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West Nile Virus: Diagnostic Challenges in Clinical Detection of Cases Dr. Neil V. Rau MD FRCP(C) Infectious Diseases Consultant The Credit-Valley Hospital.

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Presentation on theme: "West Nile Virus: Diagnostic Challenges in Clinical Detection of Cases Dr. Neil V. Rau MD FRCP(C) Infectious Diseases Consultant The Credit-Valley Hospital."— Presentation transcript:

1 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

2 zEnvironmental data (dead crow) in your region has suggested a potential risk for the onset of human cases of WNV for the past three weeks zNo human cases were seen in your region last year, despite aggressive surveillance efforts for all cases of encephalitis in the past two years zHowever, a dead crow tested positive last year zThe infectious diseases specialist at the local community hospital calls you about the following cases seen in consultation over the past four days... The date is August 26, 2002.

3 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... Is suspicion of WNV encephalitis appropriate for any or some of these cases?

4 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 post- ictal 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… The internist tells you of more cases... Are any suspicious for WNV encephalitis?

5 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… zStopped drinking three days prior to admission zHad taken ciprofloxacin prior to admission for possible soft tissue infection complicating trauma to left leg a few days before zOn clindamycin + ciprofloxacin following admission zNormal WBC, but low platelets on admission; AST increased at 83, ALT 75, ALP normal zWorsened mental status despite change in antibiotic therapy to cefotaxime. Focus on the first three cases…more details on Case 1)

6 zIntubated in ICU. Started on valium to address tremulousness zCXR - no evidence of pneumonia zAbdominal CT - no abscess zEchocardiogram - no valvular pathology or vegetations zCT Head (unenhanced) negative More details on Case 1)

7 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... zWBC 11.2, Plt 105 (Normal 150). No lymphopenia. Other bloodwork normal zUrinalysis normal; culture negative zCT Head (without contrast) negative zCXR normal except for sternotomy and prosthetic valve, calcified and tortuous aorta zStarted on vancomycin and gentamicin at time of admission Focus on the first three cases…more details on Case 2)

8 zBlood cultures negative at 48 hours zConfusion considerably better after 24 hours of antibiotic therapy zNo further fevers 24 - 48 hours after admission zTransthoracic echocardiogram did not reveal vegetations; no aortic regurgitation. zCardiologist reviewed patient 48 hours after admission and excluded endocarditis based on this information zConfusion resolving within 72 hours of admission Further details on Case 2)

9 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… zCXR - negative zUnenhanced CT Head was normal zEEG - diffuse slowing without lateralizing findings zImproving mental status within 48 hours of admission More details on Case 3)

10 Results Case 1) zCSF WBC 244 - 39%L, 49%N, 12%M zCSF RBC 11 zCSF protein 2.02, glucose normal Case 2) zCSF WBC 139 - 69%L, 17% N, 14% M zCSF RBC 4 on Tube #4; Tube #1 similar zCSF protein 1.18, glucose normal Case 3) zCSF WBC 370 - 42%L, 41%N, 17%M zCSF RBC 18 zCSF protein 1.20, glucose normal All underwent lumbar punctures at various points during their hospitalization...

11 Results Case 1)16/0826/08 SLEE<1:101:20 WNV<1:101:40PRNT1/320 (Winnipeg) Case 2)27/0830/08 SLEE<1:101:40 WNV<1:101:40 PRNT1/5120 (Winnipeg) Case 3)26/0809/09 SLEE1:201:160 WNV1:201:320PRNT 1/160 (Winnipeg) All of the three cases were WNV encephalitis

12 zThe confusion associated with encephalitis can be short lived (<72 hours) even in cases of encephalitis zThe 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 zFor a first season, in the absence of recent travel to a Dengue Fever endemic area: yA single positive titre for SLE or WNV usually proves to be a true case zThe prolonged convalescence from encephalitis relates more to the profound weakness, fatigue and exhaustion than to the residual neurologic sequelae (exception polio-like syndrome) Some Personal Observations...

13 zOnly the viruses belonging to lineage 1 have been associated with human disease zIncubation period is 3 to 14 days. zSeroprevalence the same across all age groups in the New York City experience in 1999 zHowever, the incidence of neurological disease 40 times higher in those >80 than in those <20 zApproximately half of admitted patients have sever muscle weakness z10% had complete flaccid paralysis; some initially thought to have Guillain-Barre in NYC experience Clinical Features of WNV Infection

14 zAsymptomatic - 80% of those infected zWest Nile Fever - most of the remaining 20% infected yfever + rash yfever + lymphadenopathy yfever alone; described as a Dengue Fever-like illness ymay include milder cases of aseptic meningitis, as LP not always performed in this group zMeningitis / Meningoencephalitis - less than 1% of those infected yfever + confusion ymuscle weakness in 50% of those hospitalized Clinical Spectrum of WNV Infection

15 zTreatment supportive; ribivarin and interferon unproven zOverall case fatality rate amongst hospitalized is 4 - 14% zRisk factors for death: yage > 70; mortality as high as 29% reported in Israel in 2000 yencephalitis with severe muscle weakness ydiabetes yimmunosuppression yhematologic malignancy(?) zConvalescence: yFrequent persistent symptoms in the NYC series: fatigue 67%, memory loss 50%, muscle weakness 44%, difficulty walking 49%, depression 39% Clinical Course of WNV Infection

16 zClinical presentation of WNV encephalitis is nonspecific zOther false-positive laboratory results can mislead zA patient who is improving may not undergo LP; improvement may be attributed to antibiotic treatment zAn LP is specific a diagnosis of encephalitis, while clinical diagnosis without LP is much less specific zNon-reactive acute serology can mislead; usually need convalescent results to exclude diagnosis zDelays to obtain results of serology for encephalitis cases may slow detection of other cases zA clinical prediction rule which uses clinical and LP criteria to find subsequent cases early, well before serology is available? Diagnostic Challenges in the Detection of WNV Encephalitis


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