The Global Polio Eradication Initiative (GPEI) is at a historical moment. Since its launch in 1988, the burden of polio cases has come down from an estimated 350,000 cases in 125 endemic countries to 73 cases in two endemic countries, a reduction of more than 99% [1,2]. In 2015, a total of 73 cases caused by wild poliovirus (wPV) were reported from these two countries: Pakistan (n=54; 74%) and Afghanistan (n=19; 26%) [3,4]. Compared to year 2014, these figures reflect 82% reduction of cases in Pakistan (n=306) and 32% for Afghanistan (n=28). Nigeria that reported 6 wPV cases in 2014 did not report any fresh cases in 2015 and was removed from the list of polio endemic countries in September 2015 [3,4].

The world has witnessed this tremendous progress using trivalent oral polio vaccine (tOPV) [1]. The use of tOPV has successfully eliminated wild poliovirus type 2 (wPV2), and wild poliovirus type 3 (wPV3), which have not been detected globally since 1999 and November 2012, respectively [1]. Four of the six World Health Organization (WHO) regions have been certified as polio free: the Americas in 1994, the Western Pacific Region in 2000, the European Region in 2002, and the South East Asia Region in March 2014 [2,3]. The four main strategies used to achieve polio elimination are as follows [1].: (a) Using tOPV in routine immunization; (b) Strengthened polio disease surveillance; (c) Supplemental immunization activities (SIAs); and (d) Mop-up campaigns in areas with sustained transmission.

The regions of persistent polio transmission in Pakistan are geographically grouped into four areas [5]. In the north of Pakistan, a few districts of Khyber Pakhtunkhwa (KP), agencies of The Federally Administered Tribal Areas (FATA) are examples of reservoir areas of wPV transmission [5]. Towards south, the other two reservoir areas are located in the provinces of Sindh and Baluchistan. Although the greatest challenge remains in specific small areas, eradication still seems an uphill task [5].

Main reasons behind the huge upsurge in 2014 are claimed to be militancy and ‘refusal families’ in FATA and KP. However, larger threats to polio campaign in Pakistaninclude program mismanagement, campaign design, poor data quality from the field leading to miscalculation in vaccination coverage estimates, and estimated poor quality of vaccine administered across the country [6].

Pakistan health agencies, other international agencies, and local civil society organizations have taken several steps to strengthen its OPV program. Pakistan has introduced injectable polio vaccine (IPV) in its routine Expanded Program on Immunization (EPI) starting from 20th August 2015 [5]. IPV will benefit more than four million children in Pakistan every year. Frequent movement of Afghan refugees in the bordering areas of FATA and KP already serving as polio reservoirs further complicates the situation [5]. Pakistan and Afghanistan have realized that they need to coordinate intensely in polio eradication drives.

Pakistan has never reported a polio case count as low as in 2015 and till date in 2016. The country is still aiming at a shift from the trivalent to bivalent OPV, but will not be able to completely withdraw OPV even for years after the target date, thus causing a delay in containment and certification [5, 6]. It is hoped that coordinated activities with partner support will help achieve polio-free status in the near future.

Challenges to interrupting poliovirus transmission in Afghanistan include: limited healthcare infrastructure and personnel, low routine vaccination coverage, high rates of poverty and illiteracy, cultural norms that may restrict caregiver interaction with vaccinators, and subpopulations that travel frequently to border areas of Pakistan, where wPV transmission is endemic [7]. Supplementary immunization activities (SIAs) are hampered by areas of armed conflicts, limited monitoring and evaluation of coverage, and insufficient local program accountability, and effectiveness to reach all children [7].

The frequent cross-border migration of ethnic groups shared with Pakistan requires close coordination of each country’s respective immunization efforts [7,8]. At the beginning of 2016, Pakistan and Afghanistan decided to increase micro-synchronization of polio campaigns at the border, closer monitoring of nomadic movement across borders, strengthening of transit vaccination, and holding of synchronized polio campaigns in future [5].

The critical lessons learnt from India’s elimination of WPV are as follows [8]:

Several innovative strategies, and tactics to identify and vaccinate children who were previously being missed were included [9]:

India also conducted research to help overcome technical and operational barriers including introduction of more efficacious vaccines (i.e., monovalent OPV in 2005 and bivalent OPV in 2010); seroprevalence and immunogenicity studies and operational studies such as social network analysis to provide evidence for decision-making [9].

In 2011-12, Nigeria experienced an upsurge of polio transmission and the country became a net exporter of poliovirus to polio-free countries [8,10]. However, at the end of 2013, the number of cases of wPV type 1 infection had decreased by 58%, with no wPV type 3 transmission [10]. wPV transmission in Nigeria was driven by reservoirs in northern Nigeria [10]. Additionally, three states in the northeast region suffered from increased militancy and security problems and several health-care workers doing polio work were killed [8,10].

Nigeria along with the international partners undertook several programmatic interventions like those described for India [10]. These interventions were enabled by a focused effort to obtain the necessary resources, use them effectively and transparently, provide the needed public health workforce, and ensure accountability for results [8,10]. This resulted in Nigeria being removed from polio endemic list in September 2015 [3,4].

During 2014, a total of 19/359 (5%) wPV cases were due to outbreaks following importation into previously polio-free countries in Central Africa (Equatorial Guinea and Cameroon), the Horn of Africa (Somalia and Ethiopia), and the Middle East (Iraq and Syria) [4]. Among these countries, Guinea and Iraq reported imported cases of wPV after remaining polio free for more than a decade [4]. Israel in 2013 detected wPV in environmental samples in two of its cities, which were genetically traced to Pakistan, however a massive public health campaign prevented occurrence of clinical cases [11]. Thus, as long as wPV circulates anywhere in the world, all countries are at a risk of reintroduction and also at risk for epidemics arising from such imported WPV.

Polioviruses contained in OPV (Sabin viruses) are live attenuated, which on rare occasions can revert to neurovirulence and cause vaccine-associated paralytic poliomyelitis (VAPP), clinically indistinguishable from paralytic poliomyelitis caused by wPVs [12-14]. It is estimated that each year between 250 and 500 cases of VAPP occur worldwide [1]. The number of VAPP cases far exceeded the number of wPV cases since 2012, which was ethically unacceptable and thus, led to change in strategy of polio end game.

In addition to causing VAPP, Sabin viruses may mutate and subsequently gain the ability to circulate in communities for long periods of time; these are referred to as vaccine-derived polioviruses (VDPVs) [1]. VDPVs would have also lost their attenuating mutations and therefore re-acquired both the neurovirulence and transmission characteristics of wPVs [1]. On very rare occasions, VDPVs could potentially re-establish endemic and epidemic transmission, leading to polio outbreaks from these circulating vaccine derived polioviruses (cVDPVs), and they are therefore incompatible with polio eradication [1].

Over the past decade, more than 40% of VAPP and 90% of the cVDPV cases have been caused due to the type 2 polio component contained in tOPV [15]. In 2015, 29 cases of cVDPs were reported globally with most (n=26) from non-endemic countries and two from Pakistan [4]. Since wPV2 hasn’t been reported since1999, the risks of delivering OPV2 outweigh the benefits.

There is global shortage of IPV vaccine because of technical failure to scale up vaccine production by manufacturers. The Indian Expert Advisory Group (IEAG) [19] and the WHO [20] have now advocated two fractional doses of IPV (f IPV) in routine immunization for countries facing vaccine shortages, as a risk mitigation strategy to extend coverage. The recommendation is based on two studies, one from Cuba [21] and other from Bangladesh [22]. The study from Bangladesh demonstrated a seroconversion rate of 81% to type 2 poliovirus after two doses of f IPV (0.1mL intradermal) given at 6 and 14 weeks of age [22]. This "prime boost" effect is better than that given by single, full dose (0.5 mL intramuscular). The IEAG also recommended not changing the switch date in India despite global IPV shortage [21]. India has rolled out IPV in all its states prior to the switch date. Seven high performing states Maharashtra, Odisha, Karnataka, Tamilnadu, Telengana, Andra Pradesh and Kerala will follow the fIPV schedule [19].

Some challenges for a successful switch are: withdrawal and destroying of tOPV stock; adherence to national guidelines for disposal of tOPV; validation of switch in a short time of three months by independent validation committee; prevention of accidental or intentional tOPV spread from containment sites. Some of the operational challenges for IPV introduction include: re-training of healthcare staff at all levels of health-care; changes in the operational guidelines; change in communication strategy; changes in the immunization card; assessing the new IPV schedule and delivery of IPV vaccine using BCG syringe in India, role of other formulations of IPV like the Sabin IPV.

Contributors: NT, VNY and AP conceived and planned the review. AP drafted the initial version of the manuscript and revised it with inputs from NT and VNY. All authors critically reviewed the manuscript and approved the final version.

Funding: None; Competing interest: NT is GAVI Board member representing civil society organizations and AP is special advisor to NT.

1. Sutter RW, Kew OM, Cochi SL, Aylward B. Poliovirus vaccine—live. In: Plotkin SA OW, Offit PA, ed. Vaccines. Sixth ed. Edinburgh, United Kingdom: Elsevier; 2013:598-645.

2. WHO 2014. Cases of Wild Poliovirus by Country and Year. Available from: http://polioeradication.org/Portals/0/Document/Data&Monitoring/Wild_poliovirus_ list_2009_2014_23DEC.pdf. Accessed March 4, 2016.

3. Global Polio Eradication Initiative 2016 Data and Monitoring. Avialable from: http://www.polioeradication.org/Dataandmonitoring.aspx. Accessed March 4, 2016.

4. Progress towards polio eradication worldwide, 2014-2015. Wkly Epidemiol Rec.2015;90:253-9.

5. Qazi J. End of year 2015 in polio endemic Pakistan: Yet another beginning towards end. Food Environ Virol. 2016;8:109-11.

6. Khan T, Qazi J. Hurdles to the global antipolio campaign in Pakistan: An outline of the current status and future prospects to achieve a polio free world. J Epidemiol Community Health. 2013;67:696-702.

7. Simpson DM, Sadr-Azodi N, Mashal T, Sabawoon W, Pardis A, Quddus A, et al. Polio eradication initiative in Afghanistan, 1997-2013. J Infec Dis. 2014;210:S162-72.

8. Bahl S, Kumar R, Menabde N, Thapa A, McFarland J, Swezy V, et al. Polio-free certification and lessons learned—South-East Asia region, March 2014. MMWR Morb Mortal Wkly Rep. 2014;63:941-6.

9. Nasir UN, Bandhyopadhyay AS, Montagnani F, Akite JE, Mungu EB, Uche IV, et al. Polio elimination in Nigeria: A review. Hum Vaccin Immunother. 2016;12:658-63.

10. Vaz RG, Mkanda P, Nsubuga P, Ado M, Etsano A. Public health innovations on the way to interruption of poliovirus transmission in Nigeria. J Infec Dis. 2016;Suppl 3:S65-6.

11. Kaliner E, Kopel E, Anis E, Mendelson E, Moran-Gilad J, Shulman LM, et al. The Israeli public health response to wild poliovirus importation. Lancet Infect Dis. 2015;15:1236-42.

12. de Oliveira LH, Struchiner CJ. Vaccine-associated paralytic poliomyelitis: a retrospective cohort study of acute flaccid paralyses in Brazil. Int J Epidemiol. 2000;29:757-63.

13. John TJ. Vaccine-associated paralytic polio in India. Bull World Health Organ. 2002;80:917.

14. Sutter RW, Platt L, Mach O, Jafari H, Aylward RB. The new polio eradication end game: rationale and supporting evidence. J Infec Dis. 2014;210:S434-8.

15. Aylward B, Yamada T. The polio endgame. N Engl J Med. 2011;364:2273-5.

16. Sutter RW, John TJ, Jain H, Agarkhedkar S, Ramanan PV, Verma H, et al. Immunogenicity of bivalent types 1 and 3 oral poliovirus vaccine: A randomised, double-blind, controlled trial. Lancet. 2010;376:1682-8.

17. Orenstein WA, Committee on Infectious D. Eradicating polio: How the world’s pediatricians can help stop this crippling illness forever. Pediatrics. 2015;135:196-202.

18. Deshpande JM, Nadkarni SS, Siddiqui ZA. Detection of MEF-1 laboratory reference strain of poliovirus type 2 in children with poliomyelitis in India in 2002 & 2003. Indian J Med Res. 2003;118:217-23.

19. WHO 2016 India Expert Advisory Group　(IEAG)　February 26th 2016 meeting Avialable from: http://www.who.int/immunization/sage/meetings/2016/april/3_Conclusions_recommendations_mini_ IEAG_26_Feb2016_NewDelhi.pdf. Accessed May 02, 2016.

20. Polio vaccines: WHO position paper – March, 2016. Wkly Epidemiol Rec. 2016;91:145-68.

21. Resik S, Tejeda A, Mach O, Fonseca M, Diaz M, Alemany N, et al. Immune responses after fractional doses of inactivated poliovirus vaccine using newly developed intradermal jet injectors: A randomized controlled trial in Cuba. Vaccine. 2015;33:307-13.