MMR – Measles, Mumps, Rubella

MMR vaccine

MMR vaccine is designed to protect against three things: measles, mumps and rubella.

Measles

• Measles is a virus which causes high fever, lethargy, cough, nasal discharge, conjunctivitis and a characteristic rash.  About 30% of infected patients will have complications, and 1 in 5 will be hospitalized.  1 in 1,000 develop encephalitis, and between 1 in 500 and 1 in 1,000 will die.
• Highly contagious, spread through respiratory droplets  in the air.
• Worldwide measles infection is the 5th most common cause of death in children under 5.
• Rare in the United States.  Last estimates were 31-39 million illnesses worldwide in a single year.

Mumps

• Virus that usually causes swelling of the parotid glands, but can affect any organ system.  Adolescent males can get swelling of the testes (called orchitis) which can reduce fertility or even cause sterility in rare cases.  Can also cause miscarriage.  Rarely causes encephalitis or deafness.
• Contagious, but less so than measles or chickenpox.  Spread via respiratory droplets (airborne) or by direct contact.
• Before the vaccine: 200,000+ cases.  Now: rare, with periodic outbreaks of up to a few thousand patients.

Rubella

• Virus that causes a fever and characteristic rash. Rarely causes encephalitis.
• Is a teratogen if Mom contracts rubella in pregnancy.  Leads to severe birth defects or miscarriage. Lasting effects of congenital rubella are severe, with no known treatment available.
• Spread through respiratory droplets in the air, or through the placenta. Moderately contagious.
• Before: 20,000 cases of congenital rubella per year.  Now: rare.

The vaccine

• Is a live, attenuated virus.
• CDC recommended schedule: 12-15 months, 4-6 years.
• Who should not get the vaccine?
• Ingredients: sorbitol, sodium phosphate, sucrose, sodium chloride, gelatin, human albumin, fetal bovine serum, 25 mcg neomycin.

Research citations for MMR

1. Hamborsky J, Kroger A, Wolfe S. Epidemiology and Prevention of Vaccine-Preventable Diseases: Measles.  Centers for Disease Control and Prevention. 13th ed. Washington D.C
2. World Health Organization.  Regional office of the Mediterranean. Measles: Disease Burden.  Web 20 June 2017. http://www.emro.who.int/health-topics/measles/disease-burden.html
3. Jochems CE1, van der Valk JB, Stafleu FR, Baumans V. The use of fetal bovine serum: ethical or scientific problem? Altern Lab Anim. 2002 Mar-Apr;30(2):219-27.
4. Sørup S1, Benn CS2, Poulsen A3, Krause TG4, Aaby P5, Ravn H5.Live vaccine against measles, mumps, and rubella and the risk of hospital admissions for nontargeted infections. JAMA. 2014 Feb 26;311(8):826-35.
5. Marin M1, Broder KR, Temte JL, Snider DE, Seward JF; Centers for Disease Control and Prevention (CDC). Use of combination measles, mumps, rubella, and varicella vaccine: recommendations of the Advisory Committee on Immunization Practices (ACIP). MMWR Recomm Rep. 2010 May 7;59(RR-3):1-12.
6. Orlíková H1, Malý M2, Lexová P3, Šebestová H2, Limberková R4, Jurzykowská L3, Kynčl J3,5. Protective effect of vaccination against mumps complications, Czech Republic, 2007-2012. BMC Public Health. 2016 Apr 1;16:293. 
7. Mäkelä A1, Nuorti JP, Peltola H. Neurologic disorders after measles-mumps-rubella vaccination. Pediatrics. 2002 Nov;110(5):957-63.
   1. We did not identify any association between MMR vaccination and encephalitis, aseptic meningitis, or autism.
8. Seither R, Calhoun K, Mellerson J, Knighton CL, Street E, Dietz V, Underwood JM. Vaccination Coverage Among Children in Kindergarten – United States, 2015-16 School Year. MMWR Morb Mortal Wkly Rep. 2016 Oct 7;65(39):1057-1064.
9. Gastañaduy PA1, Budd J1, Fisher N1, Redd SB1, Fletcher J1, Miller J1, McFadden DJ 3rd1, Rota J1, Rota PA1, Hickman C1, Fowler B1, Tatham L1, Wallace GS1, de Fijter S1, Parker Fiebelkorn A1, DiOrio M1. A Measles Outbreak in an Underimmunized Amish Community in Ohio. N Engl J Med. 2016 Oct 6;375(14):1343-1354.
10. Weiss C1,2, Schröpfer D3, Merten S4,5. Parental attitudes towards measles vaccination in the canton of Aargau, Switzerland: a latent class analysis. BMC Infect Dis. 2016 Aug 11;16(1):400.
11. Kuter BJ1, Brown M, Wiedmann RT, Hartzel J, Musey L. Safety and Immunogenicity of M-M-RII (Combination Measles-Mumps-Rubella Vaccine) in Clinical Trials of Healthy Children Conducted Between 1988 and 2009. Pediatr Infect Dis J. 2016 Sep;35(9):1011-20. 
12. Singh VK1. Phenotypic expression of autoimmune autistic disorder (AAD): a major subset of autism. Ann Clin Psychiatry. 2009 Jul-Sep;21(3):148-61.
13. Singh VK1, Jensen RL. Elevated levels of measles antibodies in children with autism. Pediatr Neurol. 2003 Apr;28(4):292-4.
14. Li Q1, Han Y1, Dy ABC2, Hagerman RJ3,4. The Gut Microbiota and Autism Spectrum Disorders. Front Cell Neurosci. 2017 Apr 28;11:120. 
15. Libbey JE1, Sweeten TL, McMahon WM, Fujinami RS. Autistic disorder and viral infections. J Neurovirol. 2005 Feb;11(1):1-10.
16. Mandomando IM1, Naniche D, Pasetti MF, Vallès X, Cuberos L, Nhacolo A, Kotloff KL, Martins H, Levine MM, Alonso P. Measles-specific neutralizing antibodies in rural Mozambique: seroprevalence and presence in breast milk. Am J Trop Med Hyg. 2008 Nov;79(5):787-92.
17. Boulianne N1, De Serres G, Duval B, Joly JR, Meyer F, Déry P, Alary M, Le Hénaff D, Thériault N. [Major measles epidemic in the region of Quebec despite a 99% vaccine coverage]. Can J Public Health. 1991 May-Jun;82(3):189-90.
18. Sugerman DE1, Barskey AE, Delea MG, Ortega-Sanchez IR, Bi D, Ralston KJ, Rota PA, Waters-Montijo K, Lebaron CW. Measles outbreak in a highly vaccinated population, San Diego, 2008: role of the intentionally undervaccinated. Pediatrics. 2010 Apr;125(4):747-55. 
19. Agergaard J1, Nante E, Poulstrup G, Nielsen J, Flanagan KL, Østergaard L, Benn CS, Aaby P. Diphtheria-tetanus-pertussis vaccine administered simultaneously with measles vaccine is associated with increased morbidity and poor growth in girls. A randomised trial from Guinea-Bissau. Vaccine. 2011 Jan 10;29(3):487-500.
    1. – Do not give DTP with Measles vaccine.  Associated with increased morbidity.
20. Aaby P1, Jensen H, Simondon F, Whittle H. High-titer measles vaccination before 9 months of age and increased female mortality: do we have an explanation?Semin Pediatr Infect Dis. 2003 Jul;14(3):220-32.
    1. Do not give before 9 months of age.
21. Tae BS1, Ham BK, Kim JH, Park JY, Bae JH. Clinical features of mumps orchitis in vaccinated postpubertal males: a single-center series of 62 patients. Korean J Urol. 2012 Dec;53(12):865-9. doi: 10.4111/kju.2012.53.12.865. Epub 2012 Dec 20.
22. da Costa Mdo D1, Gonçalves LR, Barbosa ER, Bacheschi LA. [Neuroimaging abnormalities in parkinsonism: study of five cases]. Arq Neuropsiquiatr. 2003 Jun;61(2B):381-6. Epub 2003 Jul 28.
23. Mäkelä A1, Nuorti JP, Peltola H. Neurologic disorders after measles-mumps-rubella vaccination. Pediatrics. 2002 Nov;110(5):957-63.
    1. No association with MMR vaccine and encephalitis, autism or aseptic meningitis.  Studied over 500,000 children.
24. D’Souza Y1, Fombonne E, Ward BJ. No evidence of persisting measles virus in peripheral blood mononuclear cells from children with autism spectrum disorder. Pediatrics. 2006 Oct;118(4):1664-75.
25. Singh VK1. Phenotypic expression of autoimmune autistic disorder (AAD): a major subset of autism. Ann Clin Psychiatry. 2009 Jul-Sep;21(3):148-61.
26. Binamer Y1. Acute hemorrhagic edema of infancy after MMR vaccine. Ann Saudi Med. 2015 May-Jun;35(3):254-6. 
27. Leung JH1, Hirai HW, Tsoi KK. Immunogenicity and reactogenicity of tetravalent vaccine for measles, mumps, rubella and varicella (MMRV) in healthy children: a meta-analysis of randomized controlled trials. Expert Rev Vaccines. 2015;14(8):1149-57
28. Ma SJ1, Xiong YQ1, Jiang LN1, Chen Q2. Risk of febrile seizure after measles-mumps-rubella-varicella vaccine: A systematic review and meta-analysis. Vaccine. 2015 Jul 17;33(31):3636-49
29. Vcev A1, Pezerovic D, Jovanovic Z, Nakic D, Vcev I, Majnarić L. A retrospective, case-control study on traditional environmental risk factors in inflammatory bowel disease in Vukovar-Srijem County, north-eastern Croatia, 2010. Wien Klin Wochenschr. 2015 May;127(9-10):345-54
30. Morris DL1, Montgomery SM, Thompson NP, Ebrahim S, Pounder RE, Wakefield AJ. Measles vaccination and inflammatory bowel disease: a national British Cohort Study. Am J Gastroenterol. 2000 Dec;95(12):3507-12.
    1. “In this cohort, monovalent measles vaccination status is not associated with inflammatory bowel disease by age 26 yr. Older age at measles vaccination needs to be examined in other studies to confirm whether it is a genuine risk for Crohn’s disease.”
31. Cheng DR1, Perrett KP2, Choo S3, Danchin M4, Buttery JP5, Crawford NW6. Pediatric anaphylactic adverse events following immunization in Victoria, Australia from 2007 to 2013. Vaccine. 2015 Mar 24;33(13):1602-7
32. Klein NP1, Lewis E2, Fireman B2, Hambidge SJ3, Naleway A4, Nelson JC5, Belongia EA6, Yih WK7, Nordin JD8, Hechter RC9, Weintraub E10, Baxter R2. Safety of measles-containing vaccines in 1-year-old children. Pediatrics. 2015 Feb;135(2):e321-9.
33. Hawken S1, Potter BK1, Benchimol EI2, Little J3, Ducharme R4, Wilson K5. Seasonal variation in rates of emergency room visits and acute admissions following recommended infant vaccinations in Ontario, Canada: a self-controlled case series analysis. Vaccine. 2014 Dec 12;32(52):7148-53
34. Macartney KK1, Gidding HF2, Trinh L3, Wang H3, McRae J3, Crawford N4, Gold M5, Kynaston A6, Blyth C7, Yvonne Z8, Elliott E8, Booy R9, Buttery J10, Marshall H5, Nissen M6, Richmond P7, McInytre PB9, Wood N9; PAEDS (Paediatric Active Enhanced Disease Surveillance) Network. Febrile seizures following measles and varicella vaccines in young children in Australia. Vaccine. 2015 Mar 10;33(11):1412-7.
    1. Australia gives Varicella at age 18 months??
35. Owatanapanich S, Wanlapakorn N, Tangsiri R, Poovorawan Y. Measles-mumps-rubella vaccination induced thrombocytopenia: a case report and review of the literature. Southeast Asian J Trop Med Public Health. 2014 Sep;45(5):1053-7.
36. Valenzise M1, Cascio A2, Wasniewska M1, Zirilli G1, Catena MA1, Arasi S1. Post vaccine acute disseminated encephalomyelitis as the first manifestation of chromosome 22q11.2 deletion syndrome in a 15-month old baby: a case report. Vaccine. 2014 Sep 29;32(43):5552-4.
37. Malaiyan J, Menon T1. Low vaccine efficacy of mumps component among MMR vaccine recipients in Chennai, India. Indian J Med Res. 2014 May;139(5):773-5.
38. Hambidge SJ, Newcomer SR, Narwaney KJ, et al.  Timely versus delayed early childhood vaccination and seizures. Pediatrics. 2014 Jun;133(6):e1492-9
    1. MMR vaccine timing – giving MMR before 15 months is associated with less febrile seizures.
39. Wilson K1, Ducharme R2, Ward B3, Hawken S4. Increased emergency room visits or hospital admissions in females after 12-month MMR vaccination, but no difference after vaccinations given at a younger age. Vaccine. 2014 Feb 26;32(10):1153-9. 
    1. Increased number of emergency visits in females only after MMR vaccination. “…translates to 192 excess events per 100,000 females vaccinated compared to the number of events that would have occurred in 100,000 males vaccinated.”
40. Ferrini W1, Aubert V, Balmer A, Munier FL, Abouzeid H. Anterior uveitis and cataract after rubella vaccination: a case report of a 12-month-old girl. Pediatrics. 2013 Oct;132(4):e1035-8. 
41. Heijstek MW1, Kamphuis S, Armbrust W, Swart J, Gorter S, de Vries LD, Smits GP, van Gageldonk PG, Berbers GA, Wulffraat NM. Effects of the live attenuated measles-mumps-rubella booster vaccination on disease activity in patients with juvenile idiopathic arthritis: a randomized trial. JAMA. 2013 Jun 19;309(23):2449-56.
    1. No increase in disease activity after MMR vaccine in patients with JIA.
42. Cecinati V1, Principi N, Brescia L, Giordano P, Esposito S. Vaccine administration and the development of immune thrombocytopenic purpura in children. Hum Vaccin Immunother. 2013 May;9(5):1158-62.
    1. “The available data clearly indicate that ITP is very rare and the only vaccine for which there is a demonstrated cause-effect relationship is the measles, mumps and rubella (MMR) vaccine that can occur in 1 to 3 children every 100,000 vaccine doses.” 
43. Mantadakis E1, Farmaki E, Buchanan GR. Thrombocytopenic purpura after measles-mumps-rubella vaccination: a systematic review of the literature and guidance for management. J Pediatr. 2010 Apr;156(4):623-8.
44. Davis RL1, Kramarz P, Bohlke K, Benson P, Thompson RS, Mullooly J, Black S, Shinefield H, Lewis E, Ward J, Marcy SM, Eriksen E, Destefano F, Chen R; Vaccine Safety Datalink Team. Measles-mumps-rubella and other measles-containing vaccines do not increase the risk for inflammatory bowel disease: a case-control study from the Vaccine Safety Datalink project. Arch Pediatr Adolesc Med. 2001 Mar;155(3):354-9.
45. Hao L1, Ma C1, Wannemuehler KA1, Su Q1, An Z1, Cairns L1, Quick L1, Rodewald L1, Liu Y1, He H1, Xu Q1, Ma Y1, Yu W1, Zhang N1, Li L1, Wang N1, Luo H1, Wang H2, Gregory CJ1. Risk factors for measles in children aged 8 months-14 years in China after nationwide measlescampaign: A multi-site case-control study, 2012-2013. Vaccine. 2016 Dec 12;34(51):6545-6552.
    1. Lack of vaccination was the leading risk factor for measles infection, especially in children born since the 2010 supplementary immunization activity. 
46. Sunil Gomber, Shilpa Khanna Arora, Shukla Das,* and V. G. Ramachandran* Immune response to second dose of MMR vaccine in Indian children Indian J Med Res. 2011 Sep; 134(3): 302–306.
47. Yadav S1, Thukral R, Chakarvarti A. Comparative evaluation of measles, mumps & rubella vaccine at 9 & 15 months of age. Indian J Med Res. 2003 Nov;118:183-6.
    1. “ Following MMR vaccination, 102 infants came for post vaccination sampling of which 92 per cent were seropositive for measles, 100 per cent for mumps and 98 per cent for rubella. In the age group of 15-18 months, of the 120 children, 67 (56%) were seronegative for measles, 84 (70%) for mumps and 86 (71.6%) for rubella. In 50 per cent of the children, there was a history of measles immunization at 9 months of age. After MMR vaccination, 100 children came for post vaccination sampling and seropositivity of 92, 96 and 94 per cent was observed for measles, mumps and rubella, respectively. The rise in the pre- and post-immunization geometrical mean titre was significant (P < 0.05) for each component of the vaccine in both the age groups.”
48. Ceyhan M1, Kanra G, Erdem G, Kanra B. Immunogenicity and efficacy of one dose measles-mumps-rubella (MMR) vaccine at twelve months of age as compared to monovalent measles vaccination at nine months followed by MMR revaccination at fifteen months of age. Vaccine. 2001 Aug 14;19(31):4473-8.
49. Pebody RG1, Gay NJ, Hesketh LM, Vyse A, Morgan-Capner P, Brown DW, Litton P, Miller E. Immunogenicity of second dose measles-mumps-rubella (MMR) vaccine and implications for serosurveillance. Vaccine. 2002 Jan 15;20(7-8):1134-40.
50. Rafiei Tabatabaei S1, Esteghamati AR, Shiva F, Fallah F, Radmanesh R, Abdinia B, Shamshiri AR, Khairkhah M, Shekari Ebrahimabad H, Karimi A. Detection of serum antibodies against measles, mumps and rubella after primary measles, mumps and rubella (MMR) vaccination in children. Arch Iran Med. 2013 Jan;16(1):38-41. 
51. Saffar MJ1, Fathpour GR, Parsaei MR, Ajami A, Khalilian AR, Shojaei J, Saffar H. Measles-mumps-rubella revaccination; 18 months vs. 4-6 years of age: potential impacts of schedule changes. J Trop Pediatr. 2011 Oct;57(5):347-51
52. LeBaron CW1, Forghani B, Matter L, Reef SE, Beck C, Bi D, Cossen C, Sullivan BJ. Persistence of rubella antibodies after 2 doses of measles-mumps-rubella vaccine. J Infect Dis. 2009 Sep 15;200(6):888-99.
53. Levine H1, Zarka S, Ankol OE, Rozhavski V, Davidovitch N, Aboudy Y, Balicer RD. Seroprevalence of measles, mumps and rubella among young adults, after 20 years of universal 2-dose MMR vaccination in Israel. Hum Vaccin Immunother. 2015;11(6):1400-5.
    1. 85.7% of 18-19 year olds were seropositive for measles.  (Rubella 90.4%, Mumps 87.0%)
54. Mahamud A1, Masunu-Faleafaga Y, Walls L, Williams N, Garcia P, Teshale E, Williams R, Dulski T, Bellini WJ, Kutty PK. Seroprevalence of measles, mumps and rubella among children in American Samoa, 2011, and progress towards West Pacific Region goals of elimination.
    1. American Samoa. Protective antibodies found in 92%, 90% and 93% of first grade students for measles, mumps, rubella respectively.  93% of students had 1 dose of MMR, 84% had 2 doses of MMR. 
55. Lebo EJ1, Kruszon-Moran DM2, Marin M1, Bellini WJ1, Schmid S1, Bialek SR1, Wallace GS1, McLean HQ3. Seroprevalence of measles, mumps, rubella and varicella antibodies in the United States population, 2009-2010. Open Forum Infect Dis. 2015 Feb 20;2(1):ofv006.
56. Gohil DJ1, Kothari ST1, Chaudhari AB2, Gunale BK2, Kulkarni PS2, Deshmukh RA1, Chowdhary AS1. Seroprevalence of Measles, Mumps, and Rubella Antibodies in College Students in Mumbai, India. Viral Immunol. 2016 Apr;29(3):159-63
57. You Jin Kim, Hae Ji Kang, Su Jin Kim, Jeong-Gu, Nam Sung Soon Kim Seroprevalence of measles-specific IgG antibodies in Korean children
58. LeBaron CW1, Beeler J, Sullivan BJ, Forghani B, Bi D, Beck C, Audet S, Gargiullo P. Persistence of measles antibodies after 2 doses of measles vaccine in a postelimination environment. Arch Pediatr Adolesc Med. 2007 Mar;161(3):294-301.
59. Jefferson T1, Price D, Demicheli V, Bianco E; European Research Program for Improved Vaccine Safety Surveillance (EUSAFEVAC) Project. Unintended events following immunization with MMR: a systematic review. Vaccine. 2003 Sep 8;21(25-26):3954-60.