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PubMed1963

SIALIDASE (NEURAMINIDASE) OF CORYNEBACTERIUM DIPHTHERIAE.

Warren, Leonard (National Institute of Arthritis and Metabolic Diseases, Bethesda, Md.) and C. W. Spearing. Sialidase (neuraminidase) of Corynebacterium diphtheriae. J. Bacteriol. 86:950-955. 1963.-The characteristics of a sialidase produced by Corynebacterium diphtheriae were studied. The enzyme was partially purified from preparations of diphtheria toxin on a column of Sephadex G-75. By this means the lethal factor of diphtheria toxin was separated, in part, from the sialidase activity. There appeared to be a close immunological relationship between the sialidases of C. diphtheriae and clostridia, since a preparation of diphtheria antitoxin was as effective an inhibitor of diphtheria sialidase as of the sialidase of three species of clostridia. Conversely, antitoxin to clostridia inhibited diphtheria sialidase. Diphtheria antitoxin was essentially inactive toward influenza virus sialidase, and was completely inactive against purified sialidase of Vibrio cholerae. Removal of sialic acid from the proteins in a preparation of diphtheria antitoxin did not alter the inhibitory activity of the antitoxin against diphtheria sialidase. The enzyme operated optimally at pH 5.5 and did not require calcium ions for activity. The substrate specificity of diphtheria sialidase appears to be the same as that of other previously described sialidases.

Corynebacterium diphtheriae↗
PubMed1997

Antibody protection to diphtheria in geriatric patients: need for ED compliance with immunization guidelines.

STUDY OBJECTIVE: Because 50% to 70% of geriatric patients have been shown to have nonproductive levels of tetanus antibodies, we postulated that this population might also have inadequate levels of diphtheria antibodies. Emergency physicians have the opportunity to immunize patients against tetanus and diphtheria. We sought to determine the seroprevalence of diphtheria antibodies in patients older than 65 years and to assess compliance with immunization guidelines in EDs. METHODS: Enzyme-linked immunosorbent assay for diphtheria antibodies was conducted in 58 outpatients of geriatric medical facility aged 65 years or older. We considered titers greater than .1 IU/mL protective. Eighteen ED personnel, ages 25 to 40 years, served as comparison subjects. The preparation used for immunization of injured patients--tetanus toxoid or tetanus and diphtheria toxoids adsorbed for adult use--was determined by means of a telephone survey of 64 New York City EDs. RESULTS: The mean age of our patients was 80 years (range, 65 to 95 years). Their mean diphtheria antibody titer was .17 IU/mL (range, .04 to .54 IU/mL). Thirty-three percent (19 of 58; 95% confidence interval [Cl], 21% to 54%) of patients had inadequate levels of diphtheria antibodies. We found no significant differences between protected and nonprotected patients with respect to age, sex, medical history, or military service. Patients with nonprotective levels of diphtheria antibodies were more likely to have inadequate tetanus antibody titers. Sixty-eight percent of patients without protection from diphtheria (13 of 19; 95% Cl, 48% to 88%) were also unprotected from tetanus, and 33% (13 of 39; 95% Cl, 19% to 47%) o those with adequate diphtheria antibodies had nonprotective levels of tetanus antibodies (P = .012). All 18 ED personnel had adequate diphtheria and tetanus antibodies. The telephone survey revealed that 30% (19 of 64) of EDs use only tetanus toxoid for immunization of injured patients. CONCLUSION: A significant percentage of geriatric patients have inadequate diphtheria antibodies. Emergency physicians must comply with immunization guidelines for injured patients to assure adequate protection from both tetanus and diphtheria.

Adult↗
PubMed1997

Adjuvanticity of pGPL-Mc and LRS in the immune responses of monkeys to oral immunization with diphtheria and tetanus toxoids.

Experiments were carried out to examine the adjuvanticity of polar glycopeptidolipids of Mycobacterium chelonae (pGPL-Mc) or the London rocket seed (LRS) when combined with diphtheria and tetanus toxoids in an oral immunization of the African green monkey. The results showed that none of the monkeys receiving diphtheria and tetanus toxoids combined with 25 mg/kg of pGPL-Mc showed an increase in the the level of diphtheria antitoxin (DA) on the third and sixth weeks following the first and the second immunizations. One monkey from this group responded with increased seroneutralizing antibodies 3 weeks after the third feeding. On the other hand, one monkey, 3 weeks after the first immunization, and three monkeys, 3 weeks after the second and third oral vaccinations, showed an increase in specific anti-diphtheria antibody responses when the toxoids were combined with 25 mg/kg of LRS. The anti-diphtheria antitoxin responses of monkeys receiving diphtheria and tetanus toxoids combined with 50 mg/kg of pGPL-Mc or 50 mg/kg of LRS were significantly enhanced compared to the groups administered 25 mg/kg of the two adjuvants. The increase was observed in four out of five pGPL-Mc administered and in three out of five LRS-receiving monkeys. The results show that pGPL-Mc induced the highest titres of anti-diphtheria antitoxin compared to LRS, whereas the level of anti-diphtheria antitoxin titre of the two monkeys receiving the toxoids alone was less than 0.1 i.u./ml of serum throughout the experiment. According to the statistical analyses, no significant differences were recorded between the diphtheria antitoxin responses of monkeys following the first, second or third administration of LRS-adjuvated diphtheria and tetanus toxoids. However, a significant difference (P < or = 0.05) was observed in the diphtheria antitoxin response between the first and the second immunization of monkeys administered with toxoids adjuvated with 50 mg/kg of pGPL-Mc. The tetanus antitoxin responses of all monkeys were less than 0.1 i.u. of antitoxin per millilitre of serum throughout the study, which is considered not to be protective. However, we have recorded an anti-tetanus antitoxin titre of more than 0.2 i.u./ml of serum in one monkey that received diphtheria and tetanus toxoids combined with 50 mg/kg of pGPL-Mc.

Adjuvants, Immunologic↗
PubMed1995

Resurgence of diphtheria.

Following the introduction of routine immunization with diphtheria toxoid in the 1940s and 1950s, diphtheria incidence declined dramatically in countries of the industrialized world. At the beginning of the 1980s many of these countries were progressing toward elimination of the disease. However, since the mid-1980s there has been a striking resurgence of diphtheria in several countries of Eastern Europe. For 1993, WHO received reports of 15,211 diphtheria cases in Russia and 2,987 cases in Ukraine. The main reasons for the return of diphtheria in these countries were: decreasing immunization coverage among infants and children waning immunity to diphtheria in adults, movements of the population during the last few years, and an irregular supply of vaccines. The outbreak spread to neighboring countries and in 1993 cases were reported in Azerbaijan, Belarus, Estonia, Finland, Kazakhstan, Latvia, Lithuania, Poland, Tajikistan, Turkey, and Uzbekistan. Epidemiological patterns of diphtheria are changing in developing countries, and the disease seems to be following patterns seen in industrialized countries 30 to 40 years ago. In developing countries, routine immunization against diphtheria was introduced in the late 1970s with the Expanded Programme on Immunization. In these countries, coverage of infants with 3 doses of diphtheria toxoid reached 46% in 1985, and 79% in 1992. Recent diphtheria outbreaks in Algeria, China, Ecuator, Jordan, Lesotho and Sudan demonstrate a shift in the age distribution of cases to older children and adults. Rapid clinical and public health responses are required to control diphtheria outbreaks. Three major measures are indicated: high immunization coverage of target groups, prompt diagnosis and management of diphtheria cases, and rapid identification of close contacts with their effective management to prevent secondary cases.

Adolescent↗
PubMed1998

A report of diphtheria surveillance from a rural medical college hospital.

A 5-year sentinel surveillance of diphtheria from 1989 to 1993 was undertaken at a rural medical college hospital. No significant change in the number of diphtheria cases was observed in spite of sustained high level of diphtheria, pertussis, tetanus vaccine-3 doses (DPT3) coverage. Most of the diphtheria cases occurred during July to November. Age distribution of diphtheria cases showed that more than 75% occurred above 2 years age (except in 1989) and around 65% cases above 3 years age. The age shift in diphtheria signified success of primary diphtheria immunisation, as well as indicated the lack of coverage with booster doses at appropriate ages. Because of high coverage with primary diphtheria immunisation there was decrease in circulating toxigenic C diphtheriae resulting in less natural boosting of antibody titre. Thus, in absence of booster immunisation, the older children and adults were more vulnerable to diphtheria. The findings of the study justified the need of emphasising importance of booster diphtheria immunisation at appropriate ages for effective control of diphtheria.

Adult↗
PubMed2005

Diphtheria, tetanus and pertussis antibodies in 10-year-old children before and after a booster dose of three toxoids: implications for the timing of a booster dose.

UNLABELLED: In an open study, 502 10-year-old children, who had received primary vaccination against diphtheria and tetanus in infancy and had varying histories of pertussis disease and vaccination, were vaccinated with diphtheria-tetanus vaccine (DT) alone or with the addition of 20 microg or 40 microg of pertussis toxoid. Diphtheria toxin neutralising antibodies, pertussis toxin IgG and tetanus toxoid IgG antibodies were measured before and 1 month after the booster. All toxoids were highly immunogenic. In pertussis toxoid recipients, median levels of pertussis toxin IgG increased to 16.5 U/ml (DTaP20) and to 36 U/ml (DTaP40) in children with non-detectable (<1 U/ml) antibodies before vaccination and to >400 U/ml in children (both DTaP20 and DTaP40) with detectable antibodies before vaccination. A total of 60 children (12%) with non-detectable (<0.01 IU/ml) diphtheria antibodies and 36 children (7%) with non-detectable (<0.01 IU/ml) tetanus antibodies before the booster had lower median antibody concentrations post-vaccination than children with detectable antibodies before the booster (diphtheria: 5.12 vs. 20.48 IU/ml; tetanus: 4.0 vs. 10.0 IU/ml). There were no differences in diphtheria and tetanus antibodies after vaccination between children who did and did not receive pertussis toxoid. CONCLUSION: 10-year-old children with non-detectable diphtheria and tetanus antibodies before the booster had lower post-vaccination antibodies than those with detectable antibodies before the booster indicating a poor immunological memory. Addition of pertussis toxoid to diphtheria-tetanus vaccine did not affect the antibody responses to diphtheria and tetanus toxoids when the three toxoids were combined as a booster. Even though immunity to diphtheria and tetanus was only estimated by surrogate markers (serum antitoxin antibodies) the results indicate that a lower age for the booster dose of diphtheria-tetanus vaccine or diphtheria-tetanus acellular pertussis vaccine should be considered.

Antibodies, Bacterial↗
PubMed2000

Epidemiology of diphtheria in South Dakota.

Respiratory diphtheria was one of the most common causes of death among children in the pre-vaccine era. Since the introduction of diphtheria toxoid vaccine in 1920s, and its widespread use by the late 1940s, diphtheria became increasingly rare in the United States. However, through the 1970s diphtheria remained endemic in some states, with reported incidence rates > 1.0 per million population in six states (Alaska, Arizona, Montana, New Mexico, South Dakota, and Washington). Starting in 1980, less than five cases have been reported each year in the United States. The majority of culture-confirmed cases have been associated with importation from other countries. Toxigenic Corynebacterium diphtheriae, the organism causing diphtheria, was thought to have become rare or even have disappeared from previously endemic areas such as South Dakota. However, during four months in 1996, 11 persons (one index case, six patients and four household contacts) in an American Indian community in South Dakota were found to be infected by C. diphtheriae; six of these isolates were toxigenic. The findings in this report indicate that despite 20 years without reported respiratory diphtheria cases, toxigenic C. diphtheriae is still present in South Dakota. The continuous circulation of toxigenic strains of C. diphtheriae emphasizes the need for health care providers throughout South Dakota to promote timely vaccination against diphtheria among persons of all ages and ethnic groups, to be aware of the clinical signs and symptoms of diphtheria so that cases can be promptly diagnosed and treated, and further public health measures can be taken to contain this serious disease.

Adolescent↗