Fact box on MMR combination vaccination for young children: Rubella

Rubella is a contagious infectious disease caused by the rubella virus. The virus is usually transmitted through droplets when coughing, sneezing, and talking. Less frequently, the rubella virus can be transmitted via contaminated surfaces and objects (e.g. door handles, drinking bottles) [1, 2].

Except in early pregnancy, rubella is usually harmless at any age. About half of those who contract rubella show no or only very mild symptoms, while others often develop cold-like symptoms such as fever, cough, headache, and a skin rash with small, bright red, non-itchy spots.

Once rubella has broken out, only the symptoms can be alleviated; treatment of the disease itself is not possible [1, 2].

Thanks to vaccination, only about 20 to 40 rubella infections are reported in Germany per year, half of them in adults [2].

If a woman contracts the rubella virus during the first four months of pregnancy, about 70 to 90 out of every 100 unborn children will develop severe malformations, for example of the inner ear, heart, eye, or brain. This is called rubella embryopathy. It can also lead to a miscarriage. From the fifth month of pregnancy onward, such damage to the unborn child occurs only rarely [1,2].

The rubella-containing vacccine is given twice to infants as part of a triple combination vaccination also for measles and mumps (MMR) or as part of a quadruple combination vaccination also for measles, mumps, and chickenpox (MMRV). After a double vaccination against rubella, a lifelong immunity is generally assumed so that, according to the current state of science, vaccination protection does not need to be refreshed later. In most cases, full vaccination protection is achieved three to four weeks after the second vaccine dose [2].

Rubella is vaccinated twice in infancy as part of a triple combination vaccination together with measles and mumps (MMR) or as part of a quadruple combination vaccination together with measles, mumps, and chickenpox (MMRV). After a double vaccination against rubella, a lifelong immunity is generally assumed so that the vaccination protection does not have to be refreshed later, according to the current state of science. In most cases, complete vaccination protection is achieved three to four weeks after the second vaccination dose [2].

The main aim of the vaccination is to prevent unprotected pregnant women from contracting rubella. Nevertheless, the vaccination benefits all population groups, as the risk of becoming infected with rubella and contracting the disease is significantly reduced [1].

Furthermore, all adults born after 1970 who were not vaccinated in childhood, who were vaccinated only once, or whose vaccination status is unclear may consider a single MMR(V) combination vaccination [2].

Erklärung der Symbole: X = für diese Personen gelten die Zahlen in der Faktenbox; (X) = auf diese Personen lassen sich die Zahlen unter Vorbehalt anwenden (in solchen Fällen ist eine Rücksprache mit ärztlichem Personal empfehlenswert); - = für diese Personen gelten die Zahlen nicht; ? = es ist unbekannt, ob die Zahlen für diese Personen gelten

In the fact box, the benefits of the MMR combination vaccination and of non-vaccination are compared in a model way for children and adolescents who come into contact with the rubella virus. In addition, the side effects of the MMR combination vaccination are compared with those of non-vaccination.

The table may be read as follows:

If unvaccinated people came into contact with the rubella virus, about 500 per 1,000 would likey contract rubella. In contrast, an average of 35 (15 to 55) per 1,000 of those vaccinated with an MMR combination vaccine would get rubella after coming into contact with the virus [2-4]. This means that on average 465 out of every 1,000 persons can be protected from contracting rubella by the MMR combination vaccination.

If unvaccinated pregnant women came into contact with the rubella virus by the 12th week of pregnancy, the unborn child of about 400 (350-450) out of every 1,000 would likely develop severe malformations due to rubella. At the same time, severe malformations of the unborn child would occur in about 16 (13-18) pregnant women with an MMR combination vaccination. This means that in about 384 out of every 1,000 pregnant women the vaccination protects against severe malformations of the unborn child up to the 12th week of pregnancy [3-4].

The MMR combination vaccination can cause febrile seizures in about 1 (0 to 2) out of every 1,000 infants [5].

The figures on the frequency of illness after contact with the rubella virus are based on model calculations with collected data from clinical practice. This includes medical information and textbook data on contact indices (proportion of infected persons among those who have contact with the virus) and manifestation indices (proportion of symptomatically ill persons among those infected). The figures based on clinical practice do not necessarily correspond to the health status of today's population and all vaccines currently offered in Germany [2-4].

The figures on side effects are from various studies with different study designs and populations, with a total of about 2,152,000 participants [5, 6].

Because the MMR(V) combination vaccination is a live vaccination with attenuated rubella, mumps, and measles viruses (and chickenpox), mild, non-transmissible "vaccine measles" may occur one to four weeks after vaccination in about 20 to 50 infants out of every 1,000 vaccinated. This is accompanied by fever and a mild measles-like rash. Mild swelling of the parotid glands (swelling of the cheeks) is also occasionally possible. Joint pain has been reported in adolescents and adults (very rarely in children). Rarely, mild swelling of the testicles has been observed. Such vaccination reactions to the MMR(V) combination vaccination are usually temporary and subside on their own without any further consequences [2].

The likelihood of contact with the rubella virus depends on many factors. These include, for example, the number of vaccinated people in the population and the possibilities for the rubella virus to spread. Contacts with the pathogen become less frequent if a majority of the population is vaccinated, which prevents the virus from spreading (herd immunity) [1].

There is no evidence for a connection between the MMR(V) combination vaccination and the occurrence of inflammatory bowel diseases, such as chronic inflammation of the gastrointestinal tract (Crohn's disease) or of the colon (ulcerative colitis). There is also no link between the occurrence of autism (profound developmental disorder) or progressive, usually fatal brain damage (subacute sclerosing panencephalitis (SSPE)) due to vaccination [1-2, 5-8].

Furthermore, there is no evidence for a connection between the MMR(V) combination vaccination and cognitive developmental delays, the development of type 1 diabetes, asthma, chronic inflammatory skin diseases (dermatitis/eczema), hay fever, blood cancer (leukaemia), the chronic inflammatory neurological autoimmune disease multiple sclerosis, gait disorders, and bacterial or viral infections [6].

The evidence base was determined by the authors of the included review and the creators of the fact box. The overall quality of the evidence is moderate.

The figures on the benefits of MMR(V) combination vaccination were extrapolated using contact and manifestation indices. These have not been explored with randomized controlled trials. However, vaccine effectiveness has been confirmed across different study populations with different study designs. These demonstrate a reduction in disease symptoms in vaccinated versus non-vaccinated individuals.

The findings on seizures due to fever and platelet deficiency could be modified by further research (moderate evidence).

• August 2021 (update of the search, update of the evidence, update of the accompanying text)
• April 2016 (development)

Information for the fact boxes were obtained from the following sources:

[1] Institute for Quality and Efficiency in Health Care (IQWiG). (2020, 2 November). Rubella. informedhealth.org. https://www.informedhealth.org/rubella-german-measles.html (11.08.2021).

[2] Robert Koch Institute (RKI). Communication of the Standing Committee on Vaccination at the Robert Koch Institute: recommendation and scientific rationale for the alignment of occupationally indicated measles-mumps-rubella (MMR) and varicella vaccination. Epid Bull 2020;2:1-22. DOI: 10.25646/6447.3.

[3] Schmitt, C. (2016) Rötelnvirus. In: Suerbaum, S., Burchard, GD., Kaufmann, S., Schulz, T. (eds) Medical Microbiology and Infectiology. Springer textbook. Springer, Berlin, Heidelberg. DOI: 10.1007/978-3-662-48678-8_57.

[4] Arbeitsgemeinschaft der Wissenschaftlichen Medizinischen Fachgesellschaften (AWMF)-Ständige Kommission Leitlinien (2014). AWMF S2k guideline. Laboratory diagnostics of pregnancy-relevant viral infections. AWMF register number 0093/0021. https://www.awmf.org/uploads/tx_szleitlinien/093-001l_S2k_Labordiagnostik_schwangerschaftsrelevanter_Virusinfektionen_2014-05-abgelaufen.pdf (11.08.2021).

[5] Feenstra, B., Pasternak, B., Geller, F. et al. Common variants associated with general and MMR vaccine-related febrile seizures. Nat Genet 46, 1274-1282 (2014). DOI: 10.1038/ng.3129.

[6] Di Pietrantonj, C., Rivetti, A., Marchione, P., Debalini, M. G., & Demicheli, V. (2020). Vaccines for measles, mumps, rubella, and varicella in children. Cochrane Database Syst Rev, (4). Art. No.: CD004407. DOI: 10.1002/14651858.CD004407.pub4.

[7] Federal Centre for Health Education (BZgA). (n.d.). Measles vaccination in children. infektionsschutz.de.
https://www.impfen-info.de/impfempfehlungen/fuer-kinder-0-12-jahre/masern/ (12.08.2021).

[8] Mentzer, D., Meyer, H., Keller-Stanislawski, B. Safety and tolerability of monovalent measles and combined measles, mumps, rubella and varicella vaccines. Bundesgesundheitsbl. 2013;56. Available at: https://www.pei.de/SharedDocs/Downloads/wiss-publikationen-volltext/bundesgesundheitsblatt/2013/2013-sicherheit-impfstoffe-masern-mumps-roeteln.pdf (11.08.2021).