Community Validation of Influenza-like Illness as a Predictor of Influenza

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Community Validation ofInfluenza-like Illness
as a Predictor of Influenza

• Jonathan L. Temte, MD/PhD Alexis Eastman,
  MS-2
• University of Wisconsin School of Medicine and
  Public Health
• Peter A. Shult, PhD, Carol J. Kirk Mary
  Wedig
• Wisconsin State Laboratory of Hygiene
• Madison, Wisconsin

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Influenza-like Illness

• Definition
• Fever of 100oF (37.8oC) or higher
• Cough and/or Sore Throat
• Not due to any other illness
• Utility
• Simple and elegant
• Clinically relevant
• Easily ascertained

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ILI uses

• Community surveillance of influenza

• Clinical identification of influenza infection
• High PPV from research protocols
• Adults
• Children

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Factors Affecting Symptoms
Host Factors
Viral Factors
Age
Viral Strain
Immune Status
Viral Subtype
Underlying Disease
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Purpose of Study

• Review the contents of a large database
• Surveillance data emerging from a partnership
  between a public health laboratory and primary
  care clinicians
• Symptoms and virus identification
• Validate ILI for influenza infection
• Communitynot researchperspective

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The Surveillance Database

• Partnership of WSLH and UW-DFM since 1994
• Major modification of symptom check off in 1997
• Opportunistic sampling with fee-exempt virus
  culture
• physicians obtain specimens, record demographic
  and symptom data, sample is transported to WSLH
  by courier.
• Standard culture methods with isolation rate
  45
• Limited, de-identified data used
• 1997-2007
• IRB approved
• 3,796 episodes of acute respiratory illness care
  available

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Preferential Collection fromChildren and Young
Adults
Range 0 103 years 55.6 female
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PredictorsWorking definition of ILI

• FCorST
• F Fever on symptom checklist
• No requirement for level or documentation
• CorST Cough and/or Sore Throat
• sFCorST (includes seasonality)
• December through March
• Period with gt 90 of influenza cases

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Outcomesinfluenza isolation

• Paradigm 1 clinical primary care
• Influenza () vs. all other specimens
• Influenza 1230
• Non-influenza no virus isolated 2566
• Paradigm 2 ideal virus capture
• Influenza () vs. non-influenza virus ()
• Influenza 1230
• Non-influenza 523

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Distribution of outcomes
Reference population Season included Criteria used Influenza () Influenza (-)
All ARI specimens Yes sFCorST () 1020 1034
All ARI specimens Yes sFCorST (-) 210 1532
All ARI specimens No sFCorST () 1082 1529
All ARI specimens No sFCorST (-) 148 1037
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Distribution of outcomes
Reference population Season included Criteria used Influenza () Influenza (-)
Virus () specimens Yes sFCorST () 1020 188
Virus () specimens Yes sFCorST (-) 210 335
Virus () specimens No sFCorST () 1082 302
Virus () specimens No sFCorST (-) 148 221
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Performance Characteristics
Criteria Reference population OR flu Sens Spec PPV NPV
FCorST All ARI 4.96 0.88 0.40 0.41 0.88
FCorST Virus () 5.25 0.88 0.42 0.78 0.60
sFCorST All ARI 7.20 0.83 0.60 0.50 0.88
sFCorST Virus () 8.66 0.83 0.64 0.84 0.62
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Additional Fiddlingassessing effects of age

• Concentrate on seasonal data
• Clinician informed by surveillance
• Concentrate on virus () specimens
• Symptomatic patient
• Early in illness
• Collection technique good
• Concentrate on age categories
• 0-4
• 5-24
• 25-64
• 65

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Effects of age(reference age 25-64
years)Binary logistic regression via Minitab
Release 13.1
Factor Odds Ratio 95 CI
sFCorST 7.55 5.81 9.80
0-4 years 0.10 0.07 0.14
5-24 years 1.21 0.90 1.65
25-64 years reference
65 years 1.67 0.86 3.25
Plt0.001
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What about little kids?the percent of ILI cases
due to
Virus 0-4 years 5 years
Influenza 34.8 84.7
Adenovirus 6.6 3.2
Parainfluenza 14.4 3.3
Rhinovirus 1.7 3.7
RSV 37.0 1.4
Herpes simplex 1.1 2.0
Enterovirus 2.9 0.8
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Conclusions

• ILI (FCorST) performs well
• Public health tool for surveillance
• Early detection of influenza
• High sensitivity ( 0.88)
• Limited by low specificity (0.40)
• but fined tuned by virological methods
• ILI (sFCorST) performs well
• Clinician tool for diagnosis of influenza
• Informed by public health surveillance
• High PPV (0.84) moderate NPV
• Excluding young children raises PPV to 0.90

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Conclusions

• Influenza is the primary cause of ILI in patients
  age 5 years
• Many viruses can cause ILI in children 0-4 years
  of age. ILI should not be used for diagnosis
  alone in this group.
• ILI for predicting influenza infection has been
  validated in a primary care, community-based
  population

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Final Words

• If influenza is in the community and your patient
  is over 4 years old
• Is it influenza?
• FCorST

Of Course
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Acknowledgements

• Wisconsin Primary Care Clinicians
• UW-DFM residency clinics
• Numerous private physicians
• UW-DFM Summer Student Research and Clinical
  Assistantship Program
• Ms. Alexis Eastman
• Wisconsin State Laboratory of Hygiene

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Additional Material
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Basic Characteristics of Surveillance System

• Mean age of patient 26.6 years
• Range 0 to 103 years
• Sex
• Female 55.6
• Male 44.4
• Time between illness onset and collection
• Mean 3.86 days
• Median 2 days
• Rate of virus isolation 44.6

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Specimens Collected duringRespiratory Virus
Season
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Collection Day(Monday through Thursday Preferred)
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Most SpecimensCollected at Optimal Time
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Percent of Specimens with Positive Virus
Isolation