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

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

Weekly

September 28, 2012 / 61(38);764-767

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 (Table, patient 11). 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 (Table, patient 6). 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 and="and" class="callout-pink" eight="eight" female="female" span="span" were="were" year="year" years="years">Table
). 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 11="11" 1="1" 48="48" a="a" acute="acute" admission.="admission." admission="admission" admitted="admitted" adult="adult" air.="air." all="all" an="an" and="and" another="another" antiviral="antiviral" because="because" before="before" but="but" child="child" children="children" common="common" conditions="conditions" cough.="cough." cough="cough" day.="day." day="day" days="days" dehydration="dehydration" diarrhea.="diarrhea." died="died" during="during" experienced="experienced" fever:="fever:" fever="fever" for="for" four="four" had="had" hospital="hospital" hospitalization="hospitalization" hours="hours" humidified="humidified" illness="illness" length="length" leukemia="leukemia" lymphocytic="lymphocytic" mechanical="mechanical" median="median" medical="medical" most="most" new="new" nine="nine" observation="observation" of="of" one="one" only="only" onset="onset" or="or" oseltamivir="oseltamivir" oxygen="oxygen" p="p" patient="patient" patients="patients" petechial="petechial" problem="problem" prolonged="prolonged" range:="range:" rash.="rash." reason="reason" received="received" required="required" requiring="requiring" respiratory="respiratory" seven="seven" six="six" stay="stay" subsequently="subsequently" supplemental="supplemental" tested="tested" the="the" three="three" treated="treated" treatment="treatment" two="two" underlying="underlying" unrelated="unrelated" ventilation.="ventilation." viruses="viruses" vomiting="vomiting" was="was" were="were" who="who" with="with" within="within" years="years">

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 aged="aged" agricultural="agricultural" all="all" among="among" and="and" at="at" attendance.="attendance." attending="attending" avoid="avoid" barn="barn" brief="brief" children="children" chronic="chronic" complications="complications" conditions.="conditions." conditions="conditions" confer="confer" contact="contact" current="current" days="days" died.="died." direct="direct" exposure.="exposure." exposure="exposure" fair="fair" fairs.="fairs." fairs="fairs" findings="findings" for="for" four="four" from="from" had="had" high="high" hospitalizations="hospitalizations" i="i" illness="illness" in="in" including="including" indirect="indirect" influenza="influenza" medical="medical" no="no" observed="observed" of="of" one="one" only="only" or="or" patient="patient" patients="patients" pens="pens" persons="persons" pigs="pigs" recommendations="recommendations" reported="reported" risk="risk" severe="severe" should="should" six="six" support="support" swine="swine" that="that" the="the" these="these" three="three" underlying="underlying" was="was" were="were" when="when" who="who" with="with" years="years">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 oseltamivir or 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 antibodies="antibodies" cross-protective="cross-protective" h3n2v="h3n2v" i="i" lack="lack" to="to" virus="virus" years="years">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 agencies="agencies" agricultural="agricultural" also="also" among="among" and="and" animal="animal" at="at" avoid="avoid" barns="barns" between="between" circulating="circulating" close="close" collaboration="collaboration" communication="communication" complications="complications" conditions="conditions" continued="continued" expand="expand" fairs="fairs" fall.="fall." for="for" guide="guide" h3n2v="h3n2v" health="health" help="help" high="high" human="human" humans="humans" infection="infection" influenza="influenza" investigation="investigation" is="is" measures="measures" medical="medical" needed="needed" not="not" of="of" ongoing="ongoing" or="or" p="p" persons="persons" pigs="pigs" potentially="potentially" public="public" reduce="reduce" related="related" risk="risk" should="should" surveillance="surveillance" swine="swine" the="the" their="their" this="this" to="to" underlying="underlying" viruses.="viruses." viruses="viruses" who="who" wish="wish" with="with" years="years">

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.

References

1. CDC. Evaluation of rapid influenza diagnostic tests for influenza A (H3N2)v virus and updated case count—United States, 2012. MMWR 2012;61;619–21.
2. CDC. Interim information for clinicians about human infections with H3N2v virus. Atlanta, GA: US Department of Health and Human Services, CDC; 2012. Available at http://www.cdc.gov/flu/swineflu/h3n2v-clinician.htm. Accessed September 21, 2012.
3. CDC. Interim guidance on case definitions to be used for investigations of influenza A(H3N2)v virus cases. Atlanta, GA: US Department of Health and Human Services, CDC; 2012. Available at http://www.cdc.gov/flu/swineflu/case-definitions.htm. Accessed September 18, 2012.
4. Balish A, Garten R, Klimov A, Villanueva J. Analytical detection of influenza A(H3N2)v and other A variant viruses from the USA by rapid influenza diagnostic tests. Influenza Other Respi Viruses 2012; doi:10.1111/irv.12017.
5. CDC. Antiviral agents for the treatment and chemoprophylaxis of influenza, recommendations of the Advisory Committee on Immunization Practices (ACIP). MMWR 2011; 60(No. RR-1).
6. Gray G, Bender J, Bridges C, et al. Influenza A(H1N1) pdm09 virus among healthy show pigs, United States. Emerg Infect Dis 2012;18:1519–21.
7. Bowman AS, et al. Subclinical influenza A virus infection among pigs exhibited at agricultural fairs, Ohio, USA, 2009–2011. Emerg Infect Dis. In press December 2012.
8. CDC. Antibodies cross-reactive to influenza A (H3N2) variant virus and impact of 2010–2011 seasonal influenza vaccine on cross-reactive antibodies—United States. MMWR 2012;61;237–41.
9. Wong, K, Greenbaum A, Moll M, et al. Outbreak of influenza A (H3N2) variant virus infection among attendees of an agricultural fair, Pennsylvania, USA, 2011. Emerg Infect Dis. In press October 2012.

* 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.