This investigation included case finding during 30 July–13 August 2012, and a subsequent swine exhibitor household cohort study. To identify cases, we (1) surveyed County A community members who called the local health department reporting illness or concern for illness, using questionnaires conducted via phone interviews; (2) requested that all cases of ILI identified by physician offices, health clinics, and hospitals in County A be evaluated for influenza and reported to the local public health department; (3) interviewed all patients who were tested for influenza virus in County A since the start of Fair A; and (4) performed contact tracing of confirmed and probable cases of (H3N2)v infection. For the swine exhibitor household cohort study, we surveyed all swine exhibitors at Fair A and their household members for ILI and risk factors for (H3N2) v. We tested persons reporting ILI and calculated attack rates for confirmed and probable (H3N2)v infection.

Confirmed cases were defined as meeting clinical and exposure criteria, with positive laboratory results for (H3N2)v. Clinical criteria were defined as ILI (subjective fever or temperature >38.0°C plus either cough or sore throat). Exposure criteria included any one of the following occurring ≤7 days before symptom onset: (1) direct contact with swine (touching swine), (2) indirect contact with swine (spending time in a swine barn at Fair A), (3) no direct or indirect contact with swine but attendance at an event or location where confirmed cases had been identified (such as Fair A), or (4) no direct or indirect contact with swine but contact with a confirmed or probable case. Probable cases met the clinical and exposure criteria described above but either did not have diagnostic testing performed or had inconclusive results. Noncases did not meet clinical and exposure criteria or tested negative for (H3N2)v.

Cases were tested for influenza virus by using reverse transcription– polymerase chain reaction (RT-PCR) analysis at ODH or CDC laboratories, according to protocols reported previously [14–16]. Respiratory specimens were obtained using nasopharyngeal swabs from patients who had symptoms at the time of survey administration and from patients who were no longer symptomatic, if symptom onset was ≤10 days from the day the survey was administered [17, 18]. Negative test results obtained for persons >4 days after symptom onset were determined to be inconclusive, given the sensitivity limits of RT-PCR; these patients were categorized as probable cases [19, 20].

We asked all confirmed and probable cases about swine exposures, symptoms, and illness in all household members. For the exhibitor household cohort, we surveyed all household members and asked additional questions about potential risk factors for (H3N2)v infection, including status as a swine exhibitor or household member of exhibitor, attendance at Fair A, presence in the swine barn at Fair A, total number of days and time per day spent in the swine barn (≤4 hours vs >4 hours), hand washing after contact with swine (none to less than half the time vs more than half the time to always), and contact with any ill person since the beginning of Fair A. We also asked about underlying medical conditions, including asthma, other chronic lung disease, heart disease (excluding hypertension), diabetes, kidney disease, immunosuppressive condition, or neurologic disorders.

We investigated the potential for human-to-human transmission among all confirmed or probable cases with illness but without swine exposure or with illness onset >4 days after last swine exposure [3, 18, 21]. Contact tracing was conducted for all residents of County A with confirmed or probable (H3N2)v infection.

We compared confirmed and probable cases to noncases by using the χ² statistic for categorical variables and simple linear regression for continuous variables. Multivariable log-binomial regression with generalized linear models was used to identify risk factors associated with confirmed and probable case status [22]. Variables were chosen on the basis of their significance in bivariate analysis (P < .05) and biologic plausibility. The attack rate was calculated as the number of cases divided by the total number of people in the exhibitor household cohort. Given that households are important in the transmission of seasonal influenza viruses, we also performed multivariable regression, identifying households as cluster units [23, 24]. Analysis was performed in SAS 9.3. (Cary, North Carolina).

This investigation was conducted as part of a public health response and was not considered to be human subjects research in accordance with the federal human subjects protection regulations and the CDC’s Guidelines for Defining Public Health Research and Public Health Nonresearch.

This investigation provides a detailed epidemiological description of (H3N2)v infections associated with an agricultural fair in Ohio during the largest known outbreak of variant influenza virus infection in the United States. From July–September 2012, 306 confirmed cases from 10 states were reported to the CDC, and 107 (35%) were from Ohio (Figure 2) [3]. This investigation includes 20 confirmed cases identified in Ohio associated with Fair A and describes one of the earliest and largest clusters of confirmed cases in the state. At the time of this investigation, the magnitude of the nationwide outbreak, including its pandemic potential, was unknown. Understanding that younger age was a risk factor, identification of a relatively low attack rate, and a lack of evidence of sustained human-to-human transmission associated with Fair A provided essential information that shaped the local and national public health response to this outbreak.

After extensive case finding and contact tracing, we identified only 1 instance of likely human-to-human transmission; however, 2 of 8 persons evaluated for the potential of human-to-human transmission were not tested for (H3N2)v infection and may have been unidentified cases. Despite this, we found no evidence of sustained human-to-human transmission. Our results are consistent with findings from the national (H3N2)v outbreak, in which 14 instances of possible human-to-human transmission were identified out of 306 confirmed cases (excluding the case associated with Fair A) [3]. Therefore, most transmission events associated with Fair A likely occurred between swine and humans. Human infection with variant influenza viruses has been associated with human-swine interactions in various settings, including agricultural fairs, farms, and other events where livestock and humans interact [25–29]. Other outbreaks of variant influenza viruses have resulted in limited or no human-to-human transmission [1, 25, 27, 28, 30, 31].

We found that younger age was an independent predictor of illness in multivariable analysis. An investigation of a 2011 outbreak of (H3N2)v infection associated with an agricultural fair in Pennsylvania also showed that younger age, especially <10 years, was a potential risk factor for infection [32]. Several serologic studies have shown lower levels of cross-reactive antibodies to (H3N2)v among children <10 years, compared with older children and adults [33–35]. Lower levels of cross-protective antibody and the high level of swine exposure experienced by many children at agricultural fairs may place them at higher risk of (H3N2)v infection. Thus, prevention strategies to limit (H3N2)v infection should target children who may have exposure to swine. This is consistent with CDC guidelines for seasonal influenza, which identify children aged <5 years as being at higher risk for influenza-associated complications. Our data were not sufficient to stratify by age <10 years [36].

By establishing the exhibitor household cohort early in the outbreak, we were able to estimate an attack rate for confirmed (H3N2)v infection (2%) and probable cases (13%). These findings are consistent with the Pennsylvania (H3N2)v infection outbreak in 2011, in which 11% of members of a children’s agricultural club who attended the fair were suspected cases with symptoms consistent with influenza [32]. But attack rates, even in similar outbreaks or epidemics, can vary depending on the population, setting (eg, school, community, or nursing home), and virus characteristics.

Approximately 150 million people attend fairs in North America every year, and several national public health recommendations were shaped in part by results from this investigation (Marla Calico, International Association of Fairs and Expositions, personal communication, December 2012). Children aged <5 years, adults aged ≥65 years, pregnant women, and people whose underlying medical conditions place them at high risk for influenza-associated complications were recommended to avoid swine and swine barns during the summer and fall of 2012 [37]. People in these categories are known to be at higher risk of developing complications from seasonal influenza and were advised to take care to prevent (H3N2)v infection [38]. This investigation did not find older age or the presence of underlying medical conditions to be significant risk factors for case status, but this may have been due to the small number of older individuals and those with medical problems in our cohort. Recommendations to fair organizers included posting signs encouraging hand washing after touching swine and monitoring the health of swine at fairs [36]. In addition, healthcare providers were encouraged to have a low threshold to test for influenza virus, especially in instances of ILI outside of the influenza season and when close contact with swine was reported [38].

There are several limitations to this investigation. First, swine exposure was widespread among the exhibitor household cohort, with 92% of all individuals reporting direct exposure to swine. This made it difficult to assess varying degrees of swine exposure as a risk factor for illness and might explain why total swine exposure time and exposure intensity (direct vs indirect) were not significant risk factors in this analysis. Second, timely testing among cases meeting exposure and clinical criteria was limited, resulting in a large number of probable cases whose illness etiology could not be confirmed or refuted. Third, testing of swine was performed at Fair A separately from this investigation, and additional details regarding clinical signs in swine, the timing of illness among swine as compared to humans, and interactions between ill swine and fair attendees was unknown. Additional details would be helpful in understanding the animal-to-human transmission dynamics of (H3N2)v during this outbreak. Fourth, for most of this analysis, we combined confirmed and probable cases, and thus misclassification of viral infection is possible. While it is unlikely that every probable case was due to (H3N2)v infection, it is likely that confirmed cases underestimate true disease incidence, since not all those who are infected are symptomatic, seek healthcare, or are tested for influenza virus. During seasonal influenza epidemics, laboratory-confirmed cases of influenza often represent a fraction of all infections [39]. Similarly, it is estimated that there are approximately 200 cases of (H3N2)v infection for every reported case [40]. With active case finding and active surveillance, we identified >4 probable cases for each confirmed case.

During August–September 2012, this investigation in Ohio provided data for public health decision making in response to the larger outbreak of (H3N2)v infection in 10 states. The low severity, relatively low attack rate, and lack of sustained human-to-human transmission helped determine that this virus had low pandemic potential, an insight that helped shape a focused public health response to this outbreak. Results from this study also helped reinforce specific recommendations to fair attendees; for example, finding that younger age was an independent predictor of illness supported the recommendation that children aged <5 years avoid swine throughout the fair season. Vigilant surveillance during future agricultural fair seasons will be essential to determine whether ongoing transmission of (H3N2)v between swine and humans continues or whether efficient human-to-human transmission of variant viruses emerges.