Albert E. Barskey IV, MPH Division of Viral Diseases

Mumps Surveillance – United States, 1994-2008 Where have we been and where are we going?
Albert E. Barskey IV, MPH Division of Viral Diseases National Center for Immunization and Respiratory Diseases 42nd National Immunization Conference March 19, 2008 Welcome. I’m Al Barskey. I’ll be presenting this morning on mumps surveillance in the United States during the period 1994 to 2008.

Overview Mumps surveillance and epidemiology
Pre-outbreak: Outbreak: 2006 Post outbreak: 2007-Present Surveillance Quality (NNDSS) Core variables (e.g. age, race, county) Extended data variables (e.g. vaccination status, lab results, transmission setting) Conclusions Today my talk will focus on the trends in mumps before the 2006 outbreak, characteristics of the outbreak, and what’s happening now with mumps. I will also review some of the quality of the surveillance data reported through the National Notifiable Diseases Surveillance System, or NNDSS. Finally, I’ll close with a few conclusions and a request for your input.

Mumps Acute, viral illness that can present with Transmission
Parotitis Other salivary gland swelling Orchitis (in post-pubertal males) Aseptic meningitis Non-specific respiratory symptoms Asymptomatic Transmission Direct contact (saliva) Respiratory droplet As you know, mumps is an acute, viral illness that can present with parotitis, other salivary gland swelling, orchitis, aseptic meningitis, non-specific respiratory symptoms, or in some cases be asymptomatic. Mumps is transmitted by direct contact or respiratory droplets.

Mumps Vaccine Licensed
1967 Mumps Vaccine Licensed 1977 1st Dose ACIP Recommendation 1989 2nd Dose ACIP Recommendation 2010 U.S. Elimination Goal 1-dose mumps vax preschool coverage 2-dose mumps vax adolescent coverage Mumps Cases % Mumps Vax Coverage Following vaccine licensure in 1967, reported case numbers declined rapidly through the early 80’s. The United States experienced a resurgence of mumps in the later half of the 80’s, which was followed by a measles resurgence. In a response to the measles resurgence, the Advisory Committee on Immunization Practices recommended routine vaccination of children with 2 doses of a measles-containing vaccine, preferably given as MMR vaccine. This, in effect, got 2 doses of a mumps vaccine into children, as well, causing case numbers to continue to fall through the 1990’s. Resurgence 2006 Resurgence Year Incidence 60/100,000

Mumps Vaccine Licensed
1967 Mumps Vaccine Licensed 1977 1st Dose ACIP Recommendation 1989 2nd Dose ACIP Recommendation 2010 U.S. Elimination Goal 1-dose mumps vax preschool coverage 2-dose mumps vax adolescent coverage Mumps Cases % Mumps Vax Coverage The rest of this presentation will examine the details of mumps surveillance during this time period, keeping in mind the mumps elimination goal set for 2010. Resurgence 2006 Resurgence Year Incidence 60/100,000

Mumps Surveillance Nationally notifiable disease since 1968
National surveillance data from NNDSS are used to guide national vaccine program and policy Core variables Age, DOB, sex, race, ethnicity, county Extended field variables Vaccination status and # doses Lab results, transmission setting, epi-link In 1968, mumps became nationally notifiable through NNDSS. National surveillance data are used to guide the national vaccine program and policy-making. Mumps cases are investigated and reported using a standard form that includes core variables such as age, date of birth, sex, race, ethnicity, county; and extended field variables that collect important additional details about each case including vaccination status, number of MMR doses received, lab results, transmission setting, and epidemiological links.

Mumps Surveillance 2007: Revised CSTE case definitions & classifications Clinically compatible illness as well as clinical case definition Probable case requires epidemiological link Laboratory confirmation Isolation of mumps virus (culture), or Detection of mumps nucleic acid (RT-PCR), or Detection of mumps IgM antibody, or Absent recent vaccination, either 4X increase in IgG titer measured by quantitative assay, or seroconversion from negative to positive using standard serologic assay of paired acute and convalescent serum specimens In 2007 the Council of State and Territorial Epidemiologists revised mumps case definitions and classifications. To be classified as a confirmed or probable case, a case now must have a clinical symptom compatible with mumps. Classification of a case as probable now requires an epidemiological link. Criteria for laboratory confirmation include isolation of the mumps virus, detection of mumps RNA by RT-PCR, detection of mumps IgM antibody, or a 4-fold rise in IgG titer measured by a quantitative assay, or seroconversion from negative to positive using a standard serologic assay of paired acute and convalescent serum specimens.

Laboratory Testing for Mumps
In persons with vaccination or disease history Serologic results should be interpreted with caution False positive and false negative lab results are possible Mumps cases cannot be ruled out by negative serology or virology laboratory results Testing for other causes of parotitis may be helpful e.g. parainfluenza Laboratory testing for mumps in vaccinated individuals or persons with disease history can be challenging. Serologic results must be interpreted with caution, as false positive and false negative results are possible. Vaccinated cases may not mount an IgM response; they may not have a 4-fold rise in IgG antibody; and they may excrete mumps virus at lower levels and for a shorter time period. Therefore, mumps cases cannot be ruled out by negative lab results. For mumps cases with negative lab results for mumps, diagnostic testing for other causes of parotitis may be helpful.

Mumps Surveillance, NNDSS 1994-2005
Reported Cases of Mumps Genotypes Isolated A, C, G, H Examining trends in mumps before the 2006 outbreak, we see the number of mumps cases declined steadily from 1994 to 2005, when the national incidence reached 0.1 per hundred thousand. The seasonal patterns of mumps, with higher incidence late winter through spring, disappeared during the latter half of this time period. Between 1994 and 1998, about 900 mumps cases were reported annually. This declined to approximately 300 cases per year between 1999 and Though relatively few specimens were submitted for genotyping, a variety of genotypes were isolated during this time period: A, C, G, and H. Only one small outbreak with 31 cases occurred during this time. This outbreak, in a New York state summer camp in 2005, was linked to a case in a visitor from the UK. Characteristics suggestive of mumps elimination, or absence of endemic disease transmission, were present during this latter time period including very low incidence and few outbreaks, lack of seasonality, and a variety of genotypes. Incidence 0.1/100,000

Age-specific Mumps Incidence Rates, 1999-2005
Incidence per 100,000 From 1999 to 2005, incidence was highest in the 1-9 year age group. From 1999 through 2003, incidence rates across age groups held steady or declined. However, it is interesting to note the increase in incidence for year-olds, here shown in yellow, from 2003 to This could have been an indication of the outbreak to come. 18-24 y/o case #s 1999 – 27 2000 – 19 2001 – 14 2002 – 17 2003 – 8 2004 – 22 2005 – 51

Vaccination Status Mumps Cases 1994-2005
73% of data on number of MMR doses is missing from NNDSS Unlike the data on age of cases, the data in NNDSS on vaccination status of mumps cases during this time period was far from complete. From 1994 through 2005, 73% of the information on number of MMR doses received was missing. The missing information is represented here by diagonal lines. There was no real improvement in collection of data on vaccination status over time. This high proportion of missing data made it impossible to assess whether mumps cases were occurring due to failure of the vaccination program, or vaccine failure. Outbreak investigations from the late 1980’s and early 1990’s had helped inform on this issue, but no useful trends in vaccination status were available from NNDSS data for this decade. Percent of Cases

Mumps Cases Reported to NNDSS, 2006
Reported cases = 6,584 Incidence 2.2/100,000 Reported Cases of Mumps Outbreak strain Genotype G In 2006, 6584 cases of mumps were reported from across the nation to NNDSS. The national incidence for this year was 2.2 per hundred thousand. Outbreak cases were first reported in late December 2005 among college students. Numbers increased, especially on college campuses, through the winter, peaked at the end of April, and declined through the summer. Small outbreaks on 3 college campuses occurred in September and October, as students returned to college.

2006 Outbreak Midwestern states (IA and surrounding) most affected geographically Highest incidence year-olds, and outbreaks on college campuses Single genotype isolated (G) from outbreak states NNDSS data: 72% of # of MMR doses missing The 2006 outbreak was focused in Midwestern states, and year-olds were the most affected age group. Although several genotypes were isolated during this year, one genetically homogenous genotype, genotype G, was responsible for the outbreak. Again, 72% of data on vaccination status was missing from NNDSS in this year, making it impossible to describe this important characteristic of the cases and better understand the outbreak using NNDSS data.

Number of Reported Mumps Cases
Mumps Cases Reported to Outbreak State* Database by Age Group and Vaccination Status, Jan-Jul 2006 Number of Reported Mumps Cases States were collecting this information though, and informed CDC very early in the outbreak that the majority of cases were occurring in vaccinated persons – predominantly in 2 dose vaccine recipients. As is reflected in data provided from state databases to CDC by the 8 most highly affected states, over half the cases had received 2 doses of MMR. *IL, IA, KS, MN, MO, NE, SD, WI

Incidence by Age Group Before and During the 2006 Outbreak
Incidence per 100,000 As mentioned, the age group most affected by mumps shifted during the outbreak. In pre-outbreak years, mumps incidence was highest in 5-9 year-olds, here shown in white. In the 2006 outbreak, though incidence increased in all age groups, it was highest in year-olds, shown in yellow.

Mumps Cases Reported to NNDSS 2005-2008
Reported Cases of Mumps In months following the outbreak of 2006, reported case numbers declined to approximately twice what they were before the outbreak. In 2007 the national incidence was 0.2 per hundred thousand, compared with 0.1 per hundred thousand in 2005. 26 cases/month 60 cases/month Incidence 0.1/100,000 Incidence 0.2/100,000 *Data provisional through 12/31/07 **Data provisional through 3/7/08

After 2006 Outbreak? 715 cases reported in 2007*
76 cases reported in Jan/Feb 2008** 3 states/grantees with higher number of reported cases to NCIRD Maine: 102 cases Las Vegas, Nevada: 27 cases, genotype H American Samoa: 41 cases Several small clusters in colleges and within households In 2007, 715 cases of mumps were reported to NNDSS from across the nation. In 2008, 76 cases have been reported via NNDSS in January and February. From direct communication with states, NCIRD is aware of more cases than what has been reported so far through NNDSS. Three areas have reported major increases in mumps cases: Maine, Las Vegas NV, and American Samoa. Small clusters continue to be reported in colleges and within households. *Data provisional through 12/31/07 **Data provisional through 3/7/08

Incidence by Age Group Before, During, and After the 2006 Outbreak
Incidence per 100,000 After the outbreak, incidence by age group patterns are similar to what they were prior to the outbreak. 5-9 year-olds, here shown in white, are again the most highly affected age group, followed by 1-4 year-olds, shown in blue. While year-olds, shown in yellow, no longer have the highest incidence, incidence in this age group remains higher than it was before the outbreak. *Data provisional through 12/31/07 **Data provisional through 3/7/08

Mumps Surveillance Quality 1994-2008
Variable 2006 2007*-present** Age 97.4% 99.6% 99.3% Vaccination Status (Y/N) 28.9% 25.6% 45.7% # MMR Doses 27.2% 27.6% 29.5% Transmission Setting 35.0% 38.0% 52.8% Epi-link 31.0% 26.9% 54.6% Any Lab Testing 21.4% 41.6% 49.6% If we examine selected variables for mumps over the time period 1994 to 2008, as illustrated during this presentation, the completeness of some mumps NNDSS variables, such as age, is quite good. Other variables that are important to understanding the recent, perplexing questions about mumps are incomplete, although some have been improving over the years. Without more complete data, it is difficult to draw reliable conclusions. We need high quality surveillance data to guide the mumps vaccine program, especially vaccine policy. For example, should we be considering a 3rd dose of mumps vaccine in outbreak settings, or routinely in settings of high transmission such as colleges? We can’t begin to answer this question without high quality and complete data on vaccination status of cases. *Data provisional through 12/31/07 **Data provisional through 3/7/08

Conclusions Surveillance Trends
Significant decline in mumps cases from 2006 outbreak caught us unaware Age trends well described in NNDSS data Surveillance data provided hint of change in age-specific incidence that occurred in 2006 Increased case numbers and clusters in 2007 and 2008 may reflect higher levels of reporting following the outbreak In conclusion, mumps cases declined significantly from 1994 to 2005, but the 2006 mumps outbreak caught us off-guard. However, there may have been a hint to the upcoming shift in age group from the data in NNDSS – where reporting on age of cases is virtually complete. Increased case numbers and clusters in 2007 and 2008 may reflect higher levels of reporting following the outbreak.

Conclusions II Surveillance Quality
Trends in vaccination status not well described Vaccination status data are key to guiding vaccine program and policy Vaccine failure or failure to vaccinate? Other key variables Transmission setting – colleges Epidemiological link – needed for case classification Laboratory testing to confirm, including genotype On the other hand, trends in vaccination status have not been well described in data submitted to NNDSS. Vaccination data are key to guiding vaccine program and policy. Given the experience in 2006, we are concerned about mumps cases occurring on college campuses. Therefore, collecting and transmitting information on transmission setting is important. Additionally, to assess progress toward mumps elimination, high quality mumps surveillance data will be needed.

Acknowledgements State and Local Health Departments All Partners
Division of Viral Diseases Jane Seward William Bellini Preeta Kutty Paul Rota Susan Redd Jennifer Rota Charles LeBaron Luis Lowe Amy Parker Carole Hickman Daoling Bi Don Latner National Center for Immunization and Respiratory Diseases Sandra Roush Disclaimer: The findings and conclusions in this presentation are those of the author and do not necessarily represent the views of the Centers for Disease Control and Prevention I would like to acknowledge my colleagues, and I thank you for your kind attention.

Thank you Now I welcome your feedback regarding roadblocks to reporting certain variables and any questions you may have.

ADDITIONAL SLIDES

Mumps Cases Reported to NNDSS 1994-2005*
*New Mexico not reportable

Mumps Cases Reported to NNDSS, 2006

Mumps Cases Reported to NNDSS January 2007* – February 2008**
**Data provisional through 3/7/08 *Data provisional through 12/31/07

Mumps Cases and Incidence Reported to NNDSS, 1994-2005
Incidence per 100,000 Reported Cases of Mumps This slide depicts mumps case numbers and incidence declining to very low levels from the late 90’s through 2005.

Mumps Cases Reported to NNDSS, 2000-2008
Reported Cases of Mumps *Data provisional through 12/31/07 **Data provisional through 3/7/08

Mumps Cases Reported to NNDSS January 2007* – February 2008**
Reported Cases of Mumps *Data provisional through 12/31/07 **Data provisional through 3/7/08

Age-specific Mumps Incidence Rates 1999-2005
Incidence per 100,000 We investigated trends for clues that an outbreak was about to occur. As we take a closer look at age-specific incidence rates, it is interesting to note the increase in rate for year-olds from 2003 to 2005. 18-24 y/o case #s 1999 – 27 2000 – 19 2001 – 14 2002 – 17 2003 – 8 2004 – 22 2005 – 51

Vaccination Status Among Cases ≥5 Years of Age, 1994-2005
Percent of Cases Since over half of the outbreak cases occurred in people who had received 2 doses of MMR, we next examined vaccination trends. However, there were few conclusions we could draw, as much of the data was incomplete.

Vaccination Status Among Cases ≥5 Years of Age, 1994-2005*
Percent of Cases *Where vaccination status known for 27%

Reported Mumps Cases by Age Group and Vaccination Status, 1994-1998
Number of Reported Mumps Cases Incidence per 100,000

Reported Mumps Cases by Age Group and Vaccination Status, 1999-2005
Number of Reported Mumps Cases Incidence per 100,000

Mumps Cases Reported to NNDSS by Age Group and Vaccination Status, 2006 Number of Reported Mumps Cases Incidence per 100,000 As reported to NNDSS, year-olds were the most highly affected age group.

Reported Mumps Cases by Age Group and Vaccination Status, January 2007* – February 2008** Number of Reported Mumps Cases Incidence per 100,000 Presently, the incidence is again highest among 5-9 year-olds, but the incidence in year-olds is still quite elevated compared to pre-outbreak levels. *Data provisional through 12/31/07 **Data provisional through 3/7/08

Completeness of Selected NNDSS Variables Over Time*
Percent Complete *2007 Data provisional through 12/31/07 **Data provisional through 3/7/08

Completeness of Selected NNDSS Variables Over Time II*
Percent Complete *2007 Data provisional through 12/31/07 **Data provisional through 3/7/08

CSTE Mumps Case Definition
Clinical case definition An illness with acute onset of unilateral or bilateral tender, self-limited swelling of the parotid and or other salivary gland(s), lasting at least 2 days, and without other apparent cause Clinically compatible illness Infection with mumps virus may present as aseptic meningitis, encephalitis, hearing loss, orchitis, oophoritis, parotitis or other salivary gland swelling, mastitis, or pancreatitis.

CSTE Mumps Case Definition cont’d
Laboratory criteria Detection of mumps IgM antibody, or Absent recent vaccination, either 4X increase in IgG titer measured by quantitative assay, or seroconversion from negative to positive using standard serologic assay of paired acute and convalescent serum specimens, or Detection of mumps nucleic acid (RT-PCR), or Isolation of mumps virus (culture)

CSTE Mumps Case Definition cont’d
Case classification Suspected: A case with clinically compatible illness or meets the clinical case definition without laboratory testing, or a case with laboratory testing suggestive of mumps without clinical information Probable: A case that meets the clinical case definition without laboratory confirmation and is epidemiologically linked to a clinically compatible case Confirmed: A case that 1) meets the clinical case definition or has clinically compatible illness, and 2) is either laboratory confirmed or is epidemiologically linked to a confirmed case

Pre-outbreak 1994-1998: 663-1467 cases per year
Some small outbreaks linked to importations Urban areas most affected geographically 5-9 year-olds most affected age group Variety of genotypes isolated (A,C,G,H) In 1994 through 1998 between 663 cases and 1467 cases were reported annually. In 1999 through 2005 between 231 and 387 cases were reported annually. A few small outbreaks linked to importations occurred, such as the 2005 summer camp outbreak in New York state, which was linked to the UK. Urban cities were most affected geographically, and 5-9 year-olds were the most affected age group. Characteristics suggestive of elimination include very low incidence, lack of seasonality, a variety of genotypes, and few outbreaks.

Pre-outbreak : Average of 892 cases per year (range cases/yr) : Average of 295 cases per year (range cases/yr) Some small outbreaks linked to importations Urban cities most affected geographically 5-9 year-olds most affected age group Variety of genotypes isolated (A,C,G,H) In 1994 through 1998, an average of 892 cases were reported annually. In 1999 through 2005, an average of only 295 cases were reported annually. A few small outbreaks linked to importations occurred, such as the 2005 summer camp outbreak in New York state, which was linked to the UK. Urban areas were most affected geographically, and 5-9 year-olds were the most affected age group. Characteristics suggestive of elimination include very low incidence, lack of seasonality, a variety of genotypes, and few outbreaks.

Challenges Understanding Recent Mumps Epidemiology
New Population (i.e., vaccinated individuals) Laboratory Diagnostics False positive, false negative IgM Difficulties culturing virus and detecting virus with RT-PCR Vaccine Failure Incomplete Surveillance Data Number of MMR doses Lab Testing Transmission Setting / Epi-link There are several challenges to understanding the recent epidemiology of mumps and addressing the potential roadblocks to its elimination from the United States by The pathogenesis of mumps in vaccinated individuals is not clearly understood. Improved diagnostics and a better understanding of vaccine-induced immunity are essential. NNDSS is the only source of comprehensive data on mumps that is available. Unfortunately, some of the key variables that are critical to understanding the recent epidemiology are far from complete, such as vaccination status, lab testing, and transmission setting.

Albert E. Barskey IV, MPH Division of Viral Diseases

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Albert E. Barskey IV, MPH Division of Viral Diseases

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