“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.
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.
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.
Though PCR clinical laboratory testing is widely used, some scientists are concerned its specificity may limit the ability to identify all variants of bird flu in wastewater
Wastewater testing of infectious agents appears to be here to stay. At the same time, there are differences of opinion about which methodologies and clinical laboratory tests are best suited to screen for specific contagions in wastewater. One such contagion is avian influenza, the virus that causes bird flu.
Wastewater testing by public health officials became a valuable tool during the COVID-19 pandemic and has now become a common method for detecting other diseases as well. For example, earlier this year, scientists used wastewater testing to learn how the H5N1 variant of the bird flu virus was advancing among dairy herds across the country.
In late March, the bird flu was first detected in dairy cattle in Texas, prompting scientists to begin examining wastewater samples to track the virus. Some researchers, however, expressed concerns about the ability of sewage test assays to detect all variants of certain diseases.
“Right now we are using these sort of broad tests to test for influenza A viruses,” Denis Nash, PhD, Distinguished Professor of Epidemiology at City University of New York (CUNY) and Executive Director of CUNY’s Institute for Implementation Science in Population Health (SPH), told the Los Angeles Times. “It’s possible there are some locations around the country where the primers being used in these tests might not work for H5N1.” Clinical laboratory PCR genetic testing is most commonly used to screen for viruses in wastewater. (Photo copyright: CUNY SPH.)
Effectiveness of PCR Wastewater Testing
Polymerase chain reaction (PCR) tests are most commonly used to distinguish genetic material related to a specific illness such as the flu virus. For PCR tests to correctly identify a virus, the tests must be designed to look for a specific subtype. The two most prevalent human influenza A viruses are known as H1N1 (swine flu) and H3N2, which was responsible for the 1968 pandemic that killed a million people worldwide. The “H” stands for hemagglutinin and the “N” for neuraminidase.
Hemagglutinin is a glycoprotein that assists the virus to attach to and infect host cells. Neuraminidase is an enzyme found in many pathogenic or symbiotic microorganisms that separates the links between neuraminic acids in various molecules.
Avian flu is also an influenza A virus, but it has the subtype H5N1. Although human and bird flu viruses both contain the N1 signal, they do not share an H. Some scientists fear that—in cases where a PCR test only looks for H1 and H3 in wastewater—that test could miss the bird flu altogether.
“We don’t have any evidence of that. It does seem like we’re at a broad enough level that we don’t have any evidence that we would not pick up H5,” Jonathan Yoder, Deputy Director, Infectious Disease Readiness and Innovation at the US Centers for Disease Control and Prevention (CDC) told the Los Angeles Times.
The CDC asserts current genetic testing methods are standardized and will detect the bird flu. Yoder also affirmed the tests being used at all the testing sites are the same assay, based on information the CDC has published regarding testing for influenza A viruses.
Genetic Sequencing Finds H5N1 in Texas Wastewater
In an article published on the preprint server medRxiv titled, “Virome Sequencing Identifies H5N1 Avian Influenza in Wastewater from Nine Cities,” the authors wrote, “using an agnostic, hybrid-capture sequencing approach, we report the detection of H5N1 in wastewater in nine Texas cities, with a total catchment area population in the millions, over a two-month period from March 4th to April 25th, 2024.”
The authors added, “Although human to human transmission is rare, infection has been fatal in nearly half of patients who have contracted the virus in past outbreaks. The increasing presence of the virus in domesticated animals raises substantial concerns that viral adaptation to immunologically naïve humans may result in the next flu pandemic.”
“So, it’s not just targeting one virus—or one of several viruses—as one does with PCR testing,” Eric Boerwinkle, PhD, Dean of the UTHealth Houston School of Public Health told the LA Times. “We’re actually in a very complex mixture, which is wastewater, pulling down viruses and sequencing them. What’s critical here is it’s very specific to H5N1.”
Epidemiologist Blake Hanson, PhD, Assistant Professor, Department of Epidemiology, Human Genetics, and Environmental Sciences at the UT Health Houston Graduate School of Biomedical Science, agreed with Boerwinkle that though the PCR-based methodology is highly effective at detecting avian flu in wastewater samples, the testing can do more.
“We have the ability to look at the representation of the entire genome, not just a marker component of it. And so that has allowed us to look at H5N1, differentiate it from some of our seasonal fluids like H1N1 and H3N2,” Hanson told the LA Times. “It’s what gave us high confidence that it is entirely H5N1, whereas the other papers are using a part of the H5 gene as a marker for H5.”
Human or Animal Sources
Both Boerwinkle and Hanson are epidemiologists in the team studying wastewater samples for H5N1 in Texas. They are not sure where the virus originated but are fairly certain it did not come from humans.
“Texas is really a confluence of a couple of different flyways for migratory birds, and Texas is also an agricultural state, despite having quite large cities,” Boerwinkle noted. “It’s probably correct that if you had to put your dime and gamble what was happening, it’s probably coming from not just one source but from multiple sources. We have no reason to think that one source is more likely any one of those things.”
“Because we are looking at the entirety of the genome, when we look at the single human H5N1 case, the genomic sequence has a hallmark amino acid change, compared to all of the cattle from that same time point,” Hanson said. “We do not see that hallmark amino acid present in any of our sequencing data. And we’ve looked very carefully for that, which gives us some confidence that we’re not seeing human-human transmission.”
CDC Updates on Bird Flu
In its weekly updates on the bird flu situation, the CDC reported that 48 states have outbreaks in poultry and 14 states have avian flu outbreaks in dairy cows. More than 238 dairy herds have been affected and, as of September 20, over 100 million poultry have been affected by the disease.
In addition, the CDC monitored more than 4,900 people who came into contact with an infected animal. Though about 230 of those individuals have been tested for the disease, there have only been a total of 14 reported human cases in the US.
The CDC posts information specifically for laboratory workers, healthcare providers, and veterinarians on its website.
The CDC also states that the threat from avian flu to the general public is low. Individuals at an increased risk for infection include people who work around infected animals and those who consume products containing raw, unpasteurized cow’s milk.
Symptoms of H5N1 in humans may include fever or chills, cough, headaches, muscle or body aches, runny or stuffy nose, tiredness and shortness of breath. Symptoms typically surface two to eight days after exposure.
Scientists and researchers have been seeking a reliable clinical laboratory test for disease organisms in a fast, accurate, and cost-effective manner. Wastewater testing of infectious agents could fulfill those goals and appears to be a technology that will continue to be used for tracking disease.
Declining health of UK’s population also affecting performance of the country’s national health service, report notes
England’s National Health Service (NHS) is “in serious trouble” due to long waiting times, outdated technology, misallocated resources, and numerous other problems, with dire consequences for the country’s populace. That’s according to a new report by NHS surgeon and former Health Minister Lord Ara Darzi, OM KBE FRS FMedSci HonFREng, who was tasked by the United Kingdom’s new Labor government to investigate the ailing healthcare system. His report may contain lessons for US healthcare—including clinical laboratories—as well.
“Although I have worked in the NHS for more than 30 years, I have been shocked by what I have found during this investigation—not just in the health service but in the state of the nation’s health,” Darzi stated in a UK government press release. “We want to deliver high quality care for all but far too many people are waiting for too long and in too many clinical areas, quality of care has gone backwards.”
Many of the problems he identified relate to wait times.
“From access to GPs (general practitioners) and to community and mental health services, on to accident and emergency, and then to waits not just for more routine surgery and treatment but for cancer and cardiac services, waiting time targets are being missed,” he wrote in his report.
For example, “as of June 2024, more than one million people were waiting for community services, including more than 50,000 people who had been waiting for over a year, 80% of whom are children and young people,” he wrote.
Accident and emergency care (A/E) “is in an awful state,” the report noted, “with A/E queues more than doubling from an average of just under 40 people on a typical evening in April 2009 to over 100 in April 2024. One in 10 patients are now waiting for 12 hours or more.”
“In the last 15 years, the NHS was hit by three shocks—austerity and starvation of investment, confusion caused by top-down reorganization, and then the pandemic which came with resilience at an all-time low. Two out of three of those shocks were choices made in Westminster,” said NHS surgeon and former Health Minister Lord Ara Darzi in a government press release. “It took more than a decade for the NHS to fall into disrepair so it’s going to take time to fix it. But we in the NHS have turned things around before, and I’m confident we will do it again.” (Photo copyright: Health Data Research UK.)
Delays in Other Critical Tests
Genetic test results are lagging as well. “In 2024, more than 35,000 genomic tests are being completed each month but only around 60% on time,” Darzi wrote.
He also noted that “only around 5% of eligible patients with brain cancer are able to access whole genome sequencing (WGS), which is important for treatment selection.” Just two-thirds (65.8%) get their first treatment within 62 days, and more than 30% wait more than 31 days for radical radiotherapy, according to the report.
Overall, “the UK has appreciably higher cancer mortality rates than other countries, with no progress whatsoever made in diagnosing cancer at stage one and two between 2013 and 2021,” he wrote.
Patients have also experienced delays in access to cardiovascular treatment. For example, in 2013-2014, high-risk heart attack patients waited an average of 114 minutes for intervention to unblock an artery, Darzi noted in his report. However, in 2022-2023, the average time was 146 minutes, a 28% increase.
“For the most part, once people are in the system, they receive high quality care,” he wrote. “But there are some important areas of concerns, such as maternity care, where there have been a succession of scandals and inquiries.”
Key Factors Leading to Delays
Darzi pointed to four key factors that have led to the problems.
Lack of funding. “The 2010s was the most austere decade since the NHS was founded, with spending growing at around 1% in real terms,” Darzi wrote, compared with a long-term average of 3.4%.
One result was that administrators took funds from the capital budget to cover day-to-day needs, leading to “crumbling buildings that hit productivity,” he noted.
“The backlog maintenance bill now stands at more than £11.6 billion and a lack of capital means that there are too many outdated scanners, too little automation, and parts of the NHS are yet to enter the digital era,” he wrote.
The COVID-19 pandemic. Given the preceding “decade of austerity,” NHS had fewer resources to deal with the crisis than most other high-income health systems, he wrote. As a result, NHS “delayed, cancelled, or postponed far more routine care during the pandemic than any comparable health system.” This led to “a bigger backlog than other health systems.”
Lack of patient and staff engagement. Patient satisfaction “has declined and the number of complaints has increased, while patients are less empowered to make choices about their care,” he wrote. In addition, “too many staff have become disengaged, and there are distressingly high-levels of sickness absence—as much as one working month a year for each nurse and each midwife working in the NHS.”
Management structures and systems. Darzi laid considerable blame on the UK’s Health and Social Care Act of 2012, which led to what he described as “a costly and distracting process of almost constant reorganization of the ‘headquarters’ and ‘regulatory’ functions of the NHS.”
One consequence, he wrote, is that too many clinicians have been deployed in hospitals instead of community-based care, despite years of promises by successive governments to put more emphasis on the latter.
National Health in Decline
Along with issues within the NHS, “the health of the nation has deteriorated and that impacts its performance,” Darzi wrote. “There has been a surge in multiple long-term conditions, and, particularly among children and young people, in mental health needs. Fewer children are getting the immunizations they need to protect their health, and fewer adults are participating in some of the key screening programs, such as for breast cancer.”
Darzi’s investigation included frontline visits to NHS facilities as well as focus groups with NHS staff and patients, the press release states. He also consulted an expert reference group consisting of more than 70 organizations and examined analyses from NHS England, the UK’s Department of Health and Social Care, and external groups.
It is interesting that there is no mention of anatomic pathology and medical laboratory testing services in Lord Darzi’s report. As reported in recent years by new outlets in the United Kingdom, delays in cancer diagnoses—often as long as six months—were severe enough that, in 2018, the NHS announced funding for a program to create a national digital pathology network to improve productivity of pathologists and shorten wait times for the results of cancer tests.
The NIH’s Researching COVID to Enhance Recovery (RECOVER) Initiative used a cohort study of more than 10,000 individuals with and without previous COVID-19 diagnoses and compared samples using 25 common laboratory tests in hopes a useful biomarker could be identified. They were unsuccessful.
Long COVID—or PASC—is an umbrella term for those with persistent post-COVID infection symptoms that negatively impact quality of life. Though it affects millions worldwide and has been called a major public health burden, the NIH/Langone study scientists noted one glaring problem: PASC is defined differently in the major tests they studied. This makes consistent diagnoses difficult.
The study brought to light possible roadblocks that prevented biomarker identification.
“This study is an important step toward defining long COVID beyond any one individual symptom,” said study author Leora Horwitz, MD (above), director of the Center for Healthcare Innovation and Delivery Science and co-principal investigator for the RECOVER CSC at NYU Langone, in a Langone Health news release. “This definition—which may evolve over time—will serve as a critical foundation for scientific discovery and treatment design.” In the future, clinical laboratories may be tasked with finding combinations of routine and reference tests that, together, enable a more precise and earlier diagnosis of long COVID. (Photo copyright: Yale School of Medicine.)
NIH/Langone Study Details
“The study … examined 25 routinely used and standardized laboratory tests chosen based on availability across institutions, prior literature, and clinical experience. These tests were conducted prospectively in laboratories that are certified by the Clinical Laboratory Improvement Amendments (CLIA). The samples were collected from 10,094 RECOVER-Adult participants, representing a diverse cohort from all over the US,” Inside Precision Medicine reported.
However, the scientists found no clinical laboratory “value” among the 25 tests examined that “reliably indicate previous infection, PASC, or the particular cluster type of PASC,” Inside Precision Medicine noted, adding that “Although some minor differences in the results of specific laboratory tests attempted to differentiate between individuals with and without a history of infection, these findings were generally clinically meaningless.”
“In a cohort study of more than 10,000 participants with and without prior SARS-CoV-2 infection, we found no evidence that any of 25 routine clinical laboratory values provide a reliable biomarker of prior infection, PASC, or the specific type of PASC cluster. … Overall, no evidence was found that any of the 25 routine clinical laboratory values assessed in this study could serve as a clinically useful biomarker of PASC,” the study authors wrote in Annals of Internal Medicine.
In addition to a vague definition of PASC, the NIH/Langone researchers noted a few other potential problems identifying a biomarker from the research.
“Use of only selected biomarkers, choice of comparison groups, if any (people who have recovered from PASC or healthy control participants); duration of symptoms; types of symptoms or phenotypes; and patient population features, such as sex, age, race, vaccination status, comorbidities, and severity of initial infection,” could be a cause for ambiguous results, the scientists wrote.
Future Research
“Understanding the basic biological underpinnings of persistent symptoms after SARS-CoV-2 infection will likely require a rigorous focus on investigations beyond routine clinical laboratory studies (for example, transcriptomics, proteomics, metabolomics) to identify novel biomarkers,” the study authors wrote in Annals of Internal Medicine.
“Our challenge is to discover biomarkers that can help us quickly and accurately diagnose long COVID to ensure people struggling with this disease receive the most appropriate care as soon as possible,” said David Goff, MD, PhD, director of the division of cardiovascular sciences at the NIH’s National Heart, Lung, and Blood Institute, in an NHLBI news release. “Long COVID symptoms can prevent someone from returning to work or school, and may even make everyday tasks a burden, so the ability for rapid diagnosis is key.”
“Approximately one in 20 US adults reported persisting symptoms after COVID-19 in June 2024, with 1.4% reporting significant limitations,” the NIH/Langone scientists wrote in their published study.
Astute clinical laboratory scientists will recognize this as possible future diagnostic testing. There is no shortage of need.
Program is open to providers that exclusively offer telehealth services, and those providers that offer the telehealth services to other hospitals
In another sign that telehealth is now an established presence in the healthcare marketplace, The Joint Commission recently implemented a new Telehealth Accreditation Program. The initiative, which took effect on July 1, 2024, aims to provide “updated, streamlined standards” enabling “safe, high-quality” delivery of telehealth services to patients, according to a press release. The organization announced the program in April.
Dark Daily has regularly commented on the importance for clinical laboratories to recognize this trend and add the necessary services to meet the expectations and needs of telehealth/virtual doctor visits where the physician orders medical laboratory tests for the patient.
“The use of telehealth in the United States increased 154% during early stages of the COVID-19 pandemic and stabilized at levels 38 times higher than levels in 2019,” said Joint Commission President and CEO Jonathan B. Perlin, MD, PhD, in the press release.
“As telehealth continues to evolve, it was imperative to create a new accreditation program to provide a framework to support the integrity of patient safety regardless of the care setting,” he added.
The accrediting organization is reacting to market demand. Patient and doctor acceptance of virtual doctor visits and telehealth consults is now an established fact.
[PHOTO OF PERLIN HERE]
“Our new Telehealth Accreditation Program helps organizations standardize care and reduce risk so that all patients, including those obtaining services remotely, receive the safest, highest-quality care with outcomes consistent with traditional settings,” said Jonathan B. Perlin, MD, PhD (above), President/CEO, The Joint Commission, in a press release. Clinical laboratory accreditation nationwide is also handled by the not-for-profit organization. (Photo copyright: International Hospital Federation.)
Eligibility
The Joint Commission describes itself as “the nation’s oldest and largest standards-setting and accrediting body in healthcare.” The not-for-profit organization certifies more than 22,000 healthcare providers in the US, according to its website, including hospitals and medical laboratories. Its evaluations are based on surveys in which qualified experts conduct inspections of the facilities to ensure compliance with patient safety and quality standards.
Accreditation is not mandatory, however many states have licensing, certification, or contracting requirements that mandate accreditation by The Joint Commission or other accrediting bodies.
The program is open to providers that exclusively offer healthcare services “via telehealth or remote patient monitoring, with no in-person visits or encounters,” according to The Joint Commission website. This can include organizations that provide:
Primary care, specialty care, or urgent care,
Medical or behavioral consultation,
Remote patient monitoring, and
TeleICU, telestroke, telepsychiatry, or teleimaging services to hospitals.
Hospitals or other healthcare providers can also apply if they have contracts to offer “care, treatment, and services via telehealth to another organization’s patients,” The Joint Commission states. Examples include acute care or psychiatric hospitals that provide telehealth services to other facilities. In this case, the hospitals can obtain telehealth accreditation for the contracted services while maintaining their current accreditation for services provided onsite.
Requirements for Certification
The requirements for accreditation are similar to those in other Joint Commission programs, the organization says. This includes “requirements for information management, leadership, medication management, patient identification, documentation, and credentialing and privileging.”
In addition, it includes requirements specific to telehealth. For example, emergency management requirements have been streamlined to account for services provided remotely. It also contains standards related to telehealth equipment as well as provider and patient education about use of the technology.
“Additionally, the program’s standards may be filtered based on the telehealth modality or service provided,” the organization’s website notes.
Other Accrediting Organizations
The Joint Commission is not the only organization that offers telehealth accreditation or certification. The Utilization Review Accreditation Commission (URAC) provides accreditation programs for telehealth and remote patient monitoring, as well as a certification program for telehealth support services.
The telehealth accreditation program consists of three modules accounting for different forms of delivery:
Provider-to-provider (one provider offers services such as consultation to another provider).
The accreditation process takes up to four months, URAC says.
The Accreditation Commission for Health Care (ACHC) offers what it describes as a telehealth “Distinction” for certain kinds of healthcare providers that it has accredited, including:
Additionally, in April 2022, ACHC announced a telehealth certification program open to “any healthcare provider or organization that delivers health-related services via electronic information and telecommunication technologies,” regardless of whether they are accredited, according to a press release.
“The pandemic really pushed healthcare providers to adopt and grow telehealth services to maintain access for patients and, as a result, many of our clients were seeking ways to optimize this offering in the context of providing quality services,” said program director Teresa Hoosier, RN, in the press release. “ACHC Telehealth Certification establishes national standards. It promotes best practices for digital healthcare services. Certification confirms quality, safety, and consistency—strengthening trust in an organization and assuring patients that they are receiving the best care possible.”
This development is a reminder that clinical laboratory managers need a consumer/patient focused strategy and operational capability to collect specimens and provide medical laboratory tests for telehealth visits when the doctors order tests. It confirms that the trend of consumers/patients using remote healthcare is real, robust, and has legs.
