Diphtheria vaccine

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Corynebacterium diphtheriae

A diphtheria vaccine is a toxoid vaccine against diphtheria toxin (DT), which is released as an exotoxin of a bacteriophage from the bacterium Corynebacterium diphtheriae . The vaccine is designed to protect the vaccinated against serious symptoms of diphtheria . Vaccinated persons can become germ carriers and thus infect others, albeit to a lesser extent than unvaccinated persons, because transmission (transmission) is more efficient in symptomatic patients. The vaccine does not protect against infection, but against the symptoms of diphtheria toxin. It confers an anti-toxic immunity.

properties

Diphtheria toxin with subunit A (orange) and B (purple)

Immunization against C. diphtheriae was first achieved in 1894 by Emil von Behring and Erich Wernicke through passive immunization with the diphtheria antitoxin . The first diphtheria vaccine was a toxoid vaccine and was developed in 1923 and approved in Germany in 1936. The active ingredient in diphtheria vaccines is the fixed exotoxin (toxoid). The diphtheria vaccine is on the World Health Organization's list of Essential Medicines . It is considered to be one of the oldest and most successful immunization measures.

In Germany, following an express recommendation, children were vaccinated from the 1960s onwards; in the GDR, children and young people were required to be vaccinated from 1961 onwards .

In Germany and other countries, diphtheria vaccines are currently on the market only in combination preparations, the abbreviations of which are DTaP, Tdap, DT or Td. In addition to a component against DT, these combinations also contain a tetanus vaccine against the toxin of Clostridium tetani (T) and pertussis vaccine against the toxin of Bordetella pertussis (aP). The small letters “t” or “p” in the abbreviations indicate lower concentrations of the respective component, “aP” stands for the acellular vaccine against whooping cough (pertussis) that is common today . The DTP vaccine was used as a combination vaccine from 1930 to 1991, until the pertussis vaccine, which was also contained in it, was replaced by a cell-free form ( acellular pertussis vaccine , aP) in 50% of the vaccinated because of pain and redness at the injection site , which was subsequently called TDaP or DTaP was designated. A monovalent vaccine for children came off the market in 2008 and for adults in 2016.

DTaP is mostly used to immunize children, while repetitive immunization in adults and primary immunization in adulthood (in people who have neither had diphtheria nor been vaccinated against it) are mostly Td or Tdap. In addition, there are currently combinations of the diphtheria vaccine with the one against the viral pathogens of polio (Polio-IPV) and herpes zoster .

The antigen content in children's vaccines is at least 30 IU per dose (“D” vaccine), in vaccines from four years of age this is reduced by 2 IU (“d” vaccine). The so-called flocculation test (Lf) is sometimes given instead of IU , one IU corresponds to 1.25 Lf. A controlled dose-finding study to select the amount of antigen was never carried out.

immunology

Neutralizing antibodies against the diphtheria toxin develop in 95% of the vaccinated, provided that the vaccination was given four times (at the age of 2, 3, 4 and 11-14 months) as a “basic vaccination” as recommended. The vaccination protection is then extended according to the recommendation of the German STIKO by two "booster vaccinations" at the age of 5–6 years and 9–17 years and then maintained for life by booster vaccinations every 10 years together with the vaccination against tetanus and whooping cough. With the booster vaccinations from 5/6 years of age, the vaccine contains a lower diphtheria toxoid content.

In other European countries, the recommendations on the frequency of booster vaccinations for adults vary greatly. B. Great Britain or the Netherlands no routine booster vaccinations are given, in Switzerland or Sweden these should be carried out every 20 years up to the age of 65.

Type and extent of vaccination protection

The antitoxic immunity produced prevents serious illnesses in the vaccinated for a number of years with decreasing effectiveness, but not its infection by the pathogen and its implantation (colonization) in the mucous membrane of the throat and nose and on the skin. As a result, slight diphtheria symptoms can occur even among vaccinated persons, but these are by far not as dangerous as the classic appearance of the disease in people without antitoxin antibodies from vaccination or previous illness. These more or less asymptomatic germ carriers can pass the pathogen on to other people or to objects, so the vaccination does not definitely interrupt the chain of infection . The vaccination causes a high, although not 100%, protection against the disease. In addition, the disease is less likely to be fatal in vaccinated people than in non-vaccinated people. Around 5,000 people worldwide develop diphtheria each year, mainly due to a lack of or inadequate vaccination.

The vaccine is based on the C. diphtheriae DT . This toxin has sequence differences to the toxin from C. ulcerans, which is also pathogenic to humans . Human diphtheria vaccines do not protect against C. pseudotuberculosis disease . It is not yet clear how well the vaccine against C. diphtheriae also protects against diphtheria diseases caused by C. ulcerans . Asymptomatic germ carriers that are colonized with toxic strains of C. diphtheriae , C. ulcerans or C. pseudotuberculosis should therefore be treated with antibiotics to eliminate the pathogens .

Side effects

Adverse drug reactions with the combined diphtheria and tetanus vaccines include injection site pain (80%), redness (25%), headache (25%), fatigue (25%) and fever (rarely). Gastrointestinal complaints were rarely observed. Allergic reactions as well as mono -, polyneuritides and neuropathies are considered individual cases .

Manufacturing

The diphtheria vaccine is produced by cell culture of C. diphtheriae in liquid culture medium . Strains are used for which a high degree of toxin production has been described. The culture is filtered and the filtrate is then fixed with formaldehyde . This denatures the B fragment of the toxin , which means that it can no longer bind to cell receptors - the toxin no longer gets into cells. The immunogenic properties are retained for a corresponding antitoxin formation. After purification, the inactivated toxin is absorbed by an adjuvant (for example aluminum hydroxide or phosphate ) to increase the immunological effect .

Individual evidence

  1. ^ A b Stanley A. Plotkin , Walter Orenstein, Paul A. Offit, Kathryn M. Edwards: Plotkin's Vaccines. Elsevier, 2017. ISBN 9780323393010 . P. 1519.
  2. ↑ Caroline Macera: Introduction to Epidemiology: Distribution and Determinants of Disease . Nelson Education, 2012, ISBN 9781285687148 , p. 251. Archived from the original on September 8, 2017.
  3. ↑ a b c d e Centers for Disease Control and Prevention : CDC Pink Book: Diphtheria .
  4. ↑ a b c d e f g BENEFIT DOCUMENTATION OF STANDARD VACCINES: DIPHTHERIA. arznei-telegramm , September 15, 2017, pp. 77-80 , accessed on November 4, 2019 .
  5. ↑ WHO Model List of Essential Medicines . In: World Health Organization . October 2013. Retrieved April 22, 2014.
  6. ↑ a b c d e f F. Hofmann: Diphtheria. From: Vaccination Compendium . Ed .: Heinz Spiess, Ulrich Heininger, Wolfgang Jilg. 8th edition. Georg Thieme Verlag, 2015, ISBN 978-3-13-498908-3 , p. 148 ff .
  7. ^ Diphtheria | Vaccines.gov. Retrieved January 19, 2019 .
  8. ↑ Robert Koch Institute : STIKO vaccination calendar 2018. Accessed on September 14, 2018 .
  9. ^ Vaccines: VPD-VAC / Tetanus / main page . Centers for Disease Control. Retrieved June 4, 2012.
  10. ↑ Diphtheria - RKI-Ratgeber , as of October 10, 2018, accessed September 19, 2019
  11. ↑ Robert Koch Institute: Vaccination against diphtheria: Frequently asked questions and answers , as of January 11, 2018, accessed September 19, 2019
  12. ^ Centers for Disease Control. Diphtheria, tetanus, and pertussis: recommendations for vaccine use and other preventive measures: recommendations of the Immunization Practices Advisory Committee (ACIP). Morbidity and Mortality Weekly Report 1991: 40 (No. RR-10) , MMWR, August 8, 1991/40 (RR10); 1-28
  13. ↑ Centers for Disease Control and Prevention: Vaccine Information Statement: Td (Tetanus, Diphtheria) .
  14. ^ A b Marlies Höck and Helmut Hahn: Corynebacteria . In: Sebastian Suerbaum, Gerd-Dieter Burchard, Stefan HE Kaufmann, Thomas F. Schulz (eds.): Medical microbiology and infectious diseases . Springer-Verlag, 2016, ISBN 978-3-662-48678-8 , pp. 314 .