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PubMed1987

[Immunologic methods for the detection of diphtheria toxin (passive hemagglutination and ELISA for toxin detection in cultures and serum)].

A competitive passive hemagglutination assay (cPHA) easy to perform and a highly sensitive ELISA have been investigated for detection of diphtheria toxin from cultures and from human serum. The sensitivity of the cPHA (8 ng toxin/ml) was high enough to detect toxin in pure cultures containing C. diphtheriae. For this application the cPHA proved to be a simple and reproducible alternative to the Elek-Ouchterlony test. Toxin in culture filtrates of nasal and tonsillar swabs containing toxinogenic strains of C. diphtheriae together with germs of the physiological flora and toxin in serum can be detected with the more sensitive Biotin/Streptavidin ELISA (0.6 ng toxin/ml). This allows the confirmation of the clinical diagnosis "diphtheria" within 24-48 h.

Animals↗
PubMed1987

[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.

Adolescent↗
PubMed1988

[Cutaneous diphtheria imported from tropical countries].

Two cases of imported cutaneous diphtheria from tropical areas are described. Vacationing in the Seychelles, a 29-year-old man injured his left malleolus a few weeks before his return to Switzerland. The wound did not heal and an ulcer developed. Microbiologic investigation yielded toxinogenic Corynebacterium diphtheriae. There were no signs of systemic intoxication. The man had not been vaccinated against diphtheria since childhood. In the second case a 51-year-old woman returned from Thailand and Nepal with two very painful ulcers between the toes of her right foot, which was reddish-coloured. Microbiologic investigation again yielded toxinogenic Corynebacterium diphtheriae and there was no sign of systemic intoxication. Treatment with erythromycin brought about complete healing of the ulcers.

Adult↗
PubMed1985

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.

Adolescent↗
PubMed1983

[Epidemiology of diphtheria in the RSFSR during mass immunization over many years].

The work defines the characteristic epidemiological features of diphtheria in the RSFSR at the present moment when a high level of antitoxic immunity is generally determined in children. With the diphtheria morbidity level having, on the whole, a sporadic character in the RSFSR, the intensification of the epidemic process has been found to occur in some regions. Changes in the ratio of morbidity rates among the urban and rural population are observed, the morbidity rate among the latter have the tendency towards increase. At present the characteristic feature of diphtheria is the prevalence of adults in the general morbidity structure. An important fact is a permanently high level of toxigenicity in Corynebacterium diphtheriae. As before, autumn is the season of the highest morbidity level.

Adolescent↗
PubMed1984

[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.

Adolescent↗
PubMed1984

[A case of diphtheria resulting in death].

A 10 years old girl admitted to the hospital on 7.5.1983. She was sent from Etimesgut Hospital with the preliminary diagnosis of diphtheria bronchopneumonia, and glomerulonephritis. Cultures taken from the throat and nose of the patient yielded toxigenic diphtheria bacilli. Inspite of antitoxin and antibiotic treatment and a tracheostomy the patient died two days later. Diphtheritic membranes occluding larynx and trachea were found at the autopsy. In six out of the nine of the family members the throat cultures were found to be positive for toxigenic C. diphtheriae. The family was visited by a woman who had a bloody nasal discharge and ulcers around her nostrils. Close contacts, including the neighbours and the classmates of the children were checked for diphtheria bacilli and all were found to be negative.

Bronchopneumonia↗
PubMed1982

[Immunity against diphtheria in mothers and their newborns in Hamburg (1980)].

The Diphtheria antitoxin level (indirect haemagglutination) was measured in blood samples respectively cord blood of 185 mothers and their newborns. Protective titers (greater than or equal to 0.1 I.U. Diphtheria antitoxin/ml) were found in 29.2% of the confined women and in 27% of their newborn babies. A review of similar investigations from the literature is given, and diphtheria toxoid boosters are recommended for youngsters and adults to improve the relatively poor immunity status against diphtheria in the population.

Diphtheria↗
PubMed1993

[Epidemiologic situation of diphtheria in the European region of the World Health Organization in 1992 and during the first half of 1993].

In sixties and seventies small number of diphtheria cases was registered in European countries and diphtheria seems to go to be eliminated. Between 1982 and 1985 the first wave of diphtheria epidemic, and since 1990 the second wave were observes. Majority of cases during the first epidemic was registered in Soviet Union, but also in Germany, Italy, Portugal, Turkey and Sweden. Since 1990 increasing numbers of cases were registered in Russia and Ukraine. Some imported cases from these countries were observed in Bielorussia, Lithuania, Latvia, Estonia, Poland, Finland, Norway. Prophylactic measures undertaken in Russia and Ukraine were not sufficient. Shortage of vaccines were the most important reason of this situation. In 1992 one case and in first six months of 1993 five cases of diphtheria were imported in Poland. Production of Td vaccine started in Poland in 1991 and vaccination of adolescents in 19 as well as vaccination of some risk groups were introduced especially in the east port of country.

Adolescent↗
PubMed1993

[Granule-accumulation in VERO cells used for determination of antitoxin titration by micro cell culture method: II. Nature of granules and influence on the potency testing of diphtheria toxoid].

Accumulation of granules occurs in VERO cells when mouse serum was added in high concentration. The nature of the granule and influence of the granule-accumulation on the potency testing of diphtheria antitoxin were studied. The concentration of triglyceride in VERO cells increased 15 folds after 24 hours of incubation by the addition of undiluted mouse serum. Kinetical study of the increase of triglyceride and electron microscope observation suggested that the accumulated granules might be oil droplets with an average diameter of 0.27 micron. The end point reaction of neutralization of diphtheria toxin by the standard antitoxin was analyzed by the addition of mouse serum to the micro cell culture using VERO cells. The mean values of the end point reactions in the cell cultures added with high concentrations of mouse serum were -2.324, -2.338 and -2.346, while that of the control group was -2.343. The variance of these mean values in the experiment and control groups were 0.0017, 0.0024, 0.0017 and 0.0021, respectively. A test of homogeneity of variance for these data showed no significant difference between them. Furthermore, antitoxin titer of the serum specimens of mouse immunized with diphtheria toxoids determined by the micro cell culture method were compared with that obtained by rabbit skin test; a high correlation between the antitoxin titers by the two techniques was recognized. The results were comparable with those of guinea-pig sera. From these results it is evident that little influence, if any, was observed in the potency testing of diphtheria antitoxin using VERO cells, in spite of the remarkable accumulation of granules.

Animals↗
PubMedDate not supplied

[The determination of diphtheria toxin in circulating immune complexes].

A method for measuring the level of diphtheria toxin in the circulating immune complexes is proposed, making use of monoclonal antibodies to COOH-terminal site of the toxin molecule. The levels of diphtheria toxin were measured in children with different clinical forms of oropharyngeal diphtheria. Levels and time course of toxin for each clinical forms have been defined. The studies demonstrated the specificity of the method and its efficacy for rapid diagnosis of diphtheria.

Adolescent↗
PubMed1997

Management of school leavers given a diphtheria and tetanus vaccine intended for children instead of the intended low dose preparation.

In November 1995, 102 school leavers in two North Staffordshire schools were given high dose diphtheria and tetanus vaccine (intended for primary immunisation of children) rather than a preparation with a low dose of diphtheria vaccine intended for adults and adolescents. We describe the management of the incident and the action taken to minimise the risk of such an error being made again. Pupils who had received the high dose vaccine and a control group were surveyed with a self-administered questionnaire. Thirteen children out of 67 given the higher dose diphtheria vaccine consulted their general practitioner and the same number had time off school, compared with none of 25 from a control school. This excess morbidity was probably attributable to the higher dose of diphtheria vaccine.

Absenteeism↗
PubMed1997

Antibody levels to diphtheria, tetanus, and rubella in infants vaccinated while on PD: a Study of the Pediatric Peritoneal Dialysis Study Consortium.

To determine whether infants who receive routine childhood immunizations while on chronic peritoneal dialysis (CPD) develop protective antibody levels/titers, we measured antibody levels/titers in infants vaccinated with diphtheria/tetanus/pertussis (DTP) and measles/mumps/rubella (MMR) while on CPD. Eight CPD patients (median age 19 months, range 9-39 months) had measurement of antibody to diphtheria and tetanus toxoids. Seven of the 8 (88%) had protective levels of IgG antibody to both toxoids. The single patient who did not have protective antibody to either diphtheria or tetanus had a low total serum IgG. However, 3 other patients who had low IgG had protective antibody levels. Serial measurements of antibody to tetanus and diphtheria were obtained in 3 of the 8 patients. All maintained protective levels to both diphtheria and tetanus toxoids for as long as 24 months postvaccination. Antibody to rubella was also measured in 5 CPD patients (median 29 months, range 19-39 months), and all had protective antibody titers despite the fact that 3 had low total serum levels. In conclusion, most but not all infants immunized while on CPD have protective antibody levels/titers to diphtherial, tetanus, rubella. Alteration of the routine schedule for immunizations does not appear to be necessary. However, periodic measurements of antibody may be indicated, particularly to live vial vaccines, prior to transplantation.

Antibodies, Bacterial↗
PubMed1998

[Isoenzymes of transferases in serum from diphtheria patients].

AIM: Investigation of serum spectrum of isoenzymes AlAT, AsAT, GGT in diphtheria in adults. MATERIALS AND METHODS: The serum spectrum of cytoplasmic and mitochondrial isoenzymes AlAT, AsAT, GGT were studied in 12 bacterium carriers and 65 patients with diphtheria. Quite original evidence has been obtained on mechanism of hyperenzymemia. RESULTS: Diphtheria is associated with enhanced activity of cytoplasmic isoenzymes in correlation with intoxication severity. Spectrum of isoenzymes AlAT and especially GGT shifted to the side of mitochondrial fractions. There were no statistically significant differences in the activity and spectrum of isoenzymes in myocarditis and in its absence. In clinical recovery the spectrum of isoenzyme activity remained changed. CONCLUSION: It is suggested that dysisoenzymemia is related to active role of hepatocytes in utilization of diphtheria toxin, that carriers are not healthy people as hyperenzymemia is associated with morphological changes in the myocardium.

Adolescent↗
PubMed2000

Diphtheria in Lithuania, 1986-1996.

Diphtheria reappeared in Lithuania in 1986 and rose to epidemic levels by 1992. Between 1991 and 1996, 110 cases of diphtheria were registered, with an incidence of 0.03-1.15/100,000 population. Most cases (84%) and all 17 deaths occurred among persons >/=15 years, most of whom had never been vaccinated. Persons 40-49 years old had the highest average annual age-specific morbidity (1.70/100,000) and mortality (0.53/100,000) rates. Low levels of immunity among individuals 40-49 years old and migration to epidemic areas in Russia and Belarus contributed to the epidemic's occurrence. Between 1991 and 1995, toxigenic Corynebacterium diphtheriae strains were isolated from 84 of all registered patients (76%), and nontoxigenic strains were isolated from 13 (12%). By 1996, two mass vaccination campaigns, which provided one dose of vaccine to individuals 25-30 years old and three doses of vaccine to persons 31-60 years old, helped reduce the number of cases. The first campaign achieved 69% coverage; the second achieved 48% coverage.

Adult↗
PubMed2001

Calibration of replacement international standard and European Pharmacopoeia Biological Reference Preparation for Diphtheria Toxoid, Adsorbed.

We report here the characterisation of a preparation of diphtheria toxoid, adsorbed, and its calibration by twenty laboratories in fourteen countries in terms of the Second International Standard (I.S.) for Diphtheria Toxoid, Adsorbed, coded sample A (DIXA) using the established World Health Organisation (WHO)/European Pharmacopoeia (Ph Eur) challenge methods. The replacement standard preparation was found to have a unitage of 160 IU/ampoule on the basis of its calibration by in vivo bioassay. Stability was assessed within the collaborative study, and as part of candidate characterisation. Results suggest that the replacement standard will have satisfactory stability. This study also provided an opportunity to investigate serology as alternative to in vivo bioassay for potency testing of diphtheria vaccines. Six laboratories participated by performing serology according to in-house protocol. The calibration of the replacement standard in a mouse Vero cell assay gave a significantly higher results than in the established WHO/Ph Eur methods. Based on the results of this study and with the agreement of participants, the candidate standard was established as the Third International Standard for Diphtheria Toxoid, Adsorbed (coded 98/560) by the WHO Expert Committee of Biological Standardization in October 1999. The same preparation was also established as the second Ph Eur Biological Reference Preparation (Ph Eur BRP, batch no. 3) by the Steering Committee of the Biological Standardisation Programme of the European Directorate for the Quality of Medicines and approved by the European Pharmacopoeia Commission.

Adsorption↗
PubMed1996

Low prevalence of diphtheria immunity in the population of Florence, Italy.

A seroepidemiological study was conducted in 1994 on a representative sample of the population of Florence in order to verify the immunity coverage against diphtheria. Subjects were divided according to sex and age class. Sera from each selected class were at least 1.5/1000 of the residing population. Diphtheria antitoxin was titrated using a quantitative ELISA test. The results show an overall adjusted prevalence of diphtheria immunity (> or = 0.01 IU/ml) equal to 63.7%. Subjects of younger age classes have good protection levels (85.5% immune under 30 years), while only half individuals aged > or = 50 years have antibody titres > or = 0.01 IU/ml. Full protection (antibody titre > or = 0.1 IU/ml) was detected only in a very small proportion of those aged > or = 40 years. Our data show (1) how a recrudescence of diphtheria could theoretically take place in older subjects living in Italy, and (2) stress the importance of periodical re-vaccination of adults.

Adolescent↗
PubMed1978

Diphtheria-toxin-resistant mutants of CHO cells affected in protein synthesis: a novel phenotype.

Stable mutants highly resistant to the protein-synthesis-inhibitor diphtheria toxin have been selected in Chinese hamster ovary (CHO) cells. Protein synthesis in extracts of mutant cells is resistant to the inhibitory action of diphtheria toxin, indicating that the lesion has affected the protein-synthesis machinery. However, about 50% of the elongation factor-2 (EF-2) activity in the mutant cells can still be ADP-ribosylated by diphtheria toxin, and this remaining EF-2 activity is similar to that present in the wild-type cells. We suggest that this result is best explained by assuming that our CHO cells contain two functional copies of the EF-2 gene, and that only one of the copies is altered in the mutants. According to this view, the mutated allele produces EF-2 resistant to ADP-ribosylation which is capable of supporting cell growth in the presence of diphtheria toxin. Although the Dipr marker seems to act dominantly in the parental CHO cells, its behavior in Dipr X Dips hybrids (CHO X CHO) is recessive as measured by cell survival in presence of the toxin. This paradoxical behavior may be due to a gene dosage effect. Segregation studies from hybrids show that the Dipr marker segregates independently of the Emtr and Thgr markers indicating that the Dipr locus is not linked to either the Emtr locus or to the X chromosome.

Adenosine Diphosphate Sugars↗