Antidiphtheria and antitetanus antitoxic immunity indices in the population of the Estonian SSR (an assessment of the effectiveness of a planned vaccine prophylaxis)]

In 1972-1974 and 1977 in the Estonian SSR children and adults were surveyed for the presence of antibodies against tetanus and diphtheria toxins (toxoids) by means of the passive hemagglutination test. The level of protection against tetanus was revealed to correspond to the proportion of child population covered by vaccination: in 1977, with 98.8% covered by vaccination, the level of protection among children aged 7 to 14 years and adolescents of 15-19 years exceeded 98%; with the increase of age (every 10-15 years) the level of protection against tetanus regularly decreased. This dynamics correlated with the existing terms of postvaccinal immunity and the epidemiological independence of tetanus as infectiion. The level of protection in child population against diphtheria in 1972-1974 and 1977 lagged behind the level of protection against tetanus and the coverage by vaccination. The diphtheria component of adsorbed DPT vaccine seemed to be unable to ensure the sufficient level and intensity of immunity under conditions of a sharply decreased risk of encounter with the infective agent. In persons aged 40 years and over the indices of immunity against diphtheria were higher than against tetanus. These indices resulted from diphtheria infection at the prevaccination period and could serve as an objective sign in following up the decrease of the process of diphtheria epidemics.     

Booster vaccination against tetanus and diphtheria: insufficient protection against diphtheria in young and elderly adults

We have recently demonstrated that single shot vaccinations against tetanus and diphtheria do not lead to long-lasting immunity against diphtheria in elderly persons despite administration at 5 year intervals. In the present study we have immunized a group of young adults against tetanus and diphtheria to compare the pre- and 28 days post-vaccination immune responses in the young group with results of the same vaccination performed in an elderly group of a previous study. We also studied protection in both groups 5 years after vaccination. We compared antibody titers at all three time points and also analyzed the T cell responses in both age groups 5 years after vaccination.Before vaccination 9 % of the elderly persons were not protected against tetanus, and 48 % did not have protection against diphtheria. In the young group all participants were protected against tetanus, but 52 % were also unprotected against diphtheria before vaccination. 28 days after vaccination 100 % of all participants had protective antibody concentrations against tetanus and only a small percentage in each age group (<10 %) was unprotected against diphtheria. 5 years later, 100 % of both cohorts were still protected against tetanus, but 24 % of the young and 54 % of the elderly group were unprotected against diphtheria. Antibody concentrations against diphtheria measured by ELISA correlated well with their neutralizing capacity. T cell responses to tetanus and diphtheria did not differ between young and old persons. We conclude that booster vaccinations against tetanus and diphtheria according to present recommendations provide long-lasting protection only against tetanus, but not against diphtheria, independently of age. In elderly persons, the level of protection is even lower, probably due to intrinsic age-related changes within the immune system and/or insufficient vaccination earlier in life.     

Diphtheria in the Maritime Territory

The results of the analysis of the present epidemiological situation in diphtheria in the Maritime Territory are presented. The data on absolute and intensive characteristics, death rate due to this infection, the vaccination status of diphtheria patients, as well as the results of the study of the level and intensity of antidiphtheria immunity in the healthy population of the territory. The study revealed that the defects of collective antidiphtheria immunity correlated with morbidity rate among adults and children. Adults aged 40-50 years and children aged 6-7 years were regarded as risk groups; among them the highest proportion of nonimmune persons and the highest diphtheria morbidity rate were registered. Stabilization achieved by the present moment was the result of the mass immunization of the adult population, ensuring the necessary coverage (92%) of vaccination in 1995.     

A comparative evaluation of the effectiveness of methods for serological sampling examinations]

Blood serum samples of 3,448 schoolchildren of grades 1-10 in 35 schools of Dushanbe were examined in the passive hemagglutination test in 1988 and 1989. The proportion of persons unprotected against diphtheria and tetanus was estimated by common methods in different kinds of selective serologic survey: mass screening (43.4-83.0%), testing in selected groups reduced 2, 3 and 5 times, cluster sampling. The reduction of the groups to be examined (from 3,033 to 250 persons) was not accompanied by essential changes (t < 2) in the characteristics of mass immunity against diphtheria and tetanus. The cluster method was shown to be highly reliable also in the study of population immunity.     

Humoral immunity to diphtheria and tetanus in pregnant women and newborn infants

Pregnant and parturient women have been examined in different regions of the USSR: Moscow, the Turkmen SSR, the Azerbaijan SSR and the Uzbek SSR. Altogether 720 placental sera and 522 funic sera have been checked for the presence of antibodies to diphtheria and tetanus toxoids in the passive hemagglutination test. Considerable groups of women with the insufficient level of immunity to diphtheria (40-66%) and tetanus (42.1-58.8%) have been revealed in different republics. Among women over 70 years the percentage of persons with the absence of antibodies or having low antibody titers has proved to be even higher. The comparative analysis of antibody titers has shown a correlation between antibody titers in mothers and newborn infants in 83.6% of cases for diphtheria toxoid and in 72.9% of cases for tetanus toxoid. These data show that among parturient women and newborn infants large groups remain unprotected against diphtheria and tetanus, which indicates the necessity of correcting the immune status of women of the productive age.     

Immune response in adult immunized with adsorbed DT-M anatoxin with reduced antigen content and Imovax-DT-adulte vaccine

The comparative study of immune response after immunization of adults with adsorbed DT toxoid with reduced antigen content and Imovax-DT-adulte vaccine, as well as the safety of these preparations, was made. The study revealed that immunization of adults with adsorbed DT toxoid having reduced antigen content, made in two injections, and the injection of Imovax-DT-dulte vaccine, as well as the successive injection of these preparations, produced the same the levels of antitetanus immunity. Antidiphtheria immunity, evaluated by the number of seroconverted to diphtheria persons following two injections immunization was similar for the two preparations, while the level of antidiphtheria antibodies was higher in persons immunized with adsorbed DT toxoid. The immune stratum index was rather high among persons aged 16-29 years. This age group exhibited the highest number of persons, seropositive to both diphtheria and tetanus. Both vaccine preparations, adsorbed DT toxoid with reduced antigen content and Imovax-DT-adulte vaccine, were found to be equally capable of inducing autoimmune reactions in the vaccinees, detected by laboratory methods.     

Epidemiological and immunological features of tetanus under conditions of long-term planned vaccine prophylaxis

The introduction of mass immunization against tetanus has resulted in the decrease of morbidity rate (5.2 times), the leveling of morbidity rate among the urban and rural population and among males and females, though no essential effect on the seasonal distribution of tetanus morbidity has been observed. Persons over 50 years of age (housewives and pensioners) have become the main groups of risk at the post-immunization period. Mass immunization against tetanus over a period of many years has ensured the existence of a sufficient immune stratum (89.9 +/- 3.0% to 100 +/- 3.0%) and a sufficient level of antitoxic immunity (means geom equal to 6.72-9.6 I.U./ml) among children. Among adults, the proportion of persons protected from tetanus decreases in older age groups from 82.1 +/- 1.3% in persons aged 31-40 years to 22.1 +/- 2.0% in persons over 60 years. The observed differences between the coverage of the population with immunization and the proportion of persons having protective titers of tetanus antibodies require constant control of the intensity of immunity and its correction with regard to its initial level, especially in persons of older age groups.     

Evaluation of the immunological effectiveness of the planned vaccinal prophylaxis of diphtheria and tetanus in Sverdlovsk and Sverdlovsk Province

The level and intensity of antitoxic immunity to diphtheria and tetanus in children and adolescents were determined. The presence of tetanus antitoxin in titers exceeding the protective level in 96.3-98.5% of the examined children and adolescents is indicative of a high actual coverage by immunization. Protective titers against diphtheria were lower. There was no essential difference in the levels of protection in children immunized according to the vaccination schedule and in those immunized with some deviations from this schedule. A considerable part of newborns and children aged 3 months had antibodies to diphtheria and tetanus antitoxins. After the third booster immunization changes in antidiphtheria immunity characteristics occurred only in 2.5% of the vaccines and no changes in antitetanus immunity characteristics were observed.     

Immunological structure of the population in a system of epidemiological surveillance of diphtheria

The characteristics of antitetanus and antidiphtheria immunity in children, adolescents and adults in Perm have been determined by means of the passive hemagglutination test, and the tendency towards the decrease of their immunity to diphtheria with the increase of their age has been established. The registered and actual coverage of children and adolescents by immunization is characterized on the basis of the presence of antibodies to the tetanus component of combined vaccines. A considerable proportion of persons at boarding schools and vocational technical schools has been found to be seronegative with respect to diphtheria. The seasonal dynamics of antitoxic immunity is presented.     

Dynamics of diphtheria morbidity and population immunity

Observations on the stratum immune to diphtheria among the population, carried out over a period of many years and involving more than 37,000 people, have shown its gradual decrease in all adult age groups. In recent years the number of adults susceptible to diphtheria exceeded the number of susceptible children by 10.6%, and in some age groups by 18.5-21.8%, which makes for the total increase of diphtheria morbidity in recent years owing to its rise among adults. Regular revaccination of the adult population against diphtheria, made simultaneously with that against tetanus, is recommended.     

Recall Responses to Tetanus and Diphtheria Vaccination Are Frequently Insufficient in Elderly Persons

Demographic changes and a more active life-style in older age have contributed to an increasing public awareness of the need for lifelong vaccination. Currently many older persons have been vaccinated against selected pathogens during childhood but lack regular booster immunizations. The impact of regular vaccinations when started late in life was analyzed in an open, explorative trial by evaluating the immune response against tetanus and diphtheria in healthy older individuals. 252 persons aged above 60 years received a booster vaccination against tetanus, diphtheria, pertussis and polio and a subcohort (n=87) was recruited to receive a second booster vaccination against tetanus, diphtheria and pertussis 5 years later. The percentage of unprotected individuals at the time of enrollment differed substantially for tetanus (12%) and diphtheria (65%). Despite protective antibody concentrations 4 weeks after the first vaccination in almost all vaccinees, antibodies had again dropped below protective levels in 10% (tetanus) and 45% (diphtheria) of the cohort after 5 years. Protection was restored in almost all vaccinees after the second vaccination. No correlation between tetanus- and diphtheria-specific responses was observed, and antibody concentrations were not associated with age-related changes in the T cell repertoire, inflammatory parameters, or CMV-seropositivity suggesting that there was no general biological “non-responder type.” Post-vaccination antibody concentrations depended on pre-existing plasma cells and B cell memory as indicated by a strong positive relationship between post-vaccination antibodies and pre-vaccination antibodies as well as antibody-secreting cells. In contrast, antigen-specific T cell responses were not or only weakly associated with antibody concentrations. In conclusion, our findings demonstrate that single shot vaccinations against tetanus and/or diphtheria do not lead to long-lasting immunity in many elderly persons despite administration at relatively short intervals. Sufficient antigen-specific B cell memory B generated by adequate priming and consecutive booster vaccinations and/or exposure is a prerequisite for long-term protection.

Trial Registration

EU Clinical Trials Register (EU-CTR); EudraCT number 2009-011742-26; www.clinicaltrialsregister.eu/ctr-search/trial/2009-011742-26/AT     

Diphtheria morbidity in Russia today

The data on diphtheria morbidity and the occurrence of carrier state for its causative agent at the period of 2001-2002 were analyzed. The rates of morbidity and detected carrier state for these years were 0.63-0.55 and 0.65-0.64 respectively. Nevertheless, in spite of the relatively low morbidity rates the presence of the toxic forms of diphtheria (400 patients for two years) and lethal cases (with lethality rate reaching 5.4%) indicated that the epidemic situation in diphtheria remained tense. The most unfavorable situation was observed in the North-Western and Central regions of Russia. In urban areas morbidity rates were still 2- to 3-fold higher in than in rural ones, but the latter showed a higher percentage of severe cases (46.6% in 2001 and 39.7% in 2002) and lethal outcomes (13.6% and 19.2%). The latter was indicative of drawbacks in the immunoprophylaxis, diagnostics and treatment of diphtheria in rural areas. In the total structure of diphtheria patients adults prevailed: 75%. The highest morbidity rates were registered among children aged 3-6 years, among adults in the age groups of 18-19 years and 50-59 years. The epidemic process developed mainly among the immunized population, which was indicated by a high proportion of vaccinated persons among those affected by this infection (62.8-66.6%) and a mild course of the disease in the majority of them. The present epidemiological situation in diphtheria was determined by patients not vaccinated against this infection. The proportion of severe cases among nonvaccinated children was 42.4-51.6% and lethal outcomes, 12.9-15.1%. Among nonimmunized adults these figures were equal to 43.1% and 9.3% respectively. The highest percentage of children, not vaccinated during the first years of their life, was registered among those in the asocial families, refugees and homeless persons. Among adults these were persons above 50 years old, as well as jobless persons of working age, pensioners and invalids, who had limited possibilities of undergoing vaccination due to their social position. It was these social and age groups that should be regarded as risk groups with respect to the severity of the course of diphtheria and lethality. To stabilize diphtheria morbidity, the full complex of prophylactic and antiepidemic measures, and primarily the immunization of the population, should be systematically carried out.     

The level of postvaccinal immunity to diphtheria, tetanus and poliomyelitis in relation to the number of inoculations]

The work was aimed at the comparative study of the intensity of immunity to diphtheria, tetanus and poliomyelitis, depending on the number of injections of adsorbed diphtheria-pertussis-tetanus (DPT) vaccine and poliomyelitis vaccine, for the purpose of finding out the possibility of reducing the antigenic load given to children without diminishing the intensity of immunity. To determine the level of immunity to diphtheria and tetanus, 1900 children under school age were serologically studied by the micromethod in the passive hemagglutination test. The intensity of immunity to poliomyelitis virus was studied in 333 children by means of the neutralization test. The immunogenic properties of the diphtheria component of adsorbed DPT vaccine were found to be less pronounced than those of the tetanus component of the vaccine, which made it impossible to reduce the antigenic load by decreasing the number of vaccinations against diphtheria. The results of the study of postvaccinal immunity to poliomyelitis suggest that during the first and second year of life the course of vaccination against poliomyelitis may be reduced to 3 injections.     

Antibody status to poliomyelitis,measles, rubella,diphtheria and tetanus,Ontario, 1969-70: deficiencies discovered and remedies required.

A serologic survey was made in 15 health unit areas, testing some 5000 individuals in the age groups 4 to 6, 11 to 13, 15 to 17 and 23 to 45 years. Two types of serious deficiency were found. Only 65% of children 4 to 6 years old had antibodies to all three types of poliovirus, the antibodies being due almost entirely to immunization with Salk vaccine. Even in children who had had six or more doses only 74% had antibodies to the three types. The high percentage of students 11 to 13 and 15 to 17 years old with poliovirus antibodies can be attributed largely to natural infection and to Sabin vaccine in the mass campaign of 1962, as well as to Salk vaccine. In children who had received Sabin vaccine as well as Salk vaccine a very high level of immunity was found. The immunity of the school-age population will decline to an insufficient level unless Sabin vaccine is used after immunization with Salk vaccine. Of children 4 to 6 years old 18% had no diphtheria antitoxin and 6% had no tetanus antitoxin. Even in those who had had six or more doses of the antigens 5% had no diphtheria antitoxin and 1 to 2% had no tetanus antitoxin. This apparently refractory state is probably due to the use of unadsorbed toxoids, and it is clear that adsorbed toxoids should be used. In the adults, diphtheria antitoxin was found in only 55% and tetanus antitoxin in only 38%.     

Improving tetanus prevention in the Krasnodar area taking the current epidemic situation into account]

An increase of percentage of elderly persons among those who fell ill with tetanus (70%) was noted against a sharp reduction of tetanus incidence under the effect of mass active immunization against this disease. A study of immunity in older and elderly individuals showed the percentage of immune persons among them to be rather low (48.8--55.6%). Due to difficulty of elderly individuals embracement by vaccination the authors suggest a single immunization scheme with a double toxoid dose (20 BU) followed by revaccination with 10 BU in one year. A total of 21 472 persons were placed under observation. The suggested immunization scheme was harmless, promoted stimulation of antitetanus immunity in persons vaccinated earlier; as to unvaccinated persons--it created a favourable immunological preparedness for revaccination, permitting to do without any antitetanus serum in case of trauma.     

Postvaccinal antidiphtheria and antitetanus immunity in patients with systemic connective tissue diseases

The retrospective evaluation of the intensity of postvaccinal immunity at different periods after the primary course of immunization against diphtheria and tetanus was made. In the sera taken from 130 children with systemic connective tissue diseases the content of antibodies to diphtheria and tetanus was determined. As revealed in this study, the protective levels of antibodies to diphtheria and tetanus toxoids were retained by both sick and healthy children for 5 years and longer. Significantly lower titers of antibodies to diphtheria and tetanus toxoids were registered in children undergoing therapy with glucocorticosteroids and cytostatics at the time of the study.     

Transplacental antibodies. Part II: Maternal antibodies against the toxins of C. diphtheriae and C. tetani

Examinations of 297 sera for diphtheria antitoxin and 160 sera for tetanus antitoxin were carried out in 1981. All sera were obtained from the cord blood of mothers between 15 and 34 years of age. The mothers were divided into four age groups each of which was further subdivided into the primipara and multipara subgroups. The aim was to assess the age-specific variations in response to active immunization against diphtheria and tetanus. The protective level of diphtheria antitoxin (at least 0.01 I.U./ml) was recorded in the serum of 96.3% of examinees and the rates of seropositivity were found to fall with increasing age. The protective level of tetanus antitoxin (at least 0.1 I.U./ml) was found in the serum of 95.2% of mothers. The serologic response encountered in groups of older mothers was a clear-cut demonstration that the country-wide mass immunization against tetanus carried out between 1974 and 1975 was highly effective and fully justified. The variations in the diphtheria and tetanus antitoxin levels found in the primipara and multipara subgroups were not statistically significant.     

Antitetanus and antidiphtheria immunity in newborns

The level of antitetanus and antidiphtheria immunity was evaluated in 280 pairs (mother-newborn) and in 56 pairs where mothers (aged 19-26 yrs.) were vaccinated in the 7th month of pregnancy with an adsorbed tetanus vaccine dose. The results revealed a high antitetanus immunity level both in mothers and newborns (93.57% and 92.85% respectively) and a low antidiphtheria protection level (79.64% and 77.14%). Immunization of pregnant women ensures a 100% passive protection of newborns against tetanus before administration of the first vaccine doses. The data obtained also proved that placental transfer of the specific circulating antibodies was high (98.58% and 95% for diphtheria). The high percentage of newborns susceptible to diphtheria toxinfection points to the need to immunize mothers-to-be with low combined diphthero-tetanus (d-T) vaccine doses and to closely observe vaccination programme (Ministry of Health) of children with combined diphthero-tetanus-pertussis vaccine (CDTPV) at an early age (two months).     

The immunization of children with combined diphtheria and tetanus vaccine in Sweden

Two groups derived from 97 children three-four months of age were vaccinated with diphtheria and tetanus vaccines containing either a routinely prepared diphtheria toxoid or a more purified preparation. Two injections were given with an interval of one month and a third injection was given one year after the first. Prior to the third injection no child was without protection against diphtheria, i.e. had an antitoxin titre less than 0.01 IU ml-1. After the third injection 95 and 94% of the children vaccinated with the routinely and more purified diphtheria toxoids, respectively, had diphtheria antitoxin titres greater than 1 IU ml-1 (estimated to provide protection for at least ten years). Systemic reactions such as fever and malaise occurred in five children. Local reactions greater than 10 cm were observed in three children and reactions greater than 5 but less than or equal to 10 cm were seen in 14% of the children. The routinely prepared combined diphtheria and tetanus vaccine, DT, produced very good immunity against diphtheria with moderate side effects. The use of a more purified diphtheria toxoid in the combined vaccine produced the same immunity and side effects.     

Duration of immunity in children who received a primary complex of inoculations with ADT-M anatoxin and an assessment of postponed secondary revaccination against diphtheria and tetanus (the results of an epidemiologic trial)

The prolonged observations of the immunological effectiveness of adsorbed diphtheria-tetanus toxoid with reduced antigen content in children who had received the primary course of immunization with this preparation showed that the preparation induced the development of prolonged and intensive immunity to both infections. In 2-3 years after the first booster immunization the protective level of diphtheria antitoxin was registered in 89.9% and that of tetanus antitoxin, in 99% of children. 6 years later the level of immunity remained practically unchanged: the titers of diphtheria antitoxin above the protection level were determined in 92% and those of tetanus antitoxin, in 97% of children. These data made it possible to increase intervals between booster immunizations to 6-7 years in children of this category. The results of the epidemiological trial made to find out the possibility of a change in the timing of the second booster immunization confirmed the expediency of postponing booster immunization from 6 and 11 years to 9 and 16 years of age.