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Considerations for the Full Global Withdrawal of Oral Polio Vaccine After Eradication of Polio

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Eliminating the risk of polio from vaccine-derived polioviruses is essential for creating a polio-free world, and eliminating that risk will require stopping use of all oral polio vaccines (OPVs) once all types of wild polioviruses have been eradicated. In many ways, the experience with the global switch from trivalent OPV (tOPV) to bivalent OPV (bOPV) can inform the eventual full global withdrawal of OPV. Significant preparation will be needed for a thorough, synchronized, and full withdrawal of OPV, and such preparation would be aided by setting a reasonably firm date for OPV withdrawal as far in advance as possible, ideally at least 24 months. A shorter lead time would provide valuable flexibility for decisions about when to stop use of OPV in the context of uncertainty about whether or not all types of wild polioviruses had been eradicated, but it might increase the cost of OPV withdrawal. © The Author 2017. Published by Oxford University Press for the Infectious Diseases Society of America.
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The Journal of Infectious Diseases
Full Global Withdrawal ofOPV • JID 2017:216 (Suppl 1) • S217
The Journal of Infectious Diseases® 2017;216(S1):S217–25
Considerations for the Full Global Withdrawal of Oral
Polio Vaccine Aer Eradication of Polio
Lee M.Hampton,1 Gaël Maufrasdu Châtellier,2 JacquelineFournier-Caruana,3 AnnOttosen,4 JenniferRubin,4 LisaMenning,3 MargaretFarrell,5
StephanieShendale,3 and ManishPatel6
1Global Immunization Division, Centers for Disease Control and Prevention, Atlanta, Georgia; 2West and Central Africa Regional Office, UNICEF, Dakar, Senegal; 3World Health
Organization, Geneva, Switzerland; 4Supply Division, UNICEF, Copenhagen, Denmark; 5Program Division, United Nations Children’s Fund (UNICEF), New York, New York; and 6Task
Force for Global Health, Atlanta, Georgia
Eliminating the risk of polio from vaccine-derived polioviruses is essential for creating a polio-free world, and eliminating that risk
will require stopping use of all oral polio vaccines (OPVs) once all types of wild polioviruses have been eradicated. In many ways,
the experience with the global switch from trivalent OPV (tOPV) to bivalent OPV (bOPV) can inform the eventual full global with-
drawal of OPV. Signicant preparation will be needed for a thorough, synchronized, and full withdrawal of OPV, and such prepara-
tion would be aided by setting a reasonably rm date for OPV withdrawal as far in advance as possible, ideally at least 24months.
Ashorter lead time would provide valuable exibility for decisions about when to stop use of OPV in the context of uncertainty
about whether or not all types of wild polioviruses had been eradicated, but it might increase the cost of OPV withdrawal.
Keywords. Oral polio vaccine; polio eradication; vaccine derived polioviruses.
Widespread use of oral polio vaccines (OPVs) since the
1960s has resulted in the eradication of wild poliovirus type 2
(WPV2), the lack of WPV3 detection since November 2012,
and the connement of WPV1 to areas of Afghanistan, Nigeria,
and Pakistan by 2016 [1–3]. OPVs are relatively inexpensive
and easy to administer and can provide good protection against
poliomyelitis and poliovirus infections [3–5]. However, the
attenuated polioviruses in OPVs can undergo genetic changes
during replication, which, in communities with low vaccination
coverage, can result in vaccine-derived polioviruses (VDPVs)
that can cause paralytic polio [6]. From January 2006 to May
2016, 721 polio cases were caused by circulating VDPVs (cVD-
PVs) [6]. Eliminating the risk for polio caused by VDPVs will
require stopping use of all OPVs in all routine immunization
services and supplementary immunization activities (SIAs).
e rst phase in the eventual cessation of all OPV use was the
globally synchronized switch (hereaer, “the switch”) from triva-
lent OPV (tOPV), which contained types 1, 2, and 3 live, attenu-
ated polioviruses, to bivalent OPV (bOPV), which contains only
types 1 and 3 attenuated polioviruses. As part of the switch, all
countries and territories using OPV ocially ceased use of tOPV
by May 2016 and withdrew all live, attenuated type 2 poliovi-
ruses from vaccine stores at all administrative levels [3, 7–9]. e
live, attenuated type 2 polioviruses were prioritized for removal
because their use had accounted for >94% of the polio cases from
cVDPVs from January 2006 to May 2016, yet no cases of polio
caused by WPV2 had been detected since 1999 [6]. Once WPV1
and WPV3 are certied as eradicated, use of bOPV will no longer
be required, and it will need to be withdrawn (Table1). Globally,
synchronizing bOPV withdrawal will help prevent the spread of
any attenuated polioviruses that could eventually become cVD-
PVs from countries that continue to use bOPV to countries that
have ceased bOPV use and will therefore have increasing popula-
tion susceptibility to poliovirus infections [10].
To build on the current stockpile of monovalent type 2
(mOPV2) vaccine established aer the switch, stockpiles of
monovalent type 1 OPV and type 3 OPV will need to be main-
tained for responding to any outbreaks of polio that occur aer
bOPV withdrawal [3, 7]. Any remaining vials or containers of
OPV (mOPV, bOPV, or tOPV) that are identied outside of
those stockpiles will need to be withdrawn [11–13].
Full OPV withdrawal will also involve stopping the man-
ufacture and distribution of bOPV, destroying all OPV with-
drawn from vaccine stores, conducting monitoring to ensure
that all OPV outside of the mOPV stockpiles has been suc-
cessfully withdrawn, and ensuring that sucient nancial
and human resources are available for this work (Figure1). To
facilitate timely initial planning for full withdrawal of all OPV
vials outside of the mOPV stockpiles, henceforth referred to
as “OPV withdrawal,” the Global Polio Eradication Initiative’s
(GPEI’s) Immunization Systems Management Group (IMG)
discussed how the withdrawal of all OPVs might benet
from the experience gained with the switch at a meeting in
September 2016. is article reects that discussion.
SUPPLEMENT ARTICLE
© The Author 2017. Published by Oxford University Press for the Infectious Diseases Society of
America. This is an Open Access article distributed under the terms of the Creative Commons
Attribution 3.0 IGO (CC BY 3.0 IGO) License (https://creativecommons.org/licenses/by/3.0/igo/)
which permits unrestricted reuse, distribution, and reproduction in any medium, provided the
original work is properly cited.
DOI: 10.1093/infdis/jix105
Correspondence: L. M. Hampton, MD, Centers for Disease Control and Prevention, 1600
Clifton Road NE, Mailstop A-4, Atlanta, GA 30329 (lhampton@cdc.gov).
S218 • JID 2017:216 (Suppl 1) • Hampton etal
MANUFACTURING AND DISTRIBUTION OF
BIVALENTOPV
As of August 2016, 6 companies were producing World Health
Organization (WHO)–prequalied bOPV for the international
market [14], with 7 additional companies producing bOPV for
their domestic markets [15]. Among the 150 countries and terri-
tories currently using OPV (Figure2), approximately 75 procure
bOPV through the United Nations Children’s Fund (UNICEF),
while the rest self-produce or self-procure bOPV. Among coun-
tries and territories procuring bOPV through UNICEF, SIAs are
the key demand driver, with routine immunization accounting for
approximately 20% of UNICEF’s procurement of 1.2 billion doses
in 2016. Similar to tOPV withdrawal, successful withdrawal of
bOPV will depend on nding a balance between the scaling back
of production by global and domestic manufacturers and ensur-
ing sucient availability of types 1 and 3 bulk and nished bOPV
to meet routine immunization, outbreak response, and planned
SIA demand through the date of OPV withdrawal [13]. Factors
that can facilitate a favorable balance include advanced notica-
tion of the date of withdrawal to manufacturers and countries,
Table1. Comparison of the Switch From Trivalent Oral Polio Vaccine (tOPV) to Bivalent OPV (bOPV) Versus the Full Withdrawal of OPVs
Comparison Switch From tOPV to bOPV Full Withdrawal of OPVs
Reason for change End of transmission of type 2 wild polioviruses made the
risks from continued regular use of OPV containing type
2 Sabin strain polioviruses outweigh the benefits
End of transmission of all 3 types of wild polioviruses will make the
risks from continued regular use of any OPV containing Sabin
strain polioviruses outweigh the benefits
Synchronization All countries using tOPV needed to withdraw all tOPV in a
synchronized manner within a short time frame to avoid
creating type 2 cVDPVs
All countries using OPV will need to withdraw all OPV in a synchro-
nized manner within a short time frame to avoid creating cVDPVs
Potential risks from incom-
plete withdrawal of vaccine
tOPV left in the cold chain and used long after the switch
could potentially result in new cVDPVs
OPV left in the cold chain and used long after full OPV withdrawal
could potentially result in new cVDPVs
OPV use in routine immuniza-
tion after event
Routine immunization programs used bOPV instead of
tOPV after the switch
No OPV should be used in routine immunization programs after full
OPV withdrawal
Introduction of new form of
OPV during event
bOPV was introduced simultaneously with the withdrawal
of tOPV during the switch
No new form of OPV will be introduced during full OPV withdrawal
Availability of OPV stockpile Monovalent OPV stockpile available for use in response
to polio outbreaks caused by type 2 polioviruses after
the switch
Monovalent OPV stockpiles will be available for use in response
to polio outbreaks caused by any type of poliovirus after OPV
withdrawal
Outbreak response resources Extensive resources available for organizing responses to
polio outbreaks caused by cVDPVs after the switch
Fewer resources may be available for organizing responses to polio
outbreaks caused by cVDPVs after full OPV withdrawal
Abbreviation: cVDPV, circulating vaccine-derived poliovirus.
Goals
Stop use of all OPV in a synchronized manner at a certain date after the eradication of polio to prevent future casesof
vaccine-associated paralytic poliomyelitis and vaccine-derived poliomyelitis caused by vaccine-derivedpolioviruses
Withdraw, inactivate, anddispose of all OPV after the eradication of polio from storage outside of controlled
monovalent OPV outbreak-response stockpiles to reduce the risk of OPV being used
Components
Cease manufacturing and distribution of bivalent OPV
Cease use of OPV
Withdraw all OPV from storage outside of controlled outbreak-response stockpiles
Dispose of all withdrawn OPV
Monitor and confirm the withdrawal and disposal of OPV
Ensure financial support for efforts to withdraw and dispose of OPV
Scope
All countries still using OPV at the date of OPV withdrawal will need to withdraw OPV,
dispose of it, andmonitor and confirm the completion of that work
Some or all countries that have ceased use of OPV prior to the date of OPV withdrawal might
also need to provide confirmation that they no longer have OPV in storage
The approach used to confirm that OPV has been fully withdrawn mightneed to be varied
from countrytocountry,depending on when countriesOPV use stopped
OPV withdrawal efforts will need to complement other measures to reduce risks from polio after use of OPV
ceases, such as the operation of a global polio surveillance system,global use of inactivated polio vaccine, and containment of
p
olioviruses in laboratories and vaccine manufacturin
g
p
lants
Figure1. Considerations for Final Withdrawal of Oral Poliovirus Vaccine (OPV), Immunization Systems Management Group, 2016.
Full Global Withdrawal ofOPV • JID 2017:216 (Suppl 1) • S219
inventories of countries’ OPV stocks, and accurate country and
global quantication of demand for bOPV. Adequate planning
and coordination among UNICEF, other GPEI partner organiza-
tions, governments, and manufacturers will be required to ensure
that appropriate supplies of both bulk stocks and nished bOPV
are available in sucient quantities to meet global demand [16].
All OPV manufacturers will need to cease production of bOPV
well in advance of OPV withdrawal. Except for manufacturers
contracted to produce mOPV bulk and nished product for the
mOPV emergency use stockpiles, all OPV manufacturers will
need to exit the market [3, 17], albeit in a closely monitored and
managed fashion that allows sucient availability ofbOPV.
As with the switch, a clear commitment from all OPV-using
countries that they will cease all bOPV use in a synchronized
manner will be required through a World Health Assembly res-
olution [18]. Aclear indication from GPEI as to the likely date
of OPV withdrawal, similar to the statement in the 2013–2018
Polio Eradication and Endgame Strategic Plan that the switch
would likely occur in mid-2016, would also be useful [7]. Since
it can take up to 24months to produce OPV, manufacturers will
require advanced notice of at least 24months to plan the cessa-
tion of bOPV production and avoid having large excess stocks
that will need to be destroyed aer OPV withdrawal [16].
Procurement policies and stock management systems that min-
imize the likelihood of stockpiling excessive amounts of bOPV in
individual countries can guide procurement decisions and help
reduce the amount of bOPV that will need to be destroyed aer
withdrawal. In particular, each country using bOPV will need
to perform a careful inventory of bOPV stocks and plan bOPV
requirements and deliveries to ensure that manufacturers have
sucient information on bOPV needs to secure sustainable
supply while avoiding overstocks. Given the time it can take to
produce OPV, such inventories will be most helpful if they are
initially conducted at least 24 months prior to the date of OPV
withdrawal. Based on the experience with the switch, early out-
reach to self-procuring countries regarding such inventories and
associated procurement planning would be especially important
because many such countries use 2- to 3-year contracts with sup-
pliers. Coordination with self-procuring countries to ensure that
there is some exibility built into their supply contracts could be
helpful. Reaching out to private sector immunization providers
and vaccine distributors about OPV withdrawal so they can fac-
tor it into their procurement planning would also be warranted.
USE OFOPV
Global guidance for the switch recommended that messaging
related to the switch emphasize both the need to stop tOPV use
and the need to use bOPV aer tOPV use stopped [19]. e
global guidance also recommended that such messaging be
aimed primarily at immunization program sta, health work-
ers, health-related nongovernment organizations, and other
key stakeholders. Given the complexity of the rationale for the
Figure2. Countries using oral poliovirus vaccine (OPV) in May 2016 following the global switch from trivalent OPV to bivalent OPV. Data are unpublished and from the
World Health Organization Immunization Repository.
S220 • JID 2017:216 (Suppl 1) • Hampton etal
Table 2. Possible Timeline of Preparations and Activities Related to Oral Poliovirus Vaccine (OPV) Withdrawal
Timinga
Area of Work for OPV Withdrawal
General Coordination Communications
OPV Collection and
Disposal Monitoring Financial Support
≥24 mo prior Date of global OPV with-
drawal set
OPV Withdrawal
Working Group
assembled by GPEI
World Health Assembly
and other relevant
bodies asked to
endorse global OPV
withdrawal date
Manufacturers set OPV
production targets
through OPV with-
drawal date
Countries plan bivalent
OPV orders in coor-
dination with rele-
vant procurement
agency (UNICEF, Pan
American Health
Organization, and
manufacturers) to
avoid overstock
Overall communica-
tions plan devel-
oped for OPV
withdrawal
Ongoing communi-
cations related to
IPV supply and
status of polio
eradication
OPV disposal prac-
tices reviewed and
evaluated by GPEI
in light of trivalent
OPV to bivalent
OPV switch
experience
Discussions held with
vaccine manufac-
turers regarding
OPV disposal
following OPV
withdrawal
OPV withdrawal
incorporated into
work of global and
regional certifica-
tion commissions
All countries that will
need to confirm
withdrawal of OPV
identified
Model developed for
estimating country
level OPV with-
drawal costs and
need for external
support
Country eligibil-
ity criteria for
external support
determined
GPEI budget finalized
for country-level
OPV withdrawal
funding
Mechanism estab-
lished for dis-
bursing funds to
countries
18–24 mo prior Detailed global plan and
guidelines developed for
OPV withdrawal
Procurement planning
guidelines developed
for countries
WHO and UNICEF
regional coordina-
tors hired for OPV
withdrawal
Core reference
materials for
global advocacy
and awareness
developed on
OPV withdrawal
Once decision on
timing is con-
firmed, letter on
OPV withdrawal
disseminated
to ministers of
health, including
need to budget
for OPV
Detailed guidelines
for OPV disposal
developed
Detailed global plan
for monitoring
OPV withdrawal
developed
Broad estimate of
funds for OPV
withdrawal
included in
countries’ annual
budgets
Materials developed
for countries to
apply for external
support
12–18 mo prior OPV withdrawal guidance,
tools, applications, and
other information, includ-
ing training materials on
OPV disposal and with-
drawal monitoring, pro-
vided from global level to
regions, including through
global workshop on plan-
ning for OPV withdrawal
National OPV with-
drawal coordinators
identified and OPV
withdrawal coordi-
nation committees
established
Continued coordination
with manufacturers
and countries regard-
ing OPV production
and distribution
Full package of
communica-
tions guidance
and materials
developed and
disseminated
Countries conduct
OPV inventories
Mechanism estab-
lished for review-
ing requests for
external support
7–12 mo prior Regional workshops for
national OPV withdrawal
coordination staff on plan-
ning for OPV withdrawal,
including OPV disposal
and monitoring OPV
withdrawal
OPV withdrawal guidance,
tools, applications, and
other information pro-
vided from regional level
to countries
National OPV with-
drawal plans
developed
Continued coordination
with manufacturers
and country vaccine
procurement officials
National media
planning
Outreach begins
to health pro-
fessional organi-
zations and key
stakeholders,
CSOs, NGOs,
and others
National OPV disposal
plans developed as
part of OPV with-
drawal plans
Agreements with
private sector
disposal contrac-
tors established if
necessary
National OPV with-
drawal monitoring
plans developed
in conjunction
with overall OPV
withdrawal and
disposal plans
Detailed national
budgets for OPV
withdrawal and dis-
posal developed
Countries’ requests
for external sup-
port submitted to
and reviewed by
GPEI
External support
funds disbursed to
countries
Full Global Withdrawal ofOPV • JID 2017:216 (Suppl 1) • S221
Timinga
Area of Work for OPV Withdrawal
General Coordination Communications
OPV Collection and
Disposal Monitoring Financial Support
6 wk–6 mo
prior
National materials and
documents for OPV with-
drawal, including OPV
disposal and withdrawal
monitoring, developed
and printed
Subnational OPV with-
drawal coordinators
identified
Trainings held for
national and subna-
tional immunization
staff
All sites involved with
OPV withdrawal
identified
Last distribution of OPV
to countries
Global, regional,
and national
media outreach
begins
Outreach begins
to private sector
immunization
providers
Trainings held for staff
involved with OPV
disposal
Sites for OPV disposal
identified
Countries conduct
OPV inventories
OPV stocks redistrib-
uted and OPV use
maximized to min-
imize the amount
of OPV on hand by
OPV withdrawal
date
NOWCC established
National and sub-
national OPV
withdrawal moni-
toring coordinators
identified
Sites to be monitored
for OPV withdrawal
identified
2–6wk prior Trainings held for
remaining national
and subnational
immunization staff
Global, regional,
and national
media outreach
continues
Trainings held for
remaining staff
involved with OPV
disposal
Monitors for OPV
withdrawal
recruited
0–14 d prior OPV withdrawn from
cold chain stores and
health facilities
Global, regional,
and national
media outreach
continues
Media monitoring
begins
Monitors for OPV
withdrawal trained
and equipped
Private sector health
facilities compen-
sated for unexpired
OPV if necessary
0 d–4wk after Problems with OPV
withdrawal iden-
tified by monitors
addressed
Issues manage-
ment plans
implemented in
response to any
problems with
OPV withdrawal
OPV disposed of
Problems with OPV
disposal identi-
fied by monitors
addressed
Visits to cold chain
stores, selected
health facilities,
and disposal sites
by monitors
NOWCCs review
reports from mon-
itors and other
sources
NOWCCs submit
initial OPV with-
drawal report to
government and
the WHO
1–3 mo after Problems with OPV
withdrawal iden-
tified by monitors
addressed
Formal evaluation of
OPV withdrawal
communications
efforts
Problems with OPV
disposal identi-
fied by monitors
addressed
Visits to remaining
health facilities
and any disposal
or cold chain sites
needing repeat
visits
NOWCCs review
reports from
immunization staff
and other sources
NOWCCs submit final
OPV withdrawal
reports to govern-
ment and the WHO
≥3 mo after Problems with contin-
ued use or storage of
OPV addressed
Global Polio
Laboratory
Network monitors
for use of OPV
Immunization pro-
gram staff and
supervisors alert
for any remaining
OPV
Financial reports on
external support
funds submitted to
GPEI by countries
Recall of unspent
external support
funds
Abbreviations: CSO, civil society organization; GPEI, Global Polio Eradication Initiative; NGO, nongovernmental organization; NOWCC, National OPV Withdrawal Certification Committee;
UNICEF, United Nations Children’s Fund; WHO, World Health Organization.
aValues indicate timing of completion of work relative to the global OPV withdrawal date.
Table2. Continued
S222 • JID 2017:216 (Suppl 1) • Hampton etal
switch, communications activities aimed at the general public,
including high prole switch-related ceremonies, were not rec-
ommended in most contexts. With OPV withdrawal, however,
communications messages can be much simpler, focusing on
the need to stop all OPV use because all wild polioviruses have
been certied as eradicated. is more simple and positive mes-
sage will be appropriate for public communications and would
complement outreach eorts and trainings aimed specically
at healthcare workers and immunization program sta. Several
countries have found that very limited tOPV use continued for
months aer the ocial switch date, when all tOPV use should
have stopped. For example, in Hyderabad and Ahmedabad
in India, postswitch tOPV use was found in a small number
of private clinics, most of which were very small facilities not
aliated with professional medical organizations [20]. Broader,
more direct communications messages both leading up to and
following the full withdrawal of OPVs might reduce the like-
lihood of OPVs being used beyond the global withdrawal of
OPVs outside of any needed outbreak responses by helping to
reach all clinics and facilities with the necessary information.
Training of immunization and logistics sta at the global,
regional, national, and local levels was essential to the success
of the switch [8] and will also be needed for OPV withdrawal.
Experience with the switch suggests that trainings that can
disseminate guidance and build technical assistance capacity
regarding OPV withdrawal should ideally begin at the global
level at least a year prior to OPV withdrawal (Table 2). Trainings
related to selected specic tasks, such as the OPV inventories
needed to inform procurement planning, may need to begin
even earlier. e global training would be followed by similar
regional trainings or planning workshops and then by national
and local-level trainings for immunization program sta and
health workers who use OPV. Preparation of training mate-
rials will need to start at least several months beforehand. As
with the switch, global materials developed by GPEI partner
organizations, particularly the WHO’s Expanded Program on
Immunization (EPI), can help with the development of regional,
country, and local materials, although these materials will need
to be adapted to local contexts. At a minimum, trainings and
planning sessions should explain the rationale for OPV with-
drawal, describe the steps needed to successfully execute it, and
identify who is responsible for those steps and the correspond-
ing timelines. Plans for OPV withdrawal developed at all levels
will similarly need to identify the steps needed to successfully
withdraw OPV, how and when to carry out those steps, and who
is responsible for each step.
Several measures not undertaken for the switch could poten-
tially aid in ensuring that use of all bOPV stops at the time of
OPV withdrawal. Expiration dates of bOPV manufactured aer
the date of OPV withdrawal has been set could be tied to the
withdrawal date, regulators could revoke the licensure of bOPV
but not mOPV, or the packaging of bOPV could be altered to
facilitate its tracking, perhaps through the integration of elec-
tronic devices into the label, barcode, or vial. However, all of
these measures would require a great deal of cooperation from
vaccine manufacturers and regulators that may not be forthcom-
ing, and eorts to implement any of them would need to start
long before the date of OPV withdrawal. Great care would also
be needed to ensure that these measures did not result in any
unintended problems.
WITHDRAWAL OFOPV
Even if the amount of bOPV remaining on the date of OPV
withdrawal is successfully minimized, it will still be import-
ant to remove any remaining OPV vials from the cold chain to
preclude its use aer the withdrawal date. While use of bOPV
within a few weeks or even months of the date of general OPV
withdrawal is unlikely to lead to the emergence of new cVD-
PVs, especially if population immunity to type 1 and 3 poliovi-
rus infection is high at the time of OPV withdrawal [10, 13], its
continued storage in the cold chain and intentional or acciden-
tal use long aer OPV withdrawal would be more problematic
[11]. Fortunately, the logistics of removing all OPV vials from
the cold chain will likely be simpler than those of the switch.
For example, the possibility of health workers confusing tOPV
and bOPV was a serious concern during the switch but will
not be an issue for full OPV withdrawal. ese simpler logis-
tics suggest that tight synchronization of OPV withdrawal is
possible.
In the case of the switch, aspirational goals were set, to com-
plete the switch globally within 2 weeks and to have individ-
ual countries select a single day on which all health facilities
stopped use of tOPV and started use of bOPV and health sta
withdrew tOPV from storage nationwide. ese goals were
logistically challenging, but aiming for them proved eective
in terms of global synchronization [8]. Of the 150 countries
and territories using OPV as of April 2016 (5 of the 155 coun-
tries and territories using OPV in 2015 ceased all routine pro-
grammatic use of OPV before April 2016), all reported ceasing
tOPV use by 12 May 2016, only 11days aer the end of the
ocial 17 April—1 May 2016 switch window [3]. A similar,
aspirational goal would likely work well for OPV withdrawal,
albeit with minor changes to simplify the logistics involved.
For example, all health facilities and countries could be asked
to stop bOPV use and withdraw all OPV not being used for
outbreak responses no later than a specied global withdrawal
date. Countries could be given the option of removing all OPV
vials from all levels of their cold chains, starting up to 2 weeks
before the global withdrawal date if other dates during that
period would be more practical for them. Countries could also
be given the option of actually withdrawing all OPV vials from
cold chain stores over 3days instead of just 1day, to reduce the
number of personnel and vehicles needed at one time to pick up
remaining OPV vials.
Full Global Withdrawal ofOPV • JID 2017:216 (Suppl 1) • S223
DISPOSAL OF WITHDRAWNOPV
e most certain way to ensure that OPV is not used aer its
withdrawal is to inactivate and destroy all OPV remaining at
that time. Clear guidance that all OPV vials outside of out-
break-response stockpiles need to be destroyed aer the date
for OPV withdrawal will reinforce this message for immuni-
zation program sta. Condence that all OPV vials have been
destroyed outside of global stockpiles would be enhanced by
careful monitoring and documentation of OPV disposal eorts,
including comparisons between the amounts of OPV known to
be disposed of and the amounts of OPV documented in inven-
tories at the time of OPV withdrawal.
Guidance provided to countries by GPEI and EPI regarding
OPV disposal should explain a range of options in detail that
can be adapted to the policies and capabilities of individual
countries. Adetailed survey of countries regarding their expe-
rience with selecting and executing methods of tOPV disposal,
as well as a careful literature review, could help improve the
quality of the guidance provided on disposal of OPV. Ideally,
any remaining OPV vials will be collected from individual cold
chain stores and then inactivated and destroyed at centralized
locations that can cover entire districts, provinces, or coun-
tries [21]. Such an approach would facilitate monitoring of dis-
posal and use of relatively ecient disposal methods. While all
remaining OPV vials can probably be destroyed within a month
of the date of full OPV withdrawal, further research could help
to better dene a realistic time frame. Strong planning and
preparation for transporting, inactivating, and disposing of
withdrawn OPV that begins well in advance of OPV withdrawal
could help countries minimize the time needed to complete the
disposal of OPV.
MONITORING AND CONFIRMING THE WITHDRAWAL
OFOPV
Monitoring the withdrawal and destruction of OPV at local,
country, regional, and global levels will help boost motiva-
tion for OPV withdrawal; provide an opportunity to identify,
remove, and destroy any remaining OPV; and conrm that OPV
will no longer be used [9]. e existence of a transparent mon-
itoring and conrmation system will encourage the synchroni-
zation of OPV withdrawal because it will give countries more
condence that other countries will also stop using OPV [22].
Conrming full OPV withdrawal may be even more important
than was conrming the completion of the switch because the
stakes involved with polio outbreaks that occur aer OPV with-
drawal will be higher.
In many ways, the monitoring and validation of the switch
provide a model for monitoring and conrming the com-
pleteness of eorts to withdraw and destroy OPV [3, 9]. For
tOPV withdrawal, monitors visited all vaccine stores from the
national to the district levels, as well as a purposively selected
sample of high-risk health facilities, but monitors did not assess
tOPV disposal sites. Avalidation committee reviewed the mon-
itors’ ndings in each country and assessed whether tOPV
had been fully removed from the supply chain, but it did not
assess whether the tOPV had been disposed of aer removal.
e national government received the validation committee’s
assessment and transmitted it to the WHO, ideally within 2
weeks of that country’s ocial cessation of tOPV use. Of the
155 countries asked to provide switch validation reports to
WHO, 147 (95%) provided them within a month of the last day
of the switch window [9]. Countries in the Americas took an
even more stringent approach by having national immuniza-
tion program supervisors visit all health facilities and by having
the Regional Certication Commission of the Americas review
countries’ validation reports and ask for additional information
or corrective measures if needed [23].
Although the vast majority of tOPV was withdrawn as planned
during the switch [9], developments since the switch have indi-
cated possible areas for improvements regarding monitoring
and conrmation of OPV withdrawal. National immunization
program supervisors in multiple countries in the Americas
found tOPV at multiple health facilities that were not included
in the sample of facilities visited by monitors, suggesting that
tOPV also might have remained at facilities not visited by
monitors in other regions. Expanding the proportion of health
facilities visited by monitors could help reduce the likelihood
of such facilities retaining OPV aer its withdrawal, as could
having monitors visit a representative sample of health facili-
ties in addition to high-risk facilities, having national immuni-
zation program supervisors visit all public facilities and report
on their ndings, and checking reports of OPV withdrawn and
destroyed against records of OPV inventories. Identifying all of
the private sector end users of bOPV with the help of vaccine
manufacturers, distributors, and professional organizations and
then monitoring a portion of these sites could help ensure that
all OPV is removed from the private sector.
In a small number of countries, the withdrawal and disposal
of tOPV took signicantly longer than expected, sometimes
because of last-minute governmental delays [24]. Involving the
Global Commission for Certication of Poliovirus Eradication
and all of the related regional certication commissions in
reviewing countries’ reports on their OPV withdrawal and dis-
posal monitoring results might further encourage governments
to fully withdraw and dispose of OPV in a timely manner and
would position the certication commissions to assist with
responses to problems with OPV withdrawal.
Although more time may be needed during OPV withdrawal
than during the switch for the collection and reporting of infor-
mation from visits to cold stores, health facilities, and disposal
sites because of the potentially greater number of sites that will
need to be visited, it will still be important to limit the time
frame of the monitoring and validation phase. For example, the
S224 • JID 2017:216 (Suppl 1) • Hampton etal
monitoring and validation phase could be extended from 2 weeks
to 3 or 4 weeks from the date of OPV withdrawal, to better align
with the amount of time most countries actually required for
switch monitoring and validation. Even aer the end of formal
monitoring visits to conrm the withdrawal of all OPV, national
immunization program supervisors should look for OPV during
routine supervisory visits and remove and dispose of any they
nd. e Global Polio Laboratory Network will supplement the
work of monitors and supervisors by performing surveillance
for OPV use through its ability to detect the attenuated Sabin
viruses found in OPV in environmental samples or stool sam-
ples [20]. Detection of attenuated Sabin viruses >4months aer
cessation of OPV use in a given area should trigger follow-up
investigations to search for any OPV still inuse.
Unlike the other components of OPV withdrawal, the moni-
toring and conrmation process could potentially involve more
than just the countries that are still using bOPV at the date of
OPV withdrawal or the countries that continued to use OPV
aer the switch (Figure2). To fully minimize the possibility of
OPV being used aer its withdrawal, all countries that have ever
used OPV, including those that ceased using it years before the
switch, should ideally conrm that all of their OPV has either
been (1) withdrawn and destroyed or (2) safely contained in an
approved poliovirus-essential facility. However, most if not all
of the countries that had stopped OPV use before the time of
the switch are countries with adequate sanitation and immuni-
zation schedules with multiple doses of IPV, and many of them
are upper-income countries with temperate climates [25]. All
of these factors reduce the likelihood that use of small amounts
of OPV in these countries aer OPV cessation could cause
outbreaks of polio. As a result, if these countries participate in
eorts to conrm that OPV has been withdrawn, much more
limited searches than those undertaken in countries using OPV
up until the date of its withdrawal may be appropriate.
FINANCIAL SUPPORT FOR OPV WITHDRAWAL
Given the importance of executing and conrming OPV with-
drawal in a synchronized manner, additional resources beyond
what is available for routine national immunization program oper-
ations may be needed [26]. For example, additional supplies and
sta may be needed for training, communications, transporting
and disposing of withdrawn OPV, and monitoring and conrming
the withdrawal and disposal. Despite the dierences in scope, it is
quite possible that similar resources will be needed overall for com-
plete OPV withdrawal as were needed for the switch. While some
areas of work, such as logistics, may cost less since there will be no
distribution of new vaccine involved, others, such as monitoring,
may require a more stringent eort and therefore more personnel
and transport resources. As with the switch, some countries may
require external nancial assistance to ensure that adequate train-
ing and communications activities are completed, in addition to
timely completion of OPV withdrawal. Countries that were able
to use GPEI-funded sta and equipment to support the switch
may need to nd alternatives for OPV withdrawal since associ-
ated GPEI funding will likely have declined by that time [27]. e
amount of external assistance required may be minimized if the
date of OPV withdrawal is set well in advance (ie, 18–24months)
to allow national governments, local donors, and in-country part-
ners to include the resources needed for the switch in their regu-
lar budgets. Based on the experience with the switch, some select
activities, such as physical vaccine inventories to inform procure-
ment decisions, would greatly benet from having funding avail-
able at least 18months prior to the date of OPV withdrawal.
If the date of OPV withdrawal and associated guidelines are
not established early enough to allow countries, manufacturers,
and other stakeholders to adequately plan, prepare, and bud-
get, the amount of external resources that will be needed for
successful OPV withdrawal will increase. For example, without
certainty about the date of OPV withdrawal or the quantities
of bOPV needed until that date, manufacturers may not pro-
duce sucient bOPV. If there is uncertainty about bOPV sup-
ply needs when manufacturers must make decisions about how
much bOPV to produce during the nal period before OPV
withdrawal, GPEI may need to work with manufacturers to
consider options for ensuring an ample supply of bOPV. Such
options many include sharing of nancial risk or bulk stockpil-
ing [13, 16]. Similarly, at a country level, GPEI may nd it expe-
dient to buy back bOPV from governments or private providers
if they overstock because of uncertainty about plans for OPV
withdrawal, particularly if a universal OPV expiration date is
not set to coincide with the date of OPV withdrawal.
CONCLUSIONS
In many ways, the experience with the global switch from tOPV
to bOPV can help inform the eventual full global withdrawal of
OPV, although the dierences in context between the two and
the detection of limited tOPV use aer the switch suggest that
some changes in procedures might be needed [8, 9, 20, 26, 28].
Given the potentially disastrous consequences of polio outbreaks
caused by cVDPVs following OPV withdrawal [25, 29], it will be
important to ensure that no OPV remains outside of polio-out-
break-response stockpiles or areas conducting outbreak-response
campaigns. Setting a reasonably rm date for OPV withdrawal
as far ahead of the withdrawal date as possible (ideally at least
24 months), involving GPEI partner support as appropriate, and
beginning preparations as soon as the date is set would greatly
enhance the OPV withdrawal process and would help minimize
the associated costs and need for donor nancial support. A
shorter lead time would provide valuable exibility for decisions
about when to stop use of bOPV in the context of uncertainty
about whether or not WPV1 and WPV3 had been eradicated,
but it may also increase the cost of OPV withdrawal. If OPV
Full Global Withdrawal ofOPV • JID 2017:216 (Suppl 1) • S225
withdrawal is thorough, comprehensive, and well synchronized,
it will eectively complement other eorts underway or planned
to reduce the risk from polio outbreaks from VDPVs aer all wild
polioviruses are eradicated. ese eorts include the develop-
ment of a new, extremely attenuated polio vaccine [30]; the global
introduction of IPV [3, 5, 7]; the conduct of bOPV SIAs shortly
before OPV withdrawal [12, 13]; the maintenance of monovalent
OPV stockpiles for rapid response to polio outbreaks [3, 5]; the
operation of a global polio surveillance system that can quickly
detect polio outbreaks [31]; and the containment of polioviruses
held in research and vaccine manufacturing facilities [32]. Taken
with these other measures, the successful full withdrawal of OPV
will be a key step toward ensuring a polio-free world.
Notes
Acknowledgments. We thank the participants in the September 2016
Global Polio Eradication Initiative Immunization Systems Management
Group meeting in Atlanta, Georgia, for insightful discussions that helped to
inform this article, and Becky Maholland, Division of Emergency Operations
Situational Awareness Geographic Information Systems, Centers for Disease
Control and Prevention, for the creation of the maps for the article.
Disclaimer. e ndings and conclusions in this article are those of
the authors and do not necessarily represent the ocial position of the
World Health Organization, UNICEF, the Centers for Disease Control and
Prevention, or the Task Force for Global Health.
Financial support. is work was supported by the World Health
Organization; the UNICEF; the Centers for Disease Control and Prevention;
and the Task Force for Global Health, on behalf of the Bill and Melinda
Gates Foundation. M. P. and J. G. were supported by the Bill and Melinda
Gates Foundation (grant OPP1095024).
Supplement sponsorship. is work is part of a supplement coordi-
nated by the Task Force for Global Health with funding provided by e
Bill and Melinda Gates Foundation and the Centers for Disease Control
and Prevention.
Potential conicts of interest. All authors: No reported conicts.
All authors have submitted the ICMJE Form for Disclosure of Potential
Conicts of Interest. Conicts that the editors consider relevant to the con-
tent of the manuscript have been disclosed.
References
1. Morales M, Tangermann RH, Wassilak SG. Progress toward polio eradication -
worldwide, 2015-2016. MMWR Morb Mortal Wkly Rep 2016; 65:470–3.
2. Kew OM, Cochi SL, Jafari HS, etal. Possible eradication of wild poliovirus type
3--worldwide, 2012. MMWR Morb Mortal Wkly Rep 2014; 63:1031–3.
3. Hampton LM, Farrell M, Ramirez-Gonzalez A, et al.; Immunization Systems
Management Group of the Global Polio Eradication Initiative. Cessation of tri-
valent oral poliovirus vaccine and introduction of inactivated poliovirus vaccine
- worldwide, 2016. MMWR Morb Mortal Wkly Rep 2016; 65:934–8.
4. Hampton L. Albert Sabin and the coalition to eliminate polio from the Americas.
Am J Public Health 2009; 99:34–44.
5. Global Polio Eradication Initiative Immunization Systems Management Group.
Introduction of inactivated poliovirus vaccine and switch from trivalent to biva-
lent oral poliovirus vaccine - worldwide, 2013–2016. MMWR Morb Mortal Wkly
Rep 2015; 64:699–702.
6. Jorba J, Diop OM, Iber J, Sutter RW, Wassilak SG, Burns CC. Update on vac-
cine-derived polioviruses - worldwide, January 2015-May 2016. MMWR Morb
Mortal Wkly Rep 2016; 65:763–9.
7. Global Polio Eradication Initiative. Polio Eradication and Endgame Strategic Plan
2013–2018. Document WHO/POLIO/13.02. http://www.polioeradication.org/
Portals/0/Document/Resources/StrategyWork/PEESP_EN_US.pdf.
8. Ramirez Gonzalez A, Farrell M, Menning L, etal. Implementing the synchronized
global switch from trivalent to bivalent oral polio vaccines – lessons learned from
the global perspective. J Infect Dis 2017; 216 (suppl 1):S183–92.
9. Farrell M, Hampton LM, Shendale S, etal. Monitoring and validation of the global
replacement of tOPV with bOPV, April-May, 2016. J Infect Dis 2017; 216 (suppl 1):
S193–201.
10. Duintjer Tebbens RJ, Hampton LM, ompson KM. Implementation of coor-
dinated global serotype 2 oral poliovirus vaccine cessation: risks of potential
non-synchronous cessation. BMC Infect Dis 2016; 16:231.
11. Duintjer Tebbens RJ, Hampton LM, ompson KM. Implementation of coordi-
nated global serotype 2 oral poliovirus vaccine cessation: risks of inadvertent tri-
valent oral poliovirus vaccine use. BMC Infect Dis 2016; 16:237.
12. ompson KM, Duintjer Tebbens RJ. Modeling the dynamics of oral poliovirus
vaccine cessation. J Infect Dis 2014; 210:S475–84.
13. Duintjer Tebbens RJ, Hampton LM, Wassilak SGF, Pallansch MA, Cochi SL,
ompson KM. Maintenance and intensication of bivalent oral poliovirus vac-
cine use prior to its coordinated global cessation. J Vaccines Vaccin 2016; 7:340.
doi:10.4172/2157-7560.1000340.
14. UNICEF. OPV. Available at: https://www.unicef.org/supply/les/OPV.pdf.
Accessed December 30, 2016 2016.
15. Decina D, Fournier-Caruana J, Takane M, Ali Dehaghi RO, Sutter R. Regulatory
elements of the withdrawal of type 2 oral polio vaccine (OPV2): Lessons learned.
J Infect Dis 2017; 216 (suppl 1):S46–51.
16. Rubin J, Ottosen A. Managing the planned cessation of a global supply market: les-
sons learned from the global cessation of trivalent oral poliovirus vaccine market.
J Infect Dis 2017; 216 (suppl 1):S40–5.
17. World Health Organization. 15th WHO/UNICEF consultation with OPV & IPV
manufacturers and national regulatory authorities. http://www.who.int/immuni-
zation/diseases/poliomyelitis/endgame_objective2/oral_polio_vaccine/WHO_
UNICEF_consultation_28July2016_Note_for_the_record.pdf?ua=1. Accessed 1
December 2016.
18. World Health Organization. World Health Assembly resolution: poliomyelitis.
Geneva, Switzerland: World Health Organization, 2015. http://apps.who.int/gb/
ebwha/pdf_les/WHA68/A68_R3-en.pdf. Accessed 30 December 2016.
19. World Health Organization. OPV switch communications planning guide. http://
www.who.int/entity/immunization/diseases/poliomyelitis/endgame_objective2/
oral_polio_vaccine/OPV_Switch-communications_planning_guide.docx?ua=1.
Accessed 30 December 2016.
20. Bahl S, Hampton LM, Bhatnagar P, etal. Notes from the eld: detection of sabin-
like type 2 poliovirus from sewage aer global cessation of trivalent oral poliovirus
vaccine - Hyderabad and Ahmedabad, India, August-September 2016. MMWR
Morb Mortal Wkly Rep 2017; 65:1493–4.
21. Global Polio Eradication Initiative. Technical guidance: mOPV2 vaccine man-
agement, monitoring, removal, and validation. http://polioeradication.org/
wp-content/uploads/2016/11/Technical-guidance-mOPV2-management-
monitoring-removal-and-validation_Oct2016_EN.pdf. Accessed 19 January
2017.
22. ompson KM, Duintjer Tebbens RJ. e case for cooperation in managing and
maintaining the end of poliomyelitis: stockpile needs and coordinated OPV cessa-
tion. Medscape J Med 2008; 10:190.
23. Pan American Health Organization. Toward the end of polio: the vaccine ‘switch’ in the
Americas. http://www.paho.org/hq/index.php?option=com_content&view=ar-
ticle&id=12862%3Atoward-end-polio-vaccine-switch-in-the-americas&-
catid=740%3Apress-releases&Itemid=1926&lang=en. Accessed 30 December
2016.
24. Fahmy K, Hampton LM, Langar H, etal. Introduction of inactivated polio vac-
cine, withdrawal of type 2 oral polio vaccine, and routine immunization strength-
ening in the Eastern Mediterranean Region. J Infect Dis 2017; 216 (suppl 1):
S86-93.
25. Duintjer Tebbens RJ, Pallansch MA, Cochi SL, Wassilak SG, ompson KM. An
economic analysis of poliovirus risk management policy options for 2013–2052.
BMC Infect Dis 2015; 15:389.
26. Shendale S, Farrell M, Hampton LM, etal. Financial support to eligible countries
for the switch from trivalent to bivalent oral polio vaccine—lessons learned. J
Infect Dis 2017; 216 (suppl 1):S52–6.
27. Global Polio Eradication Initiative. Financial resource requirements 2013–2019
(as of 1 April 2016). Geneva, Switzerland: World Health Organization, 2016.
28. Wanyoike S, Ramirez Gonzalez A, Dolan S, etal. Disposing of excess vaccines aer
the withdrawal of oral polio vaccine. J Infect Dis 2017; 216 (suppl 1):S202–8.
29. Duintjer Tebbens RJ, Pallansch MA, Wassilak SG, Cochi SL, ompson KM.
Characterization of outbreak response strategies and potential vaccine stockpile
needs for the polio endgame. BMC Infect Dis 2016; 16:137.
30. Duintjer Tebbens RJ, ompson KM. e potential benets of a new poliovi-
rus vaccine for long-term poliovirus risk management. Future Microbiol 2016;
11:1549–61.
31. Snider CJ, Diop OM, Burns CC, Tangermann RH, Wassilak SG. Surveillance sys-
tems to track progress toward polio eradication - worldwide, 2014–2015. MMWR
Morb Mortal Wkly Rep 2016; 65:346–51.
32. Previsani N, Tangermann RH, Tallis G, Jafari HS. World Health Organization
guidelines for containment of poliovirus following type-specic polio eradication -
worldwide, 2015. MMWR Morb Mortal Wkly Rep 2015; 64:913–7.
... Because global polio eradication is predicated on the achievement of the eradication of paralytic polio due to all live polioviruses, including vaccinerelated viruses [7], eliminating the risk of VAPP and cVDPVs will require stopping all use of OPV in routine immunization services and supplementary immunization activities [8,9]. The Global Commission for the Certification of the Eradication of Poliomyelitis certified the eradication of type 2 poliovirus in 2015 [10] following the last case in 1999 and type 3 poliovirus in 2019 following the last case in 2012 [11], making type 2 and type 3 polioviruses the first human pathogens to be eradicated since smallpox. ...
... The first phase of OPV withdrawal took place in 2016 with the global switch from trivalent OPV (tOPV) to bivalent OPV (bOPV) in the 155 OPV-using countries of the world, through cessation of all manufacturing and distribution of tOPV and its rapid withdrawal from clinics and storage facilities [8,9]. The type 2 vaccine virus was prioritized for removal because type 2 cVDPV (cVDPV2) cases comprised approximately 95% of all cVDPV cases during 2006 to May 2016 and approximately 30% of all VAPP cases. ...
... The type 2 vaccine virus was prioritized for removal because type 2 cVDPV (cVDPV2) cases comprised approximately 95% of all cVDPV cases during 2006 to May 2016 and approximately 30% of all VAPP cases. Additionally, the type 2 OPV vaccine virus is the most infectious and immunogenic of the 3 vaccine virus strains and interferes with the replication of other vaccine strains in the intestinal tract and, hence, the type 1 and 3 vaccine effectiveness using tOPV was lower [2,8,9]. A stockpile of monovalent type 2 (mOPV2) vaccine was established to respond to potential outbreaks of cVDPV2. ...
... The new 2019-2023 GPEI strategic plan includes continued OPV pSIAs in many GPEIsupported countries, but at a decreasing rate between now and the planned timing of globally-coordinated cessation of bivalent OPV (bOPV) (Global Polio Eradication Initiative, 2019). The GPEI led the effort to globally-coordinate cessation of serotype 2 OPV (OPV2) in 2016, and also supported global introduction of one dose of inactivated poliovirus vaccine (IPV) into all national immunization programs (not already using IPV as of 2016) (Hampton et al., 2017). The GPEI motivated IPV introduction by noting that it would offer protection from paralysis due to serotype 2 poliovirus infection for otherwise unprotected IPV recipients. ...
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Background The globally synchronised introduction of inactivated poliovirus vaccine (IPV) and replacement of trivalent oral poliovirus vaccine (OPV) with bivalent OPV (bOPV) were successfully implemented in China's routine immunisation programme in May, 2016. In response to the global shortage of Salk-strain IPV, Sabin-strain IPV production was encouraged to develop and use in low-income and middle-income countries. We assessed the immunogenicity of the current routine poliovirus vaccination schedule in China and compared it with alternative schedules that use Sabin-strain IPV (sIPV) and bOPV. Methods This open-label, randomised, controlled trial recruited healthy infants aged 60–75 days from two centres in Zhejiang, China. Eligible infants were full-term, due for their first polio vaccination, weighed more than 2·5 kg at birth, were healthy on physical examination with no obvious medical conditions, and had no contraindications to vaccination. Infants were randomly assigned (1:1:1) using permuted block randomisation (block size of 12) to one of three polio vaccination schedules, with the first, second, and third doses given at ages 2 months, 3 months, and 4 months, respectively: sIPV-bOPV-bOPV (1sIPV+2bOPV group; current regimen), sIPV-sIPV-bOPV (2sIPV+1bOPV group), or sIPV-sIPV-sIPV (3sIPV group). The primary endpoint was the proportion of infants with seroconversion to each of the three poliovirus serotypes 1 month after the third dose. Serious and medically important adverse events were monitored for up to 30 days after each vaccination. We assessed immunity in the per-protocol population (all children who completed all three vaccinations and had pre-vaccination and post-vaccination laboratory data) and safety in all children who received at least one dose of study vaccine. This trial is registered with Clinicaltrials.gov, NCT03147560. Results Between May 1, 2016, and Dec 1, 2017, we enrolled and randomly assigned 528 eligible infants to one of the three treatment groups (176 in each group); 473 infants (158 in the 1sIPV+2bOPV group, 152 in the 2sIPV+1bOPV group, and 163 in the 3sIPV group) were included in the per-protocol population. 100% seroconversion against poliovirus types 1 and 3 was observed in all three groups. Infants who received an immunisation schedule containing bOPV had significantly higher antibody titres against poliovirus types 1 and 3 than did the sIPV-only group (2048 in all three treatment groups; p<0·0001). Seroconversion against type 2 poliovirus was observed in 98 (62%) infants in the 1sIPV+2bOPV group, 145 (95%) infants in the 2sIPV+1bOPV group, and 161 (99%) infants in the 3sIPV group. No serious adverse events occurred during the study; 14 minor, transient adverse events were observed, with no significant differences across study groups. Interpretation All three study schedules were well tolerated and highly immunogenic against poliovirus types 1 and 3. Schedules containing two or three sIPV doses had higher seroconversion rates against poliovirus type 2 than did the schedule with a single dose of sIPV. Our findings support inclusion of two sIPV doses in the routine poliovirus vaccination schedule in China to provide better protection against poliovirus type 2 than provided by the current regimen. Funding Chinese Center for Disease Control and Prevention and China National Biotec Group Company.
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Oral polio vaccine (OPV) has served as the cornerstone of polio eradication efforts over the past 30 years, trivalent inactivated polio vaccine (IPV) has re-ascended to prominence in the past year, now acting as the sole source of protective immunity against type 2 poliovirus in routine immunization programmes. The Polio Eradication and Endgame Strategic plan 2013–2018, developed by the Global Polio Eradication Initiative (GPEI) outlines the phased removal of OPVs, starting with type 2 poliovirus–containing vaccines and introduction of inactivated polio vaccine in routine immunization to mitigate against risk of vaccine-associated paralytic polio and circulating vaccine-derived poliovirus. Bangladesh J Medicine Jan 2020; 31(1) : 22-28
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Background: Poliomyelitis infection continues to be endemic in few countries despite rigorous efforts for eradication. A new Bivalent Oral Polio Vaccine (BBio bOPV) was tested in a Phase III Clinical study. Methods: An observer blind, randomized, controlled clinical study was conducted comparing BBio bOPV with a licensed bOPV (SII bOPV). Initially in Part 1, 40 children 5-6 years of age were given a single dose of either vaccine in 1:1 ratio. In Part 2, 1080 infants of 6-8 weeks of age were received in 1:1:1:1 ratio one of the 3 lots of BBio bOPV or SII bOPV at 6, 10 and 14 weeks of age. Blood samples were collected to assess neutralizing antibody responses against Polio Type 1 and 3 viruses. Safety of the vaccines were recorded. Results: All children were seroprotected against both Type 1 and Type 3 polioviruses post-vaccination. More than 96% of the infants demonstrated seroconversion as well as seroprotection against both types of polioviruses. The geometric mean titres (GMT) for Type 1 and Type 3 antibodies were comparable between the groups. The 3 lots of BBio bOPV generated similar GMTs of Type 1 and Type 3 antibodies. In total 387 participants reported at least one adverse event and 18 serious adverse events. None of these events were vaccine related. Conclusions: The new bOPV vaccine demonstrated immunogenicity that was non-inferior to a licensed bOPV vaccine. Consistency in immune response by 3 consecutively manufactured lots was also demonstrated. The vaccine did not cause any adverse event. Clinicaltrials.gov.identifier: NCT02766816.
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A prospective observational study was conducted consisting of 21 patients of Juvenile-onset recurrent respiratory papillomatosis, attending the Department of Otorhinolaryngology and Head Neck Surgery at our institution, who underwent surgical excision of the papillomas followed by oral acyclovir postoperatively. The study was aimed to observe the effect of systemic acyclovir on postoperative outcomes in children having recurrent respiratory papillomatosis undergoing primary surgical excision. It was observed that the mean interval between surgeries as well as the number of surgical interventions required was significantly lesser when acyclovir was used as a postoperative adjuvant than when surgery was done alone. Hence, the interval between successive surgeries, or in other words, the time interval between relapse of the disease could be prolonged significantly with the use of postoperative systemic acyclovir. Thus, the disease could be controlled for longer periods and repeated surgeries avoided.
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The global switch from trivalent oral polio vaccine (tOPV) to bivalent oral polio vaccine (bOPV) ("the switch") presented an unprecedented challenge to countries. In order to mitigate the risks associated with country-level delays in implementing the switch, the Global Polio Eradication Initiative provided catalytic financial support to specific countries for operational costs unique to the switch. Between November 2015 and February 2016, a total of approximately US$19.4 million in financial support was provided to 67 countries. On average, country budgets allocated 20% to human resources, 23% to trainings and meetings, 8% to communications and advocacy, 9% to logistics, 15% to monitoring, and 5% to waste management. All 67 funded countries successfully switched from tOPV to bOPV during April-May 2016. This funding provided target countries with the necessary catalytic support to facilitate the execution of the switch on an accelerated timeline, and the mechanism offers a model for similar support to future global health efforts, such as the eventual global withdrawal of bOPV. © The Author 2017. Published by Oxford University Press for the Infectious Diseases Society of America.
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Withdrawal of type 2 oral poliovirus vaccine (OPV) in OPV-using countries required regulatory approval for use of inactivated poliovirus vaccine and bivalent OPV in routine immunization. Worldwide, a variety of mechanisms were used by member states, with some differences in approach observed between inactivated poliovirus vaccine and bivalent OPV. These included acceptance for use of World Health Organization (WHO) prequalified vaccines, registration and licensure pathways, participation in WHO-convened joint reviews of licensing dossiers, as well as pragmatic application of alternatively available mechanisms, when appropriate. Simple but effective tools were used to monitor progress and to record, authenticate, and share information. Essential to achievement of regulatory targets was ongoing communication with key stakeholders, including switch-country national regulatory authorities, vaccine manufacturers, partner organizations, and relevant units within WHO. Understanding of the regulatory environment gained through the OPV switch can be helpful in supporting further stages of the polio end game and other time-sensitive vaccine introduction programs. © The Author 2017. Published by Oxford University Press for the Infectious Diseases Society of America.
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The Polio Eradication and Endgame Strategic Plan 2013-2018 calls for the phased withdrawal of OPV, beginning with the globally synchronized cessation of tOPV by mid 2016. From a global vaccine supply management perspective, the strategy provided two key challenges; (1) the planned cessation of a high volume vaccine market; and (2) the uncertainty of demand leading and timeline as total vaccine requirements were contingent on epidemiology. The withdrawal of trivalent OPV provided a number of useful lessons that could be applied for the final OPV cessation. If carefully planned for and based on a close collaboration between programme partners and manufacturers, the cessation of a supply market can be undertaken with a successful outcome for both parties. As financial risks to manufacturers increase even further with OPV cessation, early engagement from the cessation planning phase and consideration of production lead times will be critical to ensure sufficient supply throughout to achieve programmatic objectives. As the GPEI will need to rely on residual stocks including with manufacturers through to the last campaign to achieve its objectives, the GPEI should consider to decide on and communicate a suitable mechanism for co-sharing of financial risks or other financial arrangement for the outer years. © The Author 2017. Published by Oxford University Press for the Infectious Diseases Society of America.
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The Global Polio Eradication Initiative has reduced the global incidence of polio by 99% and the number of countries with endemic polio from 125 to 3 countries. The Polio Eradication and Endgame Strategic Plan 2013-2018 (Endgame Plan) was developed to end polio disease. Key elements of the endgame plan include strengthening immunization systems using polio assets, introducing inactivated polio vaccine (IPV), and replacing trivalent oral polio vaccine with bivalent oral polio vaccine ("the switch"). Although coverage in the Eastern Mediterranean Region (EMR) with the third dose of a vaccine containing diphtheria, tetanus, and pertussis antigens (DTP3) was ≥90% in 14 countries in 2015, DTP3 coverage in EMR dropped from 86% in 2010 to 80% in 2015 due to civil disorder in multiple countries. To strengthen their immunization systems, Pakistan, Afghanistan, and Somalia developed draft plans to integrate Polio Eradication Initiative assets, staff, structure, and activities with their Expanded Programmes on Immunization, particularly in high-risk districts and regions. Between 2014 and 2016, 11 EMR countries introduced IPV in their routine immunization program, including all of the countries at highest risk for polio transmission (Afghanistan, Pakistan, Somalia, and Yemen). As a result, by the end of 2016 all EMR countries were using IPV except Egypt, where introduction of IPV was delayed by a global shortage. The switch was successfully implemented in EMR due to the motivation, engagement, and cooperation of immunization staff and decision makers across all national levels. Moreover, the switch succeeded because of the ability of even the immunization systems operating under hardship conditions of conflict to absorb the switch activities. © The Author 2017. Published by Oxford University Press for the Infectious Diseases Society of America.
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Objective: To examine the impact of different bivalent oral poliovirus vaccine (bOPV) supplemental immunization activity (SIA) strategies on population immunity to serotype 1 and 3 poliovirus transmission and circulating vaccine-derived poliovirus (cVDPV) risks before and after globally-coordinated cessation of serotype 1 and 3 oral poliovirus vaccine (OPV13 cessation). Methods: We adapt mathematical models that previously informed vaccine choices ahead of the trivalent oral poliovirus vaccine to bOPV switch to estimate the population immunity to serotype 1 and 3 poliovirus transmission needed at the time of OPV13 cessation to prevent subsequent cVDPV outbreaks. We then examine the impact of different frequencies of SIAs using bOPV in high risk populations on population immunity to serotype 1 and 3 transmission, on the risk of serotype 1 and 3 cVDPV outbreaks, and on the vulnerability to any imported bOPV-related polioviruses. Results: Maintaining high population immunity to serotype 1 and 3 transmission using bOPV SIAs significantly reduces 1) the risk of outbreaks due to imported serotype 1 and 3 viruses, 2) the emergence of indigenous cVDPVs before or after OPV13 cessation, and 3) the vulnerability to bOPV-related polioviruses in the event of non-synchronous OPV13 cessation or inadvertent bOPV use after OPV13 cessation. Conclusion: Although some reduction in global SIA frequency can safely occur, countries with suboptimal routine immunization coverage should each continue to conduct at least one annual SIA with bOPV, preferably more, until global OPV13 cessation. Preventing cVDPV risks after OPV13 cessation requires investments in bOPV SIAs now through the time of OPV13 cessation.
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In 2015, the Global Commission for the Certification of Polio Eradication certified the eradication of type 2 wild poliovirus, 1 of 3 wild poliovirus serotypes causing paralytic polio since the beginning of recorded history. This milestone was one of the key criteria prompting the Global Polio Eradication Initiative to begin withdrawal of oral polio vaccines (OPV), beginning with the type 2 component (OPV2), through a globally synchronized initiative in April and May 2016 that called for all OPV using countries and territories to simultaneously switch from use of trivalent OPV (tOPV; containing types 1, 2, and 3 poliovirus) to bivalent OPV (bOPV; containing types 1 and 3 poliovirus), thus withdrawing OPV2. Before the switch, immunization programs globally had been using approximately 2 billion tOPV doses per year to immunize hundreds of millions of children. Thus, the globally synchronized withdrawal of tOPV was an unprecedented achievement in immunization and was part of a crucial strategy for containment of polioviruses. Successful implementation of the switch called for intense global coordination during 2015-2016 on an unprecedented scale among global public health technical agencies and donors, vaccine manufacturers, regulatory agencies, World Health Organization (WHO) and United Nations Children's Fund (UNICEF) regional offices, and national governments. Priority activities included cessation of tOPV production and shipment, national inventories of tOPV, detailed forecasting of tOPV needs, bOPV licensing, scaling up of bOPV production and procurement, developing national operational switch plans, securing funding, establishing oversight and implementation committees and teams, training logisticians and health workers, fostering advocacy and communications, establishing monitoring and validation structures, and implementing waste management strategies. The WHO received confirmation that, by mid May 2016, all 155 countries and territories that had used OPV in 2015 had successfully withdrawn OPV2 by ceasing use of tOPV in their national immunization programs. This article provides an overview of the global efforts and challenges in successfully implementing this unprecedented global initiative, including (1) coordination and tracking of key global planning milestones, (2) guidance facilitating development of country specific plans, (3) challenges for planning and implementing the switch at the global level, and (4) best practices and lessons learned in meeting aggressive switch timelines. Lessons from this monumental public health achievement by countries and partners will likely be drawn upon when bOPV is withdrawn after polio eradication but also could be relevant for other global health initiatives with similarly complex mandates and accelerated timelines. © The Author 2017. Published by Oxford University Press for the Infectious Diseases Society of America.
Article
Until recently, waste management for national immunization programs was limited to sharps waste, empty vaccine vials, or vaccines that had expired or were no longer usable. However, because wild-type 2 poliovirus has been eradicated, the World Health Organization's (WHO's) Strategic Advisory Group of Experts on Immunization deemed that all countries must simultaneously cease use of the type 2 oral polio vaccine and recommended that all countries and territories using oral polio vaccine (OPV) "switch" from trivalent OPV (tOPV; types 1, 2, and 3 polioviruses) to bivalent OPV (bOPV; types 1 and 3 polioviruses) during a 2-week period in April 2016. Use of tOPV after the switch would risk outbreaks of paralysis related to type 2-circulating vaccine-derived poliovirus (cVDPV2). To minimize risk of vaccine-derived polio countries using OPV were asked to dispose of all usable, unexpired tOPV after the switch to bOPV. In this paper, we review the rationale for tOPV disposal and describe the global guidelines provided to countries for the safe and appropriate disposal of tOPV. These guidelines gave countries flexibility in implementing this important task within the confines of their national regulations, capacities, and resources. Steps for appropriate disposal of tOPV included removal of all tOPV vials from the cold chain, placement in appropriate bags or containers, and disposal using a recommended approach (ie, autoclaving, boiling, chemical inactivation, incineration, or encapsulation) followed by burial or transportation to a designated waste facility. This experience with disposal of tOPV highlights the adaptability of national immunization programs to new procedures, and identifies gaps in waste management policies and strategies with regard to disposal of unused vaccines. The experience also provides a framework for future policies and for developing programmatic guidance for the ultimate disposal of all OPV after the eradication of polio.
Article
The phased withdrawal of oral polio vaccine (OPV) associated with the Polio Eradication and Endgame Strategic Plan 2013-2018 began with the synchronized global replacement of trivalent OPV (tOPV) with bivalent OPV (bOPV) during April - May 2016, a transition referred to as the "switch." The World Health Organization's (WHO) Strategic Advisory Group of Experts (SAGE) on Immunization recommended conducting this synchronized switch in all 155 OPV-using countries and territories (which collectively administered several hundred million doses of tOPV each year via several hundred thousand facilities) to reduce risks of re-emergence of vaccine-derived polioviruses. Safe execution of this switch required implementation of an associated independent monitoring strategy, the primary objective of which was verification that tOPV was no longer available for administration post-switch. This strategy had to be both practical and rigorous such that tOPV withdrawal could be reasonably employed and confirmed in all countries and territories within a discreet timeframe. Following these principles, WHO recommended that designated monitors in each of the 155 countries and territories visit all vaccine stores as well as a 10% sample of highest-risk health facilities within two weeks of the national switch date, removing any tOPV vials found. National governments were required to provide the WHO with formal validation of execution and monitoring of the switch. In practice, all countries reported cessation of tOPV by 12 May 2016 and 95% of countries and territories submitted detailed monitoring data to WHO. According to these data, 272 out of 276 (99%) national stores, 3,741 out of 3.968 (94%) regional stores, 16,144 out of 22,372 (72%) district level stores, and 143,050 out of 595,401 (24%) of health facilities were monitored. These data, along with field reports suggest that monitoring and validation of the switch was efficient and effective, and that the strategies used during the process could be adapted to future stages of OPV withdrawal. © The Author 2017. Published by Oxford University Press for the Infectious Diseases Society of America.
Article
Aim: To estimate the incremental net benefits (INBs) of a hypothetical ideal vaccine with all of the advantages and no disadvantages of existing oral and inactivated poliovirus vaccines compared with current vaccines available for future outbreak response. Methods: INB estimates based on expected costs and polio cases from an existing global model of long-term poliovirus risk management. Results: Excluding the development costs, an ideal poliovirus vaccine could offer expected INBs of US$1.6 billion. The ideal vaccine yields small benefits in most realizations of long-term risks, but great benefits in low-probability-high-consequence realizations. Conclusion: New poliovirus vaccines may offer valuable insurance against long-term poliovirus risks and new vaccine development efforts should continue as the world gathers more evidence about polio endgame risks.