristics of
  the West Nile Fever Outbreak, Israel, 2000. Emerg
  Infect Dis.
• 20017675-678.

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Bibliography IV

• Sejvar J, Haddad M. Neurological Manifestations
  and Outcome of WNV Infection. JAMA.
  2003290511-515.
• Nash D, Mostashari F. The Outbreak of WNV
  Infection in the NYC Area in 1999. N Engl J Med.
  20013441807-1814.