The Polio Endgame Strategic Plan 2013-2018 outlines strategies and timelines for the eradication of both wild and vaccine polioviruses. Objective 2 of plan deals with IPV introduction, OPV2 withdrawal and RI strengthening and provides global guidance for the switch [2]. Strategic Advisory Group of Experts (SAGE) for Immunization to World Health Organization (WHO) has identified five prerequisites to track progress toward switch preparedness. These prerequisites include introduction of at least one dose of IPV; access to bOPV licensed for RI; implementation of surveillance and response protocols for type 2 poliovirus; completion of poliovirus containment activities and verification of global eradication of WPV type 2 [9]. In October 2015, SAGE reviewed these preparations for switch and concluded that the world is ready for the switch during the low season of polio transmission in April 2016. Moreover, SAGE reaffirmed that to prevent the emergence of cVDPVs; the switch must be globally synchronized in all OPV using countries between two weeks window from 17 April and 1 May 2016 [10, 11]. Accordingly, India has decided National Switch date as 25th April, 2016. Findings from a dry run conducted in May 2015 in Assam and Uttar Pradesh to field test and pilot the switch in country has suggested that switch is operationally feasible in country. Country’s preparation for OPV2 withdrawal as per SAGE criteria and other operational aspects of switch has been summarized in Table I.

Table 1 Status of Five Prerequisites and Key Operational Aspects for the Switch from Trivalent OPV to Bivalent OPV

Despite careful planning and effective implementation, the endgame is not risk-free. OPV2 withdrawal is associated with short term risk of circulating VDPV type 2 (cVDPV2s) outbreak because of silent transmission resulting from replication and mutation of type 2 vaccine virus in gut of recently immunized children. This risk is greatest in the first 6-12 months after cessation and declines with time as vaccine viruses are unlikely to circulate longer than a few months after OPV cessation [12]. Studies in Cuba, Indonesia and New Zealand have demonstrated that polioviruses were not detectable in environmental or stool samples 2-3 months after last OPV use and suggest that VDPV is unlikely to establish circulation in situations with high population immunity [8,12,13].

The long-term risks after OPV2 cessation would be mainly related to reintroduction of type 2 poliovirus from stocks stored in research facilities, manufacturing sites, and diagnostic laboratories [8,12,13]. These stocks are expected to be destroyed or contained in designated essential facilities, as specified in the current draft of the WHO Global Action Plan to Minimize Poliovirus Facility-associated Risk (known as GAP-III). Implementation of GAP-III is considered an important measure to reduce the emergence of cVDPV2s after the switch [8,14].

The risk of cVDPV outbreaks is largely related to low population immunity against particular serotype. A cross-sectional serologic assessment of immunity to poliovirus in traditional high risk areas of India in 2014 revealed that overall seroprevalence for Bihar, Madhya Pradesh and Mumbai were 97.3%, 97.9% and 86.9% for poliovirus types 1, 2 and 3, respectively. The study also concluded that areas with low RI coverage and urban migratory clusters have also achieved high levels of population immunity against all three poliovirus types [15]. According to WHO-UNICEF estimates on immunization, 2014 revision, OPV-3 coverage is 82% in India [16]. Further, no cVDPV outbreak has been reported in country since 2010 [4]. These findings suggest that country is maintaining high level of population immunity conducive to rapid decay of type 2 Sabin virus after switch and to prevent cVDPV emergences.

Boosting immunity to type 2 polioviruses preceding the switch with high-quality tOPV supplemental immunization activities (SIAs) is the cornerstone to reduce the likelihood of cVDPV2 emergence following the switch [1,10,11]. India has already done two nationwide mass campaigns in January and February, 2016. An additional SIA using tOPV and Mission Indradhanush round (MI, see later in this article) has been planned in April, 2016 in high risk areas. These campaigns in the backdrop of high seroprevalance will help to prepare the country to prevent cVDPV2 emergence or spread after the switch.

To prepare for the switch, SAGE recommended in 2012 that at least one dose of IPV to be introduced into RI schedule in all OPV using countries [9]. Adding a dose of IPV in RI might decrease incidence of overall VAPP due to all three serotypes by as much as 80-90%. The introduction of one dose of IPV led to the elimination of VAPP in Hungary [3]. Unlike OPV, immune response to IPV does not vary significantly between industrialized and tropical developing country settings [5]. Studies suggest that a single dose of IPV will effectively close immunity gaps to all 3 poliovirus serotypes in previously tOPV-vaccinated children. To test the same in India scenario, a recent study in India assessed a schedule with bOPV (at birth, 6 and 10 weeks) followed by the co-administration of bOPV and IPV (at 14 weeks) which resulted in excellent seroconversion rates (nearly 98-99% to poliovirus type 1 and 3, and 69%–78% to type 2). Intestinal mucosal immunity is required to interrupt the transmission of poliovirus. Two recent studies in India found that in infants and children with a history of multiple doses of OPV, a single dose of IPV boosted intestinal mucosal immunity and reduced the prevalence of excretion after an OPV challenge by 38%–76%, compared to no polio vaccination. Studies also indicate that IPV is more effective in boosting intestinal mucosal immunity than OPV among OPV-immunized individuals [1]. Child malnutrition is a significant health problem in India (as per NFHS-4 data, 34 % children under 5 years are underweight) and a recent trial in Pakistan demonstrated that single simultaneous administration of IPV and bOPV achieved high seroconversion rate for type 2 in malnourished (84%) as well as normal children (100%) [8].

These findings form the technical rationale that IPV will help protect against paralytic polio from type 2 polioviruses should cVDPV2s emerge, facilitate responses to any cVDPV2 outbreaks after the switch to bOPV through priming effect, will aid in eradicating WPV by boosting immunity to types 1 and 3 polioviruses and is likely to be effective in Indian setting [5,8]. It is imperative to mention that use of IPV is not primarily meant to prevent emergences of cVPDV2s but to mitigate the risk of paralytic disease occurrence and spread in case of any outbreak. [8,17]. In view of these evidences and as per SAGE 2012 recommendations, Government of India decided to introduce IPV in country [18].

Almost all countries using only OPV at the start of 2013 had committed to introduce IPV before the end of 2015 and ~90 including India have already introduced IPV as of 1st February, 2016 [19]. Rapid IPV introduction across many countries, introduction of IPV in SIA of endemic countries, requirement of maintaining a stockpile of IPV for post switch VDPV emergences and global constraints to scale up the production has led to worldwide shortages of IPV [19]. In view of IPV supply shortages, phase-wise introduction of IPV was planned in the country. In the first phase, IPV has been introduced in 6 States in India on 30th November, 2015. IPV was planned to be introduced in remaining states in April, 2016. However, due to continued global shortages and amidst the evidence from Cuba and Bangladesh indicating that the "prime-boost" effect of 2 fractional doses (1/5th of full IPV dose) at 6 and 14 weeks offer better protection than a single full dose, the Indian Expert Advisory Group for polio eradication in February, 2016 recommended GoI to go for fractional dose IPV (f-IPV) introduction in selected States/UTs [1, 20]. Accordingly, GoI has now planned for f-IPV introduction in 8 States/UTs in April, 2016. Remaining 22 States/UTs are expected to introduce single full dose IPV from 1st April, 2016. As the country has high level of population immunity against all three types of polioviruses (to prevent emergence of cVDPV2s), phased introduction of IPV is not an impediment to OPV2 withdrawal [8].

Strengthening the RI system that distributes and administers IPV will help to maximize the impact of IPV use. Though mass polio campaigns achieve high coverage, Universal Immunization Programme fully immunizes only about 65.3% of children [21]. In order to address this gap, Mission Indradhanush was launched on 25th December, 2014 which aims to rapidly increase immunization coverage in the country to >90% by 2020. Two phases of MI have already been completed in 2015 where nearly 20 lakh children were fully immunized. Phase-3 of MI will start from 7th April, 2016, which not only will help in boosting type 2 immunity before switch but also in increasing IPV coverage.