MMR vaccine

Overview
The MMR vaccine is a mixture of live attenuated viruses, administered via injection for immunization against measles, mumps and rubella. It is generally administered to children around the age of one year, with a booster dose before starting school (i.e. age 4/5). In the United States, the booster began in the mid 1990s. It is widely used around the world; since introduction of its earliest versions in the 1970s, over 500 million doses have been used in over 60 countries. As with all vaccinations, long-term effects and efficacy are subject to continuing study. The vaccine is sold by Merck as M-M-R II, GlaxoSmithKline Biologicals as Priorix, and sanofi pasteur as TRIMOVAX.

Effectiveness
Before the widespread use of a vaccine against measles, its incidence was so high that infection with measles was felt to be "as inevitable as death and taxes." Today, the incidence of measles has fallen to less than 1% of people under the age of 30 in countries with routine childhood vaccination.

The benefit of vaccination against measles in preventing illness, disability, and death has been well-documented. The first 20 years of licensed measles vaccination in the U.S. prevented an estimated 52 million cases of the disease, 17,400 cases of mental retardation, and 5,200 deaths. 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.

Measles is endemic worldwide. Although it was declared eliminated from the U.S. in 2000, high rates of vaccination and good communication with persons who refuse vaccination is needed to prevent outbreaks and sustain the elimination of measles in the U.S. Of the 66 cases of measles reported in the U.S. in 2005, slightly over half were attributable to one unvaccinated individual who acquired measles during a visit to Romania. 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.

Mumps is another viral disease of childhood that was once very common. A known but relatively rare complication of mumps is sterility in males.

Rubella, otherwise known as German measles, was also very common before the advent of widespread vaccination. The major risk of rubella is if a pregnant woman is infected, her baby may contract congenital rubella from her, which can cause significant congenital defects.

All three diseases are highly contagious.

The combined MMR vaccine was introduced to induce immunity less painfully than three separate injections at the same time, and sooner and more efficiently than three injections given on different dates.

In 2005, the Cochrane Library published a review of 31 scientific studies. One of its main results: "We could not identify studies assessing the effectiveness of MMR that fulfilled our inclusion criteria even though the impact of mass immunisation on the elimination of the diseases has been largely demonstrated." Its authors concluded, "Existing evidence on the safety and effectiveness of MMR vaccine supports current policies of mass immunisation aimed at global measles eradication in order to reduce morbidity and mortality associated with mumps and rubella."

Development, formulation and administration
The component viral strains of MMR vaccine were developed by propagation in animal and human cells. The live viruses require animal or human cells as a host for production of more virus.

For example, in the case of mumps and measles viruses, the virus strains were grown in embryonated hens' eggs and chick embryo cell cultures. This produced strains of virus which were adapted for the hens egg 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, is propagated using a human cell line (WI-38, named for the Wistar Institute) derived in 1961 from embryonic lung tissue. The use of human cell lines has led to some religious controversy.

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

The MMR vaccine is administered by a subcutaneous injection. High vaccination coverage before 2 years of age is important, and a second ("booster") injection is needed to achieve satisfactory levels of immunity and hence interrupt virus transmission. The booster may be given as early as one month after the first dose.

Safety
Adverse reactions, rarely serious, may occur from each component of the MMR vaccine. 10% of children develop fever, malaise and a rash 5–21 days after the first vaccination; 5% develop temporary joint pain. Older women appear to be more at risk to joint pain, acute arthritis, and even (rarely) chronic arthritis. Anaphylaxis is an extremely rare but serious allergic reaction to the vaccine. The vaccine product brief lists many other adverse reactions.

The number of reports on neurologic 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 transient mild form of viral meningitis. 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. 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, 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.

The Cochrane Library review found several problems in the quality of MMR vaccine safety studies. Its authors concluded by recommending the adoption of standardized definitions of adverse events. The review's abstract concludes, "The design and reporting of safety outcomes in MMR vaccine studies, both pre- and post-marketing, are largely inadequate. The evidence of adverse events following immunisation with MMR cannot be separated from its role in preventing the target diseases."

Autism
In the UK, the MMR vaccine was the subject of controversy after publication of a 1998 paper by Andrew Wakefield et al. reporting a study of twelve children who had autism spectrum disorders and bowel symptoms, in many cases with onset soon after administration of MMR vaccine. During a 1998 press conference, Wakefield suggested that giving children the vaccines in three separate doses would be safer than a single jab. This suggestion was not supported by the paper, and several subsequent peer-reviewed studies have failed to show any association between the vaccine and autism. 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. Wakefield has been heavily criticized on scientific grounds and for triggering a decline in vaccination rates, as well as on ethical grounds for the way the research was conducted.

In 2004, after an investigation by The Sunday Times, the interpretation section of the study, which identified a general association in time between the vaccine and autism, was formally retracted by ten of Wakefield's twelve coauthors. The Centers for Disease Control, the Institute of Medicine of the National Academy of Sciences, the UK National Health Service and the Cochrane Library review have all concluded that there is no evidence of a link between the MMR vaccine and autism.

MMRV vaccine
The MMRV vaccine, a combined MMR and varicella vaccine, has been proposed as a replacement for the MMR vaccine to simplify administration of the vaccines.