Op v Cessation Framework English

7/30/2019 Op v Cessation Framework English

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Framework for

Nat ional Pol icy

Makers in OPV-UsingCountr ies

Cessa

tionofroutineoralpo

liovaccine

(OPV)

useaf

terglobalp

olioeradication

WHO/POLIO/05.02


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1. Introduction2. Rationale for eventual cessation of oral polio vaccine (OPV) use in routine immunization

after eradication

3. Risks associated with OPV cessation

4. Risk management before, during and after OPV cessation: implementing the prerequisites

for OPV cessation

I Confirmation of interruption of wild poliovirus transmission globally

II Appropriate biocontainment of all polioviruses

III International stockpile of monovalent OPVs (mOPV)

IV Highly-sensitive surveillance for circulating polioviruses

V Procedure for internationally-simultaneous OPV cessation

VI Long-term routine polio immunization policy

5. Timetable for OPV cessation

6. Glossary of terms

Index

1

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Polio eradication - global overview as at 2005

By early 2005, the annual number of polio cases reported globally had been reduced by over 99 %since the Global Polio Eradication Initiative was launched in 1988. In addition, endemic wildpolioviruses had been eliminated from all but six countries in the world (Nigeria, India, Pakistan,Niger, Afghanistan and Egypt), demonstrating that the polio eradication strategies can work in allsettings. Following the large polio epidemic of 2003-2004 in west and central Africa, which spreadto 16 previously polio-free countries, a massive 'intensified' effort has been launched and isanticipated to stop polio transmission globally in the near future.With the 'intensification' of the global polio eradication effort in 2004-2005, preparations arebeing made for simultaneous oral polio vaccine (OPV) cessation soon after assurance of the

complete interruption of wild poliovirus transmission.

"After eradication of wild poliovirus, continued use of oral polio vaccine (OPV) wouldcompromise the goal of a polio-free world." Advisory Committee on Poliomyelitis Eradication(ACPE), Geneva, 21-22 September 2004

In 1988, World Health Assembly (WHA)resolution 41.28 established the goal of polioeradication as 'interruption of wild poliovirustransmission' globally. Since 1999, however,increasing scientific data demonstrate that polioeradication will also require the eventualcessation of OPV use in routine immunization

programmes. Otherwise, the continuedreintroduction of the attenuated polioviruses ofOPV into a polio-free world will result in poliocases due to vaccine-associated paralytic polio,and polio outbreaks due to circulating vaccine-derived polioviruses1.

The international oversight bodies that guide theGlobal Polio Eradication Initiative concluded in2003 and 2004 that OPV cessation should occuras soon as possible after the interruption of wild

poliovirus transmission globally, while population

immunity against polio and surveillancesensitivity for acute flaccid paralysis remain high2.Minimizing the risks associated with stoppingOPV requires careful preparation at the nationaland international levels and, eventually,simultaneous OPV cessation across all remainingOPV-using countries to ensure that no country is

placed at risk of importing a vaccine-derivedpoliovirus from an area where OPV usecontinues.

This document has been developed to providenational health policy makers in OPV-usingcountries with an overview of the rationale, risks,prerequisites and potential timetable for the globalcessation of OPV. Particular emphasis is given tothose activities required at the country level duringthe ongoing 'OPV Cessation Preparatory Phase'.

1. Introduction

1 Conclusions and Recommendations of the Advisory Committee on Poliomyelitis Eradication (ACPE),Geneva, Switzerland, 21-22 September 2004

2 WHO Informal Consultation on Identification and Management of Vaccine-derivedPolioviruses. September 2003, Geneva, Switzerland.

2


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1. Polio Cases due to Vaccine-Associated Paralytic Poliomyelitis (VAPP):the continueduse of OPV will result in a predictable burden of polio disease due to VAPP.

VAPP cases will continue to occur at a rate of 2-4 cases per one million birth cohort,wherever OPV is used. If the OPV utilization patterns of 2005 continued afterconfirmation of the eradication of wild-type poliovirus, between 250 and 500 newVAPP cases would be expected to occur worldwide each year.

While the risk of polio due to wild poliovirus currently outweighs the risk ofVAPP in most countries, this balance will change with confirmation of theinterruption of wild poliovirus transmission globally.

2. Polio Outbreaks due to circulating Vaccine-Derived Polioviruses (cVDPV):thecontinued use of OPV will result in a predictable rate of polio outbreaks due tocVDPVs.

Since 2000, four polio outbreaks due to cVDPVs have been documented inHispaniola (in 2000-2001), the Philippines (in 2001), Madagascar (in 2002) and

China (in 2004), resulting in a total of 31 polio cases. A fifth outbreak wasdescribed retrospectively in Egypt.

While low routine immunization coverage probably contributes to the conditionsthat give rise to cVDPVs, and mass campaigns with OPV eventually stopped eachreported outbreak, it appears that even major improvements in routine polioimmunization coverage would be unlikely to prevent future polio outbreaks dueto such events. Unlike smallpox, the eventual cessation of OPV must besynchronized across all countries so that the risk of cVDPV decreases rapidly anduniformly throughout the world, thus ensuring that no country is placed at riskof importing a cVDPV from an area where OPV use continues.

OPV is the appropriate and only recommended polio vaccine for achieving the eradication of wildpolioviruses worldwide3. However, OPV can alsocause in rare instances paralytic polio cases.Consequently, once wild poliovirus transmissionhas been interrupted globally, the attenuatedSabin poliovirus strains used in OPV couldcontinue to cause polio cases and outbreaks at a

rare but predictable rate. Therefore, thecontinued use of OPV after the interruption of

transmission of wild poliovirus is increasinglyconsidered inconsistent with eradication. Poliocases due to vaccine-associated paralyticpoliomyelitis (VAPP) and outbreaks due tocirculating vaccine-derived polioviruses(cVDPVs), are the two main reasons foreventually stopping the use of OPV for routineimmunization in all countries.

2. Rationale for eventual cessation oforal polio vaccine (OPV) use in routine

immunization after eradication

3 Hull HF, Lee JW. Sabin, Salk or sequential? The Lancet. March 1996 3


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In addition to these primary reasons for eventuallystopping routine OPV immunization, continueduse of the vaccine would, rarely, lead to prolongedexcretion (> 6 months) of a VDPV from a personwith a severe primary immunodeficiency

syndrome. Theoretically, these 'iVDPVs' couldthen reintroduce poliovirus into the generalpopulation. In 40 years of OPV use, 28 iVDPVshad been documented by end-2004, though nonehad been shown to cause secondary cases. Four ofthese were 'chronic' iVDPVs (excretion > 36months), all of which occurred in high-incomecountries.

Once eradication of wild poliovirus has beenconfirmed, the public health benefits of routineimmunization with OPV will no longer outweighthe burden of disease due to VAPP and cVDPVs.Despite these shortcomings of OPV, successful

eradication depends on maintaining highcoverage with this vaccine until the point ofsimultaneous OPV cessation. Decreases in OPVimmunization coverage prior to the time of OPVcessation would put polio-free countries at risk ofwild poliovirus importations and cVDPVs.

4

OPV FactsIf the worldwide OPV utilization patterns of 2005 continued after confirmation of theeradication of wild-type poliovirus, it is expected that there would be:

250 to 500 cases of VAPP per year, Up to one polio outbreak due to a cVDPV per year.

Once eradication of wild poliovirus has been confirmed, the public health benefits of routineimmunization with OPV may no longer outweigh the burden of disease due to VAPP andcVDPVs.

Hispaniola2000

22 cases

Madagascar2002

4 cases

China2004

2 cases

Philippines2001

3 cases

Polio outbreaks due to circulating vaccine-derivedpolioviruses (cVDPV), 2000-2004


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Although the burden of disease caused by VAPP

and cVDPVs will eventually outweigh thebenefits of routine OPV immunization, OPVcessation is associated with risks that must bemanaged appropriately.

For most OPV-using countries, the risksassociated with OPV cessation can be summarizedin two main categories:

1. Immediate risk of cVDPV emergence: oncecountries simultaneously stop using OPV, there willbe a time-limited, rapidly decreasing risk that avaccine-derived poliovirus could regainneurovirulence and begin to circulate, which wouldrequire an outbreak response. For any individualcountry, the risk of such an outbreak is remote anddiminishes rapidly over the 12-24 month periodimmediately following simultaneous OPVcessation. This risk will be lowest in countries withhigh routine immunization coverage at the time ofOPV cessation. Although the risk of a cVDPVoutbreak is low for individual countries, there is an

estimated 65-90% chance of such an outbreakoccurring somewhere in the world during the firstyear after simultaneous OPV cessation. This riskwill fall to 5-15% by the end of the second year ifOPV cessation can be implemented simultaneouslyworldwide, and will reduce further to 1-5% by theend of the third year.

2. Medium and long-term risks of poliovirusre-introduction: once it has been verified thatOPV is no longer being used in routineimmunization anywhere, the greatest risks to apolio-free world will be the inadvertent re-introduction of a wild, vaccine-derived or Sabinstrain of poliovirus from a polio vaccinemanufacturing site, a research facility or adiagnostic laboratory. This risk is low, asdocumented poliovirus re-introductions wererare even prior to the adoption of internationalguidelines for the containment of polioviruses bythe World Health Assembly in 1999. This risk

will diminish further as all countries fullyimplement appropriate biocontainment ofpolioviruses and verify that achievement.Achieving appropriate containment of allpolioviruses will be extremely important giventhat the potential harmful consequences of apoliovirus re-introduction will increasesubstantially as polio-susceptible individualsaccumulate after OPV cessation. The risk ofreintroduction of a vaccine-derived poliovirusfrom an iVDPV is still lower, for the reasons

noted in section 2 above.

Although the risks associated with stopping OPVuse in routine immunization are relatively small,these risks can be further reduced throughinternational implementation of appropriate riskmanagement strategies before, during and afterOPV cessation. Implementation of these riskmanagement strategies or prerequisites willinvolve close oversight by National Policy

Makers.

3. Risks associated with OPV cessation

5

Two main risk-categories associated withOPV cessation:1. Immediate risk of cVDPV emergence2. Medium and long-term risks of poliovirusre-introduction from a vaccinemanufacturing site, research facility ordiagnostic laboratory

Time (years) after T0

OPV (without SIAs)

IPV

No routine

ProbabilityofatleastonecVDPVoutbreak

0.00

0.10

0.20

0.30

0.40

0.50

0.60

0.70

0.80

0.90

1.00

0 1 2 3 4 5 6 7 8 9

Risk of cVDPV outbreaks*

* Based on Duintjer-Tebbens RJ et al. Risks of Paralytic Disease due to Wild orVaccine-derived Poliovirus after Eradication (Submitted). Probabilities assumerealistic population immunity at T0, include low, lower-middle and upper-middleincome countries (currently using OPV).


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The strategies needed to minimize and managethe risks associated with eventual OPV cessationare considered 'prerequisites' for stopping routine

immunization with this vaccine. The sixprerequisites that have been established for OPVcessation are:

I CONFIRMATION OF INTERRUPTION OFWILD POLIOVIRUS TRAN SMISSION

GLOBALLY

Issue: because of the ongoing risk of poliovirusimportations into polio-free areas, theinterruption of wild poliovirus transmissionmust be confirmed in every country in theworld prior to the cessation of routine polioimmunization anywhere.Status: in 1995 the Global Commission forthe Certification of Poliomyelitis Eradication(GCC) established the criteria forconfirming the interruption of wildpoliovirus transmission. As of end-2004,135 countries in three WHO Regions hadbeen certified polio-free (WHO regions ofthe Americas, Europe and Western Pacific).

Next Steps: intensified efforts are beingmade to interrupt the remaining chains of

wild poliovirus transmission in the last six polio-endemic countries and the six countries wherepoliovirus transmission was re-establishedfollowing importations in 2003-2004. Allcountries in regions yet to be certified as polio-freemust demonstrate zero polio cases for a minimumof three years, in the presence of 'certificationstandard' surveillance, prior to OPV cessation.

II APPROPRIATE BIOCONTAINMENT OFALL POLIOVIRUSES

Issue: all wild, vaccine-derived and Sabinpolioviruses must be placed under appropriatebiocontainment levels on a timely basis tominimize the risk of re-introduction into a polio-free world.Status: in 2003, high level biosafety requirementswere internationally agreed for vaccine-derivedand wild-type polioviruses4. By end-2004, 152

countries had initiated a survey for wild-type andvaccine-derived poliovirus infectious andpotentially infectious materials, covering over200,000 facilities. Approximately 850 facilitieswere identified with relevant infectious materials.These materials will either be destroyed or placedunder appropriate biocontainment conditions.Next Steps: by the time wild poliovirus

4. Risk management before, duringand after OPV cessation: implementing

the prerequisites for OPV cessation

6

Six prerequisites for simultaneous OPVcessation:I Confirmation of interruption of wild

poliovirus transmission globallyII Appropriate biocontainment of all

poliovirusesIII International stockpile of monovalent

OPV (mOPV)

IV Highly-sensitive surveillance forcirculating polioviruses

V Procedure for internationally-simultaneous OPV cessation

VI Long-term routine polio immunizationpolicy (i.e. national IPV decisions)

4 WHO Global Action Plan for Laboratory Containment of Wild Polioviruses (GAP II), Second edition.World Health Organization, Geneva, Switzerland, 2003. (WHO/V&B/03.11)

Wild poliovirus containment:progress with Phase I - Survey & Inventory, 2004

Polio endemicRe-established transmissionSurvey not yet startedConducting survey

Reporting completion of survey and inventory of laboratories with wild poliovirus materials


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transmission is interrupted globally, all countriesmust have completed a national survey andinventory of facilities holding wild or vaccine-derived polioviruses. The process of destroying orproperly containing those materials must be

completed twelve months later. At aninternational level, consensus must be establishedon appropriate future biosafety containmentlevels for Sabin viruses, the timing of theimplementation of such activities and themechanisms for verification. The developmentand licensure of IPV-produced from Sabin strains(SIPV) will continue to be pursued to furtherreduce the number of sites generating highvolumes of high titre wild polioviruses for IPV

production.

III INTERNATIONAL STOCKPILE OFMONOVALENT OPV (MOPV)

Issue: an international stockpile of types 1, 2 and3 monovalent OPV is needed particularly toallow a 'type-specific' response during the processof OPV cessation (thereby enhancing the impactof the outbreak response while preventing the re-introduction of other polioviruses).Status: in 2004, all producers of WHO-

prequalified OPV and their respective nationalregulatory agencies were invited to collaboratewith WHO on the development, licensure andproduction of monovalent type 1, type 2 and type3 OPV. Working estimates have been establishedfor the number of doses required of each mOPVtype, development timelines have been elaborated,and the Global Alliance for Vaccinesand Immunization (GAVI) willreview a stockpile investment case forfunding. As the result of anaccelerated vaccine developmentproject, two mOPV type 1 vaccineswere licensed in early 2005 and areundergoing large-scale fieldevaluation.Next Steps: the development,production and procurement ofmOPV for the stockpile is scheduledto begin in 2006. The mechanismsand criteria for the future use of the

stockpile must be completed and

internationally-agreed in a World HealthAssembly resolution. The potential role of IPV,and possibly antivirals, in outbreak response mustalso be fully elaborated.

IV HIGHLY-SENSITIVE SURVEILLANCE FORCIRCULATING POLIOVIRUSES

Issue: highly sensitive surveillance is requiredbefore, during and after OPV cessation toconfirm interruption of wild poliovirustransmission, document the elimination of Sabinstrains, and rapidly detect the potential re-introduction of any poliovirus.Status: in 2004, 66 polio-endemic or recently-endemic countries met or exceeded the

surveillance performance standards established bythe GCC, including most countries that areaffected or recovering from conflict such asAfghanistan, Angola, the Democratic Republic ofthe Congo and Somalia. However, declining ratesof acute flaccid paralysis (AFP) surveillance in anumber of countries that have been certifiedpolio-free, and the recent detection in Africa ofpolioviruses that were missed due to suboptimalAFP surveillance, re-affirms the need tostrengthen surveillance and maintain the full

certification surveillance criteria everywhere.Next Steps: all countries must strengthen AFPsurveillance to ensure it can be sustained atcertification standard throughout the three-yearplus period of OPV cessation and verification ofthe elimination of Sabin- and vaccine-derivedpolioviruses. In addition, high- and middle-

7

Surveillance for non-polio acuteflaccid paralysis (AFP) - 2004

< 0.5 0.5 -1

1 No AFP Surveillance

Per 100,000 population aged


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income countries should screen for iVDPVsamong individuals with primaryimmunodeficiency syndromes. At theinternational level, event-based reporting forsuspect polio will need to be fully incorporated

into the newInternational Health Regulations. Newdiagnostic tools for the OPV cessation phase,particularly IgM assays and direct moleculardetection techniques, must be fully evaluated andintegrated into the polio laboratory network.

V PROCEDURE FOR INTERNATIONALLY-SIMULTANEOUS OPVCESSATION

Issue: all countries will need to simultaneouslystop the use of OPV for routine immunization to

ensure that no country is inadvertently put at riskof importing a cVDPV from a country thatcontinues to use OPV.Status: the international bodies providingoversight to the Global Polio Eradication Initiativehave endorsed the need for eventual simultaneousOPV cessation. WHO has begun the process ofdeveloping and pilot testing guidelines for thewithdrawal of OPV from routine immunizationprogrammes. These guidelines will emphasize theneed to maintain the highest possible level of

OPV coverage until the actual time ofsimultaneous OPV cessation.Next Steps: all remaining polio-infected countriesmust interrupt wild poliovirus transmission asrapidly as possible to allow the development of afirm timeline for OPV cessation. A World HealthAssembly Resolution outlining the precise timingand process for simultaneous OPV cessation by allOPV-using countries could be required as early as2006. At the national level, detailed plans for thewithdrawal and destruction of all trivalent OPVstocks, from all levels of the country, will need tobe developed and national immunization policiesrevised accordingly. Following OPV cessation,documentation of the destruction of remainingtrivalent OPV stocks will need to be verified ineach country.

VI LONG-TERM ROUTINE POLIOIMMUNIZATION POLICY

Issue: each OPV-using country must decide

whether to stop all routine immunization against

polio after OPV cessation (after OPV cessation,IPV will be the only option for those countrieswhich decide to continue routine immunization).Status: based on an evaluation of the costs andbenefits of continued polio immunization after

OPV cessation, and the needs of other diseasepriorities, WHO is recommending that OPV-using countries do not routinely introduce IPV atthat time. WHO is, however, assisting thosepolio-free countries that have requested support toevaluate the potential role of IPV in their nationalimmunization programme. To facilitate nationaldecision-making on IPV, WHO published anIPV Position Paper in 2004 summarizing thecharacteristics, efficacy and potential role of the

vaccine. A separate WHO study detailed themajor programmatic implications of IPVintroduction, many of which are not immediatelyapparent, for most OPV-using countries (e.g. theneed to increase cold chain capacity, change thepertussis component of combination vaccines, usevaccines with a different preservative)5. Initialresults from modelling studies commissioned bythe Global Polio Eradication Initiative suggestthat for most low-income countries, theintroduction of IPV for routine immunization

would only marginally reduce the already smallrisks associated with OPV cessation.Next Steps: any OPV-using country which isconsidering the potential introduction of IPVshould systematically evaluate the risks and benefitsof continuing polio immunization following OPVcessation, including the impact this could have onother priority disease control programmes. WHOwill continue to review the potential role of IPV asadditional data are collected on the risks associatedwith OPV cessation.

85 WHO presentation at 3rd WHO/UNICEF Informal Consultation with IPV and OPV Manufacturers. June 2004,Geneva, Switzerland.


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9

The timetable for OPV cessation can be dividedinto three distinct periods correlating with the

evolution of the major polio risks and riskmanagement strategies. The precise timing ofthese phases will depend on the date ofinterruption of wild poliovirus transmissionglobally and progress towards achieving the sixprerequisites outlined earlier.Regional Certification & OPV CessationPreparatory Phase: this phase has alreadybegun and will continue for three years after thelast case of polio caused by wild-type poliovirus

is detected anywhere in the world. The majorrisk during this period will beundetected wild poliovirustransmission due to suboptimal AFPsurveillance. The national polioeradication priorities during this phaseare outlined in Box 1.OPV Cessation & VerificationPhase: this phase will begin with thesimultaneous cessation of OPVworldwide and will continue for at

least three years thereafter, untilverification of the disappearance ofSabin poliovirus strains from thehuman population globally, as well as

the absence of cVDPVs. The major risk duringthis period will be the emergence of a cVDPV

(which would trigger a type-specific outbreakresponse with the appropriate mOPV).Post-OPV Era: this period will begin with theverification of the disappearance of Sabin-strainpolioviruses, as well as the absence of cVDPVs.This period will continue indefinitely. Themajor risks during this period (in decreasingorder of potentially-damaging consequences)would be the re-introduction of a wild, vaccine-derived or Sabin-strain poliovirus.

5. Timetable for OPV cessation

Box 1: Priorities for National Policy Makers in OPV-Using CountriesOPV Cessation Preparatory Phase

Strengthen polio (AFP) surveillance to guide interruption of wild poliovirus transmission,certify eradication, and detect potential importations and cVDPVs.

Fully implement and verify appropriate containment of wild and vaccine-derived

polioviruses and prepare for Sabin-virus containment. Raise routine immunization coverage (target >90%) to minimize the risk of spread of an

imported poliovirus and the risk of cVDPV emergence. Decide - based on analysis of risks, benefits and opportunity costs - whether to stop all routine

immunization against polio after OPV cessation (when inactivated polio vaccine will be theonly option for continued routine immunization).

Conduct an iVDPVrisk assessment and establish a case management plan, if needed. Establish national plans and mechanisms for the eventual cessation of all OPV use in routine

immunization programmes and destruction of remaining trivalent OPV stocks (note:standard template will be available 12-24 months beforhand).

Further information and technical support is available from WHO country and regional offices, aswell as from the Global Polio Eradication Initiative, WHO Geneva.

Potential timeline and priority activities for eventual cessation oforal polio vaccine (OPV) for routine immunization

Interruptionof wild

poliovirus

Certify interruption ofwild virus transmission

Contain wild &vaccine-derivedpolioviruses

Develop mOPV stockpile

& criteria for useEstablish national policyon IPV use

Simultaneously stopall routine use of OPV

Contain Sabin strainpolioviruses

Verify the absence of

cVDPV & Sabin virusFully integrate poliovirussurveillance into IHR

Maintainsurveillance

Maintainstockpile

Verify

containment

Years after last circulating wild poliovirus

Certification &Preparation for OPV

Cessation

Phase of OPV cessation work

0-1 1 2 3 4 5 6 7 8

OPV Cessation &Verification

'Post OPV'Era


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10

ACPE Advisory Committee on Poliomyelitis Eradication

AFP acute flaccid paralysis

cVDPV circulating vaccine-derived polioviruses

GAVI Global Alliance for Vaccines and Immunization

GCC Global Commission for the Certification of Poliomyelitis Eradication

IHR International Health Regulations

IPV inactivated polio vaccine

iVDPV immunodeficient excretors of vaccine-derived polioviruses

mOPV monovalent oral polio vaccine

OPV oral polio vaccine

S-IPV inactivated polio vaccine produced from Sabin strains

tOPV trivalent oral polio vaccine

VAPP vaccine-associated paralytic poliomyelitis

VDPV vaccine-derived polioviruses

WHA World Health Assembly

WHO World Health Organization

6. Glossary of terms


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Avenue Appia 20 - CH-1211 Geneva 27 - Switzerlandwww.polioeradication.org

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