Secondary tracheal distortion in an adult patient after therapy for diphtheria at childhood.

We report a rare case of difficult intubation because of trachea deformation after therapy for diphtheria and subsequent tracheostomy at childhood. The patient was admitted to be subjected to a Bentall procedure, because of ascending aorta dilatation. With a detailed preanesthetic assessment and simulation for intubation by using three-dimensional technology, he was successfully intubated and the operation was accomplished uneventfully. 3D-printed models of the difficult airway enhance imaging of difficult anatomy, assist in simulation and management of potentially problematic intubation, and can be a valuable tool when dealing with airways with potential anatomical malformations.

Profile of Diphtheria Cases Hospitalized at Tertiary Referral Hospital in Indonesia: 10 Years' Experience.

This is a report about children diphtheria cases' profile in Cipto Mangunkusumo Hospital, Jakarta from 2006 to 2017. Occurrence was the highest in ≥5-years-old age group (67.7%) with male predominance (58.8%). Thirty five point three percent cases had no immunization history and 38.2% cases had incomplete booster history. Pseudomembrane occurred in all cases, mostly found in pharynx (67.6%) and tonsil (61.8%).

Diphtheria outbreak in Norway: lessons learned.

We describe an outbreak of diphtheria in Norway that occurred in 2008 and affected 3 unvaccinated family members. The epidemic caught the public health system off-guard on most levels; the diagnosis was distrusted due to its rarity, no diphtheria anti-toxin was available, and notification procedures were not rigorously followed.

Antibody Therapy: From Diphtheria to Cancer, COVID-19, and Beyond.

The dawn of the 20th century saw the formative years of developments in immunology. In particular, immunochemistry, specifically pertaining to antibodies, was extensively studied. These studies laid the foundations for employing antibodies in a variety of ways. Not surprisingly, antibodies have been used for applications ranging from biomedical research to disease diagnostics and therapeutics to evaluation of immune responses during natural infection and those elicited by vaccines. Despite recent advancements in cellular immunology and the excitement of T cell therapy, use of antibodies represents a large proportion of immunotherapeutic approaches as well as clinical interventions. Polyclonal antibodies in the form of plasma or sera continue to be used to treat a number of diseases, including autoimmune disorders, cancers, and infectious diseases. Historically, antisera to toxins have been the longest serving biotherapeutics. In addition, intravenous immunoglobulins (IVIg) have been extensively used to treat not only immunodeficiency conditions but also autoimmune disorders. Beyond the simplistic suppositions of their action, the IVIg have also unraveled the immune regulatory and homeostatic ramifications of their use. The advent of monoclonal antibodies (MAbs), on the other hand, has provided a clear pathway for their development as drug molecules. MAbs have found a clear place in the treatment of cancers and extending lives and have been used in a variety of other conditions. In this review, we capture the important developments in the therapeutic applications of antibodies to alleviate disease, with a focus on some of the recent developments.

A diphtheria outbreak in Assam, India.

Between May and July 2009 there was a small outbreak of diphtheria in adults in Assam, India, with 13 confirmed cases, 8 males and 5 females. The mean age of the confirmed patients was 21.8 +/- 10.5 years. Common signs and symptoms of these patients included low grade fever, sore throat and pseudomembranes on the tonsils. The case fatality rate was 30.8%. Neurological complications were observed in one case. None of the patients received antidiphtheric serum (ADS) since none was available.

[Assessment of different regimens of diphtheria serotherapy].

AIM: Efficacy of different treatment regimens with equine diphtheria antitoxin (EDA) was assessed on clinical samples as well as in experiments on animals. MATERIALS AND METHODS: Protective properties and serum concentration kinetics of heterologous antibodies was studied on 12 rabbits and 51 guinea pigs after intramuscular injection of different doses of EDA, in serum samples from 26 patients, which received one intramuscular injection of EDA in various doses as well as in serum samples from 10 patients with diphtheria of different severity, which were treated with EDA in total course dose 100,000-1,500,000 IU. Antitoxin concentration in serum sample was measured with passive hemagglutination assay as well as Jensen toxin neutralization test on rabbits. RESULTS: Experiments on laboratory animals received EDA in dose 150 IU/kg showed high protective effect. For example, rabbits with antitoxin level 1.0-1.25 IU/ ml in serum 24 hours after injection of EDA were 50-250 times resistant to dermonecrotic effect of diphtheria toxin compared with rabbits not received EDA. Guinea pig with antitoxin level 0.5-2.0 IU/ ml in serum 2-48 hours after injection of EDA in dose 150 IU/kg were all protected against 35-50 LD50 of diphtheria toxin. After termination of EDA injection there was sharp decrease of antitoxin level and it was not detected in serum 7 days after. Increase of antitoxin level in serum of animals was not adequate to quantity of injected EDA. Study of serum samples from 26 patients received one intramuscular injection of different doses of EDA showed that doses of antitoxin from 20,000 to 30,000 IU resulted in its presence in serum in concentration 0.5-3.0 IU/ml whereas injection of 50,000 IU or 70,000-100,000 IU resulted in serum concentrations 1.25-10.0 IU/ ml and 2.5-20.0 IU/ml respectively. CONCLUSION: Relatively low doses of EDA provided relatively high level of protection against diphtheria toxin that should be taken into account during treatment of diphtheria patients.

[Identification of heterologous antitoxin in sera of patients with diphtheria].

Using immobilized diphtheria toxin and peroxidase conjugate of monoclonal antibodies to light chains of equine immunoglobulin a method of quantification of equine antibodies against diphtheria in sera of patients after serotherapy was developed. The sensitivity of indirect enzyme-linked immunosorbent assay was 0.0005 IU/ml, and coefficient of variation did not exceed 10%. It was shown that in patients with toxic diphtheria heterologous antitoxin is eliminated within 4-6 weeks. Level of anti-diphtheria immunoglobulin under the similar severity of disease and dosage of antitoxin can vary in wide ranges and depends from individual's characteristics.

Tetanus, Botulism, and Diphtheria.

PURPOSE OF REVIEW: This article reviews the pathophysiology, epidemiology, clinical manifestations, diagnosis, and treatment of tetanus, botulism, and diphtheric neuropathy. RECENT FINDINGS: Tetanus is most common in lower-income settings, but rare cases are seen in higher-income settings because of the inadequate maintenance of vaccination status. Foodborne botulism remains rare, but botulism can also be caused by IV drug use (wound botulism) and medical use of botulinum toxin (iatrogenic botulism); botulinum toxin has also been considered a potential agent of bioterrorism. Diphtheric neuropathy is rare but has been seen in recent epidemics in the former Soviet Union, and vaccination status is inadequate in a significant proportion of older individuals, creating the potential for subsequent epidemics. SUMMARY: Tetanus, botulism, and diphtheric neuropathy are rare in higher-resource settings where most neurologists practice; however, familiarity with the unique clinical manifestations of and laboratory evaluation for these disorders is essential for the rapid diagnosis and treatment of patients with these conditions.

The Pasteur Hospital as an element of Emile Roux's anti-diphtheria apparatus (1890-1914).

Before the decisive discovery by Gaston Ramon of a vaccine ("anatoxine diphtérique") in 1923, the fight against diphtheria in France had started in 1894 with the serotherapy approach of Martin and Roux. Emile Roux, director of the Institut Pasteur, developed a dynamic concept of research/production/application expressed in the organization of a specialized hospital, the Hôpital Pasteur, which was constructed near the research laboratories and also incorporated production centres outside Paris in Marnes-la-Coquette. Roux implemented a well-defined project against diphtheria that took account of all of the logistical implications. By associating this therapeutic project with an architectural project, Roux established a coherent anti-diphtheria apparatus.

The designing of anti-diphtheria serotherapy at the Institut Pasteur (1888-1900): the role of a supranational network of microbiologists.

The development of anti-diphtheria serotherapy at the Institut Pasteur immediately follows the crisis known as the Pasteur-Koch debate. Research on diphtheria in Paris is indicative of the importance granted by Pasteurian scientists to Koch's school criticisms. After 1887, relations between French and German bacteriologists become more relaxed. A scientific and social network develops between them. It later extends to other fields of research at the Institut Pasteur, particularly therapeutic chemistry. The evolution of Franco-German relations at the Institut Pasteur is placed in the general framework of the way French universities considered German science.

Diphtheria serum and serotherapy. Development, production and regulation in fin de siècle Germany.

The development, production and state regulation of diphtheria serum is outlined against the background of industrialisation, standardization, falling standards of living and rising social conflict in fin de siècle Germany. On one hand, diphtheria serum offered a cure for an infectious disease and was a major therapeutic innovation in modern medicine. On about its side effects or long-term impact. Moreover, serum therapy promised high profitsthe other hand, the new serum was a remedy of biological origin and nothing was known for manufacturers who succeeded in stabilizing the production process and producing large quantities of serum in so-called industrial production plants. To minimize public health risks, a broad system of state regulation was installed, including the supervision of serum production and distribution. The case of diphtheria serum illustrates the indirect forms of government supervision and influence adopted in the German Empire and the cooperation and networking among science, state and industry.

The origin of the production of diphtheria antitoxin in France, between philanthropy and commerce.

Serotherapy for the treatment of diphtheria represented a major therapeutic innovation at the end of the nineteenth century. The manner in which large-scale production of this medicament was undertaken and the regulations that governed its production and distribution were important elements of public health policy in France as in other European countries. This paper describes the dominance of the Pasteur Institute in this field and, starting from this observation, explores what this event in the history of medicine can tell us about the governance of public health in fin-de-siècle France. The particular organization of this institute and its monopoly of specialist microbiological knowledge allowed it to raise money for serum production from both private and public sources, walking the line between a commercial pharmaceutical venture and a philanthropic enterprise.

Remembering Emil von Behring: from Tetanus Treatment to Antibody Cooperation with Phagocytes.

A century ago, Emil von Behring passed away. He was the first to be honored by the Nobel Prize for Medicine in 1901 for the successful therapy of diphtheria and tetanus, which he had developed from the bench to the bed. He also contributed to the foundation of immunology, since his therapy was based on passive immunization with specific antisera. Being an ambitious character, he did not shy away from friction with his colleagues Paul Ehrlich and Elias Metchnikoff and his mentor, Robert Koch. Behring was not only an excellent translational researcher but also a successful entrepreneur and early proponent of public-private partnerships.

Multidisciplinary approach to the management of a case of classical respiratory diphtheria requiring percutaneous endoscopic gastrostomy feeding.

We present a case of a Caucasian woman aged 67 years referred with a 4-day history of sore throat, dysphagia, fever and nasal blockage. Examination revealed a swollen neck and pharyngeal pseudomembrane. A throat swab was positive on culture for Corynebacterium ulcerans, with toxin expression confirmed on PCR and Elek testing. A diagnosis of classical respiratory diphtheria was made, with subsequent confirmation of the patient's domesticated dog as the source of infection. The dog had recently been attacked by a wild badger and was being treated for an ear infection. The patient made a good recovery with intravenous antimicrobial and supportive therapy; however, she subsequently developed a diphtheritic polyneuropathy in the form of a severe bulbar palsy with frank aspiration necessitating percutaneous endoscopic gastrostomy feeding. A mild sensorimotor peripheral neuropathy was also diagnosed. The patient eventually made an almost complete recovery.

Characterization of serum anti-diphtheria antibody activity following administration of equine anti-toxin for suspected diphtheria.

There is a global shortage of equine-derived diphtheria anti-toxin (DAT) for diphtheria treatment. There are few existing data on serum antibody concentrations and neutralizing activity post-treatment to support development of new therapeutics. Antibody concentrations were quantified by ELISA and anti-toxin neutralizing activity by cytotoxicity assay in serum from 4 patients receiving DAT for suspected diphtheria. Using linear mixed effects modeling, estimated mean (SE) half-life was 78.2 (20.0) hours. Maximum serum neutralizing activity ranged from 28.42-38.64 AU/mL with an estimated mean AUC1-72 of 1396.7 (399.3) AU/mL*hr. These data provide a standard of comparison for development of novel anti-toxins to replace DAT.