Immunity to tetanus in United Kingdom populations

Journal of Infection (I993) z7, 255-260

Immunity

to t e t a n u s i n U n i t e d K i n g d o m

populations

N. S. C u m b e r l a n d , A. G. Kidd a n d L. K a r a l l i e d d e

Queen Elizabeth Military Hospital, Stadium Road, Woolwich, London S E I 8 4QH, UK. Accepted for publication I7 May I993 Summary As tetanus, a totally preventable disease, is still encountered in the older age group in England and Wales, a study was carried out to assess the state of immunity to the disease in the elderly population. These levels were compared to those in recruits and service personnel in the Army. Elderly patients with underlying disease had lower levels than the elderly who were healthy. When compared with recruit population the elderly group had significantly lower levels of antibody. If tetanus is to be eliminated, an effective programme of immunisation extending throughout life must be ensured.

Introduction T e t a n u s is a notifiable and preventable disease. As with small pox and polio in this century, so should tetanus no longer be e n c o u n t e r e d in the next. A national active i m m u n i s a t i o n p r o g r a m m e initiated in I 9 6 I has resulted in the virtual elimination of c h i l d h o o d tetanus in Britain. 1 H o w e v e r , there have been cases of tetanus, some fatal, among the older age groups in E n g l a n d and Wales during the last IO y e a r s ) '3 Cases have followed surgery and others have occurred in healthy elderly persons, particularly w o m e n , following gardening i n j u r i e s ) -5 D u e to a change in Service policy for tetanus immunisation, this s t u d y was set u p to assess the i m m u n i t y against tetanus of recruits and serving personnel within the A r m y . In addition, i m m u n i t y to tetanus was d e t e r m i n e d in an elderly p o p u l a t i o n presenting to this hospital.

Subjects D u r i n g routine medical examinations b l o o d was obtained from IOI male a r m y recruits, age range I7 to 27 years (mean I9 years 7 months) and 93 female recruits, age range I7 to 25 years (mean I9 years 5 months). Individuals had been i m m u n i s e d according to the national vaccination p o l i c y ? A total of 32 serving personnel (3 females, 29 males) aged b e t w e e n 20 and 46 years (mean age 28 years) received a single booster injection of tetanus toxoid BP. Blood was then obtained for assay within 6 months. Blood was also collected f r o m IOO elderly patients with underlying disease, aged 6o to 85 years (mean age 76 years) presenting for elective surgery at this hospital, and 6o elderly individuals, w i t h o u t underlying disease, aged 7o to 8o years (mean age 75 years). All sera were obtained during I 9 9 I and maintained at - 4 0 °C until assayed. * Address correspondence to Dr L. Karalliedde. oi63-4453/93/o6o255 +06 $08.00/0

© I993 The British Society for the Study of Infection

256

N. S. C U M B E R L A N D

ET AL.

Ethical approval was obtained from the A r m y Medical Services Research Executive. Materials and methods

T h e serum concentration of I g G antibodies against tetanus toxoid of each m e m b e r of the donor groups was estimated by in vitro ELISA. T h e commercially available Virotech E L I SA test kit (Virotech, SystemDiagnostika G m b H , Cambridge Life Sciences plc), was used in association with a Titertek Multiskan microtitre plate reader (Titertek, U.K.). All sera were analysed in duplicate and according to the manufacturer's recommended instructions. Statistical methods

Logs to the base of IO of the titre readings were used to normalise data and stabilise the between-group variances. Groups of subjects were compared using the two-tailed, two sample t-test and significance levels, P, of ~< o'o5 were considered to indicate statistically significant results. Results

All recruits of both sexes, serving personnel receiving a single booster dose of tetanus toxoid and the elderly who were well were found to have titres of at least o" I International Units (IU) of tetanus antitoxin per ml. This titre is tenfold greater than what is generally accepted as sufficient to provide immunity to t e t a n u s : In the Ioo elderly with underlying disease, I2 were found to have titres of between 0"05 and o.I I U / m l of tetanus antibody. T h e distribution of the titres in the sera from each of the five groups is shown in Figure I. Table I summarises the statistical data for tetanus antibody titres in the sera from each group. T h e titres of tetanus antibody in male recruits were on average 28 % above those of female recruits (P = o.I, 95 % Confidence Interval (CI) from 6% below to 73 % above), but this is not significant. T h e antibody titres for serving personnel within 6 months of receiving a booster injection were, on average, 90 % above the titres from recruits (both sexes combined), and this is highly statistically significant (o.ooI < P < o'oo5, 95 % CI from 25 % to I89 % above). When the antibody titres of the elderly are compared, those with underlying disease were on average 2o ~/o below those of the elderly who were healthy, but these differences are not statistically significant (P = o'3, 95 ~o CI from 46 below to I9 % above). However, the antibody titres of the elderly (both groups combined), are on average 75 % below those of the recruits (both sexes combined), and these values are very highly significant (P ~ o.oooi, 95 % CI from 68 % to 8o % below). Recruits were asked to recall their last tetanus booster injection. O f those that could recall, 82 % of males and 95 % of females gave a history of tetanus immunisation during the previous IO years. Biochemical profiles were performed on all members of the elderly groups.

Immunity to tetanus in U.K. n = 101

IOC

n = 93

n = 32

n = 60

n = 100

8(

257 •

<0.1

V o.1[ osEll.o[] 5.0-10-0

¢9

60

~ 4O

20

Male recruits

Female recruits

Serving personnel

Elderly well

Elderly ill

Fig. I. Distributions of antibody titres (IU/ml) for the five subject groups.

Table I Summary of statistics for tetanus antibody titres A n t i b o d y titres I U / m l Range Group Male recruits Female recruits Serving personnel E l d e r l y well E l d e r l y ill

Sample size

Geometric mean

Mean

Median

Minimum

Maximum

Io I 93

~'66 I'3O

3'00 I'88

I'7O I'3O

o' I o o'IO

IO'OO 9"IO

32

2' 81

4' 81

2"5 °

O' I 0

I 0"00

6o IOO

o'42 o'34

0'85 0"74

o'5o o'30

o'Io 0'o5

6"3o 7"60

L o w albumin and total protein concentrations were found in eight, two had raised liver enzymes and four low transferrin concentrations. However, there was no correlation between these results and antibody titres. Discussion

A previous study showed that recruits to the Army had a mean antitetanus antibody titre of I'O9 I U / m l , 8 a value comparable to those found in this study: 3 " o o I U / m l for male and 1-88 I U / m l for females. These results are commensurate with age-related antitoxin titres defined in recent studies in the U n i t e d Kingdom. 9'1° These studies provide continuing assurance that the national immunisation programme provides adequate protection against tetanus for the I7 to 25 year age group. Similarly, both studies have shown that

258

N. S. C U M B E R L A N D

ET AL.

serving personnel have higher antibody titres than recruits. T h e mean antibody titre of 4"81 I U / m l of serving personnel in this study was higher than the I'47 I U / m l of the previous study. 8 All the serving personnel we studied had received a pre-combat tetanus booster (for the G u l f conflict) within 6 months of the assay. Since I988, the A r m e d Services tetanus immunisation policy has involved a single dose of adsorbed tetanus toxoid BP on entry to the Army, and another every 5 years up to the fifth reinforcing dose and thereafter every IO years, n This differs from the policy operative at the time of the previous study when three doses of T A B T (typhoid, paratyphoid A and B and tetanus toxoid) which contained smaller amounts of tetanus toxoid, were given on entry into the Army, and at three yearly intervals thereafter until the age of 35 Years.8 Protection against tetanus of service personnel during training and sport or combat is essential. T h e different vaccine, now given at 5 yearly intervals to obviate the need to give those with tetanus prone wounds a booster dose or tetanus immune-globulin, is justified. This policy is sufficient to maintain an antitoxin titre above o.I I U / m l , but avoids concentrations associated with adverse reactions. Poor immunity against tetanus appears to be a general problem among adults in the Western World. Recent historical and serological surveys in America indicate that a significant proportion of the population over 5o years of age remains seronegative. 12-1~ Studies from Sweden, Denmark and Finland indicate that between 44 % and 68 % of the elderly population may not be protected against tetanus. 15-17 T h u s in developed countries, those over 5o years of age are most likely to be seronegative. Age specific immunity was lower for females than males, n' 15.16 This may reflect more frequent tetanus immunisation in men as a result of injury or routinely during military service. In the United Kingdom during adult life the maintenance of immunity against tetanus by booster immunisation is the individual's responsibility: no routine revaccinations or general vaccination of adults is offered. T h e authors have no knowledge of reports on the immune status for tetanus for the elderly in the United Kingdom. This small study indicates that the elderly patients with underlying disease had less antibody than the elderly subjects who were well. When compared with the recruit population, the elderly group had significantly smaller amounts of antibody (P ~ o.oooi). Twelve of the elderly who were ill had antibody levels less than o'I I U / m l , but these amounts were not associated with any particular disease or biochemical abnormality. This study indicates that the elderly population has significantly lower titres of tetanus antibodies than does the age group I7 to 25 years. T h e status of immunity to tetanus is often ascertained from the history of immunisation. Following a case of tetanus in their practice, Bibby and Dixon questioned 6oo adults. Based on a recall of primary immunisation and a booster within the previous IO years (Department of Health recommendation) 1, only 21% were found to be protected with certainty. 18 T h e lowest prevalence of immunisation was in the females aged 3o to 6o years. We found that among the I94 members of the younger age group 73 could not recall the last date of tetanus immunisation. This finding agrees with

I m m u n i t y to tetanus in U . K .

259

H o w i e 19 who observed that patients' abilities to r e m e m b e r their past medical histories is unreliable even over short periods of time. A d d e d to this is the likelihood o f a patient changing doctors once every I6 years with the possibility of incomplete records o f i m m u n i s a t i o n . M o s t cases of tetanus follow m i n o r w o u n d s of the extremities as a result of agricultural or sporting activities. ~°'21 Because of the trivial n a t u r e o f these w o u n d s , m a n y individuals do not seek medical attention. 2°'22 It follows, therefore, that tetanus cannot be totally eliminated even by correctly a d m i n i s t e r e d prophylaxis after injury. It m a y occur even with a history of previous i m m u n i s a t i o n . 23 I n r99I there was a report of a 69-year-old farmer who developed tetanus despite having h a d a booster dose o f vaccine in r983 .6 T h e r e is scattered evidence that i m m u n i t y to tetanus deteriorates in the presence of systemic disease. L o w e r titres of tetanus antitoxin have been d e m o n s t r a t e d in patients with ulcers and neoplastic diseases of the gastrointestinal tract and in particular of the liver and biliary tract, w h e n c o m p a r e d with h e a l t h y persons of corresponding age. 24 A l t h o u g h we could find no correlation in our small s t u d y group o f the elderly, this possibility should be borne in m i n d . Individuals in their fifth decade of life should be offered i m m u n i s a t i o n especially w h e n entering hospital, particularly because protective a m o u n t s of a n t i b o d y can be i n d u c e d in this age group by imm u n i s a t i o n . 25 I f tetanus is to be eliminated, an effective p r o g r a m m e of i m m u n i s a t i o n extending t h r o u g h o u t life m u s t be ensured. W e concur with H o w i e 19 that everyone should be offered r e - i m m u n i s a t i o n every IO years and those in hospital practice should continue to bear in m i n d the remote risk of tetanus in the elderly. (The authors express their gratitude to Mrs M. M. Sims for assistance with statistical analysis and to M. L. Dawe for technical assistance. The work reported in this paper was supported by the Army Medical Research Executive under project number 438.) References I. Joint Committee on Vaccination and Immunisation. Immunisations against infectious disease. London DHSS. Scottish Home and Health Department and Welsh Office, 1988 : 25--29 . 2. Public Health Laboratory Services Communicable Disease Surveillance Centre. Tetanus Surveillance England and Wales r981-83. Brit Med ff I985 ; 29o: 696-697. 3. Personal Communication. Handsford S. Central Public Health Laboratory Service, Communicable Disease Surveillance Centre. 4. Lermard T W J , G u n n A, Sellers J, Stoddart JC. Tetanus after elective cholecystectomy and explorations of common bile duct. Lancet 1984; i: 1466-1467. 5. Parker L, Mandal BK. Post-operative tetanus. Lancet I984; ii: 407. 6. P H L S Communicable Disease Surveillance Centre. A Case of Tetanus Communicable Disease Report. I991 ; 4o(1). 7- Tasman A, Huygen FJA. Immunisation against tetanus of patients given injections of antitetanus serum. Bull W H O I962; 26: 397-4o7.

8. Faithfull-Davies DN, Parry ES, Sheffield F, Fieldhouse PM, Boxall MA. Tetanus antitoxin titres in Military Personnel. J R Army Med Corps I989; I]5: IO9--II4. 9. Jones A E, Melville-Smith M, Watkins J, Seagroatt V, Rice L, Sheffield F. Adverse reactions in adolescents to reinforcing doses of plain and adsorbed tetanus vaccines. Comm Med I985; 7: 99-1o6.

260

N. S. C U M B E R L A N D ET AL.

xo. Chikhani CG, K u m a r K. Tetanus booster every 5 years: an unnecessary routine? Arch Emerg Med 1988; 5: 4 - I I . I I. Joint Service Policy: M e m o r a n d u m on Immunological Procedures. H M S O , London 1992. 12. Hilton E, Singer C, Kozarsky P, Smith MA, Lardis PM, Borenstein M T . Status of immunity to tetanus, measles, mumps, rubella and polio among U S travellers. Ann Int Med 1991; I I 5 : 32-33. 13. Scher K S , Baldera A, Wheeler WE, Walker R, Jones CW. Inadequate tetanus protection among the rural elderly. S Med J I985; 78: I53-I56. I4. Weiss BP, Straaborg MA, Feeley JC. Tetanus and Diphtheria Immunity in an elderly population in Los Angeles County. Am J Publ Health 1983; 73: 802-8o4. 15. Christensen B, Bottiger M. Epidemiology and immunity to tetanus in Sweden. Scand J Infect Dis 1987; I9: 429-35. 16. Kjeldsen K, Simonsen I, Heron I. Immunity against diphtheria and tetanus in the age group 3o-7o years. Scand J Infect Dis I988; 2 0 : I 7 7 - I 85. I7. Viljanen M, Nieminen S. I m m u n i t y to tetanus in Finland. ScandJ Infect Dis I98O; 1 2 : 211--213 . 18. Dixon A M , Bibby JA. Tetanus immunisation state in a general practice population. Br M e d J 1988; 297: 598. 19. Howie JGR. Anyone for tetanus? Boosters advised for adults on every decade birthday. Br M e d J 1988; 297:17o-171. 2o. Edmondson RS, Flowers M W . Intensive care in Tetanus : management, complications and mortality in IOO cases. Br Med J 1979; I : 14o1-14o4. 21. Atrakchi SA, Wilson D H . Who is likely to get tetanus? Br M e d J 1977; I : 179. 22. Bowen V, Johnson J, Boyle J, Snelling C F T . T e t a n u s - - a continuing problem in minor injuries. Can J Surg 1988; 31 : 7-9. 23. Smith J W G . Diphtheria and tetanus toxoids. Br Med Bull 1969; 25: 177-181. 24. Gil IV. I m m u n i t y to tetanus in patients with chronic diseases. Vrachen bade Delo 1989; i2I-i23. 25. Ruben F L , Nagel J, Fireman P. Antitoxin responses in the elderly to tetanus-diphtheria immunisation. Am J Epidemiol 1978; lO8: 145-149.