William W. Thompson, PhDImmunization Safety Office

Office of the Chief Science OfficerCenters for Disease Control and Prevention

Impact of Seasonal Influenza

in the US

Collaborators

• David Shay, CDC Influenza Branch

• Eric Weintraub, CDC, OCSO/ISO

• Lynnette Brammer, CDC Influenza Branch

• Nancy Cox, CDC Influenza Branch

• Joe Bresee, CDC Influenza Branch

• Keiji Fukuda, WHO

Impact of Seasonal Influenza in the US

• Describe variation in deaths in US– Seasonal Variation

– Age Variation

• Describe alternative models for estimating influenza-associated morbidity and mortality

• Compare alternative model estimates

• Review estimates of influenza impact– Deaths

– Hospitalizations

– Other morbidity

Seasonal Variation in Deaths

• Currently, there are approximately 2.4 million deaths in the United States annually– 65,000 Underlying Pneumonia and Influenza deaths

• No direct measure of impact of influenza

• Strong seasonal component in US deaths– Peaks typically occur in December and January

– Peaks tend to be associated with increases in influenza activity

Seasonal Variation inAll-Cause Deaths (1972-2001)

0

10000

20000

30000

40000

50000

60000

70000

Jun

-71

Jun

-72

Jun

-73

Jun

-74

Jun

-75

Jun

-76

Jun

-77

Jun

-78

Jun

-79

Jun

-80

Jun

-81

Jun

-82

Jun

-83

Jun

-84

Jun

-85

Jun

-86

Jun

-87

Jun

-88

Jun

-89

Jun

-90

Jun

-91

Jun

-92

Jun

-93

Jun

-94

Jun

-95

Jun

-96

Jun

-97

Jun

-98

Jun

-99

Jun

-00

Jun

-01

Jun

-02

Year

Wee

kly

All-

Cau

se D

eath

s

Seasonal Variation in Underlying P&I Deaths (1972-2001)

0

1000

2000

3000

4000

5000

Jun

-71

Jun

-72

Jun

-73

Jun

-74

Jun

-75

Jun

-76

Jun

-77

Jun

-78

Jun

-79

Jun

-80

Jun

-81

Jun

-82

Jun

-83

Jun

-84

Jun

-85

Jun

-86

Jun

-87

Jun

-88

Jun

-89

Jun

-90

Jun

-91

Jun

-92

Jun

-93

Jun

-94

Jun

-95

Jun

-96

Jun

-97

Jun

-98

Jun

-99

Jun

-00

Jun

-01

Jun

-02

Year

Wee

kly

P&

I D

eath

s

Population Growth in Urban Areas of the US 1970-2000

0

25

50

75

100

125

150

175

200

225

250

1970 1980 1990 2000

Year

Mill

ions

Population Growth in Numbersof Elderly in the US 1970-2000

Mill

ions

0.0

2.0

4.0

6.0

8.0

10.0

12.0

14.0

16.0

18.0

20.0

65-74 75-84 85+

Age Group1970 2000

Age Variation in Numbers of Deaths in the US 1970-2003

-

100,000

200,000

300,000

400,000

500,000

600,000

700,000

800,000

0-4 Yrs

5-14 Yrs

15-24 Yrs

25-34 Yrs

35-44 Yrs

45-54 Yrs

55-64 Yrs

65-74 Yrs

75-84 Yrs

85+ Yrs

Age Group

Dea

ths

1970 2003

RR of All-Cause Death Versus Underlying P&I Death (NCHS 2000)

1970 2003

59

83

147

93

58 62 5743

2413

0

20

40

60

80

100

120

140

160

0-4 years

5-14 years

15-24 years

25-34 years

35-44 years

45-54 years

55-64 years

65-74 years

75-84 years

85+ years

Age Group

RR

of

Dea

th d

ue

to

All

-Cau

se v

ersu

s P

&I

Alternative Models for EstimatingImpact of Influenza in US

• Simonsen et al. (1997)– Linear Regression Model

– Modeled National Center for Health Statistics (NCHS) weekly death data from 1972-1992

• Outcomes– Underlying P&I Deaths (Most specific)

– All-Cause Deaths (Least specific, most sensitive)

• Model

Yt = a + b*t +c*t2 + d*cos (2 t /52) + f*sin(2 t /52) + et

Simonsen et al. 1997 Model

0

500

1000

1500

2000

2500

3000

3500

4000

Jul-89 Jul-90 Jul-91 Jul-92 Jul-93 Jul-94 Jul-95

P&

I D

eath

s

Alternative Models for EstimatingImpact of Influenza in US

• Thompson et al. (2003)– Poisson Regression Model– Modeled National Center for Health Statistics (NCHS)

weekly death data from 1976-2000– Incorporated WHO Influenza Surveillance Data

• Outcomes– Underlying P&I Deaths (Most specific)– Underlying Respiratory & Circulatory Deaths– All-Cause Deaths (Least specific)

• Model

Yt = exp (a + b*t +c*t2 + d*cos (2 t /52) + f*sin(2 t /52) + g * A(H1N1)% + h * A(H3N2)% + i * B%)

Circulation of A(H3N2) Viruses and Underlying P&I Deaths

Year

P&

I D

eath

s P

er 1

00,0

00

A(H

3N2)

% P

ositi

ve

P&I Death Rate A(H3N2)%

0

10

20

30

40

50

60

70

80

90

100

110

19901991

19921993

19941995

19961997

1998

0%

10%

20%

30%

40%

50%

60%

Alternative Models for EstimatingImpact of Influenza in US

• Barker & Mullooly (1980;1982)

• Two Types of Baseline Rates

– Peri-Season Baseline Rate

• October through May when influenza is not circulating above 10%

– Summer Season Baseline

• June through September

• Excess Rate = (Flu Rate) – (Non Flu Baseline Rate)

Seasonal Variation in Underlying P&I Deaths

SummerBaseline

SummerBaseline

WinterBaseline

InfluenzaPeriod

InfluenzaPeriod

0

1000

2000

3000

4000

Jul-89

Sep-89

Nov-89

Jan-90

Mar-90

May-90

Jul-90

Sep-90

Nov-90

Jan-91

Mar-91

May-91

Jul-91

Sep-91

Nov-91

Jan-92

Mar-92

May-92

Jul-92

Influenza-AssociatedAll-Cause Deaths by Model

in the US (1976-2000)

Alternative Models

Ann

ual I

nflu

enza

-Ass

ocia

ted

Dea

ths

in U

S

31,467 29,473

43,958

73,635

35,463

0

10,000

20,000

30,000

40,000

50,000

60,000

70,000

80,000

Simonsen 97 Simonsen 05 Peri Summer Poisson

Correlations Between Estimates of Influenza-Associated All-Cause Deaths

In the US (1976-2000)

Simonsen 97 Simonsen 05 Peri Summer Poisson

Simonsen 97 1.00

Simonsen 05 0.93 1.00

Peri 0.85 0.93 1.00

Summer 0.79 0.87 0.96 1.00

Poisson 0.78 0.87 0.90 0.90 1.00

Correlation Between Estimates forSimonsen 2005 and Peri-Season Models

y = 1.3305x + 4744.5R2 = 0.8729

0

20000

40000

60000

80000

100000

120000

0 10000 20000 30000 40000 50000 60000 70000

Simonsen 2005 Estimates

Per

i Sea

son

Est

imat

es

Influenza-AssociatedUnderlying R&C Death Rates

by Age For Peri-Season Model

2.4 0.4 0.4 8.7 26.046.8

85.5

165.9

445.3

0

100

200

300

400

500

<1 1 - 45 - 49

50 - 64

65 - 69

70 - 74

75 - 79

80 - 84

>= 85

Age Group

Dea

ths

Per

100

,000

Influenza-Associated Underlying R&C Deaths

by Age For Peri-Season Model

Age Group

Infl

uen

za-A

sso

ciat

ed D

eath

s

92 52719

2,945 2,4573,651

5,0176,220

13,267

-

2,500

5,000

7,500

10,000

12,500

15,000

<1 1 - 45 - 49

50 - 64

65 - 69

70 - 74

75 - 79

80 - 84

>= 85

Surveillance of Influenza-Associated Deaths Among Children in the US

• 2003/2004 influenza season was severe compared to other recent seasons, especially among children

• CDC implemented surveillance of childhood deaths associated with influenza

• Reviewed case reports, medical records, autopsy reports

Surveillance of Influenza-Associated Deaths Among Children in the US

• Results– 153 deaths among children aged < 18 years

– 96 deaths among children aged < 5 years

– 29% of the children died within 3 days of onset of the illness

– 47% of the children had previously been healthy

• CDC made influenza deaths among children a national reportable condition in October 2004

Influenza-AssociatedHospitalizations

• Thompson et al (2004)

• National Hospital Discharge Survey

• Examined data from 1979-2001

• Incorporated WHO Influenza Surveillance data

• Outcomes – Primary P&I (Most Specific)

– Any Listed P&I

– Primary R&C

– Any-Listed R&C (Least Specific)

• ModelYt = exp (a + b*t +c*t2 + d*cos (2 t /12) + f*sin(2 t /12) +

g * A(H1N1)% + h * A(H3N2)% + i * B%)

Influenza-Associated Primary R&C Hospitalization Rates

By Age (1979-2001)

0

200

400

600

800

1000

1200

1400

< 5 Yrs

5-49 Yrs

50-64 Yrs

65-69 Yrs

70-74 Yrs

75-79 Yrs

80-84 Yrs

85+ Yrs

Age Group

Influ

enza

-Ass

ocia

ted

Prim

ary

R&

CH

ospi

taliz

atio

ns P

er 1

00,0

00

Influenza-Associated Primary R&C Hospitalizations

By Age (1979-2001)

Age Group

Influ

enza

-Ass

ocia

ted

Prim

ary

R&

CH

ospi

taliz

atio

ns

20,031

34,867

29,447

18,301

26,501 27,51628,578

40,813

-

10,000

20,000

30,000

40,000

50,000

< 5 Yrs

5-49 Yrs

50-64 Yrs

65-69 Yrs

70-74 Yrs

75-79 Yrs

80-84 Yrs

85+ Yrs

Influenza-Associated HospitalizationsAmong Children Aged < 5 Years

By Study

1.20.9

1.41.1

0.6

2.6

0.0

1.0

2.0

3.0

4.0

5.0

6.0

Barker(1982)

Neuzil(2000)

Izurieta(2000)

Neuzil(2002)

Thompson(2004)

Iwane(2004)

Study

Hos

pita

lizat

ions

Per

1,0

00P

erso

n Y

ears

Excess P&I Hospitalization RatesBy Risk Status

Barker & Mullooly (1980, 1982)

0

100

200

300

400

500

600

700

800

0 - 4 5-14 15-44 45-64 65+

Age (Years)

Exc

ess

P&

I H

ospi

taliz

atio

ns

Per

100

,000

Per

sons

Low Risk High Risk

Other Influenza-Associated Morbidity

• Nichol et al (1999) LAIV Trial Aged 18-64– Severe febrile illness

– Work days missed

– Doctors visits

– Antibiotic use

• Bridges at al (2000) TIV Trial Aged 18-64– Febrile illness

– Worked days missed

– Doctors visits

Summary and Recommendations

• Influenza infections are associated with substantial morbidity and mortality every year– Improve vaccine coverage for at-risk populations currently

recommended for annual influenza vaccination by ACIP

• The very elderly are at substantially increased risk for influenza-associated morbidity and mortality– Encourage development of vaccines with improved

immunogenicity for older adults

• The aging of the US population is leading to substantially more seasonal influenza-associated morbidity and mortality every year– Prepare public health officials for the increasing burden of disease

associated with seasonal influenza over the next decade