Early Release

August 10, 2012 / 61(Early Release);1-3

Previous reports have described cases of influenza A (H3N2) variant (H3N2v) virus* infection with the influenza A (H1N1)pdm09 M gene detected in the United States during July 2011–July 2012 (1–3). This report provides 1) an update on the number of reported cases of H3N2v infections from July 12 to August 9, 2012, in the United States, 2) an updated results interpretation for the CDC Flu Real-Time Reverse Transcription Polymerase Chain Reaction (rRT-PCR) Dx Panel for A(H3N2)v for public health laboratories, and 3) an evaluation of rapid influenza diagnostic tests for the detection of H3N2v viruses.
From July 12 to August 9, a total of 153 cases of H3N2v infections were reported in Indiana (120 cases), Ohio (31), Hawaii (one), and Illinois (one). Of the 138 reported cases for which demographic information was available, 128 (93%) occurred in persons aged <18 10="10" 152="152" 27="27" 7="7" a="a" additional="additional" adults.="adults." age="age" agricultural="agricultural" all="all" and="and" as="as" at="at" cases="cases" counties="counties" deaths="deaths" direct="direct" exposed="exposed" exposure="exposure" fairs.="fairs." found="found" from="from" hawaii.="hawaii." hawaii="hawaii" hospitalized="hospitalized" illinois="illinois" illness="illness" in="in" indiana="indiana" indirect="indirect" job="job" majority="majority" median="median" no="no" occurred.="occurred." occurred="occurred" of="of" ohio="ohio" on="on" or="or" p="p" patient="patient" patients="patients" persons="persons" reported="reported" resided="resided" result="result" swine="swine" the="the" their="their" to="to" two="two" was="was" were="were" years.="years." years="years"> H3N2v viruses can be detected by qualified U.S. public health laboratories using the CDC Flu rRT-PCR Dx Panel. Initially, if specimens tested positive for influenza A, H3, and pandemic influenza A markers and negative for H1 and pandemic H1 markers, they were reported as inconclusive until confirmed as influenza A (H3N2)v at the CDC laboratory (1). On August 7, CDC updated the results interpretation of the CDC Flu rRT-PCR Dx Panel for H3N2v for public health laboratories. Specimens with these findings may now be reported as "presumptive positive for influenza A (H3N2)v virus" and, for the ongoing investigations, cases with presumptive-positive test results at the state or local public health laboratory will now be classified as confirmed, as are those cases confirmed at CDC.
The CDC Flu rRT-PCR Dx Panel is available in public health laboratories but is not a point-of-care test available to clinicians. Rapid influenza diagnostic tests (RIDTs) frequently are used for the diagnosis of influenza infection in clinical settings, and the recent outbreaks of H3N2v virus (2,3) have highlighted the need to evaluate commercially available, widely used RIDTs for their ability to detect H3N2v viruses. As an initial assessment, CDC conducted an evaluation of seven FDA-cleared RIDTs with seven H3N2v viruses (Table 1). Five 10-fold dilutions in physiological saline of each virus grown in Madin-Darby Canine Kidney (MDCK) cells were tested with all of the RIDTs in duplicate. Tests with BinaxNOW, Directigen, FluAlert, QuickVue, and Sofia were performed according to the procedures in the kit inserts for nasal washes or aspirates. Xpect tests were performed according to their procedure for nasal washes and swab specimens transported in liquid media. For the Veritor test, 100 µL of diluted specimen was added directly to the reagent tube. Positive and negative controls contained in each RIDT were run before testing the viruses in the study to verify performance of each assay lot, with the exception of FluAlert, which does not provide controls.
Only four of seven RIDTs in this study (Directigen, Sofia, Veritor, and Xpect) detected all influenza A (H3N2)v viruses (Table 2). BinaxNOW detected five of seven, and QuickVue detected three of seven. FluAlert detected only one of seven.

Reported by

Shawn Richards, Indiana State Dept of Health. Craig Conover, MD, Illinois Dept of Public Health. Mary DiOrio, MD, Ohio Dept of Health. Sarah Park, MD, Hawaii Dept of Health. Amanda Balish, MPH, Rebecca Garten, PhD, Alexander Klimov, PhD, Julie Villanueva, PhD, Lynnette Brammer, MPH, Scott Epperson, MPH, Lenee Blanton, MPH, Matt Biggerstaff, MPH, Michael Jhung, MD, Lyn Finelli, PhD, Joseph Bresee, MD, Influenza Div, National Center for Immunization and Respiratory Diseases, CDC. Corresponding contributor: Lynnette Brammer, lbrammer@cdc.gov, 404-639-3747.

Editorial Note

The H3N2v viruses identified since July 12, 2012, are similar to the 13 H3N2v viruses identified during July 2011–April 2012 (1); all sequenced viruses had the M gene from the influenza A (H1N1)pdm09 virus. As of August 9, all H3N2v patients for whom contact information was available reported contact with swine or attended an agricultural fair where swine were present. During 2011, evidence of limited human-to-human transmission of H3N2v was observed in some cases, and human-to-human transmission might occur in the current outbreak. Enhanced surveillance for influenza H3N2v virus infection is indicated, especially in regions and states with confirmed H3N2v cases. The initial goal of enhanced surveillance is to detect the source and geographic spread of these viruses, but once cases are detected, particular emphasis should be placed on detection of ongoing transmission within the community through investigation of close contacts of patients with confirmed cases. In addition, surveillance in hospitals will be important to determine whether severe illnesses are occurring as a result of H3N2v infections.
The predominance of children among persons with confirmed H3N2v infections is consistent with serologic studies that found children less likely to have cross-protective antibodies than adults (4). However, confirmation of cases in adults highlights the fact that persons of any age can be infected. Persons who are at increased risk for influenza complications (e.g., those with underlying chronic medical conditions, or who are pregnant, or aged <5 have="have" i="i" immune="immune" or="or" systems="systems" weakened="weakened" who="who" years="years">5
]) should avoid exposure to pigs and swine barns this summer, particularly if ill swine have been identified. Persons with increased risk for complications who develop influenza-like illness should see their health-care provider promptly to determine whether treatment with antiviral medications is warranted. Clinicians should consider antiviral treatment with oral oseltamivir or inhaled zanamivir in patients with suspected or confirmed H3N2v infection. Antiviral treatment is most effective when started as soon as possible after influenza illness onset (5). The sensitivity of RIDTs to detect seasonal influenza viruses compared with virus isolation or rRT-PCR varies among commercial kits but has been shown to be low in some reports (6–9). In this evaluation of seven RIDTs, the ability to detect H3N2v virus varied substantially among the tests. This evaluation emphasizes the fact that a negative RIDT result should not be considered as conclusive evidence of lack of infection with influenza A (H3N2)v. More data are needed on the clinical performance of all RIDTs in detecting H3N2v virus in various respiratory specimens. Results from RIDTs, both positive and negative, always should be interpreted in the broader context of the circulating influenza strains present in the area, level of clinical suspicion, severity of illness, and risk for complications in a patient with suspected infection. Clinicians should minimize the occurrence of false RIDT results by strictly following the manufacturer's instructions, collecting specimens soon after onset of influenza-like illness (ideally within the first 72 hours), and confirming RIDT results by sending a specimen to a public health laboratory (10). Additional CDC guidance on interpretation of RIDTs for testing of patients with suspected H3N2v infection is available at http://www.cdc.gov/flu/swineflu/h3n2v-testing.htm.
Specimens from patients with influenza-like illness in whom H3N2v is suspected should be sent to public health laboratories for additional diagnostic testing. Public health laboratories are requested to continue to contact the CDC Influenza Division immediately when they identify these viruses to coordinate transfer of the specimen to CDC for additional testing.

References

Lindstrom S, Garten R, Balish A, et al. Human infections with novel reassortant influenza A(H3N2)v viruses, United States, 2011. Emerg Infect Dis 2012;18:834–7.
CDC. Update: influenza A (H3N2)v transmission and guidelines—five states, 2011. MMWR 2012;60:1741–4.
CDC. Notes from the field: outbreak of influenza A (H3N2) virus among persons and swine at a county fair—Indiana, July 2012. MMWR 2012;61:561.
CDC. Antibodies cross-reactive to influenza A (H3N2) variant virus and impact of 2010–11 seasonal influenza vaccine on cross-reactive antibodies—United States. MMWR 2012;61:237–41.
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).
Hurt AC, Alexander R, Hibbert J, Deed N, Barr IG. Performance of six influenza rapid tests in detecting human influenza in clinical specimens. J Clin Virol 2007;39:132–5.
Faix DJ, Sherman SS, Waterman SH. Rapid-test sensitivity for novel swine-origin influenza A (H1N1) virus in humans. N Engl J Med 2009;361:728–9.
Ginocchio CC, Zhang F, Manji R, et al. Evaluation of multiple test methods for the detection of the novel 2009 influenza A (H1N1) during the New York City outbreak. J Clin Virol 2009;45:191–5.
Uyeki TM, Prasad R, Vukotich C, et al. Low sensitivity of rapid diagnostic test for influenza. Clin Infect Dis 2009;48:e89–92.
CDC. Guidance for clinicians on the use of rapid influenza diagnostic tests. Atlanta, GA: US Department of Health and Human Services, CDC; 2011. Available at http://www.cdc.gov/flu/professionals/diagnosis/clinician_guidance_ridt.htm. Accessed August 9, 2012.

* Influenza viruses that circulate in swine are called swine influenza viruses when isolated from swine, but are called variant viruses when isolated from humans. A variant virus (human isolate) might or might not have the M gene from the influenza A (H1N1)pdm09 virus, along with other genetic changes. Seasonal influenza A (H3N2) viruses that circulate worldwide in the human population have significant antigenic and genetic differences from influenza A (H3N2) viruses circulating in swine. Additional information is available at http://www.who.int/influenza/gisrs_laboratory/terminology_ah3n2v/en/index.html