Microbiologists will want to take note of the CDC’s statement that the illness can masquerade as other diseases
It is the latest example of a bacterium uncommon in the United States that has infected patients in this country—one of whom has died. The three infected patients live in separate states, but genetic analysis indicates their cases may be related.
According to the health alert, “Based on genomic analysis, these three cases (one male, two females; two adults and one child) may share a potential common source of exposure. The first case, identified in March 2021, was fatal. Two other patients were identified in May 2021, one of whom is still hospitalized. One has been discharged to a transitional care unit. None of the patients’ families reported a history of traveling outside of the continental United States.”
The CDC warned, “Symptoms of melioidosis are varied and nonspecific and may include pneumonia, abscess formation, and/or blood infections. Due to its nonspecific symptoms, melioidosis can initially be mistaken for other diseases such as tuberculosis, and proper treatment may be delayed.”
Microbiology Laboratories Should Be on Alert
Melioidosis is typically only seen in subtropical and tropical regions and can be highly fatal. It is unknown how the trio of patients who contracted the illness became infected, but according to the CDC the cases do appear to be connected.
“Testing suggests a common source of infection, but that source has not yet been identified,” a CDC representative told Gizmodo. “CDC is working with states to assess exposures or products these individuals have in common, as well as environmental samples from the states where cases have been identified. Additionally, CDC experts are providing epidemiologic assistance to help investigate the cause of infection,” the CDC added.
“Melioidosis is a serious neglected tropical disease of Southeast Asia, India, and Australia where it is a major cause of pneumonia, abscesses, and sepsis. The fact that it may be gaining a foothold in the US is concerning,” pediatrician Peter Hotez, MD, PhD (above), Dean of the National School of Tropical Medicine, Professor of Pediatrics and Molecular Virology and Microbiology at Baylor College of Medicine, and Director of the Center for Vaccine Development at Texas Children’s Hospital, told Gizmodo. Clinical laboratories and microbiologists will want to monitor these cases for future developments. (Photo copyright: Baylor College of Medicine.)
Melioidosis, also called Whitmore’s disease, was first described by Alfred Whitmore, an English pathologist, in 1912 in what is now present-day Myanmar. The bacterium (Burkholderia pseudomallei) can be found in contaminated soil and water. It is predominately found in tropical climates in Southeast Asia and northern Australia and can affect humans and many species of animals.
Researchers believe the disease may be acquired through the inhalation of contaminated dust particles or water droplets, the ingestion of contaminated water or soil-contaminated food, or other contact with tainted soil, especially through skin abrasions. It is very rare to contract melioidosis from infected individuals.
Melioidosis Masquerades as Other Illnesses
The symptoms of melioidosis are wide-ranging and non-specific and can resemble those of other illnesses. In addition, there are several types of the illness, and they can each act differently depending on where the infection is in the body. The most common symptoms of melioidosis include:
Localized Infection:
Localized pain or swelling
Fever
Ulceration
Abscess
Pulmonary Infection:
Cough
Chest pain
High fever
Headache
Anorexia
Bloodstream Infection:
Fever
Headache
Respiratory distress
Abdominal discomfort
Joint pain
Disorientation
Disseminated Infection:
Fever
Weight loss
Stomach or chest pain
Muscle or joint pain
Headache
Central nervous system/brain infection
Seizures
According to the CDC, the time between an exposure to Burkholderia pseudomallei and the first emergence of Melioidosis symptoms is not clearly defined but could range from one day to many years. However, most infected individuals begin experiencing symptoms of melioidosis within two to four weeks after exposure.
Melioidosis is difficult to diagnose, and some automated bacterial reading instruments can mistake Burkholderia pseudomallei for other bacteria. It is estimated that the disease accounts for 89,000 deaths per year worldwide. Delays in diagnosis and treatment often lead to poor patient outcomes and the mortality rate can exceed 40% in some regions, Nature reported.
The illness is typically treated with appropriate drug therapies including intravenous antimicrobial medications, such as Ceftazidime or Meropenem, followed by an oral antimicrobial therapy such as Trimethoprim-sulfamethoxazole or Amoxicillin/Clavulanic Acid. It may take several months for a patient to be cured of melioidosis, depending on the extent of the infection.
Deadly Bacterium’s Countries of Origin and Spread to the US
According to CDC data, the greatest number of melioidosis cases are reported in Thailand, Malaysia, Singapore, and northern Australia. Cases also have been reported in other Asian countries as well as Mexico and Central America.
Burkholderia pseudomallei does not occur naturally in the US, and cases of melioidosis identified in the US are usually only seen in world travelers and immigrants who come from countries where the disease is widespread. The bacterium has been found in soil in Mexico, so it is possible that it could spread to parts of the US, which has led to concern among microbiologists.
“Due to changes in weather patterns, some pathogens that normally were not present in a particular area might start causing disease,” Alfredo Torres, PhD, Associate Provost, Department of Microbiology and Immunology, University of Texas Medical Branch, told Gizmodo. “Therefore, it is important to make the health professionals aware of this pathogen and the disease that it causes, so quick identification can be done, and treatment is properly used to save lives. Without that, it might be too late for the next melioidosis patient when the proper diagnosis is done.”
The CDC has suggested that healthcare workers consider melioidosis as a possible diagnosis for patients who have compatible symptoms, even if they have not recently traveled outside of the US.
CDC Suggests Rerunning Certain Clinical Laboratory Tests
Because Burkholderia pseudomallei can be mistaken for other bacteria, the CDC also urges the rerunning of clinical laboratory tests using automated identification, especially if another bacterium that is often mistaken for Burkholderia pseudomallei is present, Gizmodo noted.
“CDC encourages healthcare workers to be aware of the potential for more cases and to report cases to their state health departments,” the CDC stated.
The CDC considers the risk of melioidosis to the public in the US to be low, and that the chances of a potential outbreak are unlikely. However, the origins of these three cases remain a mystery and warrant further investigation.
Microbiologists and clinical laboratories should be aware of and remain alert about this potentially fatal illness. It is possible that more cases will arise in the future, especially in the three states where it has already been found.
As the public gains awareness of the role clinical laboratories play in modern healthcare, increased engagement and understanding of the technology underlying many of these advances could create risk for labs without transparent reporting protocols to both patients and the public
In recent years, consumers have continually raised the bar in their expectation of quality when they interact with the healthcare system. Not only do patients expect providers—including clinical laboratories and anatomic pathology groups—to improve regularly over time, but the public has even less tolerance for medical errors of any type. Thus, a recent NPR story is one more warning to the medical laboratory profession that it should be devoting resources and effort to improving quality.
Today’s healthcare consumers and patients are more educated about and involved in the care process than ever before. While the exact science and skills may not interest the general public, the technologies underpinning much of the shift toward personalized medicine (AKA, precision medicine) are the same technologies that created the always-connected, digital lifestyles seen around the world.
With this, comes a level of scrutiny and questioning from the public that clinical laboratories or anatomic pathology groups would not have experienced even just a decade ago.
Mounting Scrutiny of Medical Laboratories and Healthcare Professionals
A recent segment on NPR’s “All Things Considered” highlighted this trend and questioned the quality control standards behind many of the procedures powering current testing. The segment also questioned the impact quality control has on the quality of biobanks used to research and create future technologies and tests.
Atul Butte, PhD (above), Director of the Institute of Computation Health Sciences at the University of California-San Francisco, presents an alternate side to Compton and Friedberg’s views in the NPR article. “I am not a believer in garbage-in, garbage out at all,” he said. “I know that no one scientist, no one clinician or pathologist is perfect … But, I’d rather take 10 or 100 so-called mediocre data sets and find out what’s in common, then to take one who says they’re perfect at doing this kind of measurement.” (Photo copyright: Santiago Mejia/San Francisco Chronicle.)
When data and previous research powers much of the innovation taking place across the modern healthcare landscape, the accuracy of said data would seem critical. Yet, without standards in place, there’s not always safeties by which to verify sample integrity and other critical concerns.
Late last year, Dark Daily reported on a study published in PLOS ONE from Radboud University in the Netherlands questioning the accuracy of more than 30,000 published scientific studies that contained misidentified or contaminated cell lines. Guidelines, such as those created for IHR and FISH HER2 testing, provide standards intended to prevent such issues from occurring or detecting them when they do occur.
Quality versus Quantity: A Gamble Worth Taking?
Apart from challenges with healthcare reform and the regulatory landscape surrounding precision medicine, medical laboratories also must struggle with the challenges of gleaning and maintaining useful, accurate information from an ever-growing trove of data produced by analyzers and assays.
Yet, these mediocre datasets include the results of tests that carried a potentially significant impact on patient lives. In the first two weeks of February alone, both the St. Louis Post-Dispatch and The Telegraph published stories related to erroneous testing related to cancer and the potential impact on the clinical laboratories involved and the patients tested.
Increased coverage shows that the world is watching what goes on in medical laboratories, hospitals, and data centers as healthcare continues to evolve. Clinical laboratories must move forward with this in mind or risk pushback and questioning from the public. Transparency regarding standards, and reporting information to patients surrounding testing or concerns, might effectively address this rising trend.
“We are moving faster and faster and faster as this whole precision medicine train is moving down the track,” Tim Allen, MD, Laboratory Director at the University of Texas Medical Branch Department of Laboratory Services, told NPR. “I suspect standardization of these things is going to become a reality much quicker than I would have expected even a few years ago.”
That quality control issues in anatomic pathology are considered newsworthy by no less than NPR is a sign of increased public attention to the quality of lab testing. The story was written to educate the public about the gap that exists in the quality control of anatomic pathology testing. All of this is consistent with the trend for providers to be transparent and report their quality metrics to the public, including patients.
At institutions such as University of Texas Medical Branch, Galveston, and Vanderbilt University Medical Center, pathologists are using diagnostic management teams to improve patient outcomes while lowering the medical costs
In simplest terms, a diagnostic management team (DMT) is described by pathologist Michael Laposata, MD, PhD, as “involving a group of experts who meet daily and focus on the correct selection of laboratory tests and the interpretation of complex test results in a specific clinical field. Typically, DMTs are led by pathologists focusing on the diagnosis of a specific group of diseases, along with physicians and other lab experts involved in the disease or health condition that is the focus of the DMT.”
How Pathologists Use Diagnostic Management Teams
“What differentiates a DMT are two changes from the classic diagnostic pathway,” continued Laposata. “First, the ordering physician gets assistance in selecting the correct tests. This can be done in several ways, such as creating expert-driven algorithms that are updated regularly to manage utilization of laboratory tests and dramatically minimize overuse and underuse. Use of such algorithms with reflex testing makes it easy for treating healthcare providers to order the right tests and only the right tests.
“The second key difference in this new diagnostic pathway is that, within the DMT’s specific clinical context, an expert-driven, patient-specific interpretation of the test results in a specific clinical context is generated by the members of the DMT,” he said. “This requires the knowledge of a true expert—not someone who may have a general idea about the meaning of a particular laboratory test result—and the participation of someone to help that expert search the medical record for relevant data to be included in the interpretation.
DMTs Typically Organized to Support Specific Diseases or Health Conditions
He pointed out that the DMT has a rather simple organization. There is a front-end and a back-end. The front-end starts when “physicians order tests by requesting evaluation of an abnormal screening test or clinical sign or symptom,” explained Laposata. “Upon receiving that request, the expert physician and colleagues in the DMT then synthesize the clinical and laboratory data and provide a narrative interpretation based upon medical evidence. This happens not only when specifically requested by the referring physician, but also for every case handled by the DMT.”
Diagnostic Management Teams are making significant contributions at the University of Texas Medical Branch (UTMB), Galveston. Pictured above, the members of UTMB’s coagulation DMT are (L-R): Jack Alperin, MD; Michael Laposata, MD; Aristides Koutrouvelis, MD; Camila Simoes, MD; Chad Botz, MD; Aaron Wyble, MD: and Jacob Wooldridge, MD. (Photo copyright: University of Texas Medical Branch, Galveston.)
The back-end of the process involves the DMT conducting an “expert-driven, patient-specific interpretation of the test results in a specific clinical context.” Here is where the participating clinical experts—supplemented by staff who conduct an informed search of the medical record to identify and collect data relevant to the diagnosis—sift through this much richer quantity of information to develop the diagnosis.
Overworked Physicians Value the Expertise, Diagnostic Accuracy of DMTs
Laposata points out that individual physicians who already may be overworked in their daily routines generally welcome the help of DMT experts who are up-to-date on the current literature, and who have decades of experience in these diseases and health conditions. He likes to point out that, in coagulation alone, a physician could have as many as 60 to 90 tests that can be ordered. He also notes that typical primary care physicians, for example, are generally not experts in selecting the best coagulation test to order for every group of symptoms, nor do they know how to order the most appropriate reflexive test to continue the diagnostic pathway.
Knowing how to interpret the results of the 60 to 90 different coagulation tests is equally challenging to most physicians.
Over the course of his career, Laposata has signed out more than 50,000 cases in the field of coagulation. “Every positive case that identified a diagnosis resulted in an earlier and more accurate diagnosis,” stated Laposata. “Every case negative for coagulopathy allowed the treating healthcare provider to focus on a diagnosis other than one related to bleeding and thrombosis.”
Using Clinical Laboratory Data to Improve Patient Outcomes, Reduce Costs
There are other reasons why a growing number of medical lab administrators and clinical pathologists believe that DMTs are the right solution at the right time. One reason is the steady reduction in reimbursement from Medicare and private payers. Another is the trend to measure and publish the quality metrics of hospitals and individual physicians.
There are ever more quality metrics that include diagnostic accuracy and total cost per healthcare encounter. Diagnostic Management Teams are proven to improve diagnostic accuracy and ensure the patient gets the right therapy faster. Both of these benefits contribute to substantial reductions in the cost per healthcare encounter.
Pathologists and clinical laboratory professionals interested in learning more about diagnostic management teams have two opportunities.
At the Galveston Island Convention Center on Feb. 6 -7, 2018, the second annual Diagnostic Management Team Conference will take place. Last year, several hundred-people attended. Information can be found at: http://www.dmtconference.com/.
Special Webinar on Diagnostic Management Teams on January 17
During this valuable webinar, you’ll hear from three experts. First to speak will be Michael Laposata, MD, PhD. He will provide you with a detailed overview of DMTs, including:
How to assemble the right team;
How to engage with referring physicians; and,
How to work through individual cases.
Laposata will introduce you to the structure and organization of effective diagnostic management teams, organized around a specific disease or health condition and made up of pathologists, other lab scientists, and physicians who are expert in their particular clinical field. The objective of the DMT is to meet daily with the goal of coming up with faster, more accurate diagnoses in support of a patient’s care team.
Experience from a Diagnostic Management Team Focused on the Liver
Next to speak will be Heather Stevenson-Lerner, MD, PhD, a liver and transplantation pathologist and Assistant Professor, Department of Pathology, UTMB. She will discuss a DMT organized around diseases of the liver. This is a useful, step-by-step description of an effective DMT, illustrated with case studies that demonstrate how diagnostic management teams can make a positive and substantial contribution to improving individual patient outcomes.
The webinar’s third presenter is Christopher Zahner, MD, a resident pathologist at UTMB. He will share how to pull together all the information needed to support DMT interpretations. From the electronic health record (EHR) system to other overlooked sources of useful data, Zahner will explain the most productive ways to assemble any information that will be useful to the diagnostic management team and that will make a positive difference in patient care.
To register for the webinar and see details about the topics to be discussed, use this link (or copy and paste this URL into your browser: https://ddaily.wpengine.com/webinar/using-diagnostic-management-teams-to-add-value-with-clinical-laboratory-tests-and-pathologists-expertise).
This is an essential webinar for any pathologist or lab manager wanting to put the lab front and center in contributing clinical value in ways that directly improve patient outcomes while reducing medical costs. With hospital lab budgets shrinking and fee-for-service payments being slashed, the time is right for your lab team to consider how organizing diagnostic management teams can be the perfect vehicle to demonstrate why clinical lab tests and expertise can be a diagnostic game-changer within your hospital or health system.
And don’t forget, your participation in this webinar can be the foundation for a highly-successful effort to collaborate with physicians and clinical services, to the benefit of both the parent hospital and individual patients. That makes this webinar the smartest investment you can make for crafting your lab’s test utilization and added-value programs in support of clinical care.
SHERLOCK makes accurate, fast diagnoses for about 61-cents per test with no refrigeration needed; could give medical laboratories a new diagnostic tool
The tool is called SHERLOCK, which stands for (Specific High-sensitivity Enzymatic Reporter unLOCKing). And it is causing excitement in the scientific community for several reasons:
It can detect pathogens in extremely small amounts of genetic matter;
Tests can be performed using urine and/or saliva rather than blood;
The tests are extremely sensitive; and they
Cost far less than the diagnostic tests currently in use.
How SHERLOCK and CRISPR Differ and Why That’s Important
Scientists have long suspected that CRISPR could be used to detect viruses. However, far more attention has been given to the its genome editing capabilities. And, there are significant differences between how CRISPR and SHERLOCK work. According to the Science article, when CRISPR is used to edit genes, a small strip of RNA directs an enzyme capable of cutting DNA to a precise location within a genome. The enzyme that CRISPR uses is called Cas9 (CRISPR associated protein 9). It works like scissors, snipping the strand of DNA, so that it is either damaged or replaced by a healthy, new sequence.
SHERLOCK, however, uses a different enzyme—Cas13a (originally dubbed C2c2 by the researchers who discovered it). Cas13a goes to RNA, rather than DNA, and once it starts cutting, it doesn’t stop. It chops through any RNA it encounters. The researchers who developed SHERLOCK describe these cuts as “collateral cleavage.” According to an article published by STAT, “All that chopping generates a fluorescent signal that can be detected with a $200 device or, sometimes, with the naked eye.”
The screenshot above is from a video in which Feng Zhang, PhD (center), a Core Member of the Broad Institute at MIT and one of the lead researchers working on SHERLOCK, and his research team, explain the difference and value SHERLOCK will make in the detection of diseases like Zika. Click on the image above to watch the video. (Video copyright: Broad Institute/MIT.)
Early Stage Detection in Clinical Laboratories
A research paper published in Science states that SHERLOCK can provide “rapid DNA or RNA detection with attomolar sensitivity and single-base mismatch specificity.” Attomolar equates to about one part per quintillion—a billion-billion. According to the article on the topic also published in Science, “The detection sensitivity of the new CRISPR-Cas13a system for specific genetic material is one million times better than the most commonly used diagnostic technique.” Such sensitivity suggests that clinical laboratories could detect pathogens at earlier stages using SHERLOCK.
The Stat article notes that, along with sensitivity, SHERLOCK has specificity. It can detect a difference of a single nucleotide, such as the difference between the African and Asian strains of Zika (for example, the African strain has been shown to cause microcephaly, whereas the Asian strain does not). Thus, the combination of sensitivity and specificity could mean that SHERLOCK would be more accurate and faster than other diagnostic tests.
Clinicians in Remote Locations Could Diagnose and Treat Illness More Quickly
Perhaps one of the most important aspects of SHERLOCK is the portability and durability of the test. It can be performed on glass fiber paper and works even after the components have been freeze dried. “We showed that this system is very stable, so you can really put it on a piece of paper and it will survive. You don’t have to refrigerate it all the times,” stated Feng Zhang, PhD, in an interview with the Washington Post. Zhang is a Core Member of the Broad Institute at MIT and was one of the scientists who developed CRISPR.
The researchers note that SHERLOCK could cost as little as 61-cents per test to perform. For clinicians working in remote locations with little or no power, such a test could improve their ability to diagnose and treatment illness in the field and possibly save lives.
“If you had something that could be used as a screening test, very inexpensively and rapidly, that would be a huge advance, particularly if it could detect an array of agents,” stated William Schaffner, MD, Professor and Chair of the Department of Preventive Medicine at Vanderbilt University Medical Center, in the Post article. Schaffner describes the Broad Institute’s research as being “very, very provocative.”
The test could radically change the delivery of care in more modern settings, as well. “It looks like one significant step on the pathway [that] is the Holy Grail, which is developing point-of-care, or bedside detection, [that] doesn’t require expensive equipment or even reliable power,” noted Scott Weaver, PhD, in an article on Big Think. Weaver is a Professor and Director at the Institute for Human Infections and Immunity University of Texas Medical Branch in Galveston, Texas.
Just the Beginning
Anatomic pathologists and clinical laboratories will want to follow SHERLOCK’s development. It could be on the path to fundamentally transforming the way disease gets diagnosed in their laboratories and in the field.
According to the Post article, “The scientists have filed several US patent applications on SHERLOCK, including for uses in detecting viruses, bacteria, and cancer-causing mutations.” In addition to taking steps to secure patents on the technology, the researchers are exploring ways to commercialize their work, as well as discussing the possibility of launching a startup. However, before this technology can be used in medical laboratory testing, SHERLOCK will have to undergo the regulatory processes with various agencies, including applying for FDA approval.
In response to healthcare’s transformation, a pathologist and a lab CEO describe two powerful ways that medical laboratories can collaborate with physicians, patients, health systems, and health insurers to deliver more value
DATELINE: Phoenix, Arizona—It may be appropriate that, with the pace of change heating up in both healthcare and the clinical laboratory industry, it was here in the hot Sonoran Desert that more than 500 medical laboratory professionals gathered last week for the annual Sunquest User Group Conference (SUG) hosted by Sunquest Information Systems. (more…)
