MMR vaccine

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MMR vaccine
MMR vaccine.jpg
MMR vaccine
Combination of
Measles vaccine Vaccine
Mumps vaccine Vaccine
Rubella vaccine Vaccine
Clinical data
Trade names M-M-R II, Priorix, Tresivac, others
Other namesMPR vaccine [1]
AHFS/Drugs.com Monograph
MedlinePlus a601176
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Pregnancy
category
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Legal status
  • AU: S4 (Prescription only)
  • UK: POM (Prescription only)
  • US: ℞-only [3] [4]
  • EU:Rx-only [5]
  • In general: ℞ (Prescription only)
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The MMR vaccine is a vaccine against measles, mumps, and rubella (German measles), abbreviated as MMR. [6] The first dose is generally given to children around 9 months to 15 months of age, with a second dose at 15 months to 6 years of age, with at least four weeks between the doses. [7] [8] [9] After two doses, 97% of people are protected against measles, 88% against mumps, and at least 97% against rubella. [7] The vaccine is also recommended for those who do not have evidence of immunity, [7] those with well-controlled HIV/AIDS, [10] [11] and within 72 hours of exposure to measles among those who are incompletely immunized. [8] It is given by injection. [12]

Contents

The MMR vaccine is widely used around the world. Worldwide over 500 million doses were administered between 1999 and 2004, [13] and 575 million doses have been administered since the vaccine's introduction worldwide. [14] Measles resulted in 2.6 million deaths per year before immunization became common. [14] This has decreased to 122,000 deaths per year as of 2012, mostly in low-income countries. [14] Through vaccination, as of 2018, rates of measles in North and South America are very low. [14] Rates of disease have been seen to increase in populations that go unvaccinated. [14] Between 2000 and 2018, vaccination decreased measles deaths by 73%. [15]

Side effects of immunization are generally mild and resolve without any specific treatment. [16] These may include fever, as well as pain or redness at the injection site. [16] Severe allergic reactions occur in about one in a million people. [16] Because it contains live viruses, the MMR vaccine is not recommended during pregnancy but may be given while breastfeeding. [7] The vaccine is safe to give at the same time as other vaccines. [16] Being recently immunized does not increase the risk of passing measles, mumps, or rubella on to others. [7] There is no evidence of an association between MMR immunisation and autistic spectrum disorders. [17] [18] [19] The MMR vaccine is a mixture of live weakened viruses of the three diseases. [7]

The MMR vaccine was developed by Maurice Hilleman. [6] It was licensed for use in the US by Merck in 1971. [20] Stand-alone measles, mumps, and rubella vaccines had been previously licensed in 1963, 1967, and 1969, respectively. [20] [21] Recommendations for a second dose were introduced in 1989. [20] The MMRV vaccine, which also covers chickenpox, may be used instead. [7] An MR vaccine, without coverage for mumps, is also occasionally used. [22]

Medical use

Priorix Priorix.jpg
Priorix

Cochrane concluded that the "Existing evidence on the safety and effectiveness of MMR and MMRV vaccine supports current policies of mass immunisation aimed at global measles eradication in order to reduce morbidity and mortality associated with measles mumps rubella and varicella." [17]

The combined MMR vaccine induces immunity less painfully than three separate injections at the same time, and sooner and more efficiently than three injections given on different dates. Public Health England reports that providing a single combined vaccine as of 1988, rather than giving the option to have them also done separately, increased uptake of the vaccine. [23]

Measles

Measles cases reported in the United States fell drastically after introduction of the measles vaccine. Measles US 1938-2019.png
Measles cases reported in the United States fell drastically after introduction of the measles vaccine.

Before the widespread use of a vaccine against measles, rates of disease were so high that infection was felt to be "as inevitable as death and taxes." [24] Reported cases of measles in the United States fell from hundreds of thousands to tens of thousands per year following introduction of the vaccine in 1963. Increasing uptake of the vaccine following outbreaks in 1971, and 1977, brought this down to thousands of cases per year in the 1980s. An outbreak of almost 30,000 cases in 1990 led to a renewed push for vaccination and the addition of a second vaccine to the recommended schedule. Fewer than 200 cases have been reported in the US each year between 1997 and 2013, and the disease is no longer considered endemic there. [25] [26] [27]

The benefit of measles vaccination in preventing illness, disability, and death has been well documented. The first 20 years of licensed measles vaccination in the US prevented an estimated 52 million cases of the disease, 17,400 cases of intellectual disability, and 5,200 deaths. [28] During 1999–2004, a strategy led by the World Health Organization and UNICEF led to improvements in measles vaccination coverage that averted an estimated 1.4 million measles deaths worldwide. [13] Between 2000 and 2018, measles vaccination resulted in a 73% decrease in deaths from the disease. [15]

Measles is common in many areas of the world. Although it was declared eliminated from the US in 2000, high rates of vaccination and good communication with people who refuse vaccination are needed to prevent outbreaks and sustain the elimination of measles in the US. [29] Of the 66 cases of measles reported in the US in 2005, slightly over half were attributable to one unvaccinated individual who acquired measles during a visit to Romania. [30] This individual returned to a community with many unvaccinated children. The resulting outbreak infected 34 people, mostly children and virtually all unvaccinated; 9% were hospitalized, and the cost of containing the outbreak was estimated at $167,685. A major epidemic was averted due to high rates of vaccination in the surrounding communities. [29]

In 2017, an outbreak of measles occurred among the Somali-American community in Minnesota, where MMR vaccination rates had declined due to the misconception that the vaccine could cause autism. The US Centers for Disease Control and Prevention recorded 65 affected children in the outbreak by April 2017. [31]

Rubella

Rubella rates fell sharply in the United States when immunization was introduced. Rubella in the US 1966-2017.png
Rubella rates fell sharply in the United States when immunization was introduced.

Rubella, also known as German measles, was also very common before widespread vaccination. The major risk of rubella is during pregnancy when the baby may contract congenital rubella, which can cause significant congenital defects. [32]

Mumps

Mumps is another viral disease that was once very common, especially during childhood. If mumps is acquired by a male who is past puberty, a possible complication is bilateral orchitis, which can in some cases lead to sterility. [33]

Administration

The MMR vaccine is administered by a subcutaneous injection, the first dose typically at twelve months of age. [12] The second dose may be given as early as one month after the first dose. [34] The second dose is a dose to produce immunity in the small number of persons (2–5%) who fail to develop measles immunity after the first dose. In the US it is done before entry to kindergarten because that is a convenient time. [35] Areas where measles is common typically recommend the first dose at nine months of age and the second dose at fifteen months of age. [8]

Safety

Adverse reactions, rarely serious, may occur from each component of the MMR vaccine. Ten percent of children develop fever, malaise, and a rash 5–21 days after the first vaccination; [36] and 3% develop joint pain lasting 18 days on average. [37] Older women appear to be more at risk of joint pain, acute arthritis, and even (rarely) chronic arthritis. [38] Anaphylaxis is an extremely rare but serious allergic reaction to the vaccine. [39] One cause can be egg allergy. [40] In 2014, the FDA approved two additional possible adverse events on the vaccination label: acute disseminated encephalomyelitis (ADEM), and transverse myelitis, with permission to also add "difficulty walking" to the package inserts. [41] A 2012 IOM report found that the measles component of the MMR vaccine can cause measles inclusion body encephalitis in immunocompromised individuals. This report also rejected any connection between the MMR vaccine and autism. [42] Some versions of the vaccine contain the antibiotic neomycin and therefore should not be used in people allergic to this antibiotic. [19]

The number of reports on neurological disorders is very small, other than evidence for an association between a form of the MMR vaccine containing the Urabe mumps strain and rare adverse events of aseptic meningitis, a form of viral meningitis. [38] [43] The UK National Health Service stopped using the Urabe mumps strain in the early 1990s due to cases of transient mild viral meningitis, and switched to a form using the Jeryl Lynn mumps strain instead. [44] The Urabe strain remains in use in a number of countries; MMR with the Urabe strain is much cheaper to manufacture than with the Jeryl Lynn strain, [45] and a strain with higher efficacy along with a somewhat higher rate of mild side effects may still have the advantage of reduced incidence of overall adverse events. [44]

A Cochrane review found that, compared with placebo, MMR vaccine was associated with fewer upper respiratory tract infections, more irritability, and a similar number of other adverse effects. [17]

Naturally acquired measles often occurs with immune thrombocytopenic purpura (ITP, a purpuric rash and an increased tendency to bleed that resolves within two months in children), occurring in 1 to 20,000 cases. [17] Approximately 1 in 40,000 children are thought to acquire ITP in the six weeks following an MMR vaccination. [17] ITP below the age of six years is generally a mild disease, rarely having long-term consequences. [46] [47]

False claims about autism

In 1998 Andrew Wakefield et al. published a fraudulent paper about twelve children, reportedly with bowel symptoms and autism or other disorders acquired soon after administration of MMR vaccine, [48] while supporting a competing vaccine. In 2010, Wakefield's research was found by the General Medical Council to have been "dishonest", [49] and The Lancet fully retracted the paper. [50] [51] Three months following The Lancet's retraction, Wakefield was struck off the UK medical register, with a statement identifying deliberate falsification in the research published in The Lancet, [52] and was barred from practising medicine in the UK. [53] The research was declared fraudulent in 2011 by the British Medical Journal . [54]

Since Wakefield's publication, multiple peer-reviewed studies have failed to show any association between the vaccine and autism. [17] [55] The US Centers for Disease Control and Prevention, [56] [57] the Institute of Medicine of the US National Academy of Sciences, [58] the UK National Health Service [59] and the Cochrane Library review [17] have all concluded that there is no evidence of a link.

Administering the vaccines in three separate doses does not reduce the chance of adverse effects, and it increases the opportunity for infection by the two diseases not immunized against first. [55] [60] Health experts have criticized media reporting of the MMR-autism controversy for triggering a decline in vaccination rates. [61] Before publication of Wakefield's article, the inoculation rate for MMR in the UK was 92%; after publication, the rate dropped to below 80%. In 1998, there were 56 measles cases in the UK; by 2008, there were 1348 cases, with two confirmed deaths. [62]

In Japan, the MMR triplet is not used. Immunity is achieved by a combination vaccine for measles and rubella, followed up later with a mumps only vaccine. This has had no effect on autism rates in the country, further disproving the MMR autism hypothesis. [63]

History

Maurice Hilleman, who developed the MMR vaccine Hilleman-Walter-Reed.jpeg
Maurice Hilleman, who developed the MMR vaccine
Two workers make openings in chicken eggs in preparation for a measles vaccine Preparation of measles vaccines.jpg
Two workers make openings in chicken eggs in preparation for a measles vaccine

The component viral strains of MMR vaccine were developed by propagation in animal and human cells. [64]

For example, in the case of mumps and measles viruses, the virus strains were grown in embryonated chicken eggs. This produced strains of virus which were adapted for chicken cells and less well-suited for human cells. These strains are therefore called attenuated strains. They are sometimes referred to as neuroattenuated because these strains are less virulent to human neurons than the wild strains.

The rubella component, Meruvax, was developed in 1967, through propagation using the human embryonic lung cell line WI-38 (named for the Wistar Institute) that was derived six years earlier in 1961. [65] [66]

Disease immunizedComponent vaccineVirus strainPropagation medium Growth medium
Measles Attenuvax Enders' attenuated Edmonston strain [67] chick embryo cell cultureMedium 199
Mumps Mumpsvax [68] Jeryl Lynn (B level) strain [69]
Rubella Meruvax II Wistar RA 27/3 strain of live attenuated rubella virus WI-38 human embryonic cell line MEM (solution containing buffered salts, fetal bovine serum, human serum albumin and neomycin, etc.)

The term "MPR vaccine" is also used to refer to this vaccine, whereas "P" refer to parotitis which is caused by mumps. [1]

Merck MMR II is supplied freeze-dried (lyophilized) and contains live viruses. Before injection it is reconstituted with the solvent provided. [70]

According to a review published in 2018, the GlaxoSmithKline (GSK) MMR vaccine known as Pluserix "contains the Schwarz measles virus, the Jeryl Lynn–like mumps strain, and RA27/3 rubella virus". [71]

Pluserix was introduced in Hungary in 1999. [72] Enders' Edmonston strain has been used since 1999 in Hungary in Merck MMR II product. [72] GSK Priorix vaccine, which uses attenuated Schwarz Measles, was introduced in Hungary in 2003. [72]

MMRV vaccine

The MMRV vaccine, a combined measles, mumps, rubella and varicella (chickenpox) vaccine, has been proposed as a replacement for the MMR vaccine to simplify administration of the vaccines. [34] Preliminary data indicate a rate of febrile seizures of 9 per 10,000 vaccinations with MMRV, as opposed to 4 per 10,000 for separate MMR and varicella shots; US health officials therefore do not express a preference for use of MMRV vaccine over separate injections. [73]

In a 2012 study [74] pediatricians and family doctors were sent a survey to gauge their awareness of the increased risk of febrile seizures (fever fits) in the MMRV. 74% of family doctors and 29% of pediatricians were unaware of the increased risk of febrile seizures. After reading an informational statement only 7% of family doctors and 20% of pediatricians would recommend the MMRV for a healthy 12- to 15-month-old child. The factor that was reported as the "most important" deciding factor in recommending the MMRV over the MMR+V was ACIP/AAFP/AAP recommendations (pediatricians, 77%; family physicians, 73%).

MR vaccine

This is a vaccine that covers measles and rubella but not mumps. [22] As of 2014, it was used in a "few (unidentified) countries". [22]

Society and culture

Religious concerns

Some brands of the vaccine use gelatin, derived from pigs, as a stabilizer. [75] This has caused reduced take-up among some communities, [75] [76] despite the fact that alternative vaccines without pig derivatives are approved and available. [75]

Related Research Articles

<span class="mw-page-title-main">Vaccination</span> Administration of a vaccine to protect against disease

Vaccination is the administration of a vaccine to help the immune system develop immunity from a disease. Vaccines contain a microorganism or virus in a weakened, live or killed state, or proteins or toxins from the organism. In stimulating the body's adaptive immunity, they help prevent sickness from an infectious disease. When a sufficiently large percentage of a population has been vaccinated, herd immunity results. Herd immunity protects those who may be immunocompromised and cannot get a vaccine because even a weakened version would harm them. The effectiveness of vaccination has been widely studied and verified. Vaccination is the most effective method of preventing infectious diseases; widespread immunity due to vaccination is largely responsible for the worldwide eradication of smallpox and the elimination of diseases such as polio and tetanus from much of the world. However, some diseases, such as measles outbreaks in America, have seen rising cases due to relatively low vaccination rates in the 2010s – attributed, in part, to vaccine hesitancy. According to the World Health Organization, vaccination prevents 3.5–5 million deaths per year.

<span class="mw-page-title-main">Measles</span> Viral disease affecting humans

Measles is a highly contagious, vaccine-preventable infectious disease caused by measles virus. Symptoms usually develop 10–12 days after exposure to an infected person and last 7–10 days. Initial symptoms typically include fever, often greater than 40 °C (104 °F), cough, runny nose, and inflamed eyes. Small white spots known as Koplik's spots may form inside the mouth two or three days after the start of symptoms. A red, flat rash which usually starts on the face and then spreads to the rest of the body typically begins three to five days after the start of symptoms. Common complications include diarrhea, middle ear infection (7%), and pneumonia (6%). These occur in part due to measles-induced immunosuppression. Less commonly seizures, blindness, or inflammation of the brain may occur. Other names include morbilli, rubeola, red measles, and English measles. Both rubella, also known as German measles, and roseola are different diseases caused by unrelated viruses.

<span class="mw-page-title-main">Mumps</span> Human disease caused by paramyxovirus

Mumps is a highly contagious viral disease caused by the mumps virus. Initial symptoms of mumps are non-specific and include fever, headache, malaise, muscle pain, and loss of appetite. These symptoms are usually followed by painful swelling around the side of the face, which is the most common symptom of a mumps infection. Symptoms typically occur 16 to 18 days after exposure to the virus. About one third of people with a mumps infection do not have any symptoms (asymptomatic).

<span class="mw-page-title-main">Rubella</span> Human viral disease

Rubella, also known as German measles or three-day measles, is an infection caused by the rubella virus. This disease is often mild, with half of people not realizing that they are infected. A rash may start around two weeks after exposure and last for three days. It usually starts on the face and spreads to the rest of the body. The rash is sometimes itchy and is not as bright as that of measles. Swollen lymph nodes are common and may last a few weeks. A fever, sore throat, and fatigue may also occur. Joint pain is common in adults. Complications may include bleeding problems, testicular swelling, encephalitis, and inflammation of nerves. Infection during early pregnancy may result in a miscarriage or a child born with congenital rubella syndrome (CRS). Symptoms of CRS manifest as problems with the eyes such as cataracts, deafness, as well as affecting the heart and brain. Problems are rare after the 20th week of pregnancy.

<span class="mw-page-title-main">Vaccine hesitancy</span> Reluctance or refusal to be vaccinated or have ones children vaccinated

Vaccine hesitancy is a delay in acceptance, or refusal, of vaccines despite the availability of vaccine services and supporting evidence. The term covers refusals to vaccinate, delaying vaccines, accepting vaccines but remaining uncertain about their use, or using certain vaccines but not others. Although adverse effects associated with vaccines are occasionally observed, the scientific consensus that vaccines are generally safe and effective is overwhelming. Vaccine hesitancy often results in disease outbreaks and deaths from vaccine-preventable diseases. Therefore, the World Health Organization characterizes vaccine hesitancy as one of the top ten global health threats.

<span class="mw-page-title-main">Vaccination schedule</span> Series of vaccinations

A vaccination schedule is a series of vaccinations, including the timing of all doses, which may be either recommended or compulsory, depending on the country of residence. A vaccine is an antigenic preparation used to produce active immunity to a disease, in order to prevent or reduce the effects of infection by any natural or "wild" pathogen. Vaccines go through multiple phases of trials to ensure safety and effectiveness.

<span class="mw-page-title-main">Childhood immunizations in the United States</span>

The schedule for childhood immunizations in the United States is published by the Centers for Disease Control and Prevention (CDC). The vaccination schedule is broken down by age: birth to six years of age, seven to eighteen, and adults nineteen and older. Childhood immunizations are key in preventing diseases with epidemic potential.

The MMRV vaccine is a combination vaccine which combines the attenuated virus measles, mumps, rubella, and varicella (chickenpox). The MMRV vaccine has similar immunogenicity and overall safety profiles to the MMR vaccine administered with or without the varicella vaccine. The MMRV vaccine is typically given to children between one and two years of age.

<span class="mw-page-title-main">Mumps vaccine</span> Vaccine which prevents mumps

Mumps vaccines are vaccines which prevent mumps. When given to a majority of the population they decrease complications at the population level. Effectiveness when 90% of a population is vaccinated is estimated at 85%. Two doses are required for long term prevention. The initial dose is recommended between 12 and 18 months of age. The second dose is then typically given between two years and six years of age. Usage after exposure in those not already immune may be useful.

A breakthrough infection is a case of illness in which a vaccinated individual becomes infected with the illness, because the vaccine has failed to provide complete immunity against the pathogen. Breakthrough infections have been identified in individuals immunized against a variety of diseases including mumps, varicella (Chickenpox), influenza, and COVID-19. The characteristics of the breakthrough infection are dependent on the virus itself. Often, infection of the vaccinated individual results in milder symptoms and shorter duration than if the infection were contracted naturally.

<span class="mw-page-title-main">Varicella vaccine</span> Vaccine to prevent chickenpox

Varicella vaccine, also known as chickenpox vaccine, is a vaccine that protects against chickenpox. One dose of vaccine prevents 95% of moderate disease and 100% of severe disease. Two doses of vaccine are more effective than one. If given to those who are not immune within five days of exposure to chickenpox it prevents most cases of disease. Vaccinating a large portion of the population also protects those who are not vaccinated. It is given by injection just under the skin. Another vaccine, known as zoster vaccine, is used to prevent diseases caused by the same virus – the varicella zoster virus.

An attenuated vaccine is a vaccine created by reducing the virulence of a pathogen, but still keeping it viable. Attenuation takes an infectious agent and alters it so that it becomes harmless or less virulent. These vaccines contrast to those produced by "killing" the pathogen.

Claims of a link between the MMR vaccine and autism have been extensively investigated and found to be false. The link was first suggested in the early 1990s and came to public notice largely as a result of the 1998 Lancet MMR autism fraud, characterised as "perhaps the most damaging medical hoax of the last 100 years". The fraudulent research paper, authored by discredited former doctor Andrew Wakefield and published in The Lancet, falsely claimed the vaccine was linked to colitis and autism spectrum disorders. The paper was retracted in 2010 but is still cited by anti-vaccine activists.

<span class="mw-page-title-main">Andrew Wakefield</span> Discredited British former doctor (born 1956)

Andrew Jeremy Wakefield is a British fraudster, discredited academic, anti-vaccine activist, and former physician.

<span class="mw-page-title-main">Measles vaccine</span> Vaccine used to prevent measles

Measles vaccine protects against becoming infected with measles. Nearly all of those who do not develop immunity after a single dose develop it after a second dose. When the rate of vaccination within a population is greater than 92%, outbreaks of measles typically no longer occur; however, they may occur again if the rate of vaccination decreases. The vaccine's effectiveness lasts many years. It is unclear if it becomes less effective over time. The vaccine may also protect against measles if given within a couple of days after exposure to measles.

<span class="mw-page-title-main">Rubella vaccine</span> Vaccine used to prevent rubella

Rubella vaccine is a vaccine used to prevent rubella. Effectiveness begins about two weeks after a single dose and around 95% of people become immune. Countries with high rates of immunization no longer see cases of rubella or congenital rubella syndrome. When there is a low level of childhood immunization in a population it is possible for rates of congenital rubella to increase as more women make it to child-bearing age without either vaccination or exposure to the disease. Therefore, it is important for more than 80% of people to be vaccinated. By introducing rubella containing vaccines, rubella has been eradicated in 81 nations, as of mid-2020.

<span class="mw-page-title-main">Vaccines for Children Program</span>

The Vaccines for Children Program (VFC) is a federally funded program in the United States providing no-cost vaccines to children who lack health insurance or who otherwise cannot afford the cost of the vaccination. The VFC program was created by the Omnibus Budget Reconciliation Act of 1993 and is required to be a new entitlement of each state's Medicaid plan under section 1928 of the Social Security Act. The program was officially implemented in October 1994 and serves eligible children in all U.S. states, as well as the Commonwealth of Puerto Rico, the U.S. Virgin Islands, American Samoa, Guam, and the Commonwealth of the Northern Mariana Islands.

<span class="mw-page-title-main">Epidemiology of measles</span>

Measles is extremely contagious, but surviving the infection results in lifelong immunity, so its continued circulation in a community depends on the generation of susceptible hosts by birth of children. In communities which generate insufficient new hosts the disease will die out. This concept was first recognized by Bartlett in 1957, who referred to the minimum number supporting measles as the critical community size (CCS). Analysis of outbreaks in island communities suggested that the CCS for measles is c. 250,000. Due to the development of vaccination against measles, the world has seen a 99% decrease in measles related cases compared cases before the vaccine was developed.

In early months of 2019, a measles outbreak occurred in the Portland metropolitan area, including the Clark County, Washington suburbs, in the United States. At the time, the outbreak was the largest outbreak in more than two decades; outbreaks in 2019 in areas including Brooklyn and Rockland County, New York have since seen far greater numbers of cases.

Extensive investigation into vaccines and autism has shown that there is no relationship between the two, causal or otherwise, and that vaccine ingredients do not cause autism. Vaccinologist Peter Hotez researched the growth of the false claim and concluded that its spread originated with Andrew Wakefield's fraudulent 1998 paper, with no prior paper supporting a link.

References

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