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Nature Reviews. Disease Primers Dec 2019Diphtheria is a potentially fatal infection mostly caused by toxigenic Corynebacterium diphtheriae strains and occasionally by toxigenic C. ulcerans and C.... (Review)
Review
Diphtheria is a potentially fatal infection mostly caused by toxigenic Corynebacterium diphtheriae strains and occasionally by toxigenic C. ulcerans and C. pseudotuberculosis strains. Diphtheria is generally an acute respiratory infection, characterized by the formation of a pseudomembrane in the throat, but cutaneous infections are possible. Systemic effects, such as myocarditis and neuropathy, which are associated with increased fatality risk, are due to diphtheria toxin, an exotoxin produced by the pathogen that inhibits protein synthesis and causes cell death. Clinical diagnosis is confirmed by the isolation and identification of the causative Corynebacterium spp., usually by bacterial culture followed by enzymatic and toxin detection tests. Diphtheria can be treated with the timely administration of diphtheria antitoxin and antimicrobial therapy. Although effective vaccines are available, this disease has the potential to re-emerge in countries where the recommended vaccination programmes are not sustained, and increasing proportions of adults are becoming susceptible to diphtheria. Thousands of diphtheria cases are still reported annually from several countries in Asia and Africa, along with many outbreaks. Changes in the epidemiology of diphtheria have been reported worldwide. The prevalence of toxigenic Corynebacterium spp. highlights the need for proper clinical and epidemiological investigations to quickly identify and treat affected individuals, along with public health measures to prevent and contain the spread of this disease.
Topics: Anti-Bacterial Agents; Corynebacterium; Diphtheria; Diphtheria Antitoxin; Humans; Vaccination
PubMed: 31804499
DOI: 10.1038/s41572-019-0131-y -
Future Microbiology Feb 2022The diphtheria-tetanus-pertussis (DTP) vaccine can prevent diphtheria, tetanus and pertussis. The component antigens of the DTP vaccine had long been monovalent... (Review)
Review
The diphtheria-tetanus-pertussis (DTP) vaccine can prevent diphtheria, tetanus and pertussis. The component antigens of the DTP vaccine had long been monovalent vaccines. The pertussis vaccine was licensed in 1914. The same year, the mixtures of diphtheria toxin and antitoxin were put into use. In 1926, alum-precipitated diphtheria toxoid was registered, and in 1937 adsorbed tetanus toxoid was put on the market. The development of numerous effective DTP vaccines quickly stimulated efforts to combine DTP with other routine vaccines for infants. This overview covers the most important information regarding the invention of DTP vaccines, their modifications and the needs that should be focused on in the future.
Topics: Antibodies, Bacterial; Diphtheria; Diphtheria-Tetanus-Pertussis Vaccine; Humans; Infant; Tetanus; Whooping Cough
PubMed: 34856810
DOI: 10.2217/fmb-2021-0167 -
Clinical Infectious Diseases : An... Jun 2020Diphtheria, once a major cause of childhood morbidity and mortality, all but disappeared following introduction of diphtheria vaccine. Recent outbreaks highlight the...
BACKGROUND
Diphtheria, once a major cause of childhood morbidity and mortality, all but disappeared following introduction of diphtheria vaccine. Recent outbreaks highlight the risk diphtheria poses when civil unrest interrupts vaccination and healthcare access. Lack of interest over the last century resulted in knowledge gaps about diphtheria's epidemiology, transmission, and control.
METHODS
We conducted 9 distinct systematic reviews on PubMed and Scopus (March-May 2018). We pooled and analyzed extracted data to fill in these key knowledge gaps.
RESULTS
We identified 6934 articles, reviewed 781 full texts, and included 266. From this, we estimate that the median incubation period is 1.4 days. On average, untreated cases are colonized for 18.5 days (95% credible interval [CrI], 17.7-19.4 days), and 95% clear Corynebacterium diphtheriae within 48 days (95% CrI, 46-51 days). Asymptomatic carriers cause 76% (95% confidence interval, 59%-87%) fewer cases over the course of infection than symptomatic cases. The basic reproductive number is 1.7-4.3. Receipt of 3 doses of diphtheria toxoid vaccine is 87% (95% CrI, 68%-97%) effective against symptomatic disease and reduces transmission by 60% (95% CrI, 51%-68%). Vaccinated individuals can become colonized and transmit; consequently, vaccination alone can only interrupt transmission in 28% of outbreak settings, making isolation and antibiotics essential. While antibiotics reduce the duration of infection, they must be paired with diphtheria antitoxin to limit morbidity.
CONCLUSIONS
Appropriate tools to confront diphtheria exist; however, accurate understanding of the unique characteristics is crucial and lifesaving treatments must be made widely available. This comprehensive update provides clinical and public health guidance for diphtheria-specific preparedness and response.
Topics: Child; Diphtheria; Disease Outbreaks; Humans; Vaccination
PubMed: 31425581
DOI: 10.1093/cid/ciz808 -
The Nurse Practitioner Oct 2023Travelers from parts of the world where diphtheria is endemic and vaccines are underutilized or unavailable may carry diphtheria, become ill, and spread the disease....
Travelers from parts of the world where diphtheria is endemic and vaccines are underutilized or unavailable may carry diphtheria, become ill, and spread the disease. This article provides an overview of diphtheria as well as management updates that are particularly critical amid new travel records and a climate of vaccine hesitancy.
Topics: Humans; Diphtheria; Travel
PubMed: 37751614
DOI: 10.1097/01.NPR.0000977916.64595.e2 -
Nursing Jun 2023Travelers from parts of the world where diphtheria is endemic and vaccines are underutilized may carry diphtheria and become ill. This article provides an overview of...
Travelers from parts of the world where diphtheria is endemic and vaccines are underutilized may carry diphtheria and become ill. This article provides an overview of diphtheria as well as management updates that are particularly critical amid a pandemic with healthcare disruptions and vaccine hesitancy.
Topics: Humans; Diphtheria; Vaccines; Vaccination
PubMed: 37212819
DOI: 10.1097/01.NURSE.0000918540.45884.d3 -
The Journal of Experimental Medicine Oct 2023The ZAKα-driven ribotoxic stress response (RSR) is activated by ribosome stalling and/or collisions. Recent work demonstrates that RSR also plays a role in innate...
The ZAKα-driven ribotoxic stress response (RSR) is activated by ribosome stalling and/or collisions. Recent work demonstrates that RSR also plays a role in innate immunity by activating the human NLRP1 inflammasome. Here, we report that ZAKα and NLRP1 sense bacterial exotoxins that target ribosome elongation factors. One such toxin, diphtheria toxin (DT), the causative agent for human diphtheria, triggers RSR-dependent inflammasome activation in primary human keratinocytes. This process requires iron-mediated DT production in the bacteria, as well as diphthamide synthesis and ZAKα/p38-driven NLRP1 phosphorylation in host cells. NLRP1 deletion abrogates IL-1β and IL-18 secretion by DT-intoxicated keratinocytes, while ZAKα deletion or inhibition additionally limits both pyroptotic and inflammasome-independent non-pyroptotic cell death. Consequently, pharmacologic inhibition of ZAKα is more effective than caspase-1 inhibition at protecting the epidermal barrier in a 3D skin model of cutaneous diphtheria. In summary, these findings implicate ZAKα-driven RSR and the NLRP1 inflammasome in antibacterial immunity and might explain certain aspects of diphtheria pathogenesis.
Topics: Humans; Diphtheria Toxin; Diphtheria; Inflammasomes; Pyroptosis; Immunity, Innate; NLR Proteins
PubMed: 37642997
DOI: 10.1084/jem.20230105 -
MMWR. Recommendations and Reports :... Apr 2018This report compiles and summarizes all recommendations from CDC's Advisory Committee on Immunization Practices (ACIP) regarding prevention and control of tetanus,...
This report compiles and summarizes all recommendations from CDC's Advisory Committee on Immunization Practices (ACIP) regarding prevention and control of tetanus, diphtheria, and pertussis in the United States. As a comprehensive summary of previously published recommendations, this report does not contain any new recommendations and replaces all previously published reports and policy notes; it is intended for use by clinicians and public health providers as a resource. ACIP recommends routine vaccination for tetanus, diphtheria, and pertussis. Infants and young children are recommended to receive a 5-dose series of diphtheria and tetanus toxoids and acellular pertussis (DTaP) vaccines, with one adolescent booster dose of tetanus toxoid, reduced diphtheria toxoid, and acellular pertussis (Tdap) vaccine. Adults who have never received Tdap also are recommended to receive a booster dose of Tdap. Women are recommended to receive a dose of Tdap during each pregnancy, which should be administered from 27 through 36 weeks' gestation, regardless of previous receipt of Tdap. After receipt of Tdap, adolescents and adults are recommended to receive a booster tetanus and diphtheria toxoids (Td) vaccine every 10 years to assure ongoing protection against tetanus and diphtheria.
Topics: Adolescent; Adult; Advisory Committees; Aged; Aged, 80 and over; Centers for Disease Control and Prevention, U.S.; Child; Child, Preschool; Diphtheria; Diphtheria-Tetanus-Pertussis Vaccine; Female; Humans; Immunization Schedule; Immunization, Secondary; Infant; Male; Middle Aged; Pregnancy; Tetanus; United States; Vaccination; Whooping Cough; Young Adult
PubMed: 29702631
DOI: 10.15585/mmwr.rr6702a1 -
Acta Medica Indonesiana Jul 2018Low adult vaccination coverage in Indonesia may contribute to a recent outbreak of diphtheria in Indonesia. Although well known as a pediatric vaccine, diphtheria... (Review)
Review
Low adult vaccination coverage in Indonesia may contribute to a recent outbreak of diphtheria in Indonesia. Although well known as a pediatric vaccine, diphtheria vaccination should be administered as booster to adolescence and adults for longer prevention. Adult vaccine differs from pediatric vaccine but have similar protection. Additionally, there is special recommendation to vaccinate pregnant women and elderly people aged 65 years or more.
Topics: Adult; Aged; Diphtheria; Diphtheria Toxoid; Female; Humans; Immunity, Humoral; Immunization, Secondary; Immunosenescence; Indonesia; Pregnancy
PubMed: 30333279
DOI: No ID Found -
The New England Journal of Medicine Sep 2019
Topics: Adolescent; Corynebacterium diphtheriae; Diphtheria; Fatal Outcome; Female; Humans; Myocarditis; Pharynx; Tachycardia
PubMed: 31553838
DOI: 10.1056/NEJMicm1814405 -
Emerging Infectious Diseases Aug 2023Corynebacterium ulcerans is a closely related bacterium to the diphtheria bacterium C. diphtheriae, and some C. ulcerans strains produce toxins that are similar to... (Review)
Review
Corynebacterium ulcerans is a closely related bacterium to the diphtheria bacterium C. diphtheriae, and some C. ulcerans strains produce toxins that are similar to diphtheria toxin. C. ulcerans is widely distributed in the environment and is considered one of the most harmful pathogens to livestock and wildlife. Infection with C. ulcerans can cause respiratory or nonrespiratory symptoms in patients. Recently, the microorganism has been increasingly recognized as an emerging zoonotic agent of diphtheria-like illness in Japan. To clarify the overall clinical characteristics, treatment-related factors, and outcomes of C. ulcerans infection, we analyzed 34 cases of C. ulcerans that occurred in Japan during 2001-2020. During 2010-2020, the incidence rate of C. ulcerans infection increased markedly, and the overall mortality rate was 5.9%. It is recommended that adults be vaccinated with diphtheria toxoid vaccine to prevent the spread of this infection.
Topics: Adult; Humans; Diphtheria; Japan; Corynebacterium; Corynebacterium Infections; Corynebacterium diphtheriae; Diphtheria Toxin; Diphtheria Toxoid
PubMed: 37486266
DOI: 10.3201/eid2908.220058