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From the Centers for Disease Control and Prevention
December 12, 2012

Influenza A (H3N2) Variant Virus-Related Hospitalizations—Ohio, 2012

JAMA. 2012;308(22):2331-2333. doi:10.1001/jama.2012.14341

MMWR. 2012;38:764-767.

1 table omitted. Available at http://www.cdc.gov/mmwr/PDF/wk/mm6138.pdf.

Since July 2012, 305 cases of infection with influenza A (H3N2) variant (H3N2v) virus containing the influenza A (H1N1)pdm09 M gene have occurred in multiple U.S. states, primarily associated with swine exposure at agricultural fairs.1 In Ohio, from July 28 to September 25, 2012, a total of 106 confirmed H3N2v cases were identified through enhanced surveillance. Whereas most H3N2v patients experienced mild, self-limited influenza-like illness (ILI), 11 of the Ohio patients were hospitalized, representing 69% of all H3N2v hospitalizations in the United States. Of these hospitalized H3N2v patients, six were at increased risk for influenza complications because of age or underlying medical conditions, including the only H3N2v-associated fatality reported in the United States to date. This report summarizes the epidemiology and clinical features of the 11 hospitalized H3N2v patients in Ohio. These findings reinforce the recommendation for persons at high risk for influenza complications to avoid swine exposure at agricultural fairs this fall.2 In addition, persons not at high risk for influenza complications who wish to reduce their risk for infection with influenza viruses circulating among pigs also should avoid swine and swine barns at agricultural fairs this fall.

Case Finding

In Ohio, testing of upper respiratory specimens was encouraged for patients with ILI (fever ≥100°F [≥37.8°C] with cough or sore throat), and epidemiologic linkages to a confirmed H3N2v case or attendance at an event where confirmed cases were identified (Ohio Department of Health, Health Alert Network: H3N2v information and recommendations, August 2, 2012).3 As part of the epidemiologic investigation, direct swine contact was defined as touching pigs; indirect swine contact was defined as visiting a swine barn at a fair without touching pigs. Respiratory specimens were confirmed as positive for H3N2v virus by testing at the Ohio Department of Health (ODH) laboratory using the CDC FLU real-time reverse transcription polymerase chain reaction (rRT-PCR) Dx Panel for influenza A (H3N2)v and at CDC by rRT-PCR and genetic sequencing.1 Information about hospitalized patients was collected using a standard CDC human infection with novel influenza A virus case report form, supplemented by review of medical records.

Case Reports

Patient A. A woman aged 61 years with type 2 diabetes, congestive cardiomyopathy, hypertension, and a past history of B-cell lymphoma, experienced cough and sneezing on August 10. Beginning 6 days earlier, she spent 4 days at a county fair where she visited a swine barn and had direct swine contact. Over the next 2 weeks, she experienced cough and fever and was treated with antibiotics for a sinus infection. On August 25, she sought care at an emergency department with worsening symptoms. The patient was transferred to a tertiary care center with hemodynamic instability and respiratory distress, and required mechanical ventilation. Her condition deteriorated, and she died on August 26. Blood cultures obtained on August 25 yielded Pseudomonas aeruginosa, and a nasopharyngeal swab was positive for H3N2v virus by rRT-PCR at ODH. Genetic sequencing of H3N2v virus from a clinical specimen from this patient at CDC was nearly identical to sequencing from several nonfatal H3N2v cases in Ohio, and from H3N2pM* viruses identified among pigs at fairs in Ohio.

Patient B. On August 2, a girl aged 4 years with cough-variant asthma requiring daily inhaled corticosteroids developed fever, 6 days after attending a county fair where she had direct swine contact. No close contacts of the patient were ill. The fever resolved after a few days, but diarrhea and cough developed, and the doses of her asthma control medications were increased. On August 11, the diarrhea continued, fever of 101°F (38.3°C) developed, and she was evaluated at an emergency department. Examination revealed dehydration, bilateral otitis media, and normal respiratory function. Chest radiography displayed hyperinflation of the lungs. The girl was treated with intravenous fluids for dehydration and ceftriaxone for otitis media, admitted overnight for hydration, and discharged the following day on amoxicillin. Before discharge, a nasopharyngeal specimen was tested using a commercial respiratory virus PCR panel; results were positive for influenza A (H3) and parainfluenza type 3 viruses. Further testing of a nasopharyngeal specimen was positive for H3N2v virus at ODH and CDC.

Of the 11 hospitalized H3N2v patients, case report forms for seven and hospital records for nine were available. The median age of the patients was 6 years (range: <1 year-61 years), and eight were female. Patients lived in eight counties and attended six fairs. Direct contact with swine prior to illness onset was reported by six patients (five children and one adult), and of these, one patient might have had direct contact with an ill pig. Indirect contact with swine during fair attendance was reported by four patients, including two children aged ≤2 years who were in strollers in swine areas, and two children with serious underlying medical conditions. Of the four children who reported indirect exposure to swine, exposure was reported to be ≥2 days for three. One child did not attend a fair, but had contact with a person who was exposed to pigs.

Among the 11 hospitalized H3N2v patients, six were considered at high risk for complications from influenza, because of age <5 years (three) or underlying medical conditions (two children, one adult). All 11 experienced fever, nine had cough, and seven had vomiting or diarrhea. One patient was admitted for an unrelated medical problem and tested for respiratory viruses because of prolonged fever and a new cough. Dehydration was the most common reason for admission. Two children were admitted for observation because of fever: one with acute lymphocytic leukemia and one with a petechial rash. Only one patient had received antiviral treatment before admission, four patients received oseltamivir treatment within 48 hours of illness onset, and six were treated with oseltamivir during hospitalization, but two were treated only for 1 day. Only one child required supplemental oxygen, and another was treated with humidified air. Patient A, who subsequently died, was the only patient requiring mechanical ventilation. Median length of hospital stay was 1 day (range: 1-3 days).

Reported by: Mary DiOrio, MD, Brian Fowler, MPH, Shannon L. Page, Richard Thomas, MPH, Kevin Sohner, Ohio Dept of Health; Andrew Bowman, DVM, Richard Slemons, PhD, Dept of Veterinary Preventive Medicine, Ohio State Univ; William G. Davis, PhD, Rebecca Garten, PhD, Stephen Lindstrom, PhD, Michael Jhung, MD, Timothy M. Uyeki, MD, Influenza Div, National Centers for Immunization and Respiratory Diseases; Celia Quinn, MD, EIS Officer, CDC. Corresponding contributor: Celia Quinn, MD, fyq6@cdc.gov, 614-728-6941.

Editorial Note: Of the hospitalized H3N2v patients described in this report, 10 of 11 were children, and six of 11 were considered at high risk for influenza complications because they were aged <5 years or had underlying medical conditions. All hospitalizations were brief and severe illness was observed only in the patient who died. Six patients reported direct contact with pigs at agricultural fairs. Among four patients with indirect swine exposure at fairs, three reported ≥2 days of fair attendance. One patient had no reported swine exposure. These findings support current recommendations that persons at high risk for influenza complications, including children aged <5 years and persons with chronic underlying medical conditions that confer high risk for severe complications from influenza, should avoid the swine barn and pens when attending agricultural fairs.2

Clinicians should be aware that rapid influenza diagnostic tests might not detect H3N2v virus.4 Specific H3N2v virus testing is available only at state public health laboratories and CDC. In two instances, rRT-PCR testing for H3N2v was positive after ≥10 days of illness in patients who were not immunosuppressed and did not receive antiviral treatment. Both patients had documented infection with other pathogens (P. aeruginosa in patient A and parainfluenza virus type 3 in patient B). Although P. aeruginosa bacteremia undoubtedly contributed to patient A's death, the role of parainfluenza virus infection in patient B's illness is unknown.

Of the six patients at high risk for influenza complications, two received antiviral treatment within 2 days after illness onset, while five of 11 patients were not treated at any time during their hospitalization. Clinicians should be aware that starting empiric antiviral treatment for 5 days with oral oseltamiviror inhaled zanamivir as soon as possible after onset of symptoms is recommended for any hospitalized patient with suspected influenza, including H3N2v, without waiting for testing results.2, 5 Beginning antiviral treatment as soon as possible also is recommended for outpatients with suspected influenza who are at high risk for influenza complications.2, 5 Five H3N2v patients reported here were not in a high risk group, highlighting the fact that H3N2v virus infection can cause illness resulting in hospitalization, even in otherwise healthy persons. The current interim recommendations from CDC also encourage early antiviral treatment of non-high–risk outpatients with suspected H3N2v virus infection.2

Public health professionals should be aware of the possibility of continued outbreaks of H3N2v virus related to agricultural fairs where swine are present. Pigs with influenza virus infection might be present at agricultural fairs, and swine might be asymptomatically infected with H3N2 or other influenza A viruses.6-7 Limited serologic studies indicate that children aged <10 years lack cross-protective antibodies to H3N2v virus.8 Persons, especially young children, might be infected with influenza viruses through direct or indirect swine exposure.9 Recommendations for preventing swine-to-human transmission of influenza viruses among the general population include staying away from pigs that appear ill (e.g., are coughing or sneezing, off feed, or lethargic) and washing hands with soap and water after contact with swine. Persons at high risk for influenza complications because of age (<5 years or ≥65 years) or underlying medical conditions should avoid swine and swine barns at agricultural fairs this fall. Persons not at high risk for influenza complications who wish to reduce their risk for infection with influenza viruses circulating among pigs also should avoid swine and swine barns at fairs this fall. Continued close communication and collaboration between human and animal health agencies for ongoing surveillance and investigation of influenza viruses among pigs and humans is needed to help guide and potentially expand measures to reduce the public health risk of H3N2v and related viruses.

Acknowledgments

Local health districts in Ohio; Sherry Sexton, Jeremy Budd, Ohio Dept of Health; Adena Greenbaum, MD, Fiona Havers, MD, Lizette Durand, DVM, EIS officers; Victoria Jiang, Su Su, Bo Shu, LaShondra Berman, Shannon Emery, Julie Villanueva, Alexander Klimov, Scott Epperson, Lyn Finelli, Susan Trock, Erin Burns, Emily Eisenberg, Joseph Bresee, Daniel Jernigan, Influenza Div, National Centers for Immunization and Respiratory Diseases, CDC.

What is already known on this topic?

Beginning in the summer of 2012, CDC reported increases in numbers of cases of human infections with influenza A (H3N2) variant (H3N2v) viruses associated with swine exposure at agricultural fairs. Nationwide, 305 cases, 16 hospitalizations, and one death across 10 states have been reported since July 2012.

What is added by this report?

Of 16 patients hospitalized with confirmed H3N2v virus infection, 11 were Ohio residents, including the only H3N2v-associated fatality to date. All but one of the Ohio patients were children, and six were considered high-risk for complications of influenza because they were aged <5 years or had underlying medical conditions; four high-risk persons became ill after indirect contact with pigs. These findings support current CDC recommendations that persons at high risk for complications of influenza should avoid exposure to swine at agricultural fairs this fall.

What are the implications for public health practice?

County and state fairs in the United States continue to occur through the month of October, highlighting the potential for continued cases of H3N2v virus infection. Persons at high risk for complications of influenza should avoid exposure to swine at agricultural fairs. Patients with suspected influenza, including H3N2v, who are hospitalized or at increased risk for influenza complications, should receive antiviral treatment with oral oseltamivir or inhaled zanamivir as soon as possible. Antiviral treatment also is encouraged for outpatients with suspected H3N2v who are not at increased risk for influenza complications.

REFERENCES: 9 Available.

*Infection of swine with H3N2 virus containing the influenza A(H1N1)pdm09 virus M gene is referred to as H3N2pM virus. Infection of humans with this virus is referred to as H3N2v virus.

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