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An evaluation of diphtheria--tetanus (adult) vaccine in unselected human volunteers.

One hundred unselected adult volunteers received an adult diphtheria (less than 2 Lf)-tetanus (greater than or equal to 40 IU) adsorbed vaccine without prior Schick testing. No volunteer had a moderate or severe reaction although 39% complained of a transient sore arm. Only 10% reported local erythema. Of the study group, 37/43 (86%) patients who were initially seronegative for diphtheria attained levels normally considered as seropositive. The results confirm the safety and efficacy of adult diphtheria-tetanus vaccine and allow its recommendation for use in 'at risk' individuals without the need for prior Schick testing.

Adult↗

Prevention of pertussis among adolescents: recommendations for use of tetanus toxoid, reduced diphtheria toxoid, and acellular pertussis (Tdap) vaccine.

The purpose of this statement is to provide the rationale and recommendations for adolescent use of tetanus toxoid, reduced diphtheria toxoid, and acellular pertussis (Tdap) vaccines. Despite universal immunization of children with multiple doses of pediatric diphtheria and tetanus toxoids and acellular pertussis (DTaP) vaccine, pertussis remains endemic with a steady increase in the number of reported cases. Two peaks in the incidence of pertussis occur in pediatric patients: infants younger than 6 months of age who are inadequately protected by the current immunization schedule and adolescents 11 through 18 years of age whose vaccine-induced immunity has waned. Significant medical and public health resources are being consumed in postexposure management of adolescent cases, contacts, and outbreaks with little beneficial effect on individuals or the epidemiology of disease. Two Tdap products were licensed in 2005 for use in people 10 through 18 years of age (Boostrix) and 11 through 64 years of age (Adacel). The American Academy of Pediatrics recommends the following: 1. Adolescents 11 to 18 years of age should receive a single dose of Tdap instead of tetanus and diphtheria toxoids (Td) vaccine for booster immunization. The preferred age for Tdap immunization is 11 to 12 years. 2. Adolescents 11 to 18 years of age who have received Td but not Tdap are encouraged to receive a single dose of Tdap. An interval of at least 5 years between Td and Tdap is suggested to reduce the risk of local and systemic reactions; however, intervals of less than 5 years can be used, particularly in settings of increased risk of acquiring pertussis, having complicated disease, or transmitting infection to vulnerable contacts. Data support acceptable safety with an interval as short as approximately 2 years. 3. Tdap and tetravalent meningococcal conjugate vaccine (MCV4 [Menactra]) should be administered during the same visit if both vaccines are indicated. If this is not feasible, MCV4 and Tdap can be administered using either sequence. When not administered simultaneously, the American Academy of Pediatrics suggests a minimum interval of 1 month between vaccines. The rationale for this strategy is to provide direct protection of immunized adolescents. With implementation of vaccine recommendations, indirect benefitalso is likely to extend to unimmunized peers and other age groups. The strategy of universal Tdap immunization at 11 to 12 years of age is cost-effective.

Adolescent↗

Selection for immune response in goats: the effect of immunization procedure on antibody response to diphtheria toxoid and human serum albumin.

The serum antibody titers to diphtheria toxoid and human serum albumin were determined in 103 goat kids from lines selected for 12 yr for high or low antibody response to diphtheria toxoid. In the 12th yr, six groups of kids were immunized with different preparations of the antigens. In all groups but one, the antigens were emulsified in Freund's incomplete adjuvant with added sonicated Mycobacterium paratuberculosis. The groups received the following treatments: Group 1 was immunized with both antigens mixed in the same syringe, Group 2 got both antigens injected separately, Group 3 got both antigens injected separately, but with a lower concentration of M. paratuberculosis, Group 4 was immunized with diphtheria toxoid only, Group 5 was immunized with human serum albumin only, and Group 6 was immunized with both antigens mixed, but without any M. paratuberculosis. The animals were immunized at 4 wk of age, and the antibody titers were determined 3 wk later by ELISA and passive hemagglutination. The mean antibody titers to both antigens were different between the selected lines (P less than .03). There was no effect of separate vs combined injections of antigens. However, there were indications of antigen suppression or competition between the antigens. Animals receiving only one antigen seemed to mount a higher antibody response to that antigen than did animals immunized with two antigens.

Animals↗

Exudative pharyngitis possibly due to Corynebacterium pseudodiphtheriticum, a new challenge in the differential diagnosis of diphtheria.

Corynebacterium pseudodiphtheriticum has rarely been reported to cause disease in humans, despite its common presence in the flora of the upper respiratory tract. We report here a case of exudative pharyngitis with pseudomembrane possibly caused by C. pseudodiphtheriticum in a 4-year-old girl. The case initially triggered clinical and laboratory suspicion of diphtheria. Because C. pseudodiphtheriticum can be easily confused with Corynebacterium diphtheriae in Gram stain, clarification of its role in the pathogenesis of exudative pharyngitis in otherwise healthy persons is of public health importance. Simple and rapid screening tests to differentiate C. pseudodiphtheriticum from C. diphtheriae should be performed to prevent unnecessary concern in the community and unnecessary outbreak control measures.

Child, Preschool↗

Status of antitoxic immunity against diphtheria in Japan. A report of the National Epidemiological Surveillance for Important Communicable Diseases.

Antitoxic immunity against diphtheria was surveyed during the period from 1962 to 1980. The survey was done by Schick test in the first decade and then by antitoxin titration of sera by the cell culture method in the recent six years. The data show clearly that the successful control of diphtheria has been accomplished in Japan as the result of active immunization. Both single (D) and combined (DP or DPT) vaccines were effective to convert Schick reaction negative. In addition, immunity was greatly improved by the introduction of the combined vaccine and one additional booster injection. However, such subsequent changes in the immunization schedule introduced in 1976 that giving the primary vaccination at older age and the omission of one booster injection at the preschool, has resulted in appearance of a high risk group below three years of age as well as in the lower immunity levels among school children. The data indicate that the continuous surveillance for diphtheria is required in this country.

Adolescent↗

[The interrelationship of biomass and toxin accumulation to the dynamics of the physicochemical parameters of Corynebacterium diphtheriae PW8 cultivation].

As established in the process the controlled cultivation of C. diphtheriae PW8, the rate of the accumulation of biomass and antigenic material increases with higher values of the redox potential of the nutrient medium (exceeding 11.0 mV). The data obtained in this study are indicative of the expediency of using the value of redox potential as an additional criterion in the evaluation of the quality of the nutrient media. The direct relationship between the productivity of the process of C. diphtheriae PW8 cultivation as regards the accumulation of biomass and antigenic material and the economic coefficients of the accumulation of biomass and antigenic material as determined by the utilized substrate has been established. The above relationship may facilitate the prognostication of the course of the process of microbial cultivation and the accumulation of diphtheria toxin, evaluated by antigenic activity.

Antigens, Bacterial↗

[Pathogenic properties of Corynebacterium diphtheriae].

The main pathogenic properties of 73 C. diphtheriae strains (their adhesive, invasive and cytotoxic activity) were characterized in the cultures of cells HEp-2 and Vero. The quantitative determination of the toxigenicity of 381 strains in the indirect hemagglutination test was made, and the strains were distributed by the degree of their toxigenicity. The characteristics of C. diphtheriae obtained with the use of in vitro experimental models, coincided with the severity of clinical manifestations of the diphtheria in humans, which made it possible to regard the models used in this study as adequate. On the basis of the chosen criteria the characterized strains could be subdivided into highly, moderately and low virulent and the degree of their potential epidemic danger could be determined.

Animals↗

[Combined vaccine against tetanus, diphtheria and polio. A randomized controlled study of immunogenicity and tolerance].

UNLABELLED: BACKGROUND, METHOD: Given the worldwide distribution of infection and the mobility of large parts of the population immunizations against tetanus, diphtheria and polio remain a challenge. This is especially true for adolescents and adults since antibodies tend to wane once immunized children enter adolescence and adulthood. A new combination vaccine against tetanus, diphtheria and polio (Td-IPV) for booster immunizations was subjected to a randomized, controlled and single-blind trial. Non-inferiority had to be demonstrated with regard to efficacy (immunogenicity) and safety in comparison to separate Td and IPV injections. RESULTS: Almost 500 subjects from community practices and occupational/immunization clinics took part. Antibody titres were equivalent for all antigens. Local and systemic reactions were equal or even less marked in the intervention group. CONCLUSION: From a public health perspective the new vaccine can make an important contribution to ensure adequate protection against tetanus, diphtheria and polio in adolescent and adult populations.

Adolescent↗

[Diphtheria in the area of antibiotics (author's transl)].

In Düsseldorf repeated incidences of severe membranous angina were observed, several cases of which had a fatal outcome. Though the bacteriological proof could only be firnished in one case, in the rest of the cases there was also the strong suspicion of diphtheria. To guarantee the final diagnosis, it is necessary, to make the throat swab before the antibiotic therapy begins since only a single dosis of penicillin jeopardises the demonstration of the infection agent. It must urgently be minded of the necessity, that in cases of suspicion a diphtheria antitoxin should be given in good time, not waiting for the bacteriological clarification, since already a whole generation of physicians from their personal experience is no longer up to date on the clinical picture of diphtheria.

Adolescent↗

Binding of the metalloregulatory protein DtxR to the diphtheria tox operator requires a divalent heavy metal ion and protects the palindromic sequence from DNase I digestion.

Transcription of the corynebacteriophage diphtheria tox operon has been shown to be regulated through a corynebacterial determined factor DtxR. The dtxR gene has been recently cloned and expressed in Escherichia coli, and shown to regulate the expression of beta-galactosidase expression from a diphtheria tox promoter/operator-lacZ transcriptional fusion. Tao et al. (Tao, X., Boyd, J., and Murphy, J. R. (1992) Proc. Natl. Acad. Sci. U.S.A. 89, 5897-5901) have recently shown by gel mobility shift assay that the binding of DtxR to the tox operator requires a divalent heavy metal ion, as well as the 27-base pair interrupted palindromic sequence. We now show the activation of DtxR in the presence of Co2+, Fe2+, or Mn2+ results in the protection of a 33- and 27-nucleotide region on the coding and non-coding strand from DNase I digestion, respectively. DtxR is also activated in the presence of Ni2+; however, this metalloregulatory factor is only weakly activated by Zn2+. The diphtheria tox regulatory region protected from DNase I digestion in the presence of activated DtxR encompasses the 27-base pair interrupted palindromic sequence.

Bacterial Proteins↗

Epidemiological features of skin diphtheria infection in Rangoon, Burma.

A survey for skin diphtheria was carried out on 493 patients with skin lesions who were attending Veneral Diseases & Dermatology Clinic in Rangoon in 1971. 63.8% of the patients had C. diphtheriae in their skin lesions. All ages and both sexes were equally affected. Skin lesions yielding C. diphtheriae on culture were indistinguishable from those associated with other bacteria including ecthyma, pyoderma and secondarily infected with parasitic infections. Out of 108 strains tested 18.5% were found to be toxigenic, mainly intermedius. No toxigenic gravis strain was encountered. No relation existed between the type of lesion and the type or toxigenicity of the infecting strain. 75% of these toxigenic strains were isolated from children under 5 years of age. The phage types of toxigenic strains isolated were: II-IV, XII, Ph r, 8, 19-20, III, IVII and IV.

Age Factors↗

Diphtheria in the eighties: experience in a south Indian district hospital.

Epidemiological and clinical analysis of 228 cases of diphtheria treated during a 10-year period from 1980-1989 is presented. No statistically significant change in the incidence over a decade was noticed. A high percentage of cases (44.74%) were noted in the age group of 5 years and above. Bilateral tonsillar and pharyngeal membranes together were seen in 60% cases. All patients were treated with diphtheria antitoxin and benzyl penicillin. Severe myocarditis (9 cases), fulminant haemorrhagic complications (2 cases), palatal palsies (11 cases) and polyneuritis and cranial nerve paralysis (2 cases) were the significant complications. Case fatality rate was 13.21%. Statistically significant increase in the mortality (p less than 0.05) was noticed in the year 1987 and onwards. In this period, myocarditis (8 out of 16 deaths) is gradually replacing laryngeal obstruction, the major cause of death in early eighties or post-tracheostomy complications (6 out of 16 deaths). Only 2 patients died of haemorrhagic diphtheria in this period.

Age Factors↗

[Study on immune persistency of combined diphtheria-pertussis-tetanus (DPT) triple vaccine].

Immune efficacy and persistency were studied by comparison of two-dose immunization of adsorbed DPT at one and two month interval and two & three dose immunization of unadsorbed DPT during 1970s and 1980s. Serological investigation showed that antibody response to diphtheria, tetanus were elicited in four groups of children after primary immunization, but, the antibody response to pertussis was poor in children immunized with unadsorbed DPT. Three kinds of antibody titres were increased significantly after booster immunization. Antibody persists more than eight years for diphtheria, about five years for tetanus and only three years for pertussis. Comparison of two-dose immunization of adsorbed DPT at two months interval and three dose immunization of unadsorbed DPT showed that antibody response to diphtheria, pertussis and tetanus were satisfied in adsorbed DPT than in unadsorbed one after primary immunization, and there is no difference between primary and booster immunization.

Antibodies, Bacterial↗

[The clinico-epidemiological characteristics of diphtheria in adults].

Of 262 patients referred with suspicion of diphtheria the diagnosis was confirmed in 145 (55.3%). Clinico-epidemiological data indicate that the severity of diphtheria course, the tendency of increase of its incidence at the UkrSSR territory and in the USSR emphasize that early diagnosis and adequate treatment are of prime importance. To achieve this not only epidemiologists and infectionists but also cardiologists, otolaryngologists and general practitioners should actively participate in management of these patients. The authors pay special attention to carriers of pathogenic strains of diphtheria corynebacteria because their growth in these conditions may be a marker of epidemiological hazard.

Age Factors↗

[The immunomodulating properties of a diphtheria bacterial vaccine in in vitro experiments].

In this investigation lymphocytes sensitized with Corynebacterium diphtheriae antigens obtained from carriers and convalescents were used. The new diphtheria bacterial vaccine Codivac, in contrast to other comparable preparations (diphtheria toxoid, staphylococcal toxoid, staphylococcal vaccine, levamisole), was found to produce a more direct effect by modulating the levels of T-lymphocytes, depending on their initial levels in the patient. Codivac, together with other preparations, can be used for the study of the problems of immunostimulation and immunocorrective therapy.

Adjuvants, Immunologic↗

[Duration of immunity in children who received a primary complex of inoculations with ADT-M anatoxin and an assessment of postponed secondary revaccination against diphtheria and tetanus (the results of an epidemiologic trial)].

The prolonged observations of the immunological effectiveness of adsorbed diphtheria-tetanus toxoid with reduced antigen content in children who had received the primary course of immunization with this preparation showed that the preparation induced the development of prolonged and intensive immunity to both infections. In 2-3 years after the first booster immunization the protective level of diphtheria antitoxin was registered in 89.9% and that of tetanus antitoxin, in 99% of children. 6 years later the level of immunity remained practically unchanged: the titers of diphtheria antitoxin above the protection level were determined in 92% and those of tetanus antitoxin, in 97% of children. These data made it possible to increase intervals between booster immunizations to 6-7 years in children of this category. The results of the epidemiological trial made to find out the possibility of a change in the timing of the second booster immunization confirmed the expediency of postponing booster immunization from 6 and 11 years to 9 and 16 years of age.

Child↗

Diphtheria, tetanus, and pertussis immunizations in adults.

Although only few cases of diphtheria are reported annually in the United States, substantial numbers of adults have declining levels of protective serum antitoxin. A recent outbreak of diphtheria in Sweden emphasizes the importance of reimmunizing adults in diphtheria toxoid, included as part of routine use of tetanus/diphtheria toxoid. Tetanus is a completely preventable disease. Yet, most of the 60 to 100 annual cases of tetanus occur in older adults with no prior history of immunization. Tetanus immunization should be a routine part of medical care of all adults. Research currently is aimed at improving the efficacy and safety of pertussis vaccine. Future vaccines may be useful in protecting health care workers and other adults who have extensive contact with children against pertussis.

Adult↗

[Physician, state and public health: the campaign against diphtheria in Belgium (1894-1914)].

On 100 deaths caused by diphtheria in Belgium at the end to the 19th century, 90% had not reached the age of 6. In the beginning of the nineties an antitoxin had been developed against the so called "terror of mothers". Very slowly, the production of sera took place, first of all in Germany, after 1894 in our country too. The battle against diphtheria became the subject of parliamentary debates (in the years 1894-1895 and 1900) and of several comments and articles in the Belgian medical press. The authorities followed the evolution of morbidity closely, commissions were charged with the study of the effectiveness of sera and of the foundation, if necessary, of an institution for serotherapy. As a result of an intensive campaign of serotherapy, the decrease of mortality rates due to diphtheria was sensational after 1910.

Belgium↗