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PubMed1997

Serological survey on the immunity to diphtheria of the northern Greek population.

The recent outbreak of diphtheria in the Newly Independent States (NIS) of the former USSR and the immigration from these high risk areas to Greece prompted us to determine the diphtheria antitoxin levels by enzyme-linked immunosorbent assays (ELISA) in 509 healthy individuals (307 males and 202 females) from northern Greece. The population under study was divided in ten age groups from 1 day to > 60 years old. Diphtheria antitoxin levels of > or = 0.1 IU/ml were considered as protective ones. 44.6% of the examined people were found susceptible. The children up to their twenties seem to be immune to diphtheria in a high proportion (86-88.4%). The diphtheria antitoxin levels declined sharply above this age (17.6% in the age group 21-30 years old). The level of protection in adults appeared to be higher in the oldest group (49%). According to these results, the adults are not properly protected. Booster doses of vaccine for them are recommended to improve the resistance of the northern Greek population from possible infection by toxigenic stains of Corynebacterium diphtheriae, imported or endogenous.

Adolescent↗
PubMed2001

A 5-year follow-up on antibody response after diphtheria and tetanus vaccination in hemodialysis patients.

Chronic renal failure is associated with a T-cell-dependent immune defect. In the past, various studies have focused on the insufficient immune response to vaccination of hemodialysis patients. An impaired vaccination response rate has been reported for vaccines against hepatitis B, influenza, tetanus, diphtheria, and others. However, no data exist on the long-term success of vaccination against tetanus and diphtheria in these patients. The aim of the present study is to investigate seroresponse to tetanus and diphtheria vaccination over a 5-year period. Antibody levels were determined by enzyme immunoassay. Antidiphtheria antibody levels of 31 hemodialysis patients were determined 5 years after vaccination. After 5 years, 10 of 31 patients (32%) had a protective antibody level against diphtheria (>/=0.1 IU/mL), whereas 12 months after vaccination, 26 of 71 patients (37%) were protected. Also, mean antibody levels significantly decreased. Furthermore, antitetanus antibody levels of 21 patients simultaneously vaccinated against tetanus and diphtheria were investigated. After 5 years, 15 of 21 patients (71%) were protected compared with 46 of 71 patients (65%) in the hemodialysis collective studied after 12 months. In the interval between 1 and 5 years after vaccination, significantly more patients in the initial nonresponder group had died than in the responder group; therefore, the overall protection rate observed in vaccinated patients increased. Our results provide evidence that during a 5-year period, antibody persistence against tetanus toxoid is better than that against diphtheria toxoid. Therefore, detection of individual antibody concentrations may be indicated to decide on revaccination.

Antibodies, Bacterial↗
PubMed1988

Molecular epidemiology of the 1984-1986 outbreak of diphtheria in Sweden.

Despite mass vaccination against diphtheria, many people have antibody titers below the protective level of 0.01 IU per milliliter. A recent outbreak of diphtheria in Sweden caused 17 clinical cases of diphtheria in the city of Göteborg; three of the patients died. A satellite outbreak occurred in Stockholm after a few months' delay. Using a new genetic probe, we analyzed 36 strains of Corynebacterium diphtheriae isolated in Sweden and Denmark during the period 1976 to 1986. Although the 36 strains can be classified in 17 different groups of C. diphtheriae (several of them containing toxigenic strains), all the clinical and fatal cases of diphtheria were caused by isolates from the same group, strongly suggesting that the outbreak in Sweden was caused by a single strain that possibly had a virulence factor separate from toxigenicity. This strain may have been imported into Sweden from Denmark, since it was isolated for the first time in Copenhagen in 1983, before the outbreak in Sweden.

Corynebacterium diphtheriae↗
PubMed1992

Specific binding of the diphtheria tox regulatory element DtxR to the tox operator requires divalent heavy metal ions and a 9-base-pair interrupted palindromic sequence.

The structural gene for diphtheria toxin, tox, is carried by a family of closely related corynebacteriophages; however, the regulation of tox expression is controlled by a Corynebacterium diphtheriae-encoded regulatory element, dtxR. The molecular cloning and sequence analysis of dtxR was recently described. Previous studies have suggested that DtxR-mediated regulation of the diphtheria tox operator involves the formation of an iron-repressor complex, which specifically binds to the tox operator. We have expressed and purified DtxR from recombinant Escherichia coli. Immunoblot analysis shows DtxR to be a single M(r) 28,000 protein band in both recombinant E. coli and the C7(-) and C7hm723(-) strains of C. diphtheriae. In addition, we demonstrate that the binding of DtxR to a diphtheria tox promoter/operator probe requires the addition of Mn2+ to the reaction mixture; however, binding may be blocked by addition of the chelator 2,2'-dipyridyl, anti-DtxR antiserum, and excess unlabeled probe to the reaction mixture. Deletion of one of the 9-base-pair inverted repeat sequences from the tox operator results in a loss of DtxR binding. The results presented here demonstrate that regulation of diphtheria toxin expression by DtxR requires direct interaction between this regulatory factor and the tox operator in the presence of a divalent heavy metal ion.

Bacterial Proteins↗
PubMed2000

Diphtheria toxoid vaccine effectiveness: A case-control study in Russia.

Prior to the completion of this and other studies, low effectiveness of diphtheria toxoid-containing vaccine was suspected to be a major contributing factor to the diphtheria epidemic that began in the Russian Federation in 1990. A vaccine effectiveness study was done in Moscow by enrolling physician-diagnosed cases and 10 control subjects per case. Controls were matched to cases by age (+/-3 months) and clinic registration. Vaccination history was abstracted from a standardized form for case-patients and from clinic vaccination records for control subjects. Two hundred seventeen case-patients and 2169 matched controls were included in the study. Most controls (92%) had received three or more doses of a diphtheria toxoid vaccine, compared with 72% of case-patients. The vaccine effectiveness for three or more doses was 97% (95% confidence interval: 94.3-98.4). Low vaccine effectiveness was not a contributing factor to the diphtheria epidemic in the Russian Federation. To control and prevent diphtheria epidemics, it is necessary to achieve and maintain high vaccination coverage with three or more doses of diphtheria toxoid among adults and children.

Adolescent↗
PubMed2000

How many doses of diphtheria toxoid are required for protection in adults? Results of a case-control study among 40- to 49-year-old adults in the Russian Federation.

During the Russian diphtheria epidemic of the 1990s, adults had an unexpectedly high rate of disease. A retrospective, matched case-control study was done to measure the effectiveness of one, two, or three or more doses of diphtheria toxoid against diphtheria among 40- to 49-year-old Russians. Thirty-nine diphtheria case-patients and 117 controls were studied. Previous vaccinations were included if one dose was received within the previous 10 years. Five cases (13%) and 33 controls (28%) had received three or more doses of vaccine. The matched odds ratio was 0.3 (95% confidence interval, 0.1-0.9) for three or more doses compared with no doses, which was a vaccine effectiveness of 70% (95% confidence interval, 10-90). A trend existed toward milder disease with increasing doses (chi2 test for trend, P=.02). The results suggest that Russian adults, who were unlikely to have acquired immunity to diphtheria through immunization or natural infection, required at least three doses of diphtheria toxoid for reliable protection against disease.

Adult↗
PubMedDate not supplied

Diphtheria and hearing loss.

OBJECTIVE: To determine if infectious diseases usually experienced in childhood have an effect on hearing ability later in life. METHODS: The Epidemiology of Hearing Loss Study (N = 3,753) is a population-based study of age-related hearing loss in adults aged 48 to 92 years in Beaver Dam, Wisconsin. As part of this study, infectious disease history was obtained and hearing was tested using pure-tone audiometry. Hearing loss was defined as a pure-tone average of thresholds at 500 Hz, 1,000 Hz, 2,000 Hz, and 4,000 Hz greater than 25 decibels hearing level in either ear. RESULTS: After adjusting for confounders, only a history of diphtheria (n = 37) was associated with hearing loss (odds ratio [OR] 2.79; 95% confidence interval [CI] 1.05, 7.36). There was no relationship between hearing loss and history of chickenpox, measles, mumps, pertussis, polio, rheumatic fever, rubella, or scarlet fever. Only two participants with a history of diphtheria and hearing loss reported having a hearing loss before age 20. CONCLUSIONS: Diphtheria in childhood may have consequences for hearing that do not become apparent until later in life. A possible biological mechanism for a diphtheria effect on hearing ability exists: The toxin produced by the Corynebacterium diphtheriae bacteria can cause damage to cranial nerves and therefore may affect the auditory neural pathway. These data may have important implications for areas facing a resurgence of diphtheria cases.

Adult↗
PubMed1976

Isolation and partial characterization of a corynebacteriophage beta, tox operator constitutive-like mutant lysogen of Corynebacterium diphtheriae.

We have isolated and partially characterized a beta-phage mutant lysogen of Corynebacterium diphtheriae, C7(betatoxct1+), which is partially insensitive to iron inhibition of diphtheria toxin production. tox expression by C7(betatoxct1+) was found to be partially constitutive. In the presence of concentrations of iron that almost completely inhibit the expression of diphtheria toxin by the wild type, C7(beta), the level of toxin production by C7(betatoxct1+) was found to be at least 25 times that of the parent. The purified tox gene product of C7(betatoxct1+) was immunologically and electrophoretically identical to, and equally as toxic as, diphtheria toxin purified from C7(beta). In addition, the partial N-terminal amino acid sequence was found to be identical to diphtheria toxin. This data strongly suggests that the mutation allowing for the constitutive expression of tox in C7(betatoxct1+) is outside of the structural gene. Furthermore, the constitutive expression of diphtheria toxin was found to be cis dominant in the double lysogen C7(betacrm45+/betatoxct1+). The data presented is consistent with the existence of a tox operator locus.

Bacteriophages↗
PubMed2000

Extensive swelling after booster doses of acellular pertussis-tetanus-diphtheria vaccines.

BACKGROUND: Diphtheria and tetanus toxoid combined with acellular pertussis (DTaP) vaccines are less reactogenic than diphtheria and tetanus toxoid combined with whole cell pertussis (DTwP) vaccines. However, local reactions increase in rate and severity with each successive DTaP dose, and swelling of the entire injected limb has been reported after booster doses. METHODS: We reviewed reports of swelling of the entire thigh or upper arm after the fourth and fifth dose, respectively, of DTaP vaccines administered in the National Institutes of Health multicenter comparative DTaP studies. Relationships were explored among reports of severe swelling, rates of other reactions, quantity of vaccine contents, and prevaccination and postvaccination antibody levels to pertussis toxin, tetanus toxin, and diphtheria toxin. RESULTS: Entire thigh swelling was an unsolicited reaction reported in 20 (2%) of the 1015 children who received 4 consecutive doses of the same DTaP vaccine. The reaction was associated with 9 of the 12 DTaP vaccines evaluated. Although there were no reports of swelling of the entire upper arm in 121 children given a fifth dose of the same DTaP, 4 (2.7%) of 146 recipients of 5 doses of a mixed schedule of DTaP vaccines experienced such swelling. Rates of other reactions were higher in children with entire thigh swelling than in those without. Of the children with entire thigh swelling, 60% had local pain, and 60% had erythema. All swelling subsided spontaneously without sequelae. There was a significant linear association between the rates of entire thigh swelling after dose 4 and diphtheria toxoid content in the DTaP products. Lesser degrees of swelling (>50 mm but less than entire limb) correlated with pertussis toxoid content after dose 4 and aluminum content after dose 5. No relationship was established between levels of serum antibody to diphtheria, tetanus, or pertussis toxin and rates of swelling of the whole thigh. CONCLUSIONS: Booster doses of DTaP vaccines can cause entire limb swelling, which is usually associated with redness and pain. Our data suggest that this extensive swelling reaction may be more common with vaccines containing high diphtheria toxoid content.

Antibodies, Bacterial↗
PubMed2006

Effect of a single tetanus-diphtheria vaccine dose on the immunity of elderly people in São Paulo, Brazil.

Epidemiological data regarding tetanus and diphtheria immunity in elderly people in Brazil are scarce. During the First National Immunization Campaign for the Elderly in Brazil in April 1999, 98 individuals (median age: 84 years) received one tetanus-dyphtheria (Td) vaccine dose (Butantan Institute, lot number 9808079/G). Inclusion criteria were elderly individuals without a history of severe immunosuppressive disease, acute infectious disease or use of immunomodulators. Blood samples were collected immediately before the vaccine and 30 days later. Serum was separated and stored at -20 degrees C until analysis. Tetanus and diphtheria antibodies were measured by the double-antigen ELISA test. Tetanus and diphtheria antibody concentrations lower than 0.01 IU/mL were considered to indicate the absence of protection, between 0.01 and 0.09 IU/mL were considered to indicate basic immunity, and values of 0.1 IU/mL or higher were considered to indicate full protection. Before vaccination, 18% of the individuals were susceptible to diphtheria and 94% were susceptible to tetanus. After one Td dose, 78% became fully immune to diphtheria, 13% attained basic immunity, and 9% were still susceptible to the disease. In contrast, 79% remained susceptible to tetanus, 4% had basic immunity and 17% were fully immune. Although one Td dose increases immunity to diphtheria in many elderly people who live in Brazil, a complete vaccination series appears to be necessary for the prevention of tetanus.

Aged↗
PubMed2003

Diphtheria seroprevalence in children living in the eastern Turkey.

OBJECTIVES: To determine the seroprevalence of diphtheria in 767 children aged 0-6 years and to identify the relationship between diphtheria seroprevalence and several sociodemographic characteristics of the study subjects in the Erzurum, Erzincan and Kars cities situated in Eastern Turkey. DESIGN: A cross sectional study. SETTING: The subjects were recruited from three cities (Erzurum, Erzincan, Kars). The sampling method of 30 clusters recommended for field studies was used for a predetermined number of selecting subjects in the rural and urban areas in each city. SUBJECTS: Of the 767 children included in this study, 423 were from Erzurum, 187 from Kars and 157 from Erzincan. Diphtheria serology was used to examine the blood samples by ELISA method. RESULTS: Positive diphtheria seroprevalence was detected in 77.9% of 767 subjects in Eastern Turkey. Seroprevalence was 74.5% in children younger than one year of age, increased to 84% at the age of 3-4 years, and reduced to 80% at the age of 4-5 years and 69.8% at the age of 5-6 years. The seroprevalence rates were similar in sex and number of siblings. Seroprevalence of diphtheria increased with educational level of parents in the rural area. CONCLUSION: Positive seroprevalence against diphtheria in eastern Turkey is disturbingly low.

Age Distribution↗
PubMedDate not supplied

Corynebacterium diphtheriae threats in cancer patients.

The aim of this study was to determine the bacteriological properties of Corynebacterium diphtheriae strains isolated from bronchiole washing and cancer lesions. Bacteriological characterization included fluorescence/double sugar urease (King/DSU) screening tests, pyrazinamidase (PYZ), CAMP-reactions and radial immunodiffusion toxigenicity assay. Microorganisms produced fluorescence under ultraviolet light and were catalase positive; urea and aesculin hydrolysis negative; fermentation of glucose, maltose and sucrose and no fermentation of mannitol and xylose; PYZ and CAMP reaction negative. The API-Coryne system was used for bacterial preliminary identification at local hospital laboratory and produced numerical profiles 1010325 and 0010325 for sucrose positive C. diphtheriae var. mitis (nitrate positive) and C. diphtheriae var. belfanti (nitrate negative), respectively. The hemagglutination, adherence to glass and polystyrene assays evaluated adhesive characteristics. Strains were toxigenic and able to adhere to glass, polystyrene and human erythrocyte surfaces (titer 4). C. diphtheriae strains isolated from cancer patients expressed adhesive characteristics similar to strains isolated from immunocompetent hosts. Circulation of toxigenic C. diphtheriae continues to present a threat for children and adults including patients with cancer in hospital environment. Laboratories should remain alert to the possibility of isolation of diphtheria bacilli from adults with neoplastic disease.

Adult↗
PubMed2002

Diphtheria immunity of different age groups in Turkey.

In Turkey, the immunization policy against diphtheria involves childhood vaccination, and no routine booster dose is administered after 12 years of age. Information about the immune status of the population is important to predict the potential for epidemics, several of which have occurred recently in neighboring countries. The aim of this study was to assess the immune status of different age groups in Turkey against diphtheria. A total of 497 blood samples were collected, and diphtheria antitoxin levels were measured by the Enzyme Linked Immunosorbent Assay method. Titers below 0.1 IU/ml were considered to show insufficient immunity. Overall, 35.8% of the population studied showed insufficient immunity against diphtheria. Immunity rates varied significantly among different age groups (P < 0.01). Protective immunity rates were highest in the 3- to 6-year age group (81.3%) and the over 60 age group (81.2%). In subjects between the ages of 10 and 59 the percentage of people with insufficient immunity was above 30%. The lowest immunity rate was observed in 20- to 29-year age group. No significant difference was seen between males and females in terms of protective effect of vaccination. This study indicates that people between the ages of 10 and 59 are susceptible to diphtheria in our country. Therefore, revaccination of adults with tetanus-diphtheria toxoids at every opportunity (military service, pregnancy, admittance to emergency room) should be considered as an immunization policy.

Adolescent↗
PubMed2002

[Antibody levels to diphtheria in various community segments].

The aim of this study was to detect the immune status of our population against diphtheria. For this purpose, the levels of diphtheria IgG antibodies in various age groups were investigated in 150 subjects aged over 20 years old, by using ELISA method. The positive immunity rate against diphtheria was found 62%, while there was no statistically significant difference between the rates of males (66.7%) and females (57.7%) (p > 0.05). Eighty percent of subjects aged between 20-29 years, 71.4% of 30-39 years, 50% of 40-49 years, 55.6% of 50-59 years, 47.6% of 60-69 years and 60% of 70-79 years old groups were found to have protective levels (over 0.01 IU/ml) of antibodies to diphtheria. There was no significant difference in immunity against diphtheria between these age groups (p > 0.05). However, 76% of subjects aged below 40 years old were immune to diphtheria, while 54% of subjects aged above 40 years old were so, with a statistically significant difference (p < 0.05). There was no significant difference in the rate of immunity between subjects in terms of occupation, levels of education, geographic location and vaccination status (p > 0.05).

Adult↗
PubMed2003

Lack of significant differences in immunity against diphtheria between populations of Eastern and Western regions of Poland.

Incidents of diphtheria in countries which were formerly part of the Soviet Union (Ukraine, Russia and Belorus) resulted in the need to evaluate thoroughly the effectiveness of preventive vaccination in Poland, especially in the border regions of the country where the biggest migration of population can be observed. The aim of this work was a comparison of the immunity to diphtheria in two geographically different regions of Poland--eastern (Lublin) and western (Zielona Gora) ones. It showed immunoprophylaxis to diphtheria that was implemented on these areas. Diphtheria antitoxin level (IgG) was determined with application of the ELISA method in 1236 (529/707) people. No significant differences were found in the level of antibodies in the groups < 2 years of age and > 19 years of age in people below the protective titre (0.1 IU/ml). The difference occurring in the interval between 2nd and 18th year of life (in western Poland 7.6% and in eastern Poland 16%) may result from different implementation of the vaccination program in these regions (booster doses). Recommendations for vaccination to diphtheria in people over 25 years of age should be implemented especially in the frontier regions of Poland adjoining countries threatened with diphtheria occurrence.

Adolescent↗
PubMed1990

[The diagnostic effectiveness of an immunoenzyme test system for determining diphtheria toxin antigens in the blood serum in a clinical laboratory trial].

The data on the approbation of the diagnostic value of the enzyme immunoassay (EIA) system for the determination of diphtheria toxin in the blood sera of diphtheria patients and persons suspected for diphtheria are presented. The EIA system was prepared on the basis of F(ab)2 fractions of purified antidiphtheria antibodies. 240 serum samples from diphtheria and tonsillitis patients and from healthy persons were studied. Diphtheria toxin was determined in all patients with the toxic form of diphtheria and in 41.3% of patients with its localized forms. Blood was taken mainly of the first week of the disease. In healthy persons the results of EIA were negative. Thus, the trial of the assay system in a clinical laboratory showed its good diagnostic effectiveness. The use of this EIA system in medical practice is believed to be quite promising.

Adolescent↗
PubMed1977

[The species C. diphtheriae].

Corynebacteria (C. diphtheriae var. gravis, mitis, minimus, intermedius, C. belfanti, C. ovis, C. ulceraus) producing diphtheria toxin are found as variants sharply differing from one another morphologically (from long branching rods to coccobacilli), culturally, biochemically and by other signs. The toxin synthesis in them was determined by genetically heterogeneous prophages tox+; tox+ virus exchange is possible between the corynebacteria. Since production of specific toxin, the cardinal sign of C. diphtheriae species, is connected with the genoms of genetically heterogeneous viruses tox+, the circle of whose hosts is very wide, it can be supposed that there is no genetically homogeneous taxonomic category "diphtheriae species". Several species of corynebacteria--lysogenized (toxigenic) or capable of being lysogenized (nontoxigenic) with tox+ viruses are included into the composition of the corynebacteria groups which medicine considers as "species" for over 80 years. A possiblity of becoming a diphtheria causative agent is determined by the capacity of corynebacteria to become infected with the circle of viruses tox+ the DNA of which can become stably integrated with the gene of this bacterium. The mentioned approach to taxonomy is possibly applicable to microorganisms in which the pathogenicity signs (the toxin) were determined, as in C. diphtheriae, in the virus genoms (Bac. botulinus).

Bacteriophage Typing↗
PubMed1978

[Identification of Corynebacterium diphtheriae by Way of Immunofluorescence (author's transl)].

The immunofluorescence technique (IF) will be demonstrated as a time-saving method for identifying Corynebacterium diphtheriae. In three test-series the IF-test was performed on 74 strains of C. diphtheriae which had been isolated in a small case of epidemic in Gelsenkirchen, on 4 strains of diphtheroids and on some strains to be found in the nasopharynx. All of these strains had been taken from blood agar, 69 toxinogenic strains of C. diphtheriae showed a clear, plainly reproducible fluorescence (Fig. 1). The diphtheroids and the other strains tested could be clearly differentiated from C. diphtheriae as a consequence of absent fluorescence of the cell wall. Because of morphological changes effected by potassium tellurite on C. diphtheriae smears made from tellurite media proved themselves to be inappropriate for the IF-test. Swabs from carriers of bacilli were not available for our IF-test. The results obtained from the blood agar, however, show that the IF-technique has to be considered as an improvement and a broadening of diphtheria diagnostics. New prospects present themselves for effecting the long aimed-at rapid diagnosis within a few hours.

Corynebacterium diphtheriae↗