Immunity status against poliomyelitis in Germany: Determination of cut-off values in International Units

One of the strategic objectives of the WHO is the eradication of poliomyelitis in all regions of the world within the next years. According to the WHO plans the transmission of wild poliovirus has to be interrupted worldwide by the end of 2002. The global certification will be held in 2005.

Although the European region is actually polio – free, it remains subject to the risk of importation from endemic regions. The most recent cases of poliomyelitis due to an importation of wild polio type 1 occurred in unvaccinated Bulgarian children [1]. To prevent such importations it is necessary to keep a high level of population immunity.

The last indigenous case of poliomyelitis was diagnosed in Germany in 1990. The last imported wild viruses were detected in patients with travel history to India and Egypt in 1992. Since that period of time there were found only 0 – 3 cases of vaccine-associated paralytic poliomyelitis (VAPP) per year. In order to prevent these VAPP – cases the vaccination strategy has been changed in Germany. Since 1998 it is recommended to use only the inactivated vaccine (IPV).

The neutralizing antibody test is the method of choice in conducting serological surveys to identify epidemiologically important immunity gaps in the population. It is considered essential to provide the precise procedure for carrying out polio neutralizing antibody tests. Use of standard reagents, the International Standard Serum (ISS), standard Sabin strains, and expression of the results in International Units (IU) is a feature aimed at obtaining consistent results. This will assure that comparison between studies can be made with confidence. An International Standard Serum does exist, but WHO recommendations do not indicate a protective level in IU [2, 3].

In the past the cut-off value for "sufficiently protected" against poliomyelitis was set if the final serum dilution giving protection against 100 ID₅₀ of challenge virus was greater or equal to 1/4 (titer 8). This condition should be substituted by expressing results in IU/ml.

The cut-off values (Co) for the protective level were calculated as follows:

for Polio 1: C₀ = 0.080 IU/ml

for Polio 2: C₀ = 0.180 IU/ml

for Polio 3: C₀ = 0.075 IU/ml

Neutralizing antibodies against poliovirus type 1, 2 and 3 were detected in 96.2% (95% confidence interval CI: 95.5%-96.9%), 96.8% (CI: 96.1%-97.5%) and 89.6% (CI: 88.4%-90.8%) of samples, respectively (Fig. 1). 85% of all tested persons had antibodies against all three virus types. Only 0.3% of tested persons had no detectable antibodies against all polioviruses.

Statistically significant regional differences in the immunity level between the adult populations in the East and West of Germany have been detected for Polio 3 (86,6% / 90,9%; p = 0,001).

The goal of eradication of poliomyelitis has been complicated by some events in 2000–2001. First, the discovery of circulation of a vaccine virus strain that mutated to regain its disease-causing ability in Hispaniola. This outbreak in the Dominican Republic and Haiti was the first in the Americas since 1991 and occurred in areas of very low vaccination coverage [7]. Second, the polio cases in Bulgaria. There had been no reported cases of polio in Europa since November 1998. In spring 2001 two gypsy unvaccinated children were paralyzed by a wild poliovirus in Bulgaria, which was imported from India [1]. These outbreaks send a warning to all countries to maintain their guard against polio, despite the rapid decline in its incidence. Sufficient surveillance systems and high levels of population immunity can prevent polio outbreaks.

The level of immunity to poliomyelitis has been checked in Germany at regular intervals.

For the first time in Germany the results were expressed in International Units. A representative serum panel from the German Health Survey was investigated. Additionally, sera from children less than 18 years old were included in this study. These sera were not representative for all selection criteria because they originated from diagnostic laboratories. A representative study of the health status of persons under an age of 18 years is prepared by the Robert Koch Institute. The pilot phase has started in 2001. Within the next years valid data will be obtained for the younger population of Germany.

The given threshold values of 0.075 lU/ml, 0.180 IU/ml, and 0.080 IU/ml were calculated for Polio 1,2,3 respectively. The calculation was based on the assumption that the new criteria (threshold in IU/ml) should give comparable results with respect to the old one (threshold of serum dilution).

Overall, neutralizing antibodies against poliovirus type 1, 2 and 3 were detected in 96.2%, 96.8% and 89.6% of samples, respectively. This seroprevalence indicates a very high level of immunity of the German population. Although the prevalence of antibodies against poliovirus was generally somewhat lower for type 3 than for types 1 and 2, it was still close to 90%.

Data presented in this study are concordant to those obtained in other countries [8, 9].

A previous seroepidemiological study in Germany as well as this one revealed substantial regional variations of immunity levels to Polio 3 [10]. Compared to the results of this study other German studies have shown remarkable lower antibody prevalence to Polio 3 among blood donors in Berlin and in hospitalized patients [11, 12].

Limitations in some of these serological studies due to non-representative samples or methodological reasons resulted in different conclusions regarding immunity status. Standardization of the neutralization test as well as expressing results of serological studies in International Units will permit better comparability of polio immune status of populations in different studies, and in different countries.

Immunity to poliomyelitis is largely dependent on humoral neutralizing antibodies, both after natural infection and after vaccination. It is unclear at present whether all those persons with a low level or no detectable antibodies are susceptible to infection; some, particularly the elderly, may be protected by memory immunity, an accelerated antibody response because the immune system has been primed previously. It has also been shown that enterovirus infections induce T-cell immunity [13]. The production of local secretory IgA antibodies in the gut mucosa may play a major role in protection [14, 15].

Although IPV offers excellent protection against disease, it is less effective in preventing poliovirus infection because of limited mucosal immunity. IPV recipients may contribute to the circulation of outbreak virus. Extensive circulation of Polio 3 was observed during 1984 outbreak in Finland. A study from the Netherlands has also shown that poliovirus circulation occurred during the early phase of the 1992–93 poliomyelitis outbreak. Most infected children had not been vaccinated [16]. A high level of immunity of the German population, including immigrants, must be monitored after the switch from attenuated to inactivated polio vaccine (OPV to IPV).