Artificial Intelligence (AI) Detects Anthrax

In an effort to combat bioterrorism, scientists in South Korea have trained artificial intelligence to speedily spot anthrax. The new technique is not 100 percent accurate yet, but it’s orders of magnitude faster than our current testing methods. And it could revolutionize how we screen mysterious white powders for the deadly bioweapon.

Researchers at the Korea Advanced Institute of Science and Technology combined a detailed imaging technique called holographic microscopy with artificial intelligence. The algorithm they created can analyze images of bacterial spores to identify whether they’re anthrax in less than a second. It’s accurate about 96 percent of the time, according to a paper published last week in the journal Science Advances.

ANTHRAX CAN KILL QUICKLY, IF LEFT UNTREATED

Anthrax is an infection caused by the bacteria Bacillus anthracis, which lives in soil. (Both the infection and the bacteria are often referred to as anthrax.) People can accidentally get anthrax infections when they handle the skin or meat of infected animals. But anthrax can also be a dangerous bioweapon: in 2001, anthrax spores sent in the mail infected 22 people and killed five of them.

Once the spores enter the body, they germinate and multiply, causing a flu-like illness that poisons the blood. At least 85 percent of people infected by inhaling the spores die if left untreated, sometimes within just one to two days after symptoms appear. (Anthrax infections of the skin, by contrast, tend to be less fatal.) For people especially at risk of contracting anthrax, like lab workers or people who work with animal hair, there’s a vaccine. For the rest of us, there are antibiotics — but these work best when they’re started as soon as possible after exposure.

IT’S IMPORTANT TO DETECT ANTHRAX FAST

So it’s important to detect anthrax fast. Right now, one of the most common methods is to analyze the genetic material of the spores or, once someone is infected, of the bacteria found in infected tissue. But that typically requires giving the spores a little time to multiply in order to yield enough genetic material to analyze. “It’s still going to take the better part of a day with the most rapid approaches to get a result,” says bacteriologist George Stewart at the University of Missouri, who has also developed an anthrax detector and was not involved in this study.

In search of a quicker screening technique, the study’s lead author, physicist YongKeun Park, teamed up with South Korea’s Agency for Defense Development. The goal is to be prepared in case North Korea is developing anthrax as a bioweapon, he says.

Park turned to an imaging technique called holographic microscopy: unlike conventional microscopes, which can only capture the intensity of the light scattering off an object, a holographic microscope can also capture the direction that light is traveling. Since the structure and makeup of a cell can change how light bounces off of it, the researchers suspected that the holographic microscope might capture key, but subtle, differences between spores produced by anthrax and those produced by closely related, but less toxic species.

THE AI COULD ID THE ANTHRAX SPORES WITHIN SECONDS

Park and his team then trained a deep learning algorithm to spot these key differences in more than 400 individual spores from five different species of bacteria. One species was Bacillus anthracis, which causes anthrax, and four were closely related doppelgängers. The researchers didn’t tell the neural network exactly how to spot the different species — the AI figured that out on its own. After some training, it could distinguish the anthrax spores from the non-anthrax doppelgänger species about 96 percent of the time.

The technique isn’t perfect, and as a tool intended to detect bioweapons, it has to be. “The drawback is that the accuracy is lower than conventional methods,” Park says. There are also multiple strains of each of the bacteria species analyzed — but the machine was trained on only one strain per species. Subtle differences between the strains might be able to throw off the algorithm, Stewart says. Still, the new technique is so rapid that it could come in handy. “It doesn’t require culturing organisms, it doesn’t require extracting DNA, it doesn’t require much of anything other than being able to visualize the spores themselves,” Stewart says.

“IT COULD ENHANCE OUR PREPARATION FOR THIS KIND OF BIOLOGICAL THREAT.”

Next, Park wants to feed the neural network more spore images, in order to boost accuracy. In the meantime, the method could be used as a pre-screening tool to rapidly determine whether a white powder that people have been exposed to is anthrax, and if they should start antibiotics. A slower, more accurate method could then confirm the results.

“This paper will not change everything,” Park says, but it’s one step toward a method that can quickly detect anthrax. “It could enhance our preparation for this kind of biological threat.”

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UW Receives Grant to Develop More Accurate Brucellosis Test for Swine, Cattle

Researchers in the Department of Veterinary Sciences at the University of Wyoming will use a $149,000 grant from the Foundation for Food and Agriculture Research to help develop a quicker, cheaper and more accurate test to detect brucellosis.

The money will help fund studies to detect swine brucellosis (Brucella suis), which is prevalent among feral swine in most of the United States, but not yet in Wyoming. B. suis also can infect domestic swine and cattle where their populations overlap.

The money will help continue efforts toward creating a polymerase chain reaction (PCR) analysis, an ongoing effort by Dr. Brant Schumaker, an associate professor in the department.

There is a growing pressure for hog producers to move from confinement production to natural or pasture-raised swine. Serologic (blood) testing cannot discriminate between cattle brucellosis (Brucella abortus) and B. suis exposures.

“I think most of the state understands how much of a problem cattle brucellosis has been in the greater Yellowstone area,” says Schumaker, epidemiologist at the Wyoming State Veterinary Laboratory. He will lead the collaborative project with Texas A&M University.

“If this disease were to come to the state, we would have a hard time differentiating between the two organisms,” Schumaker says.

UW and Texas A&M will match the grant for a total of $299,000 for the project. Funding is through the foundation’s Rapid Outcomes from Agricultural Research program.

Texas has had several instances during which cattle in contact with feral swine have tested positive for brucellosis.

“It’s very complicated to try to differentiate between swine and bovine brucellosis,” Schumaker says.

Culture testing is the current gold standard for detection, Schumaker says, but it takes at least 14 days, is about $600 per animal and requires the animal be euthanized. Only 30 to 50 percent of animals that test antibody-positive in blood are culture-positive.

Schumaker says the research is a continuation of Ph.D. student Noah Hull’s studies at UW. The team is in the final stages of testing a PCR assay for bovine brucellosis. PCR can produce millions of copies of a section of DNA in only a few hours, yielding enough DNA required for analysis.

Preliminary testing has shown researchers are able to identify more than twice the number of serologically positive animals compared to culture and obtain results in two to three hours at one-fourth the cost.

Texas A&M researchers will collect and send swine tissue samples to UW for testing. Schumaker says there are more than 29 collaborators on the grant. Members include representatives from federal, state and local governmental agencies.

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Indian Hospitals, Labs Told to Use IgM ELISA for Dengue Diagnosis

With dengue cases yet to see a marginal decrease, Health Department has directed hospitals and laboratories to use IgM ELISA as the standard method to detect dengue.

The use of antibody-based Immunoglobulin M (IgM) ELISA (Enzyme-Linked Immunosorbent Assay) test has been stressed for generation of accurate results of the viral disease.

Officials said that many hospitals and laboratories were using rapid diagnostic test (RDT) which can generate inaccurate results, that is, false positive or false negative results.

“Hospitals and laboratories have been instructed to use IgM ELISA test to confirm dengue. Use of RDT test kit can generate false results at times,” said P.G. Bhanumathi, Deputy Director of Health Services, Coimbatore.

According to senior doctors, NS1 (Nonstructural Protein 1) antigen-based rapid testing kit is normally used to detect dengue in the early stage.

Hence, chances are very high for RDT methods to generate a false negative result if samples are tested after five days.

When samples are tested using RDT method, there are also chances for the dengue virus to have cross reaction with other flavi viruses, malaria parasite, and leptospiras which may alter the actual result.

The dengue virus may also have cross reaction with immune disorders such as rheumatoid and lupus.

Health Department suspect that several medium range private hospitals and laboratories still use RDT method for dengue diagnosis.

Dr. Bhanumathi said that District Headquarter Hospital at Pollachi and Coimbatore Medical College Hospital were equipped to perform IgM ELISA test for dengue detection. In the private sector, several multi-speciality hospitals and laboratories had the same facility.

She said that hospitals and laboratories with IgM ELISA facility could perform the examination for which they need not require any approval from the government as in the case of testing A (H1N1) influenza virus.

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Taiwan CDC Unveils Locally Produced Rapid Test Kit for Dengue Virus

The Taiwan Centers for Disease Control (CDC) yesterday announced a new domestically manufactured test for screening dengue fever that is able to show results within 30 minutes.

The mosquito-borne dengue virus is one of the diseases that the agency focuses on preventing each year. In a bid to support the nation’s biotechnology industry and enhance the ability to diagnose dengue, the CDC in September 2015 held an open process to select a company for a technology transfer.

The agency in January last year signed a contract with AsiaGen Corp and received a license from the Food and Drug Administration for the AsiaGen Dengue NS1 Antigen Rapid Test Kit — the only domestic manufacturer of a dengue test kit.

The rapid test kit can detect the four dengue virus serotypes and provide results within 30 minutes, far faster than the traditional reverse transcription-polymerase chain reaction (RT-PCR) method, which takes six hours, CDC Director-General Chou Jih-haw (周志浩) said.

Before the new test was available, doctors had to diagnose dengue from a patient’s symptoms, then take blood samples for RT-PCR testing or imported rapid test kits, which are relatively expensive and unpopular, he said.

The new kit, which is of good quality and cheaper, is expected to help doctors diagnose and treat dengue faster, improving the nation’s dengue prevention ability, he added.

There have been numerous imported cases of dengue, with the top three sources of the disease over the past month being Vietnam, the Philippines and Myanmar, the agency said, adding that a total of 172 imported dengue cases had been reported as of Sunday, more than in the same period in the past six years.

As the number of dengue outbreaks in Southeast Asian countries has continued to rise, people who plan to visit the region are advised to take mosquito bite prevention measures and report to airport quarantine stations or see a doctor if they feel ill after returning to Taiwan.

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Innovate UK Gives Atlas Genetics £2m Contract for Rapid Diagnostic Platform

Innovate UK has awarded a £2 million pound contract to Bath-based company, Atlas Genetics, for its diagnostic instrument (io System) and how to best adopt it into UK sexual health clinics.

Atlas’ io system is a molecular diagnostic platform that rapidly diagnoses a broad range of infectious diseases.

According to an Atlas spokesman, it offers results within 30 minutes, allowing clinical professionals to perform infectious disease tests that are as accurate as those carried out in hospital laboratories.

The two-year contract will allow Atlas Genetics to collaborate with Aquarius Population Health, an independent health economics consultancy, and the Applied Diagnostic Research and Evaluation Unit (ADREU) at St George’s, University of London where they will research the benefits of point-of-care testing for sexual health.

The company wants to further understand how to best integrate its io system into UK sexual health clinical practices and expand its research into diagnostic pathways within sexual health. The funding will also help Atlas develop its Multi-STI (MSTI) test ahead of clinical trials.

The first of the various studies and evaluations conducted by St George’s using the io system started mid-2015.

Atlas have collaborated with St George’s on variety of other projects including i4i, phase 1 of the Small Business Research Initiative (SBRI) project, and have also performed the company’s clinical trial for the CT product, eSTI2 project.

“The (IO) system is not yet commercially available, so while nobody is using the system for patient diagnosis yet, a number of clinics have used the system in a range of different evaluations and usability studies – St Mary’s, Portsmouth, Taunton, Royal South Hants and in the US, University of Alabama, Birmingham”, the spokesman said.

Tariq Sadiq, director of the applied diagnostic and research evaluation unit at St George’s reinforced that it is an innovative approach to better understand and overcome the often complex and substantial challenges to getting cutting-edge technology adopted into the NHS.

“We believe that there are real benefits to using the io rapid diagnostic platform as patients will be able to receive the appropriate treatment immediately and thereby reduce onward transmission, and ultimately save the NHS time and money”, Sadiq said.

Clinics will be able to get patient results in 30 minutes. “This has numerous benefits including reducing loss to follow-up, immediate treatment of positive patients, less empirical treatment / better antibiotic stewardship and reduction in onward transmission and improvement in the patient experience”, the Atlas spokesman said.

John Clarkson, chief executive officer of Atlas said Innovate UK’s commitment to introducing new, pioneering approaches to healthcare validates both their technology and leading role in molecular diagnostics.

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Test Uses Nanotechnology to Quickly Diagnose Zika Virus

Washington University in St. Louis researchers have developed a test that quickly detects the presence of Zika virus in blood.

Currently, testing for Zika requires that a blood sample be refrigerated and shipped to a medical center or laboratory, delaying diagnosis and possible treatment. Although the new proof-of-concept technology has yet to be produced for use in medical situations, the test's results can be determined in minutes. Further, the materials required for the test do not require refrigeration and may be applicable in testing for other emerging infectious diseases.

Findings from the small study -- from Washington University School of Medicine and the School of Engineering & Applied Science -- is available online in the journal Advanced Biosystems.

The researchers tested blood samples taken from four people who had been infected with Zika virus and compared it to blood from five people known not to have the virus. Blood from Zika-infected patients tested positive, but blood from Zika-negative controls did not. The assay produced no false-positive results.

Among the reasons such a test is needed, according to the researchers, is that many people infected with Zika don't know they're infected. Although symptoms include fever, joint pain, muscle pain and rash, many people don't feel ill after being bitten by an infected mosquito. Testing is particularly important for pregnant women because Zika infection can cause congenital Zika syndrome, which contributes to several neurologic problems in the fetus or newborn infant.

"Zika infection is often either asymptomatic or mildly symptomatic," said Evan D. Kharasch, MD, PhD, one of the study's three senior investigators. "The most effective way to diagnose the disease is not to wait for people to develop symptoms but to do population screening."

That strategy requires inexpensive, easy-to-use and easy-to-transport tests. Kharasch, the Russell D. and Mary B. Shelden Professor of Anesthesiology, collaborated with Srikanth Singamaneni, PhD, an associate professor of mechanical engineering & materials science, and Jeremiah J. Morrissey, PhD, a research professor of anesthesiology, to create the test, which uses gold nanorods mounted on paper to detect Zika infection within a few minutes.

"If an assay requires electricity and refrigeration, it defeats the purpose of developing something to use in a resource-limited setting, especially in tropical areas of the world," said Singamaneni. "We wanted to make the test immune from variations in temperature and humidity."

The test relies on a protein made by Zika virus that causes an immune response in infected individuals. The protein is attached to tiny gold nanorods mounted on a piece of paper. The paper then is completely covered with tiny, protective nanocrystals. The nanocrystals allow the diagnostic nanorods to be shipped and stored without refrigeration prior to use.

To use the test, a technician rinses the paper with slightly acidic water, removing the protective crystals and exposing the protein mounted on the nanorods. Then, a drop of the patient's blood is applied. If the patient has come into contact with the virus, the blood will contain immunoglobulins that react with the protein.

"We're taking advantage of the fact that patients mount an immune attack against this viral protein," said Morrissey. "The immunoglobulins persist in the blood for a few months, and when they come into contact with the gold nanorods, the nanorods undergo a slight color change that can be detected with a hand-held spectrophotometer.

"With this test, results will be clear before the patient leaves the clinic, allowing immediate counseling and access to treatment."

The color change cannot be seen with the naked eye, but the scientists are working to change that. They're also working on developing ways to use saliva rather than blood.

Although the test uses gold, the nanorods are very small. The researchers estimate that the cost of the gold used in one of the assays would be 10 to 15 cents.

As other infectious diseases emerge around the world, similar strategies potentially could be used to develop tests to detect the presence of viruses that may become problematic, according to the researchers.

Reference: Rapid, point-of-care, paper-based plasmonic biosensor for Zika virus diagnosis. Advanced Biosystems, published online Aug. 10, 2017.

This work was supported by the National Science Foundation, grant numbers CBET1254399 and CBET1512043. Additional funding was provided by the Department of Anesthesiology, Washington University School of Medicine in St. Louis and the Department of Mechanical Engineering & Materials Science, Washington University in St. Louis.

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FDA Approves Emergency Use for Multiplex Zika Test

The Center for Infection and Immunity (CII) at Columbia University's Mailman School today announced that the U.S. Food and Drug Administration (FDA) has issued an Emergency Use Authorization (EUA) for the CII-ArboViroPlex rRT-PCR Test, the first multiplex assay that simultaneously tests for the presence of Zika virus, all serotypes of dengue virus, chikungunya virus, and West Nile virus, as well as a host gene that ensures the accuracy of results. Available for immediate use in clinical and research settings, the test was developed by CII scientists and an EUA application was submitted to FDA at the request of the National Institute of Allergy and Infectious Diseases (NIAID), a part of the National Institutes of Health (NIH) for use in its multi-country Zika in Infants and Pregnancy (ZIP) study.

"The ArboViroPlex Test provides an easy and efficient means to simultaneously detect Zika and three other mosquito-borne viral infections that may present with similar clinical features," says Nischay Mishra, the lead project scientist and associate research scientist at CII.

"The FDA decision to issue the EUA gives clinicians and researchers a powerful tool to diagnose and prevent the spread of Zika," adds W. Ian Lipkin, director of CII and the John Snow Professor of Epidemiology at the Mailman School of Public Health.

Lipkin, Mishra, and CII colleagues Thomas Briese and Rafal Tokarz are named on a pending international patent application for the technology.

ABOUT THE CII-ARBOVIROPLEX RRT-PCR TEST

The CII-ArboViroPlex rRT-PCR Test is an assay that detects viral RNA matching Zika virus (ZIKV), dengue virus types 1-4 (DENV), chikungunya virus (CHIKV), and West Nile virus (WNV) with a human housekeeping gene, viral RNA controls, and extraction controls that ensure the integrity of the test from nucleic extraction to the final result. Named for the four arboviruses it targets and the real-time reverse transcription polymerase chain reaction (rRT-PCR) technique it employs, the test can simultaneously detect ZIKV, DENV, CHIKV, and WNV in up to 88 samples of blood in less than two hours and ZIKV in urine (collected alongside a patient-matched serum specimen). Under the EUA, testing is authorized for patients meeting CDC Zika virus clinical criteria (e.g., signs and symptoms associated with ZIKV infection) and/or CDC Zika virus epidemiological criteria (e.g., history of residence in or travel to a geographic region with active ZIKV transmission at the time of travel, or other epidemiologic criteria for which ZIKV testing may be indicated) to aid in the diagnosis of ZIKV infection. The test, the manufacture of which will be overseen by CII, is authorized to be performed with the NucliSENS® easyMag® automated extraction platform (bioMérieux), the RNA UltraSense™ One-Step Quantitative RT-PCR System (Thermo Fisher), and CFX96 Real-Time PCR Detection System (Bio-Rad).

ABOUT EMERGENCY USE AUTHORIZATION STATUS

The CII-ArboViroPlex rRT-PCR Test has not been FDA cleared or approved. It has been authorized by the FDA under an EUA for use by laboratories certified under the Clinical Laboratory Improvement Amendments of 1988 (CLIA), 42 U.S.C. § 263a, to perform high complexity tests, or by similarly qualified non-U.S. laboratories. The test has been authorized only for the detection of RNA from ZIKV, DENV, CHIKV, and WNV, and diagnosis of corresponding infections, not for any other viruses or pathogens. It is only authorized for the duration of the declaration that circumstances exist justifying the authorization of the emergency use of in vitro diagnostics for detection of Zika virus under section 564(b)(1) of the Act, 21 U.S.C. § 360bbb-3(b)(1), unless the authorization is terminated or revoked sooner.

ABOUT ZIKA

Several Zika virus outbreaks have occurred in the past few years including the current outbreak ongoing in Brazil and a number of other Central and South American countries. In 2015, the number of suspected Zika virus cases in Brazil was estimated to be between 440,000 and 1.3 million. By February 2017, locally-transmitted cases had been reported from 50 countries and territories in the Americas, including U.S. and U.S. territories, 10 countries and territories in Asia, Oceania, and Pacific islands, and 1 country in Africa. Due to the increasing evidence of a correlation between Zika virus infection and (1) the incidence of Guillain-Barré syndrome and (2) poor pregnancy outcomes, including the development of microcephaly in the fetus or infant, the importance of diagnosing a Zika virus infection is rapidly increasing. Zika virus is primarily transmitted by mosquitoes (including Aedes aegypti). In addition, mother-to-fetus and sexually transmitted infections have been documented. Most cases of Zika virus infection are asymptomatic; however, when symptoms occur they are generally mild and flu-like. Laboratories in the United States are in need of diagnostic tools for use in the acute phase for rapid diagnosis of Zika virus infection. A public health emergency has been declared by the Secretary of Health and Human Services (HHS) on February 26, 2016, justifying the authorization of emergency use of in vitro diagnostic tests for detection of Zika virus and/or diagnosis of Zika virus infection.

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Handheld Spectral Analyzer Turns Smartphone into Diagnostic Tool

Researchers at the University of Illinois at Urbana-Champaign have developed technology that enables a smartphone to perform lab-grade medical diagnostic tests that typically require large, expensive instruments. Costing only $550, the spectral transmission-reflectance-intensity (TRI)-Analyzer from Bioengineering and Electrical & Computer Engineering Professor Brian Cunningham's lab attaches to a smartphone and analyzes patient blood, urine, or saliva samples as reliably as clinic-based instruments that cost thousands of dollars.

"Our TRI Analyzer is like the Swiss Army knife of biosensing," said Cunningham, the Donald Biggar Willett Professor of Engineering and director of the Micro + Nanotechnology Lab at Illinois. "It's capable of performing the three most common types of tests in medical diagnostics, so in practice, thousands of already-developed tests could be adapted to it."

In a recently published paper, Cunningham's team used the TRI Analyzer to perform two commercially available assays—a test to detect a biomarker associated with pre-term birth in pregnant women and the PKU test for newborns to indirectly detect an enzyme essential for normal growth and development. Their tests results were comparable to those acquired with clinic-grade spectrometer instrumentation.

"The TRI Analyzer is more of a portable laboratory than a specialized device," said Kenny Long, an MD/PhD student and lead author of the research study.

Among the many diagnostic tests that can be adapted to their point-of-care smartphone format, Long said, is an enzyme-linked immunosorbent assay (ELISA), which detects and measures a wide variety of proteins and antibodies in blood and is commonly used for a wide range of health diagnostics tests. The system is capable of detecting the output of any test that uses a liquid that changes color, or a liquid that generates light output (such as from fluorescent dyes).

The TRI Analyzer operates by converting the smartphone camera into a high-performance spectrometer. Specifically, the analyzer illuminates a sample fluid with the phone's internal white LED flash or with an inexpensive external green laser diode. The light from the sample is collected in an optical fiber and guided through a diffraction grating into the phone's rear-facing internal camera. These optical components are all arranged within a 3D-printed plastic cradle.

The TRI Analyzer can simultaneously measure multiple samples by using a microfluidic cartridge that slides through an opening in the back of the cradle. This ability to analyze multiple samples quickly and reliably makes the Analyzer suitable for patients who lack convenient access to a clinic or hospital with diagnostic test facilities or for patients with urgent health situations requiring rapid results.

"Our Analyzer can scan many tests in a sequence by swiping the cartridge past the readout head, in a similar manner to the way magnetic strip credit cards are swiped," said Long.
In addition to its applications in health diagnostics, Cunningham said the TRI Analyzer can also be applied to point-of use applications that include animal health, environmental monitoring, drug testing, manufacturing quality control, and food safety. The patented technology is available for license.

A paper describing the results in detail, entitled "Multimode smartphone biosensing: the transmission, reflection, and intensity spectral TRI Analyzer," will be published in an upcoming issue of Lab on a Chip.

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FDA Clears iCubate System, Bloodstream Infection Assay

Molecular diagnostics company iCubate announced the US Food and Drug Administration has cleared its iC-System and iC-GPC assay for the rapid detection of pathogenic bacteria associated with bloodstream infections.

The system is based on iCubate's amplicon-rescued multiplex PCR technology, which detects multiple pathogens simultaneously. iC-GPC Assay is a multiplexed, in vitro diagnostic test for identifying potentially pathogenic bacteria and clinically significant resistance markers to help in diagnosing bloodstream infections. It is the first assay from iCubate to receive FDA clearance, the firm said.

It added that the system and assay provides test results up to 48 hours faster than conventional methods. Detecting bloodstream infections with conventional microbiology methods can take between two to four days, iCubate said.

The iC-GPC assay identifies five of the most common gram-positive organisms associated with gram-positive bacteremia, including Staphylococcus aureus. It also identifies three clinically relevant antibiotic resistance markers specific to methicillin-resistant Staphylococcus and vancomycin-resistant Enterococcus.

"Improved patient treatment through personalized diagnostics is the key mission of iCubate," said company founder and chief scientific officer Jian Han. "The iCubate assay provides a new tool to physicians that will allow for improved patient management through the rapid identification of bacteria and resistance markers, which accomplishes that goal."

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New Rapid, Cost-Effective Diagnostic Test for Viral & Bacterial Infections in Development

A team of researchers at Stevens Institute of Technology are working to develop a new diagnostic test to quickly identify bacterial and viral infections, a tool that can be very benefical to doctors as it can help ensure that the right treatments are prescribed to their patients.

According to the Centers for Disease Control and Prevention (CDC), 20% to 50% of all antibiotics prescribed in hospitals in the United States are either unnecessarily given to patients with viral or other infections, or inappropriate to the type of bacterial infection. Through antibiotic stewardship, health care providers aim to reduce the amount of unnecessary antibiotics prescribed, and ensure that patients receive the right treatment for their infections—both of these goals are key to minimizing the problem of antibiotic-resistant superbugs. At least 2 million illnesses and 23,000 deaths occur in the United States each year due to antibiotic resistance. To reduce that toll and make sure patients get the right medications, doctors need new tools to rapidly and accurately diagnose infections.

At this year’s World Economic Forum Annual Meeting, public health officials from around the world called for improved diagnostics to help address the problem of superbugs around the world. To that end, in the United Kingdom the National Health Service recently launched a new initiative offering a rapid diagnostic test at pharmacies for individuals with sore throats. Now, in a recent announcement, researchers at Stevens Institute of Technology in Hoboken, New Jersey, report that they are working on a test that can quickly differentiate if an infection is bacterial or viral.

“The gold-standard diagnostic test, blood culture, can take as long as three days or more to reach a diagnosis,” explained the project’s principle investigator, Matthew Libera, ScD, in an interview with Contagion®. “Until that time, a patient could be getting no antibiotic or, more likely, an inappropriate. The infection would then simply get worse. Without information about what specific bacterial strain is causing the infection, a clinician is only able to make an educated guess about what to prescribe and how much.”

To address that problem, Dr. Libera and his team have been developing a new detection technology based on gel-tethered DNA and RNA detection probes. The test works by using RNA extracted from drops of blood sampled from a patient, which is then sprinkled onto tiny dots of a specially designed microgel on a glass microscope slide. DNA in the microgel, known as molecular beacons, act as tags for a specific bacterium or virus and glow when they come in contact with matching RNA. The test features a new microgel with DNA probes that function better than earlier iterations of similar technology.

Libera notes that while there are many molecular diagnostic technologies currently commercially available, many tend to be slow and costly. “Detection methods based on molecular diagnostics such as ours can make a diagnosis in times on the order of an hour or less. Hence, the right antibiotic can be prescribed very quickly,” says Dr. Libera. “Speed leads to better patient outcomes and lower-health care costs.”

Dr. Libera says that his team should have a working prototype of their test that clearly demonstrates the differentiating features of their approach within 12 to 18 months. Following the research and development phase, the test will still require approval from the US Food and Drug Administration. “That might be the greater practical challenge and could take more time,” notes Dr. Libera. “However, we are trying now to design our prototype tests to target applications that may give the smoothest pathway to regulatory approval.  We would hope to branch out after that.”

Source: Contagion Live

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Akonni Biosystems Awarded NIH Contract to Develop a Non-Invasive Rapid Diagnostic for Lower Respiratory Diseases in Children

Akonni Biosystems, a molecular diagnostics (MDx) company that develops, manufactures, and intends to market advanced MDx systems, today announced receipt of a Phase 1 Small Business Innovation Research (SBIR) contract (HHSN272201700063C) from the National Institute of Allergy and Infectious Diseases (NIAID), part of the National Institutes of Health (NIH) in the Department of Health and Human Services (HHS). The award will help Akonni accelerate the advancement of its proprietary technologies to address the critically unmet need for simple, effective and affordable tools to diagnose lower respiratory diseases in children.

According to the World Health Organization (WHO), acute respiratory infections are the third leading cause of death worldwide, accounting for 4.2 million deaths annually, more than 40% of which are children under the age of five.  Infectious respiratory pathogens include different types and species of bacteria, viruses, and fungi, many of which exhibit varying levels of drug-resistance, making it challenging to establish a definitive diagnosis and appropriate treatment.  Conventional diagnostic techniques require long turnaround times (e.g., cultures require 5 to 10 days) or lack the required sensitivity (e.g., lateral flow assays for influenza have limited sensitivity to as little as 10.4%).  Compounding the testing time and poor sensitivity issues is the limited ability to test for a variety of different respiratory pathogens simultaneously.  Recently developed multiplexed molecular diagnostic respiratory panels offer the potential to address these issues.

"The diagnosis of lower respiratory tract infections in children presents an additional challenge," said Dr. Rebecca Holmberg, Director of Application Development at Akonni and Principal Investigator on this project along with Dr. Christopher Cooney, Director of Engineering.  "Specimen collection of sputum is difficult for children to produce and bronchoalveolar lavage is invasive and burdensome for children, particularly for those with wheezing and coughing symptoms.   These collection methodologies also introduce variability in the quality of the specimen and is dependent on the skill and experience of the nurse or technician.  Parents can thus be deterred by the harshness of these procedures, potentially avoiding care and risking more severe outcomes as well as the further spread of the disease."

As a consequence of this continued reliance on relatively ineffective technologies, patient misdiagnosis occurs frequently.  Misdiagnosis presents several serious risks, such as public endangerment or the administration of inappropriate therapy, which is largely responsible for the increasing prevalence of drug-resistant strains.  Michael Reinemann, MPH, Director of Business Development at Akonni stated, "Akonni's unique solutions for diagnosing respiratory infections from non-invasive samples offer the potential to reduce the morbidity, mortality and cost of treatment for the millions of affected children each year.  We are excited to work on this project, which aligns very nicely with Akonni's mission to develop rapid, affordable and accurate molecular diagnostic tools that will measurably improve the health status of millions of people worldwide."

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PositiveID Successfully Detects Ebola Virus on Its Firefly Dx Prototype System

PositiveID Corporation, a life sciences company focused on detection and diagnostics, and its ExcitePCR Corporation subsidiary, announced that it has successfully detected Ebola virus on the Firefly Dx breadboard pathogen detection system (prototype system).

In a collaborated effort with assay partner GenArraytion Inc., ExcitePCR successfully detected the Ebola virus on the Firefly Dx prototype system. The Ebola virus was tested at a low number of copies via polymerase chain reaction (PCR) and the amplification curves demonstrated a cycle threshold (Ct) of 21. The automated runs successfully synthesized cDNA using a proprietary reverse transcriptase (RT) step and then completed a 40-cycle PCR to produce the results.

Rapid detection and diagnosis of the Ebola virus infection along with vaccination is imperative to quickly containing an epidemic. Ebola is an RNA virus and requires a RT step prior to PCR. Despite its potential diagnostic advantages, RT-PCR methodology (both conventional and real-time approaches) typically requires significant laboratory infrastructure, electrical power, multiple temperature-sensitive reagents, the operation and maintenance of specialized equipment, and technical expertise in molecular biology, potentially complicating deployment in resource-limited settings.

"At the height of the Ebola virus outbreak, there were multiple challenges with accurately diagnosing individuals due to the need to collect samples, take them back to a central lab, and then wait hours or even days for results," stated Lyle L. Probst, CEO and President of ExcitePCR."Firefly Dx could eliminate those challenges as a self-contained, portable lab for point-of-care/point-of-need applications, providing results in 30 minutes."

The recent outbreak of the Ebola virus disease in West Africa has highlighted both the importance of rapid and accurate diagnosis of this disease and the challenges around diagnostic testing. Throughout the 2014-2015 outbreak, diagnosis relied primarily on the testing of venipuncture blood samples from symptomatic individuals in a biocontainment laboratory facility, leading to challenges with specimen collection and data management and often a prolonged turnaround time to final results.

Mr. Probst continued, "Ebola detection is a perfect example of an application where Firefly Dx could be particularly critical in remote locations, far from lab facilities, where time to results can mean life or death. This is why we have formed ExcitePCR; to facilitate getting the necessary strategic partner and direct funding in place to complete the development of what we believe is a very important product that can change the face of biological detection."

In addition to the Ebola virus, the Firefly Dx prototype system has also successfully detected a number of other pathogenic organisms, including Zika, E. coli, influenza, MRSA, MSSA, C. diff, and others.

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Study Finds Rapid Tests for Malaria Linked to Increased Antibiotic Usage

Researchers from the London School of Hygiene and Tropical Medicine (LSHTM) discovered that introducing malaria rapid diagnostic tests across malaria-endemic regions improved antimalarial targeting, but also has prompted a slew of unintended consequences including the overuse of antibiotics.

Malaria rapid diagnostic tests are intended to improve the management of suspected malaria cases, increasing the use of first-line antimalarials in patients with confirmed malaria and encouraging the diagnosis and appropriate treatment of patients without malaria.

According to the study, published in the American Journal of Tropical Medicine and Hygiene, the analysis showed that while in most situations the rapid tests effectively limited the routine practice of prescribing malaria medications known as artemisinin combination therapies (ACTs), the technology has indirectly caused a spike in antibiotic prescriptions and other problems.  

"We found that in many places a reduction in the use of ACTs was accompanied by an increase in the use of antibiotics, which may drive up the risk of antibiotic-resistant infections," LSHTM assistant professor Katia Bruxvoort said in a statement.

Bruxvoort and her team believe that the shift to antibiotics after ruling out malaria may suggest that many patients and clinicians do not feel comfortable with standard treatment for non-malaria related fevers, which involves taking fever-reducing drugs and drinking plenty of fluids.

"We don't currently have a reliable way to determine which fevers are evidence of a bacterial infection that requires a specific antibiotic treatment and which fevers resolve with supportive care only," Bruxvoort said.

The researchers analyzed drug prescriptions written from 2007 to 2013 in over half a million patient encounters documented in 10 related studies in malaria-endemic locations of Afghanistan and Africa conducted by the ACT Consortium, a global research initiative investigating important issues around anti-malarial drugs. The studies looked at the impact of rapid diagnostic test introduction on fever case management across a range of clinical and epidemiological contexts and among various types of healthcare providers.

Rapid diagnostic tests were introduced in health facilities, community health workers, private drug shops, and pharmacies.

In most areas, 40 to 80 percent of patients who tested negative for malaria via rapid diagnostic tests were prescribed antibiotics, despite the awareness of standard treatment for fevers unrelated to malaria.

Even more worrisome for researchers, a negative test for malaria was only partially effective at limiting ACT prescriptions. For example, in two areas, Cameroon and Ghana, 39 to 43 percent of patients who tested negative for malaria still received ACTs.

Overall, 75 percent of patients studied left clinics with either antibiotics or an ACT, sparking concerns about drug-resistant malaria.

Rapid diagnostic test usage for malaria has skyrocketed globally since 2010 as World Health Organization officials have sought to reduce unnecessary prescriptions for ACTs. In Africa, where ACTs have been a major factor in the 60 percent drop in malaria deaths in the past 15 years, researchers fear the recent strides in public health could disappear if ACT-resistant malaria moves across the continent.

"Technology alone cannot solve complex health problems; community and provider education, as well as health system changes, must occur hand in hand to improve patient outcomes" Patricia Walker, president of the American Society of Tropical Medicine and Hygiene said in a statement.

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Karius Announces $50 Million in Financing for Technology Enabling Broad and Rapid Detection of Infectious Diseases

Karius, Inc., a life sciences company focused on conquering infectious diseases, today announced that the company has raised $50 million in Series A equity financing. Existing investors Data Collective (DCVC) and Lightspeed Venture Partners co-led the financing, with major participation from new investors including Tencent and Khosla Ventures. Existing investors Innovation Endeavors and Spectrum 28 participated as well.

Funds will be used to support ongoing and new clinical trials, scale up laboratory capacity, and advance commercialization of the Karius test, which uses a combination of machine learning, proprietary genomics algorithms, and next-generation sequencing to enable the broad and rapid detection of more than 1,250 pathogens. The company recently moved into a new 25,000-square foot facility, significantly increasing laboratory space and capacity to process more tests.

Using a standard blood draw, the Karius test identifies cell-free DNA fragments left by bacteria, viruses, fungi, and other eukaryotic pathogens in a patient’s bloodstream, even when living organisms are no longer detectable in the blood. Karius is the first company to put microbial cell-free DNA analysis data into the hands of clinicians, making it commercially available through its CAP-accredited and CLIA-certified laboratory service. The company can provide a potentially life-saving diagnosis for patients, typically within one business day of blood sample receipt.

"We're excited to partner with this world-class group of investors and innovators to help us conquer infectious diseases using the power of genomics," said CEO Mickey Kertesz, Ph.D. "Infectious diseases are a leading cause of mortality globally and an enormous area of unmet need. Clinical results from our early access program demonstrate that the Karius test allows clinicians to diagnose infections more rapidly and accurately. We've enabled doctors to devise precise and effective treatment plans for patients and speed recovery times. We look forward to further broadening availability of our technology in the coming months.”

“We seeded and have doubled-down on financing Karius for two reasons,” said Matt Ocko, Managing Partner at DCVC. “First, because the core team has already significantly advanced sequencing with their previous company, which we also helped finance and that was ultimately acquired by Illumina. Secondly, and more importantly, Karius is providing doctors with critical information that can save lives that would be otherwise lost to infectious disease. This new financing will help Karius do this on a global scale.”

Infectious diseases are a leading cause of death around the world, and traditional methods of testing can only detect a narrow range of pathogens and may require invasive biopsies. Earlier this summer, Karius presented data at ASM Microbe 2017 demonstrating the ability of the company’s technology to detect pathogens from cell-free DNA using next-generation sequencing.

"I am passionate about the potential of Karius' technology to save lives – and I couldn't be more excited to see what the team has accomplished since the core technology spun out of my lab," said Stephen Quake, Ph.D., Karius Scientific Co-Founder and Co-President of Chan Zuckerberg Biohub. "Karius is poised to revolutionize infectious disease diagnostics with a hypothesis-free approach that represents a major paradigm shift for medicine."

About the Karius Digital Culture™ Test

The Karius Digital Culture™ test applies advanced sequencing and analytics for the broad and rapid detection of microbial cell-free DNA through a standard blood draw. Unlike conventional culture and panel testing methods that test for a narrow range of pathogens, the Karius test can detect more than 1,250 pathogens, typically within one business day. Through Karius’ CAP-accredited and CLIA-certified laboratory service, the test empowers doctors to diagnose infections quickly while sparing patients the pain and risk of invasive biopsies, and provide rapid and more targeted treatment.

About Karius, Inc.

Karius is a life sciences company focused on conquering infectious diseases through the innovative use of next-generation sequencing to analyze microbial cell-free DNA. The company’s genomics platform delivers unprecedented insight into the microbial landscape, providing clinicians with a comprehensive test capable of identifying more than a thousand pathogens directly from blood and helping industry accelerate drug development.

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Bruker Announces Acquisition of Field-Portable Platform for Fast and Universal Immunoassay-Detection of Bacteria, Viruses and Toxins

Bruker announced the closing of a technology platform and product line acquisition to further expand its range of bacterial, viral and toxin detection solutions for homeland security bio-detection and for selected microbiology applications.  Financial details were not disclosed.

The acquired assets include intellectual property, a field-portable, electrochemical chip-based detection instrument and associated consumable kits for on-site, fast identification of selected bacteria, viruses and toxins.

Detection and identification of up to 6 bio-threats per assay chip occurs typically within 20 minutes, with excellent sensitivities and without any prior culturing steps for bacteria.  The immunoassay kits, which Bruker now can offer for bio-detection and homeland security, include:

• Biothreat Test: Bacillus anthracis, Yersinia pestis, Francisella tularensis, Brucella species, Burkholderia mallei/pseudomallei, Orthopox viruses (smallpox);
• Toxin Test I: Botulinum Toxins A, B, F; Staphylococcal Enterotoxin B; Ricin;
• Toxin Test II: Botulinum Toxin C, D, E; Staphylococcal Enterotoxin A; Abrin;

The acquired instrument platform, the portable Bio-Detector integrated (pBDi), is ready for immediate commercial launch.  Unlike other PCR-based field methods, the unique multiplex ELISA-based (enzyme-linked immunosorbent assay) detection with a novel electrochemical chip readout, allows rapid on-site identification of various bio-threats, including toxins, with very high sensitivity.

Developed for ease of use by non-scientific personnel, the pBDi can even be operated while working in protective gear under field conditions.  Fully portable and operating from internal batteries, the pBDi can be used in 'hot zones'.

Dr. Thomas Elssner, Bio-Detection Manager at the Bruker Detection division, commented: "We are very excited to offer the pBDi as an easy-to-use and robust detection system that was specifically designed for field applications, and which dramatically decreases the time and effort to assess the seriousness of bio-threat incidents.  Our new platform also allows the flexible development of new assays and consumables to address emerging threats."      

Dr. Wolfgang Pusch, Executive Vice President of Microbiology & Diagnostics at Bruker Daltonics, added: "The new pBDi system leverages our recently acquired capabilities in monoclonal antibody production to enable new, fieldable immunoassay workflows for fast toxin, viral and bacterial detection, in the future also in clinical and food microbiology.  The pBDi platform is a valuable expansion of our microbiology portfolio, consisting of the MALDI Biotyper for broad and fast microbial identification, the IR Biotyper for infection control workflows, and the Fungiplex and Carbaplex real-time PCR assays for rapid molecular testing."

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Emerging Technologies to Combat E. coli

Recalls over Escherichia coli concerns dominate the current food safety headlines, with two significant, recent occurrences.  In late May, Smucker Foods of Canada was forced to recall three brands of flour in the U.S. due to possible E. coli contamination, while wholesale restaurant food supplier Creation Gardens began recalling over 22,000 pounds of beef in early June. According to the U.S. Department of Agriculture, Creation Gardens is recalling raw ground beef and beef primal cut products, including beef patties, short ribs and sirloin. The products were produced between June 1 and June 2, 2017, and shipped to locations in Indiana, Kentucky, Ohio and Tennessee.

All told, E. coli O157 is believed to be the root of approximately 73,000 illnesses and 60 deaths every year in the U.S.

Scientists at the Massachusetts Institute of Technology (MIT) believe they may have discovered the next entry into the litany of tests and detection systems for food processors to implement to fight off E. coli.

The new test—using a liquid that binds to bacterial proteins—can be detected by either the naked eye or a smartphone, offering a much faster and cheaper alternative to existing food safety tests. The scientists developed a way to easily make complex droplets of two equally sized hemispheres, one made of a fluorocarbon and one made of a hydrocarbon. The researchers decided to explore using these droplets as sensors because of their unique optical properties. In their natural state, the liquid is transparent. When applied to the proteins found in E. coli, however, the droplets clump and become opaque.

Current food safety testing often involves placing food samples in a culture dish to see if harmful bacterial colonies form, but that process takes two to three days. Faster tests are available but are expensive and involve special instruments. With this new test, the food samples are placed atop a QR code that can be scanned with a smartphone. When E. coli are present, the droplets clump together and the QR code can’t be read.

The MIT team hopes to adapt its new technology into arrays of small wells, each containing droplets customized to detect a different pathogen and linked to a different QR code. This could enable rapid, inexpensive detection of pathogens on the factory floor, using only a smartphone.

While the researchers at MIT hope to launch a company to commercialize the technology within the next year and a half, this is just the latest example of the many different angles the industry is using to tackle food safety.

From sanitary design to packaging and processing systems involving metal and/or X-ray detection, technologies are emerging every year to ensure the safety of the global food supply chain. It is thus incumbent on everyone in the food industry to take advantage of opportunities to learn about such advances, including scientific meetings, trade shows and the vast literature on these developments.

Source: Food Safety Magazine

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bioMérieux Receives FDA Clearance for Expanded Pathogen Identification Capability on VITEK® MS

bioMérieux, a world leader in the field of in vitro diagnostics, today announced that VITEK® MS, its MALDI-TOF1 Mass Spectrometry System for rapid pathogen identification, has received 510(k) clearance from the U.S. Food and Drug Administration (FDA) for the expanded identification of mycobacteria, Nocardia and moulds. This database includes more than 15,000 distinct strains to provide extremely high accuracy and, for the first time, enables the safe identification of the Mycobacterium tuberculosis (TB) group, the most frequent non-tuberculous mycobacteria (NTM), Nocardia and the most medically important moulds. The VITEK® MS system’s newly expanded database and Mycobacterium/Nocardia and Moulds reagent kits are now commercially available in the U.S.

Mycobacteria, Nocardia and moulds are complex organisms to identify, requiring days or weeks of specific culture conditions for appropriate growth and subsequent advanced methods for reliable identification to the species level. With the newly expanded database, bioMérieux’s VITEK® MS system now offers simple, rapid, safe and reliable identification of these medically important pathogens, providing clinicians with actionable results to better manage these infections, such as tuberculosis, lung and bone infections, and other serious organ infections.

To gain new FDA clearance for these new species, bioMérieux submitted data from a multi-center study consisting of 2,695 clinical isolates for 47 moulds, 19 mycobacteria, and 12 Nocardia. The FDA clearance of Mycobacterium species was from both solid and liquid growth media.

"We are honoured to receive the first 510(k) clearance from the FDA for the identification of mycobacteria, Nocardia and moulds on a MALDI-TOF system and to provide our U.S. customers with additional features for the already well adopted VITEK® MS rapid identification system,” said François Lacoste, bioMérieux Corporate VP, Clinical Unit. "As the world leader in microbiology, one of our priorities is to continuously develop high medical value solutions that enable rapid and accurate detection of important microorganisms, with the ultimate goal of improving patient care.”

VITEK® MS is part of bioMérieux’s comprehensive and complementary range of ID/AST solutions for infectious disease diagnostics. Together, VITEK® MS for identification and VITEK® 2 for antimicrobial susceptibility testing provide seamless integration and the flexibility needed to optimize laboratory workflow and support appropriate antimicrobial treatment decisions. The combination of VITEK® MS and VITEK® 2 provides confidence in reporting results with speed and accuracy for routine diagnoses, unusual or resistant organisms, or critical clinical situations.

In cases where microorganisms are resistant to carbapenems (a very broad spectrum antibiotic class), bioMérieux has also developed and received FDA 510(k) clearance for its RAPIDEC® CARBA NP test that enables the detection of carbapenemase producers within two hours. RAPIDEC® CARBA NP helps health professionals make vital treatment decisions and facilitates implementation of infection prevention and control measures.

These highly complementary solutions help improve antibiotic stewardship in the fight against antimicrobial resistance.

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