LamdaGen and Arisan Therapeutics Receive a $2 Million NIH SBIR Phase II Grant to Develop a Dual Rapid Point-of-Care Test for Acute Dengue and Zika Viral Infections

LamdaGen Corporation and Arisan Therapeutics announced today they will share a $2 million Phase II Small Business Innovation Research (SBIR) grant from the National Institute of Allergy and Infectious Diseases, a division of the National Institutes of Health (NIH), to develop a high-sensitivity point-of-care (POC) dual diagnostic to detect both acute dengue and Zika viral infections in a single rapid test on LamdaGen's L'AuRa digital diagnostic platform.

The L'AuRa platform enables robust diagnostic testing that is simple, compact and cost-effective with no moving parts. L'AuRa technology can be integrated into designs ranging from miniaturized handhelds to small desktops to lab-based throughput systems, each providing powerful on-the-spot performance of high-sensitivity, rapid and quantitative diagnostic assays.

Global incidence of dengue has grown dramatically in recent decades with half of the world's population now at risk. In fact, incidence of both dengue and Zika are escalating and prone to unpredictable outbreaks due to climate shifts and proliferation of carriers such as mosquitoes and ticks. Currently, an estimated 390 million dengue infections occur annually. Of these, approximately 500,000 cases develop into life-threatening dengue hemorrhagic fever (DHF) or dengue shock syndrome (DSS), severe forms of the disease which result in over 25,000 deaths globally each year.

"Early diagnosis of patients with dengue, in particular, is critical for timely clinical intervention and disease control," commented Randolph Storer, CEO of LamdaGen. "Dengue and Zika are closely related and currently there is no FDA-approved multiplex POC test that can differentiate between the two during the acute phases of infection. Our collaborators at Arisan have identified highly specific antibodies for each test, which we are integrating into the development on the L'AuRa platform."

In addition to enabling differentiation between the two viruses, this highly sensitive and quantitative POC assay will have the potential to act as a prognostic for identifying patients at risk of developing severe forms of dengue including DHF and DSS based on concentration of viral antigen found in blood. Early identification of at-risk patients may help reduce mortality and morbidity by enabling immediate monitoring and medical care.

Speaking of the importance of this NIH grant, Ken McCormack, president of Arisan, added, "We are very appreciative of NIH's support and excited to move forward in our collaboration with LamdaGen to develop these potentially life-saving solutions."

About LamdaGen Corporation

Based in Menlo Park, California, LamdaGen is a developer of nano-based plasmonic biosensors and robust diagnostic systems. The company is increasing access to healthcare with its L'AuRa diagnostic platform, a game-changing technology. L'AuRa is an immuno-based platform that combines the high sensitivity and precision of ELISA with the simplicity and speed of lateral flow to enable quantitative and rapid detection of diseases, pathogens and contaminants. LamdaGen licenses its L'AuRa technology to companies in the human diagnostic, companion animal and food safety industries.

About Arisan Therapeutics Inc.

A privately held life science company based in San Diego, California, Arisan was founded to develop therapeutics for neglected and emerging viral diseases, focusing on infectious diseases with the potential for significant impact on public health and those classified as priority biodefense-related pathogens. The company's mission is to identify unmet medical needs and provide appropriate solutions through development, collaboration and partnerships to benefit patients with life-threatening infectious diseases.

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New Rapid Test Significantly More Effective for TB-diagnosis in People with HIV

A new study has shown a new point-of-care (POC) device to diagnose tuberculosis (TB) in people living with HIV to be substantially (28%) more effective at identifying TB-positive patients than the only POC TB diagnostic device currently available, Alere Determine TB LAM Ag (AlereLAM).

The new Fujifilm SILVAMP TB LAM (FujiLAM) device was shown to be more sensitive than the current POC TB test, at 70.4% compared to 42.3%. This means that FujiLAM has the potential to reduce the number of false negative test results (where someone who has TB incorrectly tests negative). The specificity of the two tests, which measures the likelihood of a test returning a false negative result, was comparable at 90.8% for FujiLAM and 95% for AlereLAM.

There is an urgent need for more rapid, point-of-care diagnostic devises for TB. The challenge is especially important for people living with HIV, because sputum-based tests (which detect TB in saliva and mucous) have consistently demonstrated suboptimal results for immunocompromised individuals.

People living with HIV often have extrapulmonary TB, where the infection has affected parts of the body other than the lungs. This is difficult to diagnose with sputum alone, and severely immunocompromised individuals may have trouble producing the sputum needed for a sample.

Instead of using sputum, both FujiLAM and AlereLAM test for TB in samples of urine, detecting lipoarabinomannan a component of a bacterium found in urine and indicative of TB infection. This present study was conducted to assess the diagnostic accuracy of FujiLAM for the detection of active tuberculosis compared with AlereLAM in hospital patients with HIV.

968 patients from three separate cohorts of hospital in-patients living with HIV in South Africa were included in the final analysis. 62% of the patients were later defined as having active TB, 9% were defined as unknown, and 29% were defined as non-TB.

The median patient age was 35, and the median CD4 count was 113 cells per copy in cohort 1, 153 cells per copy in cohort 2 and 59 cells per copy in cohort 3. Just under half (45%) had a previous history of TB. Cohort 3, which had more people with advanced HIV disease than other cohorts, had the highest sensitivity result at 81% compared to the microbiological reference standard.

Among all patients with a CD4 count less than 100 cells per copy, FujiLAM had a sensitivity of 84.2% compared with 57.3% for AlereLAM. Among patients with CD4 counts over 200 cells per copy, sensitivity was 44% and 12.2% respectively.

The findings are backed up by a previous systematic review carried out by the World Health Organization, which found similar sensitivity and specificity results for the AlereLAM device. The authors conclude that the FujiLAM point-of-care assay could save lives by enabling earlier diagnosis of HIV-associated TB in more inpatients than AlereLAM. But before it can be implemented into clinical practice, further research is warranted and outside of a research laboratory setting.

Authors of the present study led by Tobias Broger and Bianca Sossen, comment, “since AlereLAM has demonstrated survival benefit, FujiLAM might potentially further reduce tuberculosis-related mortality in people with HIV.”

“These findings will inform a WHO policy review for lipoarabinomannan-based diagnostic tests of active tuberculosis. Further research, including prospective and operational studies on the FujiLAM assay in settings of intended use and in additional patient populations, including outpatients with HIV, populations without HIV, and paediatric populations, are needed.”

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Metagenomic Sequencing Improves Diagnosis of Neurologic Infections

Metagenomic next-generation sequencing, or NGS, of cerebrospinal fluid can improve the diagnosis of neurologic infections in patients with encephalitis or meningitis, according to findings from a 1-year, multicenter, prospective study published in The New England Journal of Medicine.

During the study, metagenomic NGS identified some infections that clinical testing missed, leading to adjusted treatment in some cases, researchers reported.

“A new clinical metagenomic sequencing test of cerebrospinal fluid is able to diagnose mysterious neurological illnesses in patients that are missed by conventional approaches,” Charles Chiu, MD, PhD, director of University of California, San Francisco’s Abbott Viral Diagnostics and Discovery Center, told Infectious Disease News.

“The metagenomic next-generation sequencing test is a comprehensive test that looks for nucleic acid (DNA and RNA) from all potential pathogens — bacteria, viruses, fungi and parasites. It may be particularly useful for diagnosing neurological infections from organisms that do not grow or grow poorly in culture (eg, viruses, fungi, atypical bacteria such as Nocardia) or rare organisms that are not commonly considered in the differential diagnosis (eg, parasites such as Angiostrongylus cantonensis and Balamuthia mandrillaris, viruses such as St. Louis encephalitis virus and hepatitis E virus).”

According to Chiu and colleagues, the traditional approach to diagnosing neuroinflammatory diseases presents difficulties because of overlapping clinical manifestations of infectious and noninfectious causes, the limited availability and volume of central nervous system samples obtained through invasive procedures and a lack of diagnostic tests for rare pathogens. Because of these challenges, a cause is not identified in half of acute meningoencephalitis cases, they said.

To address this diagnostic need, the researchers enrolled 204 adult and pediatric patients from eight hospitals who presented with idiopathic meningitis with or without encephalitis or myelitis, or both. According to Chiu and colleagues, many patients were severely ill, with 48.5% having been admitted to the ICU. Patients in the study had a 30-day mortality rate of 11.3%, they reported.

Physicians diagnosed 58 infections of the nervous system in 57 patients (27.9%). According to the study, metagenomic NGS identified 13 (22%) infections that were not identified by clinical testing at the source hospital. Out of these 13 diagnoses, eight had a “likely clinical effect,” and seven resulted in treatment adjustments by physicians, the researchers found.

“The highest diagnostic yield resulted from a combination of metagenomic NGS of [cerebrospinal fluid] and conventional testing, including serologic testing and testing of sample types other than [cerebrospinal fluid],” Chiu and colleagues wrote.

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T2Candida Diagnostic Test for ICU Patients at Risk for Invasive Candidiasis

Although the diagnostic performance for all tests were modest in regards to the detection of invasive candidiasis in patients in a high-risk intensive care unit (ICU), the combination of the new test T2Candida and blood culture seemed to have the best performance, according to a study published in Open Forum Infectious Diseases.

Blood culture is the gold standard test for invasive candidiasis, comprising candidemia and deep-seated candidiasis, but the sensitivity of this test is low. The average time to blood culture positivity is approximately 2 days, and some studies have associated a 2-day antifungal therapy delay with a more than doubled mortality rate. There is, therefore, a need for rapid diagnostic testing in invasive candidiasis.

Researchers investigated the performance of T2Candida, a new diagnostic test recently approved by the Food and Drug Administration, compared with Candida mannan antigen (MAg), and blood culture for the detection of invasive candidiasis in a study cohort of 126 ICU patients at high risk for invasive candidiasis. Despite 3 days of broad-spectrum antibiotics, the patients still had sepsis. Paired sets of T2Candida, MAg, and blood culture were obtained 2 times per week for a total of 334 sets. Based on a review of patient records, patients were classified into categories of unlikely, possible, likely, or proven invasive candidiasis.

At the time of enrollment, 77% (n=92) of patients were already receiving antifungal therapy (primarily fluconazole 66%). Fifteen patients (11.9%) tested positive by T2Candida (n=11), MAg (n=10), or blood culture (n=4). At inclusion, the T2Candida species distribution was supported by the identification of colonizing isolates or blood culture in 10 of 11 cases (Candida albicans/Candida tropicalis: 8/11 [72.3%] and Candida glabrata/Candida krusei: 3/11 [27.3%]). Patients were classified as unlikely (n=98), possible (n=11), likely (n=6), and proven (n=11).

In patients in the category of proven invasive candidiasis, sensitivity was found as 55%, 45%, and 36% for T2Candida, blood culture, and MAg tests, respectively. In patients with proven or likely invasive candidiasis, the sensitivities increased to 59%, 29%, and 41% for T2Candida, blood culture, and Mag test, respectively. The sensitivity increased to 64%-65% when T2 Candida was combined with one of the other tests; whereas when T2Candida was not included, sensitivity decreased to 53%-55%. The negative predictive value for proven vs others, and proven/likely vs others was similar across all tests (94% to 96% and 90% to 95%, respectively). The positive predictive value for T2Candida in proven cases of invasive candidiasis was 50% compared with 36% for MAg testing. Positive predictive value for these tests respectively to 83% compared with 64%, in patients with either proven or likely invasive candidiasis.

Researchers concluded, “T2Candida was the biomarker that contributed the most to improving the diagnostic sensitivity while retaining a good specificity and [negative predictive value]. This makes it a promising addition to the diagnostic armamentarium. However, our study also suggests that maximal benefit of diagnostic efforts may require that sampling is initiated as early as possible, preferably before initiation of antifungal therapy, when the sensitivity and [negative predictive value] of T2Candida and [blood culture] testing are maximal and probably sufficient for excluding [invasive candidiasis].”

This work was supported in part (test kits were provided, and part of the hourly fee for the ICU doctors spent on patient record review was reimbursed to the ICU departments) by T2Biosystems.

Reference

Arendrup MC, Andersen JS, Holten MK, et al. Diagnostic performance of T2Candida among ICU patients with risk factors for invasive candidiasis [published online March 25, 2019]. Open Forum Infect Dis. doi: 10.1093/ofid/ofz136

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New Data Shows That Karius Blood Test Can Non-Invasively Detect Pathogens In Deep Infections

Karius, a life sciences company that delivers genomic insights for infectious diseases, announced new findings that show the potential clinical utility of its Karius® Test to detect pathogens causing serious infections using a simple blood draw. This includes pathogens that are otherwise difficult to culture or identify without an invasive biopsy.

The Karius Test is a non-invasive blood test based on next-generation sequencing of microbial cell-free DNA. It can identify and quantify over 1,000 clinically relevant pathogens including bacteria, DNA viruses, fungi, and parasites.

Applications include complicated pneumonia, immunocompromised patients, and endocarditis.

During an acute infection, pathogens leave microbial cell-free DNA (mcfDNA) in the blood. Even when an infection is localized, mcfDNA from the infection can be detected.

A sample workflow is illustrated below:

"Rigorous clinical studies of the Karius Test continue to show its ability to identify and quantify pathogens from a single blood test," said Karius Co-founder and CEO, Dr. Mickey Kertesz. "In some of the studies, this was the first time that a non-invasive method was able to identify pathogens that were previously only detectable with invasive biopsies."

Below are the five studies Karius presented at ASM Microbe 2019.

1.    Detection of Bartonella species in Culture-Negative Endocarditis using the
       Karius Test, a Plasma Next-Generation Sequencing test for Pathogen Detection

Bartonella species are fastidious, gram-negative bacteria that can cause culture-negative endocarditis (CNE), lymphadenitis, visceral abscesses, and fever of unknown origin. Diagnosis frequently requires sampling of infected tissue. Dr. Asim Ahmed, Karius Medical Director, will present the Karius Test's ability to identify Bartonella species in culture-negative endocarditis and will discuss how the quantitative aspect of the test may offer a means to monitor patient response to therapy.

2.    Next-generation Sequencing of Pathogen Cell-free DNA in Plasma (Karius Test)
       Reveals Nocardia Species Diversity in Clinical Infections

Nocardia can cause pulmonary, brain, skin, or disseminated infections in immunocompromised and immunocompetent patients. Nocardia is difficult to culture and often requires invasive methods for diagnosis. Dr. Asim Ahmed, Karius Medical Director, will present new findings that highlight the Karius Test's ability to uncover new insights on genus complexity of Nocardia species, which can potentially help inform treatment decisions.

3.    Sequencing of Plasma Cell-Free DNA for Pathogen Detection in Prosthetic
       Joint Infections

Currently, identification of pathogens causing prosthetic joint infections typically requires testing tissue directly from the site. In an evaluation of the Karius Test's ability to detect pathogens in prosthetic joint infections, David Danko of Weill Cornell Medicine will present how the Karius Test was able to identify pathogens in prosthetic joint infection cases. These findings highlight the potential of the Karius Test to serve as a non-invasive alternative to detect deep infections.

4.    Evaluation of Karius Plasma Next Generation Sequencing of Cell-free Pathogen
       DNA to Detect and Quantitate Cytomegalovirus, Epstein-Barr Virus, and BK
       polyomavirus

Dr. Tim Blauwkamp, Karius Chief Scientific Officer, will present new findings that show a high correlation between the Karius Test and industry-standard quantitative PCRs for Cytomegalovirus (CMV), Epstein-Barr Virus (EBV), and BK polyomavirus (BKV). These viruses can cause serious complications for immunocompromised patients. The findings highlight the Karius Test's ability to simultaneously detect and quantify CMV, EBV, and BKV.

5.    Improving the Clinical Specificity of the Unbiased Karius Test via Literature Mining

Dr. Lily Blair, Investigative Computational Biologist at Karius, will present the benefits of applying artificial intelligence methods to increase the utility of diagnostic tests for infectious diseases. Using machine learning algorithms, the Karius team processed more than 27 million abstracts from PubMed to compute how likely a microbe was to cause sepsis. Significant clinical specificity improvements are demonstrated by applying this method to the SEP-SEQ study, a study that validated the performance of the Karius Test in 350 patients with suspected sepsis recently published in Nature Microbiology.

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A Forgotten Disease': the Diagnostic Test Which Could Revive the Battle to Eradicate Yaws

A rapid diagnostic test to identify yaws, a debilitating skin disease which affects thousands of the world’s poorest children, could reinvigorate efforts to eradicate the illness, experts say.

The molecular test, which detects yaws within 30 minutes, could allow on-the-spot diagnosis in remote regions – eliminating the need to transfer disease samples for hours or even days to high-tech laboratories for expensive tests.

Yaws is a bacterial disease (caused by the bacterium Treponema pertenue) which spreads through skin-to-skin contact and causes skin lesions and ulcers all over the body. Though easily treated with a single dose of antibiotics, yaws still impacts more than 46,000 people globally—75 to 80 percent of whom are children under the age of 15 years old.

It is not fatal but if left untreated, the illness leads to chronic disfigurement and disability.

“Yaws affects children living in very rural, hard to reach communities – there is a saying that where the road ends, that is where yaws begins,” said Laud Anthony Basing, biomedical engineering research graduate at Purdue University in the US, and creator of the rapid test.

“It eats into the skin, into the bones, into the cartilage, and if you do not treat it the child will grow up with deformities or disabilities,” he added.

More than 80,000 suspected cases of yaws were reported to the World Health Organization in 2018, but the real number of infections is likely to be much higher.

Just 15 countries known to be endemic with the disease record cases, but more than 70 other nations which previously saw high rates of yaws no longer track infections.

While most people today have never heard of yaws, it was once the subject of an ambitious eradication campaign.

Between 1952 and 1964, Unicef and the WHO screened some 300 million people for the illness, in a coordinated programme which treated more than 50 million cases. Yaws was on the brink of being wiped out and reports of the disease dropped by 95 per cent.

But eradication efforts were a victim of their own success. Yaws-specific programmes were dismantled and existing health care systems were left to tackle the ‘final cases’. Resources and attention disappeared as other illnesses took priority – yaws and attempts to eradicate it were largely forgotten.

That was until 2012, when a team led by Oriol Mitjà in Papua New Guinea found that a single dose of the antibiotic azithromycin cures yaws within four weeks. The drug is safer and easier to administer than previous treatment – a penicillin injection in the buttocks.

The discovery led the WHO to renew its strategy to wipe out yaws, setting an audacious goal to eradicate the illness by 2020 – though this target is likely to be pushed back to 2030.

“The question is, did these countries [which no longer report cases] get rid of yaws in the 1950s and 1960s, or do they still have cases in isolated, poor populations where we are not looking?” said Dr Michael Marks, assistant professor and yaws expert at the London School of Hygiene and Tropical Medicine.

“Because there's currently no good estimates in much of the world, it's plausible that numbers [of cases] will actually go up as surveillance improves, before they go down,” he added.

But as the world moves closer to reaching eradication accurate and portable diagnostics are needed to confirm cases.

Currently DNA samples are either taken to laboratories and tested using a complicated technique called polymerase chain reaction (PCR), or rapid syphilis tests are used – the disease has an almost identical genetic makeup to yaws.

But to certify the illness as eliminated and paint a better picture of the global prevalence, a portable but accurate DNA test is required.

“This work is extremely important,” said Dr Kingsley Asiedu, from the WHO’s department of control of neglected tropical diseases. “We will need a molecular test that is deployable in the field soon so we can move from reference labs in cities to tests that can be used to absolutely confirm cases in remote areas.”

“We don’t want to wait until the final cases – the yaws endgame – to have these tests in use,” he added. “I would like to see Anthony’s molecular test developed and used as soon as possible.”

The new rapid yaws-specific diagnostic, which tests a swab of saliva, costs $2 per use and has yielded “impressive results” in small trials, said Dr Basing.

He was one of 30 finalists of the WHO Innovation Challenge – which saw more than 2,400 entries – and showcased the rapid test at the Africa Health Forum in Cape Verde earlier this year.

“Going forward we would like to do larger scale testing with a lot more samples,” Dr Basing said.

“But I think that by the year 2020, we can actually start the yaws eradication process with mass drug administration and with diagnosis and treatment at the same time. If we do this, within a few years we can eradicate yaws,” Dr Basing added.

But not everyone is certain the test is the answer.

“We will probably continue to use PCR in labs as we get to the final cases,” said Dr Marks. “I think this [test] is a valuable contribution and will be useful in many settings, but currently is probably not going to replace PCR.”

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New Rapid Test Diagnoses Pneumonia and Other Lower Respiratory Infections

Scientists at UEA and the Quadram Institute have developed a new, rapid way of diagnosing lower respiratory tract infections that could improve patient care and control the spread of antimicrobial resistance.

Lower respiratory infections, such as pneumonia, account for around 3 million deaths worldwide each year, and can be caused by a variety of different microbes.

Current diagnostic methods rely on growing bacteria from patient samples, but this takes two to three days and may still not identify the cause. During this time, patients are given broad spectrum antibiotics, which may not work if the infection is caused by a resistant pathogen and could trigger side-effects. This can also drive the development of antimicrobial resistance.

Dr. Justin O"Grady from UEA's Norwich Medical School and his team at the Quadram Institute have successfully developed a clinical metagenomics test to precisely identify the bacterial causes of lower respiratory infections.

Clinical metagenomics uses modern sequencing technology to study all the genetic material in a patient sample and identify the pathogens present. It can also identify genes that make the pathogens resistant to particular antibiotics.

The new method, developed with colleagues at the Norfolk and Norwich University Hospital and the Earlham Institute, reduces the time to diagnose the precise causes of infection to just six hours.

This allows rapid treatment with targeted antibiotics, resulting in improved patient outcomes whilst reducing the use of broad-spectrum antibiotics and helping in the fight against antimicrobial resistance.

Dr. O"Grady said: "Clinical metagenomics has the promise to revolutionise the diagnosis of infectious diseases, and our study describes the first rapid affordable and accurate clinical metagenomic test that could readily be used on a routine basis in a clinical setting."

The study, published in the journal Nature Biotechnology, overcomes some of the hurdles that have to date held back the widespread deployment of clinical metagenomics.

The method incorporates a step that rapidly and efficiently removes human genetic material from the sample provided by the patient, thereby leaving mainly pathogen DNA for sequencing. Funding for the study came from the Biotechnology and Biological Sciences Research Council, the Medical Research Council and the National Institute for Health Research.

Themoula Charalampous, from UEA's Norwich Medical School, said: "Respiratory samples are difficult to work with because they are mainly comprised of human genetic material. Removing this makes detecting the pathogens easier and reduces the sequencing cost and time."

The researchers worked with Oxford Nanopore Technologies, using their portable MinION sequencing device that facilitated real-time sequencing data generation and analysis. This reduces time-to-result from days to hours.

The pilot method was tested on 40 samples from patients with suspected lower respiratory infections. The team then refined the test to improve its sensitivity and reduce the time from sample to result to six hours and tested on a further 41 respiratory samples.

Dr. Gemma Kay, from UEA's Norwich Medical School, said: "The pipeline that we've developed in this study produces data that can be used not only for clinical diagnostics but for public health applications such as outbreak detection and hospital infection control."

The protocol is now being assessed in a larger multi-site clinical trial to evaluate its performance for the diagnosis of hospital acquired pneumonia.

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Loyola Research Paves Way for Simple Test for Ebola Virus

Existing tests for the deadly virus are inaccurate, expensive and can be challenging to administer, but new research from Loyola University Chicago could lead to a simple filter paper test that changes color if Ebola is present.

The breakthrough is possible thanks to the discovery of two antibodies to the deadly virus and the related Marburg virus by Loyola University Chicago professors Ravi Durvasula and Adinarayana Kunamneni.

Ebola and Marburg viruses can cause severe bleeding and organ failure, with fatality rates reaching as high as 90% in some outbreaks, according to researchers. Major Ebola outbreaks in West Africa from 2013 to 2016 resulted in more than 28,600 cases and 11,325 deaths, according to the U.S. Centers for Disease Control and Prevention. There is no cure or vaccine to treat the diseases.

Both viruses spread through direct contact with bodily fluids of an infected person, monkey, gorilla, chimpanzee or bat. Early symptoms of the diseases mimic that of common diseases, including fever, headache and diarrhea, making the need for a rapid diagnostic test critical, say researchers. Such a test could help curb outbreaks by quickly quarantining infected individuals, but current diagnostic tests are either inaccurate or expensive and require extensive training to administer, according to researchers who say antibodies could be the key to diagnosis.

An antibody is a Y-shaped protein made by the immune system that destroys viruses or pathogens when they invade the body. Using a technology called cell-free ribosome display, researchers generated two synthetic antibodies that bind to all four known types of Ebola and two known types of Marburg viruses, according to a Loyola press release.

Actual viruses were not used in the study, so there was no risk of infection to researchers or the public. Instead, researchers used nonhazardous proteins that sit on the surface of Ebola and Marburg viruses, according to a press release.

Researchers say further study is needed to validate the antibodies’ diagnostic potential. Kunamneni and Durvasula published their findings in the “American Journal of Tropical Medicine & Hygiene,” with co-authors Elizabeth Clarke, Chunyan Ye and Steven Bradfute of the University of New Mexico.

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Cepheid Receives FDA Clearance for Same-Day Extragenital Testing for Chlamydia and Gonorrhea

Cepheid announced today that it has received U.S. Food and Drug Administration (FDA) 510(k) clearance for testing throat and rectal specimens with its Xpert® CT/NG test. The test provides fast and accurate molecular detection of chlamydia and gonorrhea, making same-day consultation and treatment possible.

Xpert CT/NG test is an automated in vitro diagnostic test for qualitative detection and differentiation of DNA from Chlamydia trachomatis and/or Neisseria gonorrhoeae. In addition to the new extragenital specimens, Xpert CT/NG is indicated for use with urine, vaginal, and endocervical specimens from symptomatic and asymptomatic patients.

"Xpert CT/NG is the most sophisticated test in its class, yet it can be performed on-demand by virtually any laboratory to maximize the medical impact of the results. Adding throat and rectal sample types addresses a critical unmet need allowing for more complete patient screening," said David H. Persing, M.D., Ph.D., Cepheid's Chief Medical and Technology Officer. "Considering the increasing rates of chlamydial and gonorrheal infection, this is particularly important for public health screening programs, to capture patients who previously would have gone undiagnosed if only genital specimens were tested. [1, 2] It is not uncommon for patients to have an infection only in their throat or rectum, which may be asymptomatic. Same day consultation and treatment is critical for patient management so patients are not lost to follow up."

Detection of patients with extragenital gonorrheal and chlamydial infections is critical for optimal treatment of disease and can prevent development of antibiotic resistance in strains due to inadequate treatment regimens that do not cover extragenital sites. [3, 4] This is particularly important for men who have sex with men, where disease may be limited to the pharynx or rectum. Such infections will go undetected if only genital sites are tested. [5] Extragenital disease has also been reported in women. [6]

The clinical study used to validate the new claims was led by Drs. Jeffrey Klausner of University of California Los Angeles and Sarah Doernberg of University of California, San Francisco, and coordinated by the Antibacterial Resistance Leadership Group (ARLG), which is funded and supported by the National Institute of Allergy and Infectious Diseases of the National Institutes of Health under Award Number UM1AI104681.*

"Over the last decade, cases of chlamydia and gonorrhea have continued to increase sharply both in the Unites States and abroad necessitating better diagnostics and treatment regimens," said Dr. Jeffrey Klausner, professor of medicine and public health at the University of California, Los Angeles, and lead researcher on the study. "Screening for both genital and extragenital disease with fast turn-around times is critical for optimizing therapy for both male and female populations to reduce the spread of infection."

The Xpert CT/NG test is performed on the Cepheid GeneXpert® Systems. The test's capability to detect DNA from organisms in both genital and extragenital specimens allows for improved screening and detection in patients to ensure infections can be treated in the same day.

About Cepheid

Based in Sunnyvale, Calif., Cepheid is a leading molecular diagnostics company that is dedicated to improving healthcare by developing, manufacturing, and marketing accurate yet easy-to-use molecular systems and tests. By automating highly complex and time-consuming manual procedures, the company's solutions deliver a better way for institutions of any size to perform sophisticated genetic testing for organisms and genetic-based diseases. Through its strong molecular biology capabilities, the company is focusing on those applications where accurate, rapid, and actionable test results are needed most, such as managing infectious diseases and cancer.

*The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.

References

1. CDC. Sexually Transmitted Disease Surveillance 2017. Accessed Mar 2019. https://www.cdc.gov/std/stats17/infographic.htm
2. Patton ME, et al. Extragenital gonorrhea and chlamydia testing and infection among men who have sex with men – STD Surveillance Network, United States, 2010-2012. Clin Infect Dis. 2014 Jun;58(11):1564-70.
3. Deguchi T, Yasuda M, Ito S. 2012. Management of pharyngeal gonorrhea is crucial to prevent the emergence and spread of antibiotic-resistant Neisseria gonorrhoeae. Antimicrob Agents Chemother. 56: 4039-4040.
4. Dukers-Muijrers NHTM, Schachter J, van Liere GAFS, et al. 2015. What is needed to guide testing for anorectal and pharyngeal Chlamydia trachomatis and Neisseria gonorrhoeae in women and men? Evidence and opinion. BMC Infectious Diseases. 15;533:1-13.
5. Tao G, Hoover KW, Nye MB, et. al. 2016. Rectal infection with Neisseria gonorrhoeae and Chlamydia trachomatis in men in the United States. Clin Infect Dis. 63(10):1325-1331.
6. Cosentino LA, Danby CS, Rabe LK, et.al. 2017. Use of nucleic acid amplification testing for diagnosis of extragenital sexually transmitted infections. J Clin Microbiol. 55(9):2801-2807.

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Lumos Diagnostics and RPS Diagnostics Merge to Support International Commercialization of the FebriDx Rapid Pathogen Test

Lumos Diagnostics, a California-based full-service point-of-care (POC) diagnostic development company and previous spinoff from Australia-based Planet Innovation and RPS Diagnostics, a Florida-based commercial diagnostic developer, manufacturer, and marketer of POC diagnostic tests, announced today that they have merged. The combined company will be called Lumos Diagnostics.

Lumos Diagnostics’ initial focus is on the international launch of the FebriDx® test, a rapid, in-office POC test that incorporates a built-in safety lancet to obtain a fingerstick blood sample, rotating blood collection and transfer system, and integrated push-button buffer activation, to provide clinicians with a rapid assessment of the body’s immune response to an acute respiratory infection (ARI). The single use test identifies patients within 10 minutes that have a clinically significant underlying infection and aids in the differentiation of viral and bacterial ARIs through the simultaneous detection of both Myxovirus resistance protein A (MxA) and C-reactive protein (CRP) directly from peripheral whole blood. MxA is an intracellular protein that becomes elevated in the presence of acute viral infection and CRP is an acute-phase inflammatory protein that is elevated in the presence of clinically significant infection.

Sam Lanyon, chairman of the board for Lumos Diagnostics states, “We have evaluated many technologies over the years, and believe that combining RPS Diagnostics’ novel biomarker technology and commercial experience together with Lumos Diagnostics’ reader-based platform results in a highly strategic and synergistic union that will support a robust pipeline and commercial success.”

ARI are often highly contagious and result in more than half of all antibiotics that are prescribed for outpatient primary and urgent care visits. ARIs may be associated with nonspecific flu-like symptoms, including fever, sore throat, cough, nasal congestion, and fatigue. Bacterial infections pose the highest risk of morbidity and are the only infections that benefit from antibiotic treatment. Diagnostic uncertainty from overlapping ARI symptoms and signs combined with patient or parent pressures for antibiotic prescriptions lead to more than 50% of all unnecessary antibiotic prescriptions. Rapid single pathogen tests, such as for Strep A and Influenza, cannot differentiate colonization from true infection and are indicated for only specific respiratory conditions, accounting for about 15% and 25% of patient visits, respectively; whereas the majority of the patients have other viral infections, bacterial infections, or a microbiologically unconfirmed respiratory illness.

Clinical performance from two prospective multi-center U.S. clinical trials demonstrate the FebriDx test’s high accuracy and 97-99% negative predictive value to exclude a bacterial infection. Moreover, in a small United Kingdom outcome study, FebriDx was shown to alter clinical management decisions in 48% of patients tested and reduced unnecessary antibiotic prescriptions by 80%. By enabling a rapid diagnosis at the initial office visit, the FebriDx test may help to limit the amount of unnecessary antibiotic prescriptions that can lead to avoidable adverse reactions and antibiotic resistance, resulting in lower costs.

Robert Sambursky, MD, the president and chief executive officer of RPS Diagnostics, who will continue in the same role for the joint Lumos Diagnostics entity states, “Using FebriDx to help triage outpatient ARI is a game changer because successful antibiotic stewardship requires the clinician to first rule out a clinically significant bacterial infection. In addition, access to novel Lumos Diagnostics reader technology will facilitate next generation digital enhancements which will accelerate speed to results, allow for quantitation, and enhance objectivity of our branded product lines.”

About Lumos Diagnostics

Lumos Diagnostics provides rapid, cost effective, and complete point-of-care (POC) diagnostic test solutions that utilize proprietary digital reader platforms to help healthcare professionals more accurately diagnose and manage diseases and medical conditions. Lumos provides assay development and manufacturing services for customized POC tests as well as directly develops, manufactures, and will commercialize a suite of Lumos-branded POC tests. Conditions targeted by Lumos tests include infectious and inflammatory diseases with unmet diagnostic needs, including fever, biological threats, and infectious disease, resulting in less unnecessary treatments with associated adverse events, reduced spread of disease, and more effective antibiotic stewardship initiatives.

The FebriDx test has received Health Canada approval, Saudi FDA clearance, Singapore Health Sciences Authority registration, and is CE marked for sale in Europe. At this time, the FebriDx test has not received U.S. Food and Drug Administration (FDA) clearance and is not commercially available in the United States.

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PATH, Quansys Bio Develop New Diagnostic Tool for Malaria

PATH and Quansys Biosciences, Inc. have announced the launch of a new diagnostic tool designed to help researchers develop more sensitive and reliable malaria rapid diagnostic tests (RDTs) and to support public health surveillance. The Q-Plex™ Human Malaria Array (5-Plex) is a quantitative immunoassay that simultaneously measures multiple malaria antigens.

With almost half of the world’s population at risk for malaria and more than 200 million cases annually, the disease is a public health priority. Accurate diagnostics are critical to both disease management and public health surveillance. RDTs are a critical tool in malaria case management, particularly in remote settings, providing access to prompt diagnosis.

Many current RDTs function by detecting the histidine rich protein 2 (HRP2) to identify P. falciparum malaria and the Plasmodium lactate dehydrogenase (pLDH) antigen to diagnose P. vivax malaria and all other human malaria species. As RDTs improve in quality, there is a need to understand how these antigens behave in a malaria exposed population so that the performance of these RDTs and their potential to support malaria elimination can be fully assessed.

With a single sample, the Q-Plex™ Human Malaria Array can measure HRP2 and pLDH at low concentrations, as well as quantify P. vivax- and P. falciparum-specific LDH epitopes to distinguish between malaria species and C-reactive protein (CRP) as an indicator of inflammation.

Researchers can use the Q-Plex™ Human Malaria Array (5-Plex) as a reference test to evaluate RDTs in the development pipeline that detect malaria infections with low parasite concentrations and address the challenge of diagnosing P. falciparum malaria parasite strains that do not produce HRP2 and therefore are not detected by RDTs designed to identify the antigen.

“Quansys is excited to continue our partnership with PATH in bringing the power of multiplexing to such important world health issues,” said Chris Lyman, Director of R&D at Quansys Biosciences, “It aligns perfectly with Quansys’ goal to cure the world of communicable diseases by supporting front-line researchers with the most powerful and efficient tools possible.”

“It is important to equip researchers and the public health community with tools like the new Q-Plex™ Human Malaria Array, which has high sensitivity, requires a single sample, and may support higher throughput,” said Tala de Los Santos, PATH’s Global Program Leader, Diagnostics. “These features will assist with the development of improved diagnostics and support use for epidemiologic surveillance.”

The Q-Plex™ Human Malaria Array (5-Plex) is available and can be ordered directly from Quansys Biosciences.

This project is supported by a grant from the Bill & Melinda Gates Foundation.

About PATH

PATH is a global organization that works to accelerate health equity by bringing together public institutions, businesses, social enterprises, and investors to solve the world’s most pressing health challenges. With expertise in science, health, economics, technology, advocacy, and dozens of other specialties, PATH develops and scales solutions—including vaccines, drugs, devices, diagnostics, and innovative approaches to strengthening health systems worldwide.

About Quansys Biosciences, Inc.

At Quansys Biosciences, our teams build and develop customizable multiplex and singleplex protein assay technologies that allow pharmaceutical companies, clinical laboratories, government institutions, universities, and researchers around the world access to large amounts of quantitative data quickly and efficiently. Q-Plex Array Technology has been aiding researchers to better understand disease and improve their biological sample testing since 2005.

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Thermo Scientific SureTect Real-Time PCR Pathogen Detection System Extended Validation for Food Pathogens

Thermo Scientific SureTect PCR Assays are now validated to run on the Applied Biosystems SimpliAmp Thermal Cycler and Applied Biosystems QuantStudio 5 Food Safety System, which means a streamlined workflow that requires fewer touchpoints. Laboratories can now work more efficiently and release products quickly and confidently when helping to safeguard the world's food. AOAC PTM and NF VALIDATION certification covers SureTect Assay workflows for the detection of Salmonella species, Listeria species, Listeria monocytogenes, Escherichia coli O157:H7 and Cronobacter species (NF VALIDATION certification only) in a variety of foods and production environment samples.

Heating steps for the SureTect Assay sample preparation process are now fully automated using the SimpliAmp Thermal Cycler, taking just 25 minutes to prepare sample lysates ready for PCR. The SimpliAmp touchscreen interface makes it easy to set up and save the parameters required for SureTect Assays and other applications. When needed, the required program can be recalled and ready to use in seconds.

The Applied Biosystems QuantStudio 5 Food Safety Instrument is a high-performance benchtop platform that gives users greater control of data and combines out-of-the box installation, ease-of-use and system connectivity with powerful options to enable maximum control. The 6-channel, 96-well, cloud-enabled open platform is suitable for running the full range of PCR solutions for food safety, authenticity and quality testing. Combining the QuantStudio 5 Food Safety Instrument with user-friendly Thermo Scientific RapidFinder Analysis software makes SureTect test set-up, running and automatic result interpretation simple and helps avoid errors and subjective result determination.

"This year we are not only extending the validation scope with simplified workflows and access to powerful new instruments, but also expanding the range of SureTect Assays with new kits for additional foodborne pathogen targets important to our customers," said Bernd Hofmann, vice president, marketing, Thermo Fisher Scientific. "We continue to invest in our mission to enable our customers to make the world safer by simplifying food pathogen testing to deliver speed, accuracy and reliability of results. We expect the new SureTect Assays to launch in the second half of the year."

Validation studies to certify the SureTect Assays with the new instrumentation will match the current scope of AOAC-RI and NF VALIDATION certified workflows with the Applied Biosystems 7500 Fast Food Safety System covering an extensive range of food and production environment sample types. In addition, a 375 g milk powders and ingredients category will be added to the SureTect Salmonella species Assay range of NF VALIDATION claims as well as adding the fruits and vegetables category to the SureTect E coli O157:H7 Assay claims.

The new SureTect Assay workflows will follow the same parameters of those already available, including:

• Single enrichment protocols for faster time-to-result and streamlined workflow
• Pre-dispensed reagents, reducing handling steps and risk of operational error
• Universal PCR protocols for detecting multiple targets in the same run
• User-friendly RapidFinder Analysis software for simple set-up and avoidance of subjective interpretation

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