Polio Eradication -- Global Progress and Development of Post-Eradication Strategies:

Implications for U.S. Stockpile and Outbreak Response

PreparationsNational Vaccine Advisory Committee

February 8-9, 2005

Objectives of Session

• To provide update on polio eradication progress & plans for post-eradication era

• To provide update on U.S. success in eliminating all forms of paralytic polio & status of U.S. polio vaccine stockpile

• To elicit committee discussion re: key actions for U.S. stockpile

(III)Elimination of Paralytic Poliomyelitis in U.S.A.

Epidemiology of Polio – U.S.A. (I)

• Routine childhood immunization program– IPV (1950s) & OPV (1960s)– Elimination of indigenous wild polio (1979) &

imported wild polio (1993)

• Adverse effects of oral polio vaccine– VAPP: average 9 cases / year– Accepted as necessary consequence of OPV

use, to reduce risk of imported wild polio

Paralytic Poliomyelitis and OPV licensing United States, 1960-1969

0

500

1000

1500

2000

2500

3000

1960 1961 1962 1963 1964 1963 1966 1967 1968 1969

0

10

20

30

40

50

60

70

80

90

100non-VAPP VAPP

YEAR

No.

of

Cas

es

tOPV

VA

PP

Cas

es

type 3 mOPV

type 1 mOPV type 2 OPV

Paralytic Poliomyelitis, United States, 1980-1989

0

5

10

15

20

25

30

35

1980 1981 1982 1983 1984 1985 1986 1987 1988 1989

non-VAPP VAPP

YEAR

No.

of

Cas

es

Epidemiology of Polio – U.S.A. (II)

• Cessation of OPV in U.S.– Global polio eradication progress in 1990s:

• Lower risk of imported wild poliovirus in USA• Changing benefit / risk ratio for OPV• VAPP = unacceptable risk

– Transition to IPV:• Sequential IPV-OPV schedule (1997) • All IPV schedule (2000)

– Last VAPP cases occurred in 1999

Paralytic Polio Cases and OPV Doses DistributedUnited States, 1990-2003

0

1

2

3

4

5

6

7

8

9

10

1990 1991 1992 1993 1994 1995 1996 1997 1998 1999 2000 2001 2002 20030

5

10

15

20

25

VAPP Cases non-VAPP OPV doses in millions

Year

VA

PP

cas

es

OP

V d

ose

s in

mill

ion

sIPV-OPV

All-IPV

Epidemiology of Polio – U.S.A. (III)

• Post-OPV Cessation Era– High vaccination coverage maintained (2002 NIS)– High seroimmunity to all 3 serotypes after IPV-OPV or

all-OPV schedules (urban areas) (Prevots et al.)

• Paralytic Polio: Current & future risks– Source: Imported wild virus (primary)– Risk groups:

• Under-vaccinated children in urban areas• Vaccine refusers in religious communities

– Magnitude: very low but not zero

Epidemiology of Polio – U.S.A. (Conclusion)

• The U.S. has reached an important milestone – elimination of VAPP, through OPV cessation & transition to IPV.

• A low risk of polio cases or outbreaks in the U.S. remains until the world is polio-free.

• A polio vaccine stockpile, as approved, will help ensure an effective control of future outbreaks.

(IV)U.S. Polio Vaccine Stockpile & Outbreak Response: Status, Issues & Future Directions

Outline

• Topics: – IPV stockpile – OPV stockpile – Global collaboration– State & local

collaboration– Sabin IPV – Antiviral drug

• Order of presentation:– NVAC/ACIP Report– Current Status &

Issues– Future Directions– Points for Discussion

U.S. Polio Vaccine Stockpile: IPV (I)

• NVAC/ACIP report:– Projected / recommended = 8 million doses– Used alone / with OPV for outbreak control– Need for licensed, uncombined IPV

• Current status & issues:– Current = ~4 million doses & holding– Might be difficult to get 8 million doses of

uncombined IPV under current mechanism

U.S. Polio Vaccine Stockpile: IPV (II)

• Future directions– Continue efforts to develop uncombined IPV

stockpile through Pediatric Vaccine Stockpile– Consider other options for IPV stockpile

• Discussion points– How to maintain target supply of uncombined

IPV long-term?– IPV stockpile: U.S. issue only or global one?

U.S. Polio Vaccine Stockpile: OPV (I)• NVAC/ACIP report:

– Access to & effective use of OPV in outbreak– Needed = 8 million doses (tOPV or each mOPV

serotype)– Preferred type = mOPV, if available– Need to develop mechanism for use (IND vs other)

• Current status & issues:– IND for OPV – Need to identify vaccine manufacturer and specific

OPV product to continue

U.S. Polio Vaccine Stockpile: OPV (II)

• Future directions – Discuss regulatory options with FDA – Work with WHO & vaccine manufacturers re: mOPV– Develop IND & explore other emergency response

use mechanisms

• Discussion points– Proceed to mOPV stockpile without tOPV?– Are there other emergency response mechanisms to

use?

U.S. Polio Vaccine Stockpile: Global Collaboration (I)

• NVAC/ACIP report:– CDC, FDA, WHO & other int’l partners– Finance, create & maintain global PVS– Guaranteed & immediate U.S. access

• Current status & issues:– CDC & WHO staff – ongoing collaboration on

stockpile & outbreak response– CDC will collaborate with FDA & other agencies –

regulatory issues & mechanisms for use of vaccines

U.S. Polio Vaccine Stockpile: Global Collaboration (II)

• Future directions– Support WHO efforts to…

• License mOPV & develop mOPV stockpile• Evaluate the safety of Sabin IPV (sIPV)• Assess potential use of antiviral drug• Determine appropriate global stockpile size,

composition & regulation

• Discussion points (sIPV & antiviral drug)

U.S. Polio Vaccine Stockpile: State & Local Collaboration

• NVAC/ACIP report:– Develop polio outbreak response plans

• Current status & issues:– Outbreak response plan being drafted

• Future directions / discussion– Involve CSTE, NACCHO & others in outbreak response plan

development

U.S. Polio Vaccine Stockpile: Sabin IPV

• Global developments– Well outlined in Dr. Cochi’s presentation

• Discussion points– Efficacy? Safety? Source?– Issues for potential licensure of sIPV in US for

stockpile use?– Emergency use only (IND and/or other)?

U.S. Polio Vaccine Stockpile: Antiviral Drug

• Developments & issues– Outlined in Dr. Cochi’s talk– WHO-CDC-Private collaborative group– Exploring potential candidate antiviral drugs– Wider consideration: proposed NAS meeting

• Discussion points– Support for NAS-sponsored meeting?– Potential to add as component of stockpile?

U.S. Polio Vaccine Stockpile: Conclusions

• U.S. stockpile: not yet a reality -- optimal size, composition & use

• IPV stockpile: affected by economic issues• OPV stockpile: direction pending

– Global developments re: mOPV– Regulatory issues / emergency use options

• Potential products: evaluation / development– Sabin IPV, Antiviral Drug

Acknowledgements

• WHO– David Heymann– Bruce Aylward– Roland Sutter– Anna-Lea Jenny

• Harvard SPH & other– Kim Thompson– Rad Tebbens– Marc Collett

• CDC– Hamid Jafari– Denise Johnson– Linda Venczel– Margie Watkins– Nalinee Sangrujee– Mark Pallansch– Jane Seward– Lorraine Alexander– Kristin Kenyan

Thanks!

U.S. Polio Vaccine Stockpile: Discussion (I)

• IPV Stockpile:– How to maintain target supply of uncombined

long-term?– IPV stockpile: U.S. issue only or global one?

• OPV stockpile:– Proceed to mOPV stockpile without tOPV?

U.S. Polio Vaccine Stockpile: Discussion (II)

• Sabin IPV:– Efficacy? Safety? Source?– Issues for potential licensure of sIPV in US for

stockpile use?– Emergency use only (IND or other)?

• Antiviral drug:– Support for NAS-sponsored meeting?– Potential to add as component of stockpile?

Extra slides

Paralytic Poliomyelitis United States, 1951-1959

0

5000

10000

15000

20000

25000

1951 1952 '53 1954 '55 1956 '57 1958 '59

IPV licensed

YEAR

Pol

iom

yelit

is C

ases

*

Paralytic Poliomyelitis United States, 1970-1979

0

5

10

15

20

25

30

35

1970 1971 1972 1973 1974 1975 1976 1977 1978 1979

non-VAPP VAPP

YEAR

No.

of

Cas

es