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PubMed2005

Prevalence of IgG diphtheria antitoxin in blood donors in Rio de Janeiro.

The lack of information on the immunity of adults in Brazil against diphtheria prompted us to analyse sera from 234 blood donors aged 18-61 years (30.3% females and 69.7% males). IgG diphtheria antitoxin levels determined by means of an ELISA, validated by toxin neutralization test in Vero cells, showed that 30.7% (95% CI 25.0-37.1) of the population was fully protected (>or=1 IU/ml). The highest percentage of subjects fully protected was in the 31-40 years age group. Most of the subjects with uncertain or no protection (<1 IU/ml) were found in the 18-30 years age group (43.8%, OR 2.18, P=0.01). Antitoxin levels were not influenced by the increase in age. Males were more protected than females (80.5%, OR 0.44, P=0.01). The prevalence of 30% of individuals fully protected against diphtheria in blood donors in Rio de Janeiro supports the fact that immunity to diphtheria among healthy Brazilian adults is inadequate. To avoid diphtheria epidemics in the future the immunity among adults should be raised in the coming years.

Adolescent↗
PubMed1997

[Diphtheria booster immunization for adults].

BACKGROUND AND OBJECTIVE: Nearly 50% of adults in Germany have no measurable antibody protection against diphtheria, even though most of them will have been vaccinated against it in their childhood. We investigated how vaccination should be performed in this situation to provide lasting protection. MATERIAL AND METHODS: 100 adults (53 men, 47 women; mean age 27.7 [19-54] years) whose last diphtheria vaccination had been at least 10 years previously, were injected up to three times with customary commercial monovalent diphtheria vaccine for adults (5 IU toxoid/0.5 ml), at intervals of 4-8 weeks. Each time, before and 4-8 weeks after the latest injection, the antitoxin level was determined by cell-culture neutralization test. RESULTS: Before the vaccination 30 of the 100 subjects had protection against diphtheria (antitoxin level > 0.1 IU/ml), 24 had "basic immunity" (0.01 to < 0.1 IU/ml), and 46 no measurable protection (< 0.01 IU/ml). After the first booster the protection threshold had not been reached in seven of the 100, all of them women. The main determinant for the pre- and post-vaccination antitoxin level was the interval since the last vaccination. In addition, women had significantly lower pre- and postvaccination levels than men. But after the second and third booster the antitoxin level of the seven women had risen to above the protection threshold, while the geometric mean of the whole collective had fallen, despite further boosters. It was 0.015 IU/ml before vaccination, 1.156 IU/ml after the first booster, 0.924 IU/ml after the second, and 0.952 after the third. CONCLUSION: Those adults who were last vaccinated against diphtheria more than 20 years ago should have two booster shots, more than 8 weeks apart, so that the highest possible and most lasting antitoxin level can be achieved. Women in particular should have at least two booster shots, as their antitoxin response tends to be less than that of men.

Adult↗
PubMed1982

[Seroconversion in juvenile patients and adults after diphtheria immunization].

A total of 155 persons of the Hamburg hospital personnel aged between 15 and 64 years were immunised against diphtheria. Out of 120 prevaccination seronegative persons (including very low diphtheria antitoxin titres) 92 (76.7%) reacted with seroconversion above the diphtheria protection level after the adult dosage of 7.5 IU diphtheria toxoid. Good results were still obtained with a 2.5 IU dosage. The conversion factor of 210 in the age group of 55 to 64 year old persons was sevenfold higher than in the 15 to 24 year old group. Local reactions of the mainly slight nature were seen after vaccination in 20.8%, only immunised person showed a slight increase of temperature. It is recommended to offer reimmunisation with a 7.5 IU dosage before leaving school. Selective immunisation of certain professional groups, such as hospital personnel, should be performed according to age and history, either with 7.5 or 2.5 IU of diphtheria toxoid.

Adolescent↗
PubMed2000

Successful control of epidemic diphtheria in the states of the Former Union of Soviet Socialist Republics: lessons learned.

Epidemic diphtheria reemerged in the Russian Federation in 1990 and spread to all Newly Independent States (NIS) and Baltic States by the end of 1994. Factors contributing to the epidemic included increased susceptibility of both children and adults, socioeconomic instability, population movement, deteriorating health infrastructure, initial shortages of vaccine, and delays in implementing control measures. In 1995, aggressive control strategies were implemented, and since then, all affected countries have reported decreases of diphtheria; however, continued efforts by national health authorities and international assistance are still needed. The legacy of this epidemic includes a reexamination of the global diphtheria control strategy, new laboratory techniques for diphtheria diagnosis and analysis, and a model for future public health emergencies in the successful collaboration of multiple international partners. The reemergence of diphtheria warns of an immediate threat of other epidemics in the NIS and Baltic States and a longer-term potential for the reemergence of vaccine-preventable diseases elsewhere. Continued investment in improved vaccines, control strategies, training, and laboratory techniques is needed.

Adult↗
PubMed2005

Effect of monophosphoryl lipid A on antibody response to diphtheria toxin and its subunits.

Monophosphoryl lipid A (MPL) was evaluated for its ability to enhance the antibody response to diphtheria toxin and its fragment A and fragment B subunits. BALB/c mice were immunized subcutaneously with 1 Lf of diphtheria toxoid in the presence of 25 microg of MPL on days 0 and 14. Two weeks after the second immunization, sera were obtained from the mice and analysed for antibody response to diphtheria toxin and its subunits. A new ELISA method, developed in our laboratory, was used to measure antibody levels against the toxin, fragment A, and fragment B. It was observed that MPL significantly enhanced antibody responses to diphtheria toxin and its subunits. However, there was no statistical difference between anti-A and anti-B responses. The results indicated that MPL seems to be a potential candidate as an adjuvant for future diphtheria vaccine formulation.

Adjuvants, Immunologic↗
PubMed1994

The role of aluminium for adverse reactions and immunogenicity of diphtheria-tetanus booster vaccine.

In a randomized, double-blind clinical trial, 235 schoolchildren aged 10 years received either a regular, aluminium-adsorbed diphtheria-tetanus vaccine or the same vaccine in fluid form, in order to investigate if local side effects could be diminished by exclusion of aluminium. System reactions were rare and local reactions frequent in both groups but larger local reactions were even more pronounced in the non-adsorbed vaccine group. Antibody responses to both vaccines were excellent and even slightly higher to the non-adsorbed diphtheria-tetanus vaccine (p = 0.0135 and 0.0014 for anti-diphtheria and anti-tetanus, respectively). This study has shown that fluid diphtheria-tetanus vaccine does not solve the problem of extensive local side effects induced by the diphtheria-tetanus school booster. Alternative strategies, such as changes in vaccine composition, dosage and spacing, will have to be considered.

Adsorption↗
PubMed1990

[Diphtheria antitoxin levels in Japanese adults (10-20 years after the last vaccination)].

The serum diphtheria antitoxin levels in Japanese adults were investigated and the persistence of diphtheria toxoid effect was evaluated. The subjects consisted of 56 volunteers (20-31 years of age) who had received regular inoculations of diphtheria and pertussis vaccine (I and II or III phases). They had been immunized according to the Vaccination Law (old version) revised in 1958. The length of time after the last inoculation of diphtheria toxoid was speculated to range from 10 to 20 years. Serum diphtheria antitoxin was determined by passive hemagglutination method. Antitoxin level was 0.025 HAU/ml in 1 subject (1.8%), 0.05 in 2 (3.6%), 0.1 in 2 (3.6%), 0.2 in 8 (14.3%), 0.4 in 7 (12.5%), 0.8 in 12 (21.4%), 1.6 in 7 (12.5%) and more than 1.6 in 17 (30.4%). Results indicated that 55 of 56 (98.2%) possessed a higher level than the prophylaxis standard (0.05 HAU/ml). Since the current Vaccination Law prescribes a lower amount and fewer inoculations than the old law, the number of adults possessing prophylactic antitoxin level may decrease in the future. Further investigation of antitoxin level in adults needs to be continued.

Adult↗
PubMed2003

Diphtheria: the patch remains.

This study analysed the number of patients admitted with diphtheria to a teaching hospital in the state of Assam in India over a period of five years and compared the disease characteristics and management with outcomes and incidences of diphtheria reported in the literature. It was a retrospective analysis of data elicited from clinical records of patients admitted to hospital. A total of 101 admissions were recorded during a five-year period between March 1997 to March 2002, mostly with pharyngeal diphtheria (90 per cent). The majority of patients had no history of immunization (70 per cent). Significant presenting features were a tonsillar patch, sore throat, respiratory distress and fever. All patients were treated with anti-diphtheritic serum and intravenous antibiotics. Steroids were given to 81 per cent of patients and tracheostomy was carried out in 10 per cent of cases. The mortality was 16 per cent. Diphtheria of the respiratory tract remains a potentially fatal disease commonly presenting with membranous pharyngitis. Early diagnosis and treatment with anti-diphtheritic serum and antibiotics remain the cornerstone of treatment. Inadequate immunization cover is deemed responsible for the continued menace of diphtheria.

Adolescent↗
PubMed2006

Acellular pertussis vaccine booster combined with diphtheria and tetanus toxoids for adolescents.

BACKGROUND: The incidence of pertussis is increasing, especially in adolescents, attributed in part to waning of immunity after childhood immunization. Recently licensed in the United States for use in adolescents, acellular pertussis vaccines will provide an immunogenic and safe option for booster immunization against pertussis. METHODS: This prospective, randomized, observer-blinded, multicenter, comparative study evaluated the safety and immunogenicity of a vaccine formulated with tetanus toxoid, reduced diphtheria toxoid, and acellular pertussis antigens (Tdap) compared with tetanus and diphtheria toxoids vaccine (Td) for booster immunization in adolescents. There were 4114 healthy adolescents aged 10 to 18 years who completed childhood vaccination against diphtheria, tetanus, and pertussis who were enrolled, randomized, and received study vaccine. RESULTS: Local and general symptoms were comparable between the Tdap and Td groups. The immune response of Tdap was comparable with Td vaccine for tetanus and diphtheria seroprotection and booster responses. In addition, geometric mean concentrations of antibody to pertussis antigens, pertussis toxoid, filamentous hemagglutinin, and pertactin exceeded the antibody response elicited after infant immunization with diphtheria and tetanus toxoids and acellular pertussis antigens (DTaP) that had proven efficacy against pertussis. CONCLUSIONS: In adolescents, the studied Tdap was safe and immunogenic and induced pertussis antibodies that were higher than those associated with efficacy in infants.

Adolescent↗
PubMed2006

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.

Adolescent↗
PubMed1987

Determination of tetanus and diphtheria antitoxin content in dried samples of capillary blood: a convenient method applied to infants.

To assess the effect of vaccination of infants against tetanus and diphtheria capillary blood was drawn from 51 randomly selected healthy infants 2 years of age. The blood was applied directly to filter paper. In the laboratory the blood dots were eluted in phosphate buffered saline for 2 h at room temperature yielding 100% recovery of antitoxin activity. Serum volume in the blood dots was determined by calculation of dot area or by measuring albumin content in the eluted samples by means of rocket immunoelectrophoresis. These approaches were found to be equally applicable. Concentration of antitoxin to tetanus and diphtheria was assessed with ELISA and in vitro toxin neutralization assay respectively. Mean diphtheria antitoxin concentration was 0.53 IU/ml, and mean tetanus antitoxin concentration 4.1 IU/ml. Low initial immune response to diphtheria vaccination may be responsible for the risk among school children to have antitoxin concentration below protective level (reported elsewhere). In environments where diphtheria is disappearing a lowered vaccination response may be expected.

Blood Specimen Collection↗
PubMed1980

Influence of anti-fragment A of diphtheria toxin on passive hemagglutination with antitoxin.

Hemagglutination (HA) and toxin neutralization (TN) tests were used to titrate human and guinea-pig serum specimens taken at various stages of immunization for diphtheria antitoxin. The ratio of HA to TN titers varied significantly depending on the immune status. The ratios and the range of their variations became larger and high values exceeding five were often obtained after repeated booster immunization. Such a high value was proved to be related to the antibody against fragment A (FrA) of diphtheria toxin, since the ratio reduced significantly when anti-FrA was absorbed. Anti-FrA was not produced in children after the basic immunization with diphtheria toxoid and was detected in only one-third of vaccines after the booster injection given after 1 year. It was produced abundantly, however, when booster immunization was repeated. The pattern of production of anti-FrA in guinea pigs was similar to that in humans, when immunized with diphtheria toxoid with adjuvant. No anti-FrA was produced even when the animals were immunized repeatedly with plain diphtheria toxoid.

Animals↗
PubMed1998

An antibody induction method in mice for the potency assays of diphtheria and tetanus components in combined vaccines.

Eleven batches of Adsorbed Diphtheria-Tetanus (DT) vaccines and thirteen batches of Adsorbed Diphtheria-Pertussis-Tetanus (DTP) vaccines were tested for the potency of diphtheria and tetanus components by an Antibody Induction Method (AIM) developed in mice. The potency results obtained were found comparable and did not show any statistically significant difference with those obtained by WHO recommended lethal challenge tests for diphtheria in guinea pigs and for tetanus in mice. AIM in mice is more economical as both diphtheria and tetanus components of combined vaccine can be tested in the same experiment and the procedure also eliminates the use of guinea pigs required in the lethal challenge/conventional tests. The data obtained while testing tetanus component by the conventional antibody induction (IP) method in guinea pigs suggests that minimum requirements laid down in i.p. is too low which may be fixed as at least 3 out of 9 guinea pig sera and should contain > or = 4 units of tetanus antitoxin per ml.

Animals↗
PubMed2000

[Diphtheria antitoxin level 2 years after booster vaccination].

In a prospective, controlled, randomized, multicenter study the immunogenicity of a single (day 0) and two (day 0, 28) booster vaccination against diphtheria were compared in subjects who had received their last diphtheria vaccination more than 10 years ago. Both short-term and long-term immunogenicity was assessed by determining diphtheria antitoxin levels four weeks after vaccination and after one and two years. 102 subjects received the first booster vaccination, and 83 were vaccinated twice. Prior to the first vaccination 27% of the subjects had a diphtheria antitoxin level below 0.01 I.U./ml; after the first booster only 5% were unprotected. The second booster did not show a significant effect, however, in 1 of the 5 subjects who were still unprotected after the first booster the second elicited an antitoxin level of more than 0.01 I.U./ml. After one and two years 7% and 8% of the subjects had diphtheria antitoxin level below 0.01 I.U./ml. A serological effect of a second booster vaccination four weeks after the first one could not be demonstrated neither after one nor after two years.

Adolescent↗
PubMedDate not supplied

[Characteristics of antitoxic and antibacterial immune response in nontoxic forms of oropharyngeal diphtheria].

The enzyme immunoassay system (EIA) for differentiation of antibodies in therapeutic heterogeneous antitoxic serum and antibodies to Corynebacterium diphtheriae toxigenic strains in patients and carriers was developed. The use of EIA permitted the dynamic evaluation of the characteristics of humoral antitoxic and antibacterial immune response in 50 patients with the localized and disseminated forms of stomatopharyngeal diphtheria and 14 "healthy" carriers of toxigenic C. diphtheriae. As revealed in this study, the symptoms of the disease in patients with disseminated forms of stomatopharyngeal diphtheria developed in the presence of statistically significant low quantitative values of antitoxic and antibacterial antibodies to C. diphtheriae antigens. In the group of patients with the localized forms of the disease the initially low level of antitoxic antibodies was detected with the concentration of antibacterial antibodies remaining unchanged. During the period of convalescence the levels of antitoxic antibodies in both groups reached those of healthy persons. In case of localized forms of the disease the level of antibacterial antibodies decreased as compared with healthy persons, starting from the second week of the disease. The period of convalescence in the disseminated forms was characterized by the low concentration of antibacterial antibodies. Carrier state was formed in the presence of high levels of antitoxic antibodies and significantly low levels of antibacterial ones.

Adolescent↗
PubMedDate not supplied

[Characteristics of the antitoxic and antibacterial immune response in children with diphtheria].

As found in this study, the development of the manifest forms of diphtheria occurred in the presence of lower levels of antitoxic antibodies, than bacterial carrier state. The level of antitoxic antibodies in all patients, irrespective of the time of their examination, was higher than that of antibacterial antibodies. In the dynamics of the disease a considerable increase in antitoxic and antibacterial antibodies was observed in localized and disseminated forms of diphtheria and, to a considerably lesser degree, in toxic and subtoxic forms of diphtheria, while not observed in the process of the formation of bacterial carrier state. The dynamics of a rise in the levels of antitoxic and antibacterial antibodies in the manifest forms of diphtheria infection made it possible to differentiate between the cases of toxigenic Corynebacterium diphtheriae carrier state and those of the disease.

Antibodies, Bacterial↗
PubMed1976

[Minor diphtheria epidemic in a Cologne children's home (author's transl)].

Between May and July 1972, 12 children aged from 7 to 14 were admitted to the Cologne University Children's Hospital suspected of having diphtheria. In 10 cases the tonsils or pharyngeal cavity were affected. One case of wound diphtheria and one of nasal diphtheria were observed. The clinical suspicion was confirmed in 8 of 12 cases by detection of the pathogen Coryne-bacterium diphtheroides mitis. 11 patients were discharged from the hospital after being treated for between 2 to 6 weeks, but 5 of them needed ambulant cardiac observation. One patient died of malignant diphtheria with symptoms of cardiovascular failure. He had not been treated specifically for 1 week at first. Not one of the 12 patients had been satisfactorily immunized by active inoculation with diphtheria toxoid.

Adolescent↗
PubMed1993

Coagglutination for rapid testing of toxin producing Corynebacterium diphtheriae.

Coagglutination test was standardised for rapid detection of diphtheria toxin after primary culture of C. diphtheriae isolates on conventional Loeffler's medium. The procedure was optimised with diphtheria toxoid (DT)-antidiphtheritic serum (ADS) system wherein Cowan-I strain of Staphylococcus aureus was sensitised with ADS. Toxoid in the range of 1.02 lf/ml to 4200 lf/ml could be detected by the present procedure. Toxin of C. diphtheriae could be demonstrated in five of eight clinical isolates, this correlated with the conventional guinea pig pathogenicity test. The coagglutination test thus needs further confirmation of its potential as a simple and satisfactory test for rapid detection of toxin-producing C. diphtheriae.

Agglutination Tests↗