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During August–December 2022, toxigenic Corynebacterium diphtheriae was isolated from 25 refugees with skin infections and 2 refugees with asymptomatic throat colonization at a refugee reception center in Germany. None had systemic toxin-mediated illness. Of erosive/ulcerative skin infections, 96% were polymicrobial. Erosive/ ulcerative wounds in refugees should undergo testing to rule out cutaneous diphtheria. [ABSTRACT FROM AUTHOR]

Purpose: Diphtheria, still present in many countries of the world, is caused by toxigenic strains of species of the Corynebacterium diphtheriae complex, mainly Corynebacterium diphtheriae and the emerging zoonotic pathogen C. ulcerans. The immunoprecipitation test according to Elek is the gold standard for detection of the major virulence factor diphtheria toxin (DT) in toxigenic corynebacteria. Due to its sophisticated methodological requirements, the classical Elek test is performed mainly by specialized reference laboratories. It was revealed that the current modification of the Elek test does not detect the toxin in weakly toxigenic isolates. Therefore, a more robust method for detecting free DT is urgently needed, especially for toxigenic C. ulcerans strains which are known to produce often much lower amounts of DT than C. diphtheriae. Methods: Thirty-one tox-positive C. ulcerans isolates with a negative standard Elek test result previously determined as NTTB (non-toxigenic tox bearing) were re-analyzed in this study using a modified immunoprecipitation method optimized regarding different parameters including type and concentration of antitoxin, medium volume, inoculum distance from the antitoxin disk and position of controls. Results: All 31 C. ulcerans strains tested positive in the optimized Elek test. Conclusion: Only with a reliable and easy-to-handle method for detecting the toxigenicity of C. ulcerans, it is possible to assess the etiological role of this emerging zoonotic bacterium in human pathology. [ABSTRACT FROM AUTHOR]

Background: Vaccinations are among the most effective preventative healthcare measures. The aim of this cross-sectional study was to evaluate the adherence of adults with pre-existing pulmonary conditions to the national vaccination schedule and to identify reasons for poor adherence. Methods: All patients with an appointment at Donaustauf hospital between October 2019 and April 2020 were asked to bring their vaccination certificates for evaluation and to compete a questionnaire. To determine the adherence vaccination certificates and patients' comorbidities were correlated with the national recommendations of the German Standing Committee on Vaccination (STIKO). Results: 571 (65.6%) of all patients believed that their vaccination status was up-to-date. An appropriate vaccination status according to national recommendations (STIKO) was documented as follows: tetanus 56.4% (375/665), diphtheria 43.2% (292/676), poliomyelitis 28.5% (189/662), tick-borne encephalitis 45.4% (300/659), hepatitis A 31.0% (18/58), hepatitis B 34.6% (27/78), shingles 1.2% (6/489), influenza 21.0% (125/596, season 2019/2020), measles 38.3% (31/81), rubella 33.3% (7/21), pneumococcal disease 29.5% (175/593), pertussis 54.2% (365/674) and haemophilus influenza type b 100% (1/1). Adherence to rabies (0/2), varicella (0/28), meningococcal type ACWY (0/36) and type b (0/36) was 0%. 72% of patients would follow a physician's recommendation to get vaccinated. Conclusion: Adherence to STIKO recommendations was poor. However, patients are willing to follow a physician's recommendation for vaccination. [ABSTRACT FROM AUTHOR]

Background: Diphtheria is mainly caused by diphtheria-toxin-producing strains of Corynebacterium diphtheriae and Corynebacterium ulcerans. The recommended first-line antibiotic is penicillin or erythromycin, but reliable susceptibility data are scarce.Objectives: To define WT MIC distributions of 12 antimicrobial agents and provide data for the determination of tentative epidemiological cut-off values (TECOFFs) for potentially toxigenic corynebacteria and to evaluate the potential usefulness of a gradient test (Etest) for susceptibility testing of penicillin, erythromycin and clindamycin.Methods: For the 421 human or veterinary isolates from the period 2011-17, MICs of 12 antimicrobial agents were determined. Etest performance was evaluated for penicillin, erythromycin and clindamycin.Results: MIC distributions were characterized and TECOFFs could be set for 11 out of 24 antibiotic/species combinations. The current EUCAST clinical breakpoints, predominantly determined for Corynebacterium species other than C. diphtheriae and C. ulcerans, divide the WT MIC distributions of penicillin and clindamycin, thereby making reproducible susceptibility testing of C. diphtheriae and C. ulcerans difficult. For erythromycin, 4% of C. diphtheriae and 2% of C. ulcerans had MICs higher than those for WT isolates. Phenotypically detectable resistance to other antibiotics was rare. Etest underestimated MICs of penicillin and lower concentrations needed to be included for erythromycin, while for clindamycin the Etest was not a good surrogate method.Conclusions: MIC distributions based on reference broth microdilution for potentially toxigenic Corynebacterium spp. were developed. For five and six agents, TECOFFs were suggested for C. diphtheriae and C. ulcerans, respectively, but for Corynebacterium pseudotuberculosis the number of isolates was too low. [ABSTRACT FROM AUTHOR]

Antiretroviral therapy has made HIV infection a chronic controlled disease, where aspects of the immunoprophylaxis of infectious diseases have acquired important clinical significance. The goal of the study was to determine the clinical and laboratory predictors of antitoxic immunity against diphtheria and tetanus in HIV-infected adults. The study included 90 HIV-infected patients aged 22 to 60 years (main group). The control group consisted of 49 immunocompetent volunteers of the corresponding age. The levels of anti-diphtheria and anti-tetanus antibodies were determined by ELISA using the diagnostic test systems RIDASCREEN Diphtheria IgG and RIDASCREEN Tetanus IgG (R-Biopharm AG, Germany). Statistical processing was performed using the licensed software product STATISTICA v.6.1. Significant differences were found between the titers of antitoxic antibodies in HIV-infected and immunocompetent adults. According to the correlation analysis, the decrease in the titers of antidiphtheria antibodies was revealed with an increase in the age of the HIV-infected patient (rs=-0.21; p=0.05). The fact of smoking (rs=-0.31; p=0.003), lowered body weight (BMI<18.5 kg/m2) (rs=-0.29; p=0.006), the presence of arterial hypertension (rs=-0.38; p<0.001), a history of bone fractures over the past 5 years (rs=-0.38; p<0.001), anemia (rs=-0.21; p=0.049), thrombocytopenia (rs=-0.44; p<0.001), accelerated ESR (rs=-0.61; p<0.001), the presence of hairy leukoplakia of the tongue (rs=-0.23; p=0.027), frequent infections caused by herpes simplex (rs=- 0.52; p=0.003) and varicella zoster virus (rs=-0.34; p=0.013) are associated with low levels of antidiphtheria antibodies. A direct relationship was found between the intensity of anti-diphtheria immunity and patients receiving OST (rs=+0.54; p=0.003) and with a history of injuries with impaired skin integrity (rs=+0.31; p=0.003). Decreased anti-tetanus immunity in HIV-infected patients was also associated with smoking (rs=-0.48; p<0.001), decreased BMI (rs=-0.71; p<0.001), anemia (rs=-0.33; p=0.002), thrombocytopenia (rs=-0.75; p<0.001), a history of bone fractures over the past 5 years (rs=-0.67; p<0.001); the total number of HIV-associated opportunistic diseases (rs=-0.42; p<0.001), including the presence of oropharyngeal candidiasis (rs=-0.23; p=0.032) and hairy leukoplakia of the tongue (rs=-0.57; p<0.001), history of Herpes Zoster in the past (rs=-0.48; p<0.001), with frequent relapses of diseases caused by herpes simplex viruses (rs=-0.78; p<0.001) and repeated episodes of herpes zoster (rs=-0.74; p<0.001), as well as with pathology of the skin (rs=-0.55; p<0.001). Protective predictors of anti-tetanus antitoxic immunity strength were established: male gender (rs=+0.22; p=0.039), parenterally acquired HIV infection (rs=+0.21; p=0.05), HIV-infected patients receiving OST (rs=+0.40; p=0.041). A direct relationship was found with the decreased level of hemoglobin (rs=+0.41; p<0.001), the increase of relative number of lymphocytes in the blood (rs=+0.21; p=0.05), as well as with living in rural areas (rs=+0.40; p<0.001) and the presence of injuries with impairment of skin integrity (rs=+0.84; p<0.001). Clinical and laboratory predictors of strength of antitoxic immunity against diphtheria and tetanus in HIV-infected adults were identified, which allows us to create an individual “vaccination roadmap” for patients in this category. [ABSTRACT FROM AUTHOR]

Background: This study assessed the safety and immunogenicity of a new booster vaccine against tetanus, diphtheria, and pertussis manufactured by Serum Institute of India Pvt. Ltd (SIIPL Tdap)., Methods: The Phase II/III trial was randomized (2:1), observer blinded and active controlled. Healthy subjects aged 4-65 years received a single dose of either SIIPL Tdap or comparator Tdap vaccine (Boostrix®, GlaxoSmithKline, Belgium), and were followed-up for 30 days. Blood samples for safety and immunogenicity assessments were collected pre-vaccination and on day 30 post-vaccination. The study assessed safety and reactogenicity of SIIPL Tdap compared to the comparator Tdap as well as the co-primary immunogenicity outcomes: (i) seroprotection rates against diphtheria toxoid (DT) and tetanus toxoid (TT) and (ii) the booster response rates against pertussis toxoid (PT), filamentous hemagglutinin (FHA) and pertactin (PRN) 30 days post-vaccination in all study subjects. A margin of -10 % was used for non-inferiority testing. Secondary outcomes included the booster response rates against DT and TT, seropositivity rates against pertussis antigens, and antibody geometric mean concentrations (GMCs) for all vaccine components., Results: At Day 30 post-vaccination, SIIPL Tdap was assessed as non-inferior to the comparator Tdap in terms of: i) seroprotection rates against DT (94.4 % vs. 94.9 %) and TT (99.9 % vs. 100 %) and ii) pertussis booster response rates (93.8 % vs. 88.4 % anti-PT, 89.7 % vs. 90.9 % anti-FHA and 86.3 % vs. 84.4 % anti-PRN), for SIIPL Tdap versus comparator Tdap, respectively. GMCs for anti-PT and anti-PRN were higher in subjects vaccinated with SIIPL Tdap compared to comparator Tdap. All other secondary outcomes were comparable. The overall frequency of local and systemic solicited AEs was comparable; no treatment related SAEs were reported., Conclusions: Booster vaccination with SIIPL Tdap was non-inferior to comparator Tdap with respect to the immunogenicity of the vaccine components and was equally well tolerated. EudraCT number: 2019-002706-46., Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: IA, MM, FP, NMM, LG reports a relationship with Serum Institute of India Pvt Ltd that includes: consulting or advisory. SP, PP, SS, SD, HS, HR, MG, SG, US reports a relationship with Serum Institute of India Pvt Ltd that includes: employment., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

The article discusses the cases of cutaneous diphtheria among refugees in Germany in 2022. Also cited are the causes of diphtheria like the toxigenic strains of Corynebacterium (C.) diphtheriae, C. ulcerans, and C. pseudotuberculosis, skin contact as the primary route of transmission of diphtheria, and the recommended treatments like antibiotic eradication therapy using erythromycin and penicillin.

Purpose: The prevalence of protective anti-diphtheria toxin antibodies decreases with age. Therefore, the elderly might serve as reservoir for potentially toxigenic Corynebacterium ( C.) species ( C. diphtheriae, C. ulcerans, and C. pseudotuberculosis). This study aimed to examine the colonization rate of the nasopharynx with corynebacteria of individuals aged 65 years and older. Methods: In the period from October 2012 to June 2013, nasal and throat swabs were taken from 714 asymptomatic subjects aged 65-106 years (average age 77.2) at three regions in Germany and investigated for Corynebacterium species. Results: A total of 402 strains of Corynebacterium species were isolated from 388 out of 714 asymptomatic subjects (carriage rate 54.3%). The carriage rate was significantly higher in study participants living in retirement homes (68.4%) compared to those living autonomously at home (51.1%). Strains were isolated mostly from the nose (99%). Corynebacterium accolens was the most often isolated species (39.8%), followed by C. propinquum (24.1%), C. pseudodiphtheriticum (19.4%), and C. tuberculostearicum (10.2%). No C. diphtheriae, C. ulcerans, and C. pseudotuberculosis strains were isolated. A subsample of 74 subjects was tested serologically for anti-diphtheria antibodies. Protective anti-diphtheria toxin antibodies were found in 29.7% of the subjects; 70.3% showed no protective immunity. Conclusions: These results suggest that carriage of potentially toxigenic corynebacteria is very rare among people aged 65 and older in Germany. However, the low prevalence of protective anti-diphtheria toxin antibodies might pose a risk for acquiring diphtheria especially for the elderly. [ABSTRACT FROM AUTHOR]

From July 2022, cases of imported diphtheria with toxigenic Corynebacterium diphtheriae remarkably increased among migrants arriving in Germany. Up to 30 September 2022, 44 cases have been reported to the national public health institute, all laboratory-confirmed, male, and mainly coming from Syria (n = 21) and Afghanistan (n = 17). Phylogeny and available journey information indicate that most cases (n = 19) were infected along the Balkan route. Active case finding, increased laboratory preparedness and epicentre localisation in countries along this route are important.

Background: In June 2015, a 45-year-old man suffering from acute necrotic tonsillitis and throat phlegmon was hospitalized in Nuremberg, Germany. After emergency surgery the patient was initially treated with antibiotics. Results: A throat swab grew a toxigenic Corynebacterium diphtheriae biovar mitis strain. The patient's vaccination status was not documented and the patient was tested serologically for anti-diphtheria antibodies showing no protective immunity. Extensive control investigations were performed by the local health department showing no likely source of his infection. Conclusion: No secondary cases were found and the patient completely recovered. [ABSTRACT FROM AUTHOR]

Reports on cases of human diphtheria caused by toxigenic Corynebacterium ulcerans that were linked to occupational swine contact as well as isolation of C ulcerans from wild boars have suggested that pigs might serve as reservoir for human infections. Therefore, a prevalence study on Corynebacterium species nasal carriage in pigs and their farmers was performed between August 1 and December 31, 2009, in 41 swine farms from Bavaria, Germany. All 411 asymptomatic pigs and 29 of 30 healthy farmers were colonised with Corynebacterium strains of up to 11 different species. No potentially toxigenic Corynebacterium strain was isolated either from the pigs or from their farmers, respectively. The patterns of the species composition in the pigs and the farmers were very similar, suggesting a potential transmission of strains between animals and humans. [ABSTRACT FROM AUTHOR]

In 2010, two independent cases of cutaneous diphtheria caused by toxigenic C. ulcerans were identified in Germany. Both patients had intense occupational contact with pigs. Diagnostic work-up comprising biochemical differentiation, rpoB sequencing, matrix-assisted laser desorption/ionization time-of-flight mass spectrometry ( MALDI- TOF) analysis, real-time tox PCR and Elek test as well as public health measures including an intensified source tracing involving 83 asymptomatic pigs of an associated pig farm are presented. [ABSTRACT FROM AUTHOR]

This article shows how a new diphtheria antitoxin serum medication emerged from the efforts to produce, market, regulate, distribute and apply it in the two respective countries, France and Germany. It discusses the importance of the institutional foundations of serum production and illustrates the decisive role played by existing ways of regulating in the rapid development of new legal statutes. It explains the consequences that flowed from the respective administrative organization of marketing and dissemination. It also explores how an experimental object was transformed into an object of the public health system and stabilized by administrative means.

The article discusses the two cultures of regulation of serum production and distribution in France and Germany at the end of nineteenth century. It mentions that serum production started after a serum against diphtheria became available in pharmacies starting in August 1894. In Germany, serum sale was regulated by the state as compared to France where no direct control of the state was taken to serum production. An overview of the process of the serum production, regulation of the serum therapy in two countries and the financial aspects of the serum production are also included.

In October 2016, an adolescent boy sought care for acute genital ulceration in Cologne, Germany. We presumed a sexually transmitted infection, but initial diagnostic procedures yielded negative results. He was hospitalized because swab samples from the lesion grew toxigenic Corynebacterium diphtheriae, leading to the diagnosis of possibly sexually transmitted cutaneous diphtheria. [ABSTRACT FROM AUTHOR]

Recent outbreaks of diphtheria have drawn attention to the re-emergence of this disease. This study investigated susceptibility to diphtheria in north-east Germany and its relationship to gender and social factors. A study population of 4275 individuals recruited for the population-based Study of Health in Pomerania (SHIP) was available for analysis. IgG antibodies against diphtheria toxin were determined by ELISA and were used to define susceptibility to diphtheria (i.e., IgG titres < 0.1 IU/mL). The prevalence of susceptibility to diphtheria was 32.4%. Multivariate analysis revealed 45% increased odds of women being susceptible to diphtheria. Women who had not received diphtheria toxoid vaccination during the previous 10 years had four-fold increased odds of being susceptible to diphtheria toxin compared with unvaccinated men. None of the social factors investigated was associated with susceptibility status. It was concluded that a high proportion of middle-aged adults was susceptible to diphtheria. Women lacked seroprotection more often than men, which might be explained, in part, by gender-specific immune responses following vaccination. There is a need for information campaigns to improve public awareness of these problems. [ABSTRACT FROM AUTHOR]

Introduction: Little is known about the completeness and timely administration of recommended standard immunizations in Germany. The goal of this study was to determine compliance with official standard immunization recommendations in adolescents attending secondary schools in the city of Erlangen, Germany.Methods: Adolescents who were attending 5th grade (at approximately 11 years of age), 8th grade (14 years), or 10th and 11th grade (16-17 years) classes at any of the 13 of 14 schools that had agreed to participate were eligible to be enrolled.Results: While coverage for the primary series of diphtheria, tetanus and poliomyelitis immunizations was satisfactory (98%), coverage for measles-mumps-rubella immunizations (dose 1: 89-96%; dose 2: 60-76%) and hepatitis B (doses 1-3: 61%) was suboptimal. Of note, 39% of students had not received any immunization against pertussis. Completion of immunization series generally was significantly delayed. Furthermore, rates for recommended booster doses in adolescence were disappointingly low with 21% for tetanus component vaccines and <10% for the fifth dose of pertussis.Conclusions: Significant immunization gaps for all recommended standard immunizations in adolescents were detected. This puts individuals at risk for serious vaccine-preventable diseases, contributes to suboptimal herd immunity in the population under study leaving the potential for future epidemics, and impedes national and international targets of disease reduction or elimination. [ABSTRACT FROM AUTHOR]

The article offers information on analyzing of Nontoxigenic Corynebacterium diphtheriae Infections in Europe. Topics discussed include analyzing nontoxigenic Corynebacterium diphtheriae infections in northern Germany during 2016–2017; scale of the problem of nontoxigenic C. diphtheriae infections in Europe; and study of community antibacterial dispensing which highest in Pacific people with higher incidence of infectious diseases.

In September 2018, a child who had returned from Somalia to Germany presented with cutaneous diphtheria by toxigenic Corynebacterium diphtheriae biovar mitis. The child's sibling had superinfected insect bites harbouring also toxigenic C. diphtheriae . Next generation sequencing (NGS) revealed the same strain in both patients suggesting very recent human-to-human transmission. Epidemiological and NGS data suggest that the two cutaneous diphtheria cases constitute the first outbreak by toxigenic C. diphtheriae in Germany since the 1980s.

From 2016 through the middle of 2017, the German Consiliary Laboratory on Diphtheria noted an increase in nontoxigenic Corynebacterium diphtheriae isolates submitted from cities in northern Germany. Many patients for whom epidemiologic data were available were homeless, alcohol or drug abusers, or both. After performing routine diagnostics and multilocus sequence typing (MLST), we analyzed isolates of sequence type (ST) 8 and previously submitted isolates by whole-genome sequencing. Results were analyzed for phylogenetic relationship by core genome MLST (cg-MLST) and whole-genome single-nucleotide polymorphism profiles. Next-generation sequencing-based cg-MLST revealed several outbreak clusters caused by ST8; the geographic focus was in the metropolitan areas of Hamburg and Berlin. To achieve enhanced analytical depth, we used additional cg-MLST target genes and genome-wide single-nucleotide polymorphisms. We identified patient characteristics and detected transmission events, providing evidence that nontoxigenic C. diphtheriae infection is a potential public health threat in industrialized countries.

Background: Pertussis in adults and adolescents could be reduced by replacing traditional tetanus and diphtheria (Td) boosters with reduced-antigen-content diphtheria-tetanus-acellular pertussis (dTpa) vaccines. This study evaluated the administration of dTpa-IPV (dTpa-inactivated poliovirus) in adults ten years after they received a booster dose of either dTpa-IPV, dTpa+IPV or Td-IPV in trial NCT01277705., Methods: Open multicentre, phase IV study (www.clinicaltrials.govNCT01323959) in which healthy adults, who had received a previous dose of dTpa-IPV, dTpa+IPV or Td-IPV ten years earlier, received a single decennial booster dose of dTpa-IPV (Boostrix-polio, GlaxoSmithKline Vaccines). Blood samples were collected before and one month after booster vaccination. Antibody concentrations against all vaccine antigens were measured and reactogenicity and safety were assessed., Results: A total of 211 subjects (mean age 50.3 years) received vaccination of whom 201 were included in the according-to-protocol cohort for immunogenicity. Before the decennial dTpa-IPV booster, ≥71.0% subjects were seroprotected/seropositive against all vaccine antigens. One month after the booster dose, all subjects were seroprotected against tetanus and poliovirus types 2 and 3; ≥95.7% subjects were seroprotected against diphtheria and ≥98.3% against poliovirus type 1. Anti-pertussis booster responses for the various antigens were observed in ≥76.5% (pertussis toxoid; PT), ≥85.1% (filamentous haemagglutinin; FHA) and ≥63.2% (pertactin; PRN) of subjects. During the 4-day follow-up, the overall incidence of local AEs was 71.6%, 75.0% and 72.2% in dTpa-IPV, dTpa+IPV and Td-IPV groups, respectively. Pain was the most frequent solicited local adverse event (AE; ≥62.7% subjects) and fatigue the most frequent solicited general AE (≥18.5%). No serious AEs were reported during the study., Conclusion: A booster dose of dTpa-IPV was immunogenic and well tolerated in adults who had received a booster dose of either dTpa-IPV, dTpa+IPV or Td-IPV, ten years previously and supports the repeated administration of dTpa-IPV., (Copyright © 2015 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Corynebacterium ulcerans may cause diphtheria in humans and caseous lymphadenitis in animals. We isolated nontoxigenic tox-bearing C. ulcerans from 13 game animals in Germany. Our results indicate a role for game animals as reservoirs for zoonotic C. ulcerans.