Scand J Intect Dis 24: 753-758, 1992
Vaccine Immunity to Diphtheria: A 20-Year Follow-up Study MARGARETA BOTTIGER and GUNILLA PE'TTERSSON From the Department of Epidemiology, National BocrerrologlcoI Lnhortrtor.V. Srri~.kholm.
Scand J Infect Dis Downloaded from informahealthcare.com by University of Newcastle on 01/01/15 For personal use only.
SKY,tkW
A cohort of close to 70 children born in 1967-68 was followed for estimations of serum antitoxin levels against diphtheria. During the first 3-year-period after vaccination the mean level declined from 0.05 international units (IU) to 0.03. From the year before to the year after the booster of 0.5 LF of toxoid was given at the age of 8 years, the mean level raised from 0.01 to 0.06 IU. At 18 years the mean was again down to 0.01. Between 18 and 23 years of age a difference between the sexes was seen (higher levels in men). l h e explanation of this phenomenon must be the extra booster given to those young men who have done their compulsory military service.
M. Biittiger, MD, PhD, Department of Epidemiology, National Bacteriologiraal Laboratory, S-10.5 21 Stockholm, Sweden
INTRODUCTION In order to evaluate vaccination programmes, the immediate antibody response to the vaccination and the duration of the immunity are 2 necessary items o f information. In this context, the possible influence of the general circulation in the population of the agent in question must also be taken into consideration. Concerning diphtheria. with few exceptions (1). the circulation in Sweden during the past few decades must have been very small. Thus. studies of the immunity in the whole Swedish population ( 2 ) indicated that the older. unimmunized persons to a large extent lacked immunity and had not hcen exposed t o natural infection. Several outbreaks occurred, however, in the IYXOs especially among alcoholics and drug addicts ( I ) . Several hundred newborns were enrolled in a cohort study in I967-68. in order to study the duration of immunity primarily after the childhood polio vaccination ( 3 ) . Enough material was left over for other studies. The aim o f the present study was. h y the use of these samples, to follow the duration of post-vaccination immunity to diphtheria and to evaluate Table I . Ages of the children studied. In Fig. 1 and Table 11. only the 40 children tested at the ages of 18 and 23 arc included Children tested o n each test occasion Age (years) 1 i 4 months' 2 2 6 months 4 f 1 year 7.5 10 18
23 I'
Approximate age range.
N o . tested 62 62 67 64
45 63 40
754 M. Bottiger and G. Pettersson
S c a d J Infect Dis 24
Titre
log 10
IU
7
Scand J Infect Dis Downloaded from informahealthcare.com by University of Newcastle on 01/01/15 For personal use only.
-- 1.0
Booster
3-
1'
-
0.1 Y'
''t
*-
0.01
A
-
o-.
A
1
.
-- 0.001
1
1]=6262 67
64 45
40
20+20 Number tested
FIg. I . Geometric mean antitoxin levels against diphtheria at different ages. At the age of.23 a clear
difference was seen between males and females. as shown separately.
the vaccination programme involving the children born at the end of the 1960s, now young adults in Sweden. The results will give basic information for the evaluation of the current vaccination policy and also for the future schedules.
MATERIAL AND METHODS Sfucly group Nearly 70 children were studied, mainly those with enough serum left. Samples had been collected, on the average. 5 months, 2 and 3-5 years after vaccination, which most children had received at the ages of
Table 11. Mean antitoxin levels in IU at different ages Age at routine vaccination 3, 4.5, 6 months
8 years
Mean test age (years)
Mean antitoxin titre (IU)
1 2 4 7.5
0.05 0.04 0.03 0.01
10 18 23 M"
0.06 0.01 0.04 0.01
F h
Males: 9/20 showed increased titre levels between the ages of 18 and 23, indicating that they had rcceivcd a booster. and 1 had probably been immunized just before the age of 18. "Femalcs: 1 showed an increased titre between the ages of 18 and 23 and 1 had probably received a booster prior to 18 years of age, i.e. they had a raised level at the age of 18 which had declined at 23.
I'
Scand J Infect Dis Downloaded from informahealthcare.com by University of Newcastle on 01/01/15 For personal use only.
Scand J Intect
r\=
Dih
Vtrcc,irtcirrirniinity
21
1 2
4
6
8
10
14
18
36 39
37
X
40
29
35
383 2"
10
diphtheriri
23 Years
29$9'
Fig. 2. Geometric mean antitoxin levels against diphthcri;i iit different age\ of \ainple> collected from the 40 young adults reached at the age of 23. The twri persons with a indication of having received a booster injection before 18 (0----0) and the 9 with titre rise between I X and 23 vears of age (O-----O) are shown separately. 3, 4.5 and 6 months with plain diphtheria-pertussis-tetanus vaccine (DPT) (1) The primary series of 3 doses was completed for all children before the future schedules. Further sample4 tested were drawn before and after a booster at the age of about 7-8 years. 63 of the children were al\o tested at the age of 18 and 40 at the age of 23. Details are given in Table I . S m p l e s were not available from all the children on all occasions. Part of the cohort also received boosters as young adults, eyxxiallv before military service. 40 persons from whom samples could be collected at the age of both I X and 23 were also studied in samples collected at the age of 4 and 14 years.
Colli~rionof sumple~. For antibody studies. capillary blood (0.2 ml immediately diluted in a heparinizetl medium to a plasma dilution 1.8) was collected at intervals between 1968 and IY83. At the age of I X in 19x5 and 23 i n 1990. venous blood was obtained from the pcrsons still joining the study. Vuccitze The plain D P T vaccine contained 30 LF (flocculation unitb) of diphtheria toxoid per dose (2). For the booster at the age of ti a tetanub toxoid absorbed t o aluminium phosphate Hith 0.5 LF o f diphtheria toxoid pcr dose was generally used (Td). Vaccinations with Td o r T alone were also given to part of the cohort i n conncction with military service, The records of these vaccinations were not available Tiirritiori technique The diphtheria-antitoxin levels of the sera were tested on tissue-culture microplatcs. The method has been described in detail earlier (2). In brief, 4-fold serial dilutions of the serii wcrc challenged by 100 tissue-culture, toxic doses of diphtheria toxin. Binding WilS performed for 1 h a t rooni temperature. Two microplate wells were used for each dilution. Vero cells suspended in tissue-culture medium were finally added t o the wells. The toxic effect was read after a week and thc titre given was the dilution ciiuhlng toxic reaction in SO'% o f the wells. The WHO reference standard o f diphtheria antitoxin wa\ included in all tests. The working dilution o f 1: 1000 yielded a neutralizing titre of I:16. Antibody levels arc given both as ordinary antitoxin titres in I0 log and in international standard units ( I l J ) . The lowest dilution tested was I:H o f the finger stick samples and 1.4 of the venous serum samples. A titre o f 1 : 1 corrc\ponded t o 0,OOS I U .
755
756 M . Bottiger and G. Pettersson
Scand J Infect Dis 24
Table 111. Percentage of children falling into the 3 categories of protection A . protected; B. partly protected; C . not protected Protection category
Mean age in years 2
4
7.5
10
F
Scand J Infect Dis Downloaded from informahealthcare.com by University of Newcastle on 01/01/15 For personal use only.
A. >0. 1
23
IX
M
F
M
15.6
10.4
4.1
26.7
6.7
0
14.3
35.0
0.01- 16-fold rise (n=9) in the later phase of the study are illustrated separately. The mean titre level of the others is continuously declining. The traditional way of demonstrating the immunity status of a person or a population is to give the antitoxin titre in international units and to classify it as fully protective (titres > 0.1 IU). partly protective (titres < 0.120.01) or unprotective (titres < 0.01). This classification was constructed by Edward and Allison (4)and Edsall (5) in the 1940s. In Table 111, the percentage of the children falling in the 3 categories is shown. It was apparent that the immunity status of this cohort was not satisfactory, as, according t o the classification, nearly half the children lacked protective immunity at the age of 7-8 and 33% at the age of 18.
DISCUSSION After vaccination, the peak of the antibody response is generally reached within 2-3 months (6). Thereafter, during the following year, a rather steep decline of titre levels is first observed, after which a levelling-off occurs. The duration of the immunity is thus dependent on the initial antibody response. the immediate antibody fall and the decrease thereafter. These kinetics will vary, depending upon the nature of the antigen, how it is administered, whether live or killed and, whether with or without adjuvant.
Scand J Infect Dis Downloaded from informahealthcare.com by University of Newcastle on 01/01/15 For personal use only.
This study was initially not designed for thc follow-up of diphtheria immunity but for that of polio. N o sample was available 2 weeks after the immunization. Other studies ( 6 8 ) indicate that post-vaccination, mean anti-diphtheria toxin levels rise u p to or above 1 .O IU after 2-3 weeks. In our study. it was 0.05 1U after iihout 5 months. a i ~ iifter l ;I further = 7 years. i.e. in t h e sample taken prior to the boo\ter. it had declined to 0.01 IU. This prc-booster level of 0.01 IU is in agreement with the experience of thc authors of studies carried out in connection with an immunization study in 1987 of 0-year-old and 10-year-old children primo-vaccinated with aluminium adsorbed D T given at the age of 3. 4.5 and 6 months (9). The mean level of the post-booster scample i n t h e present \tudy taken after 1-2 years at the age o f = Y - I 0 was 0.06 I U . This indicate> that even t h e low hoostcr dose of 0.5 LF of diphtheria toxoid had a not negligable, aiitihody-stimulating effect. The fall in titre betwccn the samples drawn at the age of 10 and those collected ;it thc ape o! 18. wiis from 0.06 to 0.01 IU. The decline between these two ages can roughly be e\tim;ited a s 4-fold. but the calculation is hampered by the lack of recordings of possiblc vaccinations between thc ages of I0 and 18. Two children. 1 boy and I girl. hiid strong indications ot having received a further dose just before the age of 18. The shapes of,thc declines i n titrc between 1 and 7 years of age and between 10 and 18 are remarkably similar. indicating a continuous. linear course. This was also observed in a Danish studv (10). Thc kinetics do not differ much from that of polio antibody levels in the same populations. Sero-surveys o f immunity to diphtheria toxin representative for t h e Swedish population were carried out in 2400 persons in 1978 and IO)X4. The results indicated that the immunity was “disturbingly low”. Even in the vaccinated part of the population up t o 30%) lacked protective immunity (2). The results were much in line with the experience5 o f this study. Hopefully the immunization programme now used which was initiated in 19x6 will improve the immunity. An aluminium adsorbed DT vaccine is now used m d the schedule is spaced over 9 months and supplemented by a booster dose containing 7.5 LF at the age o f 10. The first experiences of such a schedule was studied in the children iit the age of 5 . i.e. 4 years after the 3 primary doses administered between 3 and I ? months 01 age (8. 9). The results indicated a higher immunity in these children (mean 0.06 I l l ) compared t o the children of the present study (mean 0.02 I U . interpolation between 3 ;ind h years o f age) and also other children similarly vaccinated with plain vaccine (mean 0.012 I l l ) tested at the ape of 6 years (9). The need for a booster dose in iidulthood has been discussed by several authors ( 1 1-13). Both the need for it and possible \ide reactions in adult\ have to he taken into consideration. The experience has been thiit even low hoostcr tlo\e\ give ;I good antibody response and that such vaccines d o n o t c;iusc considerable disatlviintnges (12. 14). Thus the main question is if a booster will he necessary in the future when almost all have been vaccinated in childhood. People directly exposed to infected persons professionally or who travel to high endemic areas should of course secure immunity. The conclusion of the present study is that the diphtheria antitoxin levels decline with time. The immunity in the general population should be checked. I t ;I significant part ot the future adult population shows unsatisfactory protection the need ol ;I booster later in life should be taken into consideration.
REFERENCES 1. Bjijrkholm B, BBttiger M, Christenson B. Hagbcrg I Antitoxin antihod! le\cl\ and the outconieot illness during an outbreak of diphtheria among i i l c o l ~ o l i c ~Scand . J Inlect I)i\ I N : 735-239. 1986. 2. Christenson €3. BZittiger M. Serological immunit? iliphthcria in Swcden 111 19721a n d I9X3. Sc;incl J Infect Dis 18: 227-233, 1986.
Scand J Infect Dis Downloaded from informahealthcare.com by University of Newcastle on 01/01/15 For personal use only.
758 M . Bottiger and G. Pettersson
Scand J Infect Dis 14
3. Bottiger M. Polioimmunity to killed vaccine: An 18-year follow-up. Vaccine 8: 443-445, 1990. 4. Edward D. Allison V. Diphtheria in the immunized with observations on a diphtheria-like disease associated with non-toxigenic strains of Corynebacterium diphtheriae. J Hyg 49: 205-219, 1951. 5 . Edsall G . Immunization of adults against diphtheria and tetanus. Am J Public Health 42: 393-400, 1952. 6. Jensen C. Antitoxin curve in children after active immunization with diphtheria anatoxin with special reference to duration of the antitoxic immunity. Acta Pathol Microbiol Scand 10: 137-158. 1933. 7. Vahlquist B, Olin G , Mellbin T, Melen B, Bottiger M. Kombinerad immunisering mot poliomyelit, difteri. tetanus och pertussis under 1. levnadsiret. Nord Med 68: 1331-1347, 1962. (In Swedish.) 8. Larsen R , Ullberg-Olsson K, Wickbom B. Hederstedt B. The immunization of children with combined diphtheria and tetanus vaccine in Sweden. J Biol Stand 15: 10F107, 1987. 9. Mark A, Christenson B, Granstrom M, Strandell A. Wickbom B, Bottiger M. Immunity and immunization of children against diphtheria in Sweden. Eur J Clin Microbiol Infect Dis 8: 214-219. 1989. 10. Simonsen 0. Kjeldsen K, Bentzon M, Heron I. Susceptibility to diphtheria in populations vaccinated before and after elimination of indigenous diphtheria in Denmark. Acta Pathol Microbiol Immunol Scand 95: 225-231, 1987. 11. Mathias RG, Schechter MT. Booster immunisation for diphtheria and tetanus: No evidence of need in adults. Lancet I: 1089-1091, 1985. 12. Mortimer J. Mellville-Smith M. Diphtheria vaccine for adults. Lancet 2: 1182-1183, 1986. 13. Settergren B. Broholm KA, Norrby S. Diphtheria revaccination of adults. Lancet 1: 557-558, 1987. 14. Settergren B. Broholm KA. Norrhy S R , Christenson B. Schick test as a predictor of immunity to diphtheria and of side effects after revaccination with diphtheria vaccine. Br Med J 292: 524525, 1986.
Vaccine Immunity to Diphtheria: A 20-Year Follow-up Study MARGARETA BOTTIGER and GUNILLA PE'TTERSSON From the Department of Epidemiology, National BocrerrologlcoI Lnhortrtor.V. Srri~.kholm.
Scand J Infect Dis Downloaded from informahealthcare.com by University of Newcastle on 01/01/15 For personal use only.
SKY,tkW
A cohort of close to 70 children born in 1967-68 was followed for estimations of serum antitoxin levels against diphtheria. During the first 3-year-period after vaccination the mean level declined from 0.05 international units (IU) to 0.03. From the year before to the year after the booster of 0.5 LF of toxoid was given at the age of 8 years, the mean level raised from 0.01 to 0.06 IU. At 18 years the mean was again down to 0.01. Between 18 and 23 years of age a difference between the sexes was seen (higher levels in men). l h e explanation of this phenomenon must be the extra booster given to those young men who have done their compulsory military service.
M. Biittiger, MD, PhD, Department of Epidemiology, National Bacteriologiraal Laboratory, S-10.5 21 Stockholm, Sweden
INTRODUCTION In order to evaluate vaccination programmes, the immediate antibody response to the vaccination and the duration of the immunity are 2 necessary items o f information. In this context, the possible influence of the general circulation in the population of the agent in question must also be taken into consideration. Concerning diphtheria. with few exceptions (1). the circulation in Sweden during the past few decades must have been very small. Thus. studies of the immunity in the whole Swedish population ( 2 ) indicated that the older. unimmunized persons to a large extent lacked immunity and had not hcen exposed t o natural infection. Several outbreaks occurred, however, in the IYXOs especially among alcoholics and drug addicts ( I ) . Several hundred newborns were enrolled in a cohort study in I967-68. in order to study the duration of immunity primarily after the childhood polio vaccination ( 3 ) . Enough material was left over for other studies. The aim o f the present study was. h y the use of these samples, to follow the duration of post-vaccination immunity to diphtheria and to evaluate Table I . Ages of the children studied. In Fig. 1 and Table 11. only the 40 children tested at the ages of 18 and 23 arc included Children tested o n each test occasion Age (years) 1 i 4 months' 2 2 6 months 4 f 1 year 7.5 10 18
23 I'
Approximate age range.
N o . tested 62 62 67 64
45 63 40
754 M. Bottiger and G. Pettersson
S c a d J Infect Dis 24
Titre
log 10
IU
7
Scand J Infect Dis Downloaded from informahealthcare.com by University of Newcastle on 01/01/15 For personal use only.
-- 1.0
Booster
3-
1'
-
0.1 Y'
''t
*-
0.01
A
-
o-.
A
1
.
-- 0.001
1
1]=6262 67
64 45
40
20+20 Number tested
FIg. I . Geometric mean antitoxin levels against diphtheria at different ages. At the age of.23 a clear
difference was seen between males and females. as shown separately.
the vaccination programme involving the children born at the end of the 1960s, now young adults in Sweden. The results will give basic information for the evaluation of the current vaccination policy and also for the future schedules.
MATERIAL AND METHODS Sfucly group Nearly 70 children were studied, mainly those with enough serum left. Samples had been collected, on the average. 5 months, 2 and 3-5 years after vaccination, which most children had received at the ages of
Table 11. Mean antitoxin levels in IU at different ages Age at routine vaccination 3, 4.5, 6 months
8 years
Mean test age (years)
Mean antitoxin titre (IU)
1 2 4 7.5
0.05 0.04 0.03 0.01
10 18 23 M"
0.06 0.01 0.04 0.01
F h
Males: 9/20 showed increased titre levels between the ages of 18 and 23, indicating that they had rcceivcd a booster. and 1 had probably been immunized just before the age of 18. "Femalcs: 1 showed an increased titre between the ages of 18 and 23 and 1 had probably received a booster prior to 18 years of age, i.e. they had a raised level at the age of 18 which had declined at 23.
I'
Scand J Infect Dis Downloaded from informahealthcare.com by University of Newcastle on 01/01/15 For personal use only.
Scand J Intect
r\=
Dih
Vtrcc,irtcirrirniinity
21
1 2
4
6
8
10
14
18
36 39
37
X
40
29
35
383 2"
10
diphtheriri
23 Years
29$9'
Fig. 2. Geometric mean antitoxin levels against diphthcri;i iit different age\ of \ainple> collected from the 40 young adults reached at the age of 23. The twri persons with a indication of having received a booster injection before 18 (0----0) and the 9 with titre rise between I X and 23 vears of age (O-----O) are shown separately. 3, 4.5 and 6 months with plain diphtheria-pertussis-tetanus vaccine (DPT) (1) The primary series of 3 doses was completed for all children before the future schedules. Further sample4 tested were drawn before and after a booster at the age of about 7-8 years. 63 of the children were al\o tested at the age of 18 and 40 at the age of 23. Details are given in Table I . S m p l e s were not available from all the children on all occasions. Part of the cohort also received boosters as young adults, eyxxiallv before military service. 40 persons from whom samples could be collected at the age of both I X and 23 were also studied in samples collected at the age of 4 and 14 years.
Colli~rionof sumple~. For antibody studies. capillary blood (0.2 ml immediately diluted in a heparinizetl medium to a plasma dilution 1.8) was collected at intervals between 1968 and IY83. At the age of I X in 19x5 and 23 i n 1990. venous blood was obtained from the pcrsons still joining the study. Vuccitze The plain D P T vaccine contained 30 LF (flocculation unitb) of diphtheria toxoid per dose (2). For the booster at the age of ti a tetanub toxoid absorbed t o aluminium phosphate Hith 0.5 LF o f diphtheria toxoid pcr dose was generally used (Td). Vaccinations with Td o r T alone were also given to part of the cohort i n conncction with military service, The records of these vaccinations were not available Tiirritiori technique The diphtheria-antitoxin levels of the sera were tested on tissue-culture microplatcs. The method has been described in detail earlier (2). In brief, 4-fold serial dilutions of the serii wcrc challenged by 100 tissue-culture, toxic doses of diphtheria toxin. Binding WilS performed for 1 h a t rooni temperature. Two microplate wells were used for each dilution. Vero cells suspended in tissue-culture medium were finally added t o the wells. The toxic effect was read after a week and thc titre given was the dilution ciiuhlng toxic reaction in SO'% o f the wells. The WHO reference standard o f diphtheria antitoxin wa\ included in all tests. The working dilution o f 1: 1000 yielded a neutralizing titre of I:16. Antibody levels arc given both as ordinary antitoxin titres in I0 log and in international standard units ( I l J ) . The lowest dilution tested was I:H o f the finger stick samples and 1.4 of the venous serum samples. A titre o f 1 : 1 corrc\ponded t o 0,OOS I U .
755
756 M . Bottiger and G. Pettersson
Scand J Infect Dis 24
Table 111. Percentage of children falling into the 3 categories of protection A . protected; B. partly protected; C . not protected Protection category
Mean age in years 2
4
7.5
10
F
Scand J Infect Dis Downloaded from informahealthcare.com by University of Newcastle on 01/01/15 For personal use only.
A. >0. 1
23
IX
M
F
M
15.6
10.4
4.1
26.7
6.7
0
14.3
35.0
0.01- 16-fold rise (n=9) in the later phase of the study are illustrated separately. The mean titre level of the others is continuously declining. The traditional way of demonstrating the immunity status of a person or a population is to give the antitoxin titre in international units and to classify it as fully protective (titres > 0.1 IU). partly protective (titres < 0.120.01) or unprotective (titres < 0.01). This classification was constructed by Edward and Allison (4)and Edsall (5) in the 1940s. In Table 111, the percentage of the children falling in the 3 categories is shown. It was apparent that the immunity status of this cohort was not satisfactory, as, according t o the classification, nearly half the children lacked protective immunity at the age of 7-8 and 33% at the age of 18.
DISCUSSION After vaccination, the peak of the antibody response is generally reached within 2-3 months (6). Thereafter, during the following year, a rather steep decline of titre levels is first observed, after which a levelling-off occurs. The duration of the immunity is thus dependent on the initial antibody response. the immediate antibody fall and the decrease thereafter. These kinetics will vary, depending upon the nature of the antigen, how it is administered, whether live or killed and, whether with or without adjuvant.
Scand J Infect Dis Downloaded from informahealthcare.com by University of Newcastle on 01/01/15 For personal use only.
This study was initially not designed for thc follow-up of diphtheria immunity but for that of polio. N o sample was available 2 weeks after the immunization. Other studies ( 6 8 ) indicate that post-vaccination, mean anti-diphtheria toxin levels rise u p to or above 1 .O IU after 2-3 weeks. In our study. it was 0.05 1U after iihout 5 months. a i ~ iifter l ;I further = 7 years. i.e. in t h e sample taken prior to the boo\ter. it had declined to 0.01 IU. This prc-booster level of 0.01 IU is in agreement with the experience of thc authors of studies carried out in connection with an immunization study in 1987 of 0-year-old and 10-year-old children primo-vaccinated with aluminium adsorbed D T given at the age of 3. 4.5 and 6 months (9). The mean level of the post-booster scample i n t h e present \tudy taken after 1-2 years at the age o f = Y - I 0 was 0.06 I U . This indicate> that even t h e low hoostcr dose of 0.5 LF of diphtheria toxoid had a not negligable, aiitihody-stimulating effect. The fall in titre betwccn the samples drawn at the age of 10 and those collected ;it thc ape o! 18. wiis from 0.06 to 0.01 IU. The decline between these two ages can roughly be e\tim;ited a s 4-fold. but the calculation is hampered by the lack of recordings of possiblc vaccinations between thc ages of I0 and 18. Two children. 1 boy and I girl. hiid strong indications ot having received a further dose just before the age of 18. The shapes of,thc declines i n titrc between 1 and 7 years of age and between 10 and 18 are remarkably similar. indicating a continuous. linear course. This was also observed in a Danish studv (10). Thc kinetics do not differ much from that of polio antibody levels in the same populations. Sero-surveys o f immunity to diphtheria toxin representative for t h e Swedish population were carried out in 2400 persons in 1978 and IO)X4. The results indicated that the immunity was “disturbingly low”. Even in the vaccinated part of the population up t o 30%) lacked protective immunity (2). The results were much in line with the experience5 o f this study. Hopefully the immunization programme now used which was initiated in 19x6 will improve the immunity. An aluminium adsorbed DT vaccine is now used m d the schedule is spaced over 9 months and supplemented by a booster dose containing 7.5 LF at the age o f 10. The first experiences of such a schedule was studied in the children iit the age of 5 . i.e. 4 years after the 3 primary doses administered between 3 and I ? months 01 age (8. 9). The results indicated a higher immunity in these children (mean 0.06 I l l ) compared t o the children of the present study (mean 0.02 I U . interpolation between 3 ;ind h years o f age) and also other children similarly vaccinated with plain vaccine (mean 0.012 I l l ) tested at the ape of 6 years (9). The need for a booster dose in iidulthood has been discussed by several authors ( 1 1-13). Both the need for it and possible \ide reactions in adult\ have to he taken into consideration. The experience has been thiit even low hoostcr tlo\e\ give ;I good antibody response and that such vaccines d o n o t c;iusc considerable disatlviintnges (12. 14). Thus the main question is if a booster will he necessary in the future when almost all have been vaccinated in childhood. People directly exposed to infected persons professionally or who travel to high endemic areas should of course secure immunity. The conclusion of the present study is that the diphtheria antitoxin levels decline with time. The immunity in the general population should be checked. I t ;I significant part ot the future adult population shows unsatisfactory protection the need ol ;I booster later in life should be taken into consideration.
REFERENCES 1. Bjijrkholm B, BBttiger M, Christenson B. Hagbcrg I Antitoxin antihod! le\cl\ and the outconieot illness during an outbreak of diphtheria among i i l c o l ~ o l i c ~Scand . J Inlect I)i\ I N : 735-239. 1986. 2. Christenson €3. BZittiger M. Serological immunit? iliphthcria in Swcden 111 19721a n d I9X3. Sc;incl J Infect Dis 18: 227-233, 1986.
Scand J Infect Dis Downloaded from informahealthcare.com by University of Newcastle on 01/01/15 For personal use only.
758 M . Bottiger and G. Pettersson
Scand J Infect Dis 14
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