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PubMed1989

Comparison of immune responses to diphtheria and tetanus toxoids of various mouse strains.

Immune responses of 11 mouse strains with known genetical characteristics and two outbred strains to diphtheria and to tetanus toxoids were compared. Both diphtheria and tetanus antitoxins were titrated by passive hemagglutination. From the pattern of the immune response, the mouse strains tested may be classified into four groups. [1] Strains ddY (SPF) and ddY (conv) and those with haplotype H-2b, such as C57BL/6 and C57BL/10, were high responders to both toxoids. [2] Strains with H-2d, such as BALB/c, B10.D2 and DBA/2Cr, were intermediate responders to both toxoids. [3] Strains with H-2k, H-2a or, H-2m, such as C3H/He, B10.BR, B10.BR/SgSn, B10.A/SgSnJ and B10.AKM/O1a, were high responders to diphtheria toxoid but low responders to tetanus toxoid. [4] The strain with H-2h4, B10.A (4R), was a poor responder to both toxoids.

Animals↗
PubMedDate not supplied

[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.

Adolescent↗
PubMed1975

Combined diphtheria-tetanus immunization of adults.

The administration of a combined adult-type diphtheria-tetanus vaccine to a group of 35 adults seeking booster tetanus immunization produced a secondary immune response to the diphtheria antigen in 26. A satisfactory response to the tetanus antigen was noted in all those who gave a reliable history of active tetanus immunization, including eight individuals who had not received a dose of toxoid for 25 to 28 years. No systemic reactions were observed, but significant correlation was found between local reactivity and a high post-booster titre of tetanus antitoxin. Selective use of the combined vaccine instead of tetanus toxoid alone offers a means of raising the diphtheria immunity in the adult population.

Adult↗
PubMed1955

The use of mixed diphtheria-pertussis-tetanus antigens.

The author reviews the use of mixed diphtheria-pertussis-tetanus antigens in the light of the information which has become available in recent years. When diphtheria toxoid and tetanus toxoid, adsorbed or unadsorbed, are added to either plain or adsorbed pertussis vaccine, a satisfactory level of diphtheria antitoxin can be obtained in children over 6 months of age and of tetanus antitoxin in children of any age. As to the duration of immunity, it appears that provided three doses of mixed antigens are given for the primary immunization of children 6 months old a substantial proportion will have effective antitoxin titres three years later, but that with two doses only the antitoxin levels fall more rapidly.Reviewing the evidence, the author considers that mixed antigens will be useful in future immunization campaigns, although he makes it clear that extensive investigations, particularly on the immunizing effect of the pertussis component, must be undertaken before their value can be finally assessed.The reactions to and complications after inoculation with mixed antigens are then discussed, particularly in relation to convulsions, encephalopathy, and poliomyelitis. Finally, the author considers provisional recommendations for the use of mixed antigens, pointing out that the main question in all countries is whether the advantages of giving all three antigens simultaneously to children under 6 month of age, necessary because of the pertussis mortality in the first months of life, outweigh the disadvantages.

Child↗
PubMedDate not supplied

[Influence of genetic and phenotypical factors on the efficiency of the vaccination of young children against diphtheria and measles].

The child's sex was shown to influence the character of antibody formation only after immunization against diphtheria with live measles vaccine: girls exhibited stronger reaction to vaccination than boys. Children of different gender were found to have characteristic HLA DR markers of humoral immune response to diphtheria toxoid and measles vaccine. HLA DR7 proved to be the marker of low production of antibodies to diphtheria toxoid and measles vaccine in boys.

Antibodies, Bacterial↗
PubMed1991

Diphtheria, tetanus, and pertussis: recommendations for vaccine use and other preventive measures. Recommendations of the Immunization Practices Advisory committee (ACIP).

This revision of the Immunization Practices Advisory Committee (ACIP) statement on diphtheria, tetanus, and pertussis updates the statement issued in 1985, and incorporates the 1987 supplementary statement, which addressed two issues: a) the risks and benefits of pertussis vaccine for infants and children with family histories of convulsions; and b) antipyretic use in conjunction with diphtheria and tetanus toxoids and pertussis vaccine absorbed (DTP) vaccination among children with personal or family histories of convulsions (1,2). This document presents new recommendations for epidemiologic investigation and management of contacts of diphtheria patients. The updated recommendations include a review of the epidemiology of the three diseases and descriptions of the available immunobiologic preparations with appropriate vaccination schedules. Also included are a) new information on and reassessment of the possible relation between receipt of DTP and the occurrence of serious acute neurologic illness and permanent brain damage, b) revisions in the recommendations on precautions for and contraindications to pertussis vaccine use, and c) revisions on recommendations for chemoprophylaxis for household and other close contacts of pertussis patients. The Committee has reviewed and taken into consideration the recent report by the Institute of Medicine entitled, "Adverse Effects of Pertussis and Rubella Vaccines" in making these recommendations.

Adult↗
PubMed1990

[The immunological effectiveness of small doses of diphtheria and tetanus anatoxins in the revaccination of children with allergy-altered reactivity and adults].

The possibility of decreasing the content of antigens in adsorbed diphtheria-tetanus toxoid, used for the booster immunization of children with allergically altered responsiveness and adults, is shown. Diphtheria toxoid in doses of 1-2.5 Lf and tetanus toxoid in doses of 1-2.5 binding units possessed sufficiently high immunological effectiveness in combination with low reactogenicity and good tolerance. In 6-12 months after booster immunization with decreased doses of toxoids 100% of children with allergy of different character and, respectively, 86-94% and 95% of adults have developed protective levels of antibodies to diphtheria and tetanus.

Adult↗
PubMed1986

[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.

Adolescent↗
PubMed1988

The changing epidemiology of diphtheria in Jordan.

Outbreaks of diphtheria used to occur regularly in Jordan, the last such outbreak being in 1977-78. Since that time, a massive immunization programme targeted at pre-school-age children has been markedly successful. Hence, when an outbreak of diphtheria occurred in 1982-83, it was unexpected. Of the 35 patients who were treated at the Jordan University Hospital, two died and the remaining 33 recovered uneventfully. Contrary to our findings in previous diphtheria epidemics in Jordan, this outbreak largely involved adolescents and young adults.

Adolescent↗
PubMed1986

[Serological surveillance of diphtheria].

The serological method (indirect hemagglutination test) has been used in the surveillance of diphtheria infection. The structure of immunity to diphtheria in the population of the region has been studied. The possibility of increasing intervals between booster immunizations has been confirmed. The introduction of planned booster immunizations of the adult population with diphtheria toxoid is proposed.

Adolescent↗
PubMed1995

[The clinical manifestations, diagnosis and treatment of diphtheria in adults].

Diphtheria morbidity among adult population of Moscow is growing. The tests of different modes and schemes of heterogeneous antidiphtheria serum administration have found out that the highest efficacy of serotherapy was achieved with a single intravenous dose. Another treatment of diphtheria is hemosorption. Widely used in present-day clinical practice hemosorbents provide adequate elimination of the toxin from plasma. The authors analyse the present situation in clinical symptoms, complications, lethality of diphtheria basing on the data provided by S. P. Botkin's Hospital.

Adolescent↗
PubMed1978

Studies of the diphtheria toxin receptor on Chinese hamster cells.

Concanavalin A, wheat germ agglutinin and the ovalbumin glycopeptide are all inhibitors of the cytotoxic effect of diphtheria toxin on Chinese hamster cells. Ovalbumin glycopeptide loses its inhibitory property after treatment with beta-N-acetylglucosaminidase. This demonstrates the importance of the glycopeptide structure for the mechanism of inhibition. The glycopeptide may be a toxin cell-surface receptor analogue. Diphtheria toxin-resistant mutants were isolated in order to search for cells that might have an altered toxin receptor. One mutant was 10- to 15-fold more resistant to diphtheria toxin than wild-type cells when protein synthesis was measured as a function of toxin concentration. However, when protein synthesis was measured as a function of time at a high toxin concentration, the time before onset of inhibition was identical in the mutant and wild-type cells. We present evidence indicating that the resistance of this mutant can be accounted for by a decreased affinity of toxin for a cell-surface receptor.

Cell Line↗
PubMed1999

Evaluation of a guinea pig model to assess interference in the immunogenicity of different components of a combination vaccine comprising diphtheria, tetanus and acellular pertussis (DTaP) vaccine and haemophilus influenzae type b capsular polysaccharide conjugate vaccine.

A guinea pig model to assess the immunogenicity of a combination vaccine containing diphtheria, tetanus and acellular pertussis (DTaP) vaccine and Haemophilus influenzae type b (Hib) capsular polysaccharide conjugated to tetanus toxoid (HibT) was evaluated comparatively with the mouse immunogenicity test to study the effect of combining these antigens on the immunogenicity of various components. The immunogenicity test in mice was performed by subcutaneous injection of groups of 10 animals twice at an interval of four weeks with 1/10 of a single human dose of various formulations of combination vaccines, DTaP or HibT vaccine. The animals were bled at 4 and 6 weeks and IgG or total antibodies to various components were determined by ELISA or RIA. The guinea pig immunogenicity model included groups of animals injected subcutaneously twice at an interval of six weeks with 1.5 times the single human dose of various formulations. The animals were bled at 4, 6 and 8 weeks and serum samples were tested for antibodies to various components by ELISA, RIA and/or neutralization tests. Additionally, potency of tetanus and diphtheria components was assessed as per the US Food and Drug Administration's regulations. Aluminium phosphate (AIPO(4)) adsorbed HibT vaccine or HibT as a combination with AIPO(4)adsorbed DTaP vaccine showed significant increases in IgG antibodies to tetanus toxin in mice as well increased tetanus antitoxin levels in guinea pigs as compared to soluble HibT vaccine. In general, combining DTaP and HibT vaccines did not affect the antibody levels to tetanus and diphtheria toxoids whereas DTaP-HibT combination vaccine elicited significantly lower IgG antibodies to pertussis toxin and filamentous haemagglutinin than DTaP vaccine alone, particularly after first injection. Mice showed similar Hib antibody responses for the combination and HibT alone whereas guinea pigs consistently showed lower anamnestic responses to Hib for combination formulations than for HibT alone. Reducing the amount of HibT and/or tetanus toxoid in the combination formulations reduced this suppression of Hib antibody response in guinea pigs. Suppression of Hib antibody response in combination vaccines has also been reported from recent clinical trials. Based on the results from this study, it appears that the guinea pig model may be able to predict the human response to various components of combination vaccines.

Animals↗
PubMed1997

Characterization of bacteriophages from tox-containing, non-toxigenic isolates of Corynebacterium diphtheriae.

Non-toxigenic strains of Corynebacterium diphtheriae continue to cause disease within immunized populations. A subset of these corynebacteria carry the diphtheria toxin gene but in a cryptic form. To determine whether such strains might contribute to the re-emergence of functional toxin genes, the phages and tox mutations within three clone types were examined. tox-containing, beta-related phages were isolated from two of the strain types. The third isolate appeared to harbour a defective prophage. One of the tox- phages encoded truncated, yet enzymatically-active, forms of diphtheria toxin, suggesting that it had sustained a point mutation within the latter half of its toxin gene. In contrast, the other mutant phage did not elicit the production of either a cross-reacting material or an ADP-ribosylating activity. Complementation tests employing a series of double lysogens confirmed that the mutations responsible for the non-toxigenic phenotype of all of the phages were cis dominant. Given these findings, it is reasonable to hypothesize that tox+ genes can arise within human populations by either homologous recombination between two distinct tox- phages or spontaneous reversion within a single mutant allele.

Bacteriophages↗
PubMed1991

Determination of diphtheria toxin neutralizing antibody titers with a cell protein synthesis inhibition assay.

A method which allows an accurate determination of very low titers of antibodies able to neutralize diphtheria toxin has been developed. The assay is based on the incubation of a reference amount of diphtheria toxin with different dilution of the serum and the evaluation of the residual toxicity of diphtheria toxin on Vero cells. The cells are seeded in 96-well plastic plates with the toxin-serum mixtures and the residual toxin activity is measured as the block of cell protein synthesis after incubation with [14C]leucine. Antitoxin titers as low as 0.002 IU can be reproducibly and accurately measured and the method gives a linear response in the range 0.002 to 8.0 IU/ml.

Animals↗
PubMed1996

Comparative safety and immunogenicity of an acellular versus whole-cell pertussis component of diphtheria-tetanus-pertussis vaccines in Senegalese infants.

A diphtheria and tetanus toxoid two-component acellular pertussis vaccine (DTaP), consisting of 25 micrograms glutaraldehyde-detoxified pertussis toxin (PT) and 25 micrograms native filamentous hemagglutinin (FHA), was compared with diphtheria and tetanus toxoid whole-cell pertussis vaccine (DTwP) in a randomized, double-blind manner in 286 Senegalese infants inoculated at two, four, and six months of age. In infants receiving DTaP a significantly lower rate of local reactions, crying and fever was observed than in infants receiving DTwP. One month after the third dose, the geometric mean titres for FHA antibodies were higher in the DTaP group, whereas increases in PT antibody titres were higher in the DTwP group. More than 90% of the infants had a fourfold or more increase in antibodies to both PT and FHA with either vaccine. Diphtheria, tetanus, and polio antibody responses were also measured and found to be comparable between the two groups. The results of this pilot study support the implementation of a field trial to compare the protective efficacy of these vaccines against pertussis in the same setting.

Antibodies, Bacterial↗
PubMed1997

Diphtheria immunity in Flanders.

A serological survey to determine the immunity to diphtheria in the Flemish population was conducted according to the recommendations of the World Health Organization. Immunity to diphtheria was determined on a randomised, stratified sample (1679 serum samples) from an existing serum bank (4058 serum samples) representative of the Flemish population. All age groups between 0 and 100 years were included. A tissue (Vero cell) culture toxin neutralisation assay was used to measure serum diph-theria antitoxin concentrations. The results showed that 43% of the Flemish population was protected against diphtheria (antitoxin titre, > or = 0.1 IU/ml), while 32% was susceptible (antitoxin titre, < 0.01 IU/ml); for 25%, protection was of limited duration (antitoxin titre, > or = 0.01 IU/ml and < 0.1 IU/ml). The proportion of susceptible subjects showed a significant age-related increase, with the highest values in the 35 to 44 and 45 to 54 age groups (57.9% and 55.5%, respectively). These results emphasise the need for booster immunization of adults.

Adolescent↗
PubMedDate not supplied

Serum antibodies to diphtheria-tetanus-pertussis vaccine components in Argentine children.

The Argentine vaccination schedule against diphtheria, tetanus and pertussis (DTP) recommends three doses of DTP vaccine at 2, 4 and 6 months of age, two boosters at 18 months and 6 years, a booster dose of tetanus vaccine every 10 years and two doses during pregnancy. To evaluate the effect of this schedule, antibodies against pertussis toxin (PT) and filamentous hemagglutinin (FHA) and against tetanus and diphtheria toxoids were determined by ELISA in serum samples from children (1 month to 6 years) who received different doses of DPT vaccine: 0 dose (n = 50), 1 dose (n = 25), 2 doses (n = 25), 3 doses (n = 55), first and second booster (n = 25); 25 pregnant women and their offspring, and 45 adults. High antibody levels against PT (> 140 EU/ml) and FHA (> 80 EU/ml) were recorded in mothers and in the newborn. Antibody titers against PT increased with the number of doses given and decreased with time. Full protection against tetanus (titers > 0.1 IU/ml) was observed in the group of adults (0.37 IU/ml), in mothers (4.4 IU/ml) and their newborn offspring (5.5 IU/ml), and in children after receiving the second dose of DTP vaccine (1.86 IU/ml). The immune status for diphtheria was far lower, as most of the groups lacked adequate protection. After the third dose of DTP vaccine, only 78% of the children had antibody titers above the protective level (0.1 IU/ml). Since antibody levels considered to provide full protection were only achieved after the first booster dose of DTP vaccine, the primary three-dose schedule seems to be insufficient to confer adequate immunity in all vaccinees. Because of the high proportion of non-protected adults, a booster dose of Td vaccine should be considered for this group.

Adhesins, Bacterial↗