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PubMed1985

Diphtheria in the United States, 1971-81.

After a decade-long resurgence, including a large cutaneous diphtheria outbreak in Washington State, the diphtheria incidence rate in the United States reached its lowest recorded level ever in 1980--two patients (0.01 case per million). Mortality paralleled the decline in incidence rate. Only 143 of the 3,141 US counties reported noncutaneous diphtheria patients during 1971-81; most were located in the West. The highest attack rates were experienced by children less than 15 years old (0.8 case per million) and by American Indians (22.6 cases per million). Persons immunized with three or more doses of diphtheria toxoid had a lower death-to-case ratio (1.3 per cent) than totally unimmunized persons (13.4 per cent). The reasons for the dramatic decline in diphtheria incidence rates are unclear, although it has been postulated that the gene for producing diphtheria toxin may be lost from organisms in highly immunized populations. Significant proportions of the adult and elderly populations are susceptible to diphtheria. Continuation of primary immunization with increased emphasis on the routine use of tetanus and diphtheria toxoids (Td) boosters in adults should ensure that diphtheria will remain largely a scourge of the past.

Adolescent↗
PubMed2002

Serologic immunity to diphtheria and tetanus in the United States.

BACKGROUND: Serologic data on diseases that are preventable by vaccine are useful to evaluate the success of immunization programs and to identify susceptible subgroups. OBJECTIVE: To provide national estimates of immunity to diphtheria and tetanus by measurement of serum antibody levels. DESIGN: Examination of data from the Third National Health and Nutrition Examination Survey, a representative cross-sectional sample of the U.S. population. SETTING: 89 randomly selected locations throughout the United States. PARTICIPANTS: 18 045 persons 6 years of age or older who were examined from 1988 to 1994. MEASUREMENTS: Serum samples obtained at a single time point were tested for diphtheria and tetanus antitoxin. RESULTS: Overall, 60.5% of Americans 6 years of age or older had fully protective levels of diphtheria antibody (> or =0.10 IU/mL) and 72.3% had protective levels of tetanus antibody (> 0.15 IU/mL). Ninety-one percent of Americans 6 to 11 years of age had protective levels of both diphtheria and tetanus antibody; this proportion decreased to approximately 30% among persons 70 years of age (29.5% for diphtheria and 31.0% for tetanus). Adult Mexican-Americans were slightly less likely to have protective levels of antibody to both toxins. Only 47% of persons 20 years of age or older had levels that were protective against both diseases, and only 63% of adults who were protected against tetanus were also protected against diphtheria. CONCLUSIONS: A substantial proportion of adults in the United States do not have antibody levels that are protective against diphtheria and tetanus. In addition, although the recommended vaccine is a combination of tetanus and diphtheria, only 63% of adults with protective antibody to tetanus also had protective antibody to diphtheria.

Adolescent↗
PubMed2000

Immunity to diphtheria and tetanus in England and Wales.

The immunity profile of the English and Welsh population to diphtheria and tetanus has been determined by measuring diphtheria and tetanus antitoxin levels for 3088 and 3142 sera, respectively. Time-resolved fluorimetric immunoassay - DELFIA was used to measure diphtheria antitoxin levels and an in-house, indirect ELISA to measure tetanus antitoxin levels. More than 80% of those aged between 2 and 20-24 years had protective diphtheria antitoxin levels of 0.01 IU/ml, or greater, and more than 80% of those aged between 4 and 35-39 years had protective tetanus antitoxin levels of 0.1 IU/ml, or greater. Only 29% and 53% of those aged 60 and over were protected against diphtheria and tetanus. Two increases of diphtheria antitoxin levels greater than 0.1 IU/ml and tetanus antitoxin levels greater than 1.0 IU/ml were apparent, starting at 4 and 14 years of age, which correspond with the policy of giving a diphtheria and tetanus toxoid booster on school entry and a tetanus plus low-dose diphtheria toxoid (recently introduced) booster to school leavers. This is the first comprehensive study of diphtheria and tetanus immunity in the English and Welsh population and shows that the accelerated schedule of immunisation, introduced in 1990, has effectively primed immunological memory against both these antigens and that boosting at school entry and at school leaving is effective in increasing levels of immunity.

Adolescent↗
PubMed1999

Duration of immunity to diphtheria and tetanus in young kidney transplant patients.

A considerable proportion of patients with renal transplant, evaluated many years after transplant, lack protective diphtheria antibody levels, despite primary immunization, but maintain immunity to tetanus. These patients respond to a diphtheria and tetanus booster but the duration of the response is uncertain. This study was undertaken to assess if protective antibodies evoked by primary immunization are lost quickly after transplantation, and whether the extent of the immune response to a booster influences the persistence of protective antibodies. We studied 15 patients (group 1) immediately after renal transplant and 35 patients with renal transplant for 6 +/- 4 yr who received a diphtheria and tetanus booster (group 2). Six patients (40%) of group 1 lost protective diphtheria antibodies a median time of 6.5 months after transplant. Thirty-three patients of group 2 responded to the booster with normal diphtheria antibody titers (> 1 IU/mL) in 22 cases and with low titers in 11. Four of the latter lacked immunity to diphtheria at 12 months follow-up. All patients with normal immunity maintained protective levels of diphtheria antibodies. The low responders had a creatinine clearance of 50 +/- 20 mL/min/1.73 m2. Tetanus immunity was maintained in almost all patients of both groups. In conclusion, renal transplant patients had an accelerated loss of diphtheria antibodies in the early post-transplant period. Response to a diphtheria booster identified a group at particular risk, namely the low responders, who may require frequent booster doses. This group had significantly poorer renal function than the normal responders.

Adolescent↗
PubMed1971

Simultaneous immunization with B.C.G., diphtheria-tetanus, and oral poliomyelitis vaccines in children aged 13-14.

The simultaneous administration of B.C.G. vaccine, diphtheria-tetanus toxoid aluminium hydroxide adsorbed vaccine, and oral poliovaccine was studied in 628 children aged 13-14 years between 1966 and 1969 in Newham, London. The efficacy of these vaccines was unaffected by administering them at the same time; routine simultaneous administration is considered justified when organizational difficulties prevent the attainment of high immunization rates with the vaccines given separately. No adverse reactions to B.C.G. or oral poliomyelitis vaccines took place, but 8% of children had moderately severe local reactions after diphtheria-tetanus aluminium hydroxide adsorbed vaccine, which were attributed to diphtheria toxoid.Serological studies showed the need for immunization against diphtheria, tetanus, and poliomyelitis at 13-14 years of age. Because of the adverse reactions to diphtheria toxoid, however, simultaneous administration of tetanus toxoid aluminium hydroxide adsorbed, oral poliomyelitis, and B.C.G. vaccines only is recommended at present.An "adult type" diphtheria-tetanus toxoid might overcome the problem of reactions, though in two to three years' time most children aged 13-14 years will have received diphtheria-tetanus-pertussis vaccine in infancy and reinforcement might then be accomplished by a small intradermal dose of the currently available fluid diphtheria-tetanus vaccine.Continued serological studies of diphtheria and tetanus antitoxins and polio antibody are necessary to determine the future need for reinforcement of immunity; such studies should become an essential part of the surveillance of the community immunization programme.

Adolescent↗
PubMed1987

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.

Diphtheria Antitoxin↗
PubMed2005

Respiratory diphtheria among highly vaccinated military trainees in Latvia: improved protection from DT compared with Td booster vaccination.

An outbreak of respiratory diphtheria occurred among highly-vaccinated trainees at a Latvian military academy in August-September 2000. We reviewed immunization, clinical and laboratory records and administered a questionnaire to obtain data on exposure factors. Among 207 trainees, 45 (22%) diphtheria cases and 79 (38%) carriers of toxigenic Corynebacterium diphtheriae were identified. All patients survived; 1 had severe myocarditis. Sharing cups was a risk factor for infection. Over 85% of trainees had received > or =5 doses of diphtheria toxoid. Neither infection nor disease was associated with the number of doses or interval since last dose. However, the risk of disease was lower and diphtheria antitoxin levels were higher among trainees who received their last booster dose with higher-antigen diphtheria toxoid (DT) instead of lower-antigen Td. Outbreaks of mild diphtheria can occur among highly-vaccinated persons living in crowded conditions with intense exposure; high-antigen diphtheria booster-vaccination might provide better protection under these conditions.

Adolescent↗
PubMed2000

Clinical characteristics and management of 676 hospitalized diphtheria cases, Kyrgyz Republic, 1995.

The Kyrgyz Republic experienced a widespread resurgence of diphtheria during 1994-1998. To describe the clinical characteristics and management of diphtheria patients hospitalized in 1995, a retrospective chart review was conducted. Physician-diagnosed cases of diphtheria were classified according to the system recommended by the World Health Organization and UNICEF. Among 676 patients hospitalized with respiratory diphtheria, 163 (24%) were carriers, 186 (28%) had tonsillar forms, 78 (12%) had combined types or delayed diagnosis, and 201 (30%) had severe forms of diphtheria. The highest age-specific incidence rates occurred among persons 15-34 years old, and 70% of cases were among those >/=15 years of age. Myocarditis occurred among 151 patients (22%), and 19 patients died (case fatality ratio: 3%). Diphtheria antitoxin was administered to 507 patients (75%), and all patients received antibiotics (penicillin or erythromycin). Respiratory diphtheria remains a potentially fatal disease, commonly presenting with a typical membranous pharyngitis. Early diagnosis and treatment of cases with diphtheria antitoxin and antibiotics are the cornerstones of effective treatment.

Adolescent↗
PubMed2001

Diphtheria in Thailand in the 1990s.

Diphtheria remains endemic in developing countries, but there are limited published data on the subject. Thailand's diphtheria surveillance data are relatively complete and may give a fuller picture of the situation in similar countries. After routine immunization began in 1977, the incidence of reported diphtheria decreased by >98% to <0.1 case per 100,000 persons annually in the 1990s. Despite infant immunization coverage of >90%, diphtheria cases were reported throughout the 1990s, primarily among children <15 years old. Outbreaks were linked to both persistent endemic circulation and to importation of toxigenic Corynebacterium diphtheriae; suboptimal immunization coverage in minority and disadvantaged groups contributed. A serologic survey found 25% of adults 20-39 years old and 14% of adolescents 10-19 years old lacked immunity to diphtheria; these data indicate an accumulation of susceptible adolescents and adults. Diphtheria remains a threat in Thailand; improvements in diphtheria control will depend on improving childhood immunization coverage in Thailand and the surrounding region.

Adolescent↗
PubMed2007

Determination of low tetanus or diphtheria antitoxin titers in sera by a toxin neutralization assay and a modified toxin-binding inhibition test.

A method for the screening of tetanus and diphtheria antibodies in serum using anatoxin (inactivated toxin) instead of toxin was developed as an alternative to the in vivo toxin neutralization assay based on the toxin-binding inhibition test (TOBI test). In this study, the serum titers (values between 1.0 and 19.5 IU) measured by a modified TOBI test (Modi-TOBI test) and toxin neutralization assays were correlated (P < 0.0001). Titers of tetanus or diphtheria antibodies were evaluated in serum samples from guinea pigs immunized with tetanus toxoid, diphtheria-tetanus or triple vaccine. For the Modi-TOBI test, after blocking the microtiter plates, standard tetanus or diphtheria antitoxin and different concentrations of guinea pig sera were incubated with the respective anatoxin. Twelve hours later, these samples were transferred to a plate previously coated with tetanus or diphtheria antitoxin to bind the remaining anatoxin. The anatoxin was then detected using a peroxidase-labeled tetanus or diphtheria antitoxin. Serum titers were calculated using a linear regression plot of the results for the corresponding standard antitoxin. For the toxin neutralization assay, L+/10/50 doses of either toxin combined with different concentrations of serum samples were inoculated into mice for anti-tetanus detection, or in guinea pigs for anti-diphtheria detection. Both assays were suitable for determining wide ranges of antitoxin levels. The linear regression plots showed high correlation coefficients for tetanus (r(2) = 0.95, P < 0.0001) and for diphtheria (r(2) = 0.93, P < 0.0001) between the in vitro and the in vivo assays. The standardized method is appropriate for evaluating titers of neutralizing antibodies, thus permitting the in vitro control of serum antitoxin levels.

Animals↗
PubMed1983

Incidence of cutaneous diphtheria in Bangladesh.

Corynebacterium diphtheriae (C. diphtheriae) was isolated from 23 (7%) skin ulcers out of 327 cases studied. Eight (33%) of the 23 positive cases belonged to the age group of 6 to 10 years. Of the 19 strains of C. diphtheriae typed, 18 (95%) were gravis and of which 14 (77%) were toxigenic. More than 90% of the C. diphtheriae positive ulcer cases had serum anti-toxin level at or above the protective level as against 49% of control. No diphtheria bacilli were isolated from throat of any of the skin positive cases. All the ulcers from which C. diphtheriae were isolated also harboured other definite wound pathogens. It is believed that the presence of toxigenic C. diphtheriae in skin wound might play an important role in the spread of faucial diphtheriae. It is evident from serum anti-toxin level that infected persons develop natural immunity.

Adolescent↗
PubMed1998

Quantitation of tetanus and diphtheria antitoxins in mouse sera by indirect haemagglutination.

Serum samples obtained from 75 groups of mice immunized with various doses of adsorbed tetanus vaccine, adsorbed diphtheria-tetanus vaccine and adsorbed diphtheria-tetanus-pertussis vaccine were titrated for tetanus antitoxin content by an in-vitro indirect haemagglutination (IHA) and by toxin neutralization test (TN) in mice. From these serum samples of 49 groups of mice which were immunized with combined vaccine containing diphtheria toxoid were titrated for their diphtheria antitoxin content by IHA and by i.d. toxin neutralization test (TN) in guinea pigs. Good correlations were found between the estimates obtained by in-vitro IHA and in vivo TN tests in both tetanus and diphtheria antitoxin titrations. The minimum level of tetanus or diphtheria antitoxin detectable by IHA was 0.00039 IU/ml. It is concluded that IHA is a simple, sensitive and reproducible alternative test which can replace the animal TN tests for the estimation of tetanus and diphtheria antitoxins and could reliably be used in the potency assay of tetanus and diphtheria toxoids of combined vaccines based on antibody induction in mice.

Animals↗
PubMed2000

Diphtheria epidemic in the Republic of Uzbekistan, 1993-1996.

The Republic of Uzbekistan, like the other Newly Independent States in the 1990s, experienced epidemic diphtheria during the 1990s. The outbreak in Uzbekistan began in 1993 in southern regions that bordered areas of Tajikistan that were experiencing a very intense diphtheria epidemic. However, the Uzbek epidemic rapidly spread and threatened to involve the entire country. From 1993-1996, 1169 cases of diphtheria were reported, compared with 58 in 1990-1992. Unvaccinated or only partially vaccinated cases were more likely to have clinically severe forms of diphtheria than those who were fully vaccinated. Strong epidemiologic links with the Tajik diphtheria epidemic and the predominance of mitis biotype strains of Corynebacterium diphtheriae in Uzbekistan make it likely that the Uzbek outbreak arose independently of the predominantly biotype gravis epidemic that began in Russia. The epidemic appeared to be due to low population immunity and the large-scale reintroduction of toxigenic strains of C. diphtheriae. Several mass vaccination campaigns and general enhancement of routine immunization procedures led to control of the epidemic in 1996.

Adolescent↗
PubMed2006

An adolescent-adult formulation tetanus and diptheria toxoids adsorbed combined with acellular pertussis vaccine has comparable immunogenicity but less reactogenicity in children 4-6 years of age than a pediatric formulation acellular pertussis vaccine and diphtheria and tetanus toxoids adsorbed combined with inactivated poliomyelitis vaccine.

In Canada, the fifth dose of the routine childhood immunization schedule against diphtheria, tetanus, pertussis and polio is given at 4-6 years of age. Up to 30% of children may have significant local reactions (redness, swelling) and this may be related to pertussis and diphtheria antigen content. We sought to determine if a combination product with lower content of pertussis and diphtheria toxoids (dTap) would result in fewer local reactions and not have inferior immunogenicity to a combination vaccine with higher pertussis and diphtheria content (diphtheria-tetanus-acellular pertussis-inactivated polio virus, DTaP-IPV). Healthy children aged 4-6 years with complete primary immunization series and a fourth dose of diphtheria and tetanus toxoids component pertussis inactivated polio and Haemophilus influenzae type B conjugate vaccine were randomized to one dose of dTap, followed in 4-6 weeks by one dose of IPV or control DTaP-IPV. Immediate reactions within 30 min, solicited injection site and systemic reactions within 14 days, and unsolicited adverse events (AE) within 6 weeks post-vaccination were monitored. Serum was collected prior to immunization, and 4-6 weeks after vaccine for diphtheria, tetanus and pertussis antibodies (Ab). Sample size was designed to detect > or =10% difference in injection site erythema, pain or swelling between groups 593 children at eight Canadian sites completed the study; no participant withdrew because of an AE. All safety endpoints on days 0-14 were less frequent in children randomized to the dTap than DTaP-IPV group: erythema (34.6% versus 51.7%), swelling (24.2% versus 33.8%) and pain (39.6% versus 67.2%). Fever was also less common (8.72% versus 16.9%). All children in both study groups had seroprotective Ab levels to diphtheria and tetanus at 4-6 weeks (> or =0.10 IU/mL). The majority of children in each vaccine arm had a four-fold increase in pertussis antibodies. Fever and injection site reactions are less common in 4-6 year-old-children who receive a dTap vaccine compared to DTaP-IPV, without inferior immunogenicity.

Child↗
PubMed1989

Immune status and booster effects of low doses of diphtheria toxoid in Swedish medical personnel.

During a diphtheria outbreak among Swedish alcoholics in 1984-1985, only 60% of 328 medical staff at risk for exposure had diphtheria antitoxin titers greater than or equal to 0.01 IU/ml, which is usually considered to give relative protection. 21% had levels between 0.01-0.09 IU/ml and the remaining 39% had titers greater than or equal to 0.1 IU/ml. Booster doses of 0.5 Lf-12.5 Lf of diphtheria toxoid were given to 450 vaccinees. Of 72 individuals with low pre-immunization titers, who were immunized with less than or equal to 2.5 Lf diphtheria toxoid, 40% failed to reach greater than or equal to 0.1 IU/ml when analyzed 4 weeks after vaccination. Local tenderness and swelling greater than 5 cm at the site of injection or general discomfort was found in 11% of those immunized with low dose diphtheria toxoid (less than or equal to 2.5 Lf). When the dose 0.5 Lf of diphtheria toxoid was combined with tetanus toxoid (3.75 Lf) the frequency of adverse reactions increased to 34% (p less than 0.001). The study shows that vaccination status in medical personnel must also be continuously examined in countries where diphtheria is rare and that low booster doses of diphtheria toxoid may not achieve an adequate immune response.

Adolescent↗
PubMed2002

[Diphtheria--results of an immunologic survey].

The objective of the immunological survey (IS) was in addition to assessment of the overall immunity of the Slovak population against diphtheria to test the effectiveness of vaccination and suitability of the used vaccination pattern and to assess the persistence of antibodies against diphtheria in more advanced age, and possibly the need of revaccination. The sera were tested by means of the neutralization test on cell cultures. The level of diphtheria antitoxin was assessed quantitatively. In the reaction standards were used--diphtheria toxin 79/1 1000 Lf, produced in the National Institute of Public Health and the Environment Bilthoven, Netherlands and the diphtheria antitoxin Diphtheria antitoxin equine British Standard 66/153, obtained from WHO International Laboratory for Biological Standards, Great Britain. The overall immunity assessed on a nationwide scale in Slovakia was adequate (88.2%). In the child population the level of antibodies correlated well with the administration of individual vaccinations against diphtheria. In 6- to 10-year old children the serum positivity was as high as 100%, in older children it did not drop below 95%. A more marked decline of serum positivity was found in the population above 40 years. The highest proportion of sensitive subjects was in the group of 50-59-year-old ones (45.2%). The antidiphtheritic immunity of the population under 50 years is very good. Inadequate immunity of adults above 50 years revealed the need of administering a booster dose against diphtheria which will have a positive impact on the antibody level of this age group of the population.

Adolescent↗
PubMed1989

Diphtheria-tetanus overimmunization in children with no records: can it be prevented?

A pilot study was undertaken to assess the validity of two new tests for predicting the immune response of Toronto schoolchildren with no acceptable evidence of prior administration of diphtheria or tetanus toxoid to a routine booster injection of diphtheria and tetanus (DT) toxoid. The tests, an inexpensive enzyme-linked immunosorbent assay (ELISA) fingerprick test for tetanus antibodies and a modification of the Schick skin test for susceptibility to diphtheria, were administered before the booster injection. One week later the ELISA test was repeated and the result of the modified Schick test read. On both occasions a diphtheria microneutralization assay was done for "gold standard" evidence of prior exposure to diphtheria toxoid or toxin. The results were used to determine the sensitivity and specificity of a single prebooster tetanus ELISA test or a modified Schick test for predicting which children with no records could be safely protected with only one DT booster dose instead of the primary series of three or four doses usually given to such children. Only 6 of the 34 subjects (18%) were totally without prior exposure to tetanus toxoid. Two of the six (6% of 33 subjects) appeared to mount a primary immune response to diphtheria toxoid as well. An initial ELISA titre of 0.01 IU/ml or lower correctly identified all six children needing a full series of tetanus toxoid (sensitivity for a primary immune response 100%) and falsely identified only 3 of 28 immune children as needing the series (specificity for immunity 89.3%). The modified Schick test appeared to have even greater accuracy for identifying children needing a full series of diphtheria toxoid. However, its use, entailing the costs of an extra nurse visit, would have prevented only seven more children from receiving an unnecessary full series of diphtheria toxoid than use of the baseline tetanus ELISA test alone.

Adolescent↗
PubMed1988

[Indices of diphtheria (antitoxic) immunity in the dynamics of the disease and its treatment in adults].

A total of 1,034 serum samples from 618 persons, including patients with different forms of diphtheria, carriers of the toxigenic forms of Corynebacterium diphtheriae, and angina patients, were studied. Analysis of the incidence of antibodies to C. diphtheriae toxin and their titers revealed that in more than half of all diphtheria patients no antibodies to C. diphtheriae toxin were detected upon admission to hospital. At the same time in 26% of the patients no antibodies were detected during the whole period of the disease; in such patients the toxic and subtoxic forms of diphtheria were registered twice as often as in seropositive patients. In 31% of the patients seronegative by the moment of hospitalization a rapid increase in the titers of antibodies C. diphtheriae toxin was observed in the course of the disease, which was indicative of the secondary character of immune response in patients who had been immunized earlier.

Adult↗