Immunity to diphtheria and tetanus in some of the administrative territories of the RSFSR

The article deals with the state of immunity to diphtheria and tetanus among the adult population in some administrative regions of the RSFSR. Of the children and adults covered by the survey, 91.3-96.7% were found to have protective antibody titers against diphtheria and 98.7-100%, against tetanus. An essential drop in the level of immunity to diphtheria in persons over 18 years of age was revealed: 71.7% of them were nonimmune, which correlated with the high morbidity rate among these persons. At the same time the percentage of adults nonimmune to tetanus was considerably lower than that of adults nonimmune to diphtheria, reaching only 27.1%. The state of immunity to tetanus in adults was found to depend on the seasons.     

Diphtheria-neutralizing antibody levels in healthy adults from Rio de Janeiro, Brazil

In Brazil, until 2004, the immunization policy against diphtheria involved childhood vaccination with no official routine booster dose administered after 15 years of age. This study assessed functional antibody levels against diphtheria among blood donors. A total of 140 blood samples were collected, and diphtheria antitoxin levels were evaluated by Vero cell neutralization test. The mean age of the population was 34 years old (range: 18-61 years); 37.8% females and 62.2% males. Overall, 30.7% (95%, CI: 23.4-38.7) individuals presented neutralizing antitoxin antibody titers < 0.01 IU/ml; 42.1% (95%, CI: 34.1-50.4) showed values between 0.01-0.09 IU/ml and, 27.1% (95%, CI: 20.2-34.9) had (3) 0.1 IU/ml. In the subgroup of individuals with history of diphtheria immunization during childhood (85%), a number of 28.5% showed unprotective levels of circulating neutralizing antibody (< 0.01 IU/ml). Despite the continuous progress of immunization programs directed to Brazilian population, currently healthy adults remain susceptible to diphtheria.     

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.     

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.     

A large-scale epidemic of diphtheria in Moscow in recent years: patterns of development

Data on the dynamics of diphtheria morbidity in Moscow in 1958-1999 are presented. The last epidemic which started at the end of the 1980s and reached its peak in 1994, giving a 59-fold rise in morbidity in comparison with the pre-epidemic period, is characterized in detail. During the epidemic 12,267 persons fell ill, 454 of them died (mortality rate was 4%). Having started in Moscow, the epidemic gradually spread not only over the territory of Russia, but also over some other republics of the former Soviet Union (Ukraine, Belarus, etc.). Possible causes of this epidemic emergency are considered. The ever increasing share of adult population among persons affected by the epidemic (75%) is noted. The infection adults is characterized by severity of clinical manifestations and increased morbidity among adults, is shown. Under complicated social and economic conditions (crisis situation) the increase of groups of high risk which included unemployed adults of working age, retirees as well as socially non-adapted persons, was registered. Mainly these groups determined tense epidemiological situation in diphtheria in Moscow.     

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.     

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.     

The epidemic process of diphtheria infection in the RSFSR during the introduction of epidemiological surveillance

In this work the characterization of the epidemic process of diphtheria infection on the territory of the RSFSR under the conditions of epidemiological surveillance (1983-1986) is presented. In comparison with the period of 1979-1982, an increase in morbidity rate occurred, which accounts for more complete detection of patients with mild forms of diphtheria, including persons found to be carriers of toxigenic Corynebacterium diphtheriae. Beginning from 1983, the leveling out of seasonal morbidity rises is observed. In the total number of persons affected by this infection the prevalence of adults is noted. Among them, a decrease in the morbidity rate was registered in 1986 (the maximum decrease was observed in age and professional groups of risk), which confirms the effectiveness of measures carried out for the protection of the adult population from diphtheria. Among children, a tendency towards a decrease in morbidity rate was noted in all age groups. The existing system of epidemiological surveillance on the territory of the RSFSR is capable of stabilizing diphtheria morbidity on a sporadic level and minimizing the number of fatal outcomes. The intensification of the epidemic process in some areas of the RSFSR is due to shortcomings in the realization of different measures of epidemiological surveillance.     

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.     

Epidemiological surveillance of diphtheria infection in the territory of the Azerbaijan SSR

A complex of measures carried out with a view of effecting the epidemiological surveillance of diphtheria infection has made it possible to study the level and intensity of immunity to diphtheria and tetanus, determined in the passive hemagglutination test, in the child and adult population and to reveal groups, least protected against diphtheria infection. Bacteriological studies on the biological properties of Corynebacterium diphtheriae have revealed the contamination of various groups of children with this infective agents and permitted its complete characterization with the determination of its sero-, phago- and corycinovariants.     

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.     

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.     

Specific antibodies and their role in the formation of antidiphtheria immunity

In human sera, studied with the use of the enzyme immunoassay, antidiphtheria postvaccinal antitoxic IgG and naturally acquired antibacterial IgG, IgM and IgA were detected. In the blood of children and adults aged up to 50 years antitoxic IgG were present at normal and high concentrations. In 50% of children antibacterial IgA were absent, while specific antibacterial IgM could be found at high concentrations. Changes in the content of antibacterial antibodies of different classes in sera were observed with age. More than 90% of adults had antibacterial IgA and IgG at normal and hig concentrations, while the level of IgM decreased. Under the influence of ecological, social, anthropogenic and other environmental factors the optimum levels of specific antibodies were replaced by anomalous ones, which led to an increased number of persons susceptible to diphtheria infection and in the intensity of the circulation of the infective agent. The deficiency of antidiphtheria antibacterial antibodies in the blood determined the necessity of correcting immunity by means of not only toxoid, but also bacterial antigens.     

Diphtheria and tetanus immunity among blood donors in Toronto

OBJECTIVE: To determine the diphtheria and tetanus antitoxin levels among blood donors in Toronto. DESIGN: Cross-sectional seroprevalence study. SETTING: Two fixed-site blood-donation clinics in Toronto from September to November 1994. PARTICIPANTS: Blood donors 20 years of age or older were eligible to participate; of the 781 eligible donors, 710 (90.9%) participated in the study. MAIN OUTCOME MEASURES: Diphtheria and tetanus antitoxin levels and factors associated with disease susceptibility, such as vaccination history, country of birth, age and sex. A diphtheria antitoxin level lower than 0.01 lU/mL and a tetanus antitoxin level lower than 0.15 lU/mL were considered nonprotective. RESULTS: Among the participants, 147 (20.7%) had a diphtheria antitoxin level in the nonprotective range, and 124 (17.5%) had a tetanus antitoxin level that was nonprotective. Increasing age and lack of written vaccination records were associated with susceptibility to the 2 diseases. Birth outside Canada was significantly related to tetanus susceptibility. CONCLUSION: Adults over 50 years of age who did not know their vaccination history were the least likely to be protected against diphtheria and tetanus. The greatest benefit of any immunization strategy would be gained by targeting this group.     

Diphtheria remains a threat to health in the developing world--an overview

Changes in the epidemiology of diphtheria are occurring worldwide. A large proportion of adults in many industrialized and developing countries are now susceptible to diphtheria. Vaccine-induced immunity wanes over time unless periodic booster is given or exposure to toxigenic Corynebacterium diphtheriae occurs. Immunity gap in adults coupled with large numbers of susceptible children creates the potential for new extensive epidemics. Epidemic emergencies may not be long in coming in countries experiencing rapid industrialization or undergoing sociopolitical instability where many of the factors thought to be important in producing epidemic such as mass population movements and difficult hygienic and economic conditions are present. The continuous circulation of toxigenic C. diphtheriae emphasizes the need to be aware of epidemiological features, clinical signs, and symptoms of diphtheria in vaccine era so that cases can be promptly diagnosed and treated, and further public health measures can be taken to contain this serious disease. This overview focused on worldwide data obtained from diphtheria with particular emphasis to main factors leading to recent epidemics, new clinical forms of C. diphtheriae infections, expression of virulence factors, other than toxin production, control strategies, and laboratory diagnosis procedures.     

Antidiphtheria immunity in adult population of the Orenburg region

The analysis of the level of antidiphtheria immunity in different age group of the adult population has shown that postvaccinal immunity resulting from immunization with adsorbed DT toxoid with reduced antigen content gradually decreases after the period of two years. The immune stratum remains sufficiently numerous only among persons aged 18-27 years (93.3%), persons over 38 years constitute a high risk group with respect to the possibility of diphtheria infection: the proportion of persons protected against this infection amounts to 71.3% in the age group of 38-47 years and 54.9% in the age group over 48 years, that is not sufficient.     

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.     

The prevalence of helicobacteriosis in regions of Siberia based on serological study data

687 adults in 5 regions of Siberia and 79 children and young persons in Novosibirsk were examined. IgG antibodies to H. pylori in their blood sera were determined with the use the enzyme immunoassay. The detection rate of antibodies among the adult population varied within 70-87%, depending on the region, being somewhat lower among the population north of latitude 60 degrees (75%) in comparison with the population residing south of this latitude (86%, p < 0.001). In Novosibirsk the number of seropositive persons was found to be unrelated to sex, age and clinical manifestations of digestive tract diseases. A high detection rate of antibodies to H. pylori was registered in persons aged 25-34 years with a minor increase in older age groups. In children the detection rate increased with age: 29% in children of 5-10 years old and 56% in children 11-14 years old. By the age of 15 more than a half of the children had antibodies.     

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.     

From re-emergence to hyperendemicity: the natural history of the dengue epidemic in Brazil

Background

Dengue virus (DENV) was reintroduced into Brazil in 1986 and by 1995 it had spread throughout the country. In 2007 the number of dengue hemorrhagic fever (DHF) cases more than doubled and a shift in the age distribution was reported. While previously the majority of DHF cases occurred among adults, in 2007 53% of cases occurred in children under 15 years old. The reasons for this shift have not been determined.

Methods and Findings

Age stratified cross-sectional seroepidemiologic survey conducted in Recife, Brazil in 2006. Serostatus was determined by ELISA based detection of Dengue IgG. We estimated time-constant and time-varying forces of infection of DENV between 1986 and 2006. We used discrete-time simulation to estimate the accumulation of monotypic and multitypic immunity over time in a population previously completely susceptible to DENV. We projected the age distribution of population immunity to dengue assuming similar hazards of infection in future years. The overall prevalence of DENV IgG was 0.80 (n = 1427). The time-constant force of infection for the period was estimated to be 0.052 (95% CI 0.041, 0.063), corresponding to 5.2% of susceptible individuals becoming infected each year by each serotype. Simulations show that as time since re-emergence of dengue goes by, multitypic immunity accumulates in adults while an increasing proportion of susceptible individuals and those with monotypic immunity are among young age groups. The median age of those monotypically immune can be expected to shift from 24 years, 10 years after introduction, to 13 years, 50 years after introduction. Of those monotypically immune, the proportion under 15 years old shifts from 27% to 58%. These results are consistent with the dengue notification records from the same region since 1995.

Interpretation

Assuming that persons who have been monotypically exposed are at highest risk for severe dengue, the shift towards younger patient ages observed in Brazil can be partially explained by the accumulation of multitypic immunity against DENV-1, 2, and 3 in older age groups, 22 years after the re-introduction of these viruses. Serotype specific seroepidemiologic studies are necessary to accurately estimate the serotype specific forces of infection.