Rotavirus Vaccination in the United States

Umesh D. Parashar For the Viral Gastroenteritis Team Centers for Disease Control and Prevention Atlanta, GA

TM

Viral Gastroenteritis Unit, CDC

Daniel Payne

Jackie Tate

Umesh Parashar

Ben Lopman

Margaret Cortese

Manish Patel

Jon Gentsch Baoming Jiang

Vaccine Implementation

• Feb 2006 -- RotaTeq recommended

• June 2008 -- Rotarix recommended

3

National Laboratory Surveillance

• Network of 67 laboratories

reporting since 2000

• Weekly reporting:

– # stool specimens tested for

rotavirus by EIA

– # positive tests

4 Tate et al. Pediatrics 2009 and unpublished CDC data

Vaccine introduction

Tate et al. Pediatrics 2009 and unpublished CDC data

60%-80% reduction in rotavirus +ve

Pre-Vaccine Seasonality of Rotavirus in U.S.

Nov Dec Jan Feb Mar Apr May

* 2000-2006 data

(before vaccine

introduction)

Marked Change in Seasonality in 2008 (Post-Vaccine)

Peak month of rotavirus activity

Curns, et al. PIDJ 2010.

Active Rotavirus Surveillance

• Surveillance in 3 US counties

• Enrollment of inpatients, emergency room patients, and outpatients with AGE

• Fecal specimens obtained and tested for rotavirus

8

211 194

147

168

101 104 107 101

9

44

4

27

0

50

100

150

200

250

2006 2007 2008 2009 2010 2011

Hosp

ital

izat

ions

All-cause AGE Rotavirus

All Cause Acute Gastroenteritis (AGE) and Rotavirus AGE Hospitalizations, NVSN 2006-2011

Proportion of AGE hospitalizations positive for rotavirus by EIA by year, NVSN, 2006-2011

51% 52%

6%

26%

4%

26%

0%

10%

20%

30%

40%

50%

60%

2006 2007 2008 2009 2010 2011

Per

cent

of

AG

E h

osp

ital

izat

ion

s ro

tav

iru

s +

Age Rotavirus vaccine

coverage in 2008

(≥1 dose)

< 1 year 56%

1 to < 2 years 44%

2 to < 3 years <1%

Age-Specific Rotavirus Hospitalization Rate Reduction and Vaccine Coverage, NVSN, 2008

Payne et al. CID 2011.

Age Rotavirus vaccine

coverage in 2008

(≥1 dose)

Decline in rotavirus

hospitalization rate

(2008 vs. 2006)

< 1 year 56% 66%

1 to < 2 years 44% 95%

2 to < 3 years <1% 85%

Age-Specific Rotavirus Hospitalization Rate Reduction and Vaccine Coverage, NVSN, 2008

Herd immunity?

Payne et al. CID 2011.

Possible Herd Immunity in Older Children and Young Adults -- Monthly Rate Ratio of GE discharges, 2008 vs. 2000-2006

Month Month

Lopman et al. JID 2011

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Case-Control Studies of RotaTeq Effectiveness against Severe Rotavirus Disease

Study 1 (Boom, 2010)

Study 2 (Staat, 2011)

Study 3 (Cortese, 2011)

3 doses 89%

(70, 96)

87% (71, 94)

90% (84, 94)

2 doses 82%

(15, 96)

88% (66, 96)

90% (75, 96)

1 dose 65%

(-11, 89)

74% (37, 90)

66% (16, 86)

Longitudinal Variation of Rotavirus G Types in the United States, 1996-2011

15

0

100

200

300

400

500

600

700

1997 1998 1999 2000 2001 2002 2003 2004 2005 2006 2007 2008 2009 2010 2011

G1 G2 G3 G4 G9 G12

Vaccine implementation

Gautam R, Mijatovic-Rustempasic S, Quaye O, Tam KI, Bowen M, Gentsch J, et al.

88 77 87 84 86 0

10

20

30

40

50

60

70

80

90

100

G1 G2 G3 G9 G12

Va

ccin

e E

ffec

tiv

enes

s (%

)

RotaTeq Effectiveness Against Severe Rotavirus Gastroenteritis, by Strain, NVSN, 2006-2009

Staat et al Pediatrics 2011

Detection of Rotavirus Vaccine Strains in Children with Gastroenteritis

Season RotaTeq Rotarix

2007-08 1 (retrospective) 0

2008-09 7 0

2009-10 5 1

2010-11 6 0 Gautam R, Mijatovic-Rustempasic S, Quaye O, Tam KI, Bowen M, Gentsch J, et al.

Reassortment in vivo Between RotaTeq Vaccine Strains

P[5]G1 P[5]G2 P[5]G3 P[5]G4 P[8]G6

G1 VP7 gene P[8] VP4 gene

Reassortant strain:

G1P[8] human

9 genes of WC3 parent

Slide courtesy Jon Gentsch

Intussusception Monitoring

• Active surveillance -- VSD

• National passive surveillance -- VAERS

19

JAMA. 2012;307(6):598-604.

VSD Data

Passive Reports of Intussusception after Rotavirus Vaccine Dose 1, VAERS

0

1

2

3

4

5

6

7

8

9

10

0 3 6 9 12 15 18 21 24 27 30 33 36 39 42 45 48 51 54 57 60 63 66 69 72 75

Real risk or reporting bias?

Haber et al. Pediatrics 2010

Benefit Versus Risk (If Risk Exists)

Events Rotavirus

disease averted Excess

intussusception Benefit : Risk

ratio

Deaths 14 0.2 70

Hospitalizations 55,000 51 1,100

Emergency visits 150,000 13 12,000

Outpatient clinic visits 273,000 NA NA

Desai et al. PIDJ 2012

Summary Marked declines in rotavirus disease

Appearance of a bi-annual pattern

Herd immunity

Changes in seasonal patterns

High vaccine effectiveness

Against a range of circulating strains

Strain changes after vaccine implementation

Could simply represent natural variation

No documented risk of intussusception

Cannot exclude low risk

Benefits outweigh potential risk

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New Vaccine Surveillance Network

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