On 16–17 March 2000, the National Immunization Program of the Centers for Disease Control and Prevention convened 12 consultants and 10 resource specialists to review the present status of measles in the United States and to provide individual opinions on 4 questions: Is measles currently endemic in the United States? If current information is not sufficient to make such a determination, what additional information is needed? Is it possible or desirable to establish a precise definition of "elimination"? What elements of the US immunization program should be modified or strengthened to achieve/maintain elimination?

The consultants and resource specialists are listed after the text. The meeting included a series of presentations, contained in this supplement issue of The Journal of Infectious Diseases, followed by open discussion among the consultants and delivery of their opinions.

PRESENTATIONS

The opening presentation focused on existing definitions of elimination and targets established within the United States over the years since introduction of measles vaccine in 1963. The Dahlem definition of elimination was put forth as the existing standard (reduction to 0 of the incidence of a specified disease in a defined geographic area as a result of deliberate effort). The current US target was that by year 2000, all cases could be linked within 2 generations to an imported case. It was anticipated that as many as 500 cases might occur each year as a result of importation, with limited local spread. The strategy for elimination in the United States included achieving very high coverage with 2 doses of measles-containing vaccine, aggressive surveillance, responding to cases (case investigation, outbreak response), and promoting measles control in other countries.

Introductory presentations on mathematical models of transmission indicated that interruption of indigenous transmission of measles depends on very high levels of immunity in the population. In Europe, the projection has been made that to achieve interruption of indigenous transmission, levels of susceptibility in various age groups can be no more than the following: age 1-4 years, 15% age 5-9 years, 10% and age ⩾10 years, 5%. Elimination of endemic disease does not require a total absence of indigenous cases; it requires the absence of continuing indigenous transmission, as indicated by a reproductive rate (R) of <1. (Reproductive rate: the number of secondary cases resulting from a single case. If R< 1, transmission will not be sustained.)

An important implication is that a disease can be eliminated as an indigenous problem even though there are recurrent outbreaks, a few of which might be quite large or involve a number of generations of cases. Three different approaches to estimating R were presented: the proportion of all cases that are imported, the size of outbreaks, and the duration of outbreaks. Elimination is a dynamic condition that potentially can be achieved and subsequently lost if, for example, levels of immunity are not maintained.

In the United States, from 1997 through 1999, the number of reported cases of measles was quite low, in total 338 cases. This represents an incidence of <1 case/ 1 million population. Of all cases, 34% were imported and an additional 30% have been epidemiologically linked to imported cases or caused by a virus of imported genotype. The remaining 36% of cases have been categorized as having an unknown source. In 1997, there were 6 consecutive weeks without a case of unknown source reported nationwide, and in 1998, there were 21 consecutive weeks without such a case. In 1999, there were stretches of 9 and 12 consecutive weeks without cases of unknown source. As determined by use of the proportion of all cases that are imported and the size of outbreaks in the United States, the reproductive rate of measles, R, was <0.8 for the period 1997–1999.

Molecular data support the proposition that endemic transmission of measles has been interrupted in the United States. During the 1989–1992 resurgence, 20 measles cases with virus isolation, representing outbreaks across the country, were of genotype D3. Since 1992, the only isolates of genotype D3 have been from cases imported from the Philippines (3 cases) or Guam (1 case). All other isolates have been closely related to strains currently circulating in other countries, and no genotype has occurred in a repeating pattern that would suggest an endemic strain of measles virus.

The quality of surveillance (both sensitivity and specificity) is obviously a key to determination of whether measles continues as an endemic disease. There is currently no objective standard such as exists with poliomyelitis, in which there is a relatively uniform worldwide incidence of acute flaccid paralysis due to causes other than polio in children <15 years old of 1 case/100,000 population. The presumption is made that a surveillance system that detects this incidence of non-polio acute flaccid paralysis is sensitive enough to detect polio if it is present. Studies in a limited number of sites in the United States that made use of capture-recapture methods suggest a measles-reporting efficiency of ∼40%-60%. On the other hand, the small number of previously reported cases that are discovered as a result of investigation suggests a reporting efficiency of 80%-90%. Presentations from New York City, Los Angeles, and Chicago indicated the various approaches to surveillance in these high-risk locations. Surveillance is primarily passive in each location, but suspected cases of measles are actively investigated, with attempts made to identify contacts and additional cases and to obtain laboratory specimens for confirmation. In New York City, there were no cases during 1997–1999 that were not imported or linked to importation. In Chicago, of 6 confirmed cases during 1994–1999, all were imported or linked to importation. By contrast, in Los Angeles, during 1995–1999, only 8 of 17 confirmed cases were imported or linked to importation.

Because of widespread use of private laboratories, there is not a mechanism in the United States to determine the total number of specimens tested for measles. Consequently, it is not possible to determine the total number of persons in whom measles was suspected and for whom laboratory specimens were submitted that later yielded negative results. The quality of testing in private laboratories is uncertain and not standardized.

Levels of immunity to measles in the United States are high. The National Immunization Survey indicates that >90% of 19-to 35-month-old children have received at least 1 dose of measles-containing vaccine (although there is geographic variation), and school entry surveys indicate that 98% of entering students have received at least 1 dose. Forty-eight of 50 states now require 2 doses of measles-containing vaccine for school attendance. By use of serological information from the National Health and Nutrition Examination Survey as well as immunization coverage data, it is estimated that at least 92%–93% of the US population is immune to measles. By age group, the estimates of susceptibility are as follows: age 1–4 years, 14% age 5–9 years, 8% age 10–19 years, 5% and age >20 years, 7%. These levels are very comparable to those predicted by mathematical models as necessary for measles elimination in the European region of the World Health Organization.

An important possibility when considering elimination or eradication is whether presumably immune persons exposed to measles can be successfully infected and act as transmitters of infection. A recent study in the United States indicates that although persons with preexisting antibodies may demonstrate rises in antibody titer following exposure to measles, they do not excrete virus and are unlikely to play a role in transmission.

Remarkable progress toward elimination of measles has been made in the Americas. In 1994, a target was set to eliminate indigenous transmission by 2000. Virtually all countries in Latin America and the Caribbean have carried out "catch-up" campaigns, in which all children 1–14 years of age are immunized regardless of prior history. All are working on "keep-up," to maintain high levels of coverage with routine immunization of 1-year-old children, and virtually all have carried out "follow-up" campaigns, in which all children 1–4 years of age are immunized (these will be repeated every 3–4 years). There has been a dramatic reduction in the incidence of measles in the Americas. In 1990, >250,000 cases were reported. By 1996, the number had plummeted to 2100 cases. However, there was a major outbreak in 1997, with 53,000 cases, the vast majority occurring in Sao Paulo, Brazil. In 1998, 14,000 cases were reported, and in 1999 there were 2900. As of the middle of March 2000, there had been 65 cases reported, and it appeared that only 4 countries in the Americas had continuing transmission of measles virus—Brazil, Argentina, Dominican Republic, and Bolivia. Aggressive surveillance is in place; >47,000 serum samples were tested for measles in 1998, >25,000 in 1999, and -5000 as of mid-March 2000.

In Canada, a major outbreak of measles occurred in 1995, in which Canada, with only 3.6% of the population in the Americas, accounted for nearly 50% of all cases of measles in the hemisphere. A decision was made to eliminate measles from the country. "Catch-up" campaigns were undertaken in many provinces, and by April 1997, all provinces and territories had adopted a 2-dose schedule for measles vaccine. The incidence of measles has declined dramatically. In 1997 there were >500 cases (mainly in 2 outbreaks), in 1998 there were 12 cases (5 imported or importation-related), in 1999 there were 29 cases (21 in 2 importation-related outbreaks and 6 others imported or importation-related), and as of mid-March 2000, there has been 1 (imported) case.

The hemispheric epidemic of measles in 1989–1990 resulted in 6000 deaths in Mexico. A 2-dose schedule of measles vaccine was introduced in Mexico in 1991, and in 1993 a “catch-up” campaign targeted 6- to 14-year-old children. As of mid-2000, there had been no confirmed cases of measles in Mexico since 1996, despite aggressive surveillance: >700 serum samples were tested in 1997, >1700 in 1998, and >700 in 1999.

The implications of elimination of measles in the United States include demonstration to the rest of the world that it is feasible in a sizeable area and population and demonstration of one (but not necessarily the only) approach to elimination. It will provide a step toward eventual global eradication of measles, which continues to cause nearly 1 million preventable deaths each year. Some important lessons from the effort thus far include the importance of routine immunization, the importance of surveillance, the importance of strong political commitment, and the need for a broad coalition of partners. In particular, the need to link epidemiology and laboratory (as has been done in the polio eradication initiative) was highlighted. Measles elimination targets have been set in 3 of the 6 World Health Organization regions: region of the Americas (2000), the European region (2007), and the Eastern Mediterranean region (2010). Global eradication of measles is a worthy goal, but it is important first to complete eradication of poliomyelitis and to gain more experience with regional measles elimination.

DISCUSSION AND ANSWERS TO THE QUESTIONS

Is measles currently endemic in the United States? Each of the 12 consultants (and each of the 7 resource specialists present on 17 March) concluded that measles is not endemic in the United States at present. Several mentioned that no single line of evidence was conclusive but that every line of evidence (reported cases, virological evidence, immunization coverage, ser-osusceptibility) supports the notion of nonendemicity However, participants were concerned about the stability of the situation and noted that the continued international importation of measles indicates the potential for reestablishment of endemic transmission if immunization coverage is not sustained at the current high level.

If current information is not sufficient to make such a determination, what additional information is needed? Although all experts agreed that measles is not endemic in the United States, some experts mentioned additional information that would further strengthen this judgment. Some suggested that continuing with the same low incidence, a high proportion of imported cases, and an absence of an endemic strain for a longer period of time would be even more convincing. Others indicated that they would prefer to see more-comprehensive information on a variety of factors, including a higher rate of cases investigated by laboratory testing, a higher percentage of indigenous cases with virological information, and fewer cases categorized as unknown-source cases.

Is it possible or desirable to establish a precise definition of “elimination”? There was considerable diversity of opinion about the possibility or desirability of a precise definition for “elimination.” The vast majority of experts felt that it was either not possible to precisely define elimination or not desirable to do so. In general, the experts agreed that sustained 0 incidence of measles in a country or region is not a practical goal outside the context of global measles eradication, because imported cases will continue to occur as long as measles is endemic in other countries, followed by occasional chains of indigenous transmission as a result of the high infectiousness of measles. Many participants thought that the term “elimination” is not useful and should not be used, because the common definition of elimination is 0 incidence, and attempting to redefine the term would lead to confusion. Many participants feared that use of the term “eliminated” to reflect the status of measles in a country or region would instill a false sense of security in the population and lead to decreased immunization rates, which would result in a return to endemic measles transmission.

Although precisely defining and using the term “elimination” was generally not favored, it was agreed that it would be very useful for countries and regions striving for elimination of measles to define common goals to communicate with one another and measure progress. The absence of endemic measles was considered an appropriate milestone. Establishing standard guidelines to assess this milestone was not attempted at this meeting but was recommended.

What elements of the US immunization program should be modified or strengthened to achieve or maintain elimination? On the basis of comments from the consultants, there are 3 primary areas needing improvement or strengthening- program, surveillance, and communication. Programmatically, there was unanimity about the need to maintain high coverage. Many participants believed that it is important to identify and target high-risk groups and high-risk areas to improve coverage and improve surveillance. Population-based immunization registries (confidential, computerized information systems that contain information about immunizations and children) can be important in monitoring coverage and identifying areas of risk. Every participant thought it important to support the global effort for measles control to reduce the risk of importation. International standardization of classification of measles cases would also be helpful.

There were many suggestions regarding surveillance. Surveillance of disease, immunization coverage, and vaccine safety were all thought to be important. Participants believed that current surveillance is adequate to detect ongoing transmission but might be missing isolated imported cases. Virtually every participant thought that it was important to ensure that appropriate specimens are taken from every suspected case. Availability of techniques such as use of saliva for testing would increase the collection of specimens. Information about suspected cases that are discarded (e.g., whether appropriate specimens were collected) would help assess the adequacy of surveillance. There was considerable interest in obtaining information from both public and private laboratories about how many specimens are being tested for measles virus. The need to ensure quality control in private laboratories was also mentioned. Emphasis was placed on the importance of obtaining virus isolates from all chains of transmission and from a significant proportion of isolated cases to document the genotype (s) of measles virus present.

Active surveillance was considered to be important, at least in high-risk locations (e.g., Los Angeles, New York City, Chicago) and sentinel health plans. Standardization of surveillance efforts across the country was also thought to be important. Several participants were attracted to the possibility of developing definitions and indices of measleslike illness as a method of assessing adequacy of surveillance and testing. Finally, continued and improved surveillance of immunization coverage and immunity was mentioned by several consultants.

In the area of communication and education, each of the consultants thought that it was important to improve communication with parents, providers, and policy makers. A significant proportion of US health care workers have little or no experience with measles and consequently may not have personal appreciation of its impact or think of measles when seeing a patient with fever and rash. Many consultants believed that it was essential to increase knowledge of the public's perceptions and beliefs regarding immunization and to use this information to craft appropriate communication and education messages. Marketing approaches rather than traditional public service messages or posters were thought to be most appropriate for public education.

CONCLUSION

All participants concluded that measles is no longer endemic in the United States—34 years after the first eradication target was set. This achievement is a credit to the efforts of millions of parents and children, hundreds of thousands of health workers, and thousands of policy makers and legislators who provided the political and financial support. Notwithstanding the tremendous progress that has been made, it is critical to understand that this is an inherently unstable situation and that we must maintain (and improve) our efforts to ensure that immunization levels remain very high and that surveillance is of high quality We also must strengthen our support for global measles control and work toward ultimate global eradication of measles.

MEASLES ELIMINATION MEETING PARTICIPANTS

Expert Consultants:

  • Samuel L. Katz, M.D. (Meeting Chairman), Wilburt C. Davison Professor & Chairman Emeritus, Department of Pediatrics, Duke University Medical Center;

  • Alan R. Hinman, M.D. (rapporteur), Senior Consultant for Public Health Program, Task Force for Child Survival;

  • Jonathan Temte, M.D., Ph.D. (representing the American Academy of Family Physicians), Family Practice Residency Program, University of Wisconsin;

  • Larry Pickering, M.D. (representing the American Academy of Pediatrics), Director, Eastern Virginia Medical Center;

  • John Modlin, M.D. (representing the Advisory Committee on Immunization Practices), Professor of Pediatrics and Medicine, Dartmouth Medical School;

  • Guthrie S. Birkhead, III, M.D. (representing the Council of State and Territorial Epidemiologists), New York State Department of Health;

  • Yvonne Maldonado, M.D. (representing the National Vaccine Advisory Committee), Associate Professor of Pediatrics, Stanford University School of Medicine;

  • James Cherry, M.D., Department of Pediatrics, School of Medicine, University of California, Los Angeles;

  • James Chin, M.D., M.P.H., Clinical Professor of Epidemiology, School of Public Health, University of California, Berkeley;

  • Mary des Vignes-Kendrick, M.D., Director, Health & Human Services Department, City of Houston;

  • Neal Halsey, M.D., Professor & Director of Division Disease Center, Department of International Health, Johns Hopkins University, School of Hygiene & Public Health;

  • Michael Marcy, M.D., Department of Pediatrics, Kaiser Permanente.

  • Resource Specialists:

  • Kristin Brusuelas, M.RH., Los Angeles Department of Health, Immunization Program;

  • Gaston De Serres, M.D., Ph.D., Public Health Center of Quebec;

  • Ciro De Quadros, M.D., M.P.H., Director, Division of Vaccines and Immunization, Pan American Health Organization;

  • Pamela S. Diaz, M.D., Medical Director, Acute Disease Surveillance, Chicago Department of Health;

  • Nigel J. Gay, M.D., Public Health Laboratory Service, Communicable Disease Surveillance Centre, Ministry of Health of Great Britain;

  • Jacqueline Kellachan, M.A, M.P.H., Research Scientist, II, Immunization Program/Vaccine-Preventable Surveillance, New York City Department of Health;

  • Arlene King, M.D., M.H.Sc, FRCPC, Acting Chief, Division of Immunization, Bureau of Infectious Diseases, Laboratory Center for Disease Control, Health Canada;

  • Jean-Marc Olive, M.D., Acting Coordinator, Expanded Programme on Immunization, World Health Organization;

  • David Salisbury, M.D., Principal Medical Officer, Department of Health, Ministry of Health of Great Britain;

  • Jose Santos-Preciado, M.D., National Vaccination Council, Ministry of Health of Mexico.