Hexavalent vaccine

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The hexavalent vaccine , also sixfold vaccine called, is a vaccine , which by intramuscular injection for primary immunization and booster vaccination against six different infectious diseases is used: polio , diphtheria , tetanus , pertussis , Haemophilus influenzae b type and hepatitis B . If a 2 + 1 or 3 + 1 vaccination scheme is adhered to, infants and toddlers are over 90% long-term protected against five of the six infectious diseases. The majority of those vaccinated are no longer protected against pertussis 5–7 years after vaccination. Combination vaccines are recommended because they simplify handling and increase acceptance, lower costs, reduce the number of injections and the occurrence of possible side effects, and reduce the amount of waste. The six-fold vaccine is a dead vaccine , i. H. In contrast to live vaccines such as B. the measles-mumps-rubella vaccine no functional pathogens.

Epidemiology

Polio , diphtheria , tetanus , whooping cough , Haemophilus influenzae infection type b and hepatitis B are six dangerous infectious diseases which, without vaccination , have caused or still claim several million deaths. Most of these diseases have become rare in industrialized countries due to extensive vaccinations or, like poliomyelitis, are no longer present, but can recur at any time if there is insufficient vaccination protection.

  1. Polio or poliomyelitis is transmitted by the very infectious poliovirus and is usually symptom-free. However, the dreaded symptoms of paralysis arise as a complication in 0.1 percent of all sick people. In the pre-vaccination era, there was a complete prevalence , d. H. everyone used to come into contact with the virus. In 2002 the WHO declared the Europe Region to be polio-free. The last disease of poliomyelitis acquired in Germany by a wild virus was recorded in 1990. The last two imported cases (from Egypt and India) were recorded in 1992. Symptomatic polio (wild-type) diseases currently recorded were two cases in Afghanistan and four in Pakistan in 2019, so that polio eradication is targeted for 2023.
  2. Diphtheria is an infection of the upper respiratory tract or the skin, which can be caused by the bacterium Corynebacterium diphtheriae or C. ulcerans (predominantly skin diphtheria). Dreaded are life-threatening complications from bacterial poisons (toxins), which among other things can lead to asphyxiation from throat and larynx infections. The disease, which used to be common, has decreased considerably in the western industrialized countries. Due to the high vaccination rates in childhood since 1984, only individual cases are registered in Germany. The fact that diphtheria can quickly spread again if the vaccination rate drops was observed in the former Soviet Union , where 48,000 cases occurred after the collapse of the system in 1994. In Germany, there has been a single transmission of skin diphtheria without complications in the last 40 years.
  3. Tetanus , also called tetanus , is also triggered by a bacterial toxin. The resistant spores of the bacterium Clostridium tetani are found everywhere in the soil, e.g. B. in road dust or in garden soil. Infection occurs through spores that get into wounds. The bacterium multiplies and secretes the toxin tetanospasmin , which damages the muscle-controlling nerve cells and thereby causes the typical paralysis and muscle spasms that can lead to death. Tetanus is widespread worldwide - with great regional differences. Especially in countries with poor medical care and low vaccination rates, many people fall ill and still die from this disease. In 2006 about 290,000 people, 250,000 of them from neonatal tetanus. In contrast, tetanus occurs rarely in the industrialized countries of Europe and North America thanks to extensive vaccinations and improved living conditions. In Germany, less than 15 cases of illness have been recorded annually in recent years, mostly in older adults. The Federal Statistical Office has the main diagnosis of tetanus made by the hospital in the cause of death statistics for a total of 88 deaths between 2007 and 2018.
  4. Whooping cough or pertussis is a highly contagious infectious disease caused by the bacterium Bordetella pertussis with atypical coughing attacks. a. can be life-threatening in infants. Whooping cough is also threatening because of serious complications such as pneumonia , otitis media , apneas and encephalitis. It was not until the spring of 2013 that a nationwide reporting obligation was introduced in accordance with the IfSG, so that long-term observations of the nationwide disease burden will only be reliable in a few years. In 2017, according to the Federal Statistical Office, one person died of pertusis in Germany. In countries such as the USA or Brazil, pregnant women between the 28th and 30th week of pregnancy are successfully vaccinated once to prevent the dreaded newborn peptic cough. 151,000 people worldwide contracted whooping cough in 2018, the WHO recorded 89,000 deaths.
  5. Haemophilus influenzae type b (Hib) is a bacterium that causes meningitis and other inflammatory diseases in the ear, nose and throat area such as epiglottis ,especially in small children. In the pre-vaccination era, H. influenza b was responsible for 50–65 percent of all meningitis in young children. Since some strains of H. influenzae are multi-resistant to known antibiotics , the Hib vaccination has beenrecommendedby the STIKO for all small childrensince 1990. In 2018, 36 Hib cases were recorded across Germany. In general, invasive Haemophilus influenzae infections occurred in infants and young children under 5 years of age, as well as in older people over 59 years of age.
  6. With around 240 million chronically infected people, hepatitis B is one of the most common infectious diseases in the world and can cause liver inflammation. Infection occurs through contact with the blood or other body fluids of another infected person. In 5 to 10 percent of cases, the disease is chronic, i.e. H. the hepatitis B virus stays in the body and the person continues to spread the pathogen. The rate of chronification is highest in newborns and young children. In about a quarter of all chronic hepatitis B diseases, the severity of the disease progresses can be observed, which then often leads to considerable consequential damage such as liver carcinoma or liver cirrhosis . Between 2003 and 2006, around 0.2 percent of those under 18 years of age in Germany had active hepatitis B.

Use and effect of the six-fold vaccine

The six-fold vaccine is injected intramuscularly by trained personnel and usually causes an unnoticed, non-transferable stimulation of the immune system against the aforementioned infectious diseases and the adjuvants. From the second month of life, three or two doses can be administered for basic immunization with an interval of at least one month. This should be followed by a refresh (booster) (thus 3 + 1 or 2 + 1 scheme). In 90–99% of those vaccinated, the human immune system (depending on the component) forms antibodies against the relevant diseases. In the case of whooping cough, these can still go away after 5 to 7 years.

Approved vaccines

So far, three six-fold vaccines have been approved in the European Union:

The vaccine Hexavac ® from Sanofi Pasteur MSD, which was approved in 2000, was withdrawn from the market in 2005 due to insufficient long-term protection against hepatitis B. About 5% to 20% of the vaccinated children did not develop a sufficiently high antibody titer against hepatitis B (anti-HbsAg <100 IU / l) so that long-term protection is not given.

Side effects

As with all vaccinations, local vaccination reactions such as redness, pain and swelling at the injection site can occur as side effects and are regarded as harmless side effects. These reactions are largely due to the injection, not the drug itself. As a rare side effect, an allergic reaction to ingredients in the serum can occur.

Since the six-fold vaccination is a dead vaccine , the corresponding infectious diseases cannot arise from the vaccination or even be passed on to others. The immune system becomes active, however, so that a rash or a slight fever can develop for a few days. These side effects are rare and usually mild and short-term in nature and no more common with hexavalent vaccines than with individual vaccines. Although side effects from the vaccination are known, the advantages of infection protection far outweigh a “natural” life-threatening disease.

Between 2001 and 2003, around 7.2 million vaccine doses were administered in Germany, to which 488 vaccine reactions were reported. The reports in the infants and toddlers age group mostly concerned hexavalent vaccines, mostly mild general reactions were reported, followed by febrile convulsions .

Six-Fold Vaccine Controversy

Controversies about the triggering of sudden deaths (SUD or SIDS)

In the course of three years after the introduction of the six-fold vaccine in Europe in autumn 2000, five children died within 24 hours of vaccination, so-called sudden unexplained deaths ( SUD ). The children were between 4 and 23 months old and were considered healthy. Up to this point in time, around 3 million children in Europe had been vaccinated with six-fold vaccines. The incidents were then investigated by both the Paul Ehrlich Institute (PEI, German Federal Institute for Vaccines and Biomedical Medicines) and the European Medicines Agency's scientific committee .

The cause of death remained unclear in all cases. Since convulsions were reported in the family in three of the five cases , the experts discussed this as a possible trigger. However, the clinical descriptions of the individual case reports did not provide any clear indications that family epilepsy might be a risk factor. Viral infections, metabolic diseases, allergic reactions and airway obstruction were discussed as possible other causes of death, but this could not be conclusively clarified in the absence of standardized autopsy protocols . Also, the sudden infant death syndrome (SIDS) as the cause has been considered, this is a SUD up to the first year of life by definition. However, SIDS cases have been declining in most European countries for years.

The majority of the experts came to the conclusion that a causal link between the vaccination and the death of the children has not been proven. A change in the use of six-fold vaccines was not recommended by the European Medicines Agency, as the existing evidence shows that there is no risk to the health of the population.

As a result of the first investigation into the connection with SUD, all reported, unexplained deaths of children up to the age of two in Germany were investigated in more detail, including cases of sudden infant deaths. A statistical abnormality was possibly found in the second year of life with one of the two six-fold vaccines: if the vaccine was randomly distributed, a maximum of one death was to be expected shortly after the vaccine was administered, but two deaths were determined. From the point of view of statistics, meaningful conclusions are not possible with such low numbers, but only from about a thousand times the previous investigation period. The second vaccine examined showed no abnormalities. The statistical signal that emerged was subsequently not confirmed as no further deaths related to six-fold vaccines were reported. The conclusion of the study recommends the close observation of these incidents and further, more in-depth investigations into them. A study commissioned by the RKI (TOKEN) examined the 254 unexplained, sudden and unexpected deaths between July 2005 and July 2008 for a possible connection with previous six-fold vaccinations. There was no evidence of an increased risk of sudden infant death syndrome within one week of the six-fold vaccination.

Furthermore, Munich pathologists described abnormalities in the autopsy of SUD cases, which these attributed to the vaccine Hexavac. However, this non-peer-reviewed publication was subsequently rejected because of the research method used. In particular, the non-compliance with international standards in the autopsy was heavily criticized.

A follow-up study has since shown that the statements made by the Munich pathologists were wrong and that vaccinations, including the six-fold vaccination, are not a cause of SIDS / SUD, but on the contrary may even protect against SIDS.

Controversy surrounding the suspension of Hexavac approval

After the six-fold vaccines were approved in Europe in 2000, this approval was routinely reviewed by the European Medicines Agency in 2005. At the same time, indications of insufficient long-term protection of the six-fold vaccine Hexavac against hepatitis B were examined. As a precautionary measure, the agency recommended that the approval for the combination vaccine be suspended. She emphasized that there were no safety concerns about the drug. According to the PEI, there is no urgent need for action in children who have been vaccinated with Hexavac . However, you may need to have an additional vaccination against hepatitis B later. By 2015 at the latest, it should have been communicated why the Hexavac vaccine was withdrawn from the market, whether the hepatitis B status of the children who were vaccinated at the time should not be checked and who pays for this and any additional vaccinations. Neither the PEI nor the STIKO at the RKI have issued a statement on this. The legal successor has been Sanofi since the joint venture was dissolved.

Opposing vaccination insinuate a connection between the controversy surrounding SUD cases and the withdrawal of Hexavac which, however, can not be proven. Since 2000, around 1.5 million children in Germany have been vaccinated with Hexavac , which in the hypothetical case of a connection would result in a SUD risk of less than 0.0003%.

Individual evidence

  1. ↑ a b Pablo Obando-Pacheco et al .: New perspectives for hexavalent vaccines . In: Vaccine (=  Progress in Vaccines ). tape 36 , no. 36 , August 28, 2018, ISSN  0264-410X , p. 5485-5494 , doi : 10.1016 / j.vaccine.2017.06.063 .
  2. ↑ RKI: Review of the vaccination recommendation for a single pertussis (ap) vaccination in adulthood (as of March 15, 2019). In: rki.de. Robert Koch Institute , accessed on October 30, 2019 (German).
  3. ↑ Andreas Fidrich et al .: General medicine : Safe through clinical traineeships , internship, PJ and state examination . 1st edition. Elsevier Health Sciences, 2019, ISBN 978-3-437-09684-6 , pp. 180 ( google.com [accessed October 31, 2019]).
  4. ↑ Center of Disease Control, Jennifer Hamborsky, Andrew Kroger, Charles Wolfe (Eds.): Epidemiology and Prevention of Vaccine-Preventable Diseases . 13th edition. Public Health Foundation, Washington DC 2015 ( online ).
  5. ↑ Sophia Weimer: The polio is not out of the world . June 21, 2012 ( welt.de [accessed October 31, 2019]).
  6. ↑ a b bulletin polio. In: rki.de (Robert Koch Institute). Retrieved October 30, 2019 .
  7. ↑ Diphtheria. RKI, October 1, 2018, accessed October 31, 2019 .
  8. ↑ Kliegman: Nelson Textbook of Pediatrics . 21st edition. tape 1 . elsevier, p. 1459 .
  9. ↑ Transmission of skin diphtheria within a family - first diphtheria outbreak in Germany for almost 40 years. In: rki.de (Robert Koch Institute). May 16, 2019, accessed October 30, 2019 .
  10. ↑ a b c Leaflet Tetanus. In: rki.de (Robert Koch Institute). Retrieved October 30, 2019 .
  11. ↑ Federal Statistical Office Germany - GENESIS-Online. Federal Statistical Office (Destatis), October 30, 2019, accessed on October 30, 2019 .
  12. ↑ RKI - RKI-Ratgeber - Whooping Cough (Pertussis). Retrieved October 30, 2019 .
  13. ↑ Doris Simhofer: Whooping cough (pertussis) "symptoms, diagnosis, treatment | minimed.at. March 31, 2014, accessed October 31, 2019 .
  14. ↑ WHO | Pertussis. Retrieved October 31, 2019 .
  15. ↑ Center of Disease Control, Jennifer Hamborsky, Andrew Kroger, Charles Wolfe (Eds.): Epidemiology and Prevention of Vaccine-Preventable Diseases . 13th edition. Public Health Foundation, Washington DC 2015, Chapter 8: Haemophilus influenzae type b ( online ).
  16. ↑ a b Infection epidemiological yearbook - 2018. RKI, p. 101f. , accessed on October 31, 2019 .
  17. ↑ a b RKI - RKI-Ratgeber - Hepatitis B and D. Retrieved on October 30, 2019 .
  18. ↑ a b Thomas Rühle, Erika Harzer: The approval of Hexavac® is suspended. (PDF; 202 kB) Sanofi Pasteur MSD , September 20, 2005, accessed on August 21, 2017 .
  19. ↑ HEXAVAC from the market . ( arznei-telegramm.de [accessed on October 6, 2018]).
  20. ↑ P. Reinertet al .; HEXALIS Study Group. Fever as a marker of reactogenicity of an acellular pertussis-containing hexavalent vaccine. (HEXAVAC) in a large-scale, open, randomized safety study in healthy French infants. Hum Vaccine. 2006; 2 (5): 215-21. PMID 17035735
  21. ↑ European Medicines Agency, April 2003: EMEA reviews hexavalent vaccines ( Memento of July 3, 2007 in the Internet Archive )
  22. ↑ a b No connection between vaccination with hexavalent vaccines and deaths established. Paul Ehrlich Institute , April 28, 2003, accessed on August 21, 2017 .
  23. ^ R. von Kries et al .: Sudden and unexpected deaths after the administration of hexavalent vaccines: is there a signal? Eur J Pediatr. 2005; 164 (2): 61-69 PMID 15602672
  24. ↑ TOKEN study on deaths in children between 2 and 24 months of age. RKI, January 24, 2014, accessed January 11, 2020 .
  25. ↑ B. Zinka et al .: Unexplained cases of sudden infant death shortly after hexavalent vaccination. Vaccine. 2006 Jul 26; 24 (31-32): 5779-80. PMID 15908063
  26. ^ R. von Kries: Comment on B. Zinka et al. Vaccine. 2006 Jul 26; 24 (31-32): 5783-4. Epub 2005 Jul 20. PMID 16081190
  27. ^ HJ Schmitt et al .: B. Zinka et al., Unexplained cases of sudden infant death shortly after hexavalent vaccination. Vaccine. 2006 Jul 26; 24 (31-32): 5781-2. Epub 2005 Jul 21. PMID 16084630
  28. ^ W. Maurer: "Death following hexavalent vaccination." Vaccine. 2005 Dec 1; 23 (48-49): 5461-3. Epub 2005 Jul 27. PMID 16098641
  29. ↑ MM Vennemann et al .: Sudden infant death syndrome: No increased risk after immunization. Vaccine. 2006 PMID 16945457
  30. ↑ HEXAVAC - MesVaccins.net. Retrieved April 19, 2019 .
  31. ↑ Reinhold Kerbl: Do vaccinations lower the risk of sudden infant death syndrome? Meta-analysis proves protective effect . In: Monthly Pediatrics . tape 155 , no. 9 , September 1, 2007, ISSN  1433-0474 , p. 786-788 , doi : 10.1007 / s00112-007-1601-y .