World Health Organization Guidelines for Containment of Poliovirus Following Type-Specific Polio Eradication — Worldwide, 2015

Nicoletta Previsani, PhD1; Rudolph H. Tangermann, MD1; Graham Tallis1; Hamid S. Jafari, MD1

In 1988, the World Health Assembly of the World Health Organization (WHO) resolved to eradicate polio worldwide. Among the three wild poliovirus (WPV) types (type 1, type 2, and type 3), WPV type 2 (WPV2) has been eliminated in the wild since 1999, and WPV type 3 (WPV3) has not been reported since 2012. In 2015, only Afghanistan and Pakistan have reported WPV transmission (1). On May 25, 2015, all WHO Member States endorsed World Health Assembly resolution 68.3 on full implementation of the Polio Eradication and Endgame Strategic Plan 2013–2018 (2,3) (the Endgame Plan), and with it, the third Global Action Plan to minimize poliovirus facility-associated risk (4) (GAPIII). All WHO Member States have committed to implementing appropriate containment of WPV2 in essential laboratory and vaccine production facilities* by the end of 2015 and of type 2 oral poliovirus vaccine (OPV2) within 3 months of global withdrawal of OPV2, which is planned for April 2016 (5). This report summarizes critical steps for essential laboratory and vaccine production facilities that intend to retain materials confirmed to contain or potentially containing type-specific WPV, vaccine-derived poliovirus (VDPV), or OPV/Sabin viruses, and steps for nonessential facilities† that process specimens that contain or might contain polioviruses. National authorities will need to certify that the essential facilities they host meet the containment requirements described in GAPIII. After certification of WPV eradication, the use of all OPV will cease; final containment of all polioviruses after polio eradication and OPV cessation will minimize the risk for reintroduction of poliovirus into a polio-free world.

Background

The Endgame Plan (3) set the goal of eradicating WPV and VDPV. Achieving this goal requires 1) detection of circulating polioviruses and interruption of transmission; 2) sequential cessation of the use of type-specific OPV to eliminate the risks for vaccine-associated paralytic poliomyelitis, chronic VDPV infections of immunodeficient persons, and outbreaks of circulating VDPV (cVDPV) (6,7); and 3) implementation of measures for the safe handling and containment of polioviruses to minimize the risks for facility-associated reintroduction of virus into polio-free communities. The first step toward OPV cessation will be the global, synchronized withdrawal of OPV2, which has caused approximately 90% of cVDPV cases since WPV2 was last reported in 1999. OPV2 withdrawal will be accomplished by replacing trivalent OPV (tOPV) with bivalent OPV (bOPV, protecting against types 1 and 3 in all countries using OPV for routine immunization, preceded by the introduction of a minimum of 1 dose of inactivated poliovirus vaccine (IPV), which protects against all three virus types (5). Approval to confirm the global switch from tOPV to bOPV, anticipated in April 2016, will follow review in October 2015 of whether a number of readiness criteria are met, including progress toward completion of the initial phase of poliovirus containment activities and establishment of readiness for appropriate handling of residual type 2 materials, as described below.

Methods

The Endgame Plan includes phased withdrawal of OPV strains. GAPIII was aligned to the Endgame Plan and comprises three phases (Figure): Phase I, Preparation for containment of poliovirus type 2, lasting until global readiness criteria for the switch are met (current target is end of 2015); Phase II, Poliovirus type 2 containment, lasting until all WHO regions certify WPV elimination; and Phase III, Final poliovirus containment. National authorities in all countries are currently tasked with completing Phase I and preparing for Phase II (Table 1).

The controls described in GAPIII reflect containment best practices, and are largely derived from the European Committee for Standardization Workshop Agreement 15793 (2011) — Laboratory Biorisk Management (8), with input from leaders in the field of poliovirus transmission and biorisk management.

Rationale

Reintroduction of WPV from a poliovirus facility after type-specific eradication risks the potentially disastrous consequence of reestablishing WPV transmission. When OPV use stops, many countries will maintain high population coverage with IPV, other countries will have suboptimal IPV coverage, and still others might discontinue use of IPV and all national polio immunization activities. Reintroduction of an OPV/Sabin strain from a facility creates risks for unrecognized virus transmission, reversion to cVDPV, and reestablishment of poliovirus transmission.

Most countries will have no need to retain polioviruses following WPV eradication and cessation of OPV use. Facility-associated risks in these countries can be eliminated by a thorough nationwide search for, and destruction of, all infectious and potentially infectious materials, including WPV, VDPV, and OPV/Sabin viruses. Some countries will host a limited number of essential laboratory and vaccine production facilities that serve critical program and research functions, including production of IPV and Sabin-IPV (IPV produced using attenuated strains from the Sabin oral vaccine as seed), production and storage of monovalent OPV stockpiles of each type, vaccine quality assurance, diagnostic reagent production, and crucial research. Each essential poliovirus facility should manage biorisk appropriately to minimize the risk for virus reintroduction into the community, with effective national certification and WHO verification programs to assure compliance with GAPIII. The risk for a poliovirus reintroduction can further be minimized by ensuring that essential facilities are located in areas with high levels of population immunity and acute flaccid paralysis and environmental surveillance, supplemented by efficient public health and response capacity (Table 2). Minimizing the number of essential facilities worldwide will further reduce the magnitude of risk, facilitate national and international oversight, and strengthen the likelihood that global containment standards can be met and successfully maintained.

Policy and Implementation

Phase I: Preparation for containment of all type 2 polioviruses. Phase I is currently in progress. Phase I for WPV2 will continue until the conditions of global readiness for OPV2 withdrawal have been met (Table 1), which include elimination of persistent cVDPV2 and certification of WPV2 eradication, currently planned for review in October 2015. Phase I for OPV2/Sabin2 will continue until 3 months after the switch from tOPV to bOPV. Surveyed national laboratories should include 1) all public or private facilities working with WPV2/VDPV2 and all facilities working with OPV2/Sabin2 or with fecal or respiratory materials that could contain WPV2, VDPV2, or OPV2/Sabin2 (collected at a time and place when OPV was in use), and 2) all public or private facilities that might have collections of infectious or potentially infectious WPV2, VDPV2 or OPV2/Sabin2 materials of any origin that are maintained for any reason.

Facilities that retain specimens that might contain WPV2/VDPV2 viruses must destroy or contain such materials before Phase IIa can begin. Facilities that wish to retain specimens that might contain OPV2/Sabin2 viruses (i.e., fecal or respiratory samples collected in places when OPV was in use) must destroy or contain such materials before commencement of Phase IIb. Laboratories wishing to retain historic collections of clinical materials potentially containing polioviruses, but that are not planning to implement the poliovirus containment measures described in GAPIII, must explore transfer options with designated certified essential poliovirus facilities for handling and storage arrangements.

Phase II: Poliovirus type 2 containment period. Phase II begins as soon as the criteria for global readiness for OPV2 withdrawal are met (5) and is currently planned for January 2016 (Table 1). This phase comprises two parts: the first (Phase IIa) addresses the containment of WPV2, and the second (Phase IIb) the containment of OPV2/Sabin2 polioviruses in certified essential facilities. Phase IIa begins after elimination of persistent cVDPV2 and certification of WPV2 eradication, at the time of global readiness for OPV2 withdrawal, and ends after all six WHO regions have certified WPV eradication. Phase IIb begins within 3 months of withdrawal of tOPV and the switch to bOPV, and ends within 3 months after global bOPV cessation. Essential poliovirus facilities handling and storing WPV2 or OPV2/Sabin2 materials in Phase II must be certified to implement containment procedures, and be regularly reassessed against WPV2 containment provisions described in GAPIII, including primary and secondary safeguards (Table 2). Once Phase II begins, facilities that have not received national certification for WPV2 containment will no longer be permitted to handle and store WPV2 materials. Countries or concerned facilities may apply to WHO through their national authorities for verification of containment in essential poliovirus facilities, certified by the ministries of health or other designated national authority, and declared to meet all biorisk management criteria consistent with GAPIII.

Phase III: Final poliovirus containment. Phase III also has two parts (Phases IIIa and IIIb). Phase IIIa (final containment of all WPV after polio eradication) begins when all six WHO regions have completed the certification of WPV eradication, at least 3 years after the last isolation of WPV (Table 1). Certified essential laboratories and IPV production facilities handling and storing any WPV or VDPV materials must implement final containment of all WPV provisions, including primary, secondary, and tertiary safeguards (Table 2). Once Phase III begins, facilities that have not received national certification for final containment of all WPV will no longer be permitted to handle and store any WPV materials. At the time of global bOPV cessation (currently planned for 1 year after the global declaration of WPV eradication), all countries must recall and destroy bOPV stocks. WHO will provide specific implementation guidelines for collection and destruction of bOPV from designated collection points, health facilities, or private practitioners, and national and subnational storage facilities (9).

Phase IIIb (final containment of all OPV poliovirus after bOPV cessation) will begin 3 months after global bOPV cessation (Figure) (Table 1). Certified essential poliovirus laboratories and Sabin-IPV vaccine production facilities handling and storing OPV/Sabin materials (but no WPV) must implement final provisions for containment of all OPV/Sabin polioviruses, including primary and secondary safeguards (Table 2). Once Phase IIIb begins, facilities that have not received national certification for final containment of all OPV/Sabin polioviruses will no longer be permitted to handle and store OPV/Sabin materials. Within 6 months of bOPV cessation, all countries must submit documentation that requirements for final containment of all OPV/Sabin polioviruses have been met.

Discussion

An estimated 500 facilities worldwide are currently holding type 2 polioviruses. One of the goals of poliovirus containment is to reduce this number substantially (10), dissuading candidate facilities not meeting the GAPIII containment criteria for essential facilities from holding any polioviruses.

It is important to note that poliovirus diagnostic laboratories will continue to be critical for surveillance and will remain so for years to come. Poliovirus diagnostic laboratories are not required to become certified essential poliovirus facilities to continue to perform their jobs, as long as they do not retain live polioviruses. However, laboratories that perform reference (and diagnostic) functions need to retain live polioviruses and thus be certified to meet the criteria for essential poliovirus facilities. Only designated essential poliovirus facilities that are certified to meet GAPIII containment requirements will handle and store polioviruses.

The timeline presented in GAPIII for the type-specific containment of polioviruses is short, both for candidate essential poliovirus facilities to be assessed and certified to meet GAPIII requirements, and for national authorities responsible for containment to deliver containment certificates. However, continuation of polio vaccine production, surveillance, and research is critical and must continue. To help manage the practical challenges associated with implementation of containment for essential laboratory and vaccine production facilities, interim certification of containment has been proposed. Interim certification would allow containment certification to proceed during the endgame phases of eradication in a controlled and structured manner, as issues associated with meeting the requirements for full containment certificates are addressed within pressing timelines. The proposed mechanisms will provide some degree of flexibility as facilities make the required changes, and national authorities and other governing bodies develop the required capacity to implement certification requirements.

The final containment of all WPV/VDPVs, including types 1 and 3, is approaching. After WPV transmission has been stopped, final containment of all polioviruses will minimize the risk for poliovirus reintroduction into a polio-free world once all OPV use is phased out. As is the case with variola virus, containment requirements will have to be regularly assessed and maintained, until a global decision is made to destroy all remaining poliovirus materials and prohibit any de novo synthesis.

1Polio Eradication Department, World Health Organization.

Corresponding author: Nicoletta Previsani, PhD, previsanin@who.int, 41-22-791-2866.

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