MMR vaccine

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Definition

MMR vaccine is a combined vaccine to protect children against measles, mumps, and rubella, which are dangerous and potentially deadly diseases. Alternative names are rubella vaccination, mumps vaccination, vaccine-MMR.

Description

The MMR, which does not contain mercury, consists of live viruses that have been weakened (attenuated) so that the vaccine is still capable of inducing a productive immune response but does not cause the disease that the original or "wild-type" viruses can. The MMR vaccine is a mix of three vaccines: attenuvax (measles), mumpsvax (mumps), and meruvax II (rubella).

The three-in-one MMR vaccine protects against measles, mumps, and rubella. Although single antigen (individual) vaccines are available for each part of the MMR, they are only used in specific situations, in which one of the three diseases occurs and public health officials decide to immunize infants six to 15 months of age for that particular disease. (Single antigen vaccines pose less risk to children younger than the recommended age of 15 months for the MMR.)

Measles (Rubeola)

Before vaccination, epidemics of measles peaked in the spring every two to four years. Measles is an endemic disease in many undeveloped countries and in countries where measles immunization levels are low. Because the risk of contracting measles in other countries is greater than in the United States, infants and children should be as well protected as possible before traveling.

Measles is caused by a virus that grows in the nose, mouth, throat, and the eyes, and in their secretions. It is highly communicable and may not be recognized early because the symptoms often resemble cold symptoms. The incubation period is 10 to 11 days. Measles begins with slight temperature rise and a runny nose and eyes. About the second or third day, blush-white pinpoint spots with a red rim, known as Koplick's spots, appear in the mouth. Small dark red pimples appear on the head and spread gradually over the body. These pimples grow larger and in groups, giving a blotchy appearance, which is an important difference between measles and scarlet fever. In scarlet fever, the skin appears red all over.

The respiratory symptoms grow worse. The child sneezes often, the eyes are sore, and nasal secretion becomes purulent. Light hurts the eyes (photophobia). The child's throat is sore. The rash is greatest about the fourth day, and it may last up to ten days. During the second week, the skin begins to flake off, and it continues to do so for five to ten days.

Treatment is limited to combating the symptoms of measles because antiviral drugs as of 2004 are ineffective. The disease has serious possible complications. For example, encephalomyelitis (inflammation of the brain and spinal cord) occurs in one to two cases out of 1000 patients; the disease is fatal at that same rate. Immune globulin injections help prevent or reduce measles infection if given within six days of exposure. Complications can be brought on by measles. Encephalitis occurs in one out of 6000 cases; 20 percent of these infections are fatal. Thrombocytopenic purpura (skin hemorrhages because of decreased platelet count) occur in one out of 3000 cases.

Mumps (Epidemic Parotitis)

Mumps, another viral disease, affects the salivary glands, especially the parotid gland. Children under the age of two years old seldom have mumps; adults rarely have this disease. A closer contact is necessary to transmit mumps than other contagious diseases. The incubation period lasts from two to three weeks, averaging about 18 days.

In most cases, the first sign of mumps is a swelling in the parotid glands; occasionally, mumps may begin with a slight fever, headache, and malaise before the swelling appears. Sometimes only one of the parotid glands is affected, but both may be inflamed at the same time or one after the other. The glands become swollen and tender and are painful. It hurts for the child to suck while nursing or in older children to open his mouth and eat, but otherwise he may not feel sick at all. After two or three days, the swelling begins to go down, and usually disappears by the tenth day. As a rule, keeping children isolated or out of school for two weeks is long enough to prevent communicating the infection to others. Treatment is entirely palliative; as of 2004, there was no effective antiviral treatment.

Mumps can cause certain complications. The nervous system is affected in 65 percent of patients; 10 percent display symptoms of this, and 2 percent of these cases are fatal. Testicular complications occur in 14 to 35 percent of post-pubertal boys, and complications regarding the ovaries in 7 percent of post-pubertal females. These complications are rare in prepubescent children, however. Deafness in one or both ears occurs in one out of 15,000 cases. More than half of the deaths from mumps occur in those over 19 years of age. Mumps infection during the first trimester of pregnancy increases the risk of spontaneous abortion.

Rubella (German Measles)

Rubella is also caused by a virus, but the disease is mild and last only a short time. The symptoms are like measles but are not nearly as severe, and spots never appear on the mucous membranes of the mouth. Sometimes the rash that appears on the face is the first noticeable sign of a rubella infection. The rash spreads quickly and disappears just as rapidly; sometimes it is gone from the face and the neck by the time it reaches the arms and the legs. The rash usually lasts two to four days.

Isolation from other children is brief or not carried out at all; since the infectious stage is so brief, there is little danger of passing on the infection after the rash appears. The greatest risk of German measles is fetal malformations which occur when a mother is infected in the early months of pregnancy.

Children and adults may can have rubella more than once; 3 to 10 percent of those who have had rubella and 14 to 18 percent of those immunized become infected on exposure to the virus. Some reinfections are subclinical (i.e., have no visible symptoms). In fact, some 25 to 50 percent of rubella infections are asymptomatic.

General Use

Recommended Mmr Vaccination Schedule

Because the risk of serious disease from infection with either mumps or rubella in infants is low, mumps and rubella vaccines should not be given to infants younger than 12 months old. When the measles vaccine is needed a single-antigen measles vaccine is given. However, parents of an infant less than 12 months of age should be immune to mumps and rubella so they will not expose the infant or become infected if the infant becomes ill.

The first dose of the vaccine is given to children 12 to 15 months old. The second dose of the MMR vaccine should be given at four to six years of age. All children are to be fully immunized before starting school in the United States. Children who have not the second dose as recommended should complete the immunization by 11 or 12 years of age.

Mmr Traveling Recommendations

Before infants and children of 12 months of age or older leave the United States, they should receive two doses of MMR vaccine separated by at least 28 days, with the first dose given on their birthday. Infants under 12 months of age should receive a dose of monovalent (single antigen) measles vaccine before departure. If monovalent vaccine is not available, no specific contraindication exists to giving MMR to infants six to eleven months of age. The risk for serious disease from either mumps or rubella infection among infants is low.

Infants who receive the monovalent measles vaccine or MMR before their first birthday are vulnerable to all three diseases and should be revaccinated with two doses of MMR. The first should be given when the infant is 12 to 15 months of age (12 months if the infant remains in an area where disease risk is high) and the second at least 28 days later.

Parents or adults who travel or live abroad with infants less than 12 months old should have evidence of immunity to rubella and mumps, as well as measles, to avoid becoming infected if the infants are exposed to the diseases.

An infant less than six months of age is usually protected against measles, mumps, and rubella by maternal antibodies. As a rule, the infant does not need added protection unless the mother is diagnosed with measles.

Maternal Immunity to Mmr

Most fetuses receive some natural immunity to measles from their mothers in utero. This passive immunity fades over time and is less effective in children of immunized mothers than in children of mothers who had the measles.

The duration of protection is dependent to a great extent on the maternal antibody titer and the antibodies received by the infant during pregnancy. Women who have had the disease have higher measles antibody titers than women who have not had measles but have been vaccinated. Women who have not had measles nor vaccination have no measles antibodies.

Precautions

There are few reasons not to be vaccinated. Some of these are as follows:

• being allergic to gelatin or neomycin or having had an allergic reaction to a previous MMR vaccination
• being moderately or severely ill
• being pregnant
• in males, mumps can cause inflammation of the testes; in female, the ovaries, external genitals, or breasts may be affected

Side Effects

Most of the time inactivated vaccines are given intramuscularly (IM), and live virus vaccines are given subcutaneously (SC). Vaccines that are used intramuscularly may cause local reactions (such as irritation, skin discoloration, inflammation, and granuloma formation) if injected into subcutaneous tissue. The vaccine may also be less effective if it is not given by the proper route.

Interactions

There is varying incidence of vaccine reactions. Some of these are as follows:

• fever (one out of six)
• mild rash (one out of 20)
• swollen glands (rare)
• seizure (one out of 3,000)
• pain and joint stiffness (one out of 20)
• low platelet count (one out of 30,000)
• serious allergic reaction (less than one out of 1,000,000)

Parental Concerns

Parents often express concern about combining three vaccines in one injection. As of 2004 there is no published evidence showing a benefit to separating the combination MMR vaccine into three individual shots. The CDC continues to recommend two doses of the combined MMR vaccine for all children.

Because signs of autism may appear around the time children receive the MMR vaccine, some parents worry that the vaccine causes autism. Research has not found a relationship between MMR vaccine and autism.

It is sometimes difficult for parents to adhere to the recommended vaccine schedule, including the spacing between doses. If the intervals between doses is longer than usual, there is no need to restart the series of any vaccine.

MMR vaccinations are appropriate for children with chronic diseases such as diabetes and cardiovascular condition as advised by the pediatrician.

Symptoms of low-grade fever, irritability, and soreness at the injection site following the MMR immunization can be relieved with an analgesic such as acetaminophen as recommended by the pediatrician. Cool compresses to the injection site are also comforting.

Resources

Books

Behrman, Richard E., et al., eds. Nelson Textbook of Pediatrics, 16th ed. Philadelphia: Saunders, 2000.

Horton, Richard. A Jab in the Dark: Anxiety and Rationality in the MMR Controversy. New York: New York Review of Books, 2005.

Web Sites

"Childhood Immunization Support Program." American Academy of Pediatrics. Available online at www.cispimmunize.org/ (accessed December 18, 2004).

[Article by: Aliene Linwood, R.N., DPA, FACHE]

The MMR vaccine is a mixture of three live attenuated viruses, administered via injection for immunization against measles, mumps and rubella (also called German measles). It is generally administered to children around the age of one year, with a second dose before starting school (i.e. age 4/5). The second dose is not a booster; it is a dose to produce immunity in the small number of persons (2–5%) who fail to develop measles immunity after the first dose.^[1] In the United States, the vaccine was licensed in 1971 and the second dose was introduced in 1989.^[2] 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, Serum Institute of India as Tresivac, and sanofi pasteur as Trimovax.

Contents 1 Effectiveness 2 Development, formulation and administration 3 Safety 3.1 Claims about autism 4 MMRV vaccine 5 References

Effectiveness

Measles fell sharply after immunization was introduced.

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."^[3] Today, the incidence of measles has fallen to less than 1% of people under the age of 30 in countries with routine childhood vaccination.^{[citation needed]}

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.^[4] 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.^[5]

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.^[6] 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.^[7] 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.^[6]

Mumps is another viral disease of childhood that was once very common. 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.^[8]

Rubella fell sharply when immunization was introduced.

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.^[9]

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."^[10]

Development, formulation and administration

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. 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.^[11] This cell line was originally prepared from tissues of aborted fetuses, raising religious objections.^[12]

Disease Immunized	Component Vaccine	Virus Strain	Propagation Medium	Growth Medium
Measles	Attenuvax	Enders' attenuated Edmonston strain[13]	chick embryo cell culture	Medium 199
Mumps	Mumpsvax[14]	Jeryl Lynn (B level) strain[15]
Rubella	Meruvax II	Wistar RA 27/3 strain of live attenuated rubella virus	WI-38 human diploid lung fibroblasts	MEM (solution containing buffered salts, fetal bovine serum, human serum albumin and neomycin, etc.)

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.The second dose may be given as early as one month after the first dose.^[16] The second dose is not a booster; it 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 U.S. it is done before entry to kindergarten because that is a convenient time.^[1]

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.^[17] Older women appear to be more at risk of joint pain, acute arthritis, and even (rarely) chronic arthritis.^[18] Anaphylaxis is an extremely rare but serious allergic reaction to the vaccine.^[19] One cause can be egg allergy.^[20] The vaccine product brief lists many other adverse reactions.^[21]

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.^[18][22] 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.^[23] 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,^[24] 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.^[23]

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."^[10]

Claims about autism

Main article: MMR vaccine controversy

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, including cases where onset was considered to be soon after administration of MMR vaccine.^[25] During a 1998 press conference, Wakefield suggested that giving children the vaccines in three separate doses would be safer than a single injection. 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.^[26] 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.^[26][27] Health experts have criticized media reporting of the MMR-autism controversy for triggering a decline in vaccination rates.^[28]

In 2004, after an investigation by The Sunday Times,^[29] 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.^[30] The Centers for Disease Control and Prevention,^[31] the Institute of Medicine of the National Academy of Sciences,^[32] the UK National Health Service^[33] and the Cochrane Library review^[10] have all concluded that there is no evidence of a link between the MMR vaccine and autism.

In 2007 Wakefield became the subject of a General Medical Council disciplinary hearing over allegations that his research had received funding related to litigation against MMR-vaccine manufacturers, and had concealed this fact from the editors of The Lancet.^[34] It was later revealed that Wakefield received £435,643 [about $780,000] plus expenses for consulting work related to the lawsuit. This funding came from the UK legal aid fund, a fund intended to provide legal services to the poor.^[29] In 2009 The Sunday Times reported that Wakefield had manipulated patient data and misreported results in his 1998 paper, creating the appearance of a link with autism.^[35]

MMRV vaccine

Main article: MMRV vaccine

The MMRV vaccine, a combined measles, mumps, rubella and varicella vaccine, has been proposed as a replacement for the MMR vaccine to simplify administration of the vaccines.^[16] Preliminary data indicate a rate of fever-induced seizure of 9 per 10,000 vaccinations with MMRV, as opposed to 4 per 10,000 for separate MMR and varicella injections; U.S. health officials therefore do not express a preference for use of MMRV vaccine over separate injections.^[36]

References

1. ^ ^{a b} "MMR vaccine questions and answers". Centers for Disease Control and Prevention. 2004. http://cdc.gov/vaccines/vpd-vac/combo-vaccines/mmr/faqs-mmr-hcp.htm. Retrieved on 2008-05-28. 
2. ^ Banatvala JE, Brown DW (2004). "Rubella". Lancet 363 (9415): 1127–37. doi:10.1016/S0140-6736(04)15897-2. PMID 15064032. 
3. ^ Babbott FL Jr, Gordon JE (1954). "Modern measles". Am J Med Sci 228 (3): 334–61. PMID 13197385. 
4. ^ Bloch AB, Orenstein WA, Stetler HC et al. (1985). "Health impact of measles vaccination in the United States". Pediatrics 76 (4): 524–32. PMID 3931045. 
5. ^ Centers for Disease Control and Prevention (CDC) (2006). "Progress in reducing global measles deaths, 1999–2004". MMWR Morb Mortal Wkly Rep 55 (9): 247–9. PMID 16528234. http://www.cdc.gov/mmwr/preview/mmwrhtml/mm5509a8.htm. 
6. ^ ^{a b} Parker AA, Staggs W, Dayan GH et al. (2006). "Implications of a 2005 measles outbreak in Indiana for sustained elimination of measles in the United States". N Engl J Med 355 (5): 447–55. doi:10.1056/NEJMoa060775. PMID 16885548. 
7. ^ Centers for Disease Control and Prevention (CDC) (2006). "Measles—United States, 2005". MMWR Morb Mortal Wkly Rep 55 (50): 1348–51. PMID 17183226. http://www.cdc.gov/mmwr/preview/mmwrhtml/mm5550a2.htm. 
8. ^ Jequier, Anne M. (2000). Male infertility: a guide for the clinician. Malden, MA: Blackwell Publishing. p. 118. ISBN 0632051299. http://books.google.com/books?id=ULWh1Wc1nKMC. 
9. ^ "Rubella vaccine information". National Network for Immunization Information. 2006-09-25. http://www.immunizationinfo.org/vaccineInfo/vaccine_detail.cfv?id=24. Retrieved on 2007-09-02. 
10. ^ ^{a b c} Demicheli V, Jefferson T, Rivetti A, Price D (2005). "Vaccines for measles, mumps and rubella in children". Cochrane Database Syst Rev 19 (4). doi:10.1002/14651858.CD004407.pub2. PMID 16235361. Lay summary – Abstract and plain language summary (2005-10-19). 
11. ^ ViroMed Laboratories (2004). "Selected profiles of cell cultures: WI-38". http://www.viromed.com/services/product/wi38.htm. Retrieved on 2007-09-03. 
12. ^ Pontifical Academy for Life (2005). "Moral reflections on vaccines prepared from cells derived from aborted human foetuses". Center for Bioethics, Catholic University of the Sacred Heart. http://www.academiavita.org/template.jsp?sez=Documenti&pag=testo/vacc/vacc&lang=english. Retrieved on 2008-12-03. 
13. ^ "Attenuvax Product Sheet" (PDF). Merck & Co. 2006. 1. http://www.merck.com/product/usa/pi_circulars/a/attenuvax/attenuvax_pi.pdf. Retrieved on 2009-02-04. 
14. ^ Merck Co. (1990, 1999). "MUMPSVAX (Mumps Virus Vaccine Live) Jeryl Lynn Strain" (PDF). Merck Co.. http://www.merck.com/product/usa/pi_circulars/m/mumpsvax/mumpsvax_pi.pdf. 
15. ^ Young ML, Dickstein B, Weibel RE, Stokes J Jr, Buynak EB, Hilleman MR (1967). "Experiences with Jeryl Lynn strain live attenuated mumps virus vaccine in a pediatric outpatient clinic". Pediatrics 40 (5): 798–803. PMID 6075651. 
16. ^ ^{a b} Vesikari T, Sadzot-Delvaux C, Rentier B, Gershon A (2007). "Increasing coverage and efficiency of measles, mumps, and rubella vaccine and introducing universal varicella vaccination in Europe: a role for the combined vaccine". Pediatr Infect Dis J 26 (7): 632–8. doi:10.1097/INF.0b013e3180616c8f. PMID 17596807. 
17. ^ Harnden A, Shakespeare J (2001). "10-minute consultation: MMR immunisation". BMJ 323 (7303): 32. doi:10.1136/bmj.323.7303.32. PMID 11440943. http://www.bmj.com/cgi/content/full/323/7303/32. 
18. ^ ^{a b} Schattner A (2005). "Consequence or coincidence? The occurrence, pathogenesis and significance of autoimmune manifestations after viral vaccines". Vaccine 23 (30): 3876–86. doi:10.1016/j.vaccine.2005.03.005. PMID 15917108. 
19. ^ Carapetis JR, Curtis N, Royle J (2001). "MMR immunisation. True anaphylaxis to MMR vaccine is extremely rare". BMJ 323 (7317): 869. PMID 11683165. 
20. ^ Fox A, Lack G (October 2003). "Egg allergy and MMR vaccination". Br J Gen Pract 53 (495): 801–2. PMID 14601358. PMC: 1314715. http://openurl.ingenta.com/content/nlm?genre=article&issn=0960-1643&volume=53&issue=495&spage=801&aulast=Fox. 
21. ^ ""M-M-R II (measles, mumps, and rubella virus vaccine live)"" (PDF). Merck. 2007. http://www.merck.com/product/usa/pi_circulars/m/mmr_ii/mmr_ii_pi.pdf. Retrieved on 2007-09-03. 
22. ^ Institute of Medicine (1994). "Measles and mumps vaccines". Adverse Events Associated with Childhood Vaccines: Evidence Bearing on Causality. National Academy Press. ISBN 0309074967. 
23. ^ ^{a b} Colville A, Pugh S, Miller E, Schmitt HJ, Just M, Neiss A (1994). "Withdrawal of a mumps vaccine". Eur J Pediatr 153 (6): 467–8. doi:10.1007/BF01983415. PMID 8088305. 
24. ^ Fullerton KE, Reef SE (2002). "Commentary: Ongoing debate over the safety of the different mumps vaccine strains impacts mumps disease control". Int J Epidemiol 31 (5): 983–4. doi:10.1093/ije/31.5.983. PMID 12435772. http://ije.oxfordjournals.org/cgi/content/full/31/5/983. 
25. ^ Wakefield A, Murch S, Anthony A et al. (1998). "Ileal-lymphoid-nodular hyperplasia, non-specific colitis, and pervasive developmental disorder in children". Lancet 351 (9103): 637–41. doi:10.1016/S0140-6736(97)11096-0. PMID 9500320. http://briandeer.com/mmr/lancet-paper.htm. Retrieved on 2007-09-05. 
26. ^ ^{a b} National Health Service (2004). "MMR: myths and truths". http://www.mmrthefacts.nhs.uk/basics/truths.php. Retrieved on 2007-09-03. 
27. ^ MMR vs three separate vaccines:
    • Halsey NA, Hyman SL, Conference Writing Panel (2001). "Measles-mumps-rubella vaccine and autistic spectrum disorder: report from the New Challenges in Childhood Immunizations Conference convened in Oak Brook, Illinois, June 12–13, 2000". Pediatrics 107 (5): e84. doi:10.1542/peds.107.5.e84. PMID 11331734. http://pediatrics.aappublications.org/cgi/content/full/107/5/e84. 
    • Leitch R, Halsey N, Hyman SL (2002). "MMR—Separate administration-has it been done?". Pediatrics 109 (1): 172. doi:10.1542/peds.109.1.172. PMID 11773568. http://pediatrics.aappublications.org/cgi/content/full/109/1/172. 
    • Miller E (2002). "MMR vaccine: review of benefits and risks". J Infect 44 (1): 1–6. doi:10.1053/jinf.2001.0930. PMID 11972410. 
28. ^ "Doctors issue plea over MMR jab". BBC News. http://news.bbc.co.uk/2/hi/health/5118166.stm. Retrieved on 2009-02-04. 
29. ^ ^{a b} Deer B (2008-11-02). "The MMR-autism crisis - our story so far". http://briandeer.com/mmr/lancet-summary.htm. Retrieved on 2008-12-06. 
30. ^ Murch SH, Anthony A, Casson DH et al. (2004). "Retraction of an interpretation". Lancet 363 (9411): 750. doi:10.1016/S0140-6736(04)15715-2. PMID 15016483. 
31. ^ "Measles, mumps, and rubella (MMR) vaccine". Centers for Disease Control and Prevention. 2008-08-22. http://cdc.gov/vaccinesafety/concerns/mmr_autism_factsheet.htm. Retrieved on 2008-12-21. 
32. ^ Immunization Safety Review: Vaccines and Autism. From the Institute of Medicine of the National Academy of Sciences. Report dated May 17, 2004; accessed June 13, 2007.
33. ^ MMR Fact Sheet, from the United Kingdom National Health Service. Accessed June 13, 2007.
34. ^ [1]BBC news article
35. ^ Deer B (2009-02-08). "MMR doctor Andrew Wakefield fixed data on autism". Sunday Times. http://www.timesonline.co.uk/tol/life_and_style/health/article5683671.ece. Retrieved on 2009-02-09. 
36. ^ Klein NP, Yih WK, Marin M et al. (2008). "Update: recommendations from the Advisory Committee on Immunization Practices (ACIP) regarding administration of combination MMRV vaccine". MMWR Morb Mortal Wkly Rep 57 (10): 258–60. PMID 18340332. http://www.cdc.gov/mmwr/preview/mmwrhtml/mm5710a3.htm. 

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