On the heels of monkeypox, avian or bird flu has become a hot focus of the U.S. Centers for Disease Control and Prevention (CDC)'s new contracts with a handful of commercial reference laboratories in the U.S.
Utah-based ARUP Laboratories announced on September 13 its selection as a partner in the development of an avian influenza A (H5N1) test. Tennessee-based Aegis Sciences, Boston-based Ginkgo Bioworks, Labcorp, and Quest Diagnostics were also named.
The contracts are the latest from the CDC that enable pivoting clinical laboratory and community diagnostic testing and other important services out of public health laboratories and into private commercial labs as infectious disease patterns or concerns begin to emerge.
Dr. Ben Bradley, PhD, a pathologist and medical director of virology and molecular infectious diseases for ARUP Laboratories who is based at the University of Utah School of Medicine, in an interview with LabPulse.com, said that ARUP will start by developing a yes/no polymerase chain reaction (PCR) test for H5.
H5 is one of the subtypes of influenza A virus that has been found in sick birds such as commercial poultry, Canadian geese, other bird flocks, and some dairy cows as H5N1 avian flu, or bird flu. A small number of flu A cases (15 since 2022) so far are believed to have spread from animals to humans, with one case in Missouri being investigated further.
Other flu A strains infect pigs (triple reassortant [tr] H1N1 influenza virus, trH3N2 virus, and trH1N2), and horses (H7N7 and H3N8), according to the CDC.
While the current overall threat of avian flu is low, the bird flu situation is being monitored through the CDC's flu surveillance network. Virologists are concerned about how the virus could potentially evolve, in addition to the types of flu that commonly affect people, flu B (seasonal spread) and C (milder, not thought to cause human epidemics).
"It's sometimes a challenge in infectious disease testing to make a business case for bringing on H5 testing," Bradley explained for LabPulse. "There has not been human-to-human transmission, just a handful of people who have had close interactions with infected cows or poultry. To make a business case to spend money to develop this test is challenging."
Knowing the CDC's plans to seek private partners to rev up certain infectious disease testing when needed, ARUP had already allocated resources to "high consequence pathogen response," Bradley said. The lab was in the beginning stages of developing an H5 assay at the time of the CDC's request for partnership.
Proof-of-concept work
"Doing the proof-of-concept work on an assay is a small price to pay for a potentially big effect," Bradley said. "The CDC contract incentivizes laboratories to start developing these tests earlier, even if it is not something we see as an immediate threat. We can be prepared to scale up the assay."
Dr. Ben Bradley, PhD, ARUP Laboratories, University of Utah School of MedicineBen Bradley
Bradley added, "We're not doing next generation sequencing. We're not building epidemiological links here. We're getting the lowest, most necessary rung in the ladder, which is tell me if this person has H5 yes or no, built first. And while maybe it's not sexy to build a PCR test, that's what you need. We already have the infrastructure in place and available bandwidth."
Bradley said ARUP will focus on validating its H5 assay using respiratory samples, as well as conjunctival swab samples because, with bird flu, individuals have presented with profound conjunctivitis, an eye infection very atypical for influenza viruses historically.
If avian flu is believed to be spreading in humans, and it is not currently according to officials, the H5-positive samples would be further tested using more focused assays and genomic sequencing to classify the virus by its subtype as seasonal flu (H1 or H3) and, further, to assess spike proteins. ARUP's contract is a five-year contract and will support the CDC in its public health response, Bradley said.
"In the unlikely event it does become a problem, we can solve it; we'll have a test we can plug into production," Bradley said.
“ARUP wants to be a fully integrated partner in the delivery of public health services and clinical laboratory testing, and this contract opens doors for both,” said Marc Couturier, PhD, ARUP’s head of clinical operations for Clinical Microbiology and Immunology and medical director of Emerging Public Health Crisis, Parasitology/Fecal Testing, and Infectious Disease Antigen Testing, in ARUP's announcement.
CDC testing
Flu antigens, the viral surface proteins hemagglutinin (HA) and neuraminidase (NA), and glycoprotein spikes are aspects of study with the H5N1 influenza A strain. In a September 13 CDC update, the agency said that only partial gene sequences could be obtained for the HA and NA genes. However, the HA gene sequence confirmed that the bird flu virus is clade 2.3.4.4b, and the NA sequence was confirmed as N1.
There are two amino acid differences in the HA that have not been seen in sequences from previous human cases, the CDC added.
One way flu viruses change is called "antigenic drift," the CDC explained. "Drift consists of small changes (or mutations) in the genes of influenza viruses that can lead to changes in HA and NA. Additional antigenic testing is planned.
"These amino acid differences are not known to be associated with changes to the virus's ability to infect and spread among people," the CDC said. "However, both differences are in locations that may impact the cross-reactivity of clade 2.3.4.4b candidate vaccine viruses (CVVs)."
Looking forward
With the execution of the five-year contracts, the CDC is moving closer to fulfilling a milestone in its 2024 Public Health Data strategy which is to expand its access to commercial laboratory data.
"These new contracts create more flexibility for CDC to access clinical laboratory data and work with these laboratories when needed for specific new and emerging pathogens based on their testing and data sharing capacity," the CDC said in an overview. The contracts include enhancing access to critical clinical laboratory data across more than 200 reportable conditions to support ongoing situational awareness, the CDC also said.
While 15 human cases of avian influenza A (H5) bird flu have been reported in the U.S. since April 2024, the CDC has said there is no epidemiologic evidence to support person-to-person transmission of H5 at this time. The immediate risk to the general public from H5 bird flu remains low, the CDC said last week.
Other CDC contracts
CDC's agreements with commercial labs have also focused on hepatitis C virus antibody testing and molecular RNA testing using HIPAA-deidentified "remnant" specimens randomly selected from clinical test specimens, with Quest for example.
Aegis Sciences began testing for monkeypox in 2022, along with Labcorp, Mayo Clinic Laboratories, Sonic Healthcare, and Quest.
Labcorp's other activities include a project that began in 2023 to develop a respiratory surveillance system intended to track and study the epidemiology of respiratory infection in the U.S. Tools developed from this project could ultimately support a broad network capable of detecting novel respiratory pathogen outbreaks across the country, according to the CDC.
Additionally, Ginkgo Bioworks' previously announced work on the CDC's Traveler-based Genomic Surveillance program (TGS) has been to monitor more than 30 new viruses, bacteria, and antimicrobial resistance targets, including several seasonal respiratory pathogens, such as influenza A and B, RSV, and SARS-CoV-2.
Read the CDC's contract highlights here, the Public Health Data Strategy here.
