Mumps Outbreak on a University Campus Kansas, 2006 Angela Song-En Huang, MD MPH Kansas Department of Health and Environment State Branch/CDD/OWCD Good morning

Mumps Only known cause of epidemic parotitis A vaccine preventable disease 1967- Live-attenuated mumps vaccine licensed 1977- One dose of measles-mumps-rubella vaccine (MMR) recommended 1989- Two doses of MMR recommended Now a rare disease Mumps is the only known cause of epidemic parotitis and is a vaccine preventable disease. The live attenuated mumps vaccine used in the United States was first licensed in 1967, and later became part of the measles-mumps-rubella vaccine. In 1977, the Advisory Committee on Immunization Practices recommended a single dose of MMR for children aged 12 months or older. (PAUSE) In 1989 they revised their recommendation to include a second dose of MMR in response to a large outbreak. Routine use of the vaccine has made mumps a rare disease throughout the United States and outbreaks even less common.

Mumps Outbreak at the University of Kansas (KU) — 2006 March 24 - First case in a KU student March 27 - Two more cases from KU April - Clusters of cases reported in universities around the state KU 157 Cases However, an outbreak occurred at the University of Kansas in 2006. (PAUSE) On March 24, the first case of mumps at KU was reported to the state health department. Three days later two more cases were reported at KU. All three cases lived in the same sorority house. Over the next month, other universities around the state reported cases but KU was the only school which had a large outbreak with 157 cases reported by the end of April. Fort Hays State Univ 4 Cases Kansas State Univ 2 Cases

Objectives Institute control measures Describe the outbreak at the University of Kansas (KU) Identify risk factors for disease Assess mumps vaccine coverage An investigation was launched to (PAUSE): institute control measures; describe the outbreak at KU; identify risk factors for developing disease; and assess mumps vaccine coverage.

Control Measures Isolation of cases Up to April 6: 9 days After April 25: 9 days Information disseminated to students After the cluster of cases was identified at KU, the state health department sent out a notice to physicians and public health practitioners through the secure, web-based communication system of the Kansas health alert network. The first notice recommended a 9 day isolation period. On April 7th, isolation was changed to 4 days, because the infectious period of mumps was considered to be up to 4 days after onset of active disease, and it was thought that this would increase compliance with isolation orders. However, the isolation period was changed back to 9 days on April 25, after definitive guidelines were published by CDC and to comply with Kansas regulations. KU’s student health service disseminated information from the state and local health department to the students using posters, e-mail and the school newspaper.

Outbreak Description Method Case finding using surveillance data Review medical records Case definition: KU student with disease onset February 1–May 8, 2006 Had one of the following: Acute onset of parotid or other salivary gland swelling or pain without other apparent cause Isolation of mumps virus PCR positive for mumps Physician diagnosis of mumps Databases from the state health department, the local health department, and the student health service were used to identify mumps cases. We then reviewed medical records to ascertain cases. A case was defined as illness in a KU student with disease onset between February 1 and May 8, 2006, who had one of the following: Acute onset of parotid or other salivary gland swelling or pain without other apparent cause, isolation of mumps virus from a clinical specimen, identification of mumps virus using polymerase chain reaction or PCR, or physician diagnosis of mumps.

Mumps at KU — February 1–May 8, 2006 (n=174) Isolation Days 9 4 9 Last week of classes First case reported This is the epidemic curve of the outbreak. A total of 174 cases were reported. Even though the first case of mumps was reported to the state health department on March 24, several cases had onset dates earlier than that. The number of cases rose throughout April, peaking in the third week. This was followed by a sharp fall in the week starting May 3. Interviews with physicians at the student health service found that, after isolation days were changed back to 9 days on April 25th, physicians were more selective in making the diagnosis of mumps//because of the perceived social and educational impact on the students.

Mumps at KU — February 1–May 8, 2006 (n=174) Characteristics Mean age, years 20.9 (range 18.6-33.5) Sex Male 35% Female 65% Lived in dorms 28% Student Level, n Graduate 10 (Attack Rate=0.2%) Undergraduate 164 (Attack Rate=0.8%) The mean age of the cases was 20.9 years. 35% were male; 65% were female. 28% of the students with mumps lived in the dorms. 10 cases were found in graduate students, and 164 in undergraduate students. The attack rate was lower in graduate than undergraduate students.

Methods for Case-Control Study Cases Responded to telephone interview AND met a stricter case definition Controls Telephone survey of randomly selected sample of undergraduate students c2-test and t-test to compare cases and controls Calculate odds ratio Review vaccination records To identify risk factors associated with disease, we conducted a case-control study among the undergraduate students. Cases were interviewed by telephone and then selected based on a stricter definition than was used for initial case finding.

Case Definition for Case-Control Study Answered “yes” to: “Did you have swelling of the parotid glands, the glands near your ears/cheeks?” and lasted ≥2 days OR “Did you have swelling or pain in your testicles?” Culture or PCR positive for mumps virus A case was defined as anyone who answered “yes” to the question “Did you have swelling of the parotid glands, the glands near your ears/cheeks?” and lasted 2 or more days, or males answering “yes” to the question “Did you have swelling or pain in your testicles?” In addition, anyone with culture or PCR positive for mumps virus was included.

Methods for Case-Control Study Cases Responded to telephone interview AND met a stricter case definition Controls Telephone survey of randomly selected sample of undergraduate students c2-test and t-test to compare cases and controls Calculate odds ratio To select controls, we conducted a telephone survey of 444 randomly selected undergraduate students.

Methods for Case-Control Study Cases Responded to telephone interview AND met a stricter case definition Controls Telephone survey of randomly selected sample of undergraduate students c2-test and t-test to compare cases and controls Calculate odds ratio We compared the cases and controls using chi-square test and t-test and calculated the odds ratio.

Selection of Cases and Controls 10 graduate students 1 student with disease 164 cases 443 controls From the 174 cases identified, 164 were eligible for the study after 10 graduate students were excluded. Of these, 126 (or 77%) responded to our telephone survey. 97, or 77% met the stricter case definition. From the 444 randomly selected controls, one student was excluded because he had disease. Of the remaining 443, 147, or 33% responded to the telephone survey. 126 (77%) responded to survey 147 (33%) responded to survey 97 (77%) met case definition

Statistically Significant Risk Factors Cases n=97 Controls n=147 OR (95% C.I.) Exposure to persons with mumps 34% 16% 2.8 (1.4, 5.5) Female 62% 44% 2.0 (1.2, 3.6) Lived in dorm 26% 14% 2.1 (1.0, 4.2) Worked on campus 25% 2.0 (1.0, 4.0) Analysis of the case control study revealed that several risk factors were significantly associated with illness. We asked the students “during the month before your illness, were you in close contact (meaning within three feet for several hours) with someone who was ill with mumps?” The odds of having answered “yes” to this question among cases was 2.8 times as high as the odds of answering “yes” among the controls. Other statistically significant risk factors were being female, having lived in the dormitory, or having worked or volunteered on campus.

Statistically Significant Risk Factors Cases n=97 Controls n=147 OR (95% C.I.) Age (years) 18-19 41% 18% 6.0 (2.9, 12.7) 20 23% 24% 2.6 (2.9, 12.7) 21 21% 16% 3.4 (1.5, 7.7) ≥22 15% Reference The odds of being younger than 22 years of age were up to six times greater among cases compared to controls. Other risk factors including sharing spaces, working, or participating in sports or travel were not found to be significant.

Vaccine Coverage Cases (n=97) Controls (n=147) p-value Obtained complete record 99% 95% 0.09 ≥2 doses of MMR (All subjects) 98% 0.24 Finally, we reviewed immunization records of the students to assess vaccine coverage. We were able to obtain immunization records for 99% of the cases and 95% of the controls. The proportion of students with 2 or more doses of MMR were similar.

Conclusion Outbreaks occurred in vaccinated population Vaccination can limit the extent of outbreak Outbreak control relied on early diagnosis and isolation of cases Early cases were not promptly diagnosed and reported Changing isolation days created confusion Cases had increased odds of known exposure to mumps cases, female, younger age, or living in dorms This investigation showed that an outbreak of mumps occurred in a highly vaccinated population. 99% of the students at KU had at least 2 doses of MMR. The attack rate observed in this investigation was 0.8%, which is much lower than the 30% observed in the pre-vaccine era. This shows that vaccination can limit the extent of mumps outbreaks. With a high vaccination rate among KU students, outbreak control relied on early diagnosis and isolation of cases. However, because mumps is now a rare disease, early cases were not promptly diagnosed and reported. Additionally, changing the recommended number of isolation days during the outbreak created confusion among both clinicians and public health practitioners. From the case-control study, it was shown that cases had increased odds of having known exposure to mumps, being female, being in the younger age group, or living in dormitories. Similar risk factors were also identified in a 1986-87 outbreak among university students in the Midwest.

Limitations Low response rate among controls Recall bias Case definition relied on self-reporting of parotid enlargement Lacked accurate laboratory test for diagnosis There are limitations to this investigation. The response rate was low among controls. However, the controls interviewed were representative of all controls selected. Recall bias was a concern in this investigation because cases could have been more likely to remember exposures than controls. In addition, controls were interviewed later than cases. Our case definition relied on self-reporting of parotid enlargement which was difficult to describe over the telephone. However, parotid enlargement should have been easily recognized by patients. Lastly, because there were no reliable laboratory diagnostic tools to confirm all cases of mumps, capturing true cases relied on having a strict clinical case definition.

Recommendations Mumps should be considered in patients presenting with parotitis Congregate living settings may facilitate disease transmission Continue efforts to maintain high vaccine coverage This investigation suggests that physicians should consider mumps as a differential diagnosis when patients present with parotitis, regardless of the patient's vaccination status. Public health investigators should encourage compliance to control measure during an outbreak especially for congregate living settings, such as dormitories, which may facilitate disease transmission during a mumps outbreak. Finally, we must encourage continued efforts to maintain high vaccine coverage to limit outbreaks.

Acknowledgements Lawrence County Health Department Barbara Schnitker DeeAnne Schoefeld Linda Cowles Kathy Colson Kim Ens Watkins Memorial Health Center Patricia Denning Patty Quinlan Sherry Rhine Diane Hendy KDHE Gail Hansen D. Charles Hunt Jennifer Hill Martha Siemsen Daniel Neises Trudy Shane CDC Margaret Cortese Aaron Curns Rebecca Bitsko Hannah Jordan Fatma Soud Jose M. Villalon Gustavo Dayan Kate Wytovich Charles LeBaron Mona Marin Susan Reef Mumps Response Team Diana Bensyl I would like to acknowledge the many people who worked on this outbreak. Thank you. The findings and conclusions in this report are those of the authors and do not necessarily represent the views of the Centers for Disease Control and Prevention