Abstract
Hand-foot-and-mouth disease (HFMD), which is typically seen in the younger pediatric population, is uncommon in older adolescent and young adult populations. We report on an atypical outbreak of HFMD among college students at a mid-size university in the mid-Atlantic U.S. The outbreak included 138 qualifying cases of HFMD among students at the institution between August and November 2018. All tested samples were positive for CVA6, a less common cause of HFMD. Signs and symptoms and campus mitigation strategies are described. This case report aims to highlight an atypical outbreak of HFMD for clinicians who care for older adolescent and college-aged patients in primary care and community settings, and may see cases and/or outbreaks of HFMD in these populations.
Keywords
Introduction
Hand-foot-and-mouth disease (HFMD) is a highly contagious viral illness predominantly seen in the younger pediatric population and most commonly caused by enterovirus 71 and coxsackievirus A16.1,2 Some uncommon recent HFMD outbreaks have been atypical: caused by coxsackievirus A6 (CVA6) and affecting older adolescents and young adults.1,3 In the fall of 2018, several U.S. college and university campuses reported HFMD outbreaks.4-6 This report describes the 2018 HFMD outbreak on one of these campuses (a mid-size university in the mid-Atlantic U.S.), including timeline, clinical presentation and university response.
HFMD typically affects children less than 10 years of age, with the largest incidence in those 5 years of age or younger.2,7 In North America, HFMD outbreaks are most common in the spring, summer and fall seasons.2,7 HFMD is transmitted via respiratory droplets, and the fecal-oral and oral-oral routes.2,7 Patients with HFMD are most infectious during the first week of illness.2,7 Symptoms of classic HFMD include a low-grade fever, painful oral lesions, and a maculopapular rash on the palms and soles.2,8 Atypical symptoms, including eczema coxsackium (erythematous papulovesicles extending beyond the palms, soles and mouth that can complicate atopic dermatitis), 9 desquamation, and cheek, trunk or buttock involvement may occur. 2 HFMD is usually a mild and self-limiting illness, with lesions resolving after approximately 7 to 10 days.2,7,8 Treatment is supportive.2,7 Rarely, cardiopulmonary and neurological complications, including aseptic meningitis and acute flaccid paralysis, can occur. 2 Currently in the United States, there is no available vaccine to prevent HFMD. 7
CVA6 has emerged in recent years as a cause of HFMD, even in the winter, 2 particularly among older adolescents and young adults.1,3,10-12 Recent outbreaks of HFMD affecting young adults in the United States have been attributed to CVA6,3,11,12 including the one described in this report. CVA6-associated HFMD often results in atypical8,9,11 and/or severe manifestations1,2,9,10,13 that may require hospitalization.1,12,13
HFMD is well-described in the younger pediatric population. However, literature is limited on HFMD outbreaks in older adolescents and young adults, including college students, and clinicians who care for these populations may be challenged to diagnose and manage atypical HFMD presentations. This case report describes an outbreak of HFMD caused by a less common strain and in an atypical population of college students, including presentation, mitigation strategies, and recommendations. The university’s institutional review board approved this effort as exempt research.
Case Overview and Characteristics
In late August and early September 2018, as students began fall classes around the same time as HFMD outbreaks on other college campuses in the East were reported,4-6 the first 5 cases of HFMD were seen by clinical staff at the university’s student health center (SHC). Over the next few weeks, the case numbers increased exponentially, and an outbreak of HFMD was declared by the local health department. There were 138 qualifying cases of which the SHC was aware during the outbreak, which lasted approximately 2 months and ended on November 1, 2018 per local and state health authorities. No cases of the HFMD outbreak were evaluated by the university’s student health center after this date.
Undergraduate students who were assigned male sex at birth and lived in on-campus university housing comprised the largest sample of cases (Table 1). The average age of students with HFMD during the outbreak was 19.2 years. The majority of cases (75.4%) occurred in students who lived in on-campus university housing. These on-campus cases clustered in university student housing buildings located in the same region on campus. Among cases in on-campus student housing, most occurred in buildings with suites consisting of 2 to 4 bedrooms, a shared bathroom and kitchen (76.0%). Several clusters of cases, including those both on- and off-campus, involved students who participated in club or varsity sports. Other, smaller clusters of cases were noted among students who reported participating in other university clubs or organizations, including Greek letter organizations (eg, sororities and fraternities). Some students with HFMD reported participating in both university sport and other clubs or organizations, and some reported a known exposure to HFMD from a roommate, classmate or other close contact.
SHC HFMD Case Demographic Information.
Abbreviations: HFMD, Hand-foot-and-mouth disease; SHC, student health center.
During the HMFD outbreak, affected patients typically sought evaluation by the SHC (either in person or via remote triage with a provider) within 2 to 4 days of symptom onset. Lesions (59.4%), fever (71.0%), and sore throat (81.2%) were the most common subjective symptoms reported by patients included in the outbreak. The hand and/or arm were the most frequently reported locations for lesions (76.8%), followed by foot (51.2%), face/head (19.5%), and mouth (18.3%). Lesions were commonly described by patients as “painful,” “burning,” “tingling,” “itchy,” and/or with “peeling skin.” See Table 2 for clinical signs and symptoms during the outbreak. On physical exam, providers mostly described lesions presenting as small, erythematous, and either vesicular, pustular, papular, blistered and/or macular. Providers also noted the location of the lesions, which were mostly consistent with subjective report, as well as presence of any lymphadenopathy, which was noted in the cervical region in 20.3% of cases.
SHC HFMD Signs and Symptoms.
Abbreviations: HFMD, Hand-foot-and-mouth disease; SHC, student health center.
Percentages of lesion location are based on total sample of 82 who reported lesions present; other percentages in table are out of 138 total cases.
Includes face, eyebrows, cheeks, scalp.
Of the cases documented by the SHC during the outbreak, only 1 was referred to the Emergency Department (ED). This patient presented with lesions in the throat consistent with HFMD and meningism, including a stiff neck and photophobia on exam. The patient’s lumbar puncture was negative for meningitis. One case documented by the SHC during the outbreak was noted to be a repeat case, and 2 cases were noted by providers to be “severe” with symptoms lasting 10 or more days. Five cases (3.6%) were also positive for Streptococcus pyogenes pharyngitis on either rapid test or throat culture, and 4 additional cases (2.9%) were treated presumptively for S. pyogenes pharyngitis by the evaluating clinician.
Mitigation Strategies
SHC management worked closely with clinic staff to formally track cases with the use of a standardized clinic form, and educate patients and the broader campus community, including through handouts, emails, flyers, campus TV ads, social media outreach and website postings that addressed HFMD and symptom recognition, preventive measures (eg, handwashing) and infection control (eg, cleaning recommendations). The director of university student health and wellness collaborated closely with university leadership and the university-affiliated hospital epidemiology and infection control department during the outbreak. University facilities performed additional cleaning of the on-campus student housing communal bathrooms, kitchens and other shared spaces.
The city health department was closely involved in the university outbreak response. Samples from 4 outbreak cases were analyzed by the state health department, and all were positive for CVA6. The samples sent for analysis were selected at random from cases with high clinical suspicion for HFMD, per health department instruction.
Discussion
Though typically seen in young children, HFMD can affect older adolescent and young adult populations,3-6,10,12 and outbreaks can occur, particularly in settings that are densely populated with high contacts, such as college campuses.4-6 However, clinicians in primary care and community health settings may be challenged to identify atypical presentations of HFMD, particularly among older adolescents and young adults who are not commonly affected.
Sore throat was the most common symptom reported by patients included in the outbreak (81.2%), which is consistent with other literature indicating sore throat as the most common presenting symptom of HFMD. 14 However, 40.6% of HFMD cases in the outbreak did not have lesions at the time of presentation, which is usually a feature of the illness. 2 This may be due to the atypical presentation, or to patients seeking care prior to onset of lesions. It is important for providers to consider HFMD on the differential list when evaluating college-aged patients with these symptoms.
It is critical for clinicians in primary care and community health to be aware of the possibility of a HFMD diagnosis in an older adolescent or young adult patient who may present with atypical symptoms, such as described in this report. Clinicians should receive adequate education on the risk and presentation of HFMD in older adolescent and young adult populations. Clinics in settings at higher risk for outbreaks, such as college campuses, should develop protocols to address HFMD outbreaks, including procedures for collaborating with infectious disease and public health experts, notifying and communicating with patients, parents/guardians, and the community, and outbreak mitigation and intervention measures, such as hand hygiene and enhanced cleaning of shared spaces.
In this outbreak, there were 9 cases (6.5%) that were treated for either a positive (3.6%) or presumptive (2.9%) S. pyogenes pharyngitis co-infection. Though we did not identify any literature regarding a connection between HFMD and S. pyogenes upon a brief search, this would be an area of interest for future research.
There have been no further outbreaks of HFMD on our campus to date. There is evidence suggesting that COVID-19 related non-pharmaceutical interventions (eg, school closures, lockdowns, restricted population movement) were associated with a decreased HFMD incidence in China in 2020. 15 Thus, it is possible that COVID-related infection control measures instituted on our campus are associated with the absence of further HFMD outbreaks. Nonetheless, other college campuses have reported recent outbreaks of HFMD,16,17 reiterating the importance of clinicians to be aware of the risk of HFMD and outbreaks in this population, and be prepared to address these.
There are some limitations to this work. Only qualifying cases that were known to the SHC are included in this report, but there were likely other cases on campus that were not evaluated by or known to student health. Additionally, some students may have had known exposure to HFMD through a university contact, (eg, a roommate, organization or club or sport participant) but did not report that information to the SHC. Reported participation in university organization, club or sport may or may not have been associated with patient acquisition of HFMD. The use of our clinician-developed HFMD standardized tracking form was useful in collecting consistent information, however, some case forms were incomplete due to patient or provider omission. Additional education for providers and students on form process completion may improve data documentation for future outbreaks. The effectiveness of HFMD outbreak mitigation strategies is also an area of future research.
Conclusion
Though uncommon, cases of HFMD have been identified beyond the typical younger child population in recent years, including among older adolescents and young adults3-6,10,12 that are commonly caused by CVA6.1,3,10-12 Providers in primary care and community health settings who care for older adolescents and young adults, including college students, must be aware of HFMD and its possible and atypical presentation in these populations, as well as the risk for outbreaks in certain high-risk settings, and be prepared to address these.
Footnotes
Declaration of Conflicting Interests
The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.
Funding
The author(s) received no financial support for the research, authorship, and/or publication of this article.
