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PubMed1989

[The use of DNA fingerprint analysis for the differentiation of populations of toxigenic Corynebacterium diphtheriae].

13 C. diphtheriae strains were used as a model to establish the conditions of making the fingerprint analysis of chromosomal DNA. These strains, subdivided into 7 groups in accordance with the character of their restriction splitting, were mostly isolated from territorially close sources and belonged to the same phagotype. Probably, C. diphtheriae DNA has strain variations manifested by an unequal number and location of the sites of the recognition of specific endonucleases, which may be used for the intraspecific differentiation of C. diphtheriae.

Bacteriophage Typing↗
PubMed1985

[Cloning in Escherichia coli of the mutant gene coding the diphtheria toxin].

Bacteriophage beta 45 of Corynebacterium diphtheriae was harvested. The extracted DNA of the bacteriophage was digested by the restriction endonuclease BamHI and inserted into the BamHI cleavage site of pUC19 vector plasmid. Plasmid pNVY5 containing a mutant gene crm45 of diphtheriae toxin in a 3.9 bpn fragment was isolated from the hybrid plasmids obtained. Cell free extracts of E. coli strain TG1 (pVNY5) contain the nontoxic protein crm45 possessing the specific enzymatic activity of diphtheriae toxin (ADP ribosylation on wheat elongation factor two). According to orientation of BamHI fragment in pNVY5 plasmid it is concluded that the crm45 gene is expressed using its own promoter.

Bacteriophages↗
PubMed1988

[Pharyngeal diphtheria diagnosed too late, fatal course of the disease].

In the course of an endemic lasting 13 months we saw three cases of toxic pharyngeal diphtheria. In spite of immediate treatment with serum and penicillin two patients died, including a 14 year-old girl who had been treated inadequately for two weeks. Serum along with antibiotics must be given as soon as diphtheria is suspected. Without the immediate administration of serum the mortality of diphtheria remains very high.

Adolescent↗
PubMed1987

[Determination of the toxigenicity of Corynebacterium diphtheriae by using paper indicator disks].

The method for the determination of the toxigenicity of C. diphtheriae by means of discs impregnated with diphtheria antitoxin is proposed. The discs can be prepared long before use and stored for a year. The determination of toxigenicity with these discs is not inferior in its sensitivity to the routine procedure of the immunoprecipitation test. The disc method decreases the consumption of unavailable diphtheria antitoxin by 10 times, that of culture media by 2-2.5 times: besides, it is less labor consuming.

Diphtheria Antitoxin↗
PubMed1972

International collaborative studies on potency assays of diphtheria and tetanus toxoids.

Collaborative studies showed that relative potency assays for a particular type of diphtheria toxoid (adsorbed) and for tetanus toxoid (plain and adsorbed) gave very similar results, whether the assays were carried out by toxin challenge or by antitoxin titration after immunization of experimental animals with graded doses of toxoid. The same numerical results were obtained with a scoring system as with a system based on survivals only. Although skin tests were used on a very limited scale in these studies, it seems likely that they could replace lethal tests for the diphtheria challenge assays.For both tetanus and diphtheria, the adsorbed toxoid gave a higher relative potency when combined with other antigens than as a single toxoid. Both mice and guinea-pigs were used for the lethal challenge test of adsorbed tetanus toxoid. For the single tetanus toxoid the results were the same, but for the combined toxoid (DPT vaccine) the mouse assay results were about twice those of guinea-pig assays.

Animals↗
PubMed1979

Tetanus and diphtheria immunity in urban Minnesota adults.

Tetanus and diphtheria antitoxin levels were measured in 183 urban adults, using a hemagglutination technique. Protective levels (greater than 0.01 unit/mL) of tetanus antitoxin were present in more than 85% of sera from all subjects under 40 years of age and from men between 40 and 59 years old. A minority of women (36%) between 40 and 59 years of age, and of men (41%) and women (29%) over 60 years of age, were protected. Less than one quarter of the study group had protective levels (greater than 0.01 unit/mL) of diphtheria antitoxin. The results of the study suggest that a minority of middle-aged women and older adults have been appropriately immunized against diphtheria and tetanus.

Adolescent↗
PubMed1971

Titration of diphtheria and tetanus antitoxins in sera of low titre.

Available methods for titrating diphtheria and tetanus antitoxin at low concentrations in human or animal blood are surveyed, with special attention to the amount of serum required for the test.In vivo methods, especially the rabbit or guinea-pig intradermal test for diphtheria and the mouse test for tetanus, are precise and reliable. If, however, serum levels as low as about 0.001 IU/ml have to be determined, rather large amounts of serum are required: moreover, the tests are rather time-consuming and expensive.Tissue culture methods are available only for diphtheria antitoxin titration. The titres found coincide very well with those from animal tests. The titrations are less time-consuming and more economical. These methods seem to be very promising for the replacement of animal tests. Of the real in vitro methods, the haemagglutination procedure has been investigated most thoroughly and used most frequently. Low titres can be measured using small amounts of serum, but the titres thus obtained may differ considerably from those obtained in animal tests, at least for individual sera. For mass screening, the method is very suitable.A number of other methods are briefly discussed, but they are either less suitable or have not yet been sufficiently investigated.

Animals↗
PubMed1982

Diphtheria toxin treatment of human advanced cancer.

Purified diphtheria toxin was administered i.v. to 50 patients with advanced solid tumors. The doses of toxin varied according to the different immunological status of the patients against diphtheria. The prominent toxic effects of the treatment were transient peripheral neuropathy observed in two nonimmune patients and fever (37-41 degrees) which occurred in all immune patients with cell-mediated hypersensitivity to toxin. A partial response to lasting from 2 to 4 weeks was achieved in three of 13 nonimmune patients and in one of three nonimmune patients with cell-mediated hypersensitivity. Of 21 immune patients, nine had partial response lasting from 4 to 12 weeks. Of 13 immune patients with cell-mediated hypersensitivity, six had partial and five complete response lasting from 2 to 12 and from 1 to 25+ months, respectively. The overall response rate was 48%. The results suggest that diphtheria toxin may have a role in cancer immunotherapy.

Adult↗
PubMed1983

[Circulation of the causative agent of diphtheria in immune collectives].

Prolonged observations on the spread of toxigenic C. diphtheriae carriership, made during a school year in 12 groups of immune children (3809 children), showed that the penetration of diphtherial infection could give rise to the outbreak of bacterial carriership, its level being as high as 20.9-35.1% of the total number of children in the group. The spread of bacterial carriership occurred during the first months after the penetration of the infection, achieving its peak, then followed the subsidence of the infection in the focus. Though some children in the group persistently released C. diphtheriae, almost no new cases of carriership were registered in spring. The highest spread of carriership (55.6-73%) was revealed in the first forms of boarding schools despite a higher level of antitoxic immunity in these children. Cases of the spontaneous cessation of carriership were observed. The spread and subsidence of carriership were determined by the presence or absence of a susceptible contingent. Tests on guinea pigs, carried out in the course of this study to determine the toxigenicity of C. diphtheriae, showed its variability.

Animals↗
PubMed1984

Hemorrhagic diphtheria.

Two cases of hemorrhagic diphtheria, a rare entity and severest form are reported. Both of them have been mildly ill for more than 3 days and did not seek medical attention, suddenly developed bleeding episodes with clinical evidence of diphtheria in association with severe thrombocytopenia. Inspite of antitoxin, antibiotics therapy and supportive care one died on the third day. The second case was given additional steroid therapy to the regimen and survived with diphtheria myocarditis.

Child, Preschool↗
PubMed1994

[Immunity to diphtheria of African guest workers and students].

This study investigated the immuno-protective diphtheria antitoxin titres of 38 guest workers from Mozambique and 44 students from Cameroon 18 to 35 years of age. Two methods were used to analyse the sera: the cell culture method and the indirect haemagglutination test. The results of both methods were comparable. Approximately 69% of the guest workers from Mozambique showed protective diphtheria antitoxin levels (> or = 0.1 IE/ml), 24% had a boosterrequiring basic immunity (> or = 0.01-0.09 IE/ml), whereas 7% showed no protective diphtheria antitoxin levels. This compared with 46, 35 and 19% respectively among the students from Cameroon.

Adolescent↗
PubMed1995

[Diphtheria prevention among children in Denmark].

Immunisation against diphtheria has been practised in Denmark since 1943, and has been integrated in the childhood immunisation programme since 1950. Three doses of DT-IPV, given at the ages of 5, 6 and 15 months provide an immunisation coverage of 95-99 percent. Although prevalent, with recurrent epidemics during the pre-vaccine era, with the introduction of immunisation, diphtheria has been practically eliminated for the past 40 years. However, the present epidemic in Russia and Eastern Europe emphasises that, even today, the absence of diphtheria can only be maintained through an effective immunisation programme. It is intended to reinforce the Danish immunisation programme with a fourth vaccination (with deoxythymidine) at school entry.

Adult↗
PubMed1993

Prevalence of diphtheria and tetanus antibodies in young adults in Delhi.

A total of 574 blood samples collected mainly from adult males, on a random basis, were tested for diphtheria and tetanus antibodies by Indirect Haemagglutination (IHA) test to find out the percentage of individuals with protective titres (> or = 0.015 IU/ml). A total of 502 (87.5 per cent) and 437 (76.2 per cent) of these had protective titres against diphtheria and tetanus respectively. The vaccination status of these subjects against diphtheria and tetanus was not ascertainable. The relevance of these findings is discussed.

Adult↗
PubMed1976

[Basic features of diphtheria (author's transl)].

The basic features of diphtheria, especially clinical aspects, differential diagnosis and therapy are set out insofar as they are important for the general practitioner. The doctor, not the bacteriologist, must make the diagnosis. Serotherapy must be begun as rapidly as possible, and in adequate dosage. The patients must be carefully watched over in the interests of early detection of possible complications. Rest in bed is required in every case for at least 3 to 4 weeks, longer if possible. Even mild "localized" forms can lead to toxic damage during the course or subsequently. In infants, diphtheria may run its course as the well-defined clinical picture of "diphtheria intoxication" of infants.

Adolescent↗
PubMed1996

Loss of protective immunity to polio, diphtheria and Haemophilus influenzae type b after allogeneic bone marrow transplantation.

Immunity to poliovirus, diphtheria and Haemophilus influenzae type b (Hib) was studied in 16 adult recipients of a bone marrow transplant from an HLA-identical sibling donor in order to evaluate the need for revaccinations. T-cell depletion was not done in any case. The donors and patients were studied before bone marrow transplantation (BMT) and the patients 1, 3, 6, and 12 months later. Prior to the BMT 10 of 11 patients were immune (titre > or = 4) to all vaccine poliovirus types by a standard microneutralization assay. At 12 months after BMT only two of seven patients were immune to all vaccine types, and none had immunity against an antigenically altered poliovirus type 3 strain Finland. The geometric means of antibody titres against poliovirus types 1, 2, and 3 strain Saukett and strain Finland declined gradually after 1 month postgrafting, being 4.4, 5.4, 3.3, and 1.3 respectively at 12 months after BMT. At 1 year 6 of 11 patients had immunity against diphtheria by a toxin neutralization method, but the antitoxin geometric mean level had decreased to a barely protective level, 0.01 IU/ml. The geometric mean Hib antibody concentration decreased during the first 6 months after BMT and thereafter increased slightly. A significant proportion of BMT recipients lose their protection against polio, diphtheria and Hib, and revaccinations are necessary.

Adult↗
PubMedDate not supplied

Potency assay of diphtheria antitoxin in Vero cell microcultures.

Laboratory conditions were established for the titration of diphtheria toxin and antitoxin in Vero Cell Cultures (CCT) and a comparison was made with the intradermal test (IDT) as currently used throughout the world. Working dilutions and cut off values were established by reading both the change in color of phenol red used as pH indicator and changes in cell viability in the microscope. CCT shows high reproducibility and higher detectability than IDT in the titration of both WHO Reference Standard and high titer horse antisera. In sera of guinea pigs immunized for potency testing of diphtheria toxoid the titre was approximately 10 times lower than in the IDT. The explanation is a subject of speculation. The Vero cell titration might be adopted as such for titration of diphtheria antitoxin. In the case of the toxoid potency test it could be used if the limit for the titration is adjusted to 0.2 IU considering the equivalence obtained between the two tests, by taking into account a ratio of 1:10 between CCT and IDT.

Animals↗
PubMed1997

Adverse events after school leavers received combined tetanus and low dose diphtheria vaccine.

Since October 1994, children in the United Kingdom have been offered tetanus vaccine combined with a low dose of diphtheria vaccine (Td) at the age of 15 to 18 years. It is recommended that schoolchildren who have already received a booster of tetanus vaccine at the time of an injury should be given low dose diphtheria vaccine alone. When this vaccine is not available, however, it is recommended that Td vaccine should be given to all children. This study was performed to compare the frequency of adverse events after Td vaccine in 15 year old children with and without a history of an additional tetanus booster in the preceding 10 years. Two hundred and sixty-five children were followed up-52 pupils (20%) with a history of an additional tetanus booster, 157 (59%) with no such history, and 56 (21%) whose history was unclear. Mild local reactions were common and occurred more commonly in children with a history of an additional tetanus booster. Twenty-three pupils (44%) who had received an additional tetanus booster had swelling over 2 cm diameter at the injection site, compared with only 39 (25%) of those with no such history (p < 0.013). Systemic symptoms were equally unusual in both groups. Only three children experienced symptoms attributed to vaccine that were severe enough for them to miss school or attend a doctor; and none of these had received an additional tetanus booster. We conclude that, in the absence of a supply of low dose diphtheria vaccine, offering Td vaccine to children with a history of additional tetanus booster is an acceptable policy.

Adolescent↗
PubMedDate not supplied

[Emergency laboratory diagnosis of diphtheria].

The immune response to diphtheria toxin (clinically pronounced infection or carrier state with the presence of toxigenic bacteria) or toxoid (vaccination) the blood has been found to contain lymphocytes (1.00-5.71%), specifically binding diphtheria toxoid (DTX). The method for the determination of lymphocytes, specifically binding DTX, may serve both for early diagnosis and in the process of the disease, irrespective of the injection of therapeutic serum to the patient. The result of the test is obtained 2-3 days earlier than the positive result of the bacteriological analysis. The set of immune reagents for the rapid diagnosis of diphtheria by the method of rosette formation has been developed.

Antibodies, Bacterial↗