PEDIATRICS Vol. 114 No. 4 October 2004, pp. 1065-1069 (doi:10.1542/peds.2004-0440)
SPECIAL ARTICLE |
Measles Vaccines and the Potential for Worldwide Eradication of Measles
* Division of Pediatric Infectious Disease, New England Medical Center, Tufts University School of Medicine, Boston, Massachusetts
National Immunization Program, Centers for Disease Control and Prevention, Atlanta, Georgia
Emory Vaccine Center, Emory University, Atlanta, Georgia
 |
ABSTRACT |
|---|
 TOP ABSTRACT TREND IN DISEASE CAUSED...MEASLES VACCINE EFFICACYRISK OF MEASLES AMONG...CONCERN REGARDING AUTISM AS...GLOBAL ERADICATION OF MEASLESCONCLUSIONREFERENCES |
|---|
The annual number of reported measles cases in the United States has declined from between 3 million and 4 million in the prevaccine era to <100 cases in association with the highest recorded immunization rates in history. Because of continued importation of measles into the United States, young children who are not vaccinated appropriately may experience more than a 60-fold increase in risk of disease. Unsubstantiated claims suggesting an association between measles vaccine and neurologic disorders have led to reduced vaccine use and a resurgence of measles in countries where immunization rates have declined below the level needed to maintain herd immunity. To address the possibility of worldwide control of measles, efforts to ensure high immunization rates among people in both developed and developing countries must be sustained.
Key Words: bioterrorism • measles-mumps-rubella vaccine • vaccines • measles • autism
Abbreviations: MMR, measles-mumps-rubella • ASD, autism spectrum disorders
Measles virus infection is second only to malaria in terms of the number of people who die each year as a result of complications from an infectious disease. In countries with a weak measles vaccination program, the World Health Organization estimated that in 2001, 
30 million cases of measles resulted in 745 000 deaths in children younger than 15 years.1 In other countries, where measles immunization rates are <85%, disease burden is reduced but still high, such as in Japan, where an estimated 100 000 cases and 20 to 50 deaths occurred in 2001.2 In the United States, routine measles vaccination has been part of a childhood immunization program since 1963, resulting in a 39-year downward trend in incidence of disease. Since 1997, the incidence of measles in the United States has been sustained at record low levels of <1 case/million population/y.3 The effectiveness of a comprehensive measles immunization program on disease elimination is so profound that it is appropriate to consider the possibility of global measles eradication and how obstacles to that objective might be overcome. This article reviews the remarkable impact of immunization on the interruption of measles transmission in the United States, the efficacy of the measles vaccine, the critical importance of continued vaccination as disease rates decline, the threats to continued vaccine acceptance, and, finally, the prospects for global eradication of measles.
Measles virus was first isolated in human and monkey kidney cell cultures in 1954 by Enders and Peebles, and soon thereafter, several attenuated vaccine strains were prepared from a measles isolate obtained from an infected child by the name of Edmonston.4 The Edmonston B strain was licensed in the United States in 1963 and was used widely until 1975. A formalin-inactivated measles vaccine was also licensed in the United States in 1963, but this vaccine was withdrawn in 1967 because of short-lived immunity and because of predisposition to a syndrome of atypical measles among vaccine recipients who were subsequently exposed to wild-type virus.5 A number of additional attenuated vaccines were developed from the original Edmonston strain, including the Schwarz and the Edmonston-Zagreb strains, which are commonly used outside the United States, and the Moraten strain, which is the only measles vaccine currently used in the United States.6 The combination measles-mumps-rubella (MMR) vaccine was licensed in the United States in 1971.
|
TREND IN DISEASE CAUSED BY MEASLES IN THE UNITED STATES |
|---|
|
TOPABSTRACTTREND IN DISEASE CAUSED...MEASLES VACCINE EFFICACYRISK OF MEASLES AMONG...CONCERN REGARDING AUTISM AS...GLOBAL ERADICATION OF MEASLESCONCLUSIONREFERENCES |
|---|
In the prevaccine era, between 3 and 4 million cases of measles occurred each year, resulting in several thousand deaths (Fig 1). A few years after initiation of a measles immunization program in 1963, the number of reported cases fell by >98%.6 A resurgence of measles in 1977 led to the establishment in 1978 of a national goal for the elimination of measles transmission by 1982. Although this goal was not attained, fewer than 1500 cases of measles were reported in 1982, representing the smallest number of reported cases in a single year up to that time. Over ensuing years, a gradual increase in the number of cases occurred with infection mainly in 2 groups: unvaccinated children in the first 5 years of life and individuals who were vaccinated appropriately after 12 months of age but who experienced an inadequate immune response and remained susceptible (primary vaccine failure). Because of the occurrence of measles outbreaks among vaccinated children, in 1989, the American Academy of Pediatrics and the Advisory Committee on Immunization Practices recommended a change to 2 doses of measles vaccine administered after the first 12 months of life.7 Between 1989 and 1991, there was a dramatic resurgence of measles, with 55 165 reported cases and 123 deaths, producing a case fatality rate of 2.2 deaths per 1000 cases. A low vaccination rate in young children was the single most important reason for this outbreak.8
|
As a consequence of the increased emphasis on measles immunization, a dramatic decline in the number of reported cases occurred during the 1990s (Table 1). In recent years, there have been
100 reported cases/y.3 During 2000, 99% of all counties in the United States reported no cases of measles. Analysis of the 116 confirmed measles cases in 2001 reveals a pattern of sporadic measles importation that has been consistent in recent years. Among the 116 reported cases, 54 cases were acquired outside the United States and were imported into this country by travelers.9 Among the 62 cases acquired in the United States, contact with an imported case was determined in most instances either because of an epidemiologic link with a case or by analysis of the viral isolate. Sequencing of the N gene enabled documentation that isolates were 1 of the 20 genotypes circulating in other countries of the world. In 2002, a record low of 44 measles cases was reported.
|
Despite active surveillance, there has been no evidence of an extended chain of measles transmission among individuals infected in this country, and measles is no longer endemic in the United States.3 However, the elimination of endemic measles is not equivalent to an absence of measles cases. As long as measles circulates in other countries, measles will be imported into the United States.10 The possibility of transmission to susceptible contacts mandates a commitment to high rates of immunization to prevent the reestablishment of endemic measles.
|
MEASLES VACCINE EFFICACY |
|---|
|
TOPABSTRACTTREND IN DISEASE CAUSED...MEASLES VACCINE EFFICACYRISK OF MEASLES AMONG...CONCERN REGARDING AUTISM AS...GLOBAL ERADICATION OF MEASLESCONCLUSIONREFERENCES |
|---|
Immunization with the attenuated measles vaccine produces a nontransmissible, asymptomatic infection. Approximately 95% of children who receive a single measles vaccine after 12 months of age will become immune, and
5% will remain susceptible and will be a primary vaccine failure. Among children who are vaccinated at 14 months, 98% will develop measles antibody.11 Primary vaccine failures have been attributed to the presence of residual maternal antibody at the time of vaccination, damaged vaccine, receipt of immune globulin, genetic factors, and other incompletely understood factors. After a second immunization, >99% of vaccinees experience seroconversion and develop immunity. Most individuals who experience waning humoral immunity after receiving 2 doses of measles vaccine will experience an anamnestic response and will be protected after exposure to measles virus in the community. Secondary vaccine failure (ie, measles in people who had a previously documented seroconversion after vaccination) does occur but is infrequent.12,13 One study found that 5% (9 of 175) of people who initially seroconverted after receipt of measles vaccine developed measles within 10 years of vaccination.14 Recent experience has demonstrated that prevention of endemic measles transmission is not possible in countries with a single-dose immunization program, even when vaccination rates approach 100%. The small proportion of individuals who remain susceptible as a result of primary vaccine failure after only a single vaccination will accumulate over time. When exposure occurs, the contagiousness of the measles virus may result in an outbreak even when only a small number of case contacts are susceptible. Such a situation occurred recently in Canada. Canada had not implemented a routine 2-dose measles immunization program as of 1995.15 As a consequence, there was an accumulation of susceptible older children and young adults, and outbreaks of measles occurred in these groups despite immunization rates of >90%. Some Canadian provinces experienced an incidence of measles that was >10-fold greater than the corresponding incidence in countries where a 2-dose vaccine schedule was recommended. In 1995, the Canadian National Advisory Committee on Immunization issued recommendations for routine use of a second MMR vaccine as well as for a catch-up campaign for school-aged children.16 This change in policy resulted in a declining incidence of measles to levels that now approximate rates found in other countries that recommend a 2-dose schedule. Experience in other countries such as Sri Lanka, Brazil, and South Korea have demonstrated that a single-dose vaccination strategy is insufficient to prevent periodic outbreaks of measles.17
In developing countries with high rates of endemic measles, routine immunization often is recommended at 9 months of age because of the increased risk of severe infection early in life. Immunization at this young age results in an average seroconversion rate of 85%, leaving a large number of children susceptible to disease.18 On a global basis, 98% of all deaths as a result of complications of measles occur in countries where malnutrition, especially vitamin A deficiency, is common.19 A strategic plan issued by the World Health Organization and the United Nations Children’s Fund has set a goal of reducing the number of measles deaths by 50% by 2005 compared with 1999 levels.20 To reach this goal, it will be necessary to provide measles vaccination to at least 90% of all children through routine health services and supplementary mass vaccination campaigns. In addition, effective measles surveillance and case management including vitamin A treatment and nutritional support will be essential elements of this strategy. The most effective measles immunization policy for a specific country will represent a balance of several considerations: the anticipated level of circulating maternal antibody in young children at the time of immunization, which will determine the efficacy of the vaccine; the risk of measles exposure in young children; the number of vaccine doses administered; and the need to target high-risk groups such as migrants, marginalized populations, and adults who travel to areas where measles is endemic.
|
RISK OF MEASLES AMONG VACCINE EXEMPTORS |
|---|
|
TOPABSTRACTTREND IN DISEASE CAUSED...MEASLES VACCINE EFFICACYRISK OF MEASLES AMONG...CONCERN REGARDING AUTISM AS...GLOBAL ERADICATION OF MEASLESCONCLUSIONREFERENCES |
|---|
As of December 2002, >90% of children in the United States have received a first dose of a measles-containing vaccine by 19 to 35 months of age (median age: 27 months).21 The highest recorded immunization rates have produced the lowest incidence of reported measles in US history. Nonetheless, states permit exemption from immunization requirements on the basis of medical (all states), religious (48 states), or philosophical grounds (19 states). Recent studies have addressed the relative risk of measles infection among children who are not immunized because of a personal exemption by comparing the risk of infection among vaccine exemptors with the risk among vaccinated children.22,23 A population-based retrospective cohort study evaluated all reported cases of measles that occurred in Colorado from 1987 to 1998 among children 3 to 18 years of age.22 Exemptors were 22 times more likely to become infected by measles virus than vaccinated children. Among unvaccinated school-aged children (3–10 years of age), the risk of measles was 62 times greater than among properly vaccinated students. Because herd immunity depends on maintaining high immunization rates in the community, as the number of exemptors increases, the risk of measles infection in vaccinated children increases, as a result of increased risk of exposure. Election not to receive the measles vaccine not only affects the individual but also places others in the community, especially vulnerable people (eg, infants, immunocompromised individuals) at increased risk of acquiring disease.
|
CONCERN REGARDING AUTISM AS A VACCINE COMPLICATION |
|---|
|
TOPABSTRACTTREND IN DISEASE CAUSED...MEASLES VACCINE EFFICACYRISK OF MEASLES AMONG...CONCERN REGARDING AUTISM AS...GLOBAL ERADICATION OF MEASLESCONCLUSIONREFERENCES |
|---|
In the United Kingdom, measles immunization programs suffered a setback in the late 1990s as a consequence of an alleged association between the MMR vaccine (particularly, the measles component), gastrointestinal abnormalities, and autism spectrum disorders (ASD). This hypothesis initially was based on 2 observations. First, an increase in the number of reported cases of ASD occurred during a period when increased numbers of children were being vaccinated against measles. Second, it was noted that children who experience a loss of language skills between 12 and 24 months of age as a result of regressive autism (representing
20% of ASD) tend to develop the first clearly recognizable symptoms at a time close to administration of the MMR vaccine. A temporal association between vaccine administration and onset of symptoms of ASD was interpreted as a causal association rather than 2 unrelated events occurring close together in time simply by chance. Purported support for a causal association came from publication by physicians in the United Kingdom of a nonrandomly selected case series of 12 children who had gastrointestinal symptoms and experienced regression of certain skills in the second year of life, and 8 of these families dated the onset of neurologic deterioration to within 2 weeks of MMR vaccine administration.24 In a subsequent statement, the authors retracted the interpretation of a causal association between the MMR vaccine and autism.25 In addition, this group of investigators described the results of gastrointestinal biopsies of children with ASD and reported the presence of measles virus RNA or protein.26 However, other researchers have been unable to duplicate these results. As a consequence of this controversy, measles immunization rates in certain areas of Europe have declined to <80% with a corresponding increase in measles cases, hospitalizations as a result of complications of measles, and measles-associated deaths.27–29 This issue generated considerable attention from the pubic regarding a possible harmful effect of MMR vaccine as well as from advocates of public health policy regarding the prospect of declining measles immunization rates and the return of endemic measles. In response to the controversy, a number of scientific studies have been conducted to address the possibility of a relationship between MMR vaccine administration and ASD, and each study concluded that no discernible relationship exists.30–36 The evidence suggesting a potential association between the MMR vaccine and autism has been reviewed by committees from the Institute of Medicine and from the American Academy of Pediatrics. The report from the Institute of Medicine concluded that "the evidence favors rejection of a causal relationship."37 The report by the American Academy of Pediatrics concluded that "the available evidence does not support the hypothesis that MMR vaccine causes autism or associated disorders."38
Increasing prevalence rates for autism have been reported in recent epidemiologic studies.39,40 It is not clear whether this increase represents a true increase in disease or simply a consequence of a change in the diagnostic criteria for autism, which have been modified in recent years to become more inclusive.41 Alternatively, the increase in reported ASD may be attributable to improved case ascertainment over the past 2 decades. Regardless of the uncertainty regarding the prevalence of autism, the weight of scientific evidence suggests that ASD is a consequence of a complex genetic mechanism that seems to affect brain growth and development in utero and in the first year of life.42 Diseases such as tuberous sclerosis, phenylketonuria, and fragile X syndrome demonstrate features of ASD. Environmental factors such as infection (in utero rubella infection) and maternal ingestion of thalidomide early in gestation are associated with ASD. The possibility cannot be eliminated that some cases of ASD might be related to as-yet-unknown environmental factors, but sufficient data now have accumulated that strongly argue against a role for MMR in the increased prevalence of ASD.
|
GLOBAL ERADICATION OF MEASLES |
|---|
|
TOPABSTRACTTREND IN DISEASE CAUSED...MEASLES VACCINE EFFICACYRISK OF MEASLES AMONG...CONCERN REGARDING AUTISM AS...GLOBAL ERADICATION OF MEASLESCONCLUSIONREFERENCES |
|---|
Is it possible that measles can reach the same degree of disease control (viz, worldwide eradication) as has occurred with smallpox and soon may be achieved with polio? Several conditions must be satisfied before any vaccine-based eradication program can be successful.43 First, there must be no reservoir for the virus apart from humans. This is the case for measles virus, and chronic shedding of measles virus (ie, >2 months after rash onset) has not been documented.44 Subacute sclerosing panencephalitis is caused by a persistent infection with a defective measles virus; however, this condition is not infectious. Measles virus cannot survive in the environment for more than a few hours apart from human infection or growth in tissue culture. Second, there must be an adequate test for rapid diagnosis. A sensitive and specific enzyme-linked immunosorbent assay for measles immunoglobulin M is often positive on the first day of rash and is widely available for surveillance, rapid diagnosis, and identification of measles cases. Third, a safe and effective form of intervention must be available. Although the nucleotide sequences of certain measles genes show evolutionary drift, there is only a single strain of antigenically stable measles virus, and the measles virus vaccine elicits an immune response that is active against all known isolates. Finally, evidence of a prolonged period of interruption and elimination of endogenous transmission has been demonstrated in a number of countries. On September 22, 2003, the Pan American Health Organization announced that the western hemisphere had been free of endemic measles for 10 consecutive months.45 Thus, it seems that measles satisfies the conditions needed for eradication.
Recently, the threat from bioterrorism has been raised as an obstacle to the possibility of global measles eradication. The existence of measles virus in laboratories throughout the world will serves as a reservoir of virus making it unlikely that measles immunization programs could be discontinued. However, inability to eliminate the threat from reintroduction of measles is not a sufficient basis to forgo the opportunity to eliminate the suffering caused by continued circulation of measles at the present time. In addition, the potential cost savings from global measles eradication represents an incentive to both industrialized and developing countries. The United States currently spends at least $45 million annually for the measles component of the MMR vaccine, and it has been estimated that >$1.5 billion is spent annually on prevention and treatment of measles worldwide.46 If measles were no longer circulating on a global basis, then it would be feasible to replace the 2-dose MMR vaccine schedule with either a single MMR immunization or a single MMR followed by a mumps-rubella vaccine. A recent estimate of the cumulative cost savings to 7 industrialized countries from this change projected yearly savings of between $69 and $623 million.47
|
CONCLUSION |
|---|
|
TOPABSTRACTTREND IN DISEASE CAUSED...MEASLES VACCINE EFFICACYRISK OF MEASLES AMONG...CONCERN REGARDING AUTISM AS...GLOBAL ERADICATION OF MEASLESCONCLUSIONREFERENCES |
|---|
Measles infection continues to account for nearly 50% of the 1.6 million deaths caused each year by vaccine-preventable diseases of childhood.17 In view that a safe and effective vaccine has been available for 40 years, which obstacles account for the failure to make greater progress in worldwide measles control? An important factor is the lack of appreciation of disease severity, particularly in developed countries, where measles rates are low and disease is seldom encountered. A political commitment to control measles is necessary not only in developing countries with a limited public health infrastructure, where most of the estimated yearly 31 million cases of measles occur, but also in industrialized countries, where measles is no longer a high health priority. Second, unscientific and erroneous accusations regarding a risk between measles vaccine and neurologic disorders must not be permitted to undermine the success of measles control programs. Estimates from mathematical models indicate that for industrialized countries such as the United States, herd immunity may be lost and endemic transmission of measles may be reestablished if measles immunity falls below 93% to 95%. Finally, measles is more severe in human immunodeficiency virus–infected individuals, and the burgeoning acquired immune deficiency syndrome epidemic provides an increased susceptibility to measles among increasing numbers of people. To eradicate one of humankind’s great scourges is a challenge that is not easily met. Before global eradication of measles can be achieved, additional work is needed to address operational barriers (eg, injection safety), to build political and financial commitments, and to develop effective partnerships. As has been learned from the Polio Eradication Initiative, the availability of effective vaccination strategies alone is not sufficient to ensure that eradication can be achieved.
|
FOOTNOTES |
|---|
Accepted Jun 9, 2004.
Address correspondence to H. Cody Meissner, MD, Pediatric Infectious Disease Division, Tufts-New England Medical Center, 750 Washington St, Boston, MA 02111. E-mail: cmeissner{at}tufts-nemc.org
|
REFERENCES |
|---|
|
TOPABSTRACTTREND IN DISEASE CAUSED...MEASLES VACCINE EFFICACYRISK OF MEASLES AMONG...CONCERN REGARDING AUTISM AS...GLOBAL ERADICATION OF MEASLESCONCLUSIONREFERENCES |
|---|
- World Health Organization. World Health Report, 2002. Annex 2. Available at: www.who.int/whr/2002/en/
- Nakayama T, Zhou J, Fujino M. Current status of measles in Japan. J Infect Chemother. 2003;9 :1 –7[CrossRef][Medline]
- Measles—United States 2000. MMWR Morb Mortal Wkly Rep. 2002;51 :120 –123[Medline]
- Enders JF, Peebles TC. Propagation in tissue cultures of cytopathogenic agents from patients with measles. Proc Soc Exp Biol Med. 1954;86 :277 –286
- Recommendations of the Public Health Service Advisory Committee on Immunization Practice. Measles vaccine. MMWR Morb Mortal Wkly Rep. 1967;16 :269 –271
- Strebel PM, Papania MJ, Halsey NA. Measles vaccine. In: Plotkin SA, Orenstein WA, eds. Vaccines. 4th ed. Philadelphia, PA: WB Saunders; 2003:389–440
- American Academy of Pediatrics. Committee on Infectious Disease. Measles: reassessment of the current immunization policy.
Pediatrics. 1989;84
:1110
–1113
[Abstract/Free Full Text] - National Vaccine Advisory Committee. The measles epidemic: the problems, barriers and recommendations.
JAMA. 1991;266
:1547
–1552
[Abstract/Free Full Text] - Centers for Disease Control and Prevention. Summaries of notifiable diseases in the United States, 2001. MMWR Morb Mortal Wkly Rep. 2003;50 :1 –21[Medline]
- Centers for Disease Control and Prevention. Imported measles case associated with nonmedical vaccine exemption—Iowa, March 2004. MMWR Morb Mortal Wkly Rep. 2004;53 :244 –246
- Watson JC, Hadler SC, Dykewicz CA, Reef S, Phillips L. Measles, mumps and rubella—vaccine use and strategies for elimination of measles, rubella, and congenital rubella syndrome and control of mumps: recommendations of the Advisory Committee on Immunization Practices (ACIP). MMWR Recomm Rep. 1998;47 :1 –57[Medline]
- Reyes MA, Franky De Borrero M, Roa J, et al. Measles vaccine failure after documented seroconversion. Pediatr Infect Dis J. 1987;6 :848 –851[Web of Science][Medline]
- Hirose M, Hidaka Y, Miyazaki C, et al. Five cases of measles secondary vaccine failure with confirmed seroconversion after live measles vaccination. Scand J Infect Dis. 1997;29 :187 –190[Web of Science][Medline]
- Mathias R, Meekison J, Arcand T, et al. The role of secondary vaccine failures in measles outbreaks.
Am J Public Health. 1989;79
:475
–478
[Abstract/Free Full Text] - Duclos P, Redd SC, Varughese P, Hersh BS. Measles in adults in Canada and the U.S.: implications for measles elimination and eradication.
Int J Epidemiol. 1999;28
:141
–146
[Abstract/Free Full Text] - Supplementary statement on measles elimination in Canada. Can Commun Dis Rep. 1996;22 :9 –15[Medline]
- Strebel P, Cochi S, Grabowsky M, et al. The unfinished measles immunization agenda. J Infect Dis. 2003;187 :S1 –S7
- Cutts FT, Grabowsky M, Markowitz LE. The effect of dose and strain of live attenuated measles vaccines on serological responses in young infants. Biologicals. 1995;23 :95 –106[CrossRef][Web of Science][Medline]
- World Health Organization. Measles Technical Working Group: Strategies for Measles Control and Elimination. Report of a Meeting. Geneva, Switzerland: World Health Organization; 2001 (WHO/V&B/01.37)
- Measles Mortality Reduction and Regional Elimination Strategic Plan 2001-2005. Geneva, Switzerland: World Health Organization and United Nations Children’s Fund; 2001 (WHO/V&B/01.13)
- Centers for Disease Control and Prevention (CDC). National, state, and urban area vaccination levels among children aged 19–35 Months—United States, 2002. MMWR Morb Mortal Wkly Rep. 2003;52 :728 –732[Medline]
- Feikin DR, Lexotte DC, Hamman RF, Salmon DA, Chen RT, Hoffman RE. Individual and community risks of measles and pertussis associated with personal exemptions to immunization.
JAMA. 2000;284
:3145
–3150
[Abstract/Free Full Text] - Salmon DA, Haber M, Gangarosa EJ, Phillips L, Smith NJ, Chen RT. Health consequences of religious and philosophical exemptions from immunization laws.
JAMA. 1999;282
:47
–53
[Abstract/Free Full Text] - Wakefield AJ, Murch SH, Anthony A, et al. Ileal-lympho-nodular hyperplasia, non-specific colitis, and pervasive developmental disorder in children. Lancet. 1998;351 :637 –641[CrossRef][Web of Science][Medline]
- Murch SH, Anthony A, Casson DH, et al. Retraction of an interpretation. Lancet. 2004;363 :750[CrossRef][Web of Science][Medline]
- Uhlmann V, Martin CM, Sheils O, et al. Potential viral pathogenic mechanism for new variant inflammatory bowel disease.
Mol Pathol. 2002;55
:84
–90
[Abstract/Free Full Text] - van den Hof S, Conyn-van Spaendonck MAE, van Steenbergen JE. Measles epidemic in The Netherlands, 1999–2000. J Infect Dis. 2002;186 :1483 –1486[CrossRef][Web of Science][Medline]
- McBrien J, Murphy J, Gill D, Cronin M, O’Donovan C, Cafferkey MT. Measles outbreak in Dublin, 2000. Pediatr Infect Dis J. 2003;22 :580 –584[CrossRef][Web of Science][Medline]
- Clarke T. Measles returns to Britain. Public fear of MMR vaccine blamed for increased outbreaks. Nature (Science Update). 2003;8 . Available at: www.nature.com/nsu/030804/030804-12.html
- Peltola H, Patja A, Leinikki P, Valle M, Davidkin I, Paunio M. No evidence for measles, mumps, and rubella vaccine-associated inflammatory bowel disease or autism in a 14 year prospective study. Lancet. 1998;351 :1327 –1328[CrossRef][Web of Science][Medline]
- Taylor B, Miller E, Farrington CP, et al. Autism and measles, mumps, and rubella vaccine: no epidemiological evidence for a causal association. Lancet. 1999;353 :2026 –2029[CrossRef][Web of Science][Medline]
- Kaye JA, Melero-Montes MM, Jick H. Mumps, measles, and rubella vaccine and the incidence of autism recorded by general practitioners: a time trend analysis.
BMJ. 2001;322
:460
–463
[Abstract/Free Full Text] - Dales L, Hammer SJ, Smith NJ. Time trends in autism and in MMR immunization coverage in California.
JAMA. 2001;285
:1183
–1185
[Abstract/Free Full Text] - Taylor B, Miller E, Lingam R, Andrews N, Simmons A, Stowe J. Measles, mumps and rubella vaccination and bowel problems or developmental regression in children with autism: population study.
BMJ. 2002;324
:393
–396
[Abstract/Free Full Text] - Madsen KM, Hvid A, Vestergaard M, et al. A population based study of measles, mumps and rubella vaccination and autism.
N Engl J Med. 2002;347
:1477
–1482
[Abstract/Free Full Text] - DeStefano F, Bhason PK, Thompson WW, Allsopp MY, Boyle C. Age at first measles-mumps-rubella vaccination in children with autism and school-matched control subjects: a population-based study in metropolitan Atlanta.
Pediatrics. 2004;113
:259
–266
[Abstract/Free Full Text] - Stratton K, Gable A, Shetty P, McCormick M. Institute of Medicine. Immunization Safety Review: Measles, Mumps, Rubella Vaccine and Autism. Washington, DC: National Academies Press; 2001:1–86
- Halsey NA, Hyman SL. 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. 2001;107(5) . Available at: www.pediatrics.org/cgi/content/full/107/5/e84
- Fombonne E. Is there an epidemic of autism?
Pediatrics. 2001;107
:411
–413
[Free Full Text] - Gillberg C, Wing L. Autism: not an extremely rare disorder. Acta Psychiatr Scand. 1999;99 :379 –406
- Fombonne E. The prevalence of autism.
JAMA. 2003;289
:87
–89
[Free Full Text] - Courchesne E, Carper R, Alkshoomoff N. Evidence of brain overgrowth in the first year of life in autism.
JAMA. 2003;290
:337
–344
[Abstract/Free Full Text] - Orenstein WAS, Strebel PM, Papania M, Sutter RW, Bellini WJ, Cochi SL. Measles eradication: is it in our future?
Am J Public Health. 2000;90
:1521
–1525
[Abstract/Free Full Text] - Permar SR, Moss WJ, Ryon JJ, et al. Prolonged measles virus shedding in HIV infected children, detected by reverse PCR reaction. J Infect Dis. 2001;183 :532 –538[CrossRef][Web of Science][Medline]
- Pan American Health Organization. PAHO Announces Drive to Eliminate Rubella. (Press release on September 22, 2003). Available at: www.paho.org/English/DD/PIN/pr030922c.htm
- Miller MA, Redds, Hadler S, Hinman A. A model to estimate the potential economic benefits of measles eradication for the United States. Vaccine. 1998;16 :1917 –1922[CrossRef][Web of Science][Medline]
- Carabin H, Edmunds WJ. Future savings from measles eradication in industrialized countries. J Inf Dis. 2003;187 :S29 –S35
PEDIATRICS (ISSN 1098-4275). ©2004 by the American Academy of Pediatrics
CiteULike 
Connotea 
Del.icio.us 
Digg 
Facebook 
Reddit 
Technorati 
Twitter What's this?
This article has been cited by other articles:
|
|
 |
|
  P. Asaria and E. MacMahon Measles in the United Kingdom: can we eradicate it by 2010? BMJ, October 28, 2006; 333(7574): 890 - 895. [Full Text] [PDF]
|
|
|
|
 |
|
 A. M. Fine, D. A. Goldmann, P. W. Forbes, S. K. Harris, and K. D. Mandl Incorporating Vaccine-Preventable Disease Surveillance Into the National Health Information Network: Leveraging Children's Hospitals Pediatrics, October 1, 2006; 118(4): 1431 - 1438. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Y. D'Souza, E. Fombonne, and B. J. Ward No Evidence of Persisting Measles Virus in Peripheral Blood Mononuclear Cells From Children With Autism Spectrum Disorder Pediatrics, October 1, 2006; 118(4): 1664 - 1675. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 I. D. Iankov, M. Pandey, M. Harvey, G. E. Griesmann, M. J. Federspiel, and S. J. Russell Immunoglobulin g antibody-mediated enhancement of measles virus infection can bypass the protective antiviral immune response. J. Virol., September 1, 2006; 80(17): 8530 - 8540. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 E. M. Bublil, S. Yeger-Azuz, and J. M. Gershoni Computational prediction of the cross-reactive neutralizing epitope corresponding to the monoclonal antibody b12 specific for HIV-1 gp120 FASEB J, September 1, 2006; 20(11): 1762 - 1774. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H. C. Meissner, S. E. Reef, and S. Cochi Elimination of Rubella From the United States: A Milestone on the Road to Global Elimination Pediatrics, March 1, 2006; 117(3): 933 - 935. [Full Text] [PDF]
|
|
|
|
|
|
K. M. Posfay-Barbe, U. Heininger, C. Aebi, D. Desgrandchamps, B. Vaudaux, and C.-A. Siegrist How Do Physicians Immunize Their Own Children? Differences Among Pediatricians and Nonpediatricians Pediatrics, November 1, 2005; 116(5): e623 - e633. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. M. Stern and H. Markel The History Of Vaccines And Immunization: Familiar Patterns, New Challenges Health Aff., May 1, 2005; 24(3): 611 - 621. [Abstract] [Full Text] [PDF]
|
|
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
