Measles-containing vaccines are indicated for the routine immunization of children, and children and adolescents who have not been immunized on a regular schedule. Indications for this vaccine also include adults born after 1970 who have not received immunization. Adults before 1970 can be assumed to have a natural immunity to measles. However, susceptible patients, such as health care workers, military personnel, and travelers outside of North America, should receive the MMR vaccine.[1]
It is also important to vaccinate women before or during their reproductive years, as rubella can cause congenital malformations in the fetus. Recommendations are that non-immunized female patients that wish to become pregnant are vaccinated with the MMR vaccine no less than one month before they become pregnant. If the patient is pregnant, the MMR vaccine is contraindicated, as it is a live attenuated vaccine, and therefore, there is a theoretical risk to the fetus. However, if a woman is given the MMR during pregnancy, the pregnancy should NOT be terminated based on teratogenic risk, as there is not any evidence that demonstrates a teratogenic risk from the MMR or MMRV vaccine.[2][3] In cases of measles or rubella outbreaks, pregnant women may be given the MMR vaccine as the potential benefits of vaccination outweigh the risks. The MMR vaccine should be administered after delivery to non-immunized patients, as the MMR vaccine is safe during breastfeeding.
The administration of the MMR vaccine is appropriate for specific patient populations as post-exposure prophylaxis (PEP). Patient populations that can be given the MMR vaccine as PEP include patients between 6 and 12 months old who are immunocompetent and have had an exposure in the last 72 hours and non-pregnant patients 12 months or older who are immunocompetent with exposure in the previous six days.[3] Individuals less than six months, between 6 and 12 months and have suffered exposure more than 72 hours ago, pregnant, or immunocompromised should receive an Ig preparation for PEP.[4]
The MMR vaccine works to stimulate the immune system to protect against measles, mumps, and rubella. This vaccine is live attenuated and thus is a harmless, less virulent version of the infectious agents of which it provides protection. Since the MMR vaccine is live attenuated, it has excellent efficacy but requires more than one dose to achieve this immunity.[3]
Estimates of the effectiveness of the MMR vaccine are 99% in measles prevention after a second vaccination and over 95% in the prevention of mumps and 90% in the prevention of rubella after a single dose.
The administration of the first dose should be between 12 to 15 months of age, and the second dose between 18 months of age and school entry.[1] Note that the interval between doses should not be shorter than 28 days. [1]. For unimmunized children and adolescents, the vaccine can be given in two separate doses between the ages of 12 months and 13 years. For unimmunized adults born after 1970, one dose should be given unless they are traveling outside North America, working in health care, students in post-secondary educational settings, or military personnel.
For unimmunized adults born before 1970, one dose should be given if they are students in post-secondary educational settings or traveling outside North America; two doses if they are working in health care or are military personnel. In general, as mentioned previously, unimmunized adults born before 1970 can be assumed to have natural immunity.
The recommendation is to give the first and/or second dose of MMR in advance to children who live or travel in areas where there is an outbreak of measles (defined as at least 3 cases that have a temporal and spatial relationship) and children traveling outside US borders. In the situations mentioned above, the first dose of MMR should be given between 6 and 11 months of age and with continued vaccinations according to the current calendar (2 doses of vaccine with an interval of at least 28 days ranging from 12 to 15 months).[3]
In the case of measles outbreaks, a vaccine can be given to infants after 6 months of age and then continue vaccinations according to a generally accepted schedule (two doses in 13 to 14 months and 10 years, respectively).
Children between 12 and 23 months should receive the MMR vaccine and a univalent varicella vaccine at the same visit instead of the MMRV vaccine to reduce the risk of fever and febrile seizures. The risk is estimated to be around one additional febrile seizure per 2300 to 2800 doses of MMRV vaccine in this patient cohort.[3]
Patients with laboratory confirmation of measles, mumps, or rubella immunity are considered immune to this disease, so there is no need to immunize vaccination. In practice, however, two doses of the MMR vaccine are also given in this situation, which is dictated by the lack of availability of monovalent vaccines against measles, mumps, or rubella.[3]. Seronegative patients who have proof of adequate immunization do not require further immunization.
Post-exposure Prophylaxis
Immunoglobulin (400 mg/kg) can be administered within six days after exposure. The intent is to prevent or reduce the severity of measles, but it is not given to immunocompetent persons who have received one dose of MMR after 12 months of age. This type of post-exposure prophylaxis is only for patients exposed to measles who have an increased risk of complications, and also have a contraindication to MMR vaccination. This group includes patients:
Pregnant women who have not been vaccinated and have laboratory-confirmed measles disease should receive intravenous immunoglobulin after exposure. Measles in pregnant women may have a more severe course and serious complications.[3]
Newborn babies and infants up to 6 months of age should receive immunoglobulin intramuscularly (IGIM) at a dose of 0.5 ml/kg (maximum dose 15 ml) or intravenous immunoglobulin (IVIG) 400 mg/kg within six days of exposure.
Infants aged between 6 and 12 months may receive the MMR vaccine within 72 hours of exposure or IGIM at a dose of 0.5 ml/kg (maximum dose of 15 ml) or IVIG 400 mg/kg within six days of exposure.
For children of at least 12 months of age, the MMR vaccination is preferable to IGIM or IVIG.
Children who have contraindications for MMR vaccination after exposure should receive IVIG 400 mg/kg instead of IGIM.[1]
Measles-Mumps-Rubella Vaccine
Adverse events tend to occur with the first dose. 1 to 3 weeks following vaccination, 5% of immunized children experience malaise and fever, which can present with or without a rash that lasts up to 3 days.[1][2]
Measles-Mumps-Rubella-Varicella Vaccine
Ten percent or more of vaccine recipients experience redness and pain at the injection site or a fever of 39 degrees C or less. Less than 1% to 10% of patients experience a measles-like, rubella-like or varicella-like rash in addition to swelling and a fever greater than 39 degrees C.[4][5]
Rubella-containing Vaccines
Patients receiving rubella-containing vaccines may experience acute transient arthritis or arthralgia 1 to 3 weeks post-immunization. These symptoms last 1 to 3 weeks and rarely recur. These symptoms are more common in post-pubertal females, who develop arthralgia in 25% of cases and arthritis in 10% of cases after immunization. There is not any evidence of an increased risk of new-onset chronic arthropathies.[4]
Immune Thrombocytopenic Purpura
A very rare adverse reaction to the MMR or MMRV vaccine is immune thrombocytopenic purpura (ITP), which may occur within six weeks of immunization. In most children, ITP resolves within three months without complication. In these cases, serologic status can undergo evaluation to determine the need for an additional dose. Clinicians should consider the risks of another adverse event of ITP before a second dose of the vaccine is required.
Encephalitis
Encephalitis occurs in approximately 1 per million doses, compared to 1 in 1000 with infection with the measles virus.
Febrile Seizures
Children between 12 and 23 months should receive the MMR vaccine and a univalent varicella vaccine at the same visit instead of an MMRV vaccine to reduce the risk of fever and febrile seizures. The risk is estimated to be around one additional febrile seizure per 2300 to 2800 doses of MMRV vaccine in this patient cohort.[6][7]
Allergies
The trace amount of egg or chicken protein in the MMR and MMRV vaccine is insufficient to cause an allergic reaction in those egg-allergic.
Booster doses with a measles-containing vaccine after appropriate vaccination is not necessary.
Contraindications
Relative Contraindications
Contraindications Do Not Constitute
Vaccination with the MMR vaccine requires a multi-disciplinary approach as the proper administration of the vaccine changes according to the patient population and the clinical scenario.
Vaccination of children with neurological diseases should follow accepted rules and vaccination schedules. One should remember that the risk of severe infection, the need for hospitalization, and complications in children with chronic disease are significantly higher than in the healthy population. Also, each infection causes a break in rehabilitation, which also adversely affects the child's neurological status. Also, children with chronic diseases are more likely to be in health care facilities, which makes them more vulnerable to infection.
Contraindications to MMR vaccination in children with neurological diseases are limited and temporary. They include[4]:
Contraindications to MMR vaccination do not constitute:
In children who have epilepsy, the recommendation is to administer antipyretic drugs for 6 to 12 days after administration of MMR - fever that may occur as an adverse reaction may trigger seizures.[2][3]
Another recommendation is to educate patients with a multi-disciplinary team about the perceived but false risks of vaccination. For example, the association of MMR with autism spectrum disorder (ASD) is a subject that has aroused much controversy in recent years. The hypothesis linking autism and inflammatory bowel disease with MMR vaccination was put forward in the '90s of the last century.[8] In 1998, Lancet published the article of Dr. Andrew Wakefield, in which researchers reported a link between the MMR vaccine and intestinal leukemia. Its basis was the temporal relationship between the increase in the number of ASD diagnoses (observed since the 1980s), with the rise in the number of recommended childhood vaccines - against: Haemophilus influenzae type b, hepatitis B, chickenpox, pneumococci, influenza, and measles mumps and rubella vaccine.[8][9] The thesis put forward by Wakefield's team has become the starting point for many epidemiological and prospective studies around the world that have ruled out a cause and effect relationship between vaccination (including MMR) and the occurrence of ASD or inflammatory bowel disease. Subsequent analysis proved that the increase in the number of ASD diagnoses resulted from changes in ASD recognition criteria as a neurodevelopmental disorder and increasing awareness of this problem. Besides, prospective studies have shown that ASD symptoms often occur in the first year of life, that is, before the first dose of MMR. In 2004, the journalist revealed that Wakefield's test was conducted in a manner that was not in accordance with medical ethics, and the results were falsified. Most of the authors of the study officially withdrew their unreliable applications, and the Lancet completely retracted the article in 2010.[10]
[1] | Marin M,Broder KR,Temte JL,Snider DE,Seward JF, Use of combination measles, mumps, rubella, and varicella vaccine: recommendations of the Advisory Committee on Immunization Practices (ACIP). MMWR. Recommendations and reports : Morbidity and mortality weekly report. Recommendations and reports. 2010 May 7; [PubMed PMID: 20448530] |
[2] | McLean HQ,Fiebelkorn AP,Temte JL,Wallace GS, Prevention of measles, rubella, congenital rubella syndrome, and mumps, 2013: summary recommendations of the Advisory Committee on Immunization Practices (ACIP). MMWR. Recommendations and reports : Morbidity and mortality weekly report. Recommendations and reports. 2013 Jun 14; [PubMed PMID: 23760231] |
[3] | Strikas RA, Advisory committee on immunization practices recommended immunization schedules for persons aged 0 through 18 years--United States, 2015. MMWR. Morbidity and mortality weekly report. 2015 Feb 6; [PubMed PMID: 25654610] |
[4] | Psarris A,Sindos M,Daskalakis G,Chondrogianni ME,Panayiotou S,Antsaklis P,Loutradis D, Immunizations during pregnancy: How, when and why. European journal of obstetrics, gynecology, and reproductive biology. 2019 Sep; [PubMed PMID: 31226574] |
[5] | Niederer-Loher A, [Vaccinations in pregnancy – Don’t miss the opportunity!]. Therapeutische Umschau. Revue therapeutique. 2016; [PubMed PMID: 27268451] |
[6] | Leung AK,Hon KL,Leong KF,Sergi CM, Measles: a disease often forgotten but not gone. Hong Kong medical journal = Xianggang yi xue za zhi. 2018 Oct; [PubMed PMID: 30245481] |
[7] | Ma SJ,Xiong YQ,Jiang LN,Chen Q, Risk of febrile seizure after measles-mumps-rubella-varicella vaccine: A systematic review and meta-analysis. Vaccine. 2015 Jul 17; [PubMed PMID: 26073015] |
[8] | Spencer JP,Trondsen Pawlowski RH,Thomas S, Vaccine Adverse Events: Separating Myth from Reality. American family physician. 2017 Jun 15; [PubMed PMID: 28671426] |
[9] | Woo EJ,Winiecki SK,Arya D,Beeler J, Adverse Events After MMR or MMRV Vaccine in Infants Under Nine Months Old. The Pediatric infectious disease journal. 2016 Aug; [PubMed PMID: 27167117] |
[10] | Honda H,Shimizu Y,Rutter M, No effect of MMR withdrawal on the incidence of autism: a total population study. Journal of child psychology and psychiatry, and allied disciplines. 2005 Jun; [PubMed PMID: 15877763] |