News, Analysis, Trends, Management Innovations for
Clinical Laboratories and Pathology Groups

Hosted by Robert Michel

News, Analysis, Trends, Management Innovations for
Clinical Laboratories and Pathology Groups

Hosted by Robert Michel
Sign In

CDC Enlists Five Commercial Medical Laboratories to Bolster Avian Flu Testing Capacity in the United States

Move comes following criticism from public health experts over the federal agency’s difficulties creating clinical laboratory tests for COVID-19

Amid the ongoing outbreak of the Highly Pathogenic Avian Influenza A(H5N1) bird flu virus, the US Centers for Disease Control and Prevention (CDC) announced on Sept. 13 that it is awarding contracts to five clinical laboratory companies to bolster testing capacity for “new and emerging pathogens,” including HPAI A(H5N1).

Citing Nirav Shah, MD, MPH, Senior Scholar, Clinical Excellence Research Center at Stanford University School of Medicine and co-chair of the Data and Surveillance Workgroup (DSW) at the CDC, the Associated Press (AP), reported that the agency will initially spend at least $5 million on the effort, with “plans to scale up to $118 million over the next five years if necessary.”

The five medical laboratory companies the CDC chose are:

“Previously … CDC developed tests for emerging pathogens and then shared those tests with others, and then after that, commercial labs would develop their own tests,” Shah told CNN. “That process took time. Now with these new arrangements, commercial labs will be developing new tests for public health responses alongside CDC, not after CDC.”

In a news release announcing the contract, ARUP Laboratories also characterized the move as a shift for the agency.

“The new contract formalizes ARUP’s relationship with the CDC,” said Benjamin Bradley, MD, PhD, medical director of the ARUP Institute for Research and Innovation in Infectious Disease Genomic Technologies, High Consequence Pathogen Response, Virology, and Molecular Infectious Diseases. “We continue to expand our capabilities to address public health crises and are prepared to scale up testing for H5N1, or develop other tests quickly, should the need arise.”

“To be clear, we have no evidence so far that this [bird flu] virus can easily infect human beings or that it can spread between human beings easily in a sustained fashion,” Jennifer Nuzzo, DrPH (above), Director of the Pandemic Center and Professor of Epidemiology at Brown University School of Public Health, told CNN. “If it did have those abilities, we would be in a pandemic.” Clinical laboratory leaders will recall the challenges at the CDC as it developed its SARS-CoV-2 test early in the COVID-19 pandemic. (Photo copyright: Brown University.)

Missouri Case Raises Concerns

The first human infection of HPAI was reported in late March following a farmer’s “exposure to dairy cows presumably infected with bird flu,” the CDC stated in its June 3, 2024, bird flu Situation Summary. That followed confirmation by the USDA’s Animal and Plant Health Inspection Service (APHIS) of an HPAI outbreak in commercial poultry flocks in February 2022, and the CDC’s confirmation of the first known infections in dairy herds reported on March 25, 2024.

Concerns about the outbreak were heightened in September following news that a person in Missouri had been infected with the virus despite having no known contact with infected animals. CNN reported that it was the 14th human case in the US this year, but all previous cases were in farm workers known to be exposed to infected dairy cattle or poultry.

In a news release, the Missouri Department of Health and Senior Services (DHSS) revealed that the patient, who was not identified, was hospitalized on Aug. 22. This person had “underlying medical conditions,” DHSS reported, and has since recovered and was sent home. Both DHSS and the CDC conducted tests to determine that the virus was the H5 subtype, the news release states.

At present, the CDC states that the public health risk from the virus is low. However, public health experts are concerned that risks could rise as the weather gets cooler, creating opportunities for the virus to mutate “since both cows and other flu viruses will be on the move,” CNN reported.

Concerns over CDC Testing and FDA Oversight

In the months immediately following the first human case of the bird flu virus, Nuzzo was among several public health experts sounding an alarm about the country’s ability to ramp up testing in the face of new pathogens.

“We’re flying blind,” she told KFF Health News in June, due to an inability to track infections in farmworkers. At that time, tests had been distributed to approximately 100 public health labs, but Nuzzo and other experts noted that doctors typically order tests from commercial laboratories and universities.

“Pull us into the game. We’re stuck on the bench,” Alex Greninger MD, PhD, of the University of Washington Medicine Clinical Virology Laboratory, told KFF News.

KFF reported that one diagnostics company, Neelyx Labs, ran into obstacles as it tried to license the CDC’s bird flu test. Founder, CEO, and lead scientist Shyam Saladi, PhD, told KFF that the federal agency had promised to cooperate by facilitating a license and a “right to reference” CDC data when applying for FDA authorization but was slow to come through.

While acknowledging the need for testing accuracy, Greninger contended that the CDC was prioritizing caution over speed, as it did in the early days of the COVID-19 pandemic. “The CDC should be trying to open this up to labs with national reach and a good reputation,” he told KFF.

Another problem, KFF reported, related to the FDA’s new oversight of laboratory developed tests (LDTs), which is causing labs to move cautiously in developing their own tests.

“It’s slowing things down because it’s adding to the confusion about what is allowable,” American Clinical Laboratory Association (ACLA) President Susan Van Meter told KFF.

New Testing Playbook

Jennifer Nuzzo, DrPH (above), Director of the Pandemic Center and Professor of Epidemiology at the Brown University School of Public Health co-authored a June 2024 analysis in Health Affairs that called on the CDC to develop “a better testing playbook for biological emergencies.” The authors’ analysis cited earlier problems with the responses to the COVID-19 and mpox (formerly known as monkeypox) outbreaks.

If global surveillance networks have detected a novel pathogen, the authors advise, the US should gather information and “begin examining the existing testing landscape” within the first 48 hours.

Once the pathogen is detected in the US, they continued, FDA-authorized tests should be distributed to public health laboratories and the CDC’s Laboratory Response Network (LRN) laboratories within 48 hours.

Advocates of this approach suggest that within the first week diagnostics manufacturers should begin developing their own tests and the federal government should begin working with commercial labs. Then, within the first month, commercial laboratories should be using FDA-authorized tests to provide “high throughput capacity.”

This may be good advice. Experts in the clinical laboratory and healthcare professions believe there needs to be improvement in how novel tests are developed and made available as novel infectious agents are identified.

—Stephen Beale

Related Information:

CDC Adds Commercial Lab Contracts for Infectious Disease, Bird Flu Testing

Strengthening Response to Public Health Threats through Expanded Laboratory Testing and Access to Data

ARUP Awarded CDC Contract for Bird Flu Test Development

Test Surge and Data Sharing Multiple Award Indefinite Delivery Indefinite Quantity (IDIQ) Solicitation

Interim Guidance on Specimen Collection and Testing for Patients with Suspected Infection with Novel Influenza A Viruses Associated with Severe Disease or with the Potential to Cause Severe Disease in Humans

Current H5N1 Bird Flu Situation in Dairy Cows

The US Is Entering a Riskier Season for Spread of H5N1 Bird Flu. Here’s Why Experts Are Worried

Wastewater Testing Specifically for Bird Flu Virus Will Scale Up Nationally in Coming Weeks

Wastewater Surveillance for Influenza A Virus and H5 Subtype Concurrent with the Highly Pathogenic Avian Influenza A(H5N1) Virus Outbreak in Cattle and Poultry and Associated Human Cases

Two California Farmworkers Test Positive for Bird Flu

Avian Flu Spreading in California Raises Pandemic Threat for Humans

Bird Flu Is Spreading. Why Aren’t More People Getting Tested?

Why Fears of Human-to-Human Bird Flu Spread in Missouri Are Overblown

The United States Needs a Better Testing Playbook for Future Public Health Emergencies

FDA Authorizes First At-Home COVID-19 Antigen Tests, but Roadblocks Remain for “Fast-and-Frequent” Antigen Testing

Developers of medical laboratory tests had high hopes that cheap saliva-based tests would compete with at-home OTC tests that use nasal swabs, but skepticism among scientists continues

Reverse-transcription polymerase chain reaction (RT-PCR) technology has become the standard for clinical laboratory diagnostic testing used to detect the presence of the SARS-CoV-2 coronavirus. However, to enable more widespread testing, some public health experts have called for deployment of cheap, rapid, saliva-based antigen tests that could be self-administered by consumers in their homes.

Despite the technology’s lower sensitivity compared with RT-PCR testing, the idea of “fast-and-frequent” universal antigen testing has gained support as a possible game-changer against the outbreak, the New York Times reported.

The FDA recently took a step in this direction with its first emergency use authorization for the Ellume COVID-19 at-home antigen test. But other developments suggest that these tests may fall short of the lofty vision initially outlined by the experts.

Ellume’s COVID-19 Home Test
Ellume’s COVID-19 Home Test (above) received emergency use authorization from the FDA on December 15. In a press release, Ellume claimed its rapid-antigen test, “demonstrated a sensitivity of 96% and specificity of 100%, and in asymptomatic individuals, the test demonstrated a sensitivity of 91% and specificity of 96%. This level of accuracy across both symptomatic and asymptomatic individuals is crucial in mitigating the spread of an infectious disease like COVID-19.” (Photo copyright: Ellume.)

The Promise of Rapid Antigen COVID-19 Tests

In a column he wrote for Time in July, Ashish K. Jha, MD, MPH, a practicing General Internist and Dean of the Brown University School of Public Health, described the promise of rapid antigen tests. “Imagine spitting on a special strip of paper every morning and being told two minutes later whether you were positive for COVID-19,” he wrote. “If everyone in the United States did this daily, we would dramatically drop our transmission rates and bring the pandemic under control.”

Another advocate for this approach is Michael Mina, MD, PhD, an assistant professor of epidemiology at the Harvard T.H. Chan School of Public Health and a core member of the School’s Center for Communicable Disease Dynamics (CCDD). In a commentary for Time in November he wrote, “Widespread and frequent rapid antigen testing (public health screening to suppress outbreaks) is the best possible tool we have at our disposal today—and we are not using it.”

However, one major issue with antigen testing is sensitivity. “Antigen tests require higher levels of virus than qPCR [quantitative polymerase chain reaction] to return a positive result,” Jha wrote in Time. However, he contends, “the frequency of testing and the speed of results” counter concerns about accuracy.

Even with lower sensitivity, Jha wrote, the quicker test results from antigen tests “would identify viral loads during the most infectious period, meaning those cases we care most about identifying—at the peak period of infectiousness—are less likely to be missed.”

As the FDA explains, RT-PCR molecular tests “detect the virus’ genetic material,” whereas, according to an article published in Nature, titled, “Fast Coronavirus Tests: What They Can and Can’t Do,” antigen tests can “detect specific proteins … on the surface of the virus, and can identify people who are at the peak of infection, when virus levels in the body are likely to be high.”

At-Home Antigen Tests Receive EUAs

The new antigen test developed by Ellume is “the first over-the-counter (OTC) fully at-home diagnostic test for COVID-19,” the FDA said in a press release. The user self-administers a nasal swab and places it in an analyzer connected to a smartphone app. It can deliver results in 20 minutes. The company states that its test has overall sensitivity of 95% and specificity of 97% based on a clinical study of 198 subjects in a simulated home setting.

Jeffrey Shuren, MD, JD, Director of FDA’s Center for Devices and Radiological Health, said in the FDA press release, “This test, like other antigen tests, is less sensitive and less specific than typical molecular tests run in a lab. However, the fact that it can be used completely at home and return results quickly means that it can play an important role in response to the pandemic.”

Ellume expects to deliver about 20 million tests to the US by the end of June 2021. Multiple outlets reported that the test will cost about $30, AP News reported.

Meanwhile, the FDA also authorized at-home use of Abbott’s BinaxNOW rapid antigen test, which was previously authorized for use in point-of-care settings. This test, which requires a prescription, will sell for $25.

In a series of tweets, Harvard’s Mina applauded both moves, but he wrote that they [antigen tests] still fall short of his vision for fast and frequent testing. He described Abbott’s BinaxNOW as “the type of rapid test I have been calling for,” but said he’d like to see tests priced far less and available without a prescription.

Diminishing Prospects for Saliva-based Antigen Tests?

All rapid antigen tests authorized by the FDA so far require nasopharyngeal and/or nasal swab specimens, and it appears that it may be a long time, if ever, before saliva-based antigen tests are available. The New York Times (NYT) reported in October that two companies working on antigen tests—E25Bio and OraSure (NASDAQ:OSUR)—have dropped plans to enable use of saliva.

E25Bio founder Bobby Brooke Herrera, PhD with E25Bio co-founder and Chief Technology Officer Irene Bosch
“If I was placing a bet—which I am, because I’m leading an antigen-based testing company—I would say it’s going to be very difficult for antigen-based testing to work on saliva samples,” E25Bio founder Bobby Brooke Herrera, PhD (above with E25Bio co-founder and Chief Technology Officer Irene Bosch) told the NYT. (Photo copyright: WCVB-TV.)

One advantage of a saliva-based test is that it would be easier to self-administer. “But as they continued to tinker with their tests, researchers at both E25Bio and OraSure found saliva’s performance to be more lackluster than anticipated, and were forced to pivot,” the New York Times reported. Instead, both companies will seek authorization for use of their tests with nasal swabs.

HHS Contract for Antigen Tests Brings High Rates of False Positives

A recent investigative story in ProPublica, titled, “Rapid Testing Is Less Accurate than the Government Wants to Admit,” raised additional questions about rapid antigen testing. In August, the US Department of Health and Human Services announced it had awarded a $760 million contract for 150 million Abbott BinaxNOW tests to be distributed to schools and nursing homes. But later, according to ProPublica, healthcare workers in Nevada and Vermont reported high rates of false positives.

“With the benefit of hindsight, experts said the Trump administration should have released antigen tests primarily to communities with outbreaks instead of expecting them to work just as well in large groups of asymptomatic people,” ProPublica reported. “Understanding they can produce false results; the government could have ensured that clinics had enough for repeat testing to reduce false negatives and access to more precise PCR tests to weed out false positives.”

A few weeks after the reports from Nevada and Vermont, the FDA issued a letter advising clinical laboratories and healthcare providers about the possibility of false positives, along with steps they could take to improve accuracy.

Though some experts remain hopeful about “fast-and-frequent” testing, others are skeptical and say more research is needed to assess the value of this approach. “We are open to thinking outside the box and coming up with new ways to handle this pandemic,” Esther Babady PhD, D(ABMM) of Memorial Sloan Kettering Cancer Center, told the New York Times. However, she added, “the data for that is what’s missing.”

Nevertheless, were at-home rapid saliva-based antigen tests to become a common choice for healthcare consumers, clinical laboratories that perform RT-PCR testing for COVID-19 could see a marked decrease in orders. Thus, regardless of the current state of antigen testing, its development is worth watching.

—Stephen Beale

Related Information:

How We Can Stop the Spread of COVID-19 by Christmas

Over-the-Counter Home Test for COVID-19 Gets US Green Light

‘A Major Breakthrough’: FDA Authorizes Nation’s First At-Home, Over-the-Counter COVID-19 Test

FDA Authorizes First Rapid, Over-the-Counter Home Coronavirus Test

Rapid Testing Is Less Accurate than the Government Wants to Admit

Daily Coronavirus Testing at Home? Many Experts Are Skeptical

Home Tests Could Help in the Fight Against the Coronavirus. So Where Are They?

Screening to Prevent SARS-CoV-2 Outbreaks: Saliva-Based Antigen Testing Is Better than the PCR Swab

America Needs to Radically Rethink Our COVID-19 Testing Approach

Test Sensitivity Is Secondary to Frequency and Turnaround Time for COVID-19 Surveillance

Abbott COVID-19 Tests at Center of Squabble Between Trump Administration, States

Millions of Rapid COVID-19 Antigen Tests May Help Fill the Testing Gap

When It Comes to Mining Healthcare Big Data, Including Medical Laboratory Test Results, Optum Labs Is the Company to Watch

Example is a big data-based study involving Optum and Mayo Clinic that indicates diabetes management can be too aggressive for some patients

Mayo Clinic has tapped Optum Labs’ huge data set to fuel research suggesting diabetes management can be too aggressive among those diabetics who don’t have problems controlling their glucose level. Optum Labs’ data is also being mined to investigate dozens of research initiatives, including a major fight against Alzheimer’s disease. These projects provide a glimpse into the growing role of big data in healthcare.

Because more than 70% of a typical patient’s permanent medical record consists of clinical laboratory test data, pathologists and medical laboratory scientists have a stake in the growth of big-data analytics, which are a core component in healthcare’s journey toward personalized medicine. (more…)

;