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West Nile Virus

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									Patient presentation


    M. Vlooswijk, 16-2-2005
Content
 Patient case and introduction
 Epidemiology
 Pathogenesis
 Clinical manifestations
 Diagnosis
 Treatment and prevention
 Prognosis
 Literature
Patient A.
    Man, 46 years. Medical history: blank
    Symptoms: sudden onset of myalgia, diffuse
    upper and lower limb weakness, skin rash
    During hospitalization: respiratory failure,
    prolonged ventilation and tracheostomy
    placement
    Diagnostic tests: CSF and blood titers WNV +,
    EMG: widespread axonal loss of motor axons
    of upper and lower limb
Source: Marciniak et.al. 2004
Patient A (II)
   No improvement on intravenous
   immunoglobulin G
   Complications: tracheobronchitis,
   pneumonia, Clostridium difficile infection
   and dysphagia requiring gastrostomy tube
   Total hospital stay: 98 days
   Rest impairment after rehabilitation:
   strength in upper limbs 2/3, lower limbs 2/2
Source: Marciniak et.al. 2004
Epidemiology
 West Nile Virus, arbovirus, family
 Flaviviridae
 First described in 1937
 Sporadic outbreaks in Israel and Africa
 Mid-1990’s outbreaks with severe
 neurologic disease
 First outbreak in North-America: NYC ‘99
Human cases of WNV infection in the
        USA, 1999–2003




                             Source: Lancet
                             Infect Dis 2004
Bird-mosquito-bird cycle




                           Source:Center for Disease
                              Control and Prevention
Other ways of transmission: transfusion,
organ transplants, transplacental, breast
milk, percutaneous exposure in laboratory
20% of infected persons develops mild
illness
One:150 develops severe neurological
illness
Peak incidence: August-September
In temperate climates possibly all year
Pathogenesis
 Injection of virus-laden saliva
 Infection of fibroblasts, vascular endothelial
 cells or cells of the RES  viremia 
 inflammation BBB  CNS infection
 Predilection within CNS: posterior thalamus,
 basal ganglia, brainstem, spinal anterior horn
 cells
 Mechanisms of neuronal injury: acute neuronal
 necrosis, neuronophagia
Clinical manifestations




                  Source: www.publichealthgreybruce.on.ca
Clinical manifestations (II)

Febrile illness: West Nile fever
    • Self-limited with fever, headache, malaise, back pain, myalgia and
      anorexia. Rash in 50%
Neuro-invasive disease
  West Nile encephalitis
  West Nile meningitis
  Acute flaccid paralysis
Complications
    • Myocarditis, pancreatitis, hepatitis, ocular complications
Neuro-invasive disease
 West Nile encephalitis
    Encephalopathy, evidence of CNS inflammation, acute
    inflammation or demyelination on neuroimaging, focal
    neurological deficit, EEG consistent with encephalitis,
    seizures
 West Nile meningitis
    Clinical signs of meningeal inflammation, acute infection,
    acute meningeal inflammation on neuroimaging
 Acute flaccid paralysis
    Acute progressive limb weakness, asymmetry, hyporeflexia,
    no pain/paraesthesias or numbness, electrodiagnostic studies:
    anterior-horn-cell process, increased signal in anterior spinal
    grey matter on MRI
Diagnosis
 To be considered in patients with unexplained
 febrile illness, encephalitis and/or meningitis, or
 flaccid paralysis, especially in summer or early
 fall. History of travelling to the US
 Lab:
   White bloodcell count in serum: normal or elevated
   CSF: pleocytosis, predominance of lymphocytes,
   elevated protein concentration
Diagnosis (II)
 Neuro-imaging:
   CT: no evidence of acute disease
   MRI: 30% enhancement of leptomeninges and/or
   periventricular areas, hyperintensity (T2) in basal
   ganglia, thalami, caudate nuclei, brainstem, spinal cord.
 EEG: generalized continuous slowing
 Electrodiagnostic studies:
   Normal SNAP’s
   Normal to markedly decreased CMAP’s
Diagnosis (III)
 Serologic testing:
   Detection of IgM antibody to WNV in serum or
   CSF, eg with MAC-ELISA
   When IgM in CSF, CNS infection is highly
   probable
   False-positive results: recent vaccination with
   yellow fever or Japanese encephalitis; recent
   infection with a related flavivirus (eg dengue)
Treatment and prevention
 Supportive treatment
 Trials:
   iv immunoglobulin containing anti-WNV Ab
   IFN alfa-n3
 Avoid exposure to mosquitoes (DEET)
 Drainage of standing water
 Blood donor screening for WNV
 No human vaccines yet available
Prognosis
 Mortality rates (associated with advanced age)
   Encephalitis: 12%
   Meningitis: 2%
 Functional impairment
   Acute flaccid paralysis: some improvement, no
   recovery
   Encephalitis: difficulty walking, muscle weakness,
   cognitive impairment
Literature
 Granwehr B.P. et.al. West Nile virus: where are we now?
 Lancet Infect Dis 2004; 4: 547-56
 Marciniak C. et.al. Acute flaccid paralysis associated with
 West Nile virus : motor and functional improvement in 4
 patients. Arch Phys Med Rehabil 2004; 85: 1933-8
 Labowitz Klee A. et.al. Long-term prognosis for clinical
 West Nile virus infection. Emerging Infectious Diseases
 2004; 10: 1405-11
 Petersen L.R. West Nile virus infection. UpToDate 2004

								
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