Infectious Disease Case Conference

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Infectious Disease Case Conference

• Asif Zia MD, MPH
• Emerging Infectious Disease Fellow
• Wake Forest Baptist Hospital
• August 18th, 2003

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Case 1

• 22 year old WF presented to ER on 8/7/03.
• Myalgias, neck stiffness fever and headache for 3
  days.
• Had a C/Section about a month ago, and still had
  some drainage from surgical site.
• 4 week old son in hospital with suspected
  meningitis.

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Case 1 Contd.

• Physical exam was unremarkable with no neck
  stiffness.
• LP done in ER
• CSF Protein 52
• Glucose 56
• WBC count 175 (45 Polys)
• RBC count 12
• Serum glucose 93
• Serum WBC 4.3

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Case 1 Contd.

• Given Vancomycin 1g and Ceftriaxone 2g IV in ER,
  and medicine consulted.
• Medicine admitted and discontinued antibiotics,
  but placed her on Acyclovir for possible HSV
  meningitis.
• Her symptoms improved, and she was sent home on
  8/8/03 after HSV PCR negative. All cultures were
  eventually negative.

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Case 2

• 31 year old white female presented with a 5 day
  history of fever, headache, nausea and vomiting
  on 8/8/03 to ER.
• No neck stiffness or photophobia, but had an
  erythematous rash on her face.
• Had taken one dose of azithromycin for a possible
  sinus infection.
• 11 month old baby being treated for viral
  syndrome.

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Case 2 contd.

• Physical exam showed a fever of 101.1,
  erythematous morbilliform rash on the face and
  trunk , no neck stiffness.
• LP done in ER CSF
• Protein 59
• Glucose 65
• WBC 120 (Monos 27 Polys 73)
• RBC 3
• Serum glucose 127, serum WBC 6.2

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Case 2 Contd.

• Because of a high differential polynuclear cell
  ratio and history of one tablet of Azithromycin
  she was started on Ceftriaxone 2g IV q 12 hourly
  and Vancomycin 1 g IV q 24.
• Was kept in isolation for 24 hours, and
  discharged after 48 hours with significant
  clinical improvement. All antibiotics were
  discontinued.
• All cultures including HSV PCR were negative

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Case 3

• 34 year old white female presented to ER on
  8/14/03 with a two day history of fever headache
  and neck stiffness.
• Was on her 9th day of Clarithromycin for an ear
  infection.
• Had a 22 month old son recovering from a viral
  syndrome and ear infection at home.

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Case 3 Contd.

• Physical exam was unremarkable. She had low grade
  temperature (99.1). Slight neck pain, but no
  rigidity.
• LP done. CSF
• Protein 94
• Glucose 59
• WBC 108 (93 Monos)
• RBC 2
• Serum glucose 81, serum WBC 7.3

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Case 3 Contd.

• ER gave her one dose of Vancomycin 1 g IV and
  consulted medicine.
• Medicine discontinued all antibiotics and
  admitted for 24 hour period of observation.
• Patient eventually discharged home after 48 hours
  in improved state. All cultures were negative so
  far.

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Aseptic Meningitis
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Definition

• Any meningitis (infectious or non-infectious),
  particularly one with a lymphocytic pleocytosis,
  for which a cause is not apparent after initial
  evaluation and stains and cultures of CSF.
• Rotbart, HA Infections of the central nervous
  system (Lippincott-Raven Publishers)

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Etiology

• Viruses are major cause
• Recent studies have identified a virus in up to
  70 of cases of aseptic meningitis.
• Several viruses can be the causative agent.
• Enteroviruses account for 80 to 85 of all cases
  in which a pathogen is identified.

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Etiology

• Enteroviruses
• Arboviruses
• Mumps Virus
• Lymphocytic Choriomeningitis virus
• Herpes virus
• HIV
• Adenovirus

• Influenza virus
• Measles
• Rubella
• Rotavirus
• Parvovirus
• West Nile virus
• Rabies virus

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Enteroviruses

• Diverse group of RNA viruses with more than 70
  different viruses.
• Includes Coxsackie A, B, Echoviruses and Polio
  virus.
• Spread by feco-oral and respiratory routes.
• Most common in summer months, but can occur year
  round.

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EV - Epidemiology

• MMWR reported outbreaks of Aseptic Meningitis
  associated with E 9 and E 30 this summer.
• 7 states have reported outbreaks AZ, CA, GA,
  ID, OR, SC, TX.
• As of Aug 7 NESS had received reports of 365
  enteroviruses detections in 25 states.

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EV Epidemiology - 2

• Overall E 30 was the commonest (36) in and E 9
  was 30.
• However E 9 was commonest in the eastern states
  and is thought to be involved in several
  outbreaks in the east.
• Other enterovirus serotypes were Coxsackie B1,
  Echo7, Coxsackie A9 and B4.

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EV Enterovirus 3

• Enteroviruses demonstrate a marked seasonality in
  temperate climates.
• The season in the US is from June to October.
• In 2003 the season has started early with the
  first reported E9 in January in Louisiana.

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Clinical Presentation

• Infants and children most susceptible.
• Symptoms much more severe in neonates.
• Older children and adults have less severe
  disease.
• Sudden onset with fever (76 to 100).
• Headache and photophobia are common.

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Clinical Presentation - 2

• Vomiting, anorexia, rash and diarrhea.
• URI symptoms and cough can also occur.
• Viral exanthemas. Myopericarditis and
  conjunctivitis can also occur.
• Duration is usually less than 1 week.

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Diagnosis

• CSF cell count usually 100 to 1,000.
• Neutrophils dominate in early infection.
• Lymphocyte predominance in 6 to 48 hrs.
• Elevated CSF protein and low BG (if present) are
  usually mild.

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Diagnosis - 2

• WNV has the same seasonal pattern as
  enteroviruses.
• Often associated with neurological signs and
  symptoms of aseptic meningitis.
• WNV associated meningitis tends to occur amongst
  older persons (median 46 years).
• Enterovirus meningitis occurs mostly in younger
  adults and children (median 13 yrs).

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Diagnosis - 3

• Enterovirus remains the leading cause of aseptic
  meningitis, even in areas of high WNV epizootic
  activity.
• Specimens should be tested for EV even during an
  outbreak of WNV.
• Early etiological diagnosis of aseptic
  meningitis helps to avoid unnecessary antibiotic
  treatment and additional testing MMWR (8/15/03).

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Diagnosis - 4

• Virus culture is standard technique, but time
  consuming, expensive and limited clinical use.
• Enterovirus PCR typing is available and has a
  sensitivity of 94.7 and a specificity of 97.4
  (J.clinical micro. 322590-2592)
• PCR also has a quick turn around time 5 hours.

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EV Cost implications

• Study reported in CID 1995 20931-7 by Susan K.
  Rice et al from Rhode Island.
• A statewide outbreak of aseptic meningitis
  occurred in Rhode Island in the summer of 1991.
• 408 cases reported - enteroviruses recovered in
  68 of the 90 cases that were tested.

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EV Cost implications 2

• Comprehensive chart review was done.
• Demographic, clinical characteristics and
  institutional variation in treatment were
  assessed.
• 6 isolates were serotyped all E30.
• Marked variations in treatment based on
  institutions were noted.

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EV Cost Implications 3

• Approximately 90.3 were admitted to hospital for
  an average of 61 hours.
• 45 underwent some sort of isolation.
• 73.9 received at least one dose of IV
  antibiotics.
• Usually a 3rd generation cephalospsorin or
  penicillin.

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Cost Implications 4

• CT scan more frequent at non-teaching hospitals
  (68) than Teaching hospitals (40).
• As epidemic progressed, frequency of admission
  decreased in teaching institutions, but not
  non-teaching institutions.
• Cost of in-patient treatment was 3 times higher
  than out-patient.

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Discussion

• All 3 of our patients were admitted for one or
  two days.
• All received antibiotics at some point, and one
  received acyclovir until cultures were negative.
• Some antibiotics were given because of concerns
  of partially treated bacterial meningitis.

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Discussion 2

• Enterovirus PCR available, but not requested on
  any of these patients.
• Assuming that these patients had enterovirus
  meningitis, would getting a positive PCR made a
  difference to their management?
• What would be the cost savings as well as
  potential benefit to the patient?

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Conclusion

• Enterovirus PCR should be requested routinely on
  the CSF of all patients with suspected aseptic
  meningitis.
• The information from this test used in
  correlation with the clinical picture may help
  reduce unnecessary admissions.