A new Hybrid Lyme ELISA test shows promise for faster, more accurate early detection of Lyme disease, potentially streamlining lab workflows and improving patient care.
A newly developed serologic test for Lyme disease could significantly improve early detection and streamline the diagnostic process, according to a study published in the Journal of Clinical Microbiology. Researchers say the test, called the Hybrid Lyme ELISA, offers higher sensitivity in the earliest stages of the disease than currently approved methods, potentially reshaping clinical practice.
For laboratory leaders, the emergence of the Hybrid Lyme ELISA marks a potentially pivotal shift in diagnostic testing. With Lyme disease cases approaching half a million annually in the US, labs remain at the forefront of detection and reporting, yet current two-step testing protocols are labor-intensive, time-consuming, and lack sensitivity in early-stage patients. A single-tier, high-sensitivity serologic test could streamline workflows, reduce turnaround times, and enable labs to deliver more actionable results—especially for patients who present with erythema migrans, where current methods fall short.
In a press release on the study, study co-author Gary P. Wormser, MD, New York Medical College said, “This test could potentially change the standard of clinical practice, allowing clinicians to diagnose all manifestations of Lyme disease with a time-saving one-step antibody test.”
Lyme Disease and Current Testing Challenges
Lyme disease, caused by the bacterium Borrelia burgdorferi in the US and related species in Europe, is the most common vector-borne illness in the country, with nearly half a million cases diagnosed each year, according to the Centers for Disease Control and Prevention (CDC). The earliest and most common symptom is a skin rash called erythema migrans, which appears at the site of a tick bite.
If untreated, the infection can spread and cause neurological, cardiac, and joint problems. Early antibiotic treatment is highly effective, but timely diagnosis has remained a challenge.
Since 1995, the CDC has recommended a two-step serology process: an initial antibody screening test, usually an ELISA, followed by a confirmatory test. Originally, the Western Blot was required for confirmation, but in 2019, the CDC allowed a second ELISA instead. While reliable, this sequential approach can delay results.
Neither method is sensitive enough to recommend testing for patients in the erythema migrans stage, leaving early cases often undiagnosed.
A One-Step Approach
Developed by Kephera Diagnostics in collaboration with New York Medical College and the Lyme Disease Biobank, the Hybrid Lyme ELISA employs a novel immunoassay principle. It takes advantage of a unique biological response in which antibodies generated by Borrelia infection can simultaneously bind to two related, though not identical, antigens.
This dual-binding design allows the test to achieve both high sensitivity and specificity in a single step—performance that rivals or exceeds current two-tiered testing.
In the study, the Hybrid ELISA showed sensitivity of more than 90% in patients with erythema migrans, an improvement over the low sensitivity of existing FDA-approved methods. That could make it the first serologic test capable of reliably diagnosing patients in the earliest stage of Lyme disease.
“Current two-tiered serology tests are insensitive in early Lyme disease, missing up to 70% of patients presenting with erythema migrans,” said study co-author Liz Horn, PhD, MBI, principal investigator of the Lyme Disease Biobank, a Bay Area Lyme Foundation program.
Liz Horn, PhD, MBI, principal investigator of the Lyme Disease Biobank noted, “More accurate tests are urgently needed, and the Hybrid ELISA results are very promising.”
Potential to Change Clinical Practice
As an ELISA, the new test can be run manually or on automated high-throughput systems, making it suitable for widespread use in clinical laboratories. Researchers believe it could reduce time, cost, and complexity in diagnosing Lyme disease, while providing earlier answers for patients.
“The publication of this study is an important milestone in our efforts to bring about meaningful improvements in the diagnosis of Lyme disease that will benefit both patients and clinicians,” said Andrew Levin, PhD, chief executive and scientific officer at Kephera Diagnostics. “We are very excited by the results that were achieved by the Hybrid Lyme ELISA in this initial study. Naturally, these findings will have to be corroborated in larger-scale trials, which are currently underway.”
Kephera Diagnostics is now pursuing regulatory approval for the test and plans to make it available through its CLIA-certified laboratory while larger trials continue.
Funding and Collaboration
The Hybrid Lyme ELISA was developed with support from the National Institute of Allergy and Infectious Diseases through a Small Business Innovation Research (SBIR) grant. Collaborators included scientists at New York Medical College and the Lyme Disease Biobank, which provided critical patient samples.
If validated in larger trials and approved, experts say the test could become the first widely available one-step serologic test for Lyme disease, capable of diagnosing patients from the earliest rash stage through later, systemic disease.
AI tool finds possible bird flu infections overlooked in emergency departments.
Researchers at the University of Maryland School of Medicine (UMSOM) have demonstrated a powerful new use of artificial intelligence (AI) to detect potential bird flu infections that may otherwise go unnoticed in hospital emergency departments. Their findings, published in Clinical Infectious Diseases, show that generative AI can rapidly scan electronic medical records for high-risk exposures to H5N1 avian influenza.
A press release explained that the team applied a large language model (LLM) to 13,494 emergency visits across the University of Maryland Medical System in 2024. All patients had acute respiratory symptoms—such as cough, fever, or congestion—or conjunctivitis, which can mirror early signs of bird flu. The model flagged 76 notes that mentioned possible high-risk exposures, such as working as a butcher or on a farm with livestock.
Often these exposures were “incidentally” documented—for example, as part of a patient’s occupation—rather than because clinicians suspected avian influenza. After review, 14 patients were confirmed to have had recent, relevant exposure to poultry, wild birds, or livestock. None were specifically tested for H5N1, but the model was able to surface “needle in a haystack” cases buried among thousands of routine respiratory illnesses.
“This study shows how generative AI can fill a critical gap in our public health infrastructure by detecting high-risk patients that would otherwise go unnoticed,” said corresponding author Katherine E. Goodman, PhD, JD, assistant professor of Epidemiology & Public Health at UMSOM.
“With H5N1 continuing to circulate in U.S. animals, our biggest danger nationwide is that we don’t know what we don’t know,” noted Katherine E. Goodman, PhD, JD, assistant professor of Epidemiology & Public Health at UMSOM. (Photo credit: UMSOM)
Goodman emphasized that without consistent tracking of potential exposures, infections may be slipping through the cracks.
“Because we are not tracking how many symptomatic patients have potential bird flu exposures, and how many of those patients are being tested, infections could be going undetected,” she said. “It’s vital for healthcare systems to monitor for potential human exposure and to act quickly on that information.”
Bird Flu’s Spread in U.S. Livestock and Birds
The urgency stems from the current spread of H5N1 among U.S. livestock and birds. Since early 2024, the virus has been detected in more than 1,075 dairy herds across 17 states, with over 175 million poultry and wild birds testing positive. Human cases remain rare—70 confirmed with one fatality as of mid-2025, according to the CDC—but experts caution that many more may have gone undetected due to limited testing. The emergence of strains capable of human-to-human spread remains a concern.
Efficiency and scalability were key strengths of the AI approach. “The AI review required only 26 minutes of human time and cost just 3 cents per patient note, demonstrating high scalability and efficiency,” said co-author Anthony Harris, MD, MPH, acting chair of Epidemiology & Public Health at UMSOM. “This method has the potential to create a national network of clinical sentinel sites for emerging infectious disease surveillance.”
The LLM used, GPT-4 Turbo, proved highly accurate when tested on 10,000 historical emergency visits from 2022–2023, showing a 90% positive predictive value and a 98% negative predictive value. Still, researchers noted the model occasionally flagged lower-risk exposures, such as to dogs, underscoring the need for human review.
Next Steps for Real-Time Monitoring
Looking ahead, the team hopes to integrate the tool directly into electronic health records for real-time alerts. This would allow clinicians to ask about exposures, order targeted tests, and isolate patients if needed. Currently, CDC surveillance depends on mandated lab reports, with no system to track whether clinicians are documenting animal exposure in symptomatic patients.
UMSOM dean Mark T. Gladwin, MD, called the work a glimpse of what’s possible with big data and AI. “We are at the forefront of a disruptive but incredibly promising revolution around big data and artificial intelligence,” he said. “As this study demonstrates, [we] can use AI and big data to identify early signals of emerging infectious diseases like bird flu to enable us to take action sooner to test for these diseases and keep them from spreading.”
The project relied on the University of Maryland Institute for Health Computing (UM-IHC), a collaboration established in 2022 to combine computational, clinical, and data resources across the state’s medical and academic institutions.
New recommendations from the Alzheimer’s Association call for Alzheimer’s blood tests to reach at least 90% sensitivity and specificity to be used in place of established diagnostic tools.
Alzheimer’s blood tests need to offer at least 90% sensitivity and 90% specificity before they can replace brain scans and spinal taps in diagnosis of the neurodegenerative disease, according to a new clinical practice guideline recommendation from the Alzheimer’s Association.
The health organization cautioned in a news release that “many commercially available blood-based biomarker tests do not meet these thresholds” for substituting amyloid PET imaging and cerebrospinal fluid (CSF) tests in Alzheimer’s diagnosis.
“The whole purpose of developing the clinical practice guideline is to try to create pragmatic recommendations for clinicians on how to choose the right test for the right patient at the right time,” Rebecca Edelmayer, PhD, Alzheimer’s Association Vice President of Scientific Engagement, told Medscape. “The blood- based biomarker area is still a burgeoning field,” added Edelmayer, a guideline Co-author.
Clinical laboratories may find the recommendations useful in making decisions about additions to lab test menus and in educating clinicians on appropriate test ordering.
“Pathologically, Alzheimer’s disease is defined by the accumulation of extracellular cortical plaques composed of amyloid-beta fibrils and intracellular neurofibrillary tangles containing abnormal hyperphosphorylated tau protein. These pathologies manifest many years or even decades before the onset of clinical symptoms,” the authors wrote.
Compared to “standard-of-care” amyloid PET imaging and CSF tests, blood-based biomarkers may cost less and reduce patients’ stress, the Alzheimer’s Association pointed out, adding that blood tests are not a replacement for clinical evaluations by healthcare providers.
“What we’ve learned from all of the evidence so far is that some of these biomarkers, like tau217, tend to be very accurate predictors of Alzheimer’s disease biology in the brain, and they can be used to aid in the diagnostic process early on—sometimes even before tau tangle formations can be visualized with brain imaging,” Rebecca Edelmayer, PhD, Alzheimer’s Association Vice President of Scientific Engagement, said in the Medscape article. (Photo credit: Alzheimer’s Association.)
Panel Reviews Phosphorylated-tau and Amyloid-beta
To discover the diagnostic accuracy of blood-based biomarkers in Alzheimer’s disease, a panel of 11 clinicians, convened by the Alzheimer’s Association, did a systematic review using this methodology described in the association’s statement:
Reviewed 49 observational studies and assessed 31 tests.
Focused on blood-based biomarkers including plasma phosphorylated-tau (p-tau) and amyloid beta (Aβ) tests measuring: p-tau217, ratio of p-tau217 to non-p-tau217 x 100, p-tau181, p-tau231, and ratio of Aβ42 to Aβ40.
Panelists, unaware of the tests they were reviewing, did not rank or endorse tests.
Diagnostic accuracy varied among the assays with sensitivity ranging from 49.31% to 91.41% and specificity from 61.54% to 96.72%, Neurology Advisorreported.
Tests evaluated included these, which were also recently reported on by Dark Daily:
Based on the systematic review, the panel released the following recommendations for use of blood-based biomarker tests when Alzheimer’s disease is suspected, according to the Alzheimer’s Association:
Tests with 90% sensitivity and 90% specificity or more may stand-in for PET amyloid imaging or CSF Alzheimer’s biomarker testing.
Tests with at least 90% sensitivity and 75% specificity can serve as triaging assays whereby negative results rule out Alzheimer’s “with high probability” while positive findings need confirmation with PET or CSF testing.
“For the first time, we have a rigorously evidence-based guideline that empowers clinicians to use blood biomarker tests confidently and consistently. Adoption of these recommendations will lead to quicker, more accessible, more accurate diagnoses, and better outcomes,” said Maria Carillo, PhD, Alzheimer’s Association Chief Science Officer and Medical Affairs Lead and a Co-author of the guideline.
The guideline is part of the Alzheimer’s Association resources to promote best practices. It plans development of other reports about cognitive assessment tools, clinical implementation of staging, and Alzheimer’s prevention.
Nearly all doctors call lab testing essential, but shortages and patient pressures are putting the system to the test.
Physicians across the United States certainly recognize the indispensable role of clinical laboratory testing in patient care, but growing workforce shortages, financial pressures, and rising patient demands are straining the system, according to a new survey conducted by YouGov on behalf of Siemens Healthineers.
The survey was released on July 29, during the Association for Diagnostics & Laboratory Medicine (ADLM) conference in Chicago.
The Dark Dailyrecently covered how findings at ADLM showed digital pathology trends are being slowly adopted in the US but how there’s a larger movement to connect patient care more directly.
The survey of 408 physicians, along with a parallel poll of 1,000 patients, reveals both how deeply doctors depend on laboratory professionals and how external pressures are reshaping testing decisions.
“Ninety-nine percent of physicians agree clinical lab testing is an integral part of the healthcare system,” the report states. Nearly all respondents said lab results are vital in informing treatment choices, with 98% noting they had modified a diagnosis or care plan based on test outcomes. As one physician put it, lab tests “help determine my actions” by providing crucial clarity in uncertain cases.
Doctors also reported that laboratory insights streamline the use of other healthcare resources. “Together, we help the health system and avoid unnecessary patient interventions,” one physician said, noting how test results often reduce the need for additional imaging or biopsies. In fact, 100% of surveyed physicians agreed that lab data helps them use other healthcare tools more effectively.
The Growing Strain on Labs
Despite reliance on labs, the collaboration doctors depend on is increasingly at risk. Clinical laboratory professionals manage more than 80,000 different tests across US facilities and generate roughly 14 billion results annually. Yet the workforce supporting this output is shrinking.
“When labs are short-staffed, it has a downstream effect on patient care,” 96% of doctors agreed. Another 94% expressed concern about healthcare staffing shortages more broadly. The problem is particularly acute in laboratories, where the number of training programs has dropped below 250 nationwide, leaving only about one lab scientist per 1,000 Americans.
Financial pressures are compounding the workforce issue. Though lab services account for only 4% of hospital costs, they are frequently targeted for cost-cutting. Consolidation and outsourcing have moved testing away from local facilities and toward centralized “dark labs,” largely operated by automation. While these high-tech labs maintain throughput, physicians caution that automation cannot replace collaboration. “In the age of automation, the human collaboration physicians depend on still counts,” the report warns.
Patient Demands Reshape Testing
Physicians are also feeling pressure from patients, many of whom arrive armed with information—or misinformation—from the internet. This rising “patient agency,” defined as the ability to influence healthcare decisions, is reshaping physician-patient interactions.
“Patient requests have forced me to weigh patient satisfaction against clinical judgment,” one physician admitted. Survey data shows 84% of patients expect their doctors to order requested tests, while 76% of physicians acknowledged ordering labs simply to satisfy those requests.
Zobair Younossi, MD, MPH, chairman, The Global NASH/MASH Council, said, “As a hepatologist dedicated to enhancing liver disease care, I believe that advances in laboratory testing are enabling us to ‘move the needle’ from liver biopsy toward blood-based biomarkers, allowing for earlier intervention through less invasive methods. For this shift to be successful, collaboration between clinicians and laboratory professionals is essential.” (Photo credit: MASH Alliance)
At the same time, 90% of patients said they trusted their doctor’s recommendation if the physician advised against unnecessary tests. Still, the survey underscores tension: while exploratory testing may placate patients, it can also create unnecessary costs and confusion. “Laboratory testing may be somewhat mitigating, though it can add unnecessary volume and expense for already overburdened clinical laboratories,” the report cautions.
The Hidden Role of Cost and Bureaucracy
Physicians also report external bureaucratic and financial pressures influencing test orders. About 32% said they had faced directives to reduce testing, while only 37% had visibility into the cost of lab tests they ordered. That number dropped further when asked about insurance coverage.
“Inadequate healthcare coverage may prevent patients from getting the appropriate level of laboratory testing,” the report notes. Among doctors who do know test costs, 60% admitted delaying orders due to expense concerns. From the patient side, 29% of respondents reported unpaid medical bills, with more than half saying their debt included lab testing fees.
Physicians are caught between avoiding unnecessary spending and protecting themselves from malpractice risk. Nearly 70% cited fear of being sued for misdiagnosis as a top concern, and 92% said they consider whether lab testing might reduce that risk. As one doctor put it, “Errors that negatively impact a patient’s care weigh heavy on my conscience and affect my mental health.”
A Call for Stronger Collaboration
Despite these pressures, doctors remain clear on their priorities. “Ninety-five percent agree that ordering tests to validate a patient’s care plan is their priority over conserving resources,” the report found. To achieve that, physicians want stronger ties with clinical lab professionals.
More than half—55%—said they heavily rely on lab experts to confirm which tests are most relevant, while 96% said they welcomed feedback from laboratory colleagues to improve ordering practices. “Physicians say clinical laboratory professionals are essential partners in delivering high-quality patient care, but a shrinking laboratory workforce may threaten the collaboration doctors rely on for clinical clarity,” the report concludes.
The Future of the Lab
Looking ahead, the report raises the question of whether the rise of automation-heavy dark labs will be a temporary solution or a permanent shift. For many doctors, the fear is losing the human expertise that helps interpret increasingly complex test menus.
“What physicians want are clinical partners and greater access to skilled professionals whose clinical insights help inform their patient care decisions,” the report states.
Without reinvestment in labs and workforce development, patients may face longer wait times, higher costs, and reduced trust in the system.
Ultimately, both doctors and patients recognize the centrality of the lab. The challenge now, as the survey shows, is ensuring those professionals are supported. “Recognizing laboratory professionals as collaborative clinical partners, and resourcing clinical labs as essential infrastructure rather than cost centers, is vital to safeguarding the important clinical support physicians rely on,” Siemens Healthineers concluded.
Danaher’s chief medical officer, Maximilian Schmid, says ‘infrastructure is there’ to push forward whole slide imaging.
Based on discussions at the recent Association for Diagnostics & Laboratory Medicine’s (ADLM) 2025 conference and observations from other sources, digital pathology trends continue to show sluggish adoption by clinical laboratories and anatomic pathology practices in the US. However, proponents of whole slide imaging say now is a prime opportunity to integrate the technology with a patient-centric care approach.
At least 65 vendors at the ADLM 2025 exhibitor hall indicated that their products touched whole slide imaging or digital pathology, showing this area is a hot focus for sellers.
Based on its customers, Leica has one of the largest installation bases of digital pathology scanners in the world. From that perspective, the technology is available, yet obstacles remain.
“The infrastructure is there,” said Maximilian Schmid, MD, chief medical officer at Danaher Diagnostics. “How do we bring it to the patients?”
Danaher Corporation, which held a press briefing at ADLM 2025, is parent company to Leica.
ADLM 2025 took place in Chicago July 27-31at McCormick Place. (Photo credit: Scott Wallask.)
Labcorp Report Notes Costs as a Barrier
Anyone who has followed the slow progression of digital pathology knows adoption from the diagnostic lab industry has been lukewarm. In 2024, Labcorp released a report about clinical laboratory trends that indicated cost remained a hurdle to further use of digital pathology scanners and software. Based on a survey of 115 US-based pathologists, lab managers, and lab directors, the report concluded that just 33% of respondents had started orplanned to implementdigital pathologyin lab workflows.
“Industry adoption of digital pathology has been slower than expected, largely due to high initial costs,” Deborah Sesok-Pizzini, MD, MBA, chief medical officer at Labcorp, told Today’s Clinical Lab at the time. That publication is a partner brand to Dark Daily.
Digital Pathology Trends are Rosier in Europe
Leica has been able to convey a message to its customers that despite the initial costs, the return on investment for digital pathology is high in terms of more accurate diagnoses and quicker processes, Schmid said.
“When I look ahead 10 years, digital pathology will be as normal to labs as H&E staining,” he predicted, referring to common hematoxylin and eosin stains.
He added that while Labcorp’s study reflected US trends, digital pathology adoption is stronger elsewhere, based on what Danaher and Leica see with customers.
“Europe seems to be a little bit ahead in terms digitization,” including with whole-slide imaging, he noted. However, even in the US, “academic medical centers are moving very fast in this direction.”
Schmid’s assertion about Europe is supported by other sources. For example, a business case published in July 2024 by the UK’s National Health Service (NHS) for Wales indicated that Northern Ireland and Scotland had near-fully digitized cellular pathology programs for the NHS, and England was building up its network. Wales was seen as trailing behind these countries.
“The national move towards scanning of histological material for primary diagnosis and more recently, the adoption of artificial intelligence (AI)/computational pathology to improve the accuracy, reliability and quality of reports, means that most pathologists, especially new trainees who are already using digital technology, will, in the future, choose to work in departments where digital technology will enhance and underpin their diagnosis thus benefiting the quality of patient care,” the NHS Wales business case paper stated.
Computational Pathology’s Growing Role
Computational pathology—in other words, the use of data science, information, and digital technologies for laboratory medicine—is a key to moving precision medicine forward via digital pathology, said Nicole Selenko-Gebauer, MD, MBA, group vice president and chief innovation officer at Danaher Diagnostics.
“We need to complement technology-driven focuses” with a patient-centric approach, Selenko-Gebauer added.
Even in 2022, The Dark Report had alerted its readers to the promise of computational pathology, noting Mayo Clinic Laboratories’ early success in launching related clinical assessment goals based on digital pathology and artificial intelligence. (If you’re not a Dark Report subscriber, check out our 14-day free trial.)
Taken at that viewpoint, digital pathology trends related to patient care will be an important milestone for the technology.
“A pivotal moment will be the clinical utilization of digital pathology—that it works and is accurate,” Schmid said.
Lab leaders can now align with WHO’s new product profile to develop innovative diagnostics that address gaps in newborn infection detection and antimicrobial resistance prevention.
The World Health Organization (WHO) has unveiled a new target product profile aimed at guiding the development of in vitro diagnostic tests for detecting serious bacterial infections in newborns and young infants, including neonatal sepsis—a major cause of infant mortality worldwide. This initiative comes in response to alarming statistics: 2.3 million newborns die every year, with around 15% of these deaths linked to sepsis. The burden is heaviest in low- and middle-income countries, where access to timely diagnosis and treatment remains limited.
Current diagnostic methods such as blood cultures and molecular diagnostics are often inaccessible, expensive, or unreliable, particularly in resource-limited settings. They suffer from low sensitivity, long turnaround times, and high infrastructure demands, making them poorly suited for the urgent needs of frontline healthcare facilities.
Lab Leaders See Shift in Global Standards
For laboratory leaders, WHO’s newly released target product profile for diagnosing serious bacterial infections in newborns and young infants could represent a pivotal shift in global diagnostic standards. As the demand for timely, accurate, and affordable diagnostic tools grows—particularly in low-resource settings—lab leaders have a unique opportunity to play a central role in shaping the next generation of in vitro diagnostics.
The new profile to is designed to define the essential and desirable characteristics of diagnostic tools needed to improve early detection of infections in infants aged 0–59 days. The profile covers two major clinical scenarios: use in primary health care settings and in higher-level hospitals. It’s intended to assist developers, regulators, and public health officials in designing effective tools tailored to diverse healthcare environments.
Yvan Hutin, MD, PhD, Director of the Department of Antimicrobial Resistance at WHO, emphasized the urgency of the effort, stating, “Timely and accurate diagnosis tests for serious bacterial infection is critical to reducing newborn mortality.”
Hutin’s areas of expertise include epidemiology, prevention, care and treatment of viral hepatitis, public health training, economic analyses, and financing. He has co-authored more than 120 articles in peer-reviewed journals. (Photo credit: WHO)
Silvia Bertagnolio, MD, Head of the Antimicrobial Resistance Surveillance, Evidence and Laboratory Strengthening Unit at WHO noted, “This new target product profile outlines the essential features needed in diagnostic tools to improve clinical decision-making, reduce unnecessary antibiotic use and prevent antimicrobial resistance, especially in low-resource settings where the burden of neonatal sepsis remains critical.”
Targeted Care
In many communities, healthcare workers must make critical decisions about antibiotic treatment or hospital referrals based on clinical judgment alone, without reliable diagnostics. The new tools envisioned by WHO would help identify which infants truly need antibiotics or hospitalization, allowing for more targeted and effective care.
For laboratory leaders, the release of this target product profile is more than just a technical guideline, it’s a call to action. By aligning their diagnostic development and evaluation efforts with WHO’s outlined priorities, lab leaders can help fill a critical gap in newborn and infant care, particularly in underserved regions. Their expertise will be essential in translating this profile into practical, scalable solutions that improve early detection, guide appropriate treatment, and ultimately save lives. As stewards of innovation and quality in diagnostics, lab leaders are uniquely positioned to drive meaningful progress in the global fight against neonatal infections and antimicrobial resistance.
