Cessation of Trivalent Oral Poliovirus Vaccine and Introduction of Inactivated Poliovirus Vaccine — Worldwide, 2016

Global Cessation of Use of Trivalent Oral Poliovirus Vaccine

Although the global cessation of tOPV use is essential for eliminating cVDPV2s, cessation of tOPV use carries some risks for facilitating the spread of undetected or newly emergent cVDPV2s among persons without immunity to type 2 poliovirus infections after the switch to bOPV (3–5). To stop the spread of existing cVDPV2s before the switch and to reduce risks for post-switch outbreaks (4), population immunity to type 2 poliovirus at the time of the switch was boosted through implementation of 116 supplemental immunization activities (SIAs^¶) with tOPV in 42 OPV-using countries during November 2015–April 2016. Afghanistan, Nigeria, and Pakistan also conducted SIAs with IPV in selected regions before stopping tOPV use. In addition, the synchronized timing of the switch aimed to prevent exportations of type 2 polioviruses from areas continuing to use tOPV to neighboring areas that have ceased tOPV use (3,4). All 155 countries and territories that used OPV in 2015 reported that they had terminated use of tOPV by May 12, 2016 (Figure 1). To facilitate global cessation of tOPV use, all manufacturers of OPV ended production of tOPV before the switch, after several years of communications and close coordination with the Global Polio Eradication Initiative (GPEI).**

To reduce the risk for inadvertent or intentional use of tOPV after the switch, which could lead to the emergence of new cVDPV2s (5), a combination of external and in-country monitors visited >160,000 vaccine stores and service delivery points in countries and territories participating in the switch. Monitors verified the absence of tOPV from each area’s vaccine supply cold chain and helped ensure that any tOPV they found in the cold chain was removed. The monitors’ findings in each country and territory were reviewed by a validation committee, whose assessment of whether or not tOPV had been removed from the cold chain was provided to the national government and later transmitted to WHO. By August 31, 2016, all but two countries and territories that used OPV in 2015 had submitted validation reports to WHO.

Type 2 poliovirus strains held in research or manufacturing facilities also might cause polio outbreaks if released into a population. To prevent such outbreaks, countries should ensure that all remaining type 2 polioviruses, including WPV2s, VDPV2s, and the type 2 Sabin polioviruses used in tOPV and monovalent OPV type 2 (mOPV2), are destroyed or appropriately contained in certified poliovirus-essential facilities in accordance with the third Global Action Plan to Minimize Poliovirus Facility-Associated Risk (GAPIII) (3,6).

If type 2 poliovirus outbreaks do occur, GPEI has developed a response protocol and assembled a global stockpile of mOPV2, managed by the United Nations Children’s Fund and stored under containment conditions, to be released at the direction of the WHO Director-General. As of August 31, this stockpile contained approximately 36 million mOPV2 doses in finished vials. An additional 50 million mOPV2 doses will become available between September and December 2016, and another 50 million doses by March 2017. Hundreds of millions of doses stored in bulk form are also available for conversion into finished mOPV2 doses. GPEI has also created an IPV stockpile for use in outbreak responses. Surveillance for acute flaccid paralysis cases is supplemented by environmental surveillance for polioviruses in sewage in at least 36 countries to help identify and respond to the asymptomatic spread of type 2 polioviruses in those countries (7).

Global Introduction of Inactivated Poliovirus Vaccine

To further reduce the risk for type 2 poliovirus outbreaks after the cessation of tOPV use, the WHO Strategic Advisory Group of Experts (SAGE) on Immunization recommended in 2012 that all countries’ immunization schedules include at least 1 IPV dose (3). IPV protects against paralytic polio from type 2 polioviruses, might facilitate interruption of transmission during cVDPV2 outbreaks by enhancing immunologic response to mOPV2 and reducing the duration and amount of viral shedding, and aids in eradicating WPV by boosting immunity to types 1 and 3 polioviruses in persons who have received bOPV or tOPV (3).

Efforts to introduce IPV in the 126 countries using only OPV at the beginning of 2013 have been hampered by challenges manufacturers have experienced in scaling up production to meet the increased demand for IPV, as well as increased need for IPV in SIAs targeting WPV1 in countries where polio is endemic and the need to stockpile IPV for outbreak response. As of August 31, 2016, among the 126 countries using only OPV at the beginning of 2013, a total of 105 (83%) had introduced IPV, resulting in 173 (89%) of 194 WHO member states using IPV. However, 20 countries have had to delay introduction of IPV until adequate supplies of IPV become available, which is not likely before the fourth quarter of 2017 (Figure 2). In addition, 29 countries that previously introduced IPV are expected to run out of IPV nationwide before they receive their next supply of IPV in late 2017, and Cabo Verde has opted to postpone its introduction until 2017 to avoid a similar stock-out.^††

In response to the IPV shortage, GPEI has set priorities for allocating the limited IPV supply. The highest priority countries for receipt of IPV are Afghanistan, Nigeria, and Pakistan because of ongoing indigenous WPV transmission. The second priority is the other 33 countries considered to be at high risk for cVDPV2 outbreaks. The third priority for IPV allocation is SIAs conducted in response to polio outbreaks, and the final priority is countries considered to be at low risk for polio outbreaks.^§§ All countries considered to be at high risk for cVDPV2 outbreaks are providing IPV to infants through routine immunization service delivery. To use limited supplies of IPV efficiently, SAGE has recommended that countries consider administering 2 intradermal fractional doses of IPV to children eligible for IPV, instead of 1 full intramuscular dose (8). Two fractional doses of IPV, administered at separate visits, elicit a better immune response than a single full intramuscular dose of IPV, yet each fractional dose requires only one-fifth the volume of vaccine of a full intramuscular dose. Sri Lanka and India have begun administering 2 fractional doses of IPV to children through their routine immunization services.

Discussion

The synchronized global switch from tOPV to bOPV has gone smoothly based on the reported cessation of tOPV use in all countries and territories by mid-May 2016. The 721 cases of polio caused by cVDPV2s during 2006–2016 highlight both why the switch was necessary and why multiple precautions were taken to prevent cVDPV2s from emerging or spreading after the switch (2). Maintaining strong surveillance and response systems that can detect polioviruses, and responding promptly and aggressively when poliovirus is detected, will be essential for preserving and building upon the gains made against polio since 1988. The prompt detection and destruction of any tOPV vials found in the cold chain in the future, as well as of any mOPV2 vials found outside of the global mOPV2 stockpile after completion of an mOPV2 SIA, also will help to prevent new cVDPV2s from emerging in the future. Ultimately, the success of the withdrawal of tOPV and associated activities such as the tOPV and IPV SIAs held in the months before the switch and the global introduction of IPV will be measured by the number of polio cases caused by cVDPV2s that occur after tOPV withdrawal, with fewer cases indicating a greater success.

As of August 31, 2016, no new cVDPV outbreaks had been identified in 2016 (2). In April 2016, a cVDPV2 was identified in an environmental sample collected in March 2016 in northeastern Nigeria, before cessation of tOPV use, but genetic testing indicated that it is part of a known cVDPV2 lineage that was undetected after isolation from an environmental sample in early 2014 (9). Following the protocol for responding to detection of WPV2 after the switch and using the prepared mOPV2 stockpile, SIAs with mOPV2 were implemented in northeastern Nigeria after detection of the cVDPV2.^¶¶ An SIA with fractional dose IPV is planned for the same area later in September, and SIAs with mOPV2 are planned for the high-risk neighboring countries of Cameroon, Chad, and Niger in October and November.*** The response to the identification in August of polio cases caused by WPV1 in northeastern Nigeria should lead to further strengthening of surveillance and, through vaccination, population immunity to polio infections in that area (10).

The introduction of IPV into the immunization schedules of 105 countries since 2013 is an important achievement, particularly given the challenges imposed by the global supply shortage. Continued external support for IPV introduction in countries that have not yet been able to introduce IPV but plan to do so once the supply shortages have been resolved and strengthening of routine immunization systems that distribute and administer IPV will help to maximize the benefit of IPV for all children.

The experience developed from tOPV cessation will contribute to the success of future efforts directed at the cessation of all OPV use, primarily the withdrawal of bOPV. The cooperation of all OPV-using countries and territories in ending tOPV use in a synchronized manner is an unprecedented public health achievement. This synchronized withdrawal of tOPV followed over 2 years of preparation by and communications among GPEI, its partner organizations, OPV manufacturers, and country and territorial governments, and was achieved by essential work performed by immunization workers in the countries and territories that stopped use of tOPV. Active support from senior leaders of GPEI and national ministries of health was critical, as was the cooperation of all OPV manufacturers in ceasing production and distribution of tOPV and ensuring the availability and timely delivery of bOPV. Combined with the eradication of WPV, the ultimate withdrawal of all OPV from use will enable the creation of a polio-free world.