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A multicentre serosurvey on diphtheria immunity in a French population of 1004 subjects.

Diphtheria immunity was determined in serum specimens obtained in 1994 from 1004 subjects seen in emergency departments of three distant French cities. An enzyme immunoassay was used to measure serum diphtheria antitoxin concentrations according to the following criteria: (a) antitoxin < 0.01 IU/ml: susceptibility, (b) 0.01-0.09 IU/ml: basic protection, (c) > or = 0.10 IU/ml: full protection. Among these patients, 20.3% were fully susceptible to diphtheria, 30.3% had basic but doubtful protection and only 49.4% were fully protected. Protection was different by age-groups: 73.5% of the subjects under 40 years of age, 46% between 40 and 65 and 33% over 65 were fully protected. Protection decreased with increasing age (p < 0.001)and was greater for men than women after 40 years of age (p < 0.001). The results of this exploratory study indicate that the enhancement of diphtheria immunity by boosters in adult population should be reconsidered in France as well as in many industrialized countries.

Adolescent↗

Diphtheria in Latvia, 1986-1996.

After nearly two decades without a diphtheria case in Latvia, the disease reappeared in 1986. From 1990 to 1996, case counts were highest among adults 40-49 years of age, school-aged children, and adolescents. Nonetheless, the average annualized incidence of disease was highest among infants and preschoolers. In August 1995, mass vaccination efforts began to provide adults 25-60 years of age with at least one dose of vaccine. By the end of the year, a 77% coverage rate was achieved, resulting in a decrease of reported diphtheria cases by 1996. From February to September 1997, special outreach efforts were focused on hard-to-reach populations; as a result, by June 1997, 55% of adults had received three doses of vaccine. While decreases in the incidence of and morbidity from diphtheria have occurred, additional efforts still need to be concentrated on improving vaccination coverage in adults and children <2 years of age and in reducing mortality from diphtheria.

Adolescent↗

Direct polymerase chain reaction for detection of toxigenic Corynebacterium diphtheriae strains from the Republic of Georgia after prolonged storage.

A total of 226 paired nose and throat swab specimens from 113 clinical diphtheria cases from the republic of Georgia were analyzed by direct polymerase chain reaction targeting both A and B subunits of the diphtheria toxin gene, tox. Even after prolonged transport and extensive storage (7-14 months) of the clinical specimens in silica gel packages, direct polymerase chain reaction detected the diphtheria tox gene in 54% of the specimens. Specimens obtained by throat swab were three times more likely than those obtained by nose swab to be positive for Corynebacterium diphtheriae.

Case-Control Studies↗

Tetanus and diphtheria antitoxin levels following a hospital-based adult immunization program.

A hospital-based program to immunize adults against tetanus unless specific contraindications to immunization are present has been in effect at Parkland Memorial Hospital since 1959. Adsorbed tetanus toxoid was used from 1959 to 1970, and was replaced at that time by adult type adsorbed combined tetanus/diphtheria toxoid. In the present survey, the titers of diphtheria and tetanus antitoxins were determined in sera from 97 adults admitted to the Medical Service. Titers of diphtheria antitoxin less than 0.0125 units per ml were found in only seven patients and less than 0.0125 units per ml of tetanus antitoxin in only 17 patients. This high prevalence of immunity especially to tetanus appears to reflect our practice of routine immunization of adults. Although the recommended frequency of tetanus boosters has recently been reduced for adults who have completed a full primary immunization series, susceptibility to diphtheria or tetanus or both is not uncommon among adults in the US. Unless contraindications are present, we therefore urge routine immunization of all adults seeking medical care and of all hospital personnel as a means of diminishing the risk of diphtheria and tetanus in those adult populations with a significant incidence of susceptibility to these diseases.

Adolescent↗

Corynebacterium diphtheriae endocarditis.

Two patients with Corynebacterium diphtheriae endocarditis have been observed in the past ten years. Both cases occurred sporadically. In one case toxigenic C. diphtheriae caused endocarditis in an immunized child with congenital heart disease. The second patient developed rapidly progressive valve destruction caused by a nontoxigenic strain of C. diphtheriae. These cases illustrate that C. diphtheriae may produce endocarditis in addition to its previously described diseases spectrum.

Child, Preschool↗

Diphtheria immunity in Massachusetts--a study of three urban patient populations.

To determine the status of diphtheria immunity among our patients, we measured diphtheria antitoxin levels in three separate patient populations. The technique used was toxin neutralization in rabbit skin, which allowed us to evaluate the immune status of individual patients. We studied an emergency room population, a sampling of inpatients from an urban teaching hospital, and a group of older patients from a chronic care hospital. Overall, approximately 80% of patients had adequate diphtheria antitoxin levels in their serum. However, two subgroups emerged with lower levels, with potential nonimmunity. These were certain young patients, either foreign born or with a potentially "immunocompromising disorder," and the elderly chronically ill. We conclude that while overall diphtheria immunity in our patients appears adequate, subgroups with increased risks do exist and immunization for these subgroups should be undertaken.

Adolescent↗

Influence of high titers of maternal antibody on the serologic response of infants to diphtheria vaccination at three, five and twelve months of age.

Diphtheria antitoxin was determined in serum from 44 pregnant women, of whom 26 had received one injection of diphtheria toxoid during pregnancy. Their infants were vaccinated with a combined diphtheria-tetanus vaccine at 3, 5 and 12 months of age. This vaccination schedule has been used in Sweden since 1986, replacing the old schedule of vaccination at 3, 4.5 and 6 months of age originally designed for diphtheria-tetanus-pertussis vaccine, which had not been used after cessation of general vaccination against pertussis in 1979. Serum samples from the infants were obtained at 3, 7 and 18 months of age. After 2 injections infants of mothers with high antitoxin titers, > or = 0.1 IU/ml, tended to have lower antitoxin titers than infants of mothers with low antitoxin concentrations (P = 0.067). All children had, however, antitoxin above the minimum protective level of 0.01 IU/ml. Median antitoxin titers were 1.6 IU/ml in both groups after the third booster injection. Four infants of mothers who had been vaccinated during pregnancy and who had titers of > or = 0.4 IU/ml did not reach the 0.1 IU/ml level after 2 injections: all 4 responded with high antitoxin titers after the third dose. Thus all infants were primed by 2 doses of vaccine, irrespective of maternal antibody concentration. The repressive effect of maternal antibody on titers noted after 2 doses was no longer observed after the third, booster dose.

Antibodies, Viral↗

Reduced immunogenicity of diphtheria and tetanus toxoids when combined with pertussis toxoid.

The effect of pertussis toxoid on the immunogenicity of diphtheria and tetanus toxoids (DT) was studied during a double blind efficacy trial of an acellular pertussis vaccine. Infants received DT with or without pertussis toxoid at 3, 5 and 12 months of age. Geometric mean concentrations were higher in the DT than in the DT-pertussis toxoid group 1 month (diphtheria toxoid 4.76 versus 3.58 IU/mL, P = 0.009; tetanus toxoid 4.42 versus 2.66 IU/mL, P < 0.0001) and 2 years after the third injection (diphtheria toxoid 0.15 versus 0.10 IU/mL, P < 0.0001; tetanus toxoid 0.38 versus 0.18 IU/mL, P < 0.0001). Pertussis toxoid causes a small but significant reduction of the immunogenicity of diphtheria toxoid and tetanus toxoid.

Animals↗

Development of a real-time fluorescence PCR assay for rapid detection of the diphtheria toxin gene.

We developed and evaluated a real-time fluorescence PCR assay for detecting the A and B subunits of diphtheria toxin (tox) gene. When 23 toxigenic Corynebacterium diphtheriae strains, 9 nontoxigenic C. diphtheriae strains, and 44 strains representing the diversity of pathogens and normal respiratory flora were tested, this real-time PCR assay exhibited 100% sensitivity and specificity. It allowed for the detection of both subunits of the tox gene at 750 times greater sensitivity (2 CFU) than the standard PCR (1,500 CFU). When used directly on specimens collected from patients with clinical diphtheria, one or both subunits of the tox gene were detected in 34 of 36 specimens by using the real-time PCR assay; only 9 specimens were found to be positive by standard PCR. Reamplification by standard PCR and DNA sequencing of the amplification product confirmed all real-time PCR tox-positive reactions. This real-time PCR format is a more sensitive and rapid alternative to standard PCR for detection of the tox gene in clinical material.

Corynebacterium diphtheriae↗

Emergence of an invasive clone of nontoxigenic Corynebacterium diphtheriae in the urban poor population of Vancouver, Canada.

Invasive disease due to Corynebacterium diphtheriae is rare in North America. Here we describe the emergence of a predominant clone of a nontoxigenic strain of C. diphtheriae in the impoverished population of Vancouver's downtown core. This clone has caused significant morbidity and contributed to at least two deaths. Over a 5-year period, seven cases of bacteremia due to C. diphtheriae were detected in patients admitted to Vancouver hospitals. Injection drug use, diabetes mellitus, skin colonization/infection with C. diphtheriae, and homelessness all appeared to be related to the development of bacteremia with the organism. Ribotyping of isolates recovered from blood culture revealed a predominant ribotype pattern that has not previously been reported in North America.

Adult↗

Diphtheria antitoxin levels in the Netherlands: a population-based study.

In a population-based study in the Netherlands, diphtheria antitoxin antibodies were measured with a toxin-binding inhibition assay in 9, 134 sera from the general population and religious communities refusing vaccination. The Dutch immunization program appears to induce long-term protection against diphtheria. However, a substantial number of adults born before the program was introduced had no protective diphtheria antibody levels. Although herd immunity seems adequate, long-term population protection cannot be assured. As more than 60% of orthodox reformed persons have antibody levels lower than 0.01 IU/ml, introduction of diphtheria into religious communities refusing vaccination may constitute a danger of spread of the bacterium.

Adolescent↗

Laboratory guidelines for the diagnosis of infections caused by Corynebacterium diphtheriae and C. ulcerans. World Health Organization.

These guidelines represent an application of the World Health Organization European Region's manual for the laboratory diagnosis of diphtheria for laboratories in the United Kingdom (UK), but they could be applied to laboratories overseas. The manual was rewritten in response to the re-emergence of diphtheria in eastern Europe and the emergence of other infections caused by Corynebacterium diphtheriae and C. ulcerans in the UK and overseas. The guidelines summarise our current recommendations and procedures for the microbiological diagnosis of infections caused by toxigenic and non-toxigenic isolates of corynebacteria, with particular reference to C. diphtheriae and C. ulcerans.

Adolescent↗

[Pathogenicity factors of Corynebacterium diphtheriae circulating in the Primorski region under conditions of mass immunization of population].

The study of the main pathogenicity factors of C. diphtheriae (adhesive activity, toxigenicity, detection of tox+ gene) circulating in the Primorski Territory has been made. As revealed in this study, at the period of declined epidemic process due to mass immunization of the adult and child population against diphtheria the selection of C. diphtheriae strains with weak toxigenicity and low adhesiveness was observed. No strains having tox+ genes have been detected among C. diphtheriae nontoxigenic strains circulating in the Primorski Territory.

Adult↗

[First confirmed case of laryngeal diphtheria in Djibouti].

The first bacteriologically confirmed case of laryngeal diphtheria in Djibouti was reported in 1998. It involved a three-year-old native-born infant who had been vaccinated during the first year of life with three doses of a combined vaccine against diphtheria, tetanus, poliomyelitis, and pertussis. A rapid clinical improvement was observed under erythromycin treatment. Other cases of laryngeal diphtheria have been observed. It is important to reverse decreasing vaccinal coverage in Djibouti and to warn incoming travelers of the need to be adequate immunized against diphtheria. Enhanced epidemiologic surveillance of this disease is also needed.

Child, Preschool↗

International standardization of diphtheria toxoids.

The present report is an analysis of results of assays of diphtheria toxoids carried out over a four-year period at the Laboratory of Hygiene, Department of National Health and Welfare, Ottawa, Canada. A single preparation, a crude monovalent diphtheria toxoid, was used as a reference standard for all types of preparation (purified, crude, or adsorbed). The results suggest that the use of such a standard is justified even though there is evidence to show that adsorbed and plain toxoids, and toxoids of different grades of purity, do not have identical immunization curves. The merits of the present International Standard for Diphtheria Toxoid, Plain, for the assay of all types of toxoid are discussed. The results suggest that this is not particularly suitable for adsorbed preparations, probably because of its flatter immunization curve. For the latter preparations, the proposed international standard for diphtheria toxoid, adsorbed, should prove more practical and useful.

Biological Assay↗

Problems concerning the prophylaxis, pathogenesis and therapy of diphtheria.

The first part of this article on the prophylaxis, pathogenesis and therapy of diphtheria is devoted to an epidemiological survey of the results achieved with active immunization against the disease. From these results it can be concluded that active immunization has been largely responsible for the decrease in the morbidity and mortality rates which has taken place in the past half-century.In the second part, the authors deal at length with problems relating to the pathogenesis and therapy of the disease, discussing such subjects as the different types of diphtheria bacteria, the significance of non-virulent strains, the action of bacteriophages, the plurality of diphtheria toxin, the use of antibacterial sera, and the importance of the "avidity" of antitoxic sera.Finally, taking into consideration the data presented in the preceding parts, the authors put forward their views as to the cause of diphtheria, the measures which should be taken to control it, and the most satisfactory form of therapy.

Anti-Bacterial Agents↗

[Cytopathogenic effect of diphtheria exotoxin in cultured chick embryo fibroblasts].

One hundred fifty strains of Corynebacterium diphtheriae were studied from patients with symptoms of diphtheria and from healthy persons. 136 strains (90.67%) belonged to the mitis biotype, 12 (8.0%) and 2 (1.33%) to gravis and intermedius biotypes respectively. Toxigenicity was determined by traditional in vivo methods with rabbits and plaque immunodiffusion in KL-virulence medium. From the 136 mitis biotype strains studied, 130 (95.58%) showed positive toxigenicity by both methods and 11 strains (91.66%) from gravis biotype and 2 (100%) of intermedius biotype gave same results. The cellular cytotoxicity of the diphtheriae toxin was tested on culture of chicken embryo fibroblast and were positive in 132 (97.05%) strains of mitis biotype, and in all strains of gravis and intermedius biotypes. These results suggest that the cytotoxicity test seems to be a more sensitive method for detecting diphtheriae toxin production.

Animals↗

[Interrelationship between toxigenic and non-toxigenic diphtheria microbes in the epidemic process].

A study of the circulation of toxigenic and nontoxigenic diphtheria bacilli was carried out in several carrier state foci under conditions of a natural course of the epidemic process. There were 2623 persons under observation. A total of 32158 analyses were carried out, and 2271 strains were isolated and studied. No formation of the toxigenic variants of diphtheria bacillus as a result of phage conversion was revealed in the foci of carrier state despite the wide spread in them of nontoxigenic lysosensitive cultures capable of acquiring the toxigenic properties under experimental conditions, and of the cultures which had converting corinephages. Thus, autonomy of the circulation of the toxigenic and nontoxigenic diphtheria bacilli occurred in the carrier state foci; the leading role in the change of the diphtheria bacillus type belonged to reinfection.

Bacteriophage Typing↗