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Pathogens (Basel, Switzerland) Oct 2022Only three species are known to produce a lethal exotoxin called diphtheria toxin. These are and . The diphtheria toxin gene () is carried in a family of closely... (Review)
Review
Only three species are known to produce a lethal exotoxin called diphtheria toxin. These are and . The diphtheria toxin gene () is carried in a family of closely related corynebacteriophages and therefore the toxin can be produced only through lysogenisation, in which the corynephage encoding is stably inserted into the chromosome. However, 'nontoxigenic gene-bearing' (NTTB) strains, which are genotypically -positive but do not express the protein, have been described. The emergence of NTTB strains was first observed during the 1990s diphtheria epidemic in Eastern Europe and nowadays such isolates have been detected in many countries in the world. Recently, novel species of genus have been described which might have the potential of producing the diphtheria toxin due to the possession of the diphtheria toxin gene but it has not produced toxin in laboratory tests. The circulation of NTTB strains could be related to the increased risk for diphtheria disease arising from the risk of re-emerging toxin expression. The article presents the mechanism of diphtheria toxin expression and action, recently described novel species of NTTB corynebacteria as well as the taxonomic changes within the group.
PubMed: 36365015
DOI: 10.3390/pathogens11111264 -
Pakistan Journal of Medical Sciences Jan 2024Diphtheria vaccination in the EPI program has controlled much of the childhood infection. Nevertheless, sporadic adult cases of Diphtheria come up every now and then in...
Diphtheria vaccination in the EPI program has controlled much of the childhood infection. Nevertheless, sporadic adult cases of Diphtheria come up every now and then in Pakistan and other South-Asian countries. This is, most likely, due to the lack of booster dosing of Diphtheria vaccine in adulthood. In an effort to suppress the spread of this infection, adult vaccinations need to be mandated.
PubMed: 38328652
DOI: 10.12669/pjms.40.2(ICON).8954 -
Japanese Journal of Infectious Diseases Sep 2021Tetanus toxoid, reduced diphtheria toxoid, and acellular pertussis (Tdap) vaccine is generally used for booster vaccination of infants in Europe and the United States to... (Observational Study)
Observational Study
Tetanus toxoid, reduced diphtheria toxoid, and acellular pertussis (Tdap) vaccine is generally used for booster vaccination of infants in Europe and the United States to avoid increased reactogenicity after diphtheria and tetanus toxoids and acellular pertussis (DTaP) vaccination. However, Japan has extended the use of additional DTaP vaccination without reducing the antigen dose for diphtheria and pertussis in adolescents and adults, despite limited reports on its safety in adults. This prospective, observational, questionnaire-based study investigated the occurrence of adverse events (AEs) following DTaP vaccination between June 2018 and June 2019 in participants aged 10 years or older. Of the 250 eligible participants, 235 (94%) responded regarding AEs. Among them, 133 (56.6%) reported AEs, of which 39 reported systemic AEs (16.6%) and 120 reported local AEs (51.1%) attributed to DTaP vaccination. The incidence of local AEs was markedly higher with DTaP vaccination than with non-DTaP vaccination (51.1% vs. 10.5%), and AEs appeared later (P < 0.01) and lasted longer (P < 0.01) with DTaP vaccination. However, more than 75% of these AEs resolved within 7 days. DTaP vaccination was not associated with any serious AEs. These results indicate that the DTaP vaccine can be widely used as a booster in adults as an alternative to the Tdap vaccine.
Topics: Adolescent; Adult; Antibodies, Bacterial; Diphtheria; Diphtheria-Tetanus-Pertussis Vaccine; Diphtheria-Tetanus-acellular Pertussis Vaccines; Humans; Immunization, Secondary; Incidence; Infant; Japan; Male; Prospective Studies; Tetanus; Toxoids; Whooping Cough
PubMed: 33518629
DOI: 10.7883/yoken.JJID.2020.947 -
Expert Review of Vaccines 2023Hexaxim is a hexavalent vaccine approved as primary and booster vaccination in infants 6 weeks and older, protecting against diphtheria, tetanus, pertussis,... (Review)
Review
INTRODUCTION
Hexaxim is a hexavalent vaccine approved as primary and booster vaccination in infants 6 weeks and older, protecting against diphtheria, tetanus, pertussis, poliomyelitis, hepatitis B and Haemophilus influenzae type b.
AREAS COVERED
To evaluate the immunogenicity and reactogenicity (safety) of Hexaxim (Hexyon, Hexacima) in primary and booster vaccine schedules; long-term antibody persistence; concomitant use with other childhood vaccines and use in immunocompromised infants. Hexaxim was found to be noninferior to other licensed hexavalent vaccines, being highly immunogenic for all toxoids/antigens and with an acceptable safety profile. It can be administered concomitantly with other childhood vaccines. Hexaxim can be given as a booster for infants primed with Infanrix Hexa and given in a pentavalent-hexavalent-pentavalent series. Hexaxim elicits a similar immune response and safety profile in human immunodeficiency virus (HIV) positive infants. It has the benefit of being a ready-to-use liquid formulation, minimizing dosage errors and preparation time.
EXPERT OPINION
Hexaxim has an acceptable safety profile and provides immunity against all six targeted diseases. It is an acceptable alternative to other hexavalent vaccines on the market. Further studies are required on the use of immunocompromised patients as well as the antibody persistence of each of the vaccine components.
Topics: Infant; Humans; Child; Immunization, Secondary; Immunization Schedule; Diphtheria-Tetanus-Pertussis Vaccine; Haemophilus Vaccines; Poliovirus Vaccine, Inactivated; Hepatitis B Vaccines; Vaccines, Combined; Antibodies, Bacterial
PubMed: 36545777
DOI: 10.1080/14760584.2023.2161519 -
Indian Journal of Pathology &... Apr 2024Diphtheria is an infectious disease caused by gram-positive bacilli C. diphtheriae involving nasal, pharyngeal, tonsillar, or laryngeal mucus membranes. The mortality...
INTRODUCTION
Diphtheria is an infectious disease caused by gram-positive bacilli C. diphtheriae involving nasal, pharyngeal, tonsillar, or laryngeal mucus membranes. The mortality rate is as high as 20%, with India contributing almost 78% of the world incidence.
AIMS AND OBJECTIVES
We report a fatal case of nasopharyngeal diphtheria with carrier study in close contacts.
MATERIALS AND METHODS
Seven years child presented with fever, throat pain, and earache for 3 days followed by neck swelling and noisy respiration. On examination, membrane was present in the throat, which was received for Albert and Gram staining and reported as positive for C. diphtheria like organisms followed by culture. The patient was treated with ADS and antibiotics, and intensively managed, but still succumbed to death. Follow-up was done for carriage of C. diphtheriae on the throat and nasopharyngeal swabs of siblings and close contacts. It was isolated in 3 of them. Samples were processed for Gram, Albert stain, and culture. Identification, antibiotic sensitivity, and toxigenicity were done.
RESULTS AND DISCUSSION
Four samples, one from the patient and three from contacts showed the presence of gram-positive slender bacilli with cuneiform arrangement, less cellular infiltrate on the Gram stain, and the presence of few metachromatic granules in the Albert stain. C. diphtheriae was grown on Potassium Tellurite agar. Antibiogram of all isolates was similar with resistance to Erythromycin and sensitivity to Penicillin. Isolates were confirmed by PCR and ToxA gene was detected. Contacts were treated with Penicillin and repeat swabs were negative.
CONCLUSION
Present health statistics and this study suggests, fight against diphtheria in India is far from being over. It still lurks in some remote areas. It is a need to remain vigilant, keep tracing, and treating contacts to curtail down the rate of infection. In view of the resurgence, Government has given directives to replace TT with Td in UIP. Still, a lot needs to be done.
Topics: Child; Humans; Anti-Bacterial Agents; Carrier State; Corynebacterium diphtheriae; Diphtheria; Fatal Outcome; India; Microbial Sensitivity Tests; Nasopharynx; Pharynx
PubMed: 38394413
DOI: 10.4103/ijpm.ijpm_265_23 -
Microorganisms Apr 2024(1) Background: We aim to systematically review the current evidence on immunity against tetanus, diphtheria, and pertussis in adult solid organ transplantation (SOT)... (Review)
Review
(1) Background: We aim to systematically review the current evidence on immunity against tetanus, diphtheria, and pertussis in adult solid organ transplantation (SOT) recipients, either through natural infection or vaccination. (2) Methods: This systematic review was conducted per PRISMA guidelines. We assessed the risk of bias using the Cochrane RoB 2 and ROBINS-I and summarized the findings narratively due to the heterogeneity of the studies. (3) Results: Of the 315 screened articles, 11 were included. Tetanus immunity varied between 55% and 86%, diphtheria immunity from 23% to 75%, and pertussis immunity was between 46% and 82%. Post-vaccination immunity showed variation across the studies, with some indicating reductions and others no change, with antibody responses influenced by transplanted organs, gender, age, and immunosuppressive regimens. The single randomized study exhibited a low risk of bias, while of the ten non-randomized studies, six showed moderate and four serious risks of bias, necessitating cautious interpretation of results. (4) Conclusions: SOT recipients exhibit considerable immunity against tetanus and diphtheria at transplantation, but this immunity decreases over time. Although vaccination can enhance this immunity, the response may be suboptimal, and the increased antibody levels may not persist, underscoring the need for tailored vaccination strategies in this vulnerable population.
PubMed: 38792678
DOI: 10.3390/microorganisms12050847 -
Open Forum Infectious Diseases Jan 2022Respiratory diphtheria is a potentially fatal toxin-mediated disease that is rare among highly vaccinated populations. Cutaneous infections with toxigenic are most...
BACKGROUND
Respiratory diphtheria is a potentially fatal toxin-mediated disease that is rare among highly vaccinated populations. Cutaneous infections with toxigenic are most commonly linked to travel to an endemic region. has emerged as a predominant, locally acquired cause of respiratory and cutaneous diphtheria in Western Europe. Recently, public health agencies from several highly vaccinated regions expanded their guidelines to investigate toxigenic cutaneous diphtheria regardless of travel history. With relatively unknown epidemiology of in North America, and increasing diphtheria toxin testing over the last decade, this change could lead to substantial increases in public health investigations with unclear benefits.
METHODS
This study examined the diagnostic and public health benefits of toxigenic cutaneous diphtheria investigations in the highly vaccinated population of Alberta, Canada, where travel history is not required for cutaneous diphtheria investigations. All isolates collected between 2010 and 2019 were reviewed for specimen source, toxigenicity, biovar, and associated clinical and public health data.
RESULTS
Of these, 5% of C were toxigenic and 82% were isolated from cutaneous sites. Three cases of toxigenic cutaneous disease were identified, none from patients with recent travel. Contact tracing identified asymptomatic colonization among 0%-26% of close contacts, with identical isolate profiles among colonized contacts and primary cases.
CONCLUSIONS
Cutaneous diphtheria in nonendemic regions warrants public health investigation regardless of travel history and overall vaccination levels. This study underscores the importance of including in public health guidelines to assess the overall prevalence and epidemiology of toxigenic corynebacteria.
PubMed: 34988247
DOI: 10.1093/ofid/ofab414 -
Toxins Dec 2023The production of therapeutic recombinant toxins requires careful host cell selection. Bacteria, yeast, and mammalian cells are common choices, but no universal solution... (Review)
Review
The production of therapeutic recombinant toxins requires careful host cell selection. Bacteria, yeast, and mammalian cells are common choices, but no universal solution exists. Achieving the delicate balance in toxin production is crucial due to potential self-intoxication. Recombinant toxins from various sources find applications in antimicrobials, biotechnology, cancer drugs, and vaccines. "Toxin-based therapy" targets diseased cells using three strategies. Targeted cancer therapy, like antibody-toxin conjugates, fusion toxins, or "suicide gene therapy", can selectively eliminate cancer cells, leaving healthy cells unharmed. Notable toxins from various biological sources may be used as full-length toxins, as plant (saporin) or animal (melittin) toxins, or as isolated domains that are typical of bacterial toxins, including Pseudomonas Exotoxin A (PE) and diphtheria toxin (DT). This paper outlines toxin expression methods and system advantages and disadvantages, emphasizing host cell selection's critical role.
Topics: Humans; Animals; Bacterial Toxins; Diphtheria Toxin; Immunotoxins; Neoplasms; Pseudomonas aeruginosa Exotoxin A; Recombinant Fusion Proteins; Exotoxins; Mammals
PubMed: 38133203
DOI: 10.3390/toxins15120699 -
Journal of Clinical Microbiology Nov 2021Corynebacterium diphtheriae is highly transmissible and can cause large diphtheria outbreaks where vaccination coverage is insufficient. Sporadic cases or small clusters...
Corynebacterium diphtheriae is highly transmissible and can cause large diphtheria outbreaks where vaccination coverage is insufficient. Sporadic cases or small clusters are observed in high-vaccination settings. The phylogeography and short timescale evolution of C. diphtheriae are not well understood, in part due to a lack of harmonized analytical approaches of genomic surveillance and strain tracking. We combined 1,305 genes with highly reproducible allele calls into a core genome multilocus sequence typing (cgMLST) scheme. We analyzed cgMLST gene diversity among 602 isolates from sporadic clinical cases, small clusters, or large outbreaks. We defined sublineages based on the phylogenetic structure within C. diphtheriae and strains based on the highest number of cgMLST mismatches within documented outbreaks. We performed time-scaled phylogenetic analyses of major sublineages. The cgMLST scheme showed high allele call rate in C. diphtheriae and the closely related species C. belfantii and C. rouxii. We demonstrate its utility to delineate epidemiological case clusters and outbreaks using a 25 mismatches threshold and reveal a number of cryptic transmission chains, most of which are geographically restricted to one or a few adjacent countries. Subcultures of the vaccine strain PW8 differed by up to 20 cgMLST mismatches. Phylogenetic analyses revealed a short-timescale evolutionary gain or loss of the diphtheria toxin and biovar-associated genes. We devised a genomic taxonomy of strains and deeper sublineages (defined using a 500-cgMLST-mismatch threshold), currently comprising 151 sublineages, only a few of which are geographically widespread based on current sampling. The cgMLST genotyping tool and nomenclature was made publicly accessible (https://bigsdb.pasteur.fr/diphtheria). Standardized genome-scale strain genotyping will help tracing transmission and geographic spread of C. diphtheriae. The unified genomic taxonomy of C. diphtheriae strains provides a common language for studies of ecology, evolution, and virulence heterogeneity among C. diphtheriae sublineages.
Topics: Corynebacterium diphtheriae; Diphtheria; Genome, Bacterial; Genomics; Humans; Multilocus Sequence Typing; Phylogeny
PubMed: 34524891
DOI: 10.1128/JCM.01581-21 -
Human Vaccines & Immunotherapeutics Dec 2022As one of the powerful vaccines for completely eradicating all types of poliovirus in the polio endgame period, the novel IPV, which is prepared from attenuated polio...
As one of the powerful vaccines for completely eradicating all types of poliovirus in the polio endgame period, the novel IPV, which is prepared from attenuated polio Sabin strains (sIPV) and is expected to reduce the overall biosafety risk, was licensed in Japan (sIPV-containing diphtheria-tetanus-acellular pertussis combination vaccines, DTP-sIPV) and China (sIPV) in November 2012 and January 2015, respectively. Limited by the development progress and the manufactured sIPV ability, it has to date only been used in Chinese Expanded Programme on Immunization (EPI) by sequential scheduling with bOPV and in Japan with DTP-sIPV vaccination. We herein summarize postapproval clinical studies of sIPV in both full-dose schedules and sequential schedules, focusing on China, to evaluate sIPV safety and immunogenicity in large populations to provide important data for its broad application in developing countries worldwide.
Topics: Antibodies, Viral; Diphtheria-Tetanus-Pertussis Vaccine; Diphtheria-Tetanus-acellular Pertussis Vaccines; Humans; Immunization Schedule; Poliomyelitis; Poliovirus; Poliovirus Vaccine, Inactivated
PubMed: 34213408
DOI: 10.1080/21645515.2021.1940653