Measles in the United States, 2000-07: Eliminated but the Threat Is Not Gone Amy A. Parker, M.S.N., M.P.H. Epidemiologist Centers for Disease Control and Prevention National Immunization Conference March 17-20, 2008 Good morning. I will be discussing the epidemiology of measles in the United States from 2000 through 2007.

Measles Measles is a highly infectious, acute viral disease that results in rash, respiratory symptoms, and fever.

Severity & Infectiousness 1/100 cases result in pneumonia 1/1000 to 1/2000 result in encephalitis Measles is one of the most contagious diseases known Almost all non-immune children contract measles if exposed to the virus Measles can also cause severe complications and death. 1 in 100 cases results in pneumonia, and 1 in 1000 to 1 in 2000 cases result in post-infection encephalitis. Measles is one of the most contagious diseases known. Almost all non-immune children contract measles if exposed to the virus.

Measles Epidemiology, United States, 1st Dose Recommendation 1962- 2007* 1963 Vaccine Licensed 1st Dose Recommendation 1989 2nd Dose Recommendation 2000 Elimination Declared 1-dose preschool coverage 2-dose adolescent coverage Measles Cases % Measles Vax Coverage In the pre-vaccine era, approximately 500,000 cases were reported in U.S. citizens annually. However, it was generally the whole birth cohort that was infected, most cases were unreported. The vaccine was licensed in 1963 which caused a dramatic reduction in cases. However, a resurgence occurred from 1989-91. During this timeframe, a second dose of measles vaccine was recommended. By 2000, measles was declared eliminated from the U.S. The strongest wall of defense we have in maintaining elimination is our relatively high levels of vaccination coverage. Since the 1990s, one dose coverage among 19-35 month olds has been up to 93% and two-dose coverage among adolescents with a vaccination record has been up to 87%. 1989-91 Resurgence Year *provisional 2007 data

Measles Cases by Month, United States, 1990- 2006 Winter-Spring = Jan-Jun Summer-Fall = Jul -Dec 2000 Elimination Declared This graph shows the disappearance of the seasonality and the sharp decrease in measles cases by month since the 1989-1991 resurgence, pointing to the fact that measles is no longer an endemic disease in the U.S. We are currently at historic lows. 138 100 100 86 116 44 56 37 66 55

In 2000, measles was officially declared eliminated from the United States, a remarkable public health success. Elimination is defined as the absence of endemic disease transmission.

Risk of Importation >20 million cases of measles occur worldwide each year Travel outside Western Hemisphere presents a risk for measles exposure (i.e. Europe, Japan, India) In 2006, ~30 million U.S. residents traveled abroad and 51 million international visitors entered the U.S. No regulations are in effect requiring vaccination of visitors However, the risk of importation remains a threat until measles is under better control globally. More than 20 million cases of measles occur worldwide each year. Travel anywhere outside the Western Hemisphere, including industrialized areas such as Europe and Japan, and developing countries such as India, presents a risk for measles exposure. In 2006, ~30 million U.S. residents traveled abroad and 51 million international visitors entered the U.S. No regulations are in effect requiring vaccination of visitors.

Measles Epidemiology United States, 2000- 07* Total of 501* cases Morbidity and mortality 1 in 4 cases have resulted in hospitalization (132/ 501) 1 in 250 have resulted in death (2/ 501) High outbreak containment costs Iowa (2004)– 3 cases: >2500 person-hours $142,000 Indiana (2005)– 34 cases: 3650 person-hours $167,000 Since 2000, a total of 501 measles cases have been reported. The severity of the reported measles cases in the U.S. is high. Since 2000, one in four cases have resulted in hospitalization, and 1 in 250 have resulted in death. These importations also cause substantial expenditure of local, state, and federal public health resources. In 2004 in Iowa, over 2500 hours of personnel time were expended to review flight manifests, contact exposed passengers, set up vaccination clinics, trace >1000 potentially exposed contacts, and institute and enforce quarantine orders for vaccine refusers. The outbreak only involved 3 cases, but $142,000 was spent by state and local health departments in containing it. In 2005 in Indiana, to stop the spread of infection in a vaccine refuser group, outbreak containment efforts required 3650 person-hours and containment costs totaled more than $167,000. *provisional 2007 data

Measles Cases & Percentage of Import-Associated Cases, United States, 1994- 2007* Total number of cases % importations Since 2000, the number of measles cases has ranged from 37- 116 cases per year, but the percentage of import-associated cases has increased, which is reflected by the yellow line. (Internationally imported, import-linked, and imported-virus are collectively considered to be import-associated cases) *provisional 2007 data

Characteristics of Case-Patients, United States, 2000- 07 U.S. RESIDENT STATUS: Residents: 368 (73%) Nonresidents: 133 (27%) VACCINATION STATUS: 395 cases age-appropriate for vaccination Unvaccinated (201) or Unknown (90): 291 (74%) Vaccinated with ≥ 1 dose: 104 (26%) It is primarily U.S. residents being affected, comprising 73% of cases since 2000. About 3/4 of the 395 patients who were age-appropriate for vaccination had 0 doses or unknown vaccination status. This shows us that our main issue is not vaccine failure. *provisional 2007 data

Vaccination Status of Measles Patients by Age, 2000- 07* ≥1 dose 0 doses/ Unknown Total <1 y n/a 80 80 (16%) 1-4 y 12 73 85 (17%) 5-19 y 31 85 116 (23%) 20+ y 63 157 220 (44%) 106 395 501* (79%) This chart looks at the vaccination status by age groups of the cases since 2000. The children less than one can’t be vaccinated, but they represent a small percentage of cases. The preschool and school-aged children, a reachable population, represent 40% of the cases. Within these two groups, 79% were unvaccinated or had unknown vaccination status. A majority of case-patients in the final group, which were persons over 20 years of age, were unvaccinated or had unknown vaccination status. However, this group is generally harder to reach. *provisional 2007 data

Characteristics of 39 Measles Outbreaks during Post-Elimination Geography: Reported in 16 states Size: 3- 34 cases/outbreak (median= 4 cases) Duration: Short in duration (median= 19 days) Seasonality: Occurred year-round Viral genotyping: 9 viral genotypes were associated with the outbreaks: B3, D3, D4, D5, D6, D7, D8, G2, H1 Importation status: Since 2004, all outbreaks traced to an imported source Documenting the number of outbreaks is also key, because outbreaks demonstrate that the chain of transmission is more than a single importation. An outbreak is defined as 3 or more cases. During 2000-07, 39 outbreaks occurred in 16 states. All outbreaks that occurred during this timeframe were small with 3- 34 cases per outbreak (with a median of 4 cases per outbreak). The outbreaks were short in duration (with a median of 19 days) and occurred year-round. The 9 viral genotypes listed here were associated with the outbreaks. Additionally, since 2004, all outbreaks reported have been traced to an imported source.

Outbreaks in Unprotected Populations 2005 Indiana: unvaccinated girl traveled to Romania, became infected, and transmitted measles to 33 persons (primarily unvaccinated) upon return home. 2008 San Diego: unvaccinated boy traveled to Switzerland, became infected, and spread the virus to 11 unvaccinated children upon return home. 2008 Arizona: unvaccinated and infected foreign visitor from Switzerland spent >20 hours in ER and was hospitalized. To date, 5 additional people have been infected, including a hospital employee. The hospital screened 480 employees and those who could not prove history of vaccination or immunity were tested, 22 were seronegative, and vaccine was provided. I want to highlight 3 outbreaks that occurred, primarily in unprotected populations. In 2005 in Indiana, an unvaccinated girl traveled to Romania, became infected, and transmitted measles to 33 persons, most of whom were unvaccinated children, upon her return home. In 2008 in San Diego, an unvaccinated boy traveled to Switzerland, became infected, and spread the virus to 11 unvaccinated children upon his return home. Currently an outbreak is occurring in Arizona. An unvaccinated and infected foreign visitor from Switzerland spent more than 20 hours in ER and was hospitalized. To date, 5 additional people have been infected, including a hospital employee. The hospital screened 480 employees and those who could not prove history of vaccination or immunity were tested, 22 were seronegative, and vaccine was provided. These outbreaks tell us a great deal about who we need to target.

Keeping Our Finger on the Pulse These outbreaks demonstrate that we cannot let our guard down. Surveillance indicators are an important way of measuring the quality of our surveillance. There are several surveillance indicators for measles. These outbreaks also demonstrate that we cannot let our guard down. Surveillance indicators are an important way of measuring the quality of our surveillance. There are several surveillance indicators for measles.

Measles Surveillance Indicator: Percent Completeness of Information for Key Variables One surveillance indicator is the percent completeness of information for key variables that are entered into the National Notifiable Diseases Surveillance System. From 2000- 07, this indicator ranged from 56- 87%. *provisional 2007 data

Measles Surveillance Indicator: Percent of Cases with Viral Specimen Sent to CDC This indicator is the percent of measles cases with viral specimen sent to CDC. This ranged from 21-70%. Although we have genotypes for all of the recent outbreaks and about 25-30% of single case chains, for genotyping, we would like a sample from every chain. There is room for improvement in collection of samples for viral detection (such as the collection of throat swabs).   *provisional 2007 data

Measles Surveillance Indicator: Percent of Confirmed Cases that are Lab-Confirmed Another surveillance indicator is the percent of confirmed cases that are lab confirmed. This ranged from 58-93%. However, in an outbreak, not all cases need to be lab-confirmed. *provisional 2007 data

Measles Surveillance Indicator: Median Number of Days from Symptom Onset to Public Health Report This surveillance indicator is the median number of days from symptom onset to public health report. It ranged from 1 to 6 days. Higher numbers are worse for this indicator. We’d like reporting to occur the first day or sooner. *provisional 2007 data

Summary High measles vaccination coverage has successfully maintained measles elimination, but we remain at risk. >500 cases have occurred since 2000. Primarily imported or import-linked ~3/4 cases unvaccinated ~3/4 cases U.S. residents Though the 39 outbreaks have been limited in size and duration, they have caused substantial economic impact Risk populations: vaccine refusers, persons traveling abroad, health care workers Surveillance performance is generally good, but improvements would be desirable. High measles vaccination coverage has successfully maintained measles elimination, but we remain at risk of importation, especially from developed areas of the world. However, >500 cases have occurred since 2000. These have primarily been imported or import-linked cases, ~3/4 of the cases have been unvaccinated, and ~3/4 of the cases have been among U.S. residents. Though the 39 outbreaks since 2000 have been limited in size and duration, they have often caused a substantial economic impact. The risk populations are vaccine refusers, persons traveling abroad, and health care workers. Surveillance performance is generally good, but improvements would be desirable.

Implications With >20 million cases occurring globally, the risk of measles importations and outbreaks will continue for the foreseeable future. Continued elimination of measles transmission depends primarily on continued maintenance of high vaccination coverage – which may be difficult in the absence of disease and in the presence of increased concern over vaccine adverse events. Special vaccination efforts should be directed at populations at risk -- foreign travelers, vaccine refusers, and health care workers. School vaccination requirements should be enforced in a manner which does not make it easier to decline vaccination than to be vaccinated. Vaccination levels of health care workers in health care facilities should be reviewed periodically. With >20 million cases occurring globally, the risk of measles importations and outbreaks will continue for the foreseeable future. Continued elimination of measles transmission depends primarily on continued maintenance of high vaccination coverage – which may be difficult in the absence of disease and in the presence of increased concern over vaccine adverse events. Special vaccination efforts should be directed at populations at risk -- foreign travelers, vaccine refusers, and health care workers. School vaccination requirements should be enforced in a manner which does not make it easier to decline vaccination than to be vaccinated. Vaccination levels of health care workers in health care facilities should be reviewed periodically.

Acknowledgments Susan Redd Charley LeBaron Jane Seward Jim Alexander Bill Bellini Paul Rota Jenny Rota I’d like to acknowledge the people listed here, especially Susan Redd for her tireless work in gathering the surveillance data. “The findings and conclusions in this presentation have not been formally disseminated by the Centers for Disease Control and prevention (CDC) and should not be construed to represent any CDC determination or policy.”

Extra Slides

Key Variables (Surveillance Indicator) Clinical case definition Hospitalization Lab testing Vaccine information Date reported to health department Transmission setting Outbreak related Epidemiologic linkage Date of birth Onset date

Preventable Cases Preventable: 203 Non-preventable: 298 Confirmed measles cases were defined as preventable if they occurred among persons for whom vaccination is recommended by the Advisory Committee on Immunization Practice, but who had not received 1 or more doses of measles-containing vaccine. Cases were considered non-preventable if they occurred among persons who had received 1 or more doses of measles containing vaccine, were not vaccinated and for whom vaccination is not recommended, or were born before 1957 and therefore presumed immune. Of the 501 reported measles cases, 203 were considered preventable and 298 were considered non-preventable.

Measles Surveillance Indicator: Percent of Cases with Imported Source The first indicator is the percent of cases with imported source. Since 2000, this indicator ranged from 30-73%. *provisional 2007 data

Breakdown of Sources of Measles Cases, 2000- 07 Imported Cases Epi-linked Cases Import-virus only Unknown 231 (46%) 150 (30%) 27 (5%) 93 (19%) From 2000-07, 46% of reported measles cases in the U.S. were imported. The remaining were U.S. acquired, of which 30% were import-linked, 5% were import-virus only, and 19% had unknown sources of exposure. Due to measles being endemic globally, we expect to have imported cases. However, our goal is to detect these cases early. High numbers of epi-linked cases means that the imported virus had a chance to spread. When we have unknown sources, it means that we missed the first case, allowing the possibility of transmission to occur. *provisional 2007 data through Dec 31

Indigenous Spread from Imported Measles Cases, United States, 2000-07 This graph shows the spread from imported cases. It is the number of epi-linked cases divided by the total imported cases per year. 2005 had more spread cases than imports, because of the outbreak in Indiana among vaccine exemptors that spread to 33 people. Year *provisional 2007 data through Dec 31