West Nile Virus Infection in the United States: A Review and Update

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West Nile Virus Infection in the United States A
Review and Update

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Abstract and Introduction

• 1999.8, a cluster of patients admitted to medical
  ICUs in New York City
• S/S was fever, confusion, GI complaints, muscle
  weakness
• West Nile virus (WNV), first time in Western
  Hemisphere
• following 2 years , cases appeared in areas near
  New York and the East Coast

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Abstract and Introduction

• 60 y/o man fever, weakness, and nausea for 3 days
  under the impression of PN
• Within 4 days, confused and proximal muscle
  weakness with DTR decrease, urinary retention,
  and respiratory difficulty
• IV with ceftriaxone and acyclovir
• EMG/NCV axonal-type polyneuropathy
• plasmapheresis ?for 6 weeks gradual improvement
  

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A Cluster of Cases 1

• following 2 wks, 4 additional pts with similar
  neurologic S/S
• 80 y/o man , unresponsive and cardiac arrest ,
  previous suffered from fever, headache, weakness,
  and diarrhea for 1 wk
• flaccid paralysis developed ?motor axonopathy.
• IV ceftriaxone clindamycin ? died with MI ,
  hypotension , DIC , and hepatic and renal
  insufficiency

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Case 2

• 75 y/o man with prostate cancer
• fever, confusion, tremors, and urinary
  incontinence
• flaccid paralysis developed ?axonal-type
  polyneuropathy
• IV ampicillin, ceftriaxone, and acyclovir
• died after 3 weeks

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Case 3

• 87 y/o woman with colon and breast CA
• Headache, diarrhea, fever, mild dysarthria, and
  weakness diagnosed of dehydration
• Became febrile, lethargic, confused, and
  diffusely weak ? axonal polyneuropathy
• IV ceftriaxone and acyclovir
• plasmapheresis for presumed GBS ? died

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Case 4 and 5

• NYCDOH notified ? D.D with viral
  meningoencephalitis, GBS, toxin exposure, and
  botulism ? spinal fluid viral analysis
• 8.27, 4th patient enter in MICU
• 8.28, 5th patient, 57 y/o man with fever,
  confusion, and vomiting
• Not weak but quite agitated
• IV ampicillin, ceftriaxone, and acyclovir
  ?discharged

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Cases analysis

• All BT above 38.4C , 4 above 39C and had GI
  complaints
• 3 died ? autopsies ? Microglial nodules and
  perivascular inflammation
• Positive immunohistochemical stain for flavivirus
  ? PCR showed WNV
• Following 3 case , not as ill , younger , and no
  severe muscle weakness
• All 8 had relative lymphocytopenia , WBC ranged
  from 4.3 to 17.9/µL

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Investigation

• 8 pts relatively healthy, active, older persons
  aged between 58 and 87 y/o
• 4-square-mile radius of one another
• Fever and GI symptoms followed acute change in
  mentation, severe muscle weakness with flaccid
  paralysis and/or EMG evidence of axonal
  neuropathy
• CSF and blood, outdoors in the evening hours in
  the 2 weeks before the onset of illness

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Investigation

• St Louis encephalitis (SLE) virus
• emergency mosquito control
• brochures in 8 languages
• daily updates faxed to city hospitals
• hot line around the clock during a 2-month
  period
• state, city, and 4 counties involved

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Disease in Birds

• Early June several birds that had nervous system
  disorders
• During July and August, increased reports of dead
  birds but cause unknown
• Exotic birds died after the human outbreak (SLE
  does not sicken its host )
• West Nile-like virus

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The Correct Diagnosis

• Brains of the 3 encephalitis patients
• West Nile-like virus by CDC
• First time found in the Western Hemisphere
• Strain's DNA more than 99.8 identical to a WNV
  strain

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Patient Characteristics

• End of 1999, 62 people with WNV infection, 7 of
  these had died
• 1/3 recalled a mosquito bite
• Infected bird either migrated or imported,
  infected mosquitoes, or a viremic person
• Overwinter in mosquitoes and return the next
  summer
• 677 persons , seroprevalence of 2.6
• About 8200 WNV infections (1700 with febrile
  illnesses)

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Patient Characteristics

• Seroprevalence , Two (3) of 73 horses, 10 (5)
  of 189 dogs, and 0 (0) of 12 cats
• Wild birds in 5 city , 50 of sampled birds in
  Queens, 2 in Staten Island
• WNV infection, 25 (20 definite, 5 probable)
  horses , 20 (4 of 20) mortality
• 1 year of follow-up , fatigue (67), memory loss
  (50), difficulty in walking (49), muscle
  weakness (44), and depression (38)

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Characteristics of WNV Infection

• A member of the Flaviviridae , single-stranded
  RNA viruses , 2 genera flavivirus and pestivirus
  
• Transmission by mosquitoes,ever isolated from
  ticks
• Japanese, St Louis, and Murray Valley
  encephalitis viruses Kunjin virus
• Incubation period 5 to 15 D
• Primary reservoir Wild birds main vector
  mosquito, specifically, several Culex species
  

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Clinical Infection

• Majority clinically silent , nclude fever,
  headache, myalgias, pharyngitis, conjunctivitis,
  and diarrhea
• Nonpruritic roseolar or maculopapular rash In
  about half of patients(19 in the break)
• Lymphadenopathy
• Encephalitis or meningitis(lt1)
• Leukocytosis or leukopenia relative
  lymphocytopenia

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Clinical Infection

• CSF demonstrates leukocytosis or an elevated
  protein level
• Isolating WNV from or showing viral antigen
• IgM-capture ELISA for serum and CSF
• PRNT R/O cross-reactions with other flaviviruses
  
• Viral culture has not been successful

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Reappearance in 2000

• February, the virus was found in a red-tailed
  hawk
• 21 with WNV, 19 of whom with encephalitis or
  meningitis
• 480 pools of mosquitoes comprising 14 species, of
  which 90 were Culex
• Expanded to include 12 states and the District of
  Columbia

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Year 2001

• 66 cases (64 with encephalitis or meningitis and
  2 with fever but without neurologic illness)
• Infected birds were reported in 27 states
• 679 horses , 904 mosquito pools
• 75 y/o man from Uruguay, fever, chills, decreased
  mentation, and weakness
• WNV was confirmed quickly

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2002 and Beyond

• ArboNET report all cases of viral encephalitis,
  aseptic meningitis in those aged 17 and older,
  and GBS
• IgM-capture antibody by ELISA both blood and CSF
  
• PCR(specificity100)
• False-positive viral IgM and IgG ELISA previous
  yellow fever vaccination previous or current
  infection with other related flaviviruses
  residence in areas where WNV is endemic

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Diagnosis

• 2/3 have antibody at 6 months, decreased to one
  third after 1 year
• WNV-specific PRNT help clarify possible errors
• Treatment is supportive
• Ribavirin, interferon, and other antivirals
• Vaccine , yellow fever vaccine or the dengue
  virus chimera

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How Great a Threat This Year

• Climate and weather
• Hot, dry weather , Extremely high temperatures
  but not in 2000(cool, wet summer )
• Density and age of both vector and human
  population

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