PolioPipeline_08

8/4/2019 PolioPipeline_08

1/81

New Roadmap or VDPV

Elimination

In 2008, the World Health Assembly (WHA) requestedthe development of a new strategy to complete the job ofpolio eradication. The Global Polio Eradication Initiative(GPEI) subsequently developed the new GPEI StrategicPlan 2010-2012. At the start of 2011, epidemiologicalimpact of the new Strategic Plan was already beingseen, in particular in some of the worlds most tenacioushistoric polio reservoirs. And while challenges remain,it is now clear that the interruption of wild poliovirus

(WPV) transmission globally is realistically achievable inthe near-term. With this feasibility established, effortsmust now intensify to prepare for the post-eradicationera, in order to meet the overall goal of the GPEI: toensure that no child will ever again be paralysed by aWPV or a vaccine-derived poliovirus (VDPV).

To this effect, in 2011 the GPEI will produce and developa new Roadmap for VDPV Elimination. While variousstrategy and policy documents for post-eradication havebeen elucidated in the past, including for the eventualcessation of oral polio vaccine (OPV) from routineimmunization programmes, this Roadmap will consolidate

and supersede all previously-published policy documents.The Roadmap will be regularly updated as new policiesare spelled out, and will aim to provide global policymakers at global, regional and country levels an overviewof the necessary steps and tools required to fully preparefor the post-eradication era.

Summer 2011

Issue 8Inside this Issue

1 New Roadmap or VDPV Elimination

2 OPV Cessation - time to proceed by serotype?

4 Managing transition period ater OPV cessation

8 Call or research proposals

An update of ongoing research in the Global Polio Eradication Initiative

thepoliopipeline

Post-eradication - preparingor a lasting polio-ree world

The world has seentremendous gains in polioeradication over the pastyear. India and Nigeria saw areduction in cases o almost95% rom 2009 to 2010, andcases o wild poliovirus type 3

(WPV3) ell by 92% globallyover the same period. In act,the last reported case in Indiahad onset o paralysis on13 January 2011, and India maybe on the verge o eradicatingpolio.

This progress comes just asa study published in Vaccinereports that the economicbenefts o eradicating poliowould be at least US$40-50

billion, urther cementing thecase or polio eradication.And while challenges remain,research will continue to play akey role in urther evaluating andsensitising strategic approachesto successully interrupt wildpoliovirus transmission globally.Look orward to the next PolioPipeline, which will ocus onoperations and communicationsresearch.

However, now that theeasibility o polio eradicationhas been clearly recognized,important questions need tobe asked: at what point shouldthe use o oral polio vaccine

(OPV) be ceased, and should

it be stopped by individual

serotype? For example, wild

poliovirus type 2 (WPV2) has

been eradicated globally since

1999, and since then all type 2

cases are related to the vaccine

itsel. Is it possible to produce

an aordable inactivatedpolio vaccine (IPV)? How can

the risk o vaccine-derived

polioviruses be eectively

managed immediately ater

OPV cessation?

These and urther questions are

the ocus o this issue.

Work has already begun

on fnding the answers.

For example, the Strategic

Advisory Group o Experts

on Immunization (SAGE) IPV

Working Group has been

working on providing key

advice on policy and remaining

knowledge gaps. Similarly, the

World Health Organization

(WHO) and UNICEF have been

working with manuacturers

to prepare a new agenda to

create an adequate stockpile o

monovalent oral polio vaccine

(mOPV). But there is much more

work which needs to be done

to prepare or the days when

transmission o WPV fnally

ceases, and research will play a

critical role in these plans.

The new Roadmapwill consolidate all

previously-published policydocuments, including the

OPV Cessation Frameworkpublished in 2005


2/82

thepoliopipelineAn update of ongoing research in the Global Polio Eradication Initiative Summer 2011 Issue 8

At the same time, the Roadmap will clearlyoutline the humanitarian and economicbenefts o a lasting polio-ree world (thenet benefts o polio eradication having

been estimated at US$40-50 billion),and as such will provide the internationaldonor community with justifcation orcontinued investment into the GPEI or

the post-eradication era, to acilitatelong-term planning and budgetingprocesses.

OPV cessation time toproceed by individualserotypes?Discussions are ongoing to kickstartthe process by removing serotype 2components rom existing routineimmunization vaccines

Since 1999 (when wild poliovirustype 2 - WPV2 - was eradicated globally),increasing scientifc data demonstratethat polio eradication will also requirethe eventual cessation o oral poliovaccine (OPV) in routine immunizationprogrammes. Otherwise, the continuedreintroduction o the attenuatedpolioviruses o OPV into a polio-reeworld will result in polio cases dueto vaccine-associated paralytic polio

(VAPP), and polio outbreaks due tocirculating vaccine-derived polioviruses(cVDPVs).

VAPP cases are extremely rare. The total VAPP risk is approximately 2-4 per onemillion birth cohort. VAPP results romsmall genetic mutations which the livevaccine-virus undergoes when replicatingin the human gut (ie which make the virusrevert to being neurovirulent). Childrenwith immunodefciencies tend to be at

substantially higher risk o developing VAPP ater immunization. Based oncurrent usage o trivalent OPV aroundthe world, between 250 and 500 VAPPcases occur annually.

Equally rare, the attenuated OPV virusescan - over time - genetically change romthe original strain contained in OPV tobecome a cVDPV, eectively regainingboth the ability to cause paralysis inhumans, and to circulate, similar to wildpolioviruses (WPVs). Worldwide overthe past ten years, over 10 billion doseso OPV have been administered to morethan 2.5 billion children, and as a resultmore than 3.5 million polio cases wereprevented. During that time, 18 outbreaks

o cVDPVs have occurred in 16 countries,resulting in 510 VDPV cases.

It has long been understood that thesmall risk o VAPP and VDPVs paled insignifcance to the tremendous publichealth benefts associated with OPV,particularly when WPV transmissionwas widespread. Every year, hundreds

o thousands o cases due to WPV areprevented. Well over eight million caseshave been averted since largescaleadministration o OPV began twentyyears ago. But it has also been longunderstood that there would come a timewhen the balance o beneft versus risko trivalent OPV would begin to tip. Inother words, when the only cases o poliooccurring are due to VAPP or cVDPVs, andthe risk o WPV cases occurring has beenvirtually eliminated (in many countries othe world which have already interrupted

WPV transmission, the use o OPV hasalready been stopped due to this risk,and replaced with routine immunization

with IPV). On a global level, that balancewould be right around the time o globalinterruption o WPV transmission. Thatis why the cornerstone strategy or theposteradication era is to eliminatethe risk posed by OPVs by eventuallystopping the use o all live oral polio

vaccines, or routine and supplementaryimmunization, as soon as possible aterthe eradication o WPVs.

OPV cessation, it has been oreseen,would occur as soon as possible aterthe last case o WPV has been detectedglobally. At a time when immunitylevels remain relatively high and diseasesurveillance sensitive. But with the largeproportion o VAPP cases caused by thetype 2 serotype contained in trivalentOPV, and WPV2 transmission havingalready been successully interrupted(since 1999), calls are becoming louderto remove all type 2-containing OPVat this time already. In other words, tostop using type-2 oral vaccine virus evenbeore the remaining strains o WPV1 andWPV3 transmission have been globallyinterrupted.

The call makes sense rom a publichealth point o view, especially sincethe availability o the new bivalent OPV(introduced in late 2009) , containing onlytype 1 and type 3 serotypes (the only twoWPV serotypes remaining in circulation).It would essentially mean that bivalentOPV would replace trivalent OPV acrossthe board, in routine immunizationprogrammes.

Based on current OPV usage, between 250 and 500 VAPP cases occur every year,a large proportion due to the type 2 component in trivalent OPV

A lasting polio-ree world:Ensuring no child will ever again be paralysed by a wild- or vaccine - derived poliovirus

WHO


3/83


The discussions, led frst and oremostby the Strategic Advisory Group oExperts on Immunization (SAGE) and itssubsidiary body the SAGE IPV WorkingGroup (established to advise SAGEon pre and posteradication poliovaccination policy), is a recognitionthat the expected shit in balance rombeneft to risk - or type 2-containingOPV - has indeed already occurred. Butis a global OPV type 2 cessation eort, atthis time - even beore WPV eradication -operationally easible?

The primary risk associated with OPVtype 2 cessation would be the rapidincrease in susceptible populations topoliovirus type 2. This in turn wouldincrease the risk o new type 2 cVDPVsemerging, in the immediate interimperiod ollowing OPV type 2 cessation.Equally important would be the rapidstopping o any eventual residual type 2

cVDPVs, ongoing rom just immediatelyprior to OPV type 2 cessation. To saelyimplement an OPV type 2 cessationprogramme would thereore require theimplementation o a number o strategiesto manage these risks.

In the frst instance, the ormalvalidation o the global interruption oWPV2 transmission will need to occur,due o the ongoing risk o poliovirusimportations into polio-ree areas. This

will be particularly important in the threeRegions which remain endemic to WPV1and WPV3 transmission (Arica, theEastern Mediterranean and South-EastAsia).

Highly sensitive surveillance or allpolioviruses, including type 2 wild andvaccine-derived polioviruses will needto be maintained, both to documentthe elimination o type 2 poliovirustransmission (including residualtype 2 cVDPVs), and to rapidly detectthe potential re-introduction or re-emergence o any type 2 poliovirus(WPV or cVDPV). At the same time,outbreak response capacity will have tobe maintained, including ensuring thesupply and management o stockpiles oappropriate type 2-containing vaccinesto acilitate an appropriate outbreakresponse should it be necessary.

All WPV2 and Sabin type 2 virusesmust be placed under appropriate

biocontainment levels on a timely basisto minimise the risk o re-introductioninto a type 2 polio-ree world.

Adequate supplies o bivalent OPV andIPV will need to be secured. IPV willbe needed or countries that elect toretain type 2 poliovirus in laboratories,or countries that produce IPV, and orcountries choosing to introduce IPV asa risk mitigation strategy, particularlyto maintain type 2 population immunity

and thereby reduce the consequenceso a potential re-introduction or re-emergence o type 2 polio.

And fnally, the cessation o OPV type 2will need to be synchronized, eitherglobally or regionally, to ensure that nocountry is inadvertently put at risk oimporting a type 2 cVDPV rom a countrythat continues to use type 2 containingOPV.

Preparing or OPV type 2cessationManaging the risks by:

Validating global interruptiono WPV2 transmission

Maintaining sensitivesurveillance and outbreakresponse capacity

Appropriately containing alltype 2 polioviruses

Ensuring supplies o bivalentOPV, and aordable IPV

Synchronizing OPV type 2cessation globally/regionally

I properly implemented, OPV type 2cessation would have signifcant publichealth benefts. Over the past ten years,more than 80% o all cVDPV cases weredue to type 2. O the estimated 250-500annual VAPP cases, up to 38% are dueto type 2. These case numbers wouldno longer occur. In addition to thesesignifcant humanitarian benefts, OPVtype 2 cessation would provide the GPEIwith a push or global OPV cessationo all oral polio vaccines. Feasibility oOPV cessation would be underscored inpractice, and would ensure a trial runor all OPV cessation. Key lessons wouldbe learnt to ensure that this process canbe implemented in the saest and mostefcient manner.

For these reasons, the SAGE IPV WorkingGroup at its April 2011 meeting concludedthat it would be appropriate to considerplanning or the cessation o routine OPVimmunization against type 2 polioviruses.Research will continue to play a key role inpreparing or both the eventual cessationo all OPVs and the potential cessation otype 2 OPV. Policy bodies, including anExpert Consultation on VDPVs and thenext SAGE meeting, both in November2011, and the Executive Board o WHO

in January 2012 are expected to reviewurther arguments. But it is entirelyeasible that come this time next year, theGPEI will be in the midst o a OPV type 2cessation programme, as it continues onits fnal stretch to rapidly interrupt theremaining chains o WPV1 and WPV3transmission globally. Public health andprogrammatic arguments certainly wouldspeak avourably or such an approach.

Signifcant benefts o OPV

type 2 cessation Up to 200 VAPP cases prevented

every year

Up to 80% ewer cVDPV events

Feasibility o OPV cessationtranslated into practice,providing key lessons or allOPV cessation

OPV type 2 cessation: bivalent OPV would replacetrivalent OPV across the board

WHO


4/84


Managing transitionperiod ater OPVcessationPeriod between OPV cessation andelimination o residual VDPVs key tolasting polio-ree world

Saely managing the transition periodollowing cessation o oral polio vaccine(OPV) rom routine immunizationprogrammes (ie the period between OPVcessation and the elimination o anyresidual vaccine-derived polioviruses -

VDPVs) will be key to securing a lastingpolio-ree world. This will require in thefrst instance the ability or countries

to maintain population immunityagainst polio. Following OPV cessation,inactivated polio vaccine (IPV) will be theonly option with which to do so.

Recognizing that current costs o IPVare substantially higher than OPV,the Global Polio Eradication Initiative(GPEI) has intensifed its programme owork to study a range o aordable IPVstrategies. The our branches o this workare: schedule reduction (evaluating the

use o one or two IPV doses to immunizeand/or prime children); dose reduction(evaluating ractional dose IPV givenintra-dermally by needle-ree device ormicro-needle patch to spare antigen);antigen reduction (using adjuvant toreduce antigen contents per dose);and, production cost reduction (urtheroptimising production processes andproducing IPV in developing countrieswith less or non-inectious strains).

An animal study completed in 2010

suggested that a ten-old reduction oIPV antigen is easible with inclusion oan oil-in-water adjuvant. This approachis currently being evaluated in humanstudies.

In collaboration with the NetherlandsVaccine Institute (NVI) , and more recentlythe National Institute or Public Healthand the Environment (RIVM) in theNetherlands, clinical lots o seed-strainso IPV produced rom Sabin poliovirus

have been prepared. Traditional IPVis manuactured using wild poliovirusand an inadvertent biocontainmentailure could be associated with seriousconsequences in some areas o theworld in the post-eradication era (ieareas with high population density,

inadequate sanitation inrastructureand low population immunity levels).Sabin seed strains or IPV have theadvantage over wild polioviruses thatthey are attenuated, and hence aresaer or handling and IPV production in

developing country settings in the post-eradication era.

In this frst phase o a broader intendedtechnology transer programme, this newtechnology will be transerred to twomanuacturers or vaccine production:Panacea Biotech, Ltd in India, and LG LieSciences, Ltd in the Republic o Korea.Both manuacturers have confrmed theirintention to use all reasonable eorts toapply or registration o their Sabin IPVproducts in the country o productionwithin our years rom the dates oconclusions o the bilateral agreementwith RIVM. WHO and RIVM will continuethe technology transer programme thisyear with urther manuacturers.

In addition, six research collaborationsare ongoing to assess urther attenuatedpoliovirus strains, including with theUniversity o Caliornia at San Francisco,the US Centers or Disease Control andPrevention (CDC), the National Institute

or Biological Standards and Control(NIBSC) in the United Kingdom, theUniversity o Leeds, and two projects withState University o New York (SUNY).

The other option to address risks o VDPVsis treatment with antiviral drugs. Dozenso antiviral compounds have been testedor activity against polioviruses, withtwo promising candidates now in clinicaldevelopment. Such antivirals could playa key role in ensuring that inections

are rapidly cleared in immunodefcientindividuals who might be chronicallyshedding poliovirus. At the same time,antivirals could oer protection orpersons exposed to poliovirus (eg throughunintentional laboratory exposure) andor communities exposed to cVDPVs.

Finally, progress continues to be made indeveloping an OPV stockpile to respondto residual cVDPVs. By the end o 2010,nine monovalent OPVs (or type 1 and

type 3 polio) had been licensed, anda global stockpile is under tender. Theglobal stockpile o monovalent OPVs, andinternationally-agreed processes or itsmanagement and use, will be critical tocarry out timely response to any residualcVDPVs in the post-eradication era.

Available and upcomingpublications Progress report by the GPEI Secretariat to the

64th World Health Assembly, 16-24 May 2011,Geneva, Switzerland. Available at http://www.polioeradication.org/ResourceLibrary.aspx.

Report o the 2nd meeting o the IndependentMonitoring Board, April 2011. The report othe 3rd meeting, July 2011 will be availablesoon at www.polioeradication.org .

GPEI Financial Resource Requirements(FRR) - July update. Available at www.polioeradication.org .

2011 edition of WHOs International traveland health (vaccination recommendations ortravellers). April 2011. Available at www.who.int/ith/en.

Meeting of the Strategic Advisory Group ofExperts on immunization: conclusions andrecommendations. Weekly EpidemiologicalRecord. 20 May 2011, vol 86, 21 (pp 205-220) .

Progress towards interrupting wild poliovirustransmission worldwide: January 2010 -March 2011. Weekly Epidemiological Record.13 May 2011, vol 86, 20 (pp189-204).

Monitoring progress towards global polioeradication: poliovirus surveillance, 2009-2010.Weekly Epidemiological Record. 15 April2011, vol 86, 16 (pp 153-160).

Outbreak of poliomyelitis, Republic of the

Congo, September 2010-February 2011.Weekly Epidemiological Record. 8 April 2011,vol 86, 15 (pp 141-152).

Performance of acute accid paralysis (AFP)surveillance and incidence o poliomyelitis,2010. Weekly Epidemiological Record. 1 April2011, vol 86, 14 (pp 129-140).

Bakker WAM, Thomassen YE, van der Pol LA(2010). Scale-down approach or animal-reepolio vaccine production. In: Noll Th, ed., Cellsand Culture; Proceedings o the 20th ESACTmeeting, June 17-20, 2007, Dresden, Germany.Springer, Dordrecht, 4(6 ):541 550

Thomassen YE, van Sprang ENM, van derPol LA, Bakker WAM (2010). Multivariatedata analysis on historical IPV productiondata or better process understanding anduture improvements. Biotechnol. Bioeng.107(1):96104

Westdijk J, Brugmans D, Martin J, van t OeverA, Bakker WAM, Levels L, Kersten G (2011).Characterization and Standardization o Sabinbased Inactivated Polio Vaccine. Proposalor a new antigen unit or inactivated poliovaccines. Vaccine 29(18):33903397

Verdijk P, Rots NY, Bakker WAM (2011).Clinical development o a novel inactivatedpoliomyelitis vaccine based on attenuatedSabin poliovirus strains. Expert Review o

Vaccines. 2011; 10:635-644

John TJ, et al. Monovalent type 1 oralpoliovirus vaccine among inants in India:

Report o two randomized double-blind

controlled trials. Vaccine, 2011, doi:10.1016/j.

vaccine.2011.04.133 in press
http://apps.who.int/gb/ebwha/pdf_files/WHA64/A64_26-en.pdfhttp://www.polioeradication.org/ResourceLibrary.aspxhttp://www.polioeradication.org/ResourceLibrary.aspxhttp://www.polioeradication.org/Portals/0/Document/Data&Monitoring/IMB_Reports/IMB_Report_April2011.pdfhttp://www.polioeradication.org/http://www.polioeradication.org/http://www.polioeradication.org/http://www.who.int/ith/enhttp://www.who.int/ith/enhttp://www.who.int/wer/2011/wer8621/en/index.htmlhttp://www.who.int/wer/2011/wer8621/en/index.htmlhttp://www.who.int/wer/2011/wer8620/en/index.htmlhttp://www.who.int/wer/2011/wer8620/en/index.htmlhttp://www.who.int/wer/2011/wer8616/en/index.htmlhttp://www.who.int/wer/2011/wer8616/en/index.htmlhttp://www.who.int/wer/2011/wer8616/en/index.htmlhttp://www.who.int/wer/2011/wer8615/en/index.htmlhttp://www.who.int/wer/2011/wer8615/en/index.htmlhttp://www.who.int/wer/2011/wer8614/en/index.htmlhttp://www.who.int/wer/2011/wer8614/en/index.htmlhttp://www.who.int/wer/2011/wer8614/en/index.htmlhttp://www.who.int/wer/2011/wer8614/en/index.htmlhttp://www.who.int/wer/2011/wer8615/en/index.htmlhttp://www.who.int/wer/2011/wer8615/en/index.htmlhttp://www.who.int/wer/2011/wer8616/en/index.htmlhttp://www.who.int/wer/2011/wer8616/en/index.htmlhttp://www.who.int/wer/2011/wer8620/en/index.htmlhttp://www.who.int/wer/2011/wer8620/en/index.htmlhttp://www.who.int/wer/2011/wer8621/en/index.htmlhttp://www.who.int/wer/2011/wer8621/en/index.htmlhttp://www.who.int/ith/enhttp://www.who.int/ith/enhttp://www.polioeradication.org/http://www.polioeradication.org/http://www.polioeradication.org/http://www.polioeradication.org/Portals/0/Document/Data&Monitoring/IMB_Reports/IMB_Report_April2011.pdfhttp://www.polioeradication.org/ResourceLibrary.aspxhttp://www.polioeradication.org/ResourceLibrary.aspxhttp://apps.who.int/gb/ebwha/pdf_files/WHA64/A64_26-en.pdf


5/85


Global status o licensure and pre-qualifcation processes or monovalentOPV type 1, 2 and 3 and bivalent OPV

Monovalent OPV type 1 (mOPV1)

Licensed in mOPV1 mOPV1 mOPV1 mOPV1 mOPV1 mOPV1 mOPV1

Panacea Sanof Pasteur GSK Novartis Bio Farma Hakine Bharat

India 23 December 2004(BF&SP bulks)

23 April 2009 04 September2008

4 September 2008 4 April 2010 13 March 2007(BF bulks)

Ongoing(BF bulks)

France / 25 March 2005 / / / / /

Egypt / 19 April 2005 7 February 2006 / / / /

Belgium / / 18 July 2005 / / / /

Pakistan On going 31 July 2006 12 September2005

6 June 2008 23 October 2009 / /

Nigeria 22 August 2006 7 August 2009 2 February 2006 18 July 2008 9 June 2008 / /

Italy / / / 14 December 2007 / / /

Indonesia June 2006 (SAS)* / 2006 (SAS)* / 20 February 2006 / /

Letter to UN torecommend use

6 April 2005 21 April 2005 30 August 2005 20 December 2007 21 March 2007 / /

PQ completed 3 November 2009 8 May 2008 29 October 2009 3 November 2009 3 November 2009 3 November 2009 15 June 2011

Monovalent OPV type 3 (mOPV3)Licensed in mOPV3 mOPV3 mOPV3 mOPV3

Panacea GSK Novartis Bharat

India 10 August 2005(BF&NOV bulks)

4 September 2008 4 September 2008 17 March 2008(BF bulks)

France / / / /

Belgium / 20 December 2006 / /

Egypt / / / /

Pakistan On going 20 August 2007 6 June 2008 /

Nigeria 2 July 2007 31 October 2007 31 December 2008 /

Italy / / 14 December 2007 /

Indonesia / / / /

Letter to UNto recommend use 13/09/2005 (BF bulks)07/08/2007 (NOV bulks) 21 March 2007 20 December 2007 /

PQ completed 5 October 2010 5 October 2010 5 October 2010 15 June 2011

Monovalent OPV type 2 (mOPV2)

Licensed in mOPV2 mOPV2

Panacea GSK

India 27/07/2007 (BF & NOV bulks) or stockpile and CT /

France / /

Belgium / 7 April 2011

Egypt / /

Pakistan / /

Nigeria / /

Italy / /

Indonesia / /

PQ completed 9 March 2011 11 May 2011

Bivalent OPV containing type 1 and 3 (bOPV1&3)

Licensed in bOPV1&3 bOPV1&3 bOPV1&3 bOPV1&3

Panacea Panacea GSK Bio Farma

India BF bulks25 November 2009

SP bulks23 May 2011

2nd Clinical trial planned inJuly 2011


France / / / /

Belgium / / 9 October 2009 /

Egypt / / / /

Pakistan / / 08 February 2010 /Nigeria / / 23 April 2010 /

Italy / / / /

Indonesia / / / Ongoing

CT status Completed Completed Completed Completed

PQ status 10 December 2009 26 May 2011 29 October 2009 26 May 2010

Continued on page 6*SAS: special access scheme or specifc use, PQ: pre-qualifcation, CT: clinical trial, BF: Bio Farma, SP: Sanof Pasteur, NOV: Novartis


6/86


Bivalent OPV containing type 1 and 3 (bOPV1&3)Licensed in bOPV1&3 bOPV1&3 bOPV1&3 bOPV1&3

Hakine Bharat Sanoi Pasteur Novartis

India BF bulks25 February 2010

22 March 2010 2nd Clinical trial planned inJuly 2011


France / / Dossier submitted on

28 February 2011

/

Belgium / / / /

Egypt / / / /

Pakistan / / / /

Nigeria / / / /

Italy / / / Dossier submitted on27 May 2011

Indonesia / / / /

CT status Completed Completed Completed Completed

PQ status 19 March 2010 15 June 2011 On going On going

New lab procedures morereliably detect VDPVs andreduce time to confrmpoliovirus by 50%New knowledge will help urther elucidatepost-eradication strategies

Routine and supplemental

immunization activities using live(attenuated), Sabin-vaccine strains arethe best strategy to eradicate polio butcan also lead to circulation o Sabin-Like (SL) viruses, and consequently tovaccine-derived polioviruses (VDPVs) thatare related to vaccine strains but withsignifcant genetic changes. The latter areo programmatic interest as they can gainability to provoke acute accid paralysis(AFP) in inected people. Detecting theseviruses can be also challenging due to

both genetic and antigenic changes.

Since 2007, and as part o the continuousmonitoring and improvement o poliovirusdiagnostics, the global specialized poliolaboratory at the US Centers or DiseaseControl and Prevention (CDC) has madegreat eorts to set up rapid and reliablemethods to detect VDPVs, including theones that have gained the capacity to betransmitted rom person-to-person. Theoutcome is two validated new methods,

using real-time reverse transcriptasepolymerase chain reaction (rRT-PCR), tosay i the polioviruses isolated rom stoolsamples are wild or Sabin-like and, in a

second step, i the latter are VDPV or not.Importantly, these new procedures havealso reduced the average time needed toconfrm poliovirus by 50% (rom 42 daysto 21 days).

Consequently, in 2009, the Global PolioLaboratory Network (GPLN) has startedto implement a validated new testingalgorithm using both methods. Additionaldata gathered since then clearly show

that this new algorithm is aster and morereliable or the detection o both wildpolioviruses and VDPVs. Then, urthergenetic characterization o suspected

VDPVs by sequencing, along with clinicaland epidemiological data, allow theclassifcation as (i) circulating VDPVsor (ii) immunodefciency-associated

VDPVs (iVDPVs). Notifcation o these VDPVs by the GPLN during past yearshas considerably increased knowledge onprevalence, geographical location and key

virological and clinical eatures o theseviruses.

The implementation o rRT-PCRprocedures was signifcantly expandedin 2010, and has played a critical partin urther enhancing detection o allpolioviruses, to enable rapid outbreakresponse. Data gathered since theimplementation o this new algorithmsince 2009 will be reviewed in late 2011during an extended consultation on

VDPVs, to urther sensitise strategies orearly detection, reporting and response to

VDPV emergences. These strategies will becritical or the post-eradication era.

New knowledge oprevalence o iVDPVsOverview o WHO-supported research oniVDPVs and outcomes to date

The Global Polio Eradication Initiative(GPEI) has committed to supporting aseries o studies in up to ten middle andlow-income oral polio vaccine (OPV)-

using countries to generate inormationregarding the prevalence o long-termpoliovirus excretion among persons withprimary immune defciencies (PIDs). Ithas been confrmed that persons withprolonged poliovirus excretion, such ascan be the case with those suering romPIDs, could theoretically transmit virusto contacts and the general populationollowing interruption o wild poliovirustransmission. These polioviruses are calledimmunodefciency-associated vaccine-derived polioviruses (iVDPVs), suggestingthese viruses have replicated and evolvedin immuno-compromised individuals. Theobjectives o this study series are to:

1) estimate the prevalence o vaccine-derived poliovirus (VDPV) excretionamong persons diagnosed with primaryimmune (B-cell or combined B/T-cell)defciency disorders;

2) genetically characterize VDPVs isolatedrom persons with PIDs; and

3) ollow-up/monitor study subjects who

have tested positive or VDPV excretionto determine duration o excretion.

This inormation is essential tounderstanding the uture risk o VDPV


7/87


circulation, development o eectiveimmunization policies, and ultimatelypolio eradication. Whereas the risk ocirculating VDPVs (cVDPVs) will likely betime-limited ollowing OPV cessation, therisk o reintroduction o VDPVs by persons

with PIDs may persist as long as there arepersons excreting iVDPVs. The successulsurveillance o these viruses will thereoretake on an increasing importance andit has been suggested that this studyseries could serve as a roadmap or thedevelopment o national surveillancesystems to detect and respond to iVDPVs.A pilot eort or such a surveillancesystem has been implemented in Egyptas part o the work associated with thisstudy series.

In April 2011, the World HealthOrganization (WHO) hosted a meetingo study investigators and other relevantexperts in order to review progress andresults to date among the dierent iVDPVPrevalence Studies and the Egypt iVDPV

Surveillance Project. The meeting agendaincluded a discussion o the possibleapplication o polio antivirals or thetreatment o chronic poliovirus excretors.Some preliminary results o countriesin which enrolment and data collectionexceeds six months appear in the ollowingtable. These results illustrate in particularthat the incidence o excretors is lowand no long-term excretors have beenidentifed to date in any o the studies.

CountriesNo. o

Patientsenrolled

CVID(common variableimmunodefciency)

PoliovirusExcretors

Long-term

Excretors

Project

status

China 167 22 3 0 completed

Russia 136 27 0 0 completed

Tunisia 82 14 6 0 completed

Philippines 62 6 1 0 ongoing

Sri Lanka 32 7 3 0 ongoing

Iran 43 16 1 0 ongoing

Egypt 9 0 0 0 ongoing

TOTALS 3 completed *

*Additional studies are being implemented in Bangladesh and Senegal.

Upcoming meetings and events

International Workshop on Polio Eradication:

Securing the gains - cross-regional

collaboration in protecting polio-ree areas,

21-22 July 2011, Urumqi, Xinjiang, China WHO Regional Committee for Africa, 29

August - 2 September 2011, Abidjan, Cte

dIvoire

WHO Regional Committee for South-East

Asia, 6-9 September 2011, Jaipur, India

WHO Regional Committee for Europe, 12-15

September 2011, Baku, Azerbaijan

Polio Research Committee (PRC), 17-18

September 2011, Sapporo, Japan

WHO Regional Committee for the Americas,

26-30 September 2011, Washington DC, USA 17th Informal Consultation of the Global

Polio Laboratory Network, 27-28 September

2011, Geneva, Switzerland

WHO Regional Committee for the Eastern

Mediterranean, 2-5 October 2011, Cairo, Egypt

WHO Regional Committee for the Western

Pacifc, 10-14 October 2011, Manila,

Philippines

Expert Consultation on VDPVs, November

2011, Geneva, Switzerland

World Health Organization 2011

All rights reserved. Publications o the World HealthOrganization are available on the WHO web sitewww.who.int or can be purchased rom WHO Press, WorldHealth Organization, 20 Avenue Appia, 1211 Geneva 27,Switzerland ( tel.: +41 22 791 3264; ax: +41 22 791 4857;e-mail: [email protected]). Requests or permissionto reproduce or translate WHO publications - whetheror sale or or noncommercial distribution - shouldbe addressed to WHO Press through the WHO web site(http://www.who.int/about/licensing/copyright_orm/en/index.html).

The designations employed and the presentation o the

material in this publication do not imply the expression oany opinion whatsoever on the part o the World HealthOrganization concerning the legal status o any country,territory, city or area or o its authorities, or concerningthe delimitation o its rontiers or boundaries. Dottedlines on maps represent approximate border lines orwhich there may not yet be ull agreement.

The mention o specifc companies or o certainmanuacturers products does not imply that theyare endorsed or recommended by the World HealthOrganization in preerence to others o a similar naturethat are not mentioned. Errors and omissions excepted,the names o proprietary products are distinguished byinitial capital letters.

All reasonable precautions have been taken by the WorldHealth Organization to veriy the inormation contained

in this publication. However, the published materialis being distributed without warranty o any kind,either expres sed or implied. The responsibility or theinterpretation and use o the materia l lies with the reader.In no event shall the World Health Organization be liableor damages arising rom its use.

In all studies, excretors have beensought out through both the testing oknown or suspected persons with PIDs orthrough the investigation of acute accidparalysis (AFP) cases. Only very ew o theparticipating countries have establishedregistries o persons with PIDs. Based

on experience to date, AFP surveillanceappears to be the most eective orm odetection o iVDPVs. Having a treatment tooer patients could acilitate surveillanceeorts.

A total o 531 patients have been enrolledto date in the country study sites whichreported results at this meeting. 14 (2.6%)o these were ound to excrete poliovirus(as per the results table above). However,none so ar have proven to be long-term

(> 6 months) excretors. 92 out o those531 (17%) enrolled patients sueredrom common variable immunodefciency

(CVID), suggesting that the upper 95%

confdence bounds associated with

a chronic excretor within this group

remains substantially above zero. Among

the key data this study series can oer

are the upper bounds o how many

cases can be typically expected rom a

given population, but it was noted that

additional data could be recorded to add

value to the study results. The benefts

o these studies could be maximized as

ollows:

1) For Polio Eradication: Better

defning the risks associated with

iVDPVs and providing a model or

the eventual integration o this

work into routine surveillance.

2) For Patients with PIDs: Preventing

a new generation o excretors andidentiying potential recipients o

antiviral treatment.
http://www.who.int/mailto:[email protected]://www.who.int/about/licensing/copyright_form/en/index.htmlhttp://www.who.int/about/licensing/copyright_form/en/index.htmlhttp://www.who.int/about/licensing/copyright_form/en/index.htmlhttp://www.who.int/about/licensing/copyright_form/en/index.htmlmailto:[email protected]://www.who.int/


8/8


The Polio Research Committees call or proposals

The Polio Research Committee (PRC) iscurrently soliciting research proposals tosupport the implementation and evaluation

o the Global Polio Eradication Initiative(GPEI) Strategic Plan 2010-2012, withparticular ocus on the ollowing topics.

1. Operational research

A key aspect o the GPEI Strategic Plan2010-2012 is to continuously review thequality o surveillance or supplementaryimmunization activities (SIAs) and fllcritical gaps in quality. The GPEI is interestedin research proposals to aid the process oidentifcation o high-risk areas, supportand acilitate evidence-based solutions

to improve programme immunizationoperations.

Operational research priorities to be consideredor unding include:

a. Identifcation o key issues in areaswith persistent polio transmission and/or repeated importations resulting inre-established transmission;

b. Social research to understand migratorypopulations and implications to thepolio epidemiology in polio-inectedcountries (e.g., the size and pattern omigration and their knowledge, attitudeand practice towards immunization andgeneral healthcare seeking behaviour);

c. Evaluation o alternative operation modelor the quality coverage o migratorypopulations during SIAs; and,

d. Evaluation o initiatives to improveoperations in areas with compromisedsecurity (e.g., short interval additionaldoses, alternative operational model toaddress security risks).

2. Communication researchThe Independent Monitoring Board (IMB)report released in April 2011 recommendedthat the GPEI address complex operationalor interpersonal difculties in localcommunities (worms eye view orealities on the ground). Accordingly, theGPEI is soliciting proposals in the areao communication research, which helpidentiy and address challenges and monitorperormance in polio communication.

Some potential communications research

subjects include:a. Evaluation o risk perception and risk

communication among vaccine recipientsand health workers;

b. Innovative survey approaches to generate

social data which does not rely on sel-reported process indicators;

c. Analysis o non-compliance and

anti-vaccine behaviour (e.g., rumoursurveillance) in order to develop betterdesigned and more appropriately targetedinterventions; and,

d. Evaluation o dierent communicationinterventions to promote knowledge,behaviour change and improve acceptance,including improved documentation oboth successes and challenges concerningthe demand or polio vaccine.

3. Evaluation o improving and utilizing IPV

The ability to aordably maintain immunityagainst polio in countries which choose todo so will be key to saely managing thetransition period ollowing OPV cessation,ater which inactivated polio vaccine (IPV)will be the only appropriate polio vaccine.

Preparing or the wider use o IPV, the GPEIhas intensifed its programme o work tostudy a range o aordable IPV strategiesand assess the easibility and eectivenesso IPV introduction.

Especially, the ollowing ocus are o interest:a. Evaluation o immunological mechanisms

and persistence o priming among inantsvaccinated with IPV;

b. Assessment o impact o adding IPV onSIA quality (e.g., coverage); and,

c. Assessment o VDPV emergence ater theswitch rom OPV to IPV-only schedulein national immunization programme indeveloping countries.

4. Improving routine immunization

activities with GPEI inrastructureEnsuring strong immunization systems orthe delivery o routine childhood vaccineshas been one o the our core strategies othe GPEI since its launch in 1988. The GPEIis interested in a pilot project to utilizeGPEI assets (e.g., skilled human resource,immunization inrastructure, operatingknow-how) to improve the quality o routineimmunization.

5. Improving acute faccid paralysis (AFP)

surveillance

Surveillance for cases of acute accidparalysis (AFP) is the core strategy employedby the GPEI to detect the transmission owild polioviruses or circulating vaccine-derived polioviruses, guide SIA strategy,

and acilitate the eventual certifcation

o eradication. In some areas o the world,

there are still surveillance gaps in key high-

risk areas. The GPEI is interested in a pilotproject to address these known gaps through

the use o new technology (e.g., geographic

inormation system - GIS, or short message

service - SMS).

Research proposals are invited rom GPEI

sta (e.g., EPI managers) and independent

institutions/investigators, as well as private

cooperations.

Procedure or submission o proposals:All research proposals should include the

ollowing inormation:

a. Research question/objectives (e.g.,

research questions, reerence to

published literature and cutting-edge

science, description o how the results

will be utilized).

b. Qualifcation o investigators and

collaborators (e.g., track record o

researchers, capability o laboratory,

necessary contractual arrangements).

c. Budget request (e.g., appropriate or

work anticipated).

d. Study design and methodology (e.g.,

detailed activities, timelines, deliverables,

availability o necessary capacities,

easibility o methods, plans or ethical

and government approvals).

The standard research proposal orm is

available at http://www.polioeradication.

org/Research/Grantsandcollaboration/

Howtoapply.aspx

Researchers are invited to submit proposals

by 31 July 2011 to the Research and Product

Development team, GPEI, WHO Geneva, by

email to [email protected]
http://www.polioeradication.org/Research/Grantsandcollaboration/Howtoapply.aspxhttp://www.polioeradication.org/Research/Grantsandcollaboration/Howtoapply.aspxhttp://www.polioeradication.org/Research/Grantsandcollaboration/Howtoapply.aspxmailto:[email protected]:[email protected]://www.polioeradication.org/Research/Grantsandcollaboration/Howtoapply.aspxhttp://www.polioeradication.org/Research/Grantsandcollaboration/Howtoapply.aspxhttp://www.polioeradication.org/Research/Grantsandcollaboration/Howtoapply.aspx

PolioPipeline_08

Documents

Transcript of PolioPipeline_08