Norovirus Outbreaks on College and University Campuses

Abstract

Objective –

To describe norovirus outbreaks at colleges and universities.

Participants –

None. Conducted 9/2016-3/2018.

Methods –

College and university norovirus outbreaks reported to the U.S. National Outbreak Reporting System (NORS, 2009–2016) or published and indexed by EMBASE, PubMed, and Web of Science (1985-2017) were analyzed.

Results –

Seventy-seven norovirus outbreaks were reported to NORS and 23 were identified in the systematic literature review. Outbreaks occurred more frequently during the beginning of the school year (September-February). NORS outbreaks were more often spread by person-to-person transmission (61%) and, in published outbreaks, by food (57%). The reported exposures of published outbreaks were campus dining (n=8) and ill food service workers (n=7). Higher attack rates were associated with smaller on-campus population size, social networks or residences, and specific food exposures. Common control measures were communal area disinfection and health/hygiene education.

Conclusions –

Recommendations summarized to prevent and control norovirus outbreaks at colleges or universities.

BACKGROUND

Norovirus is estimated to cause 18% of gastroenteritis cases worldwide, including 19–21 million cases of gastroenteritis and 56,000–71,000 hospitalizations annually in the United States (U.S.)^1,2.

Illness is characterized by diarrhea, vomiting, fever, and stomach pain and is generally mild and self-limiting, though deaths do occur in the elderly, young children, and immunocompromised individuals^2,3. Norovirus spreads through person-to-person, waterborne, environmental, and foodborne routes and can have high outbreak control and management costs^4,5. Educational institutions are a site for outbreaks. Between 1993 and 2011, 10% of published norovirus outbreaks occurred in college/university, school, or daycare settings⁶ and 6.1% of those reported to the U.S. National Outbreak Reporting System (NORS) between 2009 and 2012 occurred in schools or day cares⁷.

College and university campuses are conducive settings for norovirus outbreaks. The residential style (including shared rooms, bathrooms, and common areas) and student-to-student contact (campus events, recreation, college sports) may aid the rapid student-to-student spread of norovirus⁸. College athletes may be particularly at risk (due to the contact nature of sports) and may spread illness to both fellow athletes and non-athletes on campus⁹. The risk of transmission between and among students and staff may also increase in dining halls because of the large numbers of students and staff eating in a confined space and consuming similar foods prepared by specific individuals⁸. In addition, shellfish and self-service salad bars may be associated with norovirus outbreaks^10-13.

Outbreaks on college and university campuses are a common occurrence, yet to the best of our knowledge, trends among college and university norovirus outbreaks have not been comprehensively summarized. Thus, in this project, for norovirus outbreaks in higher education settings, we aim to assess characteristics of norovirus outbreaks and summarize existing prevention and controls measures.

METHODS

The NORS database was analyzed to identify confirmed or suspected norovirus outbreaks that occurred on college and university campuses, spread by any mode of transmission (i.e., environmental contact, foodborne, person-to-person, unknown/indeterminate, and waterborne), and with a first illness onset date during January 1, 2009 to December 31, 2016. NORS is an Internet-based passive reporting system used by local, state, and territorial public health agencies in the United States to report to the Centers for Disease Control and Prevention (CDC) all foodborne and waterborne disease outbreaks as well as enteric disease outbreaks resulting from person-to-person contact, environmental contamination, animal contact, and other or unknown modes of transmission. To supplement NORS reports with additional norovirus genotype information, NORS records were matched to CaliciNet records using an algorithm based on outbreak identification numbers. CaliciNet is a norovirus outbreak laboratory surveillance network of federal, state, and local public health laboratories in the United States which collects information on norovirus genotypes implicated in outbreaks¹⁴. Data were aggregated and analyzed using R 3.3.0¹⁵.

Outbreaks were defined as two or more cases of a similar illness associated with a common exposure, such as a setting or a food item. An outbreak was considered “confirmed” if two or more laboratory-confirmed norovirus cases were reported; outbreaks with fewer than two laboratory-confirmed norovirus cases were considered “suspected” based on the reporting jurisdiction’s etiology determination criteria. Primary cases were defined as case-patients with an exposure at the primary exposure location (i.e., college or university campus) during the outbreak exposure period of interest. Secondary cases were defined as case-patients with no exposure to the primary exposure location during the outbreak exposure period of interest. The settings of interest were colleges and universities; we did not include summer or sports camps or other community events held on college and university campuses. Of note, school, college, and university outbreaks are reported in NORS using the option, “School/college/university,” for all modes of transmission. Therefore, all report comment fields were reviewed for the terms indicating the outbreak occurred among students on a college or university campus (e.g., “university”, “college”, “dorm”, “fraternity”, “sorority”, or “medical school”). For any reports with ambiguous setting information, the reporting state was contacted for clarification of whether the outbreak occurred among college and university students on a college or university campus. Fall was defined as September to November, winter as December to February, spring as March to May, and summer as June to August.

To identify all published, peer-reviewed articles describing norovirus outbreaks on a college or university campus, we conducted searches in the EMBASE, PubMed, and Web of Science databases using a search string for titles or abstracts including words relating to “norovirus”, “campus” or “university”, and “outbreak.” Articles published between January 1985 and June 2017 were included (Please see Supplementary Table 1 for full search strings). The references of the full texts of eligible articles were also reviewed to identify other eligible articles. Two independent reviewers first screened titles and abstracts and then screened the full-text of the selected articles based on inclusion/exclusion criteria. Inclusion criteria were that full-length articles (1) had to be accessible in the English language, (2) had to involve a norovirus outbreak taking place on a college or university campus (including campus-based vocational schools or military training schools) with at least 2 cases in a 1-month period, and (3) had at least two cases involved in the outbreak confirmed to be norovirus positive by RT-PCR, enzyme-linked immunosorbent assay (ELISA), or electron microscopy (EM). Outbreaks reported to have taken place in daycares or camps on college campuses were excluded. Duplicate outbreaks recorded in multiple publications were also excluded. Of note, no articles identified in NORS were also identified in the literature review.

For each identified norovirus outbreak, two independent reviewers, using a data extraction protocol (registered in PROSPERO), extracted data from the article regarding outbreak general characteristics, symptoms, source and transmission routes, and outbreak control steps. Any discrepancies were resolved through discussion between the independent reviewers or, if necessary, a third independent reviewer. The final reconciled database was analyzed in Prism 5.0 (La Jolla, California) using descriptive statistics (e.g. proportions).

Student population size was categorized according to the Carnegie Classification of Institutions of Higher Education (1,000 students as small, 1,000-10,000 as medium, and greater than 10,000 as large)¹⁶. Fall was defined as September to November, winter as December to February, spring as March to May, and summer as June to August (all identified published outbreaks were in the Northern Hemisphere). Attack rates were taken directly from the article text, and if none were reported, they were calculated by the reviewers as the number ill over the number exposed. To identify potential outbreak risk factors, attack rates and risk factors (e.g., campus size, department of study, food items, gender, student classification, residence location, student or faculty/staff status) were compared. Attack rates by student population size were compared by using the Kruskal-Wallis test for significance followed by post-hoc Steel-Dwass all-pairs comparison test in R using the NSM3 package^17,18. Some studies explicitly stated whether the attack rates among different potential risk factors were significantly different, but for those that did not, the attack rates between potential risk factors were compared by the authors using the Fisher’s exact test.

RESULTS

A total of 77 college and university norovirus outbreaks were reported to NORS by 28 states during 2009–2016 (Figure 1). Winter was the season with the most outbreaks reported (40, 52%), with 21 (27%) reported in spring, 12 (16%) reported in fall, and four (5%) in summer (Figure 2A). Forty-seven (61%) of the norovirus outbreaks were laboratory-confirmed. Of these 47 outbreaks, 37 (79%) outbreaks were caused by genogroup II and ten (21%) by genogroup I noroviruses, and a total of 29 (62%) could be further sequenced and genotyped (see Supplementary Table 2 for genotype data). Outbreaks lasted a median of nine days (range: 2–56); the median number of cases per outbreak was 31 cases (range: 2–433). Diarrhea (median 100%) had the highest median symptom frequency followed by vomiting (90%), nausea (88%), chills (77%), muscle aches (69%), stomach pain (67%), headache (61%), and fever (43%; Figure 3A). Comparatively, 13,890 norovirus outbreaks in other settings (e.g., healthcare facilities, restaurants, and schools or child day cares) were reported to NORS during the same period. These non-college and university norovirus outbreak reports had a median duration of nine days (range: 1–404) and a median of 23 primary cases (range: 2–699).

Figure 1:

Count of United States college and university outbreaks reported to the National Outbreak Reporting System (n=77) and identified from a systematic literature review (n=14, two additional US-based outbreaks were reported as “Southeast” and “Mid-Atlantic” and so could not be assigned to a state), 1980-2016. Please see Methods for detail

Figure 2:

Monthly distribution of college and university outbreaks by primary mode of transmission reported to the National Outbreak Reporting System (NORS; A, n=77) and identified from a systematic literature review (B, n=16), 1980-2016.

Figure 3.

Distribution of symptom frequencies among college and university norovirus outbreaks reported to the National Outbreak Reporting System (NORS; A, n=77) and identified from a systematic literature review (B; n=23). Bars represent box and whiskers plot of frequency of each symptom across different college and university outbreaks, showing lower bound value, first quartile, median, third quartile, and upper bound value. Number of outbreaks reporting symptom frequencies are indicated below each symptom and differ because not all outbreaks listed the frequency of each symptom.

A majority of the college and university norovirus outbreak reports (47, 61%) indicated that transmission was primarily person-to-person, while 18 (23%) were foodborne, 11 (14%) were unknown or indeterminate, and one (1%) was environmental (Figure 2A). Fifteen (19%) reports indicated secondary transmission occurred, of which a median of eight secondary cases (range: 1–125) were reported. Of these 15 outbreaks, 11 (73%) reported secondary person-to-person transmission, one (7%) reported secondary foodborne transmission, and one (7%) reported secondary environmental and person-to-person transmission. Of the 18 foodborne college and university outbreaks, contributing factors were reported in five (28%), all of which implicated infectious food workers as the source. Specifically, two of these five outbreaks indicated bare hand contact by a food worker, two indicated glove hand contact by a food worker, and one indicated non-specific food worker contamination.

Among the college and university outbreaks for which health care seeking data were reported, 2,181 case-patients sought healthcare (52.9 visits per 100 case-patients), 420 case-patients visited the emergency room (10.1 visits per 100 case-patients), and 38 case-patients were hospitalized (0.8 hospitalizations per 100 case-patients). Among the 2,915 case-patients for whom information on gender was reported, 49% were male and 51% were female. Among the 77 norovirus outbreaks reported on college and university campuses, 30 (39%) reported information on the total number of people exposed among students and/or faculty and staff, including the proportion of those that became ill (i.e., attack rate). Among the 29 reports with information on students, the median attack rate was 11% (range: 0.1–66.7%). Among the eight reports with information on faculty and staff, the median attack rate was 2% (range: <0.1–8.9%).

The literature search identified 270 non-duplicate articles (Figure 4), 94 articles were selected from titles and abstracts according to the inclusion and exclusion criteria, and two additional articles were identified from a review of the bibliographies. After comparison of the full-text with inclusion and exclusion criteria, the final database consisted of 20 articles describing 23 distinct norovirus outbreaks between 1985 and 2017, with two articles describing multiple outbreaks.

Figure 4:

23 outbreaks matching the eligibility criteria were included in the systematic review following a review of titles, abstracts, and full-length articles identified by the search string. The flow diagram shows the process of arriving at these 23 outbreaks, with each row showing a different step of review and elimination of articles not matching eligibility criteria. Two independent reviewers were involved in each step of the process, with a third reviewer available to resolve discrepancies.

All published campus outbreaks were in the Northern hemisphere with the majority of outbreaks in North America (17, 74%) and the remainder in Asia (5, 22%) or Europe (1, 4%). Outbreaks in Asia (China, n=3; Japan, n=1; Thailand, n=1) and Europe (Austria, n=1) were similar to those in North America (Canada, n=1; United States, n=16) regarding seasonality, number of cases, and mode of transmission (data not shown). As with NORS outbreaks, a large number of published outbreaks (17, 74%) took place during the fall and winter months (Figure 2B). Fall season marked the time with the greatest number of published campus outbreaks (12, 52%) with five (22%) in winter, four (17%) in spring and two (9%) in summer. Four outbreaks occurred soon after students had returned from a university break, with two publications hypothesizing that students traveling off-campus for holidays may have acquired and introduced pathogens upon returning. Nineteen (83%) outbreaks utilized RT-PCR as a confirmatory technique; the remaining studies were published prior to 1992 and the development of norovirus amplification¹⁹ and thus used ELISA or electron microscopy. Of these 19 RT-PCR confirmed outbreaks, 13 (68%) outbreaks specified a norovirus genogroup: 10 (53%) were GII and three (16%) GI; the other six outbreaks did not specify genogroup (see Supplementary Table 2 for genotype data). The median outbreak duration was 12 days (range: 3–40), and the number of cases peaked at a median of five days (range: 1–25) following the outbreak onset. Eight studies listed the duration of symptoms; median duration across those studies was two days (range: 1.1–2.1). Nausea (87%) had the highest median symptom frequency (Figure 3B) followed by chills (78%), vomiting (78%), diarrhea (68%), headache (65%), stomach pain (64%), muscle aches (58%), and fever (47%). Overall, the median number of cases was 148 cases (range: 19–1,002). Nineteen outbreaks reported student case counts, among which the median number of cases was 125 (range: 12–787). Nine outbreaks reported faculty and staff case counts, and of these, the median number of cases was 10 (range: 0–40).

The most common mode of transmission was foodborne (13 outbreaks, 57%; Figure 2B); six (26%) were caused by an unknown or indeterminate mode of transmission and four (17%) by person-to-person transmission. Fourteen (61%) outbreaks described a confirmed or suspected source of infection. Of these 14 outbreaks, eight (57%) implicated communal dining as a contributing factor to the outbreak. Seven (50%) of these 14 outbreaks reported a food service worker as the likely source, based on detection of norovirus in a food service worker stool sample or the food service worker reported having close contact with a norovirus positive person. Salad bar items were reported as a confirmed or suspected source in three outbreaks, and meats (e.g. turkey, chicken, ham) were identified as a confirmed or suspected source in six outbreaks. Two studies did not identify a direct cause but suspected that lack of access to handwashing supplies in communal bathrooms may have been an outbreak contributing factor. Of the 14 outbreaks with information on both student population size and attack rate, the median attack rate was 6%. The median attack rate for small campus student populations (18%; n=4) was significantly higher than for large campus student populations (1%; n=6;p=0.02;). However, the median attack rate for medium campus student populations (8%; n=4) was not significantly different than small campus student populations (p=0.20) or large campus student populations (p=0.48). Certain foods, such as lettuce and ready-to-eat meats, were associated with higher attack rates^20-22. Two studies reported a significant association between gender and attack rate but offered different findings - one found significantly higher attack rates among males compared to females²³, yet the other found higher attack rates among females compared to male²⁴. Location of residence had a significant association with attack rate in 2/4 studies^24,25 and department/area of study in 2/2 studies^24,26. However, student classification (e.g., freshman, sophomore, junior, senior) was not associated with attack rate. In 1/1 study, the attack rate was significantly higher among students compared to employees (i.e., faculty and staff)²³. For additional details of factors associated with attack rates, please review the Supplementary Table 3.

Ten articles reporting on 11 outbreaks described control strategies applied in response to the norovirus outbreak on campus. In six outbreaks, disinfection of communal areas^24-28 and strategies to improve health/hygiene education on campus^8,25-28 were reported. In five outbreaks, health education was provided only to students^8,25-27 and one specified health education provided for both students and kitchen workers²⁸. In five outbreaks, the dining hall was suspected as the source of the outbreak and was reported to have been closed^20,24,28,29; another outbreak resulted in the entire campus being closed²⁵. Four studies reported a drastic reduction of cases within three days of implementation of outbreak control measures^25-28, specifically campus closure, health education, and disinfection²⁰ (n=1); health education and disinfection^26,27 (n=2); and kitchen closure, health education, and disinfection²⁸ (n=1).

DISCUSSION

The goal of this study was to assess the characteristics of norovirus outbreaks on college and university campuses and to summarize existing prevention and control measures in this setting. There were three noteworthy results. First, norovirus outbreaks had different prevalence based on season: most outbreaks were reported in winter (NORS) and fall (published outbreaks). Second, the mode of transmission most frequently reported in NORS reports was person-to-person and in published reports it was foodborne. Third, significant differences in attack rates by student population size, residence location, gender, and area of study were reported in various past published outbreaks, though the sample size of studies was small.

Both the NORS analysis and literature review found that norovirus outbreaks on college and university campuses in the Northern Hemisphere (the only hemisphere for which data were available in both data sources) were most prevalent during the colder months. This is consistent with previous accounts of the norovirus seasonality across all settings and modes of transmission. Specifically, Ahmed et al. found 71% of all norovirus outbreaks occurred during the cool months (October-March in the Northern Hemisphere, April-September in the Southern Hemisphere)³⁰. Interestingly, the number of published outbreaks peak in November whereas NORS outbreaks peak in February, yet this earlier peak among published outbreaks may exist due to the paucity of person-to-person norovirus outbreaks reported in the literature. Moreover, the climate during these months in the Northern Hemisphere leads to individuals remaining indoors and in close contact with others for longer periods. Therefore, prevention measures seem to be crucial during fall and winter months as summarized in Figure 5.

Figure 5:

Summary of existing key norovirus outbreak control and prevention recommendations for college and universities^20,42,49-51.

In the NORS analysis, 61% of campus outbreaks were reported as person-to-person transmission (Figure 2). This finding is consistent with previous summary of NORS reports from August 2009 to July 2015 that found 7,557 (76%) of 9,919 total norovirus outbreaks were propagated by person-to-person transmission³¹. The literature review found that, among the published campus norovirus outbreaks, foodborne transmission (57%) was more frequently reported compared to person-to-person transmission (35%). Foodborne outbreaks were also more often found by Matthews et al. in their systematic review of all published norovirus outbreaks⁶. The contradictory findings from the two outbreak data sources (NORS and published articles) may be a result of ascertainment, reporting, and/or publication bias. First, the outbreak ascertainment ability of NORS reporting agencies varies, with certain settings and facilities more capable of identifying and reporting norovirus outbreaks than others. For example, a closed population, such as a long-term care facility, may more easily recognize a cluster of illnesses than a restaurant outbreak. Reporting bias may exist because outbreaks with more limited or less notable information may be more frequently reported in NORS compared to published outbreaks. NORS outbreaks are geographically limited to the United States and its territories and reporting agencies are required to submit only four pieces of information to create a NORS outbreak report. Publication bias may result in a greater percentage of published norovirus outbreaks of foodborne versus other transmission route^32,33. Some reasons may include more limited data in person-to-person outbreaks compared to foodborne, an inability to identify the causative event or person in person-to-person outbreaks, and journals may, intentionally or unintentionally, prefer to publish more unique or notable outbreaks. We hypothesize that compared to surveillance biases in NORS, publication biases more likely provide a skewed view of the actual distribution of transmission modes.

Despite the discrepancies in data sources, person-to-person and foodborne outbreaks combined account for over 80% of all college and university outbreaks in the NORS and the literature review data. Therefore, the implementation of prevention and control measures targeting these two modes of transmission would likely prove most effective at reducing the impact of norovirus outbreaks on college and university campuses. Prevention and control measures that have been used include education campaigns on the importance of handwashing with soap and water after using the restroom and before eating, isolation of individuals with diarrhea and/or vomiting, and exclusion of ill food workers until at least 48 hours after symptoms of diarrhea and/or vomiting have subsided (Figure 5). While six published outbreaks focused on health and hygiene education as a tactic to decrease spread of norovirus, only one emphasized increasing handwashing and knowledge of foodborne illness among food service workers²⁸. This suggests that increasing handwashing knowledge among food service workers may be underutilized as a method of norovirus prevention. It is important to note that standard water-less hand sanitizer liquids, foams, and gels are not effective against norovirus^34-36.

Finally, attack rates on college and university campuses were reported in isolated published reports to depend on student population size, residence location, gender, and area of study. First, norovirus outbreaks small student populations (<3000 students) had significantly higher attack rates than large student populations (≥3000 students). Second, the location of student residence was associated with a higher attack rate in 2/4 studies^24,25. Past studies have demonstrated such trends in transmission with college campus outbreaks of respiratory diseases, frequently within friendship circles or residents of the same residence hall³⁷. The study also found that social organization among students in residence halls impacted spread. The norovirus studies relating attack rate to residence hall^24,25, department of study^24,26, and gender^23,24 suggest that similar principles of contact influencing spread may be similar in norovirus compared to influenza outbreaks despite the different mode of transmission. As such, temporary disruption of such social networks or clustering of cases may help break the chain of norovirus transmission during outbreaks³⁸. Military schools combine risk factors of university settings and military settings, with cadets living and working in close proximity to one another, eating more homogenous meals than at other universities, and using the same equipment^39-42.

Overall, this study has a number of strengths and limitations. Although all states and most U.S. territories participate in NORS, the first limitation is that reporting of outbreaks is voluntary and only four variables are required to create a NORS report. Therefore, reporting and data completeness vary by reporting site and among individual reports. Report completeness is also a limitation of published articles since variables including attack rate, genotype, mode of transmission, source, symptoms, and outbreak control steps were not specified for every study. Because reporting through NORS is voluntary, many norovirus outbreaks do not get recorded. Further, published outbreaks may represent high profile outbreaks and are subject to publication bias. Thus, our outbreaks may not be representative of the majority of outbreaks but rather represent the sample that is in CDC NORS database and the literature. Another limitation of the methodology is that four non-US outbreaks were unavailable in English, and therefore final results may be biased towards the English-speaking settings. The final limitation of the study is that college and university outbreaks may be underreported in NORS because reports must have explicitly stated the outbreak was at a college or university by selecting “School/college/university” or describing it in the comments. The first strength of the study is the comprehensive review of norovirus outbreaks at college and universities using data from 77 NORS reports and 20 published articles identified through a systematic review. The second strength is the systematic review methodology with multiple reviewers to ensure accurate article identification, data abstraction, and data reconciliation. Furthermore, searching three major databases (PubMed, Embase, and Web of Science) allowed for inclusion of a broad range of articles prior to article selection. In fact, two institutions (Emory University and the CDC) independently conducted this systematic review and obtained the same 20 articles.

Certain precautions have been described regarding prevention and control of norovirus in high-risk settings that may be applicable to college and university campuses. Although norovirus is environmentally persistent, with high temperature stability and resistance to alcohol-based hand sanitizers, prevention is achievable by educating individuals about the importance of washing hands with soap and water, environmental disinfection with products effective against norovirus⁴³, proper handling of food, self-isolation of infected individuals, and policies to exclude ill employees and food service workers from work until at least 48 hours after symptoms have subsided^38,43,44. The CDC recommends disinfecting healthcare surfaces with a solution made with 5 tablespoons to 1.5 cups of sodium hypochlorite in one gallon of water, though alone this may not be completely effective at eliminating norovirus^44,45. In fact, a study found wiping clean a fecally-contaminated surface with a detergent-soaked cloth followed by disinfection with a combination of bleach and detergent to be more effective⁴³. Furthermore, a key prevention and control measure on college campuses is the monitoring of student visits to campus health facilities. Early identification and potential management of norovirus outbreaks is possible if surveillance systems are established to alert campus administrators of increased reports of gastrointestinal symptoms. A study by Moe et al. suggests that students on campuses may be more likely to seek healthcare earlier due to easy access to “free” healthcare or mandatory health insurance coverage on campuses⁸. The CDC Vessel Sanitation Program provides health education and hands-on inspection for prevention of gastroenteritis in the cruise ship industry⁴⁶. However, to date, there are no widely-available, best-practice guidelines for preventing and controlling the spread of norovirus at colleges and universities. Colleges and universities have commonly utilized disinfection of communal areas to control outbreaks. However, it is also crucial to emphasize handwashing with soap and water, isolation of ill students and faculty, and exclusion of ill employees - particularly food service workers - until at least 48 hours after symptoms have subsided. We provide a summary of targeted prevention and control strategies for norovirus outbreaks (Figure 5 and Supplementary Table 4). The summary is based on these past experiences and available norovirus recommendations, but controlled studies are needed to further confirm these interventions and prevention measures. By using these recommendations and incorporating described trends, colleges and universities may be better equipped to prevent or limit the size and duration of norovirus outbreaks on their campuses.