Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “DIPHTHERIA”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 613 records · Page 34Linked to original sources
PubMedDate not supplied

Exit-site infections by non-diphtheria corynebacteria in CAPD.

Non-diphtheria corynebacteria species cause disease in risk populations such as immunocompromised patients and patients with indwelling medical devices. Despite reports of exit-site infection and peritonitis caused by non-diphtheria corynebacteria, these organisms are frequently dismissed as contaminants. During a 10-year observation period, we prospectively identified 8 cases of exit-site/tunnel infections caused by 2 different species of corynebacteria (Corynebacterium striatum in 5 and C. jeikeium in 3 cases). Four patients experienced a second episode of exit-site infection 3 months (2 cases), 25 months, and 40 months, respectively, after termination of an oral cephalosporin therapy of 4 to 6 weeks' duration. Non-diphtheria corynebacteria accounted for 9% of all exit-site infections during the study period. All catheter-related infections healed; no catheter had to be removed. The diagnosis of catheter-related non-diphtheria corynebacteria infection may be suspected when Gram stain shows gram-positive rods and with colony morphology and commercial biochemical identification systems. Susceptibility of non-diphtheria corynebacteria to antibiotics may vary, especially in C. jeikeium. Virtually all Corynebacterium species are sensitive to vancomycin. Empirical antibiotic therapy with vancomycin should be initiated while antibiotic susceptibility testing is being carried out. Oral cephalosporin may be an alternative treatment regimen for exit-site infections if sensitive. This study highlights the importance of non-diphtheria corynebacteria as emerging nosocomial pathogens in the population of end-stage renal disease patients on on continuous ambulatory peritoneal dialysis.

Adult↗
PubMed1992

Clinical reactions and immunogenicity of the BIKEN acellular diphtheria and tetanus toxoids and pertussis vaccine in 4- through 6-year-old US children.

OBJECTIVE--To compare the immunogenicity and reactogenicity of a two-component acellular pertussis vaccine with a whole-cell diphtheria and tetanus toxoids and pertussis vaccine (W-DTP) when administered as a booster to children 4 through 6 years of age. DESIGN--This was a randomized, double-blind study. SETTING--Children in this study were from three general pediatric practices (two were private, one was university-affiliated). PARTICIPANTS--Three hundred and sixteen 4- through 6-year-old children who had received four previous W-DTP immunizations at the recommended times were studied. SELECTION PROCEDURES AND INTERVENTIONS--Children were randomly assigned in a 1:3 ratio to receive either W-DTP or one of three lots of acellular diphtheria and tetanus toxoids and pertussis vaccine (A-DTP). The A-DTPs contained 3.75 micrograms each of lymphocytosis promoting factor and filamentous hemagglutinin protein nitrogen per 0.5 mL and the same concentrations of diphtheria and tetanus toxoids as W-DTP. Serum samples were obtained on the day of immunization and 4 to 6 weeks later. Adverse reactions were recorded by parents at 6, 24, 48, and 72 hours. MEASUREMENTS AND RESULTS--An indirect enzyme-linked immunosorbent assay (ELISA) method determined IgG antibody response to lymphocytosis promoting factor, filamentous hemagglutinin, and tetanus toxoid; a CHO cell assay measured neutralizing antibodies to pertussis toxin; and serum neutralization on VERO cells assayed diphtheria antitoxin. One month after booster doses were administered, the geometric mean antibody levels for A-DTP vs W-DTP were IgG filamentous hemagglutinin, 362 vs 104 ELISA U/mL; IgG lymphocytosis promoting factor, 408 vs 81 ELISA U/mL; CHO cell, 210 vs 107; diphtheria, 21.7 vs 12.1 U/mL; and tetanus, 2.86 vs 2.04 Eq/mL. Following immunization with A-DTP, local and systemic adverse experiences were 30% to 50% and 20% to 30% fewer, respectively, as compared with W-DTP. CONCLUSIONS--The BIKEN A-DTP vaccine used in this study demonstrates enhanced immunogenicity to lymphocytosis promoting factor, filamentous hemagglutinin, and other measured antigens and less reactogenicity compared with licensed W-DTP [corrected].

Antibodies, Bacterial↗
PubMed2003

An experimental divalent vaccine based on biodegradable microspheres induces protective immunity against tetanus and diphtheria.

In an endeavor towards development of multivalent vaccines based on biodegradable microspheres, we tested the immunologic performance of several divalent microsphere formulations against tetanus and diphtheria. Microspheres were made by separate microencapsulation of tetanus and diphtheria toxoid in poly(lactide-co-glycolide) by either spray-drying or coacervation. Guinea pigs were subcutaneously immunized by a single injection of the divalent vaccines or, for control, an equivalent dose of a licensed vaccine containing both antigens adsorbed on aluminium hydroxide. All microsphere formulations were strongly immunogenic, irrespective of particle size and hydrophobicity. End point titers of ELISA antibodies, mainly of the IgG1 subtype, were comparable to those obtained after immunization with the licensed vaccine. The microspheres provided increasing levels of antibodies, during the 16 weeks of testing, and the antibodies were weakly polarized towards tetanus. The induced antibodies were also toxin neutralizing, as determined for both diphtheria (1-4 IU/mL) and tetanus (5-9 IU/mL) 8 weeks after immunization. These neutralization levels were several orders of magnitude above the level considered minimum for protection (0.01 IU/mL). When the animals were challenged with tetanus or diphtheria toxins 6 weeks after immunization, microsphere vaccines produced protective immunity that was comparable to or better than that induced by the licensed divalent vaccine. In conclusion, this study showed that a single administration of biodegradable microsphere vaccines provided protective immunity against diphtheria and tetanus, and that this immunization approach might be feasible for multivalent vaccines.

Animals↗
PubMed1995

High-yield production of diphtheria toxin mutants by high-density culture of C7 (beta)tox+ strains grown in a non-deferrated medium.

A high-density growth approach was utilized to produce mutated diphtheria toxin from two strains of Corynebacterium diphtheria: C7 (beta)(tox-201,tox-9) and C7 (beta)(tox-107). The cross-reacting mutants (CRM) of the diphtheria toxin are CRM9 and CRM107; both of them carry the mutation in their binding site and, as a result, have 1/300 of the systemic toxicity of the wild-type diphtheria toxin. Since iron inhibits diphtheria toxin production, the traditional approach has been to grow the bacteria in a very low iron concentration. The procedure described here involved the use of a modified, non-deferrated, growth medium that provided fast and high-density growth of the bacteria, and which, when associated with simultaneous depletion of glucose and iron, enhanced the toxin production. Oxygen-enriched air was supplied to enable the bacteria to grow to a cell density giving an absorbance of 70 at 600 nm (15-20 g/l dry weight). The maximum toxin concentration in the culture supernatant was 150 mg/l. The CRM products, which remained stable following microfiltration and ultrafiltration, could be easily purified using a two-step chromatography procedure.

Corynebacterium diphtheriae↗
PubMed2001

Epidemiology of three cases of severe diphtheria in Finnish patients with low antitoxin antibody levels.

During the 1990-1998 diphtheria epidemic in the newly independent states of the former Soviet Union, more than 150,000 infections and 5,000 deaths occurred. During this period, more than 10 million trips were made from Finland to Russia or vice versa. This resulted in only 10 cases of diphtheria in Finland. There was no secondary spread to healthcare workers or other close contacts. Three patients had severe respiratory tract diphtheria. All three were middle-aged men who had made a short visit to Russia, during which time they had intimate contact with local women. These findings suggest diphtheria was transmitted mainly by direct saliva contact. All patients with severe diphtheria had a non-protective level of antitoxin antibodies during the first days of the disease. Only the patient whose antibody titre rose rapidly to a protective level (>1 IU/ml) had an uncomplicated recovery. The other two, one of whom died, had myocarditis and severe polyneuropathy.

Adult↗
PubMedDate not supplied

Diphtheria immunity of Albanian and other eastern European immigrants in Greece compared with the local population--the risk of reemergence in Greece.

A large number of immigrants have come to Greece from diphtheria-endemic countries during the past 8 years. Information on the immune status against diphtheria among immigrants from Albania and the New Independent States (NIS) of the former USSR, as well as the Greek population, is essential in planning public health control measures. The main objective of the study was to determine the risk of the spread of diphtheria if new cases arrived in the country. Diphtheria antitoxin (DAT) in sera from 185 healthy individuals from northern Greece and 227 immigrants from Albania and the NIS was titrated using a quantitative ELISA test. The participants were adults aged 22 to 46 years. Titers were considered as protective when DAT levels were higher or equal to 0.1 IU/ml. Albanian immigrants exhibited the highest rates of protective titers (99 of 167, 59.3%), while lower immunity rates were detected among immigrants from the NIS (20 of 60, 33.3%) (1.5 < OR = 2.9 < 5.4, p = 0.0007) as well as among Greek participants (47 of 185, 25.4%) (2.8 < OR = 4.4 < 7.0, p = 0.00001). Immunity rates did not differ between Greek and NIS participants. DAT levels of persons with protective titers differed between the three population groups (analysis of variance, p = 0.0005), with the highest mean DAT values detected among NIS immigrants (0.613 IU/ml). Lower values were found among protected Albanians (0.482 IU/ml) and Greeks (0.314 IU/ml). There was no significant age- and sex-related difference in immunity rates and DAT levels among the groups. The low immunity rates among Greek adults might suggest that they have had no natural contact with toxigenic strains of corynebacteria. A booster dose of diphtheria toxoid for local adults is recommended, to reduce their risk of acquiring toxigenic strains from individuals who may carry the bacteria without exhibiting clinical disease.

Adult↗
PubMed1982

Characteristics of guinea-pig immune sera elicited by a synthetic diphtheria toxin oligopeptide.

Several oligopeptides of different lengths contained within the Cys 186-Cys 201 first disulfide loop of the diphtheria toxin molecule have been synthesized by a solid-phase method. 125I-labeled rabbit antibodies raised against diphtheria toxin reacted specifically with oligopeptides linked to m-nitrobenzhydrylamine resin when the amino acid chain length was equal to or greater than 10 residues. The synthetic tetradecapeptide (STDP) corresponding to the sequence Gly 188-Cys 201 was used to immunize guinea-pigs. The immune sera obtained reacted with the whole diphtheria toxin molecule as judged by an antigen-linked immunosorbent assay. Anti-STDP sera exhibited a clear, albeit limited, neutralizing effect against the lethal action of diphtheria toxin on cultivated Vero cells. The anti-STDP sera were also able to partially block the ADP-ribosylation of elongation factor 2 mediated by whole diphtheria toxin. In contrast, anti-STDP sera were almost inactive on the enzymic activities of either toxin fragment A or crm 45, a mutant protein which lacks the 15,000 mol. wt C-terminal sequence of the toxin molecule. On the basis of the results obtained, a possible localization of the Cys 188-Cys 201 loop region on the toxin molecule is proposed.

Animals↗
PubMed1987

Corynebacterium diphtheriae in the environment of carriers and patients.

A total of 533 throat and nasopharyngeal cultures were obtained from 328 staff who nursed cases of diphtheria and carriers of Corynebacterium diphtheriae; none yielded C. diphtheriae. Only one out of 189 environmental samples relating to 22 patients and carriers was positive. In addition, one carrier with chronic skin disease was found to have widespread colonization with C. diphtheriae. Several samples both from his hospital room and home yielded C. diphtheriae, indicating that he was a 'disperser.'

Carrier State↗
PubMed1989

Immunity to diphtheria in a sample of adult population from central Italy.

A sample of 643 healthy subjects from central Italy aged 20 to 80, were screened for diphtheria antitoxin. Serum diphtheria antitoxin was assayed by a new passive haemagglutination technique using turkey red blood cells sensitized with diphtheria toxoid, after having performed a correlation study between this technique and the reference in vivo neutralization test. Of the studied population 26.7% showed a lack of serum antitoxin titres considered to be protective. The rate of susceptible subjects increased with age, showing the highest value (38.9%) in the sixth decade of age. Males proved less protected than females; 53.2% of the male population aged 50-59 were lacking a protective anti-diphtheria immunity. On the basis of present results, a periodical revaccination of the entire adult population with reduced doses of diphtheria toxoid would be advisable.

Adult↗
PubMed1995

Immunoglobulin E responses to diphtheria and tetanus toxoids after booster with aluminium-adsorbed and fluid DT-vaccines.

Immunoglobulin E responses to diphtheria and tetanus toxoids were investigated in pre- and postbooster samples of 104 children given, at 10 years of age, a DT booster with either an adsorbed (n = 51) or a non-adsorbed, fluid vaccine (n = 53). Vaccination with adsorbed DT is part of a national immunisation programme and represents the first regular booster given to these children, primarily immunised with three doses of adsorbed DT at age 3-6 months. The vaccines, with a content of 30 Lf of diphtheria toxoid and 7.5 Lf of tetanus toxoid per millilitre, were given for booster in a dose of 0.25 ml as a deep subcutaneous injection. In the prebooster samples, 3 and 14% had measurable IgE to diphtheria and tetanus, respectively. These rates rose to 94 and 92% in the postbooster samples, respectively. The median (range) of IgE to tetanus among recipients of the adsorbed vaccine was 0.59 PRU ml-1 (< 0.1-17.5), as compared to 0.27 (< 0.1-8.22) in the recipients of the fluid vaccine (p = 0.027). The median IgE response to diphtheria toxoid in the whole group was 1.8 (< 0.1-17.5), with no significant difference between the two vaccines (p = 0.76). There was no correlation between the IgE and IgG responses (r < 0.07, p > 0.5) but the two IgE responses as well as the ratios of IgG/IgE showed strong correlations (r > 0.7, p < 0.001). The study thus revealed unexpectedly high rates of IgE responses to diphtheria and tetanus toxoids in a regular DT booster vaccination programme, which were associated to high rates of local side effects.(ABSTRACT TRUNCATED AT 250 WORDS)

Adjuvants, Immunologic↗
PubMed1996

Immunization against diphtheria with special emphasis on immunization of adults.

A massive diphtheria epidemic in Eastern Europe has resulted in increased anxiety that this disease could spread to other countries. This fear is realistic because there is a gap in the diphtheria immunity in large segments of the adult population in many industrialized countries. Experience to date suggests that an immunity gap in adults coupled with the presence of large numbers of susceptible children and adolescents creates the potential for an extensive epidemic. To prevent epidemics, countries should consider the immunogenicity and duration of protection provided by diphtheria toxoid given to children in the primary series and as booster doses. This paper reviews general issues related to the formulation of diphtheria immunization strategies, especially the need for booster doses in adults and the rationale for use of lower-strength diphtheria toxoid for persons older than 6 years of age.

Adult↗
PubMed2026

Molecular epidemiology and antimicrobial resistance determinants of Corynebacterium diphtheriae causing infections in Karachi, Pakistan, 2023-2024.

OBJECTIVES: Diphtheria remains endemic in Pakistan, with cases increasing following the COVID-19 pandemic despite ongoing vaccination programs. This study analyzes the genomic diversity, virulence, and antimicrobial resistance patterns of pharyngeal diphtheria strains collected during the Karachi outbreak. METHODS: Corynebacterium diphtheriae isolates from a tertiary care hospital laboratory in Karachi (August 2023-October 2024) were included. Antimicrobial susceptibility testing and whole-genome sequencing of phenotypically confirmed isolates were performed. Phylogenetic and bioinformatics analyses were performed using diphtOscan and AMRFinderPlus tools. RESULTS: A total of 47 pharyngeal C. diphtheriae isolates were included. The median age of patients was 7 years, and the male-to-female ratio was 1.6:1. The tox gene was present in 89.4% of isolates, while only 29% (n = 13/45) demonstrated toxin production. Genomic analysis identified 10 sequence types; ST384 and ST698 were most prevalent. Phenotypically, 34% (n = 16) were resistant to both erythromycin and penicillin, and 49% (n = 23) were multidrug-resistant. The most prevalent resistance genes were sul1 (100%), erm(X) (76.6%), and pbp2m (51.1%). CONCLUSION: Circulation of diverse C. diphtheriae strains with alarming antimicrobial resistance underscores the need for genomic surveillance to evaluate transmission trends. We further highlight the limitations of the Elek test in detecting toxin production and the need for improved diagnostics in low- and middle-income countries.

Antimicrobial resistance↗
PubMed2004

Anti-diphtheria antibody seroprotection rates are similar 10 years after vaccination with dTpa or DTPa using a mathematical model.

The reduced antigen content diphtheria, tetanus and pertussis (dTpa) vaccine (Boostrixtrade mark) has been shown to induce a strong booster response to all the vaccine components in 4-6 year olds. However, anti-diphtheria antibody levels were observed to be lower when compared to the "full strength" paediatric DTPa vaccine. To assess the impact of this difference on long-term protection, a mathematical model was developed to predict diphtheria antibody decay over time. The model was based on a linear decrease in log-transformed antibody concentrations after the first year post-vaccination. When applied to data collected 3.5 years after vaccination of 4-6 year olds with either DTPa or dTpa, the model predicted that 10 years post-vaccination, 98.6% of subjects vaccinated with dTpa were likely to remain seroprotected against diphtheria, compared to 99.6% vaccinated with DTPa. Therefore, the difference observed in diphtheria antibody geometric mean concentrations 1 month after booster vaccination at 4-6 years with dTpa or DTPa is unlikely to be of clinical relevance 10 years later at the time of the adolescent booster.

Adult↗
PubMed1999

Evaluation of single- and dual antigen delayed fluorescence immunoassay in comparison to an ELISA and the in vivo toxin neutralisation test for detection of diphtheria toxin antibodies.

An evaluation of the delayed fluorescence immunoassay (Delfia) against an ELISA method for determination of diphtheria antitoxin levels in serum was performed. The Delfia was also validated in the in vivo toxin neutralisation test (Txn) in rabbits. Two variants of the Delfia were studied, a single-antigen Delfia (sDelfia) with only the diphtheria toxin included and a dual-antigen Delfia (dDelfia) with tetanus toxoid included for simultaneous detection of antibodies against two antigens. The diphtheria antitoxin cut-off levels in the sDelfia and the dDelfia were 0.004 and 0.002 AU/ml, respectively, which is lower than the internationally accepted level showing any protection against diphtheria (0.01 IU/ml). Both Delfia variants showed good correlation with the ELISA procedure above the ELISA cut-off level of 0.02 AU/ml. Results from samples assayed in the in vivo Txn assay indicated that the low antitoxin levels detected by the Delfia were valid. These results show that the Delfia could be considered as an in vitro reference method for detection of diphtheria antitoxin in seroepidemiological surveys and vaccine studies.

Animals↗
PubMed1987

A comparison of the indirect haemagglutination test with the toxin neutralization test for the estimation of diphtheria antitoxin in mouse sera.

Serum samples from 42 groups of mice immunized for different immunization periods with various doses of Adsorbed Diphtheria-Tetanus Vaccine, Adsorbed Diphtheria-Tetanus and Pertussis Vaccine and a standard diphtheria toxoid were assayed for their diphtheria antitoxin content by indirect haemagglutination (IHA) and by toxin neutralization (TN) tests. A very good correlation of 0.91 was obtained between the results of the two methods. There was no statistically significant difference between the IHA and the TN titres obtained. Adsorption with sheep red cells and treatment of the sera with 2-mercaptoethanol had no effect on the IHA titres. The minimum level of antitoxin detectable by the IHA test was 0.00039 IU ml-1. IHA proved to be a sensitive, specific and reproducible method which can be used reliably for the assay of diphtheria antitoxin in mouse sera.

Animals↗
PubMed1999

Prevalence of diphtheria toxin antibodies in human sera from a cross-section of the Italian population.

A polycentric study was carried out between 1993 and 1995 in order to evaluate diphtheria immunity on a representative sample of population from different areas of Italy. To determine diphtheria antitoxin, sera from 5187 apparently healthy subjects, divided according to sex and age groups, were titrated using an ELISA indirect method. A basic protective titre of diphtheria antitoxin (> 0.01 IU ml-1) was found in 4080 (78.6%) subjects. No statistically significant differences between males and females were observed. Our findings show that the proportion of susceptibles increases with age and a high proportion of adults no longer has diphtheria antitoxin at protective levels since toxigenic C. diphtheriae circulation is presently lacking in Italy.

Adolescent↗
PubMed1990

Sandwich-dot immunobinding assay (Sandwich-DIA), a new immunological method for the detection of diphtheria toxin.

In this paper we describe a new assay for diphtheria toxin in bacterial cultures, based on a sandwich-dot immunobinding method. This method uses horse polyclonal diphtheria antitoxin as the coating antibody and mouse monoclonal diphtheria antitoxin as the detecting antibody. The sensitivity of this new method is within a range of 5-10 ng toxin per ml in Corynebacterium diphtheriae cultures. We did not observe any false-positive reactions. As a solid phase we used nitrocellulose disks which bind protein more strongly than the commonly used plastic solid phase. Results with strong toxin producers of C. diphtheriae can be obtained as soon as 11 h after starting a bacterial test culture. To detect weak toxin producers, the cultivation period must be extended to about 18 h and the results can be obtained after about 24 h. The method presented in this paper is simpler, faster and more reliable than currently used methods.

Corynebacterium diphtheriae↗
PubMed2001

The prevalence of diphtheria immunity in healthy population in Poland.

The degree of seroprotection against diphtheria in Poland was evaluated by determination of IgG antibodies to Corymebacterium diphtheriae toxin (IgG-DTAb). The study population consisted of 4,829 healthy subjects aged from 1 day to 85 years from 7 regions of Poland. Serum samples collected between 1996 and 1998 were assayed for IgG-DTAb antibodies using a toxoid enzyme immunoassay. Neutralization of toxin in Vero cells was performed as a reference method with the WHO standard for human diphtheria antitoxin. The study revealed a lack of seroprotection (IgG-DTAb < 0.1 IU/ml) in 23% of individuals, basic seroprotection (0.1-1.0 IU/ml) in 64%, and effective seroprotection (> 1.0 IU/ml) in 13%. The non-protected group consisted of non-vaccinated children below 2 months of age (10%), individuals between 2 months and 18 years old (20%) and greater than 19 years old (70%). Of the adults, 32% were seronegative, 63% had basic seroprotection and only 5% were fully protected; 43% of adults between 30 and 64 years, who had not been vaccinated at least during the previous 10 years were not protected against diphtheria. The geometric mean titre (GMT) of IgG-DTAb was 0.25 IU/ml in the total population. Age-related GMTs differed significantly from each other and were higher (0.44 IU/ml) in individuals from 2 months to 18 years old, compared with 014 IU/ml and 0.17 lU/ml in children under 2 months and adults, respectively. No significant difference was found in the GMTs of men and women in all age groups. We conclude that the currently used vaccination programme in Poland is highly effective and assures protection against diphtheria in the majority of the population in the 10-year period following the last booster. However, a significant proportion of adults between 30 and 64 years lack protection and this indicates a need for booster immunization for this group.

Adolescent↗