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What is the History of Measles Vaccine in America and Other Countries?


History of measles vaccine in America and other countries
Image source: CDC PHIL

Two measles vaccines were first licensed in 1963, both containing the Edmonston B measles strain isolated by John Enders in 1954. Rubeovax, a live attenuated vaccine, was manufactured by Merck while Pfizer-Vax Measles-K, an inactivated (killed) virus vaccine, was manufactured by Pfizer.1

At the time of vaccine approval, a single dose of the live attenuated Rubeovax was reported to be 95 percent effective at preventing measles, and protection from measles infection lasted at least 3 years and eight months. However, 30 to 40 percent of children who received Rubeovax experienced fever of 103 degrees or higher beginning on or around the sixth day following vaccination, lasting between 2 to 5 days. 30 to 60 percent of individuals who received Rubeovax also developed a “modified measles rash”.2 Due to the high number of side effects, public health officials and Merck officials recommended that Rubeovax be administered in conjunction with measles immune globulin, as co-administration significantly reduced reactions from the vaccine.3 4

Pfizer-Vax Measles–K, Pfizer’s inactivated measles virus vaccine given in a series of 3 vaccines at one month intervals, was much less reactive, however, the vaccine offered limited effectiveness against the disease. In fact, the majority of children who received the vaccine had no detectable levels of measles antibodies one year later.5 By 1965, reports of a new and abnormal measles-like illness began to surface in children previously vaccinated with inactivated measles virus vaccine and exposed to measles. Symptoms of atypical measles included rash, swelling, fever, pneumonia, and pleural effusion.6 Pfizer’s inactivated vaccine was taken off the market in 1968.7

Prior to 1963, as a result of the highly reactive nature of the live measles virus, Enders, had made the Edmonston measles strain available for other researchers to work with to encourage them to further attenuate the virus for vaccine use.8 As a result, additional live attenuated measles vaccines using the Edmonston B measles strain also became available in 1963, including M-Vac, manufactured by Lederle Pharmaceuticals, and other generic measles vaccines manufactured by various pharmaceutical companies including Parke Davis, Eli Lilly, and more. Pfizer also introduced Pfizer-Vax Measles-L, a live attenuated measles vaccine, in 1965. However, by 1975, all early approved measles vaccines had been discontinued and replaced with two newer, and more attenuated vaccines.9

These two further attenuated live measles vaccines were developed for use in the mid-1960’s as a result of the numerous unwanted side effects related to the earlier live vaccines. Lirugen, manufactured by Pitman Moore-Dow, was developed from the Schwarz strain of measles, a strain derived from further attenuating the Edmonston A strain.10 This vaccine was approved for use in 1965 but discontinued in the United States by 1976.11 The Schwarz strain remains in use outside of the United States. Merck further attenuated the Edmonston B strain and in 1968, its Attenuvax live attenuated vaccine, using the Moraten measle strain, was approved for use in the United States.12 Attenuvax is currently the measles vaccine found in Merck’s Measles, Mumps, and Rubella combination vaccine, MMRII,13 as well as Merck’s Measles, Mumps, Rubella, and Varicella vaccine, ProQuad.14

In 1967, public health officials announced that measles could be eradicated from the United States within a few months, with the introduction and use of measles vaccines.15 However, mass vaccination of infants beginning at approximately one year of age and the push for all children entering school to receive a dose of measles vaccine, did not result in measles eradication and outbreaks continued to occur in highly vaccinated populations.16 17 By 1971, public health officials noted that measles outbreaks were on the rise, and blamed the increasing number of measles cases on unvaccinated populations as well as the lack of legislation in many states to require measles vaccination as a condition of school entry. Public health officials acknowledged that vaccine failure played a role in outbreaks, and blamed failure on several factors including early vaccination prior to 9 months of age, the use of measles gamma globulin, improper vaccine handling and storage, as well as the 3 to 5 percent failure rate of the vaccine. The goal of measles eradication in the United States was no longer considered to be something that could be achieved quickly, and possibly not something achievable after all.18

Measles outbreaks continued to occur throughout the 1970’s and 1980’s, mainly affecting pre-school and school aged children.19 Despite the continued outbreaks, in 1979, public health officials launched an effort to eradicate measles in the United States through vaccination, by October 1st, 1982.20 In 1982, there were a record low 1,697 reported cases of measles in the United States21 and while public health officials conceded that they did not meet their goal, they publicly stated eradication to be “right around the corner”.22 Measles cases decreased again to 1,497 in 1983, before resurging to a reported 2,534 cases in 1984.23 By 1985, there were 2,813 reported measles cases, with 44 percent of cases occurring in children who were appropriately vaccinated with measles vaccine.24

In 1989, another resurgence of measles occurred and by the end of the year, 18,193 cases of measles were reported to the CDC,25 with over 40 percent of cases occurring in fully vaccinated individuals.26 The CDC blamed the outbreaks on both the failure of implementing vaccine programs, particularly those aimed at vaccinating preschool children, as well as on vaccine failure. While blaming the measles outbreaks on vaccine failure, the CDC continued to report a 95 percent measles vaccine effectiveness rate, all while denying that vaccine induced immunity was waning. However, in 1989, the CDC’s Advisory Committee on Immunization Practices (ACIP) updated its measles vaccine recommendations, recommending that all children receive 2 doses of MMR vaccine prior to school entry, with the first dose of at 15 months, and the second dose at 4 to 6 years of age, prior to Kindergarten or first grade.27

As well, in 1989, the CDC also sponsored a study involving the use of two separate measles vaccines that targeted minority children living in the Los Angeles area. One of the two measles vaccines used in the study was an experimental, unlicensed vaccine, however, this information was not disclosed to parents. 28 The experimental vaccine was a high dose measles vaccine aimed at overwhelming the natural maternal antibodies that protect infants from infection during the first year of life. The presence of maternal antibodies at time of vaccination can lead to vaccine failure and the risk of measles infection later in life.  This experimental measles vaccine was in use outside of the country, however, by 1990, studies noting a higher death rate in female children receiving the vaccine began to appear in medical journals. The Los Angeles study was halted in 1991, however the public was not informed of the use of the experimental vaccine until 1996. While the CDC claims that no vaccine injuries resulted from the use of this unlicensed vaccine, one child that took part in the study died of a bacterial infection. The CDC, however, maintains that the death was not related to vaccination. 29

In 1998, concerns over safety of the combination measles-mumps-rubella vaccine surfaced following a published case study on 12 previously healthy children who developed severe gastrointestinal disorders after MMR vaccination.30 Eight of the twelve children involved in the study also developed autism, with parents and personal physicians reporting that symptoms began soon after receiving the MMR vaccine. As well, the 13 physicians involved in the study also reported that they had investigated over 40 similar cases. While these researchers were not claiming that the MMR vaccine was responsible for causing the reported gastrointestinal health problems, they urged that more research be done on the subject.31

Following publication, scientists involved in the study, including lead author Dr. Andrew Wakefield, became subject of an enormous backlash from public health officials and vaccine policymakers, in attempt to discredit the study.32 By the late 2000’s, Wakefield and two contributing researchers, Dr. John Walker-Smith and Dr. Simon Murch, became the subjects of disciplinary action from the United Kingdom’s General Medical Council (GMC) over misconduct claims in association with the study. In May 2010, Wakefield and Walker-Smith both lost their medical licenses, having been found guilty of misconduct by the GMC.33 Walker-Smith appealed the verdict and in 2012, a U.K. high court reversed the decision, with the presiding judge criticizing the GMC’s disciplinary panel’s decision, stated that "It would be a misfortune if this were to happen again."34 Since the publication of Wakefield et al’s controversial case study, independent researchers have replicated the findings.35 Yet, despite this additional scientific literature, Wakefield continues to be demonized by the press and medical community.36 37

In August 2014, William Thompson, a senior scientist at the CDC, came forward with allegations that CDC researchers purposely omitted data that would show a link between the MMR vaccine and autism among African American boys.38 According to Thompson, researchers involved in the 2004 study went as far as destroying data that would demonstrate an association between autism and the MMR vaccine. After these allegations came to light, Florida Senator Bill Posey called for an investigation of the CDC scientists involved in the study to determine whether fraud had been committed in an attempt to cover up a link between the MMR vaccine and autism. 39 The cover-up of the autism-MMR link by the CDC became the subject of Vaxxed: From Cover-Up to Catastrophe, a documentary that had been scheduled to make its debut at New York City’s Tribeca Film Festival in April of 2016. However following an onslaught of media attacks against the film, the documentary was dropped from the festival’s lineup,40 41 and debuted instead at Manhattan’s Angelika Film Center in April of 2016.42 Government officials have yet to investigate the allegations brought forward by Thompson against his fellow CDC scientists.

In early January of 2015, the CDC began investigating an outbreak of measles linked to the Disneyland theme park resort in California. In a statement released on January 23, 2015, the CDC announced that 51 confirmed cases of measles had been linked to the outbreak and encouraged vaccination against measles.43 The measles cases linked to Disneyland set off a media frenzy, and hundreds of measles outbreak news stories followed, with many reports blaming and vilifying the parents of unvaccinated children.44 As a result of the outbreak, several state legislators began introducing vaccine legislation, with bills aimed at eliminating or severely restricting religious and conscientious/philosophical vaccine exemptions. Vaccine choice advocates were extremely successful in defeating many of the restrictive vaccine bills, however, California lost its personal belief exemption and Vermont lost its philosophical exemption, but retained its religious vaccine exemption.45 In 2015, there were only 188 reported cases of measles in the United States, 46 with 147 cases linked to the outbreak in California,47 which was a 72 percent decrease in measles cases from one year earlier.48

Currently, the CDC’s Advisory Committee on Immunization Practices continues to recommend that all children receive 2 doses of MMR vaccine, with the first dose administered between 12 and 15 months of age, and the second dose administered between 4 and 6 years of age, prior to entering kindergarten or first grade.49

Measles vaccination rates remain high in the U.S. with the CDC currently reporting that 94 percent of children entering kindergarten50  and more than 92% of high school students have received two doses of MMR vaccine. 51

IMPORTANT NOTE: NVIC encourages you to become fully informed about Measles and the Measles vaccine by reading all sections in the Table of Contents , which contain many links and resources such as the manufacturer product information inserts, and to speak with one or more trusted health care professionals before making a vaccination decision for yourself or your child. This information is for educational purposes only and is not intended as medical advice.

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References

1 Hendriks J, Blume S Measles Vaccination Before the Measles-Mumps-Rubella Vaccine Am J Public Health. 2013 Aug;103(8):1393-401

2 Terry LL The Status of Measles Vaccines - A Technical Report J Natl Med Assoc. 1963 Sep; 55(5): 453–455.

3 Ibid

4 Galambos L, Sewell JE Networks of Innovation: Vaccine Development at Merck, Sharp & Dohme, and Mulford, 1895-1995. Cambridge University Press, 1997.

5 Terry LL The Status of Measles Vaccines - A Technical Report J Natl Med Assoc. 1963 Sep; 55(5): 453–455.

6  Rauh LW, R. Schmidt R Measles immunization with killed virus vaccine. Serum antibody titers and experience with exposure to measles epidemic. 1965. Bull World Health Organ. 2000; 78(2): 226–231.

7 CDC Selected Discontinued U.S. Vaccines Epidemiology and Prevention of Vaccine-Preventable Diseases, 13th Edition

8 Hendriks J, Blume S Measles Vaccination Before the Measles-Mumps-Rubella Vaccine Am J Public Health. 2013 Aug;103(8):1393-401

9 Institute of Medicine Committee to Review Adverse Effects of Vaccines. Adverse Events Associated with Childhood Vaccines (Evidence Bearing on Causality). Washington, DC: The National Academies Press. 1994 Chap. 6. P. 118

10 Ibid

11 CDC Selected Discontinued U.S. Vaccines Epidemiology and Prevention of Vaccine-Preventable Diseases, (The Pink Book) 13th Edition

12 Institute of Medicine Committee to Review Adverse Effects of Vaccines. Adverse Events Associated with Childhood Vaccines (Evidence Bearing on Causality). Washington, DC: The National Academies Press. 1994 Chap. 6. P. 118

13 FDA Measles, Mumps and Rubella Virus Vaccine, Live  May 16, 2017

14 FDA Measles, Mumps, Rubella and Varicella Virus Vaccine Live. Oct 23, 2018

15 Sencer DJ, Dull HB, Langmuir AD Epidemiologic basis for eradication of measles in 1967. Public Health Rep. 1967 Mar; 82(3): 253–256.

16 Baratta RO, Ginter MC, Price MA et al. Measles (rubeola) in previously immunized children. Pediatrics. 1970 Sep; 46(3):397-402.

17 Wood DL, Brunell PA Measles control in the United States: problems of the past and challenges for the future. Clin Microbiol Rev. 1995 Apr; 8(2): 260–267.

18 Conrad JL, Wallace R, Witte JJ The epidemiologic rationale for the failure to eradicate measles in the United States. Am J Public Health. 1971 November; 61(11): 2304–2310.

19 Wood DJ, Brunell PA. Measles Control in the United States: Problems of the Past and Challenges for the Future. Clin Microbiol Rev 1995; 8(2): 260-267. 

20 Hinman AR, Brandling-Bennett AD, Nieburg PI. The opportunity and obligation to eliminate measles from the United States. JAMA. 1979 Sep 14; 242(11):1157-62.

21 CDC Current Trends Measles -- United States, 1982 MMWR Feb. 04, 1983; 32(4);49-51

22 Associated Press U.S. Cases of Measles Are Almost Eradicated. The New York Times. Oct. 3, 1982

23 CDC Current Trends Measles -- North America, 1984 MMWR Jun. 21, 1985; 34(24);366-70

24 CDC Measles -- United States, 1985 MMWR Jun. 06, 1986; 35(22);366-70

25 CDC Summary of notifiable diseases, United States, 1989 MMWR October 5, 1990; 42 (53); 1-67

26 CDC Current Trends Measles -- United States, 1989 and First 20 Weeks 1990 MMWR Jun 01, 1990; 39(21);353-355,361-363

27 CDC Measles Prevention: Recommendations of the Immunization Practices Advisory Committee (ACIP) MMWR Dec 29, 1989; 38(S-9);1-18

28 Cimons M CDC Says It Erred in Measles Study. Los Angeles Times. Jun. 17, 1996

29 Fisher BL. Measles Vaccine Experiments on Minority Children Turn Deadly. NVIC Commentary. June 1996. Vol 2 No 2. Online. 

30 Wakefield AJ, Murch SH, Anthony A et al. Ileal-lymphoid-nodular hyperplasia, non-specific colitis, and pervasive developmental disorder in children. Lancet. 1998 Feb 28;351(9103):637-41. (Retracted)

31 NVIC Research into Vaccines, Autism and Intestinal Disorders Published in the Lancet Press Release. Mar. 3, 1998

32 Ibid

33 Boseley S Andrew Wakefield struck off register by General Medical Council. The Guardian. May. 24, 2010

34 Aston J MMR DOCTOR JOHN WALKER-SMITH WINS HIGH COURT APPEAL. The Independent. Mar. 7, 2012

35 Beck S Scientists fear MMR link to autism. The Daily Mail. May 28, 2006

36 Buncombe A Andrew Wakefield: How a disgraced UK doctor has remade himself in anti-vaxxer Trump’s America. The Independent. May 4 , 2018

37 Blanchard S Discredited doctor Andrew Wakefield who falsely claimed MMR jabs lead to autism is handed 'bad science' award - 20 years after his 'fatally flawed' report was published The Daily Mail. Oct. 16, 2018

38 Attkisson S (Audio) CDC Addresses Allegations on Vaccine-Autism Link Omission. SharylAttkisson.com Aug. 29, 2014

39 Posey B (Transcript) Congressman Wants CDC Investigated for Tampering With MMR Study The Vaccine Reaction. Aug. 1, 2015

40 Cáceres M When the Media Thinks and Concludes for the People. The Vaccine Reaction. Mar. 29, 2016

41 Mercola J Robert De Niro Enters the Vaccine Safety Battle. Mercola.com Apr. 26, 2016

42 Ryzik M Anti-Vaccine Film, Pulled From Tribeca Film Festival, Draws Crowd at Showing. The New York Times. Apr. 1, 2016

43 CDC U.S. Multi-State Measles Outbreak, December 2014-January 2015CDC Health Alert Network Jan. 23, 2015

44 Fisher B Measles in Disneyland: Third MMR Shot and Vaccine Exemption Ban? Jan. 28, 2015

45 NVIC State Vaccine Legislation in America 2015-2017. Oct 25, 2017

46 CDC Summary of Notifiable Infectious Diseases and Conditions — United States, 2015. MMWR. Aug. 11, 2017; 64(53);1–143

47 CDC Measles Cases and Outbreaks. Nov. 15, 2018

48 CDC Summary of Notifiable Infectious Diseases and Conditions — United States, 2014 MMWR. Oct. 14, 2016; 63(54);1-152

49 CDC Prevention of Measles, Rubella, Congenital Rubella Syndrome, and Mumps, 2013: Summary Recommendations of the Advisory Committee on Immunization Practices (ACIP). MMWR. Jun. 14, 2013; 62(RR04);1-34

50  CDC. Vaccination Coverage for Selected Vaccines, Exemption Rates, and Provisional Enrollment Among Children in Kindergarten — United States, 2016–17 School Year MMWR Oct. 13, 2017; 66(40);1073–1080

51 CDC. National, Regional, State, and Selected Local Area Vaccination Coverage Among Adolescents Aged 13–17 Years — United States, 2017 MMWR Aug. 24, 2018; 67(33);909–917


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