Download Diagnostic Challenges In Clinical Detection Cases

West Nile Virus:
Diagnostic Challenges in Clinical
Detection of Cases
Dr. Neil V. Rau MD FRCP(C)
Infectious Diseases Consultant
The Credit-Valley Hospital and
Halton Healthcare Services
Instructor, University of Toronto
The date is August 26, 2002.
 Environmental data (dead crow) in your region has
suggested a potential risk for the onset of human cases
of WNV for the past three weeks
 No human cases were seen in your region last year,
despite aggressive surveillance efforts for all cases of
encephalitis in the past two years
 However, a dead crow tested positive last year
 The infectious diseases specialist at the local community
hospital calls you about the following cases seen in
consultation over the past four days...
Is suspicion of WNV encephalitis appropriate
for any or some of these cases?
1) A 70 yo diabetic male with regular alcohol intake who presents with
fever, tremulousness, and confusion. Streptococcus viridans isolated
in 1/4 blood cultures from admission...
2) A 73 yo man who underwent bovine prosthetic valve surgery one
month ago, and now presents with fever and fatigue over the past
week. Brought to hospital because of confusion over preceding 24
hours...
3) A 72 yo man with minor left internal capsule CVA 1986 who
presents with headache, exhaustion over the past week. He now
has right lower facial droop and worsening mentation. Fever history
equivocal...
The internist tells you of more cases...
Are any suspicious for WNV encephalitis?
4) A 68 yo healthy woman with one week of intractable vomiting, fever
followed by a one day history of decreased verbal output, difficulty
getting out of bed...
5) A 65 yo predialysis man who presents with fever and confusion. On
the day of admission, has a generalized seizure followed by postictal obtundation requiring ICU admission…
6) A 55 yo woman with breast ca, received XRT one week ago.
Presents with one week history of fever and weakness. Evanescent
rash prior to admission. No dysuria, but mild pyuria on urinalysis
noted on admission…
Focus on the first three cases…more details on
Case 1)
A 70 yo diabetic male with regular alcohol intake who presents with
fever, tremulousness, and confusion. Streptococcus viridans isolated
in 1/4 blood cultures from admission…
 Stopped drinking three days prior to admission
 Had taken ciprofloxacin prior to admission for possible soft tissue
infection complicating trauma to left leg a few days before
 On clindamycin + ciprofloxacin following admission
 Normal WBC, but low platelets on admission; AST increased at 83,
ALT 75, ALP normal
 Worsened mental status despite change in antibiotic therapy to
cefotaxime.
More details on Case 1)
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Intubated in ICU. Started on valium to address tremulousness
CXR - no evidence of pneumonia
Abdominal CT - no abscess
Echocardiogram - no valvular pathology or vegetations
CT Head (unenhanced) negative
Focus on the first three cases…more details on
Case 2)
2) A 73 yo man who underwent bovine prosthetic valve surgery one
month ago, and now presents with fever and fatigue over the past
week. Brought to hospital because of confusion over preceding 24
hours...
 WBC 11.2, Plt 105 (Normal 150). No lymphopenia. Other bloodwork
normal
 Urinalysis normal; culture negative
 CT Head (without contrast) negative
 CXR normal except for sternotomy and prosthetic valve, calcified
and tortuous aorta
 Started on vancomycin and gentamicin at time of admission
Further details on Case 2)
Blood cultures negative at 48 hours
Confusion considerably better after 24 hours of antibiotic therapy
No further fevers 24 - 48 hours after admission
Transthoracic echocardiogram did not reveal vegetations; no aortic
regurgitation.
 Cardiologist reviewed patient 48 hours after admission and
excluded endocarditis based on this information
 Confusion resolving within 72 hours of admission
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More details on Case 3)
3) A 72 yo man with minor left internal capsule CVA 1986 who
presents with headache, exhaustion over the past week. He now
has right lower facial droop and worsening mentation. Fever history
equivocal…
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CXR - negative
Unenhanced CT Head was normal
EEG - diffuse slowing without lateralizing findings
Improving mental status within 48 hours of admission
All underwent lumbar punctures at various
points during their hospitalization...
Results
Case 1)
 CSF WBC 244 - 39%L, 49%N, 12%M
 CSF RBC 11
 CSF protein 2.02, glucose normal
Case 2)
 CSF WBC 139 - 69%L, 17% N, 14% M
 CSF RBC 4 on Tube #4; Tube #1 similar
 CSF protein 1.18, glucose normal
Case 3)
 CSF WBC 370 - 42%L, 41%N, 17%M
 CSF RBC 18
 CSF protein 1.20, glucose normal
All of the three cases were WNV encephalitis
Results
Case 1)
SLEE
WNV
16/08
<1:10
<1:10
26/08
1:20
1:40
PRNT
1/320 (Winnipeg)
Case 2)
SLEE
WNV
27/08
<1:10
<1:10
30/08
1:40
1:40
PRNT
1/5120 (Winnipeg)
Case 3)
SLEE
WNV
26/08
1:20
1:20
09/09
1:160
1:320
PRNT
1/160 (Winnipeg)
Some Personal Observations...
 The confusion associated with encephalitis can be short lived (<72
hours) even in cases of encephalitis
 The CSF protein is high (well above the upper limit of normal, often
>1.0) in cases of encephalitis. Does this differ from other forms of
encephalitis - a research question
 For a first season, in the absence of recent travel to a Dengue Fever
endemic area:
A single positive titre for SLE or WNV usually proves to
be a true case
 The prolonged convalescence from encephalitis relates more to the
profound weakness, fatigue and exhaustion than to the residual
neurologic sequelae (exception polio-like syndrome)
Clinical Features of WNV Infection
 Only the viruses belonging to lineage 1 have been
associated with human disease
 Incubation period is 3 to 14 days.
 Seroprevalence the same across all age groups in the
New York City experience in 1999
 However, the incidence of neurological disease 40 times
higher in those >80 than in those <20
 Approximately half of admitted patients have sever
muscle weakness
 10% had complete flaccid paralysis; some initially
thought to have Guillain-Barre in NYC experience
Clinical Spectrum of WNV Infection
 Asymptomatic - 80% of those infected
 West Nile Fever - most of the remaining 20% infected
fever + rash
fever + lymphadenopathy
fever alone; described as a Dengue Fever-like illness
may include milder cases of aseptic meningitis, as LP not always
performed in this group
 Meningitis / Meningoencephalitis - less than 1% of those infected
fever + confusion
muscle weakness in 50% of those hospitalized
Clinical Course of WNV Infection
 Treatment supportive; ribivarin and interferon unproven
 Overall case fatality rate amongst hospitalized is 4 14%
 Risk factors for death:
age > 70; mortality as high as 29% reported in Israel in 2000
encephalitis with severe muscle weakness
diabetes
immunosuppression
hematologic malignancy(?)
 Convalescence:
Frequent persistent symptoms in the NYC series: fatigue 67%,
memory loss 50%, muscle weakness 44%, difficulty walking
49%, depression 39%
Diagnostic Challenges in the Detection of WNV
Encephalitis
 Clinical presentation of WNV encephalitis is nonspecific
 Other false-positive laboratory results can mislead
 A patient who is improving may not undergo LP; improvement may
be attributed to antibiotic treatment
 An LP is specific a diagnosis of encephalitis, while clinical diagnosis
without LP is much less specific
 Non-reactive acute serology can mislead; usually need convalescent
results to exclude diagnosis
 Delays to obtain results of serology for encephalitis cases may slow
detection of other cases
 A clinical prediction rule which uses clinical and LP criteria to find
subsequent cases early, well before serology is available?