The federal agency shipped tests to five commercial clinical laboratory companies, augmenting efforts by public health labs
Medical laboratories in the US are ramping up their efforts to respond to an outbreak of monkeypox that has been spreading around the globe. Microbiologists and clinical laboratory scientists will be interested to learn that this infectious agent—which is new to the US—may be establishing itself in the wild rodent population in this country. If proved to be true, it means Americans would be at risk of infection from contact with rodents as well as other people.
The Centers for Disease Control and Prevention (CDC) announced on May 18 that it had identified the infection in a Massachusetts resident who had recently traveled to Canada. As of August 3, the federal agency was reporting 6,617 confirmed cases in the US.
“Because there are no other non-variola orthopoxviruses circulating in the US, a positive test result is presumed to be monkeypox,” states the APHL press release.
“As we focus on the US response, we keep a close watch on the global outbreak. Infectious diseases don’t respect borders, as we know,” said Chris Mangal (above), director of public health preparedness and response, APHL, in a press release. “I am proud of how LRN member laboratories have rapidly and effectively responded to this emergency. This is precisely what the LRN was intended to do. Should this outbreak continue to grow, preparing for expanded testing and increasing capacity beyond LRN laboratories is important to ensuring we are ready for a surge in testing.” (Photo copyright: Association of Public Health Laboratories.)
Commercial Labs Get Involved
Seeking to bolster testing capacity, the federal Department of Health and Human Services (HHS) announced on June 22 that the CDC had begun shipping OrthopoxvirusPCR tests to five commercial lab companies. They include:
“By dramatically expanding the number of testing locations throughout the country, we are making it possible for anyone who needs to be tested to do so,” said HHS Secretary Xavier Becerra in an HHS press release.
Labcorp was first out of the gate, announcing on July 6 that it was offering the CDC-developed test for its customers, as well as accepting overflow from public labs. “We will initially perform all monkeypox testing in our main North Carolina lab and have the capacity to expand to other locations nationwide should the need arise,” said Labcorp chief medical officer and president Brian Caveney, MD, in a press release.
Mayo Clinic Laboratories followed suit on July 11, announcing that the clinic’s Department of Laboratory Medicine and Pathology would perform the testing at its main facility in Rochester, Minnesota.
“Patients can access testing through Mayo Clinic healthcare professionals and will soon be able to access testing through healthcare professionals who use Mayo Clinic Laboratories as their reference laboratory,” Mayo stated in a press release.
Then, Quest Diagnostics announced on July 13 that it was testing for the virus with an internally developed PCR test, with plans to offer the CDC test in the first half of August.
The lab-developed test “was validated under CLIA federal regulations and is now performed at the company’s advanced laboratory in San Juan Capistrano, Calif.,” Quest stated in a press release.
Public Health Emergency?
Meanwhile, the CDC announced on June 28 that it had established an Emergency Operations Center to respond to the outbreak. A few weeks later, on July 23, World Health Organization (WHO) Secretary-General Tedros Adhanom Ghebreyesus, PhD, declared that the outbreak represented “a public health emergency of international concern.”
He noted that international health regulations required him to consider five elements to make such a declaration.
“WHO’s assessment is that the risk of monkeypox is moderate globally and in all regions, except in the European region where we assess the risk as high,” he said in a WHO news release. “There is also a clear risk of further international spread, although the risk of interference with international traffic remains low for the moment. So, in short, we have an outbreak that has spread around the world rapidly, through new modes of transmission, about which we understand too little, and which meets the criteria in the International Health Regulations.”
Still, public health authorities have made it clear that this is not a repeat of the COVID-19 outbreak.
“Monkeypox virus is a completely different virus than the viruses that cause COVID-19 or measles,” the CDC stated in a June 9 advisory. “It is not known to linger in the air and is not transmitted during short periods of shared airspace. Monkeypox spreads through direct contact with body fluids or sores on the body of someone who has monkeypox, or with direct contact with materials that have touched body fluids or sores, such as clothing or linens. It may also spread through respiratory secretions when people have close, face-to-face contact.”
The New York Times reported that some experts disagreed with the CDC’s assessment that the virus “is not known to linger in the air.” But Professor of Environmental Health Donald Milton, MD, DrPH, of the University of Maryland, told The Times it is still “not nearly as contagious as the coronavirus.”
The Massachusetts resident who tested positive in May was not the first known case of monkeypox in the US, however, previous cases involved travel from countries where the disease is more common. Two cases in 2021—one in Texas and one in Maryland—involved US residents who had recently returned from Nigeria, the CDC reported. And a 2003 outbreak in the Midwest was linked to rodents and other small mammals imported to Texas from Ghana in West Africa.
“Labcorp and Quest don’t dispute that in many cases, their phlebotomists are not taking blood from possible monkeypox patients,” according to CNN. “What remains unclear, after company statements and follow-ups from CNN, is whether the phlebotomists are refusing on their own to take blood or if it is the company policy that prevents them. The two testing giants say they’re reviewing their safety policies and procedures for their employees.”
One symptom of monkeypox, the CDC states, is a rash resembling pimples or blisters. Clinicians are advised that two swabs should be collected from each skin lesion, though “procedures and materials used for collecting specimens may vary depending on the phase of the rash.”
“Effective communication and precautionary measures between specimen collection teams and laboratory staff are essential to maximizing safety when manipulating specimens suspected to contain monkeypox virus,” the CDC notes. “This is especially relevant in hospital settings, where laboratories routinely process specimens from patients with a variety of infectious and/or noninfectious conditions.”
Perhaps the negative reaction to the CDC’s initial response to the COVID-19 outbreak in the US is driving the federal agency’s swift response to this new viral threat. Regardless, clinical laboratories and pathology groups will play a key role in the government’s plan to combat monkeypox in America.
DNA analysis of early plague victims pinpoints Black Death’s start on Silk Road trading communities in mountain region of what is now modern-day Kyrgyzstan in Central Asia
Microbiologists and clinical laboratory scientists will likely find it fascinating that an international team of scientists may have solved one of history’s greatest mysteries—the origin of the bubonic plague that ravaged Afro-Eurasia in the mid fourteenth century. Also known as the Black Death, the plague killed 60% of the population of Europe, Asia, and North Africa between 1346-1353 and, until now, the original source of this disease has largely gone unsolved.
In their study published in the journal Nature, titled, “The Source of the Black Death in Fourteenth-Century Central Eurasia,” the authors outlined their investigation of cemeteries in the Chüy Valley of modern-day Kyrgyzstan. The tombstone inscriptions showed a disproportionally high number of burials dating between 1338 and 1339 with inscriptions stating “pestilence” as the cause of death.
Archeological evidence combined with ancient DNA analysis of early plague victims enabled scientists to pinpoint the Black Death’s origins in Kyrgyzstan. “We have basically located the origin in time and space, which is really remarkable,” geneticist Johannes Krause, PhD (above), Professor at the Max Planck Institute for Evolutionary Anthropology, who co-led the study, told The Guardian. “We found not only the ancestor of the Black Death, but the ancestor of the majority of the plague strains that are circulating in the world today.” These new research findings may help microbiologists and clinical pathologists gain new insights into how current strains of Yersinia pestis can be better diagnosed. (Photo copyright: Max Planck Institute.)
Big Bang of Plague
Using 30 skeletons that were excavated from these cemeteries in the late 1880s and moved to St. Petersburg, Russia, the scientists analyzed the DNA of ancient pathogens recovered from the remains of seven people. They discovered Yersinia pestis (Y. pestis) DNA in three burials from Kara-Djigach, which lies in the foothills of the Tian Shan mountains.
According to another article in Nature, the scientists showed that a pair of full Y. pestis genomes from their data were direct ancestors of strains linked to the Black Death, and that the Kara-Djigach strain was an ancestor of the vast majority of Y. pestis lineages circulating today.
“It was like a big bang of plague,” Krause stated at a press briefing, Nature reported.
The research team concluded that the Tian Shan region was the location where Y. pestis first spread from rodents to people, and that the local marmot colonies likely the prevalent rodent carriers of plague.
“We found that modern strains [of the plague] most closely related to the ancient strain are today found in plague reservoirs around the Tian Shan mountains, so very close to where the ancient strain was found. This points to an origin of Black Death’s ancestor in Central Asia,” Krause explained in a Max Planck Institute news release.
He told Nature that fleas likely passed the marmot-based infection on to humans, sparking a local Kyrgyzstan epidemic. The disease then spread along the Silk Road trade routes, eventually reaching Europe, where rats (and the fleas that they carried) spread the disease.
Understanding Context of Plague
Writing in The Conversation, Associate Professor of Medieval and Environmental History Philip Slavin, PhD, University of Stirling, who co-authored the study, explained that Kara-Djigach is unlikely to be “the specific source of the pandemic,” but rather that the “disaster started somewhere in the wider Tian Shan area, perhaps not too far from that site,” where marmot colonies were likely the source of the 1338-1339 outbreak.
Making a modern-day comparison, Krause told Nature, “It is like finding the place where all the strains come together, like with coronavirus where we have Alpha, Delta, Omicron all coming from this strain in Wuhan.”
Slavin maintains that understanding the “big evolutionary picture” is key when studying the phenomenon of emerging epidemic diseases.
“It is important to see how these diseases develop evolutionary and historically, and avoid treating different strains as isolated phenomena,” he wrote in The Conversation. “To understand how the diseases develop and get transmitted, it is also crucial to consider the environmental and socioeconomic contexts.”
Scientists have spent centuries debating the source of the Black Death that devastated the medieval world. The multidisciplinary process used by the Slavin/Krause-led team provides a lesson to clinical laboratory managers and pathologists on the important role they play when collaborating with colleagues from different fields on scientific investigations.
Employer group in Houston plans to use the numbers to pressure lawmakers for policy changes involving how hospitals and health plans price their services
Clinical laboratory leaders will probably not be surprised to learn that wide disparities exist between what Medicare pays hospitals and what is paid by private insurers and employers. That’s according to analysis by the Houston Business Coalition on Health (HBCH) which examined costs and billing practices at four of the region’s top hospitals, each a flagship for its respective health system.
This study—by a business group concerned about the spiraling cost of healthcare for their employees—is significant because it indicates that some large employers are willing to become more aggressive in driving down healthcare costs. In the Houston study, three of these hospitals—Houston Methodist, Memorial Hermann, and HCA Houston Medical Center—charged more than 250% over Medicare, noted a press release, which stated the group plans to use the numbers to lobby Texas lawmakers for policy changes.
“The prices employers paid to hospitals are unsustainable and negatively impact business growth, family quality of life, and resources needed for other critical community social needs,” said HBCH executive director Chris Skisak, PhD, in the press release. “Our intent in sharing and publicizing these resources is to facilitate direct discussions with health systems and employers to better understand the ramifications to Houston businesses and the greater community.”
The HBCH describes itself as a resource for local employers and healthcare providers seeking to promote cost-effective healthcare delivery and health benefits. It has 60 members that collectively provide healthcare coverage for 500,000 area residents.
“We’re entering a new age of transparency and it’s clear from these tools that pricing is not directly correlated with quality, but rather on what the market will bear,” said HBCH executive director Chris Skisak, PhD (above), in a press release. “While this is cause for concern, there are opportunities for change and these resources will enable employers and health plans to negotiate future contracts to select health systems that offer the best value—the highest quality at the lowest costs.” (Photo copyright: Houston Business Journal.)
Hospital Claims Medicare Reimbursement Flawed
A spokesperson for Memorial Hermann disputed the HBCH’s analysis, telling the Houston Chronicle that “Medicare reimbursement is a flawed and an inappropriate benchmark to use for commercial payments, as Medicare payments do not cover the cost of services provided.”
But the HBCH analysis also disclosed that each hospital was charging private insurers more than double the breakeven, defined as the amount needed “to make up for any shortfalls from public sector payers such as Medicare and Medicaid and uninsured patients.” And they “achieved a commercial profit margin of more than 45%” over the breakeven.
The fourth hospital, Baylor St. Luke’s, charged 216% over Medicare and had a commercial profit margin of close to 20%.
The Medicare claims data came from a RAND study, titled, “Prices Paid to Hospitals by Private Health Plans.” The 53-page report is accompanied by a downloadable spreadsheet with details on prices at more than 4,000 hospitals in 49 states plus the District of Columbia. Released in May, it covers data from 2018 through 2020.
The HBCH analysts combined data from this report with data from the NASHP Hospital Cost Tool (HCT), which was released in April. The HCT allows anyone with a web browser to look up cost metrics for 4,600 hospitals in the US. The numbers, available through 2019, include revenue, profitability, and breakeven points. It also incorporates an earlier set of the RAND Medicare claims data.
An NASHP press release notes that the breakeven calculation “accounts for a hospital’s operating costs, profit or loss from public coverage programs, charity care and uninsured patient hospital costs, Medicare disallowed costs, and a hospital’s other income and expense.”
The HBCH press release notes that hospitals need only 127% of Medicare to break even.
National Numbers
Nationally, the RAND study found wide variations in prices paid by private health plans from state to state. “In Texas, prices paid to hospitals for privately insured patients by employers averaged 252% of what Medicare would have paid,” the HBCH press release noted.
But that places Texas around the middle of the pack compared with other states. According to a Rand press release, prices charged to commercial payers were over 310% of Medicare in Florida, West Virginia, and South Carolina. But in Arkansas, Hawaii, and Washington, the numbers were below 175% of Medicare. The overall national average was 224%, the study found.
The RAND report’s downloadable spreadsheet breaks out the numbers by state and for individual health systems by name.
Numbers like these could have policy ramifications as employers seek to reduce the costs of providing health benefits. “The data is already being used to guide a new path forward,” states the HBCH press release. “As an example, HBCH and its members are working to demand transparency and change policies in the upcoming Texas 88th Legislative Session to eliminate anti-competitive language between hospitals and health plans.”
Clinical laboratory managers and pathologists working in hospitals and health systems will want to watch how employer groups respond to future studies of hospital pricing compared to the Medicare program. Employers increasingly are dissatisfied with the status quo in how hospitals and doctors price their services to health insurers.
It is reasonable to expect more studies to be published that compare what hospitals charge private health insurers versus what they are paid by the Medicare program.
Genetic testing for the health and wellbeing of beloved pets is not unlike clinical laboratory testing to develop personalized treatments for humans
Clinical laboratory professionals know that the same patients who complain about a $10 copay for their own laboratory testing will happily pay veterinarians tons of cash to test and treat their beloved pets. And as genetic testing for humans becomes commonplace, more people are seemingly willing to pay for genetic analyses of their pets as well.
In June, animal health company Zoetis, Inc. announced it had completed the acquisition of pet care genetics company Basepaws. The financial terms of the deal were not disclosed.
California-based Basepaws is a privately-held company that provides pet owners with analytics, genetic tests, and early health risk assessments for their pets through oral microbiome analysis. Founded in 2017, Basepaws was responsible for the creation of the first at-home genetic testing platform for cats.
Basepaws sells easy-to-use genetic testing kits for cats that allow pet owners and veterinarians to better understand an individual pet’s predisposition to certain illnesses and increase the likelihood of early detection and treatment of those diseases.
It’s not unlike the drive toward personalized medicine and genetic testing that is at the core of human precision medicine.
Different Breeds, Different Needs
Basepaws has a slogan: “Different breeds, different needs.” This means, according to their website, each individual cat has a unique composition of genetic traits that can relate to its needs for optimal health and wellbeing. Obviously, this would apply to all pets.
“As a pioneer in pet care genetics, the California-based Basepaws offers easy-to-use genetic screening tools for the early detection of disease risk in pets, as well as individualized breed and health reports that can identify traits, biomarkers, and potential hereditary conditions for pets. Basepaws helps pet owners and veterinarians understand an individual pet’s risk for disease and can lead to more meaningful engagements and increased likelihood of early detection and treatment of disease,” states a Zoetis press release announcing the acquisition.
“The addition of Basepaws will enhance our portfolio in the precision animal health space and inform our future pipeline of pet care innovations,” said Kristin Peck, CEO of Zoetis, in the press release. “Working together, we can continue to provide veterinarians and pet owners with more comprehensive ways to proactively manage the health, wellness, and quality of care for their animals.”
“Basepaws and Zoetis both consist of pet lovers with a passion for science, and our mission is to create better and longer lives for our pets through knowledge and data,” Anna Skaya (above), CEO of Basepaws, told ROI-N.J. “We look forward to expanding our business and the impact of our genetic products with the global scale and [research and development] experience of Zoetis, the world leader in animal health. We believe that, together, we can bring the benefits of a more proactive healthcare approach to pet parents around the world.” Genetic testing for optimum pet health is not unlike the drive for personalized clinical laboratory genetic testing for humans. (Photo copyright: Los Angeles Times.)
Test Results for Hundreds of Genetic Disorders and Health Markers
Basepaws currently sells three DNA test kits for felines on their webpage. The current price for an oral health test kit that identifies active signs of dental diseases is $69. Their breed and cat health DNA test kit, which provides results for over 115 known feline genetic markers, is $129. Their most comprehensive testing kit is a whole genome sequencing (WGS) kit which is currently on sale for $399.
After receiving a test kit by mail, the purchaser registers the kit online, takes a single buccal swab from their kitty’s inner cheek, and then mails the sample to Basepaws. Lab personnel then extract the cat’s DNA from the sample and perform quality checks to ensure the sample is acceptable for genetic testing. It takes four to six weeks for consumers to receive test results.
According to the company’s website, Basepaws’ WGS test provides results related to 43 genetic disorders that are represented by 65 health markers. The listing of genetic disorders contained in the Health Marker section of the Basepaws report includes data on:
Metabolic disorders,
Musculoskeletal and connective tissue disorders,
Renal disorders,
Cardiovascular disorders,
Blood disorders,
Eye disorders,
Endocrine disorders,
Skin disorders, and
Autoimmune disorders.
“The Basepaws team has done an amazing job demonstrating how genetic testing and data can improve how we care for the pets in our lives,” Abhay Nayak, Executive Vice President at Zoetis, told ROI-NJ. “With the addition of Basepaws, Zoetis will continue to strengthen our portfolio of products for precision animal health, across genetics, diagnostics, and data analytics for pets and livestock. We are also excited by how Basepaws’ feline genomic and microbiome database will help enhance our [research and development] capabilities and inform the future of our pet care pipeline.”
Zoetis, based in Parsippany, N.J., manufactures vaccines, medicines, clinical laboratory diagnostics, and other technologies for the benefit of companion pets and livestock. The Fortune 500 company generated $7.8 billion in revenue in 2021, according to its website.
The article also stated that the global animal genetic testing market was valued at $990 million in 2020 and is only expected to rise.
Thus, spending money keeping our pets healthy is not only a typical element of Americans’ lives, but also a mega-billion-dollar industry. With at-home genetic testing for humans increasing in popularity, it’s likely testing for animals will follow that trend as well.
In the future, some clinical laboratory organizations may want to consider assessing the animal DNA testing market for its potential to be a useful source of new revenue, especially because potential customers will pay cash when they order genetic tests for their dogs and cats.
In fact, the UB study suggests traditional anatomical methods for determining the evolutionary relationships between species may not be as accurate as once thought, an article in SciTechDaily reported.
Nevertheless, the UB’s research into convergent evolution is unlocking new insights into how genes evolve over time and this new knowledge may help researchers develop genetic tests that more accurately identify different diseases and health conditions.
Additionally, studies that bring a better understanding of how beneficial genetic mutations work their way into a species’ genome might also aid researchers in developing personalized clinical laboratory testing and therapies based on manipulating a patient’s genetic sequences in ways that would be beneficial.
Gene Sequencing More Accurate at Determining Evolutionary Relationships
The UB study suggests that existing evolutionary (phylogenetic) trees may need to be reconsidered. To put a finer point on the findings, a UB news release on the study states, “determining evolutionary trees of organisms by comparing anatomy rather than gene sequences is misleading.”
The UB scientists used genetic sequencing to quickly—and more cost effectively—determine evolutionary relationships as compared to traditional morphology (anatomy and structure), according to the news release.
They found genetic data that revealed surprising relationships about where the sequenced species originated, and which differed with prior conclusions that were drawn based on the species’ appearance. The findings suggest there may be need to “overturn centuries of scientific work in classifying relation of species by physical traits,” the UB scientists said.
“For over a hundred years, we’ve been classifying organisms according to how they look and are put together anatomically, but molecular data often tells us a rather different story,” said Matthew Wills, PhD (above), Professor of Evolutionary Paleobiology, Milner Center for Education at the University of Bath, in the news release. “Our study proves statistically that if you build an evolutionary tree of animals based on their molecular data, it often fits much better with their geographical distribution.” This new use of genetic sequencing could lead to improved precision medicine treatments and clinical laboratory testing. (Photo copyright: University of Bath.)
Molecular Data Leads to New Insights into Convergent Evolution
The UB study’s use of genetic sequencing led the researchers to a greater understanding of convergent evolution, defined by “a characteristic evolving separately in two genetically unrelated groups of organisms,” according to UB.
For example, wings are a widely developed characteristic. But they are not necessarily a sign of relatedness when it comes to birds, bats, and insects.
“Now with molecular data, we can see that convergent evolution happens all the time—things we thought were closely related often turn out to be far apart on the tree of life,” Wills said, adding, “Individuals within a family don’t always look similar; it’s the same with evolutionary trees, too.”
Family Trees: Morphology Versus Molecular
In their paper, the UB researchers acknowledged the importance of phylogenies (evolutionary history of species) in areas of biology, including medicine. They aimed to study a better way to produce accurate phylogenetic trees.
“Phylogenetic relationships are inferred principally from two classes of data: morphological and molecular,” they wrote, adding, “The superiority of molecular trees has rarely been assessed empirically.”
So, they set out to compare the two approaches to building evolutionary trees:
Traditional morphology analysis, and
Phylogenetic trees developed using molecular data.
Using 48 pairs of morphological and molecular trees, they mapped data geographically.
“We show that, on average, molecular trees provide a better fit to biogeographic data than their morphological counterparts, and that biogeographic congruence increases over research time,” the researchers wrote.
Biogeography a Better Gauge of Relatedness than Anatomy
The study also found animals on molecular trees lived geographically closer as compared to groups on morphological trees.
For example, molecular studies put aardvarks, elephants, golden moles, swimming manatees, and elephant shews in an Afrotheria group, named for Africa, which is where they came from. Therefore, the biogeography matches, however the appearances of these mammals clearly do not, the UB scientists point out.
“What’s most exciting is that we find strong statistical proof of molecular trees fitting better not just in groups like Afrotheria, but across the tree of life in birds, reptiles, insects, and plants,” said Jack Oyston PhD, UB Department of Biology and Biochemistry Research Associate and first author of the study, in the news release.
The researchers believe their findings support the accuracy of genetic-themed trees.
“It being such a widespread pattern makes it much more potentially useful as a general test of different evolutionary trees. But it also shows just how pervasive convergent evolution has been when it comes to misleading us,” Oyston added.
Advantages of Molecular Data
In their Nature Communications Biology paper, the UB scientists wrote that molecular data offer up these advantages over morphology:
Widely available in vast quantity.
Opportunity exists to “search, repurpose, and reanalyze sequenced data alongside novel sequences.”
Less subjectivity in researchers’ analysis.
Well-developed data at the ready and “still in their infancy.”
The University of Bath’s study of convergent evolution, phylogenetic trees, and comparison of molecular data versus morphology, has implications for medical laboratories. Should their research lead to new insights into how genes evolve over time, diagnostics professionals may have new information to identity diseases and work with others to precisely treat patients.
