Community Validation of

Influenza-like Illness as a Predictor of

InfluenzaJonathan 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

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

ILI uses

Clinical identification of influenza infection High PPV from research protocols

Adults Children

Age 65+

Age 25-64

Age 5-24

Age 0-4

ILI in WisconsinOct. 2007 thtough Sept. 2008

Community surveillance of influenza

Factors Affecting Symptoms

AgeAge

ImmuneImmuneStatusStatus

UnderlyingUnderlyingDiseaseDisease

Viral StrainViral Strain

Viral SubtypeViral Subtype

Host Factors Viral Factors

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

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

Preferential Collection from

Children and Young Adults

0

50

100

150

200

250

300

350

0 5 10

15

20

25

30

35

40

45

50

55

60

65

70

75

80

85

90

95

100

Age of Patient

No

. o

f S

pecim

en

s Range: 0 – 103 years

55.6% female

PredictorsWorking 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

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

Distribution of outcomes

Reference

population

Season

included

Criteria

used

Influenza (+)

Influenza (-)

All ARI specimens

Yes

sF+CorST (+)

1020 1034

sF+CorST (-)

210 1532

No

sF+CorST (+)

1082 1529

sF+CorST (-)

148 1037

Reference

population

Season

included

Criteria

used

Influenza (+)

Influenza (-)

Virus (+) specimens

Yes

sF+CorST (+)

1020 188

sF+CorST (-)

210 335

No

sF+CorST (+)

1082 302

sF+CorST (-)

148 221

Distribution of outcomes

Performance Characteristics

Criteria Referencepopulation

OR

flu

Sens Spec PPV NPV

F+CorST All ARI 4.96 0.88 0.40 0.41 0.88

F+CorST Virus (+) 5.25 0.88 0.42 0.78 0.60

sF+CorST All ARI 7.20 0.83 0.60 0.50 0.88

sF+CorST Virus (+) 8.66 0.83 0.64 0.84 0.62

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+

Effects of age(reference age = 25-64 years)Binary logistic regression via Minitab –

Release 13.1Factor Odds Ratio 95% CI

sF+CorST 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

* P<0.001

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

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

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

Final WordsIf influenza is in the community and

your patient is over 4 years oldIs it influenza?

F+CorST

“Of Course”

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

Additional Material

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%

Specimens Collected during

“Respiratory Virus” Season

0

50

100

150

200

250

300

350

0 4 8 12 16 20 24 28 32 36 40 44 48 52

Weeks after July 1st

Nu

mb

er

of

Sp

ecim

en

s

Collection Day(Monday through Thursday

Preferred)

0

5

10

15

20

25

SUN MON TUE WED THU FRI SAT

% o

f S

pec

imen

s

Most SpecimensCollected at Optimal Time

0102030405060708090

100

0 3 6 9 12 15 18 21 24 27 30

Days after Onset of Illness

Cu

mu

lati

ve P

erce

nta

ge

Percent of Specimens with Positive Virus

Isolation

0

0.1

0.2

0.3

0.4

0.5

0.6

0 1 2 3 4 5 6 7

Days after Onset of Illness

% p

osit

ive