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Polio endgame: the global introduction of inactivated polio vaccine Expert Rev. Vaccines 14(5), 749–762 (2015)
Manish Patel*1, Simona Zipursky2, Walt Orenstein3, Julie Garon3 and Michel Zaffran2 1 Task Force for Global Health, 325 Swanton Way, Atlanta, GA 30330, USA 2 World Health Organization, Geneva, Switzerland 3 Emory University, Atlanta, GA, USA *Author for correspondence: [email protected]
In 2013, the World Health Assembly endorsed a plan that calls for the ultimate withdrawal of oral polio vaccines (OPV) from all immunization programs globally. The withdrawal would begin in a phased manner with removal of the type 2 component of OPV in 2016 through a global switch from trivalent OPV to bivalent OPV (containing only types 1 and 3). To mitigate risks associated with immunity gaps after OPV type 2 withdrawal, the WHO Strategic Advisory Group of Experts has recommended that all 126 OPV-only using countries introduce at least one dose of inactivated polio vaccine into routine immunization programs by end-2015, before the trivalent OPV-bivalent OPV switch. The introduction of inactivated polio vaccine would reduce risks of reintroduction of type 2 poliovirus by providing some level of seroprotection, facilitating interruption of transmission if outbreaks occur, and accelerating eradication by boosting immunity to types 1 and 3 polioviruses. KEYWORDS: eradication . immunization . inactivated polio vaccine . oral polio vaccine . polio . poliomyelitis
The eradication of polio is a top global health priority. Since the World Health Assembly (WHA) endorsed the goal to eradicate polio in 1988, the number of polio cases has drastically declined (FIGURE 1) from an estimated 350,000 cases per year in 1988 to only 416 cases in 2013 and 342 cases in 2014 (as of 24 December 2014) [1]. This success has been largely related to wide-scale use of oral polio vaccine (OPV) in developing countries that face the highest burden of polio disease with incremental net benefit estimates of ~40–50 billion US dollars [2]. OPV is the most effective vaccine against the wild poliovirus (WPV), and the benefit from its use in these countries has been immense. OPV has been the vaccine of choice in the eradication effort as it induces both oral and intestinal mucosal immunity thus leading to decreased transmission of wild viruses by reducing the amount of WPV excreted when reinfected. OPV can also immunize close contacts or boost their immunity through secondary spread [3]. In addition, it has the added benefits of being extremely affordable and easy to administer even by volunteers with limited training. OPV will continue to be the vaccine of choice for most countries until WPV is eradicated [4]. However, the use of OPV comes along with
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two rare but important potential consequences. First, the live attenuated vaccine can also very rarely cause paralytic polio in vaccinated individuals or close contacts (vaccine-associated paralytic polio [VAPP]). In addition, individuals can shed slightly modified polio vaccine viruses into the environment. Accumulation of mutations can occur through circulation of these modified polio vaccine viruses in the community, particularly in communities with lower population immunity to polio. With sufficient mutations, these vaccine viruses may achieve the same transmissibility and neurovirulence as WPV (circulating vaccine-derived polioviruses [cVDPV]) [5,6]. Therefore, efforts to eradicate paralytic polio must focus on both WPV as well as OPV vaccine viruses. Inactivated polio vaccine (IPV) is also an important tool to help achieve and maintain polio eradication. IPV consists of inactivated (killed) wild-type poliovirus strains of all three poliovirus types [7]. Because IPV is an inactivated vaccine and not a ‘live’ attenuated vaccine, it carries no risk of VAPP or VDPV. This combined with the need for ongoing immunity against polioviruses after eradication of polio and withdrawal of OPV makes IPV the ideal vaccine choice in the post-eradication
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Figure 1. Clinical cases of polio related to wild poliovirus globally (1988–2013)†. † As of 24 December 2014. Data available from [1].
era. While IPV provides high levels of systemic immunity preventing poliovirus invasion of the CNS, thereby protecting against paralysis, IPV does not replicate in the gut and thus induces substantially lower levels of intestinal immunity compared with OPV [8]. Thus, IPV when used exclusively is less effective than OPV in reducing fecal-oral transmission but does boost intestinal immunity in individuals with previous gut exposure to wild or vaccine virus [9,10]. IPV does not provide protection to others through secondary spread and indirect immunization. However, IPV is effective at limiting viral shedding from the nasopharynx so it should be equivalent to OPV in preventing oral-oral transmission [11]. In May 2013, the WHA endorsed the Polio Eradication and Endgame Strategic Plan (the Plan), which provides a detailed approach and concrete timeline for complete polio eradication [12]. The Plan highlights the importance of using OPV until the elimination of types 1 and 3 (type 2 has not been seen since 1999) is confirmed, but also calls for initiating a phased withdrawal of OPV globally to address risks associated with the OPV (cVDPVs and VAPP). The phased withdrawal of OPV could begin as early as 2016, with the removal of type 2 OPV through a global switch from trivalent OPV (tOPV) to bivalent OPV (bOPV, containing only types 1 and 3). This switch from tOPV to bOPV would have to occur in a coordinated manner globally during a 2-week window to minimize risks of cVDPV generation and importation from areas of ongoing tOPV use. To manage risks related to the type 2 immunity gaps in the population resulting from removal of the type 2 component of 750
OPV, the WHO Strategic Advisory Group of Experts (SAGE) on immunization has recommended that all OPV-only using countries introduce at least one dose of IPV in their routine immunization programs before the end of 2015, prior to the tOPV-bOPV switch [13–17]. These risks include the reemergence of polio cases related to this serotype from breaks in laboratory containment, potential continued use of this component of OPV by some areas after the rest of the world has stopped and reseeding of the population by chronic immunedeficient shedders [18]. The need to introduce IPV into 126 OPV-only using countries globally by the end of 2015 represents an unprecedented challenge for global public health. Polio eradication & endgame strategic plan, 2013–2018
The Plan, developed by the Global Polio Eradication Initiative (GPEI) to complete the eradication and containment of polioviruses, differs from previous plans to eradicate polio in that it comprehensively addresses strategies for both WPV and vaccine-related poliovirus [12]. The Plan outlines four objectives (FIGURE 2). Objective 1 deals with WPV detection and interruption. Objective 2 calls for the introduction of IPV, the phased withdrawal of OPV and the strengthening of immunization systems in priority countries. Objective 3 outlines the containment and certification strategy. Objective 4 relates to the legacy planning activities after the eradication of polio, which would entail applying lessons learned from GPEI and its infrastructure to other global health priorities and initiatives [19]. Expert Rev. Vaccines 14(5), (2015)
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Objective 1 Poliovirus detection and interruption Objective 2 Stregthening immunization systems and OPV withdrawal
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Objective 3 Containment and certification
Finalize long-term containment plans
Complete containment and certification globally
Objective 4 Legacy planning
Legacy plan: consultaion and development
Legacy planning implementation
Figure 2. Polio eradication and endgame strategic plan†. † www.polioeradication.org/Portals/0/Document/Resources/StrategyWork/PEESP_EN_US.pdf (Last accessed, 22 July 2014); note that according to the current polio situation, the last WPV case did not occur by the end of 2014 as anticipated according to this Plan. Legacy Plan refers to activities after the eradication of polio which would entail applying lessons learned from GPEI and its infrastructure to other global health priorities and initiatives. bOPV: Bivalent oral polio vaccine; cVDPV: Circulating vaccine-derived polioviruses; IPV: Inactivated polio vaccine; OPV: Oral polio vaccine; OPV2: Type 2 oral polio vaccine; WPV: Wild polioviruses.
This review focuses on the technical rationale and programmatic implications related to Objective 2 which calls for: .
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Introducing at least one dose of IPV into the routine immunization schedule of all OPV-only using countries before the end of 2015. Replacing tOPV with bOPV (tOPV-bOPV switch) in 2016 in all OPV-using countries – setting the stage for eventually ending bOPV use in 2019–2020. Leveraging the use of GPEI resources to strengthen routine immunization in 10 focus countries with high polio risk where GPEI has committed significant field assets: Afghanistan, Angola, Chad, Democratic Republic of the Congo, Ethiopia, India, Nigeria, Pakistan, Somalia and South Sudan.
Rationale for OPV withdrawal
Three countries (Pakistan, Afghanistan and Nigeria) have never interrupted transmission of their indigenous viruses and are considered ‘endemic’. These countries continue to be reservoirs for re-infecting other countries worldwide. In 2013 and 2014, polio cases were also detected in seven additional countries (Equatorial Guinea, Ethiopia, Cameroon, Iraq, Kenya, Somalia and Syria) that were previously polio free (as of 21 June 2014). Although OPV is the most effective vaccine in endemic and high-risk areas to interrupt wild poliovirus transmission, with success seen in reducing the number of WPV cases globally, the estimated number of polio cases caused by OPV is likely to exceed those related to WPV (FIGURE 3). informahealthcare.com
OPV contains live attenuated strains of poliovirus that are also referred to as the ‘Sabin strains’ [3]. Five types of OPV are currently available: tOPV, bOPV1 & 3, monovalent OPV [mOPV]1, mOPV2 and mOPV3, with tOPV being the most commonly used form in routine immunization activities in low- and middle-income countries globally [16]. The selection of the type of OPV for mass campaigns known as supplementary immunization activities (SIAs) and future routine immunization is evolving due to two factors. Changing epidemiology of circulating polio strains
Since November 2012, all cases of polio related to wild virus have been type 1. There has been no natural circulation of type 2 WPV since 1999 when the last case was detected in Aligarh, India. Type 3 WPV was last detected in November 2012 in Nigeria, although the virus has not yet been certified as eradicated [1]. This change in epidemiology of WPV has guided the selection of OPV with the predominant use of bOPV (containing types 1 and 3) and mOPV1 in SIAs during recent years. Cases associated with OPV
OPV in very rare cases can lead to paralysis after spontaneous reversion to neurovirulence of one of the attenuated Sabin viruses in the vaccine. OPV may cause VAPP in the vaccine recipient or a close contact at an estimated rate of 4.7 cases per 1 million births in OPV-using countries [20]. There are an estimated 498 VAPP cases (range, 255–1018) globally per 751
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Figure 3. Reported paralytic cases of wild poliovirus (WPV) versus estimated cases of paralysis associated with OPV (VAPP and cVDPV) assuming ongoing use of OPV worldwide†. † VAPP cases are not reported globally thus number of VAPP cases are depicted in the figure as average annual WHO estimates of 500 cases per year based on global incidence [20]; cVDPV cases are actual counts based on WHO reports as of 10 December 2014. ‡ Assumes interruption of wild poliovirus transmission after 2014 according to the GPEI Eradication Plan. cVDPV: Circulating vaccine-derived polioviruses; OPV: Oral polio vaccine; VAPP: Vaccine associated paralytic polio. Data available from [1].
year [20]. Of these, about 26–31% are estimated to be caused by the type 2 component of OPV [20,21]. Typically, poliovirus isolates from VAPP demonstrate only limited genetic divergence from the parental OPV strains and cases occur among vaccine recipients or close contacts without sustained community transmission. In contrast, cVDPVs additionally take on the transmissibility characteristics of WPV and can widely spread in a community. They are not likely to be related to contact with a recent vaccine recipient as is seen in most cases of VAPP [6]. Almost all cVDPV outbreaks (97%) in recent years have been caused by a type 2 OPV-derived virus (FIGURE 4) and is likely related to the increasing immunity gap to type 2 from increasing use of bOPV in SIAs during recent years [22]. Other very rare forms include VDPVs in persons with a primary immunodeficiency syndrome, who chronically shed virus, usually from an initial vaccination (immunodeficiency VDPVs [iVDPVs]) and VDPVs not known to be associated with an outbreak or immunodeficiency (ambiguous VDPVs). Because naturally circulating wild type 2 viruses have not been detected since 1999 and nearly all cVDPVs occurring in recent years are related to the type 2 component of OPV, the first phase of the Plan calls for the removal of the type 2 component of OPV through a globally synchronized switch from tOPV to bOPV (BOX 1). The SAGE Working Group on Polio, which advises SAGE on technical and policy guidance related to IPV 752
and the Endgame, has recommended that the trigger for OPV type 2 withdrawal would be the global absence for at least 6 months of all persistent type 2 cVDPVs [23]. Persistent transmission is defined as the transmission of the same lineage of cVDPV for more than 6 months. In addition, the SAGE Polio Working Group recommends specific criteria for judging OPV2 withdrawal readiness globally, one of which includes the introduction of at least one dose of IPV into routine immunization systems of all OPV-only using countries (BOX 2) [24]. Withdrawal of type 1 and 3 OPV will occur globally after the certification of eradication of their respective WPV. Risks associated with OPV withdrawal
It should be noted that intense efforts are being undertaken by GPEI to minimize risk of cVDPV2 re-emergence after interruption of cVDPV2 transmission including introduction of IPV in the routine immunization schedule, large-scale rounds of SIAs with tOPV prior to the tOPV-bOPV switch in high-risk countries, globally coordinated and synchronized switch from tOPV to bOPV, validation and certification process to confirm absence of tOPV stocks in all countries and containment of the type 2 strain. Without the introduction of IPV into routine immunization programs, the initial phase of OPV withdrawal – switch from tOPV to bOPV – would lead to a decline in population immunity to disease from type 2 virus due to unvaccinated and unexposed newborns. This gradual increase in the number of persons susceptible to type 2 poliovirus (and types 1 and 3 after complete OPV cessation) raises three main types of risk to the population [25].
Immediate time-limited risk of cVDPV2 emergence
After countries simultaneously discontinue use of OPV2, some type 2 poliovirus strain may still persist in the community with duration of persistence depending on the level of population immunity [26]. Although intense efforts are planned for removal and disposal of tOPV, some areas may not destroy all tOPV and may continue to use it for a limited time despite recommendations for stopping vaccination and destroying the vaccine. Continued use of tOPV after global cessation would put the country and potentially its neighbors at risk of cVDPV2 outbreaks. Verification efforts will be more intense in countries with the highest risk of cVDPV2 and thus likelihood of continued tOPV use would be greatest in countries with lower risk of cVDPV2 emergence. Cessation of production of Expert Rev. Vaccines 14(5), (2015)
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and vaccination with OPV type 2 will ultimately halt the generation of new cVDPVs globally but a time-limited risk of cVDPV2 re-emergence could exist from the possibility of residual OPV type 2 regaining neurovirulence and establishing transmission. Modeling estimates the risk of a cVDPV2 outbreaks following effectively coordinated OPV2 cessation to be greatest during the first 1–2 years after cessation, with the highest risk in the first several months [18]. Assuming successful global coordination, there is a very small risk during the third year and if no cVDPVs have occurred during the first 3 years, the risk is minimal thereafter. The risk of a cVDPV outbreak in any given country is low and will vary depending on factors associated with polio transmission such as population immunity against type 2, which can be inferred from vaccination coverage with the type 2 component (i.e., tOPV boosts before OPV2 cessation in high-risk countries), population density, sanitation and hygiene.
source of this virus introduction remains unknown. While this outbreak was controlled by achieving high population immunity to type 2 virus at the time, and there was no evidence of extensive person-to-person transmission of the virus, the experience highlights the potential risk in a population with immunity gaps, as would occur if all polio vaccination against type 2 viruses – including IPV – was stopped. Spread of virus from rare immune-deficient individuals who are chronically infected with iVDPV
Persons with primary immunodeficiencies, a group of genetic disorders that increase risk of chronic or recurrent infections, Box 1. Justifications for withdrawal of the type 2 component of oral polio vaccine. .
Medium & long-term risk of WPV outbreaks
Type 2 WPV re-introduction from a vaccine manufacturing site, research facility, diagnostic laboratory or a bioterrorism event is possible and difficult to predict. A reintroduction of poliovirus or emergence of cVDPV2 could potentially result in a substantial polio outbreak or even re-establishment of global transmission. There have been previous instances when type 2 WPV was reintroduced into a population. During 2002– 2003, contamination of OPV with a WPV type 2 laboratory reference strain (MEF-1) led to 10 acute flaccid paralysis cases in India, after naturally transmitted wild type 2 virus was apparently eliminated in 1999 [27]. The laboratory or institutional informahealthcare.com
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Type 2 wild polioviruses has not been circulating naturally since the last case was detected in 1999 in Aligarh, India thus eliminating the need for the type 2 component of the vaccine. Since 2009, 97% of all vaccine-derived polioviruses have been due to type 2 virus. Approximately 26–31% of all vaccine-associated paralytic polio cases are related to type 2 component of OPV. Presence of type 2 component in the vaccine reduces the immune response to types 1 and 3 poliovirus requiring more doses of trivalent OPV to reach herd immunity thresholds for those types compared with the number of doses of bivalent OPV to reach those same immunity thresholds.
OPV: Oral polio vaccine.
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Box 2. The trigger and the five prerequisites for the switch from trivalent OPV to bivalent OPV [67]. The trigger for setting a definitive date for the withdrawal of the type 2 component of the oral polio vaccine globally will be the absence of all persistent circulating vaccine-derived type 2 polioviruses for at least 6 months. The 5 prerequisites endorsed by the World Health Assembly that must be in place prior to the withdrawal of OPV2 in all OPV-using countries include: Expert Review of Vaccines Downloaded from informahealthcare.com by Nanyang Technological University on 04/24/15 For personal use only.
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Introduction of at least one dose of inactivated poliovirus vaccine; Access to a bOPV that is licensed for routine immunization; Implementation of surveillance and response protocols for type 2 poliovirus (including constitution of a stockpile of monovalent oral polio vaccine type 2); Completion of Phase I poliovirus containment activities, with appropriate handling of residual type 2 materials; Verification of global eradication of wild poliovirus type 2.
bOPV: Bivalent oral polio vaccine; OPV: Oral polio vaccine.
who receive OPV prior to cessation may continue to excrete iVDPVs for a prolonged period of time. This is a very rare situation with WHO surveillance reporting fewer than 100 chronic excretors of iVDPV since the introduction of OPV in 1961 [28]. It is theoretically possible that the long-term iVDPV excretors could spread viruses to an unimmunized community although, because of the low prevalence of prolonged or chronic iVDPV excretors globally, the probability is estimated to be
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Polio endgame: the global introduction of inactivated polio vaccine Expert Rev. Vaccines 14(5), 749–762 (2015)
Manish Patel*1, Simona Zipursky2, Walt Orenstein3, Julie Garon3 and Michel Zaffran2 1 Task Force for Global Health, 325 Swanton Way, Atlanta, GA 30330, USA 2 World Health Organization, Geneva, Switzerland 3 Emory University, Atlanta, GA, USA *Author for correspondence: [email protected]
In 2013, the World Health Assembly endorsed a plan that calls for the ultimate withdrawal of oral polio vaccines (OPV) from all immunization programs globally. The withdrawal would begin in a phased manner with removal of the type 2 component of OPV in 2016 through a global switch from trivalent OPV to bivalent OPV (containing only types 1 and 3). To mitigate risks associated with immunity gaps after OPV type 2 withdrawal, the WHO Strategic Advisory Group of Experts has recommended that all 126 OPV-only using countries introduce at least one dose of inactivated polio vaccine into routine immunization programs by end-2015, before the trivalent OPV-bivalent OPV switch. The introduction of inactivated polio vaccine would reduce risks of reintroduction of type 2 poliovirus by providing some level of seroprotection, facilitating interruption of transmission if outbreaks occur, and accelerating eradication by boosting immunity to types 1 and 3 polioviruses. KEYWORDS: eradication . immunization . inactivated polio vaccine . oral polio vaccine . polio . poliomyelitis
The eradication of polio is a top global health priority. Since the World Health Assembly (WHA) endorsed the goal to eradicate polio in 1988, the number of polio cases has drastically declined (FIGURE 1) from an estimated 350,000 cases per year in 1988 to only 416 cases in 2013 and 342 cases in 2014 (as of 24 December 2014) [1]. This success has been largely related to wide-scale use of oral polio vaccine (OPV) in developing countries that face the highest burden of polio disease with incremental net benefit estimates of ~40–50 billion US dollars [2]. OPV is the most effective vaccine against the wild poliovirus (WPV), and the benefit from its use in these countries has been immense. OPV has been the vaccine of choice in the eradication effort as it induces both oral and intestinal mucosal immunity thus leading to decreased transmission of wild viruses by reducing the amount of WPV excreted when reinfected. OPV can also immunize close contacts or boost their immunity through secondary spread [3]. In addition, it has the added benefits of being extremely affordable and easy to administer even by volunteers with limited training. OPV will continue to be the vaccine of choice for most countries until WPV is eradicated [4]. However, the use of OPV comes along with
informahealthcare.com
10.1586/14760584.2015.1001750
two rare but important potential consequences. First, the live attenuated vaccine can also very rarely cause paralytic polio in vaccinated individuals or close contacts (vaccine-associated paralytic polio [VAPP]). In addition, individuals can shed slightly modified polio vaccine viruses into the environment. Accumulation of mutations can occur through circulation of these modified polio vaccine viruses in the community, particularly in communities with lower population immunity to polio. With sufficient mutations, these vaccine viruses may achieve the same transmissibility and neurovirulence as WPV (circulating vaccine-derived polioviruses [cVDPV]) [5,6]. Therefore, efforts to eradicate paralytic polio must focus on both WPV as well as OPV vaccine viruses. Inactivated polio vaccine (IPV) is also an important tool to help achieve and maintain polio eradication. IPV consists of inactivated (killed) wild-type poliovirus strains of all three poliovirus types [7]. Because IPV is an inactivated vaccine and not a ‘live’ attenuated vaccine, it carries no risk of VAPP or VDPV. This combined with the need for ongoing immunity against polioviruses after eradication of polio and withdrawal of OPV makes IPV the ideal vaccine choice in the post-eradication
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Figure 1. Clinical cases of polio related to wild poliovirus globally (1988–2013)†. † As of 24 December 2014. Data available from [1].
era. While IPV provides high levels of systemic immunity preventing poliovirus invasion of the CNS, thereby protecting against paralysis, IPV does not replicate in the gut and thus induces substantially lower levels of intestinal immunity compared with OPV [8]. Thus, IPV when used exclusively is less effective than OPV in reducing fecal-oral transmission but does boost intestinal immunity in individuals with previous gut exposure to wild or vaccine virus [9,10]. IPV does not provide protection to others through secondary spread and indirect immunization. However, IPV is effective at limiting viral shedding from the nasopharynx so it should be equivalent to OPV in preventing oral-oral transmission [11]. In May 2013, the WHA endorsed the Polio Eradication and Endgame Strategic Plan (the Plan), which provides a detailed approach and concrete timeline for complete polio eradication [12]. The Plan highlights the importance of using OPV until the elimination of types 1 and 3 (type 2 has not been seen since 1999) is confirmed, but also calls for initiating a phased withdrawal of OPV globally to address risks associated with the OPV (cVDPVs and VAPP). The phased withdrawal of OPV could begin as early as 2016, with the removal of type 2 OPV through a global switch from trivalent OPV (tOPV) to bivalent OPV (bOPV, containing only types 1 and 3). This switch from tOPV to bOPV would have to occur in a coordinated manner globally during a 2-week window to minimize risks of cVDPV generation and importation from areas of ongoing tOPV use. To manage risks related to the type 2 immunity gaps in the population resulting from removal of the type 2 component of 750
OPV, the WHO Strategic Advisory Group of Experts (SAGE) on immunization has recommended that all OPV-only using countries introduce at least one dose of IPV in their routine immunization programs before the end of 2015, prior to the tOPV-bOPV switch [13–17]. These risks include the reemergence of polio cases related to this serotype from breaks in laboratory containment, potential continued use of this component of OPV by some areas after the rest of the world has stopped and reseeding of the population by chronic immunedeficient shedders [18]. The need to introduce IPV into 126 OPV-only using countries globally by the end of 2015 represents an unprecedented challenge for global public health. Polio eradication & endgame strategic plan, 2013–2018
The Plan, developed by the Global Polio Eradication Initiative (GPEI) to complete the eradication and containment of polioviruses, differs from previous plans to eradicate polio in that it comprehensively addresses strategies for both WPV and vaccine-related poliovirus [12]. The Plan outlines four objectives (FIGURE 2). Objective 1 deals with WPV detection and interruption. Objective 2 calls for the introduction of IPV, the phased withdrawal of OPV and the strengthening of immunization systems in priority countries. Objective 3 outlines the containment and certification strategy. Objective 4 relates to the legacy planning activities after the eradication of polio, which would entail applying lessons learned from GPEI and its infrastructure to other global health priorities and initiatives [19]. Expert Rev. Vaccines 14(5), (2015)
Polio endgame
Last WPV case 2013
Expert Review of Vaccines Downloaded from informahealthcare.com by Nanyang Technological University on 04/24/15 For personal use only.
Objective 1 Poliovirus detection and interruption Objective 2 Stregthening immunization systems and OPV withdrawal
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2015
Wild poliovirus interruption
Strengthen immunization systems Address prerequisites for OPV2 cessation
Last OPV2 use 2016
Review
Global certification
boPV cessation
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2019
2017
Outbreak response [especially cVDPVs]
Complete IPV introduction and OPV2 withdrawal
IPV and OPV in routine immunization
Objective 3 Containment and certification
Finalize long-term containment plans
Complete containment and certification globally
Objective 4 Legacy planning
Legacy plan: consultaion and development
Legacy planning implementation
Figure 2. Polio eradication and endgame strategic plan†. † www.polioeradication.org/Portals/0/Document/Resources/StrategyWork/PEESP_EN_US.pdf (Last accessed, 22 July 2014); note that according to the current polio situation, the last WPV case did not occur by the end of 2014 as anticipated according to this Plan. Legacy Plan refers to activities after the eradication of polio which would entail applying lessons learned from GPEI and its infrastructure to other global health priorities and initiatives. bOPV: Bivalent oral polio vaccine; cVDPV: Circulating vaccine-derived polioviruses; IPV: Inactivated polio vaccine; OPV: Oral polio vaccine; OPV2: Type 2 oral polio vaccine; WPV: Wild polioviruses.
This review focuses on the technical rationale and programmatic implications related to Objective 2 which calls for: .
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Introducing at least one dose of IPV into the routine immunization schedule of all OPV-only using countries before the end of 2015. Replacing tOPV with bOPV (tOPV-bOPV switch) in 2016 in all OPV-using countries – setting the stage for eventually ending bOPV use in 2019–2020. Leveraging the use of GPEI resources to strengthen routine immunization in 10 focus countries with high polio risk where GPEI has committed significant field assets: Afghanistan, Angola, Chad, Democratic Republic of the Congo, Ethiopia, India, Nigeria, Pakistan, Somalia and South Sudan.
Rationale for OPV withdrawal
Three countries (Pakistan, Afghanistan and Nigeria) have never interrupted transmission of their indigenous viruses and are considered ‘endemic’. These countries continue to be reservoirs for re-infecting other countries worldwide. In 2013 and 2014, polio cases were also detected in seven additional countries (Equatorial Guinea, Ethiopia, Cameroon, Iraq, Kenya, Somalia and Syria) that were previously polio free (as of 21 June 2014). Although OPV is the most effective vaccine in endemic and high-risk areas to interrupt wild poliovirus transmission, with success seen in reducing the number of WPV cases globally, the estimated number of polio cases caused by OPV is likely to exceed those related to WPV (FIGURE 3). informahealthcare.com
OPV contains live attenuated strains of poliovirus that are also referred to as the ‘Sabin strains’ [3]. Five types of OPV are currently available: tOPV, bOPV1 & 3, monovalent OPV [mOPV]1, mOPV2 and mOPV3, with tOPV being the most commonly used form in routine immunization activities in low- and middle-income countries globally [16]. The selection of the type of OPV for mass campaigns known as supplementary immunization activities (SIAs) and future routine immunization is evolving due to two factors. Changing epidemiology of circulating polio strains
Since November 2012, all cases of polio related to wild virus have been type 1. There has been no natural circulation of type 2 WPV since 1999 when the last case was detected in Aligarh, India. Type 3 WPV was last detected in November 2012 in Nigeria, although the virus has not yet been certified as eradicated [1]. This change in epidemiology of WPV has guided the selection of OPV with the predominant use of bOPV (containing types 1 and 3) and mOPV1 in SIAs during recent years. Cases associated with OPV
OPV in very rare cases can lead to paralysis after spontaneous reversion to neurovirulence of one of the attenuated Sabin viruses in the vaccine. OPV may cause VAPP in the vaccine recipient or a close contact at an estimated rate of 4.7 cases per 1 million births in OPV-using countries [20]. There are an estimated 498 VAPP cases (range, 255–1018) globally per 751
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Figure 3. Reported paralytic cases of wild poliovirus (WPV) versus estimated cases of paralysis associated with OPV (VAPP and cVDPV) assuming ongoing use of OPV worldwide†. † VAPP cases are not reported globally thus number of VAPP cases are depicted in the figure as average annual WHO estimates of 500 cases per year based on global incidence [20]; cVDPV cases are actual counts based on WHO reports as of 10 December 2014. ‡ Assumes interruption of wild poliovirus transmission after 2014 according to the GPEI Eradication Plan. cVDPV: Circulating vaccine-derived polioviruses; OPV: Oral polio vaccine; VAPP: Vaccine associated paralytic polio. Data available from [1].
year [20]. Of these, about 26–31% are estimated to be caused by the type 2 component of OPV [20,21]. Typically, poliovirus isolates from VAPP demonstrate only limited genetic divergence from the parental OPV strains and cases occur among vaccine recipients or close contacts without sustained community transmission. In contrast, cVDPVs additionally take on the transmissibility characteristics of WPV and can widely spread in a community. They are not likely to be related to contact with a recent vaccine recipient as is seen in most cases of VAPP [6]. Almost all cVDPV outbreaks (97%) in recent years have been caused by a type 2 OPV-derived virus (FIGURE 4) and is likely related to the increasing immunity gap to type 2 from increasing use of bOPV in SIAs during recent years [22]. Other very rare forms include VDPVs in persons with a primary immunodeficiency syndrome, who chronically shed virus, usually from an initial vaccination (immunodeficiency VDPVs [iVDPVs]) and VDPVs not known to be associated with an outbreak or immunodeficiency (ambiguous VDPVs). Because naturally circulating wild type 2 viruses have not been detected since 1999 and nearly all cVDPVs occurring in recent years are related to the type 2 component of OPV, the first phase of the Plan calls for the removal of the type 2 component of OPV through a globally synchronized switch from tOPV to bOPV (BOX 1). The SAGE Working Group on Polio, which advises SAGE on technical and policy guidance related to IPV 752
and the Endgame, has recommended that the trigger for OPV type 2 withdrawal would be the global absence for at least 6 months of all persistent type 2 cVDPVs [23]. Persistent transmission is defined as the transmission of the same lineage of cVDPV for more than 6 months. In addition, the SAGE Polio Working Group recommends specific criteria for judging OPV2 withdrawal readiness globally, one of which includes the introduction of at least one dose of IPV into routine immunization systems of all OPV-only using countries (BOX 2) [24]. Withdrawal of type 1 and 3 OPV will occur globally after the certification of eradication of their respective WPV. Risks associated with OPV withdrawal
It should be noted that intense efforts are being undertaken by GPEI to minimize risk of cVDPV2 re-emergence after interruption of cVDPV2 transmission including introduction of IPV in the routine immunization schedule, large-scale rounds of SIAs with tOPV prior to the tOPV-bOPV switch in high-risk countries, globally coordinated and synchronized switch from tOPV to bOPV, validation and certification process to confirm absence of tOPV stocks in all countries and containment of the type 2 strain. Without the introduction of IPV into routine immunization programs, the initial phase of OPV withdrawal – switch from tOPV to bOPV – would lead to a decline in population immunity to disease from type 2 virus due to unvaccinated and unexposed newborns. This gradual increase in the number of persons susceptible to type 2 poliovirus (and types 1 and 3 after complete OPV cessation) raises three main types of risk to the population [25].
Immediate time-limited risk of cVDPV2 emergence
After countries simultaneously discontinue use of OPV2, some type 2 poliovirus strain may still persist in the community with duration of persistence depending on the level of population immunity [26]. Although intense efforts are planned for removal and disposal of tOPV, some areas may not destroy all tOPV and may continue to use it for a limited time despite recommendations for stopping vaccination and destroying the vaccine. Continued use of tOPV after global cessation would put the country and potentially its neighbors at risk of cVDPV2 outbreaks. Verification efforts will be more intense in countries with the highest risk of cVDPV2 and thus likelihood of continued tOPV use would be greatest in countries with lower risk of cVDPV2 emergence. Cessation of production of Expert Rev. Vaccines 14(5), (2015)
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Figure 4. Reported paralytic cases of cVDPV by type worldwide, 2000–2014†. † As of 24 December 2014. cVDPV: Circulating vaccine-derived polioviruses. Data available from [68,69].
and vaccination with OPV type 2 will ultimately halt the generation of new cVDPVs globally but a time-limited risk of cVDPV2 re-emergence could exist from the possibility of residual OPV type 2 regaining neurovirulence and establishing transmission. Modeling estimates the risk of a cVDPV2 outbreaks following effectively coordinated OPV2 cessation to be greatest during the first 1–2 years after cessation, with the highest risk in the first several months [18]. Assuming successful global coordination, there is a very small risk during the third year and if no cVDPVs have occurred during the first 3 years, the risk is minimal thereafter. The risk of a cVDPV outbreak in any given country is low and will vary depending on factors associated with polio transmission such as population immunity against type 2, which can be inferred from vaccination coverage with the type 2 component (i.e., tOPV boosts before OPV2 cessation in high-risk countries), population density, sanitation and hygiene.
source of this virus introduction remains unknown. While this outbreak was controlled by achieving high population immunity to type 2 virus at the time, and there was no evidence of extensive person-to-person transmission of the virus, the experience highlights the potential risk in a population with immunity gaps, as would occur if all polio vaccination against type 2 viruses – including IPV – was stopped. Spread of virus from rare immune-deficient individuals who are chronically infected with iVDPV
Persons with primary immunodeficiencies, a group of genetic disorders that increase risk of chronic or recurrent infections, Box 1. Justifications for withdrawal of the type 2 component of oral polio vaccine. .
Medium & long-term risk of WPV outbreaks
Type 2 WPV re-introduction from a vaccine manufacturing site, research facility, diagnostic laboratory or a bioterrorism event is possible and difficult to predict. A reintroduction of poliovirus or emergence of cVDPV2 could potentially result in a substantial polio outbreak or even re-establishment of global transmission. There have been previous instances when type 2 WPV was reintroduced into a population. During 2002– 2003, contamination of OPV with a WPV type 2 laboratory reference strain (MEF-1) led to 10 acute flaccid paralysis cases in India, after naturally transmitted wild type 2 virus was apparently eliminated in 1999 [27]. The laboratory or institutional informahealthcare.com
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Type 2 wild polioviruses has not been circulating naturally since the last case was detected in 1999 in Aligarh, India thus eliminating the need for the type 2 component of the vaccine. Since 2009, 97% of all vaccine-derived polioviruses have been due to type 2 virus. Approximately 26–31% of all vaccine-associated paralytic polio cases are related to type 2 component of OPV. Presence of type 2 component in the vaccine reduces the immune response to types 1 and 3 poliovirus requiring more doses of trivalent OPV to reach herd immunity thresholds for those types compared with the number of doses of bivalent OPV to reach those same immunity thresholds.
OPV: Oral polio vaccine.
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Box 2. The trigger and the five prerequisites for the switch from trivalent OPV to bivalent OPV [67]. The trigger for setting a definitive date for the withdrawal of the type 2 component of the oral polio vaccine globally will be the absence of all persistent circulating vaccine-derived type 2 polioviruses for at least 6 months. The 5 prerequisites endorsed by the World Health Assembly that must be in place prior to the withdrawal of OPV2 in all OPV-using countries include: Expert Review of Vaccines Downloaded from informahealthcare.com by Nanyang Technological University on 04/24/15 For personal use only.
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Introduction of at least one dose of inactivated poliovirus vaccine; Access to a bOPV that is licensed for routine immunization; Implementation of surveillance and response protocols for type 2 poliovirus (including constitution of a stockpile of monovalent oral polio vaccine type 2); Completion of Phase I poliovirus containment activities, with appropriate handling of residual type 2 materials; Verification of global eradication of wild poliovirus type 2.
bOPV: Bivalent oral polio vaccine; OPV: Oral polio vaccine.
who receive OPV prior to cessation may continue to excrete iVDPVs for a prolonged period of time. This is a very rare situation with WHO surveillance reporting fewer than 100 chronic excretors of iVDPV since the introduction of OPV in 1961 [28]. It is theoretically possible that the long-term iVDPV excretors could spread viruses to an unimmunized community although, because of the low prevalence of prolonged or chronic iVDPV excretors globally, the probability is estimated to be
