C International Epidemiologies! Association 1998
Printed in Great Britain
International Journal of Epidemiology 1998:27:916-925
Immunity to tetanus, diphtheria and
poliomyelitis in the adult population
of Sweden in 1991
Margareta B6ttiger,a Olle Gustavsson and Ake Svenssonc
Background During 1990 and 1991 a survey of immunity was carried out in Sweden. The
main purpose was to estimate the level of immunity to diphtheria, tetanus and
polio in the adult population. In total, 4800 people, randomly selected according
to a stratified, two-stage, sampling plan, were contacted and asked to contribute
a blood sample. Of those selected, 70.6% gave a blood sample.
Methods
Estimates and confidence intervals of the proportion of the population with
antibodies exceeding some titre was calculated. The population was divided
according to sex, year of birth (five age groups) and residence (four regions).
Results
In age groups that were bom after the introduction of childhood vaccination,
5*90% and 75-90% of people have demonstrable antibodies at a protective level
against tetanus and. diphtheria respectively. Those bom earlier, especially women,
are poorly protected with less than 50% having protective antibody levels for both
tetanus and diphtheria. Differences between men and women were particularly
seen in the age groups bom between 1930 and 1950. Less than 5% of the Swedish population lacked the protective level antibodies against polio types 1, 2 and
3 respectively.
Conclusions Vaccination against tetanus, which can be combined with vaccination against
diphtheria, can be recommended especially to women born before 1950 and with
no documented previous vaccination. The same recommendation can be given
for men born before the 1930s. As regards poliomyelitis, general booster vaccination of the adult population does not appear to be necessary at present.
Keywords
Diphtheria, tetanus, poliomyelitis, serology, vaccination, immunity
Accepted
2 February 1998
During 1990 and 1991, the National Bacteriological Laboratory
in Sweden (SBL) (since then re-organized as the Swedish Institute for Infectious Disease Control) planned and carried out a
new survey of immunity based on a random sample of the
population. The main purpose was to estimate the level of immunity to diphtheria, tetanus and polio in the adult population
in Sweden. In this paper, the results and conclusions concerning
particular infections are presented. The design, execution and
the methods used to analyse the results of the survey are
described in a separate article.1
The epidemiology of the three infections are different. All
three infections are at present covered by the general childhood
vaccination programme. However, only in the case of poliomyelitis has there been an effort to give the entire population
' Department of Epidemiology, Swedish Institute for Infectious Disease
Control Sweden.
b
County Medical Officer, VSsternorrland. Sweden.
c
Department of Mathematical Statistics, Stockholm University, Sweden.
protection by vaccination of adults. Swedish men have, since
the 1940s, been given a tetanus vaccination during compulsory
military service.
Background
Tetanus in Sweden
In contrast to the majority of diseases caused by microbes and
against which vaccination affords protection, the possibility of
eradicating the tetanus microbe is not practicable. The bacterium is ubiquitous, especially in the soil. Thus, we shall always
have to depend upon vaccination to avoid tetanus.
The number of tetanus cases from 1920 to 1950 was estimated to be 50 to 100 per year.2 Thereafter the numbers declined
gradually. From 1969 to 1985, on average, between three and
four cases were reported per year. Analyses 3 ' 4 showed that the
disease mainly affected older unvacdnated people. From 1986
to 1994, 12 cases were reported; eight of these in people bom
before 1920 and none had documented vaccination.
916
IMMUNITY IN SWEDEN
917
Table 1 Antigen contents per dose of vacdnes against tetanus and diphtheria in Sweden
Basic
Boosters
Adults
Years
1943-1947
1952-1962
1962-1979
1979-1990
1965-1973
1973-1986
1987-1990
1940-1942
1942-1944
1950-1956
1957-1961
1962-1990
Y
1
Age
(year)
1-15
Y
Y
3
<1
Y
N
3
<1
N
Y
3
<1
7.5
Y
1
7-8
0.5
3.75
Y
1
10
7.5
1.9
Y
1
10
1
recruits
recruits
adults
adults
adults
Diphtheria
(Lf)
40-50
12-15
30
12.5-15
12.5
0.5
0-0.5
Tetanus
(Lf)
12-19
5-10
3.75
Pertussis
Aluminiumphosphate
3-11
13-56
10-15
7.5-1.0
3.75-7.5
All tetanus vaccines used in Sweden were produced by
the National Bacteriological Laboratory.5'6 The strength and
composition have varied. Table 1 gives a survey of the D and T
vaccine doses used.
Vaccinations were first performed in Sweden on military
personnel during World War n. General vaccination of infants
with a combined diphtheria-tetanus-pertussis vaccine (DTP) or
only DT was introduced during the 1950s and was estimated to
cover 97-99% of children by the end of the decade. All Swedish
men have to do compulsory military service, with their first tour
of duty at about the age of 20. Since the 1940s and until 1990,
a tetanus vaccination (T or Td) has been given on this first tour.
Tetanus-toxoid prophylaxis (T or Td) was a common routine
after injuries up to the 1980s. Since 1990, such prophylaxis has
been mainly recommended for the unvaccinatedL or the not fully
vaccinated. Those who have received four doses are regarded as
protected for 30 years. 7
Diphtheria in Sweden
During Word War L there were up to 40 000 cases of diphtheria
in Sweden in a population of less than 6 million. In the 1920s
and 1930s, the disease decreased drastically without any vaccination and at the end of 1930s only sporadic cases were seen.
During World War IL the disease was introduced from Finland
and led to the mass vaccination of children. In the following
30 years, diphtheria almost disappeared; a few imported cases
were notified. In 1984-1986, smaller outbreaks occurred in
Gothenburg on the west coast of Sweden and in Stockholm
on the east coast. 8 ' 9 Since 1988, no cases of diphtheria have
been reported in Sweden.
Only Swedish diphtheria-toxoid vaccine prepared by the
National Bacteriological Laboratory has been used in Sweden.
The vaccines have been composed as shown in Table 1. The first
vaccine was prepared in the early 1940s 10 ' 11 and was given
during the period 1943-1947 mainly to children under 15 years
of age. About 60% were estimated to have participated with
at least one injection. Between 1947 and 1952 there was no
general vaccination programme. Diphtheria-tetanus toxoid
(DT) and diphtheria-tetanus-pertussis vaccine (DTP) were successively introduced during the 1950s 15 and from 1958 onwards it was estimated that all children were offered three doses
of DTP or DT before the age of 12 months. The vaccination
No. of
doses
Y
1
Y
1
Y
1
Y
1
coverage was estimated to be up to 97-99%. 1 4 From 1965 onwards an extra vaccine dose containing a minute dose of 0.5 Lf
diphtheria toxoid (Td) was given to schoolchildren. 15
Poliomyelitis in Sweden
Poliomyelitis was formerly a severe disease in Sweden with
the first outbreak reported in 1881. 16 In the 1950s, before the
vaccination era, morbidity was on the average, 17 per 100 000
inhabitants. 17 The proportions of adults and children were equal.
The natural immunity was lower than in any other country
at that time. 18 Between 1957 and 1962, up to two-thirds of
the population were vaccinated. Since 1962, polio has been
eliminated in Sweden. Only a few unvaccinated people have
been afflicted. With one exception, all were infected abroad. 20
The circulation of polio in the population ceased simultaneously
with the disease.21 Interest in immunity to poliomyelitis has
again been activated by the World Health Organization's (WHO)
declaration that it aims to eliminate the disease by the year
2000. 22
In 1957, inactivated poliovacdne (IPV) from Eli Lilly, USA,
was distributed. From 1958 to 1988, IPV produced by the
Swedish National Bacteriological Laboratory (NBL) was used. A
long-term study of this vaccine was published in 1992. 23 From
1988 to 1995, IPV imported from the Netherlands' national
vaccine-producing institute (RTVM) was used. Since IPV confers
immunity mainly by producing IgG-antibodies, i.e. humoral
immunity, it is comparatively easy to carry out an evaluation of
the immunity by sero-epidemiological studies. In contrast, the
immunity evoked by live, attenuated, oral vaccine (OPV) depends partly on antibodies—which generally do not rise to very
high levels—and partly on local, intestinal immunity. 24 All
experience shows that specific neutralizing antibodies in the
blood protect against paralytic disease.
The population studied, with the exception of foreigners,
has been vaccinated with IPV vaccine and almost all with the
Swedish vaccine. Many foreigner—all children but also many
adults—have received the vaccination or a booster in Sweden.
The general vaccination schedule comprises three initial doses
and one booster dose 4-5 years later. The age groups born
between 1949 and 1959 that received the first and antigenically
weak vaccine distributed in 1957-1959 have been offered a fifth
dose since the 1970s.25
918
INTERNATIONAL JOURNAL OF EPIDEMIOLOGY
As vaccination in Sweden makes us mainly dependent on
serum antibodies, it is most important to check the antibody
status at regular intervals. As the only countrywide study was
undertaken over 20 years ago in 1968, 19 it was high time to
carry out a new one in the 1990s.
Material and Methods
Population studied
The reference population was people born before 1973 and
entered in a parish register. In Sweden, all permanent residents
are entered in a parish register, regardless of citizenship. The
total number eligible for the survey was about 6 million.
Sampling plan
In total, 4800 people, randomly selected according to a stratified, two-stage, sampling plan, were contacted and asked to
contribute a blood sample. In the first stage of the sample, a
number of parishes were selected. In the second stage, a sample
of 48 people was taken from each of the selected parishes. The
sample is stratified in such a way that four people of each sex
born before 1930, between 1931 and 1945 and between 1946
and 1955 and six bom between 1956 and 1965 and between
1966 and 1972 were selected.
The survey was planned to give results regarding the proportion of the population that had antibodies exceeding some
titre with a precision about ± 5 % , when divided according to
sex and year of birth (five age groups) or divided according to
sex and geographical areas (four regions). The four geographical
areas are referred to as Southern (S), Western (W), Central (C)
and Northern (N) Sweden.
Statistical methods
In total, 3390 (70.6%) of the 4800 people selected gave a blood
sample. The response rate differs considerably between ages
and geographical areas. In analysing the results of the survey,
we have treated non-participation as uninformative, i.e. we
have postulated that non-response is due to chance and is not
related to the presence or absence of antibodies in the blood. A
comprehensive description of how the survey was planned and
analysed is given in a special report.'
Comparisons between immunity in different regions or
between the sexes are made by comparing the estimates pairwise with regard to their estimated precision. The results of these
comparisons are represented by a division of the regions into
homogeneous groups that consist of regions which cannot
be shown to differ significantly. Homogeneity of the titre
distributions for different age cohorts is tested by a x -test.
Unless otherwise stated statistical significance is implied by a
P-value <0.05.
Serological assays
Tetanus
As regards tetanus, for the first half of the samples, a combined,
direct ELJSA and a competitive inhibition ELJSA were used, as
described earlier. 26 ' 27 However, this method was very laborious.
Thus, during the study a comparative evaluation was made
between this ELISA method and the toxin-binding immune
assay (ToBI).28 Comparisons and harmonization of both methods
were successfully carried out and a change to the latter was
made for the second half of the investigation. Both methods
allowed a sensitivity level down to a concentration of 0.0100.015 international units (IU)/ml which corresponds to the
internationally accepted protection level, 0.01 lU/ml. 29
Diphtheria
Diphtheria-antitoxin levels were determined by neutralization
tests on Vero cell cultures in microplates. 30 " 32 The challenge
dose of the toxin was 100 cell-culture toxic doses. The titrations
on microplates were carried out as follows: 75 ul of culture
medium were added to each well followed by 25 |il of serum—
each serum to two wells. Titrations were carried out in fourfold
dilution steps from 1:4 in the first row up to 1:16 384. A serum
standardized against the reference serum of the WHO was
included in each test as a control. A dilution of the reference
serum containing 0.01 ru/ml, i.e. the level which is considered
to offer protection, 33 ' 34 corresponded in our test system to a
neutralization of the toxin up to the dilution of 1:16. This level
was used as the level affording protection.
Polio
For polio 25 ul of virus suspension (type 1 Mahoney, type 2 Mef
1 or type 3 Saukett) diluted to contain 10-50 CCH>50, was
dropped into each well. Binding occurred at 37°C for 3 h. A cell
suspension (100 ul) was added and the plates were incubated at
37°C. Virus controls were tested in tenfold dilutions, ten wells
per dilution. Readings were carried out after 6 days by microscopic examination. The value of the 50% endpoint was used as
the titre. 1 9 ' 2 5 ' 3 5
Results
Immunity to tetanus
The estimated proportions of men and women with acceptable
immunity (0.01-0.015 IU) to tetanus are given in Table 2. In the
Table 2 Immunity to tetanus by sex and year of birth. Estimates and 95% confidence intervals (CI) and P-values for comparisons between men
and women
Women
Born during
1966-1972
1956-1965
1946-1955
1931-1945
<1930
All
Estimated
proportion immune (%)
98.6
88.3
53.5
44.3
30.3
55.4
Men
95% CI
(96.5-99.5)
(84.3-91.4)
(47.5-59.4)
(38.2-50.7)
(25.0-36.3)
(52.7-58.2)
Estimated
proportion immune (%)
98.6
95.4
89.9
83.2
50.1
80.1
95% CI
(95.8-99.5)
(92.2-97.3)
(84.9-93.4)
(78.1-87.2)
(42.8-57.3)
(77.3-82.6)
P-value
ns
0.006
<0.OOl
<0.001
<0.001
<0.001
IMMUNITY IN SWEDEN
919
Table 3 Immunity to diphtheria by sex and year of birth. Estimates and 95% confidence intervals (CI) and P-values for comparisons between
men and women
Women
Born during
1966-1972
1956-1965
1946-1955
1931-1945
•=1930
All
Estimated
proportion immune (%)
87.2
77.6
40.4
45.4
25.8
48.8
Men
Estimated
proportion immune (%)
93.4
87.3
61.1
64.8
24.6
61.5
95% CI
(82.5-90.7)
(73.0-81.7)
(34.9-46.1)
(39.4-51.6)
(20.4-32.1)
(45.9-51.7)
age groups bom after the introduction of general childhood vaccinations, which covered the whole country by the end of the
1950s, more than 85% of both men and women are protected.
For those born earlier men are better protected than women.
The proportion of protected women declines rapidly to under
50% among those bom before 1945. Concerning the men,
levels of over 80% were found in the age groups born between
1931 and 1950. Among the elderly both men and women are
poorly protected. The main trends were similar in all parts of
Sweden. The only significant difference found was that women
in Western Sweden seem to have a higher percentage of
protection than women in Central and Southern Sweden. No
significant differences between regions were found for men.
Immunity to diphtheria
The estimated proportions of men and women in different age
cohorts with an antibody level (i.e. >0.01 IU/ml, i.e. titre 1:16) are
shown in Table 3. It is estimated that over 75% of those bom after
1956 have satisfactory protection, irrespective of sex. However,
for those bom before 1955, the situation is different. For women
bom between 1931 and 1955, the percentage is about 40%, and
for men, about 60%. In the oldest age cohorts, only about 25%
of both men and women have satisfactory protection. The
95% CI
(89.3-96.0)
(82.7-90.8)
(54.5-67.3)
(59.1-70.1)
(20.3-29.5)
(58.9-64.1)
P- value
0.04
0.002
<0.001
<0.001
n.s.
<0.001
proportions protected of those who were not included in the
child vaccination programme are significantly different between
men and women for all but the oldest age group.
A closer examination shows that grouping according to year
of birth as used in the planning of the study and in Table 3 hides
some interesting patterns. It turns out that about 56% of the
women born between 1932 and 1941 have satisfactory protection but only 33% of those bom between 1942 and 1945. A
similar but much smaller difference is observed for men. This is
obviously due to the vaccinations given between 1943 and 1947
mentioned above.
Women in Western Sweden are protected to a greater extent
than women in other regions. There also seem to be regional
differences for men. A further division of the data which also
takes age into account means dividing the sample into 48 distinct groups. The number of people in each group is small and
the statistical variation becomes large. However, some significant differences are observed. Among the middle-aged and older
population, those living in Western Sweden had comparatively
better protection than those living in other parts. The population in the North had the lowest levels in this age group.
The proportions of men and women with litres exceeding
different levels are shown in Figure 1. The threshold level for
64
256
1024
4096
Titre
Figure 1 Immunity to diphtheria. Proportion of women and men (shaded) with titres exceeding different levelts. Estimates
and 95% confidence intervals (CI)
920
INTERNATIONAL JOURNAL OF EPIDEMIOLOGY
B-1930
H1931-1945
D1946-1955
H1956-1965
H1966-1972
16
4096
Figure 2a Immunity to diphtheria. Tltre distribution according to year of birth for women with titres >4
B-1930
H1931-1945
D1946-1955
01956-1965
S 1966-1972
4096
Figure 2b Immunity to diphtheria. Titre distribution according to year of birth for men with Utres >4
satisfaaory protertion used by us corresponds to the litre 1:16
(corresponding to the WHO protection level of 0.01 IU/ml).
Interpolation between the titre levels 1:64 and 1:256 indicates
that about 40% of men and 30% of women possess good protection according to the WHO standard (0.1 IU/ml, corresponding to the titre 1:160).
In Figures 2a and 2b, the distribution of titre levels for those
having a measurable antibody level are given for men and
women divided according to year of birth. There is a significant
difference between the age groups both for men and women
(P«s 0.001).
Immunity to poliomyelitis
The percentages of men and women with demonstrable antibodies (i.e. titre s>l:4) against the three types of polio, respectively, in different age groups are illustrated in Table 4. It is dear
that the immunity to polio is high. In total, antibodies against
the three types were present at the dilution s»l:4 in over 95%
IMMUNITY IN SWEDEN
921
"fable 4 Immunity to poliomyelitis by sex and year of birth. Estimates and 95% confidence intervals (CI) and P-values for comparisons between
men and women
Women
Bora during
Type 1
1966-1972
1956-1965
1946-1955
1931-1945
*1930
All
Type 2
1966-1972
1956-1965
1946-1955
1931-1945
<1930
All
Type 3
1966-1972
1956-1965
1946-1955
1931-1945
<1930
All
Men
Estimated
proportion immune (%)
95% CI
Estimated
proportion immune (%)
95% CI
P-value
96.8
98.1
(98.4-99 9)
(97.0-99.5)
(95.0-98 9)
(96.9-99.7)
(94.2-98.2)
(97.2-98.7)
98.8
95.8
95.4
95.9
93.0
95.4
(96.6-99.6)
(92.7-97.6)
(92.2-97.4)
(92.7-97.7)
(89.0-95.6)
(94.1-96.4)
n.s.
0.01
n.s.
0.03
0.03
<O.0Ol
99.7
99.3
99.6
99.7
96.5
98 5
(98.1-99.9)
(98.1-99.7)
(98.1-99.9)
(96.8-99.9)
(91.6-98.5)
(97.1-99.3)
99.7
99.1
99.6
95.7
93.8
97.1
(97.0-99.9)
(97.5-99.7)
(96.3-99.7)
(92.5-97.6)
(89.6-96.4)
(95.8-98.0)
n.s.
n.s.
n.s.
0.04
n.s.
n.s.
98.8
97.5
95.5
99.1
96.4
(97.0-99.5)
(94.9-98.8)
(92.6-97.3)
(97.0-99.7)
(93.2-98.1)
(96.2-98.1)
97.3
97.6
89.7
94.4
90.0
93.4
(94.2-98.8)
(95.6-98.7)
(85.4-92.8)
(91.3-96.7)
(84.1-93.9)
(91.6-94.7)
n.s.
n.s.
0.01
0.01
<0.01
<0.001
99 6
98.8
97.6
99.1
97.3
of the samples. Women lacking immunity were 1.9% against
type 1, 1.5% against type 2 and 2.7% against type 3. The corresponding proportions for men were 4.6%, 2.9%, and 6.6%,
respectively. There are significant differences between men and
women for types 1 and 2. As is seen in Table 4, these differences
seem to relate to the oldest age cohorts.
The proportion of those Immune is somewhat lower in the
oldest age cohorts. However, it seems that people bom between
1931 and 1945 are protected to a higher degree than those born
between 1946 and 1955. The differences are in all cases relatively small, even though some of them are statistically significant. No differences could be found between people living in the
four regions of Sweden.
The low titre sera were also tested in undiluted sera. The
percentages totally lacking antibody activity were 1.6, 1.0 and
1.5%, respectively, for the three types of polio (both sexes).
The estimated proportion of women and men with a titre
exceeding different levels are shown in Figures 3a and 3i». As
has been experienced in most earlier studies, the type 2 antibody titres reach high levels and the type 1 titres in this
study are also high, while the type 3 titres are slightly
lower. The median values (i.e. the titre levels exceeded by
50% of the population) are approximately 1:256, 1:256 and 1:64,
respectively.
A comparison between the age cohorts show that, among
those with titres >1:4, there are significant differences
(P < 0.001) for the three types of polio and for both sexes.
Older people tend to have higher titre levels to different polio
types when compared to the young.
Discussion
The immunity pattern to tetanus and diphtheria does not seem
to be influenced by the variation in vaccine used.
Tetanus
Concerning the laboratory methods for determining immunity,
it may be argued that one should not change method in the
middle of a study. The old method turned out to be laborious
and needed extensive counting. The problem of sera with low
titres that had to be re-titrated and also controls not fitting in
encouraged us to try the new, toxin-binding, inhibition test.
This method turned out to be easier and as reliable, and therefore, after double checking of a number of samples at varying
titre levels, we decided to use this method.
The young adults of both sexes who were bom after the
introduction of general childhood vaccinations, i.e. those born
at the end of the 1950s and later, are well protected. The wide
gap between the sexes in the oldest age groups can probably
be explained by at least two factors. The majority of men were
vacdnated during military service since the World War n and
boys and men have been more exposed to injuries which have
led to prophylactic vaccinations.
A number of studies confirm the dose association between
vaccination coverage and immunity and poor immunity in the
older population. 36 " 38 However, people who have not had the
recommended primary vaccination comprising three doses may
still retain their immunological memory for long periods and
react with a rapid booster response when challenged.
922
INTERNATIONAL JOURNAL OF EPIDEMIOLOGY
—•—Type 1
- - • - Typ«2
--A--Typo3
TTtre
Figure 3a Immunity to poliomyelitis. Estimated proportion of women with tltres exceeding different levels
1 0
0.Q--
0.8
0.7-
°
0.40.30.20.1-
TTtre
Figure 3b Immunity to poliomyelitis. Estimated proportion of men with titres exceeding different levels
Diphtheria
Immunity at the 0.01 IU level in young adults up to 30 years of
age, i.e. those born in 1960 and later, is 75% or higher. In those
born in 1930 or earlier, this level was reached by less than 30%.
Noticeable is the comparatively high immunity among those
bom between 1932 and 1941. These age groups were offered
vaccination with one to three doses during World War n. The
phenomenon was also observed in an earlier study.30 This finding and the high immunity in the vaccinated younger generation
bom after 1960 indicates a close correlation between vaccination and immunity. It also seems that those born before 1920
have protection to a somewhat greater extent than those born
during the 1920s. Such a difference may be explained by
natural immunity acquired by the oldest who were born at a
time when diphtheria was prevalent.
A comparison between men and women shows a consistently
better general immunity among men than among women.
The majority of men had received an extra booster (Td) during
military service, although this dose was very small (0.5 Li).
The difference between the sexes is most apparent in the age
groups bom in 1931-1955. One small exception is the oldest
women in the western part of Sweden. A diphtheria outbreak
IMMUNITY IN SWEDEN
in Gothenburg in 1984 led to mass vaccination, in particular of
many middle-aged and elderly women.
In spite of the low general immunity in the population born
before general childhood vaccinations were introduced, diphtheria did not spread widely when it was introduced in the
1980s. It mainly hit the socially deprived with reduced immune
defences.8 It is evident both from old and recent experiences
that the combination of a lack of spedfic immunity and poor
living standards is necessary for a widespread epidemic. 8 ' 34 ' 40
However, a few, quite healthy, isolated cases such as hospital
personnel exposed to a high dose of diphtheria, also contracted
the disease during the 1985 epidemic.
This study was timely—it was carried out just before it became
obvious, in 1993, that diphtheria had spread and become a great
problem in the former Soviet Union, especially in the area of
St Petersburg. 40 Knowledge of actual immunity to the disease
in the Swedish population has become of great value and formed
a basis for our evaluations of the adult population at risk of
contracting diphtheria in Sweden.
Poliomyelitis
The last, nationwide, sero-epidemiological study of polio—
but with a different kind of sampling—in 1968 showed that the
population of Sweden had protective antibodies in dose to
100%, except in those age groups born at the end of the 1940s
up to the end of the 1950s. 19 The 1968 study and a supplementary study 41 indicated that over 25% of recruits born in
the 1950s lacked antibodies to polio type 3 and 10% to type 1.
The above-mentioned age groups were informed over a 10-year
period about the situation and offered a free booster vaccination. The remaining, slightly lower, antibody prevalence among
males born in the period 1946-1955, i.e. 10% lacked the stated
immunity level to type 3, indicates that perhaps not all and
particularly men were reached by the booster campaign.
On the whole, however, the immunity status of the population must be regarded as very satisfadory. The majority of those
whose vaccination immunity is lower than the stated level of
1:4 may still possess immunological memory, as was shown in a
previous spedal study. The ann'body-titre levels showed a
pattern similar to that in earlier studies. The median titres were
highest against type 2 and lowest against type 3. In this survey,
the type 1 and type 2 antibody distributions are remarkably
similar, with a median titre around 1:256, while the type 3
median titre, as in earlier studies, is lower, i.e. almost 1:64.
Apparently even this level of type 3 immunity has been protective in Sweden, as we were not affeded by the outbreak in
Finland in the 1980s, in spite of the dose connections between
the two countries. It is furthermore of interest, in this context,
to discuss the importance of different variants of poliovirus
type 3. Experience tells us that the type 3 poliovirus is more
mutagenic than the other types. 42 ' 43 The Saukett strain which
is used as seed virus in the vaccine was isolated in the 1940s in
the USA. Serum from Saukett-vacdnated children neutralized
the epidemic type 3 strain isolated in Sweden in 1957 five times
less effidently than the Saukett strain. The type 3 strain that
caused the Finnish outbreak was, in our tests, four times less
effldent. 44 We have thus also to take into consideration these
antigenic variations in evaluating the immunity.
In contrast to immunity to diphtheria and tetanus, no geographical differences were seen as far as polio immunity was
923
concerned and only small differences were seen between age
groups. The explanation of this may be that, in contrast to the
two vaccinations against diphtheria and tetanus, the polio vaccination was offered to and also reached the majority of the
population, and not only children. 19 The adult population, the
majority of whom were already naturally immune, thus to a
large extent received an effective booster with this killed vaccine. In people already possessing some naturally induced
immunity, a potent, killed vaccine gives rise to a better antibody
response than administration of an oral, attenuated, vaccine
virus, which does not multiply effectively in naturally immune
people. 19 ' 45 Older people actually had slightly higher antibody
titres than the young.
In this study immigrants now settled in Sweden appeared to
be as well proteded as Swedes. Many of them would have been
offered vaccination on entering the country, but the majority of
those coming from developing countries are likely to be naturally immune. As many return to visit their native countries it
must be wise to be extra cautious and recommend at least one
booster.
It should be pointed out here, too, that up to the end of the
1980s so-called enhanced poliovaccine was not used in Sweden.
The results presented were achieved with an ordinary, unconcentrated vaccine containing originally, before formalin treatment, about 10 million (107) cell-culture infectious doses per
millilitre.23 With the enhanced vaccine, 46 the effed can be expected to be even better. A further improvement would be to
give the fourth dose a little later than at the age of 6, as is the
rule in Sweden. A booster at the age of 10 improved the immune response. 44 A booster as late as possible, when one can
still reach all children, would, from the immunological point of
view, be the most effective for long-term protection.
Conclusions
People who were born after the general childhood vaccinations
were introduced are satisfadorily protected against tetanus and
diphtheria. Those born before this era—espedally women—are
less well protected; over 50% of older women lack protective
antibody levels.
Older people who do not have a documented vaccination
against tetanus should be encouraged to have themselves vacdnated. Documentation of vaccination should be promoted.
Older people—espedally those who come into in contact with
the soil, i.e. who work in agriculture, forestry and gardening—
should be made aware of the risks.
The unvaccinated, healthy population runs a small risk of
contracting diphtheria while staying in Sweden or visiting similar countries as tourists. However, it is advisable that everyone,
irrespective of age and sex, should have a documented, valid
vaccination, espedally those running an increased risk, such as
the sodally deprived, those exposed professionally or people
who travel to areas where the disease is endemic.
In Sweden, and very likely also in other countries with no
epidemic diphtheria, the outcome of sero-epidemiological studies
is directly correlated to the vaccination status of the population.
Knowledge of the sero-epidemiology is therefore a useful tool
for vaccination policy-makers.
The WHO is now in a very active phase in its endeavour to
hit the target of eliminating poliomyelitis and the virus causing
924
INTERNATIONAL JOURNAL OF EPIDEMIOLOGY
it by the year 2000.47 In evaluating the feasibility of success,
many factors have to be taken into consideration, such as the
absence of disease and circulating virus. One of the background
factors to be taken into consideration is the immunity, as measured by the prevalence of neutralizing antibodies in the population. It is thus important that such studies should be carried
out elsewhere. As regards Europe, favourable results of immunity studies have recently been reported. Thus, in Germany the
prevalence of immunity was over 90% to types 1 and 2 and 80%
against type 3. In north-eastern Italy, the corresponding figures
were over 98% to all three types.49 In the industrialized parts
of Europe, the majority of the reports are favourable, with the
exception of concern about type 3 immunity in some areas. The
Americas have already declared that polio has been eliminated. 50
20
Bdttiger M, Mellin P, R o m a n u s V, Soderstrom T, Wessle'n T, von
Zeipel G. Epidemiological events surrounding a paralytic case of
poliomyelitis in Sweden. Bull World Health Organ 1979;57:99-103.
21
Gard S. Poliovacdnation and epidemiologic situation in Scandinavia.
10th Symposium of European Association for Poliomyelitis and Allied
Diseases, Warsaw 1964. Proceedings, 10, p p . 1 1 1 - 3 .
22
Global eradication of poliomyelitis in the year 2000. In the Forty-first
World Health Assembly, Geneva, 2 - 1 3 May 1988: Resolutions and
Decisions Annexes (Resolution WHA 41.28). Geneva: World Health
Organization, 1988, p.26.
23
B6ttiger M, Larsson B. Swedish inactivated pollovaccine: Laboratory
standardization and clinical experience over a 30-year period.
Biologicals 1992:20:267-75.
24
O n o r a t o IM, Modlin JF, McBean AM, Thorns ML, Losonsky GA,
Bernln R. Mucosal immunity Induced by enhanced-potency inactivated and oral polio vacdnes. J Infect Dis 1991,163:1-6.
25
Bottiger M. A study of the serotmmunity that has protected the
Swedish population against poliomyelitis for 2 5 years. Scand J Infect Dis
1987:19:595-601.
26
S i m o n s e n O, Bentzon MW, Heron I. ELISA for t h e routine determination of antitoxic Immunity to tetanus. J Biol Standard 1986:14:
231-39.
27
Simonsen O, Schou C, Heron I. Modification of t h e ELISA for the
estimation of tetanus antitoxin in h u m a n sera. J Biol Standard 1987;
15:143-57.
28
H e n d r i k s e n CFM, v.d. Gun JW, Nagel J, Kreeftenberg JG. The
toxin binding inhibition test as a reliable in vitro alternative to the
toxin neutralization test in mice for t h e estimation of tetanus
antitoxin in h u m a n sera. J Biol Standard 1988; 16:287-97.
29
Scheibel L The uses and results of active t e t a n u s Immunization.
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30
Christenson B, Bottiger M. Serological i m m u n i t y to diphtheria in
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31
Miyamura K, Nishio S, Ito A, Murata R, K o n o R. Micro cell culture
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titration. J Biol Stand 1974;2:189-201.
32
Miyamura K, Tajtri E, Ito A, Murata R, Kono R. Micro cell culture
method for determination of diphtheria toxin and antitoxin using
VERO cells, n . Comparison with rabbit skin m e t h o d and practical
application for sero-epidemiological studies. J Biol Stand 1974;2:
203-09.
33
Griffith AH. The role of immunization in the control of diphtheria.
DevBiol Stand 1979,43:3-13.
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