Innovative in-office test, when integrated with UTI microbiology testing performed by clinical laboratories, could contribute to better patient outcomes
Treatments for certain bacterial infections are becoming less effective due to antimicrobial resistance (AMR). Now, after a 10-year-long worldwide competition, the first multi-million euro prize for an accurate, rapid, and cost effective clinical laboratory test for diagnosing and treating urinary tract infections (UTIs) went to Sysmex Corporation’s subsidiary Astrego. This milestone event could benefit tens of millions of people who suffer from UTIs annually.
Astrego, of Uppsala, Sweden, won the €8 million (US$8.19 million) Longitude Prize on AMR for its PA-100 AST System. The new diagnostic technology will “transform treatment of urinary tract infections and brings the power of clinical laboratory testing into a doctor’s office,” according to a news release from Challenges Works, the United Kingdom-based organization that organized and awarded the prize.
The Astrego system is, according to Challenge Works’ website, a “game-changing solution” in “a novel point-of-care diagnostic test that rapidly and accurately identifies the presence of a bacterial infection and the right antibiotic to prescribe.”
“We launched the Longitude Prize on AMR (in 2014) to create the urgent ‘pull’ needed to get innovators working on one of the biggest life-and-death challenges facing humanity. Hundreds of teams [that] competed with multiple solutions [are] now close to market thanks to the prize,” said Tris Dyson, Managing Director, Challenge Works, in a news release.
The new diagnostic technology “could herald a ‘sea change’ in antibiotic use” according to the judges of the competition, The Guardian reported.
“The PA-100 AST System (above) creates a future where patients can quickly and accurately get a diagnosis and the correct treatment when they visit the doctor,” said Sherry Taylor, MD, UK National Health Service, Temple Fortune Medical Group, London, in the Challenge Works news release. “Accurate, rapid diagnosis of bacterial infections that help doctors and health workers to manage and target antibiotics, will slow the development and spread of antibiotic resistant infections, improve healthcare and save potentially millions of lives,” she added. In-office point-of-care systems like the PA-100 may reduce the number of doctor orders for UTI tests to clinical laboratories while contributing to better patient outcomes. (Photo copyright: Sysmex.)
How the Test Works
In the UK, people are treated for UTIs more than any other infection. It takes about three days for doctors to receive the results from traditional microbiology testing. They then prescribe an antibiotic to treat the infection. But about half of “infection-causing bacteria are resistant to at least one antibiotic,” according to a news release from the Geneva, Switzerland-based NESTA Foundation which funded the Longitude Prize on AMR.
“It’s impossible to overstate how critical it is to address AMR [antimicrobial resistance]. By 2050, it is predicted to cause 10 million deaths a year—matching those caused by cancer—and cost $1 trillion in additional health costs,” the news release states.
UTI are more common in women and the reason for eight million healthcare appointments annually in the US, according to Medscape.
The PA-100 AST system makes it possible for patients to provide a small urine sample during their appointments with doctors, find out if they have a bacterial infection in 15 minutes, and receive the “right antibiotic to treat it within 45 minutes,” NESTA said. Sysmex describes the PA-100 AST as an “automated phenotypic analyzer, based on EUCAST standards,” that combines “phase-contrast microscopy and nanofluidics to make available antibiograms at point of care.” It enables healthcare providers to perform antimicrobial susceptibility testing (AST) in-office rather than sending out urine samples to microbiology laboratories.
The systems works as follows, according to the Sysmex website:
As a urine sample passes through the chip, “single bacterial cells are trapped in individual channels.”
Meanwhile, “larger cellular components” are filtered and kept out of the nanofluidic chip.
Contrast-phase microscopy enables real-time monitoring of cell growth. “Resistant bacteria keep a higher growth rate during incubation, while susceptible ones grow slowly or lyse.”
Expert computer software identifies that bacterial strain, delivers an “easy to interpret antibiogram after assay completion” and provides an “informed prescription decision” on which antibiotic is expected to fight the infection.
“The PA-100 AST System challenges bacteria present in a patient’s urine with microscopic quantities of antibiotics in tiny channels embedded in a cartridge the size of a smartphone,” said Mikael Olsson, CEO and co-founder of Sysmex Astrego, in The Microbiologist.
“We rapidly pinpoint whether a bacterial infection is present and identify which antibiotic will actually kill the bugs, guiding doctors only to prescribe antibiotics that will be effective,” he added.
Sysmex is conducting more studies in the UK and working with regulators in Europe for clearances, according to Olsson.
Older Antibiotics May Make Comeback
It’s possible that use of the PA-100 system to identify the best antibiotic to treat infections could lead to a resurgence in the use of previously retired antibiotics.
“Roughly 25-30% of patients have infections resistant to older first-line antibiotics which have been retired as a result; this means the remaining 70-75% of patients could still benefit from those older drugs,” Pathology in Practice reported, adding, “Since the PA-100 AST System identifies which specific antibiotic can treat an infection, it will likely allow retired antibiotics to be brought back into service because the test is able to demonstrate when an infection is susceptible to their effects.”
Many people could benefit from the older antibiotics, Challenge Works noted.
Revolutionizing Healthcare
The Sysmex Astrego’s PA-100 AST System is a significant development.
“Currently, I send the urine sample off for analysis, and it usually takes around three days to come back with results,” said Sherry Taylor, MD, UK National Health Service, Temple Fortune Medical Group, London, in the Challenge Works news release. “Having a bedside test that would enable rapid diagnosis through antibiotic susceptibility testing would revolutionize general practice and patient care. It’s all about using antibiotics only when necessary and appropriate.”
Each individual test costs about €25 (US$25.72), The Guardian reported, adding that ramped up production may lower the price.
The PA-100 AST System is the latest example of a diagnostic/therapeutic solution developed in Europe rather than the US, which is often slower to award regulatory clearance.
It also is another test that will be performed outside of traditional clinical laboratory settings, demonstrating the trend to move medical laboratory tests closer to patients.
The researchers believe their test ‘could reduce the number of unnecessary prostate cancer biopsies by 32%,’ UEA reported
New diagnostic technologies may make it possible for men to provide a urine sample that can allow a clinical laboratory to not only accurately diagnose prostate cancer but also help determine whether it is an aggressive form of prostate cancer. Researchers in the United Kingdom (UK) recently described just such a test in an online, peer-reviewed journal.
Development of a non-invasive method of diagnosing prostate cancer would be significant for anatomic pathologists in the United States. In the US alone, approximately 248,000 men will be diagnosed with this type of cancer in 2021. Prostate biopsies represent a major proportion of case referrals to community pathology groups.
Moreover, were such a non-invasive test for prostate cancer also able to identify those individuals with fast-growing prostate cancers, that would help urologists make more informed treatment decisions.
A Disease Men More Commonly Die ‘With’ Rather than ‘From’
According to CDC statistics, most men over the age of 80 will have some form of slow-growing prostate cancer when they die. However, a percentage of men each year contract a rapidly growing aggressive form of the cancer, and until recently, diagnosing which cancer a patient was fighting often required multiple invasive prostate needle biopsies. But that may soon change.
Researchers at the University of East Anglia (UEA) Norwich Medical School in the United Kingdom (UK) have developed a non-invasive urine test for prostate cancer that they say also can determine the aggressiveness of the disease. Knowing this may help physicians better assess a patient’s risk prior to ordering invasive needle biopsies, a UEA article notes.
The UEA test may also allow for self-collection of the biological sample, and if it proves accurate, the test could bring additional revenue to clinical laboratories that would perform the urine testing.
“In this work we develop a test that predicts whether a patient has prostate cancer and how aggressive the disease is from a urine sample. This model combines the measurement of a protein-marker called EN2 and the levels of 10 genes measured in urine and proves that integration of information from multiple, non-invasive biomarker sources has the potential to greatly improve how patients with a clinical suspicion of prostate cancer are risk-assessed prior to an invasive biopsy,” they wrote.
“While prostate cancer is responsible for a large proportion of all male cancer deaths, it is more commonly a disease men die with rather than from,” said Daniel Brewer, PhD, one of the lead researchers on this study. “Therefore, there is a desperate need for improvements in diagnosing and predicting outcomes for prostate cancer patients to minimize over-diagnosis and overtreatment whilst appropriately treating men with aggressive disease, especially if this can be done without taking an invasive biopsy.
“Invasive biopsies come at considerable economic, psychological, and societal cost to patients and healthcare systems alike,” he added. Brewer is Senior Lecturer in Cancer Bioinformatics and a group leader within the Cancer Genetics Team at UEA’s Norwich Medical School.
“Our new urine test not only shows whether a patient has prostate cancer, but it importantly shows how aggressive the disease is. This allows patients and doctors to select the correct treatment,” said Daniel Brewer, PhD (above), Senior Lecturer and Lead Researcher, UEA Norwich Medical School, in the news release. (Photo copyright: Eastern Daily Press.)
Possibility of Reducing Needle Biopsies by 32%
Called “ExoGrail,” the UEA’s new test builds on their earlier development of the Prostate Urine Risk (PUR) and ExoMeth tests. The test works by integrating two biomarkers.
Levels of gene expression of 10 genes related to prostate cancer.
The researchers tested ExoGrail on urine samples from 207 patients at Norfolk and Norwich University Hospital (NNUH) who also had needle biopsy samples available.
According to the published study, the UEA ExoGrail urine test enabled:
Results comparable to the biopsy findings.
Identification of people with prostate cancer and people without it.
Risk scoring that noted aggressive prostate cancer and need for biopsy.
Potential to reduce unnecessary biopsies by 32%.
“ExoGrail resulted in accurate predictions even when serum PSA [protein-specific antigen] levels alone proved inaccurate; patients with a raised PSA but negative biopsy result possessed ExoGrail scores significantly different from both clinically benign patients and those with low-grade Gleason 6 disease, whilst still able to discriminate between more clinically significant Gleason ≥ 7 cancers,” the researchers stated in their published study.
“The adoption of ExoGrail into current clinical pathways for reducing unnecessary biopsies was considered, showing the potential for up to 32% of patients to safely forgo an invasive biopsy without incurring excessive risk,” they noted.
Prostate Cancer Patients May Soon Have Options
While more research is needed, the new UEA Norwich Medical School ExoGrail test introduces compelling non-invasive methods for diagnosing prostate cancer. Patients with findings of aggressive cancer can proceed to biopsies, while others determined to have non-aggressive forms of prostate cancer may be able to avoid more invasive tests and the associated costs and stress.
Additionally, men may soon be able to collect their own specimens without the need to visit the primary care doctor or a patient service center.
A follow-up study underway at the University of East Anglia and the NNUH involves sending 2,000 men in the UK, Europe, and Canada home testing “prostate screening boxes” to “to collect men’s urine samples at-home,” according to a UEA new release, which noted that “the Prostate Screening Box has been developed in collaboration with REAL Digital International Limited to create a kit that fits through a standard letterbox.”
“We have developed the PUR (Prostate Urine Risk) test, which looks at gene expression in urine samples and provides vital information about whether a cancer is aggressive or ‘low risk,’” said Jeremy Clark, PhD, Senior Research Associate at UEA’s Norwich Medical School.
“The Prostate Screening Box part sounds like quite a small innovation, but it means that in future the monitoring of cancer in men could be so much less stressful for them and reduce the number of expensive trips to the hospital,” he added.
Anatomic pathologists and clinical laboratory managers will want to follow the progress of these clinical studies. A non-invasive, urine-based test for prostate cancer could be a game-changer if it can detect prostate cancer with comparable accuracy to the tissue-based diagnostics that are the current standard of care in the diagnosis of prostate cancer.
A legal, supervised injection site (SIS) affiliated with Vancouver Coastal Health found 86% of drugs tested with strips contained fentanyl when tested with these medical lab test kits
Here’s an unexpected application of point-of-care testing (POCT) that may surprise pathologists and medical laboratory leaders. In a sort of “guerilla-warfare” street experiment that applies diagnostic technologies to a problem, the manager of a needle-exchange program in the Bronx has been helping heroin and other opioid users discover if a product they are about to ingest is contaminated by handing out test strips designed for testing urine.
The addicts participating in these special programs use the POCT urine test strips to test their drugs for the presence of fentanyl, a powerful synthetic opioid analgesic similar to morphine that can increase the potency of opioids to lethal levels. Rehab program directors adopted this approach to help prevent overdoses and deaths among drug users.
Reducing Overdoses with Test Strip Handouts
Opioids such as morphine are often prescribed to cancer or surgery patients to treat severe pain. However, according to a National Institute on Drug Abuse (NIDA) fact sheet, fentanyl is “50 to 100 times more potent than morphine.” When fentanyl is mixed with heroin or cocaine and sold on the streets, the potent mix can be deadly, NIDA explained.
Test strips ordered from Canada designed to check patients’ urine for fentanyl are being used by St. Ann’s Corner of Harm Reduction (St. Ann’s) in the Bronx, New York. The strips are being used to check drug users’ syringes for fentanyl, according to a National Public Radio Shots article. The idea is to inform drug users of what they have in hand and possibly encourage them to choose not to take the drug, use less, or slow things down, Shots reported.
“If you’re doing dope, we’ll give you a test strip so you can test and see if there’s fentanyl,” stated Van Asher, Data Manager at St. Ann’s, in the Shots article.
Whether an unlicensed individual distributing test strips to drug users violates state or federal regulations was not broached in the Shots article.
St. Ann’s gives out about 15 strips a day each costing $1, Shots noted. St. Ann’s staff is sharing data collected on the encounters with the Centers for Disease Control and Prevention (CDC) and with New York health departments.
Finding Fentanyl with Test Strips in Canada
St. Ann’s isn’t the first to use urine test strips for drug checking. Vancouver Coastal Health (VCH) in British Columbia, Canada, launched a pilot program for drug-checking in 2016 at its Insite facility.
At Insite’s “supervised injection site” facility (above) in Vancouver, British Columbia, drug users can “legally” inject illegal drugs. Directors of this program have adapted point-of-care urine test kits typically used in medical laboratory testing to allow drug users to test their heroin and opiate drugs for the presence of fentanyl. The goal is to reduce overdoses and deaths from users unknowingly ingesting fentanyl. (Photo copyright: CBCNews.)
Insite began to test drugs for the presence of fentanyl in the fall of 2016. Data from 173 tests performed in July and August found that 86% of drugs tested contained fentanyl, noted a VCH news release.
“These initial results confirm our suspicion that the local drug supply is overwhelmingly contaminated with fentanyl. We’re hoping this information can help people who use drugs,” stated Mark Lysyshyn, MD, MPH, VCH Medical Health Officer and Professor of Medicine at University of British Columbia.
The test works when the client dilutes the substance with a few drops of water. A positive or negative result for fentanyl is revealed within seconds.
The test strip used by Insite was designed to check for fentanyl in urine, not for checking drugs, noted the VCH statement. Insite intends to review the pilot program test data and decide whether to continue testing services after the pilot program concludes.
Alexander Walley, MD, Director of the Addiction Medicine Fellowship Program and Assistant Professor of Medicine at Boston Medical Center, stated the test may aid users’ decision-making.
“Even when they know they’re going to be positive for fentanyl, the experience of somebody testing their drugs and seeing that it’s fentanyl has an impact. It really encourages them to use more safely,” he stated in the Shots article.
Overdose Deaths Due to Fentanyl in America
A CBC News, Manitoba, article called the death rate due to fentanyl ingestion a “Canada-wide disaster.” However, the problem is significant in the US as well.
Death rates from synthetic opioids, including fentanyl, rose more than 72% from 2014 to 2015 in the US, according to the CDC.
In New York City, fentanyl is increasingly being linked to overdoses. In 2016, nearly half (44%) of drug deaths involved drugs mixed with fentanyl. That’s a 16% increase over 2015, according to a NYC Health press release.
A report from the Tennessee Department of Health noted that 1,451 people died from drug overdose in 2015. That’s a state record. Deaths associated with fentanyl rose significantly from 69 in 2014 to 174 in 2015, the report noted.
How Fentanyl Works and Why It Is Dangerous
Here are some fentanyl facts from the NIDA:
Fentanyl works by binding to opioid receptors located in areas of the brain that control pain and emotions;
People may experience side effects such as euphoria, drowsiness, nausea, confusion, addiction, respiratory arrest, unconsciousness, coma, and death;
Increased risk of overdose exists when drug users are unaware a drug they are ingesting contains fentanyl.
Clinical laboratory directors and pathology groups nationwide might want to follow the progress of test strip services at St. Ann’s Corner and Insite’s SIS. This twist on traditional POCT—using urine test strips to look for the presence of fentanyl in substances—could aid their own communities achieve public awareness, change behaviors, and save lives.
