Transcript 2. Polio End-game - Impact on Vaccination Policy

Polio End-game: What are the
implications on polio vaccination
policy?
Dr Raju Shah
What more for – a polio free India!
2010*
No WPV from any source since
January 2011
India is no longer an endemic
country!
Last detected case January 2011
* data as on 30 October 2010
cVDPV cases, India 2009-2011
•cVDPV cases detected in 2009-10
•100% due to type 2
Type 2
District
2009
2010
2011
Badaun
3
0
0
Bulandshahar
2
0
0
Ghaziabad
0
1
0
Meerut
2
0
0
Moradabad
2
0
0
Pilibhit
4
0
0
Shahjahanpur
2
1
0
Total
15
2
0
iVDPV & aVDPV cases, India 2009 to 2012*
iVDPV
State
Chhattisgarh
Punjab
Tamil Nadu
Uttar Pradesh
Odisha
Total
*: data as on 10 March 2012
Type 1
aVDPV
Type 2
Type 3
1
1
1
1
1
1
3
1
State
Type 1
Assam
Bihar
Karnataka
Madhya Pradesh
Rajasthan
Uttar Pradesh
West Bengal
1
Total
1
Type 2
3
1
1
1
4
1
11
ambiguous VDPV (aVDPV): origin uncertain e.g. single isolate from single AFP case, non-immunodeficient person
What is the polio 'endgame'?
5
'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
6
The endgame: addressing risks due to the oral
polio vaccine (OPV) after eradication
•
Cases of Vaccine-Associated Paralytic
Poliomyelitis (VAPP): very rare severe adverse
event; occurs in OPV recipients or a close contact.
•
Outbreaks of circulating vaccine-derived
poliovirus (cVDPV): very rare event; occurs when
vaccine virus regains ability to paralyze and circulate.
7
Evolution of the 'Post-Eradication' Timeline
Last WPV case
Years
Global Cert
Comm (1995)
OPV cessation
0
2
4
6
8
10
12
Wild virus
Certification
eradication
The 'Polio Endgame' refers
to management of the
'post-eradication' risks due
to OPV.
Expert Advisory
Meeting (1998)
Wild virus Certification &
eradication containment
ACPE (2004)
Wild virus
eradication
Certification &
containment
VDPV elimination?
World Health
Assembly (2008)
Wild virus
eradication
Certification &
containment
VDPV elimination
& validation
Post-OPV
surveillance
8
Why is the world now rethinking
the Polio Endgame?
9
cVDPVs (Global): Problem in Eradication
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)
10
Risks of Polio After 'Eradication'
with Continued OPV Use
Risk
Frequency
to date
Annual
burden
Evolution
over time
VAPP
2-4/m birth cohort
250-500
stable
iVDPV
39 identified
~1
decreases
~20
increases
(since 1962)
cVDPV
0-3* per year
11
*based on current understanding
Recent developments allow a major
'rethink' of the endgame
•
New bivalent vaccine (bOPV) outperforms trivalent
OPV.
•
New diagnostics show type 2 OPV is the main
problem.
•
New, very low cost 'IPV options' can allow all
countries to continue type 2 immunization if they
want/need to.
12
Best Solution
• Switch to IPV from OPV
Problem is COST!!!
Any developing country can afford?
Background: Countries with IPV Use
Standalone IPV
IPV - penta combo
IPV - hexa combo
Unknown
Not applicable
Data in WHO HQ as of Sep 2010
The boundaries and names shown and the designations used on this map do not imply the
expression of any opinion whatsoever on the part of the World Health Organization
concerning the legal status of any country, territory, city or area or of its authorities, or
concerning the delimitation of its frontiers or boundaries. Dotted lines on maps represent
approximate border lines for which there may not yet be full agreement.
 WHO 2010. All rights reserved
“IPV would serve
as a kind of
Insurance policy.”
Roland Sutter
WHO, Research and production coordinator
GPE
How does universal or selective use of IPV
helps?
Humoral immunity: a number of trials have
addressed this question
• One dose of IPV after multiple doses of OPV
effectively closes the remaining immunity gaps
(~90% of seronegative cases will seroconvert)
• In seropositive individuals, a dramatic boosting of
antibody titers is seen (~70-90%)
• After boosting, the antibody persist and then decline
to a new baseline that is higher that before the IPV
booster dose
Thinking of Affordable IPV Strategy:
Approaches:
Reduce number
of doses
Reduce amount
of dose
Reduce antigen
content
Reduce
production cost
• Use fewer doses per schedule
• Develop intradermal (ID) device or microneedle patch to stretch doses
• Use adjuvant to reduce antigen contents per
dose
• Enables IPV production in developing countries
with less or non-infectious strain
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
0
P1
P2
* includes seroconversion & priming
P3
1/5th fractional dose
Current price
(low volume)
Expected price
(high volume**)
** assumes full dose price of < US$1.5/dose at high volume
18
IPV introduction
• Benefit – impact on RI ?
• Timing/Age/Doses/Route – follow global SAGE
recs or our own ?
• Frequency: 2 doses to all or in known cVDPV
risk areas?
Schedule of IPV administration
How to harvest optimal immunity gains of IPV:
(seroconversion and antibody titers)
• IPV performance is negatively affected by levels of
maternally-derived antibody
• So the timing of IPV administration should be delayed to
minimize the interference effect
• The DTP3 visit (14 weeks in the EPI schedule) may offer the
best compromise in terms of timing
IPV should be introduced in routine programs at least 6
months before an anticipated switch from tOPV to bOPV
What are the major elements of
the 'New Polio Endgame'?
21
New Polio Endgame: Guiding Principles
•
Phased removal of Sabin/OPV viruses,
beginning with highest-risk (type 2).
•
Elimination of type 2 in parallel by switching
from tOPV to bOPV for routine EPI & campaigns.
•
Introduction of 1 IPV dose to boost immunity 6
months prior to a tOPV-bOPV switch & provide
type 2 'priming'.
22
New 'Endgame' strategy: parallel risk management
Last wild polio case
Years
trivalent OPV cessation
0
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
VDPV elimination
& validation
8
10
12
Post-OPV
surveillance
Post-OPV
surveillance
bivalent OPV 1&3
(bOPV) cessation
23
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.
24
Advantages of the New Approach
•
Accelerate type 1 & 3 eradication (with bOPV)
•
Address >90% of VDPV risk while surveillance &
response capacity is optimized
•
Substantially shorten the post-eradication phase
•
Boost routine immunization coverage (i.e. IPV at
DPT3) and bridge immunity gaps
25
Potential Disadvantages of the New Approach
•
Distraction to wild poliovirus eradication efforts in few
countries. (to stop ongoing cVDPV2s; to coordinate
tOPV-bOPV switch).
•
Complications of adding a new vaccine (IPV) to shedule.
(however, GPEI has introduced many new vaccines already).
•
Risk of failure to stop new cVDPV2s as this is totally new
stretegy. (but, with this approach could even 'restart'
tOPV temporarily if needed).
•
Risk of outbreaks of cVDPV 3 & 1. ( introduce IPV two
doses)
26
Key target dates for a tOPV-bOPV switch
timeline –
SAGE Polio Working Group (March 26, 2012)
• By end-2012: cessation of the ongoing cVDPV2 in Nigeria
• By September 2013 (latest): introduction of one
supplementary IPV dose at an immunization contact (at
or above age 14 weeks) in all OPV-using countries
• By April 2014: replacement of tOPV with bOPV for
routine & supplementary immunization globally (possibly
linked to a Global Immunization Week)
IPV in all OPV-using countries could begin latest by
7 September 2013, to enable a global tOPV-bOPV switch
by April 2014, possibly linked to the
'global immunization week'.
Thanks