Global polio-eradication efforts have led to a dramatic decrease in polio cases, from an estimated 350,000 cases in 125 countries in 1988 to 72 cases in 2015. As of January 2016, endemic transmission of polio caused by wild polioviruses (WPVs) had been interrupted in all countries except Pakistan and Afghanistan. Indeed, the Global Commission for Certification of the Eradication of Poliomyelitis recently certified that type 2 wild poliovirus, one of three strains responsible for centuries of human paralysis and disfigurement, has been eradicated. Type 2 poliovirus now exists only in laboratories and in trivalent oral polio vaccine (tOPV) in an attenuated form, though in rare circumstances it surfaces in the community, through persistent transmission, in the form of outbreaks of vaccine-derived viruses. Getting to this point has not been easy. Sustaining our wins and traversing the last mile of the eradication journey calls for escalation of global immunization activities on an unprecedented scale.

Oral polio vaccine (OPV) has been the lynchpin of successful control of paralytic polio. However, in very rare instances, it has been associated with cases of paralysis caused by vaccine-associated paralytic polio (VAPP) or circulating vaccine-derived polioviruses (cVDPVs) — the latter when the viruses included in the vaccine have mutated over time, acquiring the neurovirulence and transmissibility of WPV. For this reason, it is of paramount importance to discontinue the use of OPV after polio eradication has been certified. Since the last case of naturally occurring type 2 WPV in 1999, continued use of OPV2 (the type 2 component of tOPV) has paralyzed an estimated 1600 to 3200 people with VAPP and more than 600 people with type 2 cVDPV.1 Because routine use of type 2–containing vaccine is no longer needed, the global community has a moral imperative to discontinue it as soon as programmatically feasible. Because WPV types 1 and 3 have not yet been eradicated, however, the phased withdrawal of OPV antigens will begin with a shift from tOPV (containing types 1, 2, and 3) to bivalent OPV (bOPV, containing types 1 and 3).

Risks and Risk-Mitigation Strategies for Switching from Trivalent Oral Polio Vaccine (tOPV) to Bivalent OPV (bOPV).

Global cessation of OPV2 use poses a low but real risk of outbreaks of cVDPV2 or WPV infections associated with declining immunity to type 2 poliovirus.2 The overarching strategy for reducing this risk is to maximize immunity against type 2 before and after withdrawal of the vaccine and to prepare for an appropriate outbreak response. Doing so requires a comprehensive, multipronged approach (see table).

First, it is important to stop current cVDPV2 outbreaks in advance of the switch, through aggressive tOPV vaccination in any place where cVDPV2 is detected. Programs with lower routine coverage will have to boost type 2 immunity through additional tOPV campaigns just before OPV2 withdrawal.2 A high level of immunity, especially OPV2-induced intestinal immunity, will prevent sustained transmission of vaccine viruses, which could lead to generation of new cVDPV2s.

Second, all countries should have access to enough inactivated polio vaccine (IPV) to administer at least one dose to all children through the routine immunization program. IPV provides immunity against all three polioviruses without generating any infectious vaccine-associated polioviruses. Introduction of IPV is intended to provide some immunity against type 2 viruses in new birth cohorts to mitigate future outbreaks of type 2 WPV and type 2 cVDPVs, should the viruses be reintroduced.3 IPV, however, may not prevent cVDPV2 emergence, which will be greatest during the first 6 to 12 months after OPV2 withdrawal.

Third, there had to be certified eradication of type 2 WPV, which has been accomplished.

Fourth, all countries must have destroyed type 2 WPV or securely contain it in essential laboratory and vaccine-production facilities by the end of 2015 and must do the same with OPV2 within 3 months after it is withdrawn.

Fifth, a global stockpile of monovalent type 2 OPV should be available to control outbreaks of type 2 polio, should type 2 viruses be reintroduced.

Finally, leaders of the Global Polio Eradication Initiative (GPEI) should finalize a protocol for surveillance of and response to such outbreaks.

Recently, the Strategic Advisory Group of Experts on Immunization (SAGE) reviewed progress on these readiness indicators.1,4 All high-risk countries are on track for introducing IPV. Supply shortages will delay introduction by a few months in some low-risk countries but are unlikely to increase the short-term risk of cVDPV2. SAGE also recommended accelerating implementation of the containment plan. Overall, it determined that the benefits of withdrawing OPV2 outweighed the risks, reaffirming the decision to proceed with the global switch from tOPV to bOPV between April 17 and May 1, 2016. Furthermore, it reiterated that OPV2 withdrawal must be synchronized worldwide. A prolonged, staggered withdrawal would pose a risk of continuous generation of cVDPV2s and potential exportation of these viruses to regions or countries with susceptible children born after the switch. Withdrawal of OPV2 during the seasonally low-transmission month of April further reduces the risk of type 2 polio outbreaks.

Switching from tOPV to bOPV may sound simple, but synchronization requires global coordination on an unprecedented scale. To use bOPV in routine immunization, all countries must either license a bivalent vaccine or accept one that is prequalified by the World Health Organization. Recent trial data and use of bOPV in campaigns since 2009 indicate that it is safe and more immunogenic to types 1 and 3 than is tOPV.5 Multilevel efforts to manage the global supply of OPV have begun, including discontinuation of tOPV production, scale-up of bOPV production, initiation of interactions between procurement agencies or manufacturers and countries, management of countrywide tOPV inventories to ensure that stocks are adequate until the switch and to track collection and destruction afterward, and allocation of funds for procuring bOPV. Fundamentally, countries will strive to avoid having either excess or insufficient quantities of tOPV leading up to the switch and to ensure the availability of bOPV after the switch.

Coordinated communication among global health organizations, countries, manufacturers, and funders is imperative to ensure synchronized OPV2 withdrawal with minimal disruption in vaccination services to children worldwide. Successful synchronization also requires GPEI leaders and countries to monitor the timely completion of preparatory steps both globally and within each country (e.g., managing of tOPV inventories; bOPV licensure, procurement, and shipment; securing of financial resources; establishment of communication; and training of logisticians, health workers, and monitors). Equally, if not more, important, however, will be the monitoring of outcomes of withdrawal of the vaccine in April 2016. Although it is nearly impossible to monitor every vaccination service point — India alone has more than 26,000 — a targeted monitoring strategy for high-risk areas, such as facilities storing large stocks of tOPV, could provide further reassurance of low risk of cVDPV2 reemergence. Countries will need to dispose of residual tOPV stocks using their existing pharmaceutical-waste-disposal procedures to avoid continued use of the discontinued vaccine.

More preparation for the switch is required in the coming months, and for completing polio eradication in the coming years. But collaboration in eradication efforts has reached a high point never before achieved by the immunization community. Getting here has required tireless effort and practical innovation in science, policy, and implementation. Capitalizing on the gains made to date should push overall polio eradication over the finish line and may pave the way for measles eradication and future global health initiatives.