Speeding Up Subtyping May Catch More Bird Flu

The typical timeline for subtyping influenza A specimens has sped up to help identify emerging avian flu cases in the United States, and an expert shares strategies for meeting the increased demand for testing.

In response to this season’s high flu activity and the ongoing avian flu outbreaks, the Centers for Disease Control and Prevention (CDC) has advised clinicians and laboratories to conduct subtype testing on all influenza A–positive specimens from hospitalized patients, especially those in intensive care settings, according to the health advisory.

Accelerated testing to distinguish avian flu from cases of seasonal influenza A should be done within 24 hours of hospital admission, if possible, in order to help optimize patient care and assist with infection control and case investigations, the CDC noted.

Options for Testing

The advisory acknowledged that most influenza tests ordered in clinical settings do not distinguish avian flu from seasonal flu. Specimens from patients that are positive for the influenza A virus but negative for seasonal flu subtypes such as A(H1) and A(H3) should be prioritized for further testing in a public health laboratory, according to the advisory.

Some commercial laboratories offer subtyping for influenza A(H5) in the clinical setting, and the US Food and Drug Administration (FDA) maintains a list of typing and subtyping tests for influenza A.

Speedier Subtyping Improves Outcomes

“Given the high burden of respiratory infections in the winter, expedited subtyping of influenza is essential to differentiating seasonal respiratory viruses such as flu with H3 or H1 subtypes, SARS-CoV-2, or RSV [respiratory syncytial virus] from other more pathogenic strains, such as flu with a H5 subtype,” said Rebecca Yee, MD, an assistant professor of pathology at The George Washington University in Washington, DC, in an interview.

“Certain subtypes, like avian or swine-origin influenza, warrant notification of public health authorities to ensure prompt contact tracing and surveillance for exposed individuals,” said Yee, who also serves as chief of microbiology and clinical microbiology laboratory director at The George Washington University Hospital, Washington, DC.

Clinical Challenges 

“Currently, the biggest challenge in flu subtyping in the clinical setting is that there are no FDA-approved tests that can subtype H5,” Yee told Medscape Medical News. “Bringing on a test for H5 subtyping is not as easy as it sounds. Every test that a clinical laboratory performs need to be validated or verified to ensure high performance characteristics, such as sensitivity and specificity, are met,” said Yee. “Given that there are no FDA-approved tests that can detect H5 virus, clinical laboratories need to have the expertise and capacity to bring on a laboratory-developed test that is rigorously validated to ensure accuracy,” she noted.

Fortunately, several national reference laboratories have a test to detect and subtype influenza A (H5) virus, and a clinical laboratory can contact their state or local public health laboratory to see whether they can support the volume or turnaround time, Yee said. “There may also be state-specific guidance to assist the laboratories and clinicians,” she added.

Meanwhile, FDA-approved tests can determine H3 vs H1 subtypes, often in < 2 hours, Yee said. Although these tests only subtype H3 or H1, they represent a majority of the circulating strains, and a patient who tests positive for the H3 subtype is less likely than a patient with H1 to be infected with H5, Yee noted.

Another clinical challenge to expedited flu subtyping is reimbursement, which is not high for flu subtyping panels, said Yee. “One way to mitigate this concern during this period is for clinicians to establish a testing algorithm specific for their patient population that is feasible for the laboratory in terms of cost but also, staffing demands. For example, respiratory testing in certain high-risk patient groups such as those in the ICU [intensive care unit], immunocompromised, or with appropriate exposure get automatic testing on the full syndromic panel with subtyping, while other patients may get reflex testing for influenza-positive samples,” she said.

“One of the lessons learned from the COVID-19 pandemic response was that the lack of available testing at the start of the pandemic severely hindered timely diagnosis, delayed critical public health interventions, and compromised patient care, leading to prolonged transmission and overwhelmed healthcare systems,” Yee told Medscape Medical News.

Managing Demand

“While it is too soon to see the impact of the new tests being offered for H5 subtyping, we are still at a better place this time around since patients and hospitals have several options to get testing performed,” she noted. Although laboratories may not be able to bring on a test for subtyping themselves, they continue to have the capacity to send tests to reference laboratories, she said. “Having these tests already available at the reference labs allows hospitals to develop a clear plan and workflow for testing to minimize delay of results, since we already know the appropriate specimen type, collection, and shipping requirements,” Yee added.

“Clinicians need to work very closely with the clinical microbiology laboratory as well as hospital administration to understand how to handle surges in testing demand,” Yee told Medscape. “Specifically, the clinical laboratory needs to be able to have enough staffing, reagent availability, and instrument capacity to provide testing,” she said.

When it comes to flu testing and subtyping, there is no one-size-fits-all workflow, said Yee. Stakeholders at each hospital need to understand the impact of increased testing on a laboratory’s workflow and budget, she said. Open communication and collaboration are needed across hospital teams to meet reasonable efficiency levels, whether by developing a modified testing algorithm or bringing on a new test, Yee said.

Yee had no financial conflicts to disclose.