In 1962, immediately preceding the licensure of the first measles vaccines in the United States, when measles was a nearly universal disease, Alexander Langmuir described the medical importance of measles to the country and put forth the challenge of measles eradication [1]. Although most patients recovered without permanent sequelae, the high number of cases each year made measles a significant cause of serious morbidity and mortality Langmuir showed that >90% of Americans were infected with the measles virus by age 15 years [1]. This equated to roughly 1 birth cohort (4 million people) infected with measles each year. Not all cases were reported to the public health system; from 1956 to 1960, an average of 542,000 cases were reported annually.By the late 1950s, even before the introduction of measles vaccine, measles-related deaths and case fatality rates in the United States had decreased markedly, presumably as a result of improvement in health care and nutrition. From 1956 to 1960, an average of 450 measles-related deaths were reported each year (∼1 death/ 1000 reported cases), compared with an average of 5300 measles-related deaths during 1912–1916 (26 deaths/ 1000 reported cases) [2]. Nevertheless, in the late 1950s, serious complications due to measles remained frequent and costly. As a result of measles virus infections, an average of 150,000 patients had respiratory complications and 4000 patients had encephalitis each year; the latter was associated with a high risk of neurological sequelae and death. These complications and others resulted in an estimated 48,000 persons with measles being hospitalized every year [3]. In 1966, 3 years after licensure of the first measles vaccines, Sencer et al. [4] announced the first of 3 efforts to terminate indigenous measles transmission in the United States. Subsequent measles-elimination goals were announced in 1978 and in 1993. The fundamental strategy for all 3 elimination efforts consisted of achieving high vaccination coverage among preschool- and school-aged children, careful surveillance of cases, and rigorous outbreak control [4–6]. Although the first 2 elimination efforts did not achieve elimination, they resulted in a substantial reduction in measles incidence: An average of 1.3 cases per 100,000 population was reported during 1982–1988, compared with an average of 313 cases per 100,000 during 1956–1960 (figure 1). Nevertheless, a resurgence of measles occurred during 1989–1991, again demonstrating the serious medical burden of the disease. More than 55,000 cases, 123 deaths, and 11,000 hospitalizations were reported [7]. Two major causes of this epidemic were vaccine failure among a small percentage of school-aged children who had received 1 dose of measles vaccine and low measles vaccine coverage among preschool-aged children.

Figure 1.

Reported US measles incidence, 1950–2001. *, First initiative was termed "eradication."

The measles resurgence also demonstrated the high financial cost of measles in a developed country. Mason et al. [8]. found that the average expense for a measles hospitalization at Los Angeles Children's Hospital during the resurgence was $9264 [8]. Hatziandreu et al. [9].estimated that the average cost (direct and indirect) of a measles case in 1994 was $1000. The same study estimated total annual costs of measles in the absence of a vaccination program of $3.8 billion with 1859 deaths. The United States spends ∼$45 million annually for the measles component of measles-mumps-rubella vaccine, to avoid this burden [9].

On the basis of the lessons learned from the measles resurgence and the first 2 elimination efforts, the elimination strategy for the third effort was refined. Four major lessons were learned. First, high coverage with the first dose of measles vaccine is required by age 2 years to prevent measles in preschool-aged children. Second, school students require especially high levels of immunity because of their high risk of exposure to measles. Higher immunity can be achieved with 2 doses of measles vaccine. Third, well-implemented state requirements for immunization are very effective in achieving high 1-dose measles vaccine coverage among students (requirements that were amended to achieve high 2-dose coverage). Fourth, molecular epidemiology is a powerful tool for tracking measles virus strains and for identifying potentially endemic strains [10].

The refined strategies of the third ongoing measles-elimination effort have achieved success. Measles is no longer endemic in the United States [11]. Since 1997, the reported annual incidence has been <1 case/1 million population. The majority of cases are international importations or the result of limited domestic spread following imported cases. All other cases in recent years are believed to be due to unidentified importations. The end of endemic measles transmission in the United States has both domestic and international importance. Domestically, the absence of endemic exposure to measles means few persons in the United States will be infected and risk complications of measles. This decreased risk of exposure provides protection to groups not protected directly by vaccination: children too young for routine vaccination; the few persons who, although vaccinated, are not protected, primarily from failure to mount an adequate response to vaccine; persons for whom vaccine is contraindicated (e.g., those with immunodeficiency); and persons who choose not to be vaccinated.

Although the absence of endemic measles in the United States has substantial domestic benefits, the greatest benefit lies in its meaning for international measles control programs (12).

Measles is the greatest vaccine-preventable killer of children in the world today and the eighth leading cause of death among persons of all ages worldwide[13–14] . In many countries, resources are not available to treat measles cases or for adequate hospital care for patients with complications. Coupled with poor nutritional status, the lack of access to high-quality medical care leads to case fatality rates of >150 deaths/1000 cases in some populations [15]. In the absence of measles vaccination, the World Health Organization (WHO) estimates that 4.5 million children would die annually as a result of measles and its complications. As recently as 1998, WHO estimated that 888,000 measles deaths occurred [16]. Global eradication of measles could prevent these deaths in perpetuity.

The Dahlem Conference on Eradication specified certain criteria that must be met before eradication of a disease can be considered feasible from a scientific perspective. Among these criteria are that humans must be essential to the life cycle of the agent, sensitive and specific diagnostic tests must be available, and there must be an effective intervention. To these 3 criteria, many would add a fourth—demonstration of prolonged interruption of transmission in a large geographic area [17]. The first 3 criteria have been satisfied for measles [18]; however, the fourth remains of great concern.

The United States, with a population of 288 million, is the largest country to have documented sustained interruption of endemic measles. The US experience demonstrates that endemic measles can be eliminated in a large, diverse, developed country with a routine 2-dose measles vaccine strategy. The US experience in elimination plus those of other countries that have interrupted endemic measles transmission support the scientific basis for the feasibility of global measles eradication. We hope that the experience of the United States and other countries that have interrupted endemic measles will encourage other countries to accelerate efforts to better protect their populations from this disease.

Much more work is needed before a worldwide goal for measles eradication is established. Feasibility must be demonstrated in more countries, particularly in Asia and Africa, with densely populated cities. Scientific feasibility is a necessary precondition for a global eradication effort but alone is not sufficient. The political will of both developed and developing countries is also needed. Specifically, the developed countries must be convinced that measles is a sufficiently serious burden in their populations to warrant the steps needed to eliminate endemic measles transmission within their borders. In the near term, developing countries must be convinced that strengthening measles-control and -elimination efforts will benefit their populations immediately in many ways, including reducing measles morbidity and mortality, and in strengthening routine health programs to deliver other preventive services, including other vaccines. Their near-term success in control and elimination will pave the way for attaining global eradication.

In summary, a milestone has been reached. For the first time, the public health community has documented that one of the most contagious diseases, a disease that has thwarted >2 decades of attempts to eliminate it, is no longer endemic in the United States. The evidence for this achievement is presented in this supplement of The Journal of Infectious Diseases.

We congratulate the US health professionals for achieving this success by building strong immunization programs nationwide. In particular, we recognize the thousands of nurses, doctors, and pharmacists in the public and private sectors who have participated in measles vaccination. Their diligent efforts have translated the possibility of ending endemic measles within our borders into a reality We dedicate this supplement on measles elimination in the United States to them.

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Guest Editor: Walter A. Orenstein,
Walter A. Orenstein
Guest Editor
National Immunization Program, Centers for Disease Control and Prevention
,
Atlanta, Georgia
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Mark J. Papania
Mark J. Papania
Guest Editor
National Immunization Program, Centers for Disease Control and Prevention
,
Atlanta, Georgia
Reprints or correspondence: Dr. Mark Papania, National Immunization Program, Mailstop E-61, Centers for Disease Control and Prevention, 1600 Clifton Rd., Atlanta, GA 30333 (mpapania@cdc.gov)
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