By the mid-1980s poliomyelitis was declining in many regions of the world due to mass OPV immunization activities. Encouraged by the success of the smallpox eradication program, the World Health Assembly declared in 1988 that polio should be eradicated worldwide by year 2000. A global campaign was initiated and successfully stopped disease in most countries of the world. However, failure to eliminate wild virus circulation in several isolated geographic pockets forced repeated postponements of the eradication deadline. At present, there are four countries where wild poliovirus is still endemic. Political instability in regions near the Pakistan/Afghanistan border and resistance of the population to polio immunization in northern Nigeria both resulted in insufficient vaccine coverage. In northern India, exhaustive efforts to increase and maintain high vaccine coverage have been thwarted by extremely low OPV efficacy [9
]. The reasons for the low efficacy are not understood; seroconversion and disease reduction rates have improved in the last two years by introducing supplementary vaccination with monovalent OPV against the predominant serotype of circulating virus [10
]. These countries remain a source of continuing re-introduction of wild virus into countries where transmission had previously stopped.
Although IPV was being used primarily in just three countries, supply of this product became limited due to the demand for imported monkeys used for its manufacture in primary monkey kidney cells. In the late-1970s, a group of researchers at the National Institute for Public Health in the Netherlands created a new product, called enhanced potency IPV (eIPV) [11
]. The vaccine was made from purified virus grown in large bioreactors. Further improvement was made at Pasteur-Merieux by replacing primary monkey kidney cells with Vero cells [12
]. The vaccine contained more protective D-antigen and could be combined with other vaccines such as DTP, further improving its cost-efficiency and re-igniting an interest in IPV.
Despite great progress with polio eradication, news on the OPV front was not all good. Cases of vaccine-associated paralytic poliomyelitis (VAPP) in vaccine recipients and their contacts were reported [13
]. It was a rare phenomenon, occurring at a rate of one in several hundred thousands of first-dose vaccine recipients. The genetic instability of the Sabin strains and their propensity to produce virulent derivatives after passage was well established, and VAPP was its clinical manifestation. It appeared to be an unfortunate side effect that represented an acceptable risk when assessed against the enormous benefits of OPV use. However, this risk-benefit equation changed after eradication of wild-type poliomyelitis in industrialized countries, making OPV the only source of paralytic polio. With the availability of enhanced potency IPV, the recommended vaccination schedule in these countries was changed from all-OPV to either a combination of two doses of eIPV followed by two doses of OPV [14
], or IPV alone. At the beginning of the 21st
century, most industrialized countries have switched to exclusive use of IPV ().
Past and projected global poliovirus vaccine usage
Reverted vaccine virus with increased virulence had been previously considered unable to spread beyond immediate contacts. The first discovery of circulating vaccine-derived polioviruses (cVDPV) occurred in 2000 during investigation of a polio outbreak in the Dominican Republic and Haiti that was caused by a recombinant between a derivative of Sabin 1 strain and an unidentified enterovirus [15
]. Similar outbreaks caused by cVDPV were shown to have occurred previously, although they had not been recognized, and they continue to occur [16
]. Cases of VAPP are restricted to single vaccine recipients and their immediate contacts, whereas cVDPV can circulate even in well-immunized communities [18
] and cause multiple outbreaks of polio in areas of low population immunity. In addition, several immunodeficient individuals were identified who were persistently infected with vaccine poliovirus and excreted VDPV strains for years [19
]. These two discoveries led to the realization that complete eradication of poliomyelitis must include eventual eradication of the live vaccine itself [22
Cessation of OPV use was always a part of the polio eradication campaign scenario, based on cost-saving expectations as well as prevention of VAPP. The existence of VDPVs, their ability to produce outbreaks, and the demonstration that they exhibit pathogenicity similar to wild-type strains significantly changed the risk-benefit analysis associated with the endgame of the polio eradication campaign [23
]. This coincided with a global shift in public perception of international security risks that was provoked by the events of September, 2001. It became obvious that the emergence of large populations of unvaccinated individuals following OPV cessation could risk re-starting a global polio pandemic caused by either VDPV, wild-type polioviruses, or chemically synthesized virus [24
] re-introduced into circulation either accidentally or intentionally [25
]. The actual risk of re-starting polio circulation is not known, but limited experimental data suggest it could be quite serious [27
]. Although mathematical modeling predicted a more optimistic scenario [28
], all analyses indicate that an immunological vacuum brings a high risk of polio outbreaks. Their magnitude and our ability to contain them remain uncertain.