Invited Commentary: Stopping Polio Immunization

Harry F. Hull1,2, R. Bruce Aylward1 and Julie Milstien1

1 Department of Vaccines and Biologicals, World Health Organization, Geneva, Switzerland.
2 Present address: The Minnesota Department of Health, Minneapolis, MN.

Abbreviations: IPV, inactivated polio vaccine; OPV, oral polio vaccine; VDPV, vaccine-derived poliovirus; WHO, World Health Organization


    INTRODUCTION
 TOP
 INTRODUCTION
 REFERENCES
 
As the world comes closer to eradicating wild polioviruses, the question of when and how polio immunization will be stopped increasingly demands our attention. Formal discussions on this issue began with a series of meetings at the World Health Organization (WHO) in Geneva, Switzerland, starting in 1998 and a meeting co-sponsored by WHO and the International Association for Biologicals held in Paris, France, June 28–30, 2000. Participants of the first WHO-convened meeting concluded that vaccination with oral polio vaccine (OPV) should stop and that vaccination with inactivated polio vaccine (IPV) can stop when 1) wild polioviruses have been eradicated, 2) laboratory strains of wild poliovirus have been contained, and 3) sufficient evidence exists that vaccine-derived polioviruses (VDPVs) will circulate for only a limited period (1Go). International consensus has been established on the process for certifying eradication of wild polioviruses, and a global action plan for laboratory containment of wild polioviruses is already being implemented in four of the six WHO regions (2Go). As a result of these meetings, additional research has been initiated to ensure that the strategy for eventually stopping polio immunization is based on the most current and complete data available.

The paper by Conyn-van Spaendonck et al. in this issue of the Journal is an important contribution to the debate on stopping polio immunization (3Go), as it furthers our understanding of two specific issues. First, it provides data on the duration of immunity provided by IPV. Conyn-van Spaendonck et al. found that modern, enhanced-potency IPV produces serologic immunity of long duration, building upon earlier Dutch studies (4Go). The findings from their study are supported by the lack of polio cases in the IPV-immunized population during the 1992–1993 polio outbreak in the Netherlands (5Go). This point is important for planning immunization policy in the increasing number of countries that use IPV.

The second issue that this paper (3Go) helps to address is whether there is a risk of persistent circulation of VDPVs in the posteradication era. Conyn-van Spaendonck et al. describe a pattern of population immunity consistent with the absence of circulating VDPVs. Despite use of trivalent OPV to control polio outbreaks in 1978 and 1992–1993 among a population of religious objectors to vaccination, and the ongoing use of OPV to immunize a small percentage of Dutch Reformed children in neighboring countries, a significant proportion of this population has no antibodies to poliovirus. This finding is clear evidence that widespread transmission of VPDV is not sustained in that setting. Although VDPVs do not persist in the Netherlands, the high living standards (good sanitation and lack of crowding), temperate climate, and small population do not permit extrapolation of these data to many of the impoverished and densely populated countries in the tropics. It has previously been suggested that such factors should be considered when evaluating the overall risk of persistent VDPV circulation in the posteradication era (6Go). In fact, a report presented at the Paris meeting noted that a type 2 poliovaccine virus had recombined with another enterovirus and had circulated in Egypt during the 1980s (7Go), although it rapidly disappeared completely with effective, routine immunization and National Immunization Days (NIDs) for polio eradication (8Go).

Additional research on the potential for persistent circulation of VDPVs is in progress and will be published soon, as will further data on the prevalence and duration of chronic VDPV infection among immunodeficient persons. The timely completion of this research is important; the earlier a decision can be reached on the global strategy for stopping polio immunization, the better. The major issues driving the need for such a decision relate to long-term planning and production of the future global supply of polio vaccines.

While vaccine producers are capable of delivering the massive quantities of OPV currently needed for National Immunization Days, today's sufficient capacity would quickly become excess capacity in the posteradication era. Although the major manufacturers have committed to meeting OPV demand through the end of the polio eradication initiative, there will be increasing pressure to convert these facilities to other, more profitable uses once eradication has been achieved. Even if OPV were the only vaccine to be widely used after eradication, the long-term supply issues would not be straightforward. When other "endgame" strategies for the eradication initiative are considered, these issues become even more complex and include such aspects as investment in new facilities, regulation of products, and containment of production, depending on the identity of the vaccines, the immunization strategies to be used, and the need for stockpiles.

Consider, for example, the scenario that would result were there a marked increase in use of IPV. Were it necessary or appropriate to expand IPV production to cover the entire world in the posteradication era, a minimum of 5–7 years would be needed to bring new facilities into production should additional countries choose to introduce that vaccine. Moreover, use of IPV in the posteradication era would raise important issues for manufacturers, as all current IPV is made from wild polioviruses, organisms that would be subject to maximum laboratory containment at that time. Another scenario would result when one considers a strategy proposed for stopping polio immunization, in which each one of the three components of trivalent OPV would be removed as that polio serotype ceases to circulate. While such a strategy sounds straightforward, use of the resulting bivalent OPV formulation raises important regulatory as well as production issues (9Go).

Regardless of the strategy used to stop polio immunization, there will be a need to produce and stockpile monovalent formulations of OPV, and possibly IPV, to address the risk of outbreaks in the postimmunization era (10Go). Although some monovalent preparations were licensed in the past, these licenses have lapsed in most countries. From both the production and regulatory perspectives, substantial time will be required to ensure the availability of such vaccines.

An international consensus on the global strategy for eventually stopping polio immunization is needed as early as possible to permit vaccine manufacturers to meet the resulting demand, whether for existing or for new formulations of OPV or IPV. The longer a decision is delayed, the higher the risk that a sufficient supply of the chosen vaccine just may not be available.


    NOTES
 
Reprint requests to Dr. R. Bruce Aylward, Department of Vaccines and Biologicals, World Health Organization, 1211 Geneva 27, Geneva, Switzerland (e-mail: aylwardb{at}who.ch).


    REFERENCES
 TOP
 INTRODUCTION
 REFERENCES
 

  1. Global eradication of polio: report of the meeting on the scientific basis for stopping polio immunization. Geneva, Switzerland: World Health Organization, 1998. (Document WHO/EPI/GEN/98.12).
  2. WHO global action plan for laboratory containment of wild polioviruses. Geneva, Switzerland: World Health Organization, 1999. (Document WHO/V&B/99.32).
  3. Conyn-van Spaendonck MAE, de Melker HE, Abbink F, et al. Immunity to poliomyelitis in the Netherlands. Am J Epidemiol 2001;153:207–14.[Abstract/Free Full Text]
  4. Rümke HC, Oostvogel PM, van Steenis G, et al. Poliomyelitis in the Netherlands: a review of population immunity and exposure between the epidemics in 1978 and 1992. Epidemiol Infect 1995;115:289–98.[ISI][Medline]
  5. Oostvogel PM, van Wijngaarden JK, van der Avoort HGAM, et al. Poliomyelitis outbreak in an unvaccinated community in the Netherlands, 1992–93. Lancet 1994;344:665–70.[ISI][Medline]
  6. Fine PEM, Carneiro IAM. Transmissibility and persistence of oral polio vaccine viruses: implications for the global poliomyelitis eradication initiative. Am J Epidemiol 1999;150:1001–21.[Abstract]
  7. Yang CF, Naguib T, Yang ST, et al. Prolonged circulation of Sabin 2 derived polioviruses. Presented at the International Association for Biologicals meeting (Progress in polio eradication: vaccine strategies for the end game), Paris, France, June 28–30, 2000.
  8. Birmingham ME, Aylward RB, Cochi SL, et al. National Immunization Days: state of the art. J Infect Dis 1997;175(suppl 1):S183–8.[ISI][Medline]
  9. Parkman PD. An assessment of the safety and efficacy implications of removing the type 2 strain from the trivalent oral poliovirus vaccine. Presented at The Scientific Basis for Stopping Polio Immunization meeting, World Health Organization, Geneva, Switzerland, March 23–25, 1998.
  10. Fine PEM, Sutter R, Orenstein WA. Stopping a polio outbreak in the post-eradication era. Presented at the Polio Vaccines for the Post Eradication and Post-Immunization Era meeting, World Health Organization, Geneva, Switzerland, January 19–20, 2000.
Received for publication August 7, 2000. Accepted for publication August 29, 2000.


Related articles in Am. J. Epidemiol.:

Immunity to Poliomyelitis in the Netherlands
Marina A. E. Conyn-van Spaendonck, Hester E. de Melker, Frithjofna Abbink, Nazrin Elzinga-Gholizadea, Tjeerd G. Kimman, and Ton van Loon
Am. J. Epidemiol. 2001 153: 207-214. [Abstract] [FREE Full Text]