Pertussis vaccine

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Quadruple vaccine against diphtheria, tetanus, pertussis and poliomyelitis

A pertussis vaccine (synonym: whooping cough vaccine ) is a vaccine against a whooping cough disease (pertussis). The pertussis vaccine is on the World Health Organization's list of Essential Medicines . The World Health Organization recommends the use of pertussis vaccines in a quintuple vaccine with vaccines against diphtheria , tetanus , hepatitis B and Haemophilus influenzae b.

properties

Pertussis toxin

The pertussis vaccine used in Europe (with the exception of Poland) is a toxoid vaccine that immunizes against the pertussis toxin and partly also against the filamentous hemagglutinin , pertactin (a porin ) and agglutinogens in a fixed form. The active components of the pertussis vaccines used in Europe (with the exception of Poland) no longer contain pathogen cells, but are acellular (abbreviated to AP ). The acellular pertussis vaccine used in Germany contains either cell-free extracts of Bordetella pertussis (T-type vaccines, named after the Japanese manufacturer Takeda ) or highly purified individual components of the pathogen (B-type vaccines, named after the Japanese manufacturer Biken ) as antigens . These acellular pertussis vaccines were approved in Germany in 2005. As a rule, an increase in effectiveness is used through adsorption on an adjuvant such as aluminum hydroxide and aluminum phosphate . The active components in today's pertussis vaccines in the USA are the fixed proteins pertussis toxin and FHA , in some cases also pertactin and fimbriae of types 2 and 3 (in Daptacel ). The pathogen produces a number of other toxins and other virulence factors , especially adenyl cyclase , which is also pathogenic to humans - hemolysin and tracheal cytotoxin. Due to decreasing herd immunity and mutations of the pathogen, the number of infections has increased in recent years.

Single vaccines

After a method for isolating B. pertussis was published in 1906 by the work of Jules Bordet and Octave Gengou , the search for vaccines began. The first pertussis vaccines - based on killed cells of the pathogen (whole cell vaccine, English whole-cell pertussis vaccine , abbreviated wP ) - were in 1912 by Bordet and Gengou, 1913 by Charles Nicolle and 1914 by Thorvald Madsen developed. A whole-germ vaccine was tested during a whooping cough epidemic on the Faroe Islands (1923/24). Although the vaccine failed to prevent most of the infection, it did significantly reduce mortality and severity of symptoms among those who were vaccinated. In a clinical study carried out in 1926 it was observed that vaccination protects against the onset of the disease rather than after the onset of the disease (vaccine effectiveness about 75%). With this knowledge, a whooping cough outbreak in 1929 in the Faroe Islands could be better countered.

In a new, second generation of vaccines, killed pathogens were centrifuged and then partially cleaned. These whole germ vaccines were first introduced in 1933 through the work of Madsen. Bacteriologist Pearl Kendrick refined them and began clinical studies on children in the late 1930s and early 1940s. In addition, she and her colleagues combined a DTP combination vaccine in 1942 , which was then approved in the USA in 1948.

After the undesirable side effects of whole-germ vaccines, the development of acellular vaccines ( AP ) began in Japan in the 1970s . From 1981 these were used.

In 1975 the Standing Vaccination Commission (STIKO) limited its recommendation for the use of the whole-germ vaccine due to the increased number of side effects (mainly strong local reactions, febrile seizures and individual encephalopathies) to children at increased risk. In the GDR , however, the whole-germ vaccine was used unabated. In 1991, the STIKO extended the vaccination recommendation again. The DTwP vaccine was used as a combination vaccine from 1930 to 1991, until the pertussis vaccine also contained in it was replaced by a cell-free form ( acellular pertussis vaccine , aP) in 50% of those vaccinated in the USA due to pain and redness at the injection site , which was subsequently was referred to as TDaP or DTaP. The wP vaccine contains endotoxins of B. pertussis that cause stronger side effects. The aP vaccine became available in Germany in 1995. In 2000 the vaccination recommendation was extended to older children (from 9 to 17 years of age) and from 2009 to adults.

Today's vaccine combinations

In Germany and in most other European countries, pertussis vaccines are currently only available on the market in combination preparations, especially those with the abbreviations DTaP and Tdap . In addition to components of B. pertussis ( aP ), these combinations also contain tetanus vaccine against the toxin of Clostridium tetani ( T or t ) and diphtheria vaccine against the toxin of Corynebacterium diphtheriae ( D or d ). The small letters t and d in the abbreviations indicate lower concentrations of the respective component. DTaP is mostly used to immunize children, while Tdap is mostly used for repeat immunization of adults and primary immunization in adulthood (in people who have neither had diphtheria nor were vaccinated against it) . There are also combinations of the pertussis vaccine with the polio vaccine (Polio-IPV) and the varicella vaccine . The whole-germ vaccine wP continues to be used in other areas , such as the Middle East, Africa and South America. A single pertussis vaccine is currently not available since the last one (PAC MÉRIEUX by Sanofi Aventis ) was withdrawn from the market in 2005.

immunology

After repeated vaccination with aP vaccine, depending on the vaccine, neutralizing antibodies against the pertussis toxin develop in 71–85% of those vaccinated, compared with around 78% of those vaccinated with the wP vaccine. The vaccination protection decreases between 2 and 10% per year, with a faster decrease for the AP vaccine. On average, the acellular pertussis vaccine produces only slightly lower and shorter immunity than its cell-containing predecessor wP, but has fewer side effects:

In Germany, the STIKO recommends a basic immunization with four vaccinations (at the age of 2, 3, 4 and 11-14 months). The vaccination protection should then be extended by two booster vaccinations at the age of 5-6 years and 9-17 years and then be maintained for life by booster vaccinations every 10 years.

Type and extent of vaccination protection

Those vaccinated with aP are largely protected from the disease after infection, but may be temporarily colonized with Bordetellen and thus represent a source of infection as more or less asymptomatic carriers. It can also be transmitted via contaminated objects, since B. pertussis is resistant to dehydration and can survive outside the organism for a few days. Because of the high contagion index in non-immune humans, B. pertussis can spread epidemically in populations with a low infection rate . But even in regions with a high vaccination rate with the aP vaccine, the pertussis pathogen remains endemic , as the decrease in immunity allows colonization. Therefore, from today's perspective, the AP vaccine can neither establish reliable herd immunity nor even eradicate the pathogen. The pertussis vaccine does not work against the toxins from B. parapertussis or B. holmesii , which also lead to a whooping cough-like clinical picture, but this occurs less often and is usually lighter and shorter than that caused by B. pertussis . Nevertheless, the aP pertussis vaccine protects against a disease that is caused by Bordetella parapertussis . Vaccination protection tends to correlate more strongly with antibodies against protactin and fimbriae than with antibodies against pertussis toxin - however, antibodies against pertussis toxin protect against the symptoms of whooping cough.

Side effects

Adverse drug effects with aP vaccine include pain, swelling, and redness at the injection site. With the WP vaccine, 10 to 50% of those vaccinated develop reddening at the injection site or fever. Febrile convulsions occur in 1% of those vaccinated with WP. The younger the person vaccinated, the less pronounced the adverse drug effects. The wP vaccine should not be used in children over 7 years of age.

Trade names

Trade names for combination vaccines that also contain a pertussis vaccine are z. B. Boostrix , Covaxis , Hexacima , Hexyon , Pa-Vaccinol , Pac-Mérieux , Acel-P and Infanrix in Europe and in the USA Infanrix and Daptacel for children (DTaP) and Boostrix and Adacel for adults (Tdap).

Individual evidence

  1. ↑ WHO Model List of Essential Medicines . In: World Health Organization . October 2013. Retrieved April 22, 2014.
  2. ↑ ES Bar-On, E. Goldberg, S. Hellmann and L. Leibovici: Combined DTP-HBV-HIB vaccine versus separately administered DTP-HBV and HIB vaccines for primary prevention of diphtheria, tetanus, pertussis, hepatitis B and Haemophilus influenzae B. (HIB) . In: Cochrane Database Syst Rev . No. 4, 2012, p. CD005530. doi : 10.1002 / 14651858.CD005530.pub3 . PMID 22513932 .
  3. ^ A b Stanley A. Plotkin , Walter Orenstein, Paul A. Offit, Kathryn M. Edwards: Plotkin's Vaccines. Elsevier, 2017. ISBN 9780323393010 . Pp. 729, 730.
  4. ^ A b c Burghard piece, Burkhard Schneeweiß, Heinz-Josef Schmitt, Carl Heinz Wirsing von König: News about pertussis and pertussis vaccines . In: Deutsches Ärzteblatt (1996), Volume 93, Issue 49, pp. A-3270-3276. ( PDF ).
  5. ↑ a b c d e f Centers for Disease Control and Prevention : CDC Pink Book: Pertussis .
  6. ^ NH Carbonetti: Pertussis toxin and adenylate cyclase toxin: key virulence factors of Bordetella pertussis and cell biology tools. In: Future microbiology. Volume 5, number 3, March 2010, pp. 455-469, doi : 10.2217 / fmb.09.133 , PMID 20210554 , PMC 2851156 (free full text).
  7. ↑ a b c Robert Koch Institute : RKI-Ratgeber Whooping Cough (Pertussis) , online status: November 27, 2017, accessed September 19, 2019
  8. ^ AA van der Ark, DF Hozbor, CJ Boog, B. Metz, GP van den Dobbelsteen, CA van Els: Resurgence of pertussis calls for re-evaluation of pertussis animal models. In: Expert review of vaccines. Volume 11, number 9, September 2012, pp. 1121–1137, doi : 10.1586 / erv.12.83 , PMID 23151168 .
  9. ↑ a b c d Institute of Medicine (US) Committee to Review the Adverse Consequences of Pertussis and Rubella Vaccines, Christopher P. Howson, Cynthia J. Howe, Harvey V. Fineberg: Histories of Pertussis and Rubella Vaccines . National Academies Press (US), 1991 ( nih.gov [accessed August 12, 2020]).
  10. ^ A b c Marta Granström: The History of Pertussis Vaccination: From Whole-Cell to Subunit Vaccines . In: Stanley A. Plotkin (Ed.): History of Vaccine Development . Springer, New York 2011, ISBN 978-1-4419-1338-8 , pp. 73-82 , doi : 10.1007 / 978-1-4419-1339-5_10 .
  11. ^ A b T. Jefferson: Why the MRC randomized trials of whooping cough (pertussis) vaccines remain important more than half a century after they were done . In: Journal of the Royal Society of Medicine . tape 100 , no. 7 , July 2007, p. 343-345 , PMID 17606757 , PMC 1905874 (free full text).
  12. ↑ Thorvald Madsen: VACCINATION AGAINST WHOOPING COUGH . In: Journal of the American Medical Association . tape 101 , no. 3 , July 15, 1933, p. 187-188 , doi : 10.1001 / jama.1933.02740280007003 .
  13. ↑ Jeffrey P. Baker and Samuel L. Katz: Childhood vaccine development: an overview . In: Pediatric Research . tape 55 , no. 2 , February 2004, p. 347-356 , doi : 10.1203 / 01.PDR.0000106317.36875.6A , PMID 14630981 .
  14. ↑ Working results of the Standing Vaccination Commission of the Federal Health Office: Recommendation of the Standing Vaccination Commission of the Federal Health Office on whooping cough vaccination . In: Federal Health Gazette . No. 9 , May 2, 1975 ( rki.de [PDF]).
  15. ↑ a b c d Robert Koch Institute: Epidemiological Bulletin May 24, 2017 / No. 21, p. 188. In: rki.de. Retrieved August 11, 2020 .
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  17. ↑ JD Cherry: How can we eradicate pertussis. In: Advances in Experimental Medicine and Biology . Volume 634, 2009, pp. 41-51, doi : 10.1007 / 978-0-387-79838-7_4 , PMID 19280847 .
  18. ↑ Pertussis (whooping cough): RKI advice for doctors
  19. ↑ Last monovalent pertussis vaccine from the Arznei-Telegram market of July 2005.
  20. ↑ a b L. Zhang, SO Prietsch, I. Axelsson, SA Halperin: Acellular vaccines for preventing whooping cough in children. . In: The Cochrane database of systematic reviews . 9, September 17, 2014, p. CD001478. doi : 10.1002 / 14651858.CD001478.pub6 . PMID 25228233 .
  21. ↑ a b c d e f g h World Health Organization (WHO): Pertussis vaccines: WHO position paper - September 2015. In: Releve epidemiologique hebdomadaire. Volume 90, Number 35, August 2015, pp. 433-458, PMID 26320265 .
  22. ^ A. Allen: Public health. The pertussis paradox. In: Science . Volume 341, number 6145, August 2013, pp. 454–455, doi : 10.1126 / science.341.6145.454 , PMID 23908204 .
  23. ^ Robert Koch Institute: STIKO vaccination calendar 2018 (PDF) Retrieved on September 14, 2018 .
  24. ^ Robert Koch Institute: Vaccination against Pertussis: Frequently Asked Questions and Answers , December 14, 2012, accessed on September 18, 2019.
  25. ↑ Pertussis Frequently Asked Questions , [Centers for Disease Control and Prevention], online April 1, 2019, accessed September 19, 2019
  26. ↑ J. Liko, SG Robison, PR Cieslak: Do Pertussis Vaccines Protect Against Bordetella parapertussis? In: Clinical Infectious Diseases . Volume 64, Number 12, June 2017, pp. 1795-1797, doi : 10.1093 / cid / cix221 , PMID 28369240 .
  27. ^ Paul Ehrlich Institute : Vaccines against pertussis (whooping cough) ( Memento from March 2, 2016 in the Internet Archive ). Retrieved February 29, 2016.