The Evolving 'Polio Endgame'
Strategy
Orientation for IEAG
15 March 2012
1
Background
2
Main risks if routine OPV is continued after
wild poliovirus eradication
•
Cases of Vaccine-Associated Paralytic Poliomyelitis
(VAPP): very rare severe adverse event, occurring in OPV
recipients or a close contact.
•
Outbreaks of circulating vaccine-derived poliovirus
(cVDPV): very rare event; > 1 paralytic polio case with
isolation of related but non-identical VDPV viruses.
3
Other risk: long-term poliovirus excretors
(iVDPVs: 1o immunodeficiency-associated VDPVs)
53 iVDPVs (> 6 months excretion)
8 known to excrete >5 years.
Immunodeficiencies linked to
prolonged poliovirus excretion
cvid
agamma
Type 2 (34) > Type 1 > Type 3
ab deficient
scid
hypogamma
From:
–
Industrialized countries (22)
–
Middle income countries (31)
–
Low income countries
ICF
MHC-II def
XLA
unknown
4
'After interruption of wild
poliovirus, continued use of OPV
would compromise the goal of a
polio-free world.
Expert Consultation on Vaccine-derived
Polioviruses (VDPVs), Sept 2003, Geneva
5
Evolution of the 'Post-Eradication' Timeline
Last WPV case
Years
Global Cert
Comm (1995)
0
OPV cessation
2
4
6
8
10
12
Wild virus
Certification
eradication
Certification &
containment
The 'Polio Endgame' refers
to management of the
'post-eradication' risks due
to OPV.
Expert Advisory
Meeting (1998)
Wild virus
eradication
ACPE (2004)
Wild virus
eradication
Certification &
containment
VDPV elimination?
World Health
Assembly (2008)
Wild virus
eradication
Certification &
containment
VDPV elimination &
validation
Post-OPV
surveillance
6
Why is the world now rethinking
the Polio Endgame?
7
Recent developments allow a major 'rethink'
of the polio endgame
•
New diagnostics and experience currently suggest type 2
cVDPV is the main 'post-eradication' problem.
•
New bivalent vaccine (bOPV) is proven to outperform
tOPV for types 1 & 3 and a viable option to replace tOPV.
•
New, very low cost 'IPV options' could allow all countries
to continue type 2 immunization if they want/need to.
8
Current Understanding of cVDPVs (Global)
Circulating Vaccine-Derived
Poliovirus Oubreaks
(cVDPVs) 2000-2010
Type 1 (79 cases)
Type 2 (450 cases)
Type 3 (9 cases)
Since 2009, 97% of
cVDPV cases are due
to type 2
(& 40% of VAPP)
9
Current Understanding of cVDPVs (India)
Spot map of VDPVs
2011-12
India: 90% of VDPVs
are type 2 & 100% of
cVDPVs are type 2
Type 1
Year
Data as on 7 March 2012
Type 2
Type 3
Total
a
i
c
a
i
c
a
i
c
2009
1
1
0
4
0
15
0
0
0
21
2010
0
0
0
2
1
2
0
0
0
5
2011
0
0
0
4
2
0
0
1
0
7
2012
1
Total
2
1
1
0
10
3
17
0
1
0
34
10
Trend in Type 2 Polio Protection (India)
Moradabad
Nov 2007
(N=121)
AFP cases UP
Nov 08 – mid
09 (N =169)
Moradabad
May 2009
(N=534)
UP & Bihar
Aug 2010
(N=1280)
UP & Bihar
Aug 2011
(N=1246)
Age
6-7 mos
6-11 mos
6-7 mos
6-7 mos
6-11 mos
Type 2
56%
33.7%
75%
65%
85%
Reduced emergence of type 2 cVDPVs is
associated with improving type 2 immunity
11
Bivalent OPV Efficacy & Use
Seroconversion after 2 x bOPV
vs. tOPV, India, 2008-2009
bivalent OPV use
as of Sept 2011
100
90
80
79.5
71
70
60
53.2
49.1
50
40
30
20
10
Introduced
Dec 09-Aug 11
0
bOPV
tOPV
Type 1
bOPV
tOPV
Planned by
end-2011
Type 3
12
Affordable IPV options in the short-term,
1/5th of 1 dose of IPV can induce a
response in >90% of children
1/5th of 1 dose of IPV could be very
affordable (<$0.5/dose)
IPV price
($ per dose)
Response* after 1 dose
(%, intradermal IPV, Cuba)
100
$3
90
80
70
60
50
$0.6
40
< $0.3
30
20
Full-dose
10
1/5th fractional dose
0
P1
P2
* includes seroconversion & priming
P3
Current price
(low volume)
Expected price
(high volume**)
** assumes full dose price of < US$1.5/dose at high volume
13
What are the major elements of
the 'New Polio Endgame'?
14
New Polio Endgame: Guiding Principles
•
phased removal of Sabin viruses, beginning with
highest-risk (type 2).
•
elimination of VDPV type 2 in parallel with
eradication of last wild polioviruses by switching
from tOPV to bOPV for routine EPI & campaigns.
•
early introduction of at least 1 dose of IPV to boost
immunity prior to a tOPV-bOPV switch (& provide
type 2 priming if further doses required).
15
A new 'Endgame' strategy: parallel instead of
sequential risk management
Last wild polio case
Years
0
trivalent OPV cessation
2
Sequential risk
management
Wild virus
eradication
Certification &
containment
Parallel risk
management
Wild virus
eradication
Certification &
containment
VDPV2 elimination &
validation
OPV2 cessation
& IPV introduction
4
6
8
VDPV elimination &
validation
10
12
Post-OPV
surveillance
Post-OPV
surveillance
bivalent OPV 1&3
(bOPV) cessation
16
Potential Advantages of the New Approach
•
accelerate eradication of type 1 & 3 wild poliovirus by
routine use of bOPV (and possibly IPV)
•
address >90% of the VDPV risk when global
surveillance/response capacity is highest
•
substantially shorten the post-eradication phase (&
reduce a major source of donor/partner anxiety)
•
possibly boost eradication effort with new energy &
routine immunization coverage (i.e. if IPV dose at DPT3)
17
Potential Disadvantages of the New Approach
•
distraction to wild poliovirus eradication efforts (to
stop ongoing cVDPV2s; to coordinate tOPV-bOPV switch).
•
complications of adding a new vaccine (IPV) (however,
GPEI has introduced many new vaccines already).
•
sudden 'price shock' for donors as requires early
presentation of longer-term financing requirements.
•
risk of failure to stop new cVDPV2s (but, with this
approach could even 'restart' tOPV temporarily if needed).
18
Impact of the new Endgame Strategy on
Major Cost Drivers for 2013-2018
'Core costs*' - stable
OPV campaign costs - decrease
IPV costs - additional
* staff & technical assistance, surveillance & lab, research, outbreak response, stockpiles.
19
Some Implications for IPV
•
IPV could be scaled up much earlier than anticipated (i.e.
tOPV-bOPV switch could be prior to April 2014).
•
standalone IPV would be used for the 'tOPV-bOPV switch'
with hexavalent having a 'post-OPV' role (e.g. from 2017-18).
•
a fractional (1/5th dose) intradermal IPV option may be
essential for acceptability, cost, supply, manufacturer risk.
•
the probability of expanded, longterm IPV use would
increase substantially.
20
Recent Developments
& Next Steps
21
•
SAGE Nov 2011: recommended endgame strategy be
based on phased, not simultaneous, Sabin strain removal.
•
WHO Executive Board Jan 2012: requested endgame
strategy & timeline for phased Sabin strain removal.
•
SAGE Apr 2012: to discuss introduction of 1 dose of IPV at
DTP3 contact in all OPV-using countries at least 6 months
prior to a global tOPV-bOPV switch (as early as Apr 2014).
•
World Health Assembly, May 2012: to consider a
resolution on the tOPV-bOPV switch.
22
Summary
•
a new definition of, and strategy for, the 'endgame' may
accelerate eradication & reduce long-term risks.
•
depending on IPV price and strategy, the new endgame
could be cost-neutral through certification.
•
by emphasizing the delivery of 1 IPV dose at the DPT3
contact, the new strategy should help to strengthen the
focus & coverage of routine immunization.
23
Extra Slides
24
Work streams
Policy development
Major Issues (examples)
• Phased vs. simultaneous removal of Sabin viruses
• Geographic extent and schedule for IPV use
Supply & Product
Development
• Global bOPV availability (i.e. national producers)
• Feasibility of restarting tOPV production from bOPV
• Regulatory issues, supply & price for largescale ID IPV use
Research
• Nature of immune response & duration of priming after 1 IPV dose
• Further characterization of VDPV risks
• Criteria to validate WPV type 2 elimination; cVDPV2 elimination
Surveillance &
containment
• Containment requirements for type 2 after tOPV-bOPV switch
• Supplementary surveillance (incl. environmental surveillance)
Operations &
logistics
• Synchronization of tOPV-bOPV switch globally
• Safe handling/destruction of residual stocks
Budget &
financing
• Budget implication of IPV introduction
• Multi-year business & financing plan
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