College campus outbreaks require timely, effective public health measures

After the ninth case of serogroup B invasive meningococcal disease, linked to a Princeton University outbreak, claimed the life of a student in March 2014, CDC officials reported the attack rate of disease on the Princeton campus to be 134 cases per 100,000 students — 1,400 times greater than the national average.

Since the outbreak at Princeton in 2013, there have been three other college outbreaks of serogroup B meningococcal disease: the University of California Santa Barbara (UCSB), where five cases also occurred that year; and this year at Providence College in Rhode Island, where five cases were reported; and at the University of Oregon, where seven cases occurred.

Also this year, another common vaccine-preventable disease, mumps, has caused a number of outbreaks on U.S. campuses; the University of Virginia reported cases of mumps in February and the University of Texas’ Austin campus reported six cases in July. However, none of those compared with the largest and most recent outbreak at the University of Illinois at Urbana-Champaign, where there were 101 confirmed cases of mumps.

Infectious Disease News spoke with several infectious disease and college health experts about the heightened risk for vaccine-preventable outbreaks on college campuses, the impact of these outbreaks outside the college campus setting, and the best strategies to deter them in the future.

Photo by Ryan Zaragoza

An ideal setting for pathogenic transmission

Living conditions and behaviors on college campuses compound in such a way that residential students are made susceptible by lax vaccination requirements and enforcement, according to James C. Turner, MD, professor of internal medicine at the University of Virginia. State laws govern vaccine enforcement by college administrations, and many jurisdictions do little to support college enforcement beyond legislatively established standards, which in some cases are inadequate, he said.

“The living, learning and social density on college campuses increases the opportunity for pathogens to be passed from person to person,” Turner told Infectious Disease News. “Particularly with introductory courses, there are large classes with several hundred students packed into hot, dry lecture halls, where coughing and sneezing can easily pass pathogens from one person to another.”

According to the CDC, meningococcal disease is transmitted by direct contact with respiratory and throat secretions from carriers infected with Neisseria meningitidis bacteria. Likewise, the mumps virus is spread through direct contact with saliva or mucus from an infected person’s mouth, nose and throat.

“One of the key things that happens on college campuses is an intense mixing of students, combined with behaviors of visiting bars and exchanging respiratory secretions when people are partying,” Jessica R. MacNeil, MPH, epidemiologist for the division of bacterial diseases at the CDC, told Infectious Disease News. “It’s really the behavior of college students and their social activities that put them at increased risk.”

MacNeil noted that these transmission characteristics, coupled with the intimate close contact between students away at universities, make college campuses the perfect environment for outbreaks of meningococcal disease to occur.

“Schools, in general, are places where infectious diseases can quickly be spread, but more so at college campuses where students have close contact, but also close intimate contacts,” Angela Vassallo, MPH, MS, director of infection prevention and epidemiologist at Providence Saint John’s Health Center in California, told Infectious Disease News. “Students eat together and often share food and drinks, so there are many ways when you live in a close-contact environment that infectious diseases can be spread.”

According to the CDC, meningococcal disease presents itself with a sudden onset of fever, headache, stiff neck, rapid breathing, vomiting or rash. The average fatality rate for patients infected with serogroup B meningococcal disease is 11.2%. Three of the seven students who were part of the Princeton outbreak reported long-term symptoms, including unilateral hearing loss, neurocognitive deficits and chronic headaches.

Seven students were affected by serogroup B meningococcal disease during outbreaks on the campuses at UCSB and Providence. While none of these cases proved to be fatal, the attack rates of serogroup B meningococcal disease among students were 22.1 per 100,000 students at UCSB and 44 per 100,000 students at Providence; that was 234 times and 500 times, respectively, greater than the incidence rate for persons aged 17 to 22 years in the general U.S. population.

One of the students in the UCSB outbreak was forced to undergo bilateral foot amputations due to complications related to meningococcemia.

Mumps also is a dangerous disease, leading to long-term health problems and even death. In 2015, the University of Illinois at Urbana-Champaign reported upwards of 100 cases of mumps connected to its campus. Symptoms of infection included flu-like symptoms, swollen salivary glands, puffy cheeks and swollen jaw.

“Whenever you have sororities, fraternities, sports teams and people in very close quarters to each other over extended periods of time, it is fertile ground for passing on and creating epidemics,” Sheldon Howard Jacobson, PhD, director of the Simulation and Optimization Laboratory at the University of Illinois at Urbana-Champaign, told Infectious Disease News. “Which is basically what we could experience here with mumps.”

Turner pointed to the residential aspects of college life as a major risk factor for the spread of rare diseases like measles, mumps and meningococcal disease.

According to the CDC, all of the cases of meningococcal disease recorded during the Princeton University outbreak were students who lived in six of the 50 undergraduate campus dormitories. In addition, every case associated with Princeton, UCSB, and Providence, occurred in undergraduate students, while no cases were reported in graduate students, faculty, staff, local community members or family members of infected students.

“The number one and probably most important cause of outbreaks on college campuses is dormitory living,” Aaron E. Glatt, MD, hospital epidemiologist at South Nassau Communities Hospital on Long Island, New York, and a spokesman for the Infectious Diseases Society of America, told Infectious Disease News. “You have people living together, living on top of each other to a certain extent, in relatively small, not necessarily well-aerated spaces. If somebody gets sick with a mild illness, they’re going to continue on with their regular activities, and that can easily spread various viruses quickly.”

However, immediate connections in the college outbreaks between each case of serogroup B invasive meningococcal disease were difficult for officials to establish. For example, the five students involved in the UCSB outbreak had little in common, but three were involved in Greek life. The outbreak was ultimately only remotely connected to a widely attended Halloween event adjoining campus, according to the National Foundation for Infectious Diseases (NFID).

“Some students tend to aggregate in large numbers at Greek houses or private apartments, and all of these things just facilitate the passage of pathogens from one person to another,” Turner said. “Halloween is a big one, along with St. Patrick’s Day and Greek rush periods, either in the fall or the spring. We see a lot of issues, particularly with respiratory and gastrointestinal diseases, during those times.”

Outbreaks expand beyond campus

Although many vaccine-preventable diseases flourish in this high-risk environment, the impact of larger outbreaks often can be felt beyond college campuses.

“College students are really less self-contained than we think they are because they’re going to the grocery store, they’re interacting in the community, they’re going to work and they may be going home to visit grandma — who might be particularly vulnerable to catching some sort of infection that the college student might have,” Emily Martin, MPH, PhD, assistant professor in the department of epidemiology at the University of Michigan School of Public Health, told Infectious Disease News. “So, we have to be concerned. These students are sort of a bridge population that might enable the spread of the disease outside of the college setting.”

Such was the case in 2006, when an outbreak of mumps primarily affecting college students resulted in thousands of cases within Iowa, and spread to neighboring states, researchers reported in MMWR. It was the largest mumps outbreak recorded since 1988, and many clusters that were linked to campus parties or nearby bars included young adults who were not enrolled in nearby colleges, according to Patricia M. Quinlisk, MD, MPH, state epidemiologist and medical director of the Iowa Department of Public Health and an Infectious Disease News Editorial Board member.

“During 2006, we had outbreaks not only among those who were on campus, but among the young adults in the community,” Quinlisk said in an interview. “Even though some of the other young adults were not students, they were of the age and a social group that they would go to the same kind of venues and show up at the same parties, and they ended up getting mumps also.”

Such transmissions are extremely problematic, as these young adults practice many of the same risky behaviors as college students. By comparison, Quinlisk said that family members and caregivers exposed to infected students are much less likely to go to work when ill or have intimate contact with others in their communities, but still play a notable role in the spread of an outbreak.

“There was an Iowa-Nebraska event, and the athletes from Iowa weren’t allowed to go when they were sick so that they didn’t spread it to the other Nebraskan athletes,” Quinlisk said, recounting one of the more unusual clusters uncovered during the outbreak. “Unfortunately, some of the Iowa parents who were coming down with mumps went and spread it to other parents in the bleachers, and Nebraska ended up having cases among the parents of athletes. It was an interesting time.”

Adequate response needed to curtail outbreak

Before the outbreaks of serogroup B meningococcal disease at Princeton and UCSB, outbreak response was limited to post-exposure antibiotic chemoprophylaxis for close contacts and hygiene campaigns to educate students about transmission prevention, according to a report published by the NFID.

“Since 2009, there have been seven outbreaks of serogroup B meningococcal disease on college campuses,” MacNeil said. “Some of these outbreaks have taken place over a really long period of time, which has made things challenging from a communications standpoint, because cases keep happening. Until Princeton, there was nothing that we could do to really control these outbreaks, because there was no vaccine available.”

In November 2013, the FDA granted emergency investigational new drug status for Bexsero (4CMenB, GlaxoSmithKline) to be used to control the outbreak at Princeton University. This expanded-access investigational new drug status made the vaccine available to the population determined to be at risk in the outbreak, defined as any student, staff or faculty member of Princeton, according to CDC reports.

“[4CMenB] had been licensed in Europe at the time of the Princeton University and UCSB outbreaks, so we were able to bring it to both of those college campuses to vaccinate students in response to the outbreak,” MacNeil said. “More recently, in the last couple of years, there were two additional serogroup B outbreaks, and in both of those cases, the universities vaccinated their students with a serogroup B vaccine as a response.”

According to CDC reports, the emergency vaccination campaign at Princeton was successful in achieving high vaccine coverage in the at-risk population. Between Dec. 9, 2013 and Feb. 20, 2014, vaccine coverage of the target population was 94.9% for a single dose and 89.1% for two doses of 4CMenB. Furthermore, 96.6% of undergraduate students — the most vulnerable population on campus — received at least one dose of the vaccine.

Following the outbreaks at Princeton and UCSB, both 4CMenB and Trumenba (MenB-FHbp, Pfizer) have been licensed for use in the U.S. The Advisory Committee on Immunization Practices recommends these vaccines for individuals aged 10 years and older with certain medical conditions identified as being at increased risk for serogroup B meningococcal disease outbreaks. It also recommends both serogroup B meningococcal vaccines for individuals aged 16 to 23 years as “category B” vaccinations, defined as vaccines for use on the basis of individual clinical decision-making, not for routine use among the recommended age group.

“Immunization offers the best line of defense at this time,” Jacobson said. “The earlier this is done, the more likely that a large-scale outbreak can be suppressed. In fact, mass immunization can be implemented proactively even before a case surfaces, to prevent such an outbreak.”

However, even though most students entering college have already been vaccinated against mumps during childhood, the disease still poses a threat on campus, according to Jacobson.

“The University of Virginia had 20 to 30 cases this past school year, and we have nearly 100% compliance with the recommended two [measles-mumps-rubella (MMR)] shots and so having two MMR shots doesn’t completely protect you from having a mumps outbreak,” Turner said. “The mumps vaccine, unfortunately, even with two shots is approximately 92% to 93% effective in preventing disease.”

Furthermore, according to the CDC, mumps vaccine protection may wane, prompting universities to consider administering booster doses in response to an outbreak.

“The mumps component of the MMR vaccine appears to be the weak link and does not provide the level of immunogenicity, even after the second shot,” Jacobson said. “University of Illinois, Urbana-Champaign, health officials are trying to add a third shot not only for students, but also for the entire community within the university.”

Averting an on-campus crisis

During the outbreak at Princeton University, a hygiene campaign was initiated by the institution to educate students on limiting disease transmission through increased hygiene. The campaign implemented posters, brochures, meetings, mass emails, a dedicated website and later an outreach program engaging students to spread awareness among peers.

“Good general infection prevention practices can deter the spread of infectious disease, such as washing your hands before you eat, washing your hands after using the restroom, sharing or not sharing food,” Vassallo said. “I would recommend not to share drinks — also not to share food — but in particular not to share drinks. When someone is sharing a drink with others, saliva and bodily fluids are left on the surface or inside the drink that can help promote the spread of disease.”

Additional deterrents suggested by Vassallo and the other specialists included rigorous enforcement of vaccination requirements by college administration, public health and physicians. Proper immunization is a concern on college campuses because of the number of students traveling from diverse locations. Because of this, international students complicate the threat of disease on campuses due to the vagueness and unreliability of foreign vaccination records, according to Jacobson.

This same logic also must be applied to domestic students traveling abroad, Turner said, in order to ensure campuses remain free of vaccine-preventable diseases.

“We have to remember there is also a huge push by American universities to encourage study abroad and travel abroad and, as many more U.S. students travel abroad to these areas, they can potentially bring endemic diseases back,” Turner said. “We cannot forget about the domestic student traveling and then importing diseases as well.”

Turner noted that optimal vaccination coverage on college campuses is the best way to help protect against outbreaks of rare and fatal diseases like serogroup B invasive meningococcal disease. This sentiment was shared by Martin, who added that campus outbreaks such as these provide strong support for proper vaccination efforts among at-risk populations.

“We now know that a well-vaccinated student body can prevent the introduction of mumps or meningococcal meningitis, or can slow the spread if an outbreak does begin,” Martin said. “As infectious disease professionals, these outbreaks provide insight into how well vaccines work when an infection is spreading in close quarters, particularly with more recently introduced vaccines. In addition, each event is a test of our public health response systems, allowing us to refine our tools for case-finding, communication and the ability to quickly vaccinate large groups of people.” — by David Costill and Dave Muoio

Editor’s note: A version of this article was previously published in Infectious Diseases in Children, a SLACK Incorporated publication.

• References:
• Cohn AC, et al. Clin Infect Dis. 2010;doi:10.1086/649209.
• Cortese MM, et al. Clin Infect Dis. 2008;doi:10.1086/529141.
• McNamara LA, et al. Pediatrics. 2015;doi:10.1542/peds.2014-4015.
• Quinlisk P, et al. MMWR Morb Mortal Wkly Rep. 2006;55(Dispatch):1-3.
• Reef S, et al. MMWR Morb Mortal Wkly Rep. 2006;55:1152-1153.
• Shaffner W, et al. National Foundation for Infectious Diseases. 2014; http://www.nfid.org/meningococcal-b. Accessed November 20, 2015.
• Soeters HM, et al. MMWR Mortal Wkly Rep. 2015;64:606-607.
• For more information:
• Aaron E. Glatt, MD, can be reached at Mercy Medical Center, 1000 North Village Ave., Rockville Centre, NY 11570.
• Sheldon Howard Jacobson, PhD, can be reached at the University of Illinois, 201 N. Goodwin Avenue (MC258), Urbana, IL 61801-2302; email: shj@illinois.edu
• Jessica R. MacNeil, MPH, can be reached at nipinfo@cdc.gov.
• Emily Martin, MPH, PhD, can be reached at etmartin@umich.edu.
• Patricia M. Quinlisk, MD, MPH, can be reached at patricia.quinlisk@idph.iowa.gov.
• James C. Turner, MD, can be reached at University of Virginia, PO Box 801094, Charlottesville, VA 22908; email: jct4w@virginia.edu.
• Angela Vassallo, MPH, MS, can be reached at Providence Saint John’s Health Center, 2121 Santa Monica Blvd., Santa Monica, CA 90404; email: angela.vassallo@providence.org.

Disclosures: Glatt, Jacobson, MacNeil, Martin, Quinlisk, Turner and Vassallo report no relevant financial disclosures.

Are antivirals an effective treatment for influenza in college students?

Antiviral treatments work, and can prevent influenza complications.

College campuses are a place where you can get extensive transmission because of close contact, and where diseases can take off and affect more individuals than would be the case elsewhere. This does not mean that treatment necessarily will affect further transmission — fairly weak evidence suggests that treating individuals will cut down on transmission. It may happen, but we really do not have good data saying that it will happen.

However, the same kind of criteria that the CDC has promulgated about treating people with underlying conditions and/or those who are developing severe complications extends to a university campus. We will have people with asthma who will have other underlying conditions, and those people should clearly be treated. The problem in treating other individuals is that at onset of disease it is difficult to say who will be developing severe complications. This is because in certain influenza viruses, such as H1N1, severe complications did occur in healthy adults without underlying conditions, but it was hard to predict at onset.

With that in mind, I would suggest that it is better to treat with antivirals. Given that the only side effect we have with antivirals are gastrointestinal complications — which can be helped by taking drugs early with food — we should err on the side of using more than using less to prevent complications. Our meta-analysis, which was published in The Lancet a few months ago, indicates quite clearly that you do prevent complications of influenza with antiviral treatment. The data are strongest, paradoxically, in those who do not have underlying conditions — in other words, in healthy adults. So, why not move from there to using the drugs in situations where you would be preventing complications, when you cannot predict who will get the complications?

Arnold S. Monto, MD, is a professor in the department of epidemiology at the University of Michigan School of Public Health. He can be reached at asmonto@umich.edu. Disclosure: Monto reports receiving fees from Biocryst GlaxoSmithKline and Roche. 

• Reference:
• Dobson J, et al. Lancet. 2015;doi:10.1016/S0140-6736(14)62449-1.

Evidence suggesting antivirals reduce influenza complications is flawed.

Evidence from manufacturer-sponsored trials shows that — if taken within 48 of hours of influenza-like illness symptoms appearing — Tamiflu (oseltamivir phosphate, Genentech) shortens symptom duration by about 16 hours. This effect is seen in people with infuenza or with similar illnesses caused by a variety of other agents, meaning that the action of the drug is not influenza virus-specific. The effect is not seen in children with asthma, or elderly patients with asthma, or in the general population, including those with underlying pathologies. In asymptomatic people, oseltamivir is likely to suppress symptoms from appearing.

There is no other robust evidence of a beneficial effect.

Oseltamivir consumption is associated with nausea, bowel changes, vomiting, renal and neurospychiatric harms. Relenza (zanamivir, GlaxoSmithKline) has a similar, but somewhat weaker profile, and is better tolerated. However, flaws in trial design mean that we have no experimental evidence of the effects of these drugs in affecting influenza complications (eg, pneumonia or person-to-person spread).

These conclusions are based on our 5-year review of 150,000 pages of regulatory material that we have made available. Both drugs have been tested in trials in both types of influenza viruses in current circulation (H1N1 and H3N2), and they are licensed for use against all viruses because they target a part of the virus surface that rarely mutates.

Tom Jefferson, MD, is an honorary research fellow at the Centre for Evidence-Based Medicine at the University of Oxford. He can be reached at jefferson.tom@gmail.com. Disclosure: Jefferson reports relationships with Boehringer Ingelheim, GlaxoSmithKline, IMS Health, Roche, Sanofi Pasteur and Sanofi-Synthelabo. 

• Reference:
• Jefferson T, et al. Cochrane Database Syst Rev. 2014;doi:10.1002/14651858.CD008965.pub4.