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Myocarditis
Published in Mary N. Sheppard, Practical Cardiovascular Pathology, 2022
Myocarditis is the most common cause of death in diphtheria by the action of exotoxin produced by Corynebacterium diphtheriae resulting in widespread necrosis of myocytes with little mainly macrophage inflammation. Although still a cause of morbidity and mortality in developing countries, diphtheria is now rare in the West due to vaccination as well as mumps. Bacterial endotoxin is also considered to play a role in meningococcal myocarditis. Myocarditis may be a complication of β-haemolytic streptococci due to bacterial exotoxins.
Respiratory Infections
Published in Miriam Orcutt, Clare Shortall, Sarah Walpole, Aula Abbara, Sylvia Garry, Rita Issa, Alimuddin Zumla, Ibrahim Abubakar, Handbook of Refugee Health, 2021
Diphtheria, caused by the bacterium Corynebacterium diphtheriae, is a potentially fatal infection that can affect the nose and throat and sometimes the skin. C. diphtheriae infections are rare in vaccinated populations, but there have been recent outbreaks, most notably among Rohingya refugees who fled from their homes in Myanmar to Bangladesh during the 2018 genocide. Suspect diphtheria when there is pharyngeal infection with a white-grey pseudomembrane with patches and lymphadenopathy leading to the characteristic ‘bull neck’. The bacteria produces an exotoxin that mediates effects including cardiac (myocarditis) and neurological (cranial nerve palsies and peripheral neuritis). Note that diphtheria can be a cause of non-healing skin ulcers, which have grey membranes. Notify the local public health body and refer for testing where cases are suspected. Treatment is with antibiotics (penicillin/macrolide), antitoxin and isolation. Close contacts should have prophylaxis and booster vaccination (see WHO guidance).2
Diseases of the Nervous System
Published in George Feuer, Felix A. de la Iglesia, Molecular Biochemistry of Human Disease, 2020
George Feuer, Felix A. de la Iglesia
Diphtheria is a disease caused by the lysogenic strains of Corynebacterium diphtheriae.393,597 During active infection, prophage genomes are incorporated into DNA. The disease is now rare in most countries due to the fact that children are immunized at an early age. Absorption occurs at the local site of bacillar infection and most intensely following pharyngeal and bronchial infections.248 Diphtheria toxin is extremely potent, 10-4 mg will kill a guinea pig.130,248,449 it exerts a profound action of the peripheral nervous system causing extensive proximal demyelination in the ganglia and adjacent nerve roots, mainly in places where the blood-brain barrier is incomplete. Cardiac effects are also very frequent, mainly connected with abnormalities of carnitine metabolism leading to decreased oxidation of long chain fatty acids and accumulation of triglycerides.610
Clinical profile and risk factors for mortality in children admitted with diphtheria: an observational study
Published in Infectious Diseases, 2023
Vishnu Mohan, Venkatesh Chandrasekaran, Sujatha Sistla
Whenever a diagnosis of diphtheria was suspected clinically, a nasopharyngeal/throat swab was sent for Albert stain and culture for Corynebacterium diphtheriae. Albert stain positivity was found in 45% of the study population, while C. diphtheriae was isolated in the cultures of 62% children in the study set, thus making them laboratory confirmed cases. TOX gene estimation was planned for all prospective cases, however; due to limitations due to the corona virus disease (COVID) pandemic, it was performed on 26 culture positive isolates, all of which showed C. diphtheriae TOX-PCR positivity. Krishnan et al. isolated C. diphtheriae from 29 samples (5.23%), all of which turned out to be TOX PCR positive [11]. Parande et al. found that close to 9% of the study population were Laboratory confirmed cases, and also identified ten different patterns of antibiograms in the culture isolates [12]. In our study, however, antibiotic susceptibility of the isolates was not performed.
A combined DTaP-IPV vaccine (Tetraxim®/Tetravac®) used as school-entry booster: a review of more than 20 years of clinical and post-marketing experience
Published in Expert Review of Vaccines, 2022
Catherine Huoi, Juan Vargas-Zambrano, Denis Macina, Emmanuel Vidor
Strains of Corynebacterium diphtheriae or Corynebacterium ulcerans can cause diphtheria disease. In countries with robust diphtheria vaccination programs, the incidence of diphtheria is extremely low [8–10]. However, diphtheria remains endemic in some areas of the world and regular small diphtheria outbreaks/resurgence are reported, mainly from Southeast Asia, the Indian subcontinent, South America, Africa, and Eastern Europe [11–15]. This reflects inadequate VCR and demonstrates the importance of sustaining high levels of immunity through the highest possible coverage in childhood, adolescence, and adulthood [16]. Individuals who are unvaccinated or incompletely vaccinated can also contract diphtheria during travel to endemic areas, as the bacterium spreads mainly through respiratory droplets. The World Health Organization (WHO) recommends a three-dose primary series as the foundation for building lifelong immunity to diphtheria. But in the absence of natural boosting, the humoral immunity conferred by primary vaccination wanes over time [10,16,17] and booster doses are hence needed for continued protection. WHO’s recommendations include a minimum of three booster doses: one during the second year of life (at 12–23 months of age), one at primary school entry (4–7 years of age), and one during adolescence (9–15 years of age) [16].
Tagraxofusp as treatment for patients with blastic plasmacytoid dendritic cell neoplasm
Published in Expert Review of Anticancer Therapy, 2020
Sophia S. Lee, Deborah McCue, Naveen Pemmaraju
Toxins in anti-cancer therapies have been used due to their pro-apoptotic activity in various pathways, including shutting down protein synthesis [37]. One of the toxins used is an exotoxin secreted by Corynebacterium diphtheriae. Tagraxofusp consists of a chimeric junction between this toxin and IL-3, resulting in a pro-apoptotic state when administered to appropriate tumor cells. IL-3 is a cytokine that promotes hematopoietic stem cell differentiation. IL-3R is composed to two subunits (α and β). The α subunit, known as CD123, directly binds to IL-3 cytokine. Diphtheria toxin’s binding domain is replaced with a recombinant human IL-3 protein in order to target leukemic cells that highly express CD123 (Figure 1). Once bound to the receptor, tagraxofusp is internalized by receptor mediated endocytosis and inhibits intracellular protein synthesis via increasing ADP ribosylation of elongation factor 2. This ultimately leads to cell death [6,10,37].