Immunization against poliomyelitis: risk/benefit/cost in a changing context

Abstract

Benefit/risk factors in immunization against poliomyelitis are examined from the viewpoint of the relative risk and efficacy of killed and live poliovirus vaccines in the currently changing contexts of poliomyelitis prevalence in developed and developing countries. Risk factors include virus of vaccine origin gaining access to the CNS, and failure of the vaccine to immunize. Data are presented to illustrate the degree to which the respective risks occur in developed and developing countries. The ultimate elimination of risk by eradication of wild and vaccine virus from the population is discussed. The application of both approaches -- killed or inactivated poliovirus vaccine (KPV) and live, attenuated poliovirus vaccine (LPV) have been shown to be efficacious in protecting the individual and the community, but in some developing nations, adequately potent LPV still leaves a significant number of people at risk. This failure also is evident in the low rates of seroconversion. These effects appear to be due to the presence in the saliva and in the enteric tract of inhibitors to infection with the attenuated virus strains. Parenterally administered KPV results in higher rates of seroconversion. To reduce frequency of vaccine failure attributable to blocking factors in the enteric tract and to maximize efficiency in immunization, especially in developing nations where protection is needed early in life, a study was designed to establish the optimum antigen content for parenterally administered KPV which would produce seroconversion with a single dose. A figure illustrates the dose-response relationship observed; another figure shows the antigen-dose-dependence for inducing the desired effect. A single dose of KPV containing a sufficient quantity of antigen was capable of inducing seroconversion uniformly in infants. Such a vaccine would avoid the risk of paralysis due to LPV failures in the developing countries where this tends to occur, and the risk of LPV-associated paralysis, especially evident in developed countries where LPV now is the principal cause of polio. Surveillance data gathered in the US from the time of introduction of LPV in 1961-62 through 1977 reveal 201 cases of paralytic polio that can be considered LPV-associated. This includes 169 so classified by the Center for Disease Control (CDC) and 32 classified as indirect community contacts. From 1969 through 1977, 87 such cases occurred: 24 among vaccine recipients, 47 among direct contacts of vaccines, and 16 among indirect contacts. KPV has been free of incrimination in vaccine-associated polio since 1955. In the US alone more than 462 million doses of vaccine have been distributed. LPV is described as relatively safe, despite the fact that a small but definite risk accompanies its use. To eliminate exposure to this risk, it has been suggested that KPV be used for routine immunization. When all of the indirect and direct costs and benefits are considered, the economic differences between LPV and KPV are not as great as vaccine costs alone. Further, the real prospect exists for use of a more economical cell substrate for making KPV than from either primary monkey kidney cells or diploid cells.