12/2/2009

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Obstacles in Poliovirus Eradication

Kostya ChumakovCenter for Biologics Evaluation and Research, 

Food and Drug Administration

12/2/2009

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Mikhail P. ChumakovNovember 14, 1909 – June 11, 1993

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• Basic reproduction number R0– R0 depends on strain virulence, hygiene, etc.

• Effective reproduction number Re = R0 * S– S is susceptibility of population

• If Re < 1 the transmission will stop– If R0 = 10, population immunity level must be >90%

• R can be manipulated by• Re can be manipulated by– Transmissibility (hygiene and sanitation level)

– Susceptibility (population immunity)

Polio Eradication Progress

198820092009

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World‐wide Polio Incidence

0

100.000

200.000

300.000

400.000

500.000

600.000

700.000

800.000

01.0002.0003.0004.000

2000

2001

2002

2003

2004

2005

2006

2007

2008

2009

0

1

2

3

4

5

6

AMR WPR

EUR

WHA

0

1980

1982

1984

1986

1988

1990

1992

1994

1996

1998

2000

2002

2004

2006

2008

01975 1980 1985 1990 1995 2000 2005 2010 2015

Why Polio Hasn’t Been Eradicated Yet?

Take 1: Why wasn’t transmission of wild polioviruses stopped?

• Incomplete understanding of epidemiology and pathogenesis of poliomyelitis

• Complex social, economic, and cultural factors

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There are known knowns; these are things we know we knowknow we know. 

There are known unknowns; that is to say we know there are some things we do not know.

But there are also unknown unknowns ‐ the ones we don't know we don't know.

Donald Rumsfeld

12/2/2009

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Why wasn’t transmission of wild polioviruses stopped yet?

• Failure to reach critical level of population p pimmunity– Failure to vaccinate

– Vaccine failure

Failure to Vaccinate in Northern Nigeria

Spread of Poliovirus in 2003-2006

23 countries with imported virus.

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Nigeria and Equatorial Africa

4

2736

26

25

2

2

138

2 610

2413

2

32

2

3

382

27

3

45

2

18

27 1020 8

15

2008 2009

Endemic countries in Asia: 2009

24

49272

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The number of doses per child

UP, Bihar in redRest of India, in black

Jacob John et al., Commentary, August 2006

Nicholas Grassly et al., Science, November 2006

Per dose protective efficacy of tOPV againsttype 1 poliovirus, India 1997‐2005

80% AFP cases in those who received ≥10 doses, 96% with ≥4 dosesMost cases in 5-11 months of ageAnnual birthrate = 32 / 1000Monthly birth cohort = 530,000Total population: 250,000 million

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N.Grassly, Lancet, 2007

Other obstacles

• Circulating pathogenic VDPV

• Immunodeficiency‐associated VDPV

• Inadequate surveillance

• Containment challenges

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200546 Cases

2000-0121 Cases

20013 Cases

20042 Cases

2006-075 Cases

Vaccine‐derived polio outbreaks

1988-9330 Cases

2005-062 Cases

2001-025 Cases

20053 Cases

20051 Case

7 Contacts2008-094 Cases

2005-09292 Cases

2005-0920 Cases

Immunodeficiency‐associated Vaccine‐Derived Polioviruses

Type 3Type 2Type 1

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Can poliovirus be contained?

• Enormous logistical challengeo ous og s ca c a e ge

• Research establishments

• Vaccine manufacturers

• Clinical specimens

• Permafrost

• Chronic excretors

• Chemical synthesis

Breaches in Surveillance or Cryptic Circulation?Orphan Polioviruses

Central Africa Type I

Central Africa

Southern Sudan Type III

Central Africa Type III

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Three phases of disease prevention

• ControlR d ti f bidit t i ll t bl l l– Reduction of morbidity to socially acceptable level

• Elimination– Reduction of morbidity to zero by applying measures used to control the disease 

• EradicationPermanent elimination of disease making it unnecessary to– Permanent elimination of disease making it unnecessary to continue medical interventions

P li li i ti i t iblPolio elimination is not possible as long as OPV is used

Stopping vaccination will lead to new tb k f li litioutbreaks of poliomyelitis

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Polio immunization must continuePolio immunization must continue even after eradication

OPV in its present form is unacceptable

IPV appears to be the only option

When we succeed in stopping wild poliovirus transmission willwild poliovirus transmission, will it mean that polio is eradicated? 

It depends on what your definition of th d “i ” ithe word “is” is.

William J. Clinton

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The Main Obstacle:

The lack of a clear strategic goal

Are we eradicating the disease or the virus?

We can’t wait for alms from the Nature. Our objective is to take it by force.

I.V.MichurinI.V.Michurin

12/2/2009

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IPV

Stop wt polio circulation

OPV

World-wide certification

Surveillance

PolioEradication Endgame Strategies

Replace with IPV ?Yes No

Stop OPV ?Yes No Continue indefinitely → risk of

VAPP and VDPV outbreaks

OPV cessation must be synchronous

Strategies

OPV can be phased out gradually and replaced with IPV Containment (BSL-3/polio)

Stockpile for emergency response

OPV cessation must be synchronous

Sabin IPV becomes a priorityMinimizing vulnerabilityEconomical sustainabilityCombination vaccines: broad protectionStrengthening EPI

Thank you

• Ellie Ehrenfeld

• Olen Kew

• Vadim Agol

• Eckard Wimmer