1. Community Validation of Influenza-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

2. Influenza-like Illness  Definition  Fever of 100 o F (37.8 o C) or higher  Cough and/or Sore Throat  Not due to any other illness  Utility  Simple and elegant  Clinically relevant  Easily ascertained

3. ILI uses  Clinical identification of influenza infection  High PPV from research protocols  Adults  Children  Community surveillance of influenza

4. Factors Affecting Symptoms Age ImmuneStatus UnderlyingDisease Viral Strain Viral Subtype Host Factors Viral Factors

5. 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  Community—not research—perspective

6. 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

7. Preferential Collection from Children and Young Adults Range: 0 – 103 years 55.6% female

8. Predictors Working definition of ILI  F+CorST  F = Fever on symptom checklist  No requirement for level or documentation  CorST = Cough and/or Sore Throat  sF+CorST (includes seasonality)  December through March  Period with > 90% of influenza cases

9. Outcomes influenza 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

10. Distribution of outcomes Reference population Season included Criteria used Influenza (+) Influenza (-) All ARI specimens Yes sF+CorST (+) 10201034 sF+CorST (-) 2101532 No sF+CorST (+) 10821529 sF+CorST (-) 1481037

11. Reference population Season included Criteria used Influenza (+) Influenza (-) Virus (+) specimens Yes sF+CorST (+) 1020188 sF+CorST (-) 210335 No sF+CorST (+) 1082302 sF+CorST (-) 148221 Distribution of outcomes

12. Performance Characteristics CriteriaReference population OR flu SensSpecPPVNPV F+CorST All ARI4.960.880.400.410.88 F+CorST Virus (+)5.250.880.420.780.60 sF+CorST All ARI7.200.830.600.500.88 sF+CorST Virus (+)8.660.830.640.840.62

13. Additional Fiddling assessing 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+

14. Effects of age (reference age = 25-64 years) Binary logistic regression via Minitab – Release 13.1 FactorOdds Ratio95% CI sF+CorST7.55*5.81 – 9.80 0-4 years0.10*0.07 – 0.14 5-24 years1.210.90 – 1.65 25-64 yearsreference 65+ years1.670.86 – 3.25 * P<0.001

15. What about little kids? the percent of ILI cases due to: Virus0-4 years5+ years Influenza34.884.7 Adenovirus6.63.2 Parainfluenza14.43.3 Rhinovirus1.73.7 RSV37.01.4 Herpes simplex1.12.0 Enterovirus2.90.8

16. Conclusions  ILI (F+CorST) 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 (sF+CorST) 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

17. 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

18. Final Words If influenza is in the community and your patient is over 4 years old Is it influenza? F+CorST “Of Course”

19. 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

20. Additional Material

21. 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%

22. Specimens Collected during “ Respiratory Virus ” Season

23. Collection Day (Monday through Thursday Preferred)

24. Most Specimens Collected at Optimal Time

25. Percent of Specimens with Positive Virus Isolation