By Emily Hayes, LabPulse.com editor in chief
FROM Kalorama’s partner publication Lab Pulse.com 

Testing for the tau protein in blood could help predict the outlook for the rare and deadly Creutzfeldt-Jakob disease (CJD), a discovery that also has implications for research in Alzheimer’s disease and other neurodegenerative disorders, researchers reported in JAMA Neurology on May 6.

Tau is a protein associated with neuronal damage, and previous research has found elevated tau levels in patients with CJD. But tau levels are typically obtained through cerebrospinal fluid (CSF), acquired via lumbar puncture — an invasive procedure. What if tau could be measured through blood samples instead?

Blood testing of total tau (t-tau) was found to be a unique predictor of survival in patients with sporadic CJD (sCJD), and it is more convenient than other methods for estimating a patient’s prognosis, reported a team led by Adam Staffaroni, PhD, a neuropsychologist at the University of California, San Francisco (UCSF) Memory and Aging Center.

“These findings further bolster the value of blood-based biomarkers based on their minimally invasive and relatively inexpensive nature and build on prior studies that suggested patients with sCJD and controls can be discriminated with relatively high accuracy using blood-based assays,” the group wrote.

The results promise to improve clinical care and help ensure that clinical trials in neurodegenerative diseases are adequately powered, according to the researchers. However, the findings still need to be validated in larger studies before they can be put into practice.

Getting a handle on a grim diagnosis

CJD belongs to a family of human and animal prion (abnormal forms of cellular proteins) diseases. Like Alzheimer’s and Huntington’s disease, it causes psychiatric symptoms and decline, but it does so much more quickly.

According to the U.S. National Institutes of Health (NIH), only 350 cases of CJD are reported annually; on average, CJD occurs at about age 60, and individuals with the disease rarely live past a year. The sporadic type of CJD is the most common, accounting for 85% of cases. CJD is typically diagnosed through electroencephalography, CSF diagnostics, and MRI, with confirmation in autopsy after death.

Baseline total tau on CSF tests and a polymorphism at the codon 129 genotype are currently used to help predict how long patients will live, but there has been interest and some research published about the potential for blood testing as a noninvasive biomarker for CJD and other neurological disorders, Staffaroni and colleagues noted.

In the current study, the researchers sought to determine the utility of plasma and CSF biomarkers compared with other characteristics of CJD by evaluating patients referred to the UCSF Memory and Aging Center with probable or pathology-proven disease between 2004 and 2018. On average, CJD patients live for four months, but lifespan is highly variable, with some surviving for weeks and others for years, the authors noted.

“Accurate prediction of disease duration has implications for clinical management, helping patients and families prepare for the disease course,” they wrote. “Accurate prediction of survival time also affects clinical trial design, as stratifying patients based on expected disease course can improve a trial’s power, thereby reducing costs and ultimately maximizing the number of trials that can be funded. This is especially germane in sCJD, given the rarity of the disease and variable survival time.”

In addition to blood and CSF tests, the researchers assessed five other factors associated with survival:

  • Sex
  • Age
  • Genotyping of the prion protein gene at codon 129
  • The Barthel index, a measure of ability to carry out daily life activities
  • The Medical Research Council (MRC) prion disease rating scale, which assesses cognitive function as well as life activities

Of these five factors, three — codon 129 genotyping and scores on the Barthel index and the Medical Research Council scale — significantly correlated with the length of survival, with lower levels of function predicting a faster disease course, Staffaroni and colleagues reported.

The plasma total tau level and the Barthel index each had independent value for predicting length of life, a statistically significant finding, they wrote. And as with plasma biomarkers, the CSF t-tau level remained associated with survival after controlling for the Barthel index and codon 129 genotype, the researchers noted.

“The correlation between CSF and plasma t-tau level, together with the concordance of CSF and plasma t-tau level in predicting survival time, further strengthens our finding that plasma tau level may be a useful biomarker in this cohort,” they wrote.

Building the evidence base for plasma tau

The UCSF investigators wrote that the data are in line with prior research, in that plasma t-tau correlated with the rate of disease progression, matching a study of 45 patients by Thompson et al (Journal of Neurology, Neurosurgery & Psychiatry, September 2018, Vol. 89:9, pp. 955-961). Plasma t-tau did not correlate with survival in that study, they noted, but Thompson and colleagues had not controlled for baseline functional severity.

In the UCSF study, the plasma t-tau level did correlate with survival regardless of functional severity at baseline. Furthermore, the researchers found that the level of plasma neurofilament light (NfL), the level of CSF t-tau, the ratio of t-tau to phosphorylated tau, and the level of neuron-specific enolase (NSE) were also significantly associated with the length of survival, but less so than plasma t-tau.

“Importantly, when baseline functional status and plasma t-tau levels were modeled together, both were strong, independent predictors of survival time,” the group wrote. “This suggests that clinical measures and plasma t-tau level could be combined to further improve prediction accuracy.”

What this means for Alzheimer’s

The results still need to be validated in a larger cohort, and assays are currently only available for research use, though commercial tests are in development. Elevated plasma t-tau is found in patients with many other conditions, including the neurodegenerative diseases Alzheimer’s and frontotemporal dementia, as well as acute brain injuries. However, its value as a biomarker has been questioned in other diseases like Alzheimer’s partly because the plasma t-tau levels did not match the CSF t-tau levels, Staffaroni and colleagues wrote.

“One explanation for the high correlation between CSF and plasma tau level in sCJD is that the rapidity and amount of neurodegeneration may result in continuous, high quantities of tau in the periphery that overcome the peripheral mechanisms of elimination,” the researchers wrote. “Others have argued that higher plasma t-tau concentrations in sCJD may be driven by preterminal cases having higher t-tau levels.”

CJD is an excellent model for treatments targeting the prion-like pathogenesis of neurodegeneration, Staffaroni et al wrote, adding that “rapid decline in prion disease may allow clinical trials to detect a drug effect more quickly than trials enrolling patients with slowly progressing conditions.”

“This study adds to research in other dementia disorders, such as Alzheimer disease, suggesting that blood-based assays may revolutionize the way that neurodegenerative diseases are diagnosed and monitored,” they wrote.

As with Alzheimer’s, the field needs to standardize methods for testing, optimize cutoff points, and replicate the research before moving these biomarkers into the clinic or using them in clinical trials, the authors advised.

 

Introducing accurate test results to the place where patient care is occurring is a compelling concept for improved care.  And that is reflected in the growing year-over-year revenues for products that are successful at getting that done.  POC has not converted in every category, and it’s not for everything.  Indeed, lab-based tests remain stalwart in clinical diagnosis in major market hospitals, where they offer superior sensitivity and specificity and volume advantages.

Yet it the POC market grows larger every year, and 2018 was no exception.  This according to Kalorama Information’s latest point of care market study: https://kaloramainformation.com/product/worldwide-market-for-point-of-care-testing/

There are cost concerns, there are adoption challenges.  And there are technology limitations.  But Kalorama finds each year these boundaries are pushed.  POC markets grow faster than non-POC markets, and faster than the average of the in vitro diagnostics industry.    In 2018, sales of POC testing reached $22.3 billion, increasing 7.5% from $20.7 billion in 2017. That’s fast, more than twice as fast as the whole market grew.  New technologies and increased demand contributed to growth in the markets. A contributing factor to slower growth in some segments was pricing strategies that continued to discount the cost of POC diagnostic testing in some segments and higher cost in other segments of testing.  In 2023, the total global POC diagnostic testing market is expected to reach $30 billion, displaying growth of 6.1% over the forecast period 2018-2023.

“In 2018, sales of POC testing reached $22.3 billion, increasing 7.5% from $20.7 billion in 2017.  That’s fast, more than twice as fast as the whole market grew.  “

Diagnostic tests performed outside the central laboratory or decentralized testing is generally known as point-of-care (POC). Over the years, the increasing introduction of transportable, portable, and handheld instruments has resulted in the migration of POC testing from the hospital environment to a range of medical environments including the workplace, home, disaster care and most recently, convenience clinics.

The menu for POC continues to expand.  In the past 5-10 years, POC products were developed in the following categories: HbA1c, B-Type Natriuretic Peptide (BNP), whole-blood lactate, D-Dimer, C-Reactive Protein (CRP).

Moreover, POC test devices have contributed significantly to the growth of the overall diagnostics market over the past 10 years. More diagnostic manufacturers have pursued CLIA waiver status for their POC devices and CE Mark for POC or self-use.  At the same time more, decentralized test venues invest in non-waived rapid tests and instruments.  POC testing appe

ars to be headed for an even bigger role in diagnosis and monitoring patient care.  New technologies are allowing POC devices to produce quantitative lab-quality test results that can be transferred automatically to an information system, a remote caregiver service for consultation or an electronic medical record.

Molecular POC tests in physician office are already available for respiratory infections and more.  The capacity to provide precise answers for time sensitive tests such as sexually transmissible diseases and other infections will drive the market for POC molecular test devices.  Ease of use is a plus for hospital labs.  Worldwide, lab budgets are being cut for test send-outs and there are not enough trained technologists to run molecular tests in their present configuration.

Diagnostics are generally a market of focus – the new pharma model tailors therapy to the individual’s particular disease physiology often determined by the results of a diagnostic test.  So, more tests – molecular and immunoassays – will come to market, some will have a high price tag and some not.  Price will not be the deciding factor.  Test adoption in this scenario is based on performance data, contribution to patient outcome and cost/benefit analysis.

A major factor in achieving this goal of more precise and personalized therapeutic options is the use of advanced algorithm driven information technologies that can turn test data into actionable medical decision-making information.  This trend is driven by the involvement of major information technology companies and payers that are tired of paying for drugs that often have limited positive patient outcome.

Information about diseases, therapies and tests is readily available via the Internet and a growing number of apps on personal digital assistants (PDAs) including all sorts of smart phones.  Wearable devices participate in this area by collecting vital sign data that are then analyzed by IT tools to provide health care improvement instructions.

Kalorama Information’s report can be found at: https://kaloramainformation.com/product/worldwide-market-for-point-of-care-testing/

 

 

[by Christina Chew]  It is increasingly common to test in panels to gain clarity on disease while treatment will be most effective.  Numerous multiplex products are on the market, and their effectiveness has been shown in studies, but there are challenges with reimbursement.   In this article, we will look at the current status of syndromic testing.   Syndromic and other microbiology diagnostic markets are covered in our report The Worldwide Microbiology Market (Traditional Microbiology, Microbiology/Infectious Disease Immunoassays, Molecular Microbiology, Mass Spectrometry in Microbiology)

“With these FDA clearances and new tests being introduced over the last decade, companies are placing bets on syndromic testing taking off. Siemens Healthineers, for example, is betting that syndromic testing will boost its diagnostics franchise by acquiring Luxembourg-based Fast Track Diagnostics in 2018.”

Since the discovery of duplex DNA in 1953 by Watson and Crick, the diagnostics area has witnessed tremendous growth in the field of molecular diagnostics, particularly in areas such as improved sensitivity, versatility of technology and automation. In the past decade, molecular diagnostics has resulted in a paradigm shift in clinical practice by enabling rapid detection of pathogens in blood cultures, respiratory specimens, stool, etc. During this time, we have also witnessed the launch of a single molecular test, such as the Abbott ID NOW (formerly Alere i) to a multiplex molecular panels with more than five targets, such as the FilmArray Blood Culture Identification (BCID) panel by BioFire Diagnostics, LLC (a Biomerieux company). This revolutionary multiplex tests enable rapid diagnosis of certain infections thus allowing healthcare providers make clinical management decisions in a timely manner.

The word syndromic comes from the root syndrome meaning a set of medical signs and symptoms that are correlated with each other or with a specific health-related cause. Often, patients can present with symptoms that are non-specific, but a combination of them can suggest certain diagnoses.

There have been a number of multiplex respiratory panels that can detect 5 or more pathogens simultaneously that have been FDA cleared. Upper respiratory infection is very common and afflicts millions of people in the US each year. It is the most cited reason for doctors’ visits. The first multiplex panel to receive FDA clearance was the Luminex xTAG RVP v1, which received clearance in 2008. This was followed by the Luminex xTAG-RVP Fast clearance three years later. They test 12 and 8 targets, respectively, with turnaround time of 8 and 6 hours. The NxTAG RPP (Luminex), which was cleared in 2015 can detect 20 pathogens at once with a turnaround time of 4 hours. GenMark Diagnostics’ eSensor RVP assay is performed on the XT-8 system and targets 14 pathogens with a turnaround time of 8 hours. Of all the commercialized respiratory multiplex tests, BioFire’s FilmArray respiratory panel (FA-RP) provides results in an hour, the fastest among its competitors.

Another growing infectious disease multiplex molecular test is in the gastrointestinal (GI) area. Conventional test methods for GI pathogens, such as culture, antigen tests and microscopic exams are not only time consuming but also costly and have limited sensitivity. According to the World Gastroenterology Organization, there are 2 billion new cases annually, resulting in 1.9 billion deaths among children under 5 years old. And according to the Centers for Disease Control and Prevention (CDC), GI illnesses account for 76 million emergency department (ED) visits and hospitalizations in the US each year. The severity of foodborne illnesses makes the case for faster and more sensitive molecular tests.

There are three FDA cleared multiplex assays that can detest more than 5 stool pathogens – xTAG GI pathogen panel and Verigene Enteric Pathogens by Luminex and BioFire FilmArray GI panel from BioFire. A study conducted at the University of Texas Medical Branch found that the BioFire FilmArray GI panel improved patient care due to its ability to identify a broad range of pathogens in an hour, allowing for proper treatment while reducing the need for further diagnostic tests and hospitalization. The authors also found that overall health care cost could have been reduced by almost $300 per patient if the FilmArray GI panel was used. This study definitely makes a compelling case for the need of GI multiplex syndromic tests.

With these FDA clearances and new tests being introduced over the last decade, companies are placing bets on syndromic testing taking off. Siemens Healthineers, for example, is betting that syndromic testing will boost its diagnostics franchise by acquiring Luxembourg-based Fast Track Diagnostics in 2018. Siemens Healthineers currently does not have commercialized molecular tests for infectious diseases. Fast Track Diagnostics (FTD) offers a wide range of tests, such as respiratory, GI, STI, and touts its capability to distinguish between viral or bacterial infection in one test. So far, FTD has not received FDA clearances for its tests yet.

However, reimbursement remains a challenging topic with syndromic multiplex testing. Multiplex assays are assigned various billing codes related to the number of targets in the tests. However, in late 2018, Palmetto deemed the multiplex viral panels do not meet Medicare’s “reasonable and necessary” criteria. Palmetto also stated that there is a lack of clinical utility when it comes to rapid and sensitive nucleic acid testing in decreasing the use of antibiotics. Finally, the Medicare contractor determined that syndromic surveillance isn’t part of Medicare benefits. This is a set back for syndromic testing. It may take years of clinical studies to prove the clinical utility and ROI of syndromic tests to gain a reversal of this decision.

Syndromic multiplex testing is relatively new to the market and is performed in a clinical microbiology setting. It is anticipated that it will become increasingly common over time and can be used in point-of-care settings. Given that reimbursement is a challenge, it may not be adopted as readily as many had hoped. The long turnaround time, lack of flexibility in some panels and cost considerations may delay POC adoption. Kalorama’s prediction of growth in the molecular POC space hasn’t materialized. Until the reimbursement challenges is resolved, growth in syndromic molecular multiplex testing could be slowed.
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Christina Chew

Special Projects Analyst, Kalorama Information

The CDC reports a late peak and possible second wave to what was previously thought to be a weaker flu season compared to recent years. This is important for IVD makers, as respiratory IVD markets are driven to a great extent by the severity of the flu season. While the total number of cases remains below 30M, and thus less than last year, recent weeks saw a small peak and there’s a new strain that is demonstrating virulence.

The CDC reports a late peak and possible second wave to what was previously thought to be a weaker flu season compared to recent years. This is important for IVD makers, as respiratory IVD markets are driven to a great extent by the severity of the flu season. The chart  accompanying depicts the flu cases in thousands for the weeks of 2019.  instead of fully declining, there was a late peak in February. While the total number of cases remains below 30M, and thus less than last year, recent weeks saw a small peak and there’s a new strain that is demonstrating virulence.

Per the CDC:  Since October 1, there have been nearly 26.3 million cases of the flu, as many as 12.4 million flu-related medical visits, and up to 31,200 deaths caused by the flu. Nine children died from the flu last week, bringing the total of pediatric deaths this season to 64. There are two main groups of influenza viruses: influenza A and influenza B.

Respiratory systems such as those that detect flu are a key component of the true molecular point of care market, representing decentralized rapid or CLIA waived systesm. And revenues for respiratory represents nearly sixty percent of this market according to the Market and Potential for Molecular Point of Care Diagnostic Tests 2019
https://kaloramainformation.com/product/the-market-and-potential-for-molecular-point-of-care-diagnostic-tests-2019/

According to that report, the flu season’s severity in 2017/18 created an opportunity for new systems.  This year, a new strain is concerning.  The H3N2 strain belongs to the influenza A family. In addition to the typical symptoms of flu, which include fevers, chills, body aches, and rigors [shaking chills], it additionally has the potential of causing several severe complications, including very high fevers.

CDC estimates that the burden of illness during the 2017–2018 season was also high with an estimated 48.8 million people getting sick with influenza, 22.7 million people going to a health care provider, 959,000 hospitalizations, and 79,400 deaths from influenza (Table 1). The number of cases of influenza-associated illness that occurred last season was the highest since the 2009 H1N1 pandemic, when an estimated 60 million people were sick with influenza6.

While this flu season has not been quite as severe as seasons past, there has been a recent uptick in a less common flu strain, the H3N2 virus, now accounting for over 50 percent of new cases, according to recent data from the CDC. There have been 350,000 hospitalizations according to the agency.

Since near patient-testing systems using PCR technology first appeared on the market, the leading IVD market research publisher Kalorama Information has provided sound market estimates and forecasts for their usage. As these systems move from novel to closer to a routine usage, our 2019 update provides essential information for marketers in IVD.

Kalorama’s report is a true look at the clinical market for molecular systems, both CLIA-waived and those CLIA-moderate that can be used in an office visit. The report incorporates systems in development as of 2019 and updates on competitor laggards in previous editions that have not produced products.

Companies in the molecular point-of-care market include: Abbott, Roche, Biomerieux BioFire and Danaher’s Cepheid, among others.

Detection of infectious disease promptly and accurately is important because the burden of infectious disease is high.  In the United States, chronic lower respiratory diseases were the third leading cause of death in 2015, behind only heart disease and cancer.  The Center for Disease Control and Prevention (CDC) reports that 155,041 people died in the United States in 2015 due to chronic lower respiratory diseases.

Infectious diseases are all the more troubling because they may harm long after the disease is treated.  These secondary effects – cancer, heart disease – increase the stakes and suggest the need for testing. 

Clinical microbiology laboratories perform tests to detect, isolate, identify and characterize microorganisms that cause infectious diseases, and also perform antibiotic susceptibility tests.   Traditional microbiology, including culture, microscopy, use of stains plus fluorogenic and chromogenic substrates, and other technologies has b used for several decades in microbiology laboratories.  Microbiology tests may be performed using traditional microbiology techniques, or by using newer technologies including immunoassays, molecular microbiology (PCR or other nucleic acid amplification methods), or mass spectrometry.

The following represent recent developments in microbiology that are innovative.  For each, we’ve detailed the company, the area the development is in (disease being treated or general procedure such as blood culture), the location of the company so that interested readers can pursue them, and the detail on the innovation and the status (FDA or CE cleared, market = marketed for some time, service, RUO or other).

This table represents some recent innovations in infectious disease diagnostics.  For more analysis please see our Infectious Disease World Market Analysis report.

Company Location Area Details Stats
Abbott Abbott Park, IL flu a/b, strep A ID NOW CLIA Waived POC FDA
Abbott Diagnostics U.S. various Iridica molecular-testing platform CE
Abbott Diagnostics U.S. HIV ARCHITECT HIV Ag/Ab Combo assay FDA
Accelerate Diagnostics U.S. blood culture CRE in blood culture dev
Accelerate Diagnostics U.S. blood culture BacAccelerate ID/AST Blood Culture Assay CE
Advanced Biological Lab Luxembourg HCV Anti-E1/E2-based ELISA for HCV management dev
AdvanDx U.S. blood culture Candida QuickFISH CE
AdvanDx U.S. blood culture gram-positive/negative QuickFISH CE
AdvanDx U.S. HAIs mecA XpressFISH, MRSA FDA
Alere U.S. HAIs BinaxNOW PBP2a test CE, FDA
Alifax Italy blood culture Automated blood culture FDA,CE
Aperiomics U.S. microbiome Absolute-Biome, microbiome sequencing RUO
Aseptika Limited UK resp inf bacterial protein in sputum, CF, asthma, COPD CE
Atomo Diagnostics Australia panel AtomoRapid dengue and chikungunya dev
Beckman Coulter Brea, CA Sepsis Early Sepsis Indicator DxH900 Hematology System CE
Biocartis Switzerland ebola Ebola test with Janssen Diagnostics on Idylla dev
Biohit OYJ Finland microbiome Genetic Analysis AS’s Dysbiosis microbiome for IBD CE
BioInnovation Solutions Switzerland filoviruses, such as Ebola and Marburg dev
bioMereiux France various AE-180 /AE-240 mid throughput immunoassay system FDA
bioMereiux France pneumonia 18 bacteria/8virus/7gene panel
bioMérieux France mass spec assays for Knome sequencing platform dev
bioMérieux France ID/AST VITEK MS, ID/AST on Shimadzu mass spec CE, FDA
bioMérieux France ID/AST BacT/ALERT Virtuo, 15 min result mkt
Bioneer Corp Korea Ebola AccuPower EBOV real-time RT-PCR RUO
Bioneer Corp Korea Zika AccuPower ZIKV Multiplex Zika, dengue, CHIKV CE
Bioneer Corp. Korea Ebola AccuPower EBOV real-time RT-PCR Nigeria
Bio-Rad Hercules, CA malaria multiplex MAG PIX FDA
Bruker Biosciences U.S. blood culture MALDI Sepsityper Solution, positive blood culture CE
Bruker Biosciences U.S. blood culture integrate MALDI Biotyper with BD Phoenix dev
Cajetmo Heredin University Lima, Peru chagas qPCR on clot samples low blood leads dev
Canon BioMedical U.S. Lyme with T2 Biosystems, Lyme Disease, PCR dev
Cepheid U.S. TB Xpert MTB/RIF, TB & rifampin-resistance FDA
Cepheid U.S. TB Xpert XDR-TB, extensive drug resistance, PCR dev
Cepheid U.S. ebola Xpert Ebola, PCR EUA
Cepheid U.S. MRSA Xpert MRSA/SA Blood Culture (BC) FDA
Cepheid/Danaher HIV Gene Expert HIV-1 Qual FDA
Ceres Nanosciences U.S. lyme Nanotrap Lyme Antigen (LA) Test srvc
Chembio Diagnostics U.S. ebola DPP Ebola with Integrated BioTherapeutics dev
Chembio Diagnostics U.S. zika zika added to DPP Fever Panel assay dev
Chembio Diagnostics U.S. malaria DPP Malaria dev
ChromaCode Carlsbad, CA tick-borne 12 spiecies tick panel service
Co-Diagnostics HBDC U.S. TB LogixSma-RT TB Kit mkt
Coris BioConcept Belgium chagas T. cruzi satDNA OligoC-TesT, PCR mkt
CTK Biotech U.S. CHICKV OnSite Chikungunya IgM Combo Rapid Test CE
Curetis AG Germany response Acumen’s AcuSept panel, sepsis immune response dev
DiaSorin Italy campy LIAISON Campylobacter stool test mkt
DiaSorin Italy GI Liaison bacterial stool-testing panel CE
Diaxonhit France avidity portfolio active vs older infections mkt
Diaxonhit France sepsis BJI InoPlex test staph antibodies in blood CE
DiscoGnosis Project EU panel LabDisk 12 pathogens- malaria, dengue, CHICKV dev
DNA Genotek/OraSure Canada microbiome OMNIgene•GUT microbiome collection kit, stool self collect CE, RUO
DPZ Diagnostics Germany ebola Diagnostics-in-a-Suitcase dev
DxNA U.S. Valley Fever Valley Fever (coccidioidomycosis) dev
Dynamiker Biotechnology China fungi ELISA invasive fungal disease CE
EKF Diagnostics UK sepsis Stanbio LiquiColor Procalcitonin, automated analyzers CE
EliTech Group South Logan, UT HSV 2 multiplex six channel test
Enigma Diagnostics UK TB MDR-TB on Enigma Mini Laboratory dev
Epistem Holdings UK TB Genedrive TB and resistance CE
Fast-Track Diagnostics Luxembourg Ebola FTD Ebola assay CE
Fio Corporation Canada ebola Corgenix ReEBOV Ebola antigen on Deki Reader EUA; FDA
Fio Corporation Canada lassa Corgenix ReLASV Lassa virus antigen on Deki Reader CE
Fio Corporation Canada micro Deki Reader Malaria & Dengue, LF CE
GBDbio U.S. TB TB REaD POC test, fluorescent beta lactamase enzyme dev
Genalyte Inc. U.S. ebola Ebola antigens and IgM/IgG antibodies dev
Genalyte Inc. U.S. ebola Ebola antigens and IgM/IgG antibodies dev
GenArraytion U.S. zika MultiFlex Mosquito-borne Panel, zika etc RUO
GeneDrive Manchester, UK Hepatitis C Genedrive POC HCV ID Kit CE
GeneDrive Manchester, UK
GeneDrive Manchester, UK hep C 100% specificity test CE
Genetic Analysis Norway microbiome Dysbiosis test microbiome imbalance in irritated bowel syndrome CE
Global BioDiagnostics UK TB TB, Reporter Enzyme Fluorescence dev
Globavir Biosciences U.S. dengue PanGlob RT-PCR Dengue market
Gold Standard Diagnostics U.S. syphilis AIX1000 Rapid Plasma Reagin (RPR) Automated FDA
Great Basin Scientific U.S. PCR Staph ID/R Blood Culture Panel FDA
Hain Lifescience Germany TB GenoType MTBDRsl, colonies & sputum CE
ICDPR Dhaka, Bangledesh cholera Cholkit Dipstick Assay market
Inflamatix Burlingame, CA Sepsis multigene sepsis panel dev
Institute for Preventitive Research Gottigen, Germany treporema Pallidum LAMP technology dev
Jena University Jena Germany MIC MIC determinaion in two hours with LOC tech. dev
LabCorp U.S. Zika Altona’s RealStar Zika Virus RT-PCR Kit srvc
Luminex Austin, TX flu a/b Aries FDA
Luminex Austin, TX GI Verigene II GI assay dev
Luminex U.S. panel GenArraytion MultiFlex Mosquito-borne Panel- Zika, CHICKV, Dengue dev
Lumora UK malaria malaria test, LAMP, with FIND and Eiken mkt
Magnolia Medical San Mateo, CA blood culture U South Car. Study shows 4 fold decrease in contaminiation study
Mass. Institute of Technology U.S. panel Matrix Multiplexed Diagnostic – ebola, dengue, yellow fever dev
Mayo Medical Lab U.S. microbiome microbiome diagnostics on Whole Biome’s Complete Biome Test service
MBio Diagnostics U.S. malaria LightDeck Malaria cartridge dev
MBio Diagnostics U.S. malaria LightDeck Malaria cartridge dev
MBio Diagnostics U.S. instr LightDeck, multiplexed immunoassay platform, cartridge dev
Medical Innovation Ventures Malaysia dengue ProDetect Dengue tests CE
MeMed Diagnostics Israel response ImmunoXpert pathogen immune response proteins CE
Meridian Bioscience Cincinatti, OH CMV Althethia CMV Test FDA
Meridian Biosciences U.S. TB illumigene Mycoplasma Direct assay, improved CE, FDA
Meridian Biosciences U.S. dengue TruQuik CE
Meridian Biosciences U.S. malaria illumigene Malaria CE
Milford Molecular Diagnostics U.S. ebola Ebola RT-PCR srvc
MIT Cambridge, MA gene editing SHERLOCK Diagnostic Platform cas13 dev
Nanologix U.S. instr NanoLogix N-Assay, ELISA dev
OmniBiome Therapeutics U.S. microbiome maternal infections that lead to preterm labor service
OraSure Technologies U.S. ebola OraQuick Ebola Rapid Antigen Test EUA
Ortho Clinical Diagnostics Raritan, N.J. HIV HIV Combo Reagent Pack and Calibrator (VITROS® HIV Combo test) FDA
Quansys Biosciences U.S. resp 14‐plex Pneumococcal Array dev
Quidel San Diego, CA h. pylori Quick chaser test
Quidel San Diego, CA viral gastroenteritis Solana GAS assay small footprint
Quidel U.S. resp Sofia RSV Fluorescent Immunoassay waived
Quidel U.S. resp Sofia Strep A+ Fluorescent Immunoassay waived
Qvella Corp Canada sample Field Activated Sample Treatment pathogen concentration & Dx dev
Research & Diagnostic Antibodies U.S. sepsis PliNOSa Assay Kit CE
Response Biomedical Canada sepsis RAMP Procalcitonin CE
Roche Indianapolis, IN zika cobas zika test 6800/8800 pooled assay FDA
Roche Indianapolis, IN CT/NG RT PCR cobas FDA, CE
Roche Indianapolis, IN HPV cobas 6800/8800 FDA
Sandia National Labs Livermore, CA choldera, staph, e.coli combined immunoassay and NAAT service
Siemens Healthineers Tarrytown, NY hep/HIV HIV, CHIV, EHIV and viral hep. Tests for Attelica Solution pre-market approval FDA
Singulex U.S. pathogens single-molecule counting technology dev
Stellenbosch University South Africa TB Risk 4 test for TB dev
Sysmex Kobe, Japan various UF-5000 blue laser flow cytometry market
Thermo Fisher Scientific U.S. MERS Middle East Respiratory Syndrome Coronavirus (MERS-CoV) EUA
Thermo Fisher Scientific U.S. flu CDC’s influenza A (H7/N9) virus EUA
Transasia Bio-Medicals India STD ErbaLisa Syphilis mkt
U. of California, Irvine U.S. HCV HCV-AGS EIA acute HCV in urine dev
uBiome U.S. microbiome SmartGut, fecal sample seq for a microbiome study of the gut service
University Hopsital Cologne, Germany HAIs rapid test for carbapenmases dev
University of Hong Kong Hong Kong RSV saliva test for respiratory disease dev
USC Los Angeles, CA malaria PODS early stage malraia optics technology dev
ViroCyt U.S. sample ViroTag & Virus Counter 3100 dev

1.5 Billion Yet-Unclaimed Revenue in The LATAM IVD Market: Report

There is IVD sold almost everywhere in the world but revenue growth is not found everywhere. For most of the top IVD companies, adding scores of millions in growth would be helpful to business plans. That’s why growth regions such as Latin America offer promise beyond their market size. The maturation of IVD markets in developed countries (growth rate 1%-2%) has IVD companies casting their nets in developing countries where rising incomes and standards of living are anticipated to spark a new health consciousness population with growing demands for quality medical care.

A New Report From Kalorama Information Projects $1.5 Billion in as-yet-unclaimed market dollars in the Latin American in vitro diagnostics market in the next five years.

Latin America (LATAM) is a key target for IVD manufacturers.  Kalorama’s report, IVD in Latin America, focuses on the market for reagents and instruments in the most important countries of the continent. Argentina, Brazil, Chile, Colombia, Mexico, and Peru are singled out for a deeper level of analysis; the countries of Bolivia, Costa Rica, Cuba, Dominican Republic, Ecuador, El Salvador, Guatemala, Guyana, Haiti, Honduras, Nicaragua, Panama, Paraguay, and Uruguay are also considered to provide a complete overview of the region. Combined, these countries represent a population of 626.5 million; a large potential IVD market audience. Brazil and Mexico represent the two largest countries in terms of population, accounting for more than half of LATAM total population. For this reason, these two countries have been the focus for many IVD suppliers in recent years.

However, as economic conditions strengthen in other countries and demand increases for quality health services, there are additional opportunities in countries such as Argentina and Chile.

The estimated GDP for the countries studied in this research is an average of 0.1% annual growth for the year 2017 but consists of a declining GDP for Venezuela; excluding Venezuela, the region records 2.2%. GDP per capita is reported at $16,635 on average for the region.

Inequalities and social deprivation are always present in Latin America, where poverty is not declining; in fact, it sometimes increases. Although not all the countries in Latin America present similar circumstances or have the same players, there is a permanent and historical social inequality present in all countries of the region. Throughout the region there are highly educated citizens with high economic income; while there are also citizens without or with low education with financial struggles.

Over the last years, the countries in the Atlantic zone grew more rapidly than those in the Pacific zone, basically because of the rise in the price in commodities, currently slowing and declining. Venezuelan, Argentinian and Brazilian currencies have experiences wide currency fluctuations, mostly declining in value. Additionally, both Argentina and Venezuela are going through a high inflation rate process.

The total revenues calculating the IVD market in LATAM are generated by the sales of reagents, consumables, controls, calibrators and solutions categorized in well-defined segments. The market for IVD in Latin America is estimated at $2.4 billion in 2018 and will grow at 8.4%. That’s nearly one billion and a half dollars of extra market value that companies will compete for. Population growth, government insurance, newly insured patients and updated healthcare facilities will drive growth.

Brazil is the largest in vitro diagnostics market within Latin America and represents 45% of the market. Mexico ranks second with an estimated 19%.  Brazil, Chile and Colombia are among the highest growers.

Key IVD Market Competitors in Latin America

Abbott

Abbott Laboratories is a global, diversified healthcare company active in pharmaceuticals, nutritionals, devices and diagnostics. Abbott’s diagnostic product strength is its sheer presence worldwide. In LATAM, the company dominates in immunoassay-based microbiology and molecular microbiology, and is competitive in all countries in immunoassays.

Market Share for IVD Players in Latin America with rankings can be found in Kalorama Information’s New Research Report on Latin American IVD

Danaher

Beckman Coulter, Inc., a subsidiary of Danaher Corporation (DHR), has developed, manufactured, and marketed IVD tests for more than 75 years. The company reports that more than 275,000 Beckman Coulter systems operate in both diagnostics and life sciences laboratories on six continents.   Beckman Coulter’s strength is in chemistries, immunoassays, flow cytometry and hematology.   Danaher also operates the blood analyzer leader, Radiometer, and histology leader Leica Biosystems.

Becton Dickinson

Becton Dickinson (BD) is a leading global medical technology company that develops, manufactures and sells medical devices, instrument systems and reagents. Founded in 1897 and headquartered in Franklin Lakes, New Jersey, BD employs nearly 30,000 associates in more than 50 countries throughout the world. The company serves healthcare institutions, life science researchers, clinical laboratories, the pharmaceutical industry, and the general public.  BD has operated in China since 1994 and in India since 1996. In LATAM, the company specializes in microbiology, flow cytometry, and molecular solutions.

bioMérieux

bioMérieux is present in more than 150 countries through 39 subsidiaries and a large network of distributors. bioMérieux is best known for its microbiology business that includes immunoassays, traditional microbiology, and chromogenic media; however, the company is moving to capitalize on its acquisition of Organon Technika’s molecular technology, BOOM, and NASBA technologies.

Roche

Roche Diagnostics dominates clinical chemistry, urinalysis, POC, and hematology and is competitive in molecular and immunoassays. Roche is the world’s largest supplier of clinical diagnostics products; Roche’s global product sales are still almost twice its nearest competitor. Roche is also the world leader in in vitro diagnostics and tissue-based cancer diagnostics, and a frontrunner in diabetes management. Roche’s personalized healthcare strategy aims at providing medicines and diagnostic tools for patient disease management. Roche’s Ventana Medical Systems business also contributes to their market strength.

Siemens Healthineers

The Siemens Healthineers business is one of the world’s largest suppliers to the healthcare industry and a major player in medical imaging, laboratory diagnostics, medical information technology, and hearing aids. The diagnostics division includes products for clinical chemistry, drug testing, hematology, coagulation, immunoassay, infectious diseases, microbiology, molecular diagnostics, plasma proteins, point of care testing, blood gases/electrolytes, and urinalysis. In addition, Siemens operates a clinical laboratory and offers laboratory informatics and automation.

Two big developments in direct-to-consumer testing in October.  While one lab giant has teamed up with a major drugstore retailer to offer consumers the ability to test themselves at portals, another has opened it’s website to online tests.  We cover direct to consumer testing, routine and genetic, in our market research report on the topic. (https://www.kaloramainformation.com/Direct-Consumer-DTC-9588755/).  An updated study is planned in January.

It was previously thought that the space where consumers would be most likely to order testing would be in the genetic space, where companies like 23andMe and Ancestry.com have signed up subscribers to have DNA samples taken to detect nationality and ancestry.  These of course are target customers for health and wellness genetic tests.

On the routine side we forecasted a small growthy market but we were less sanguine.  Theranos, was, at the time of the reports publication showing the first signs of its downfall.  Retail outlets like AnyTestNow attempted the concept, and to a degree they still exist and prosper in scale, but their market exposure is limited. There aren’t locations everywhere.  Our optimistic forecasts considered that large players in test performance would enter the space.

Now two developments have occurred in routine patient testing to take note of:

Quest has launched QuestDirect, an enhanced consumer-initiated testing service that empowers patients to manage and take control of their healthcare by ordering health and wellness lab testing from the convenience of their home.    To order, consumers can visit the QuestDirect website to conveniently shop online and choose their own lab tests. Independent physicians will provide oversight and, if appropriate, order the testing. Consumers can make an appointment online to visit one of Quest’s 2,200 patient service centers. Results are typically available within a week and can be accessed through MyQuest, where they can be easily shared with a consumer’s own doctor, or a with a family member through the new “My Circle” feature that allows approved family members and other users to connect through MyQuest.  Complete blood counts, complete molecular profiles, urine tests, are among those that can be utilized.

The entire clinical lab services market is premised on patients visiting doctors at a normal rate and physicians ordering tests as needed.  There never seemed to be a reason to think that would change, until now.

Similarly, Walgreens and LabCorp announced a large-scale expansion of their LabCorp at Walgreens collaboration. The two companies have agreed to open at least 600 LabCorp patient service centers at Walgreens stores across the U.S. over the next four years, inclusive of the 17 locations that have opened since they first announced their consumer-focused initiative in June 2017.  LabCorp at Walgreens locations are currently open in Florida, Colorado, North Carolina and Deerfield, Illinois, serving as an important part of LabCorp’s network of nearly 2,000 patient service centers across the U.S. Consumers and healthcare providers continue to have a positive response to the existing locations, which offer specimen collection services for LabCorp testing in a secure, comfortable environment. The sites are located near the pharmacy area inside the Walgreens store, providing a convenient location for consumers to access important health services and information.

It should be noted that both moves are early and are launched in a moment where the average consumer does not know tests and what they mean.  They know they have blood taken, and may be aware of a few key tests, such as cholesterol and glucose.  Greater knowledge of tests, and their meanings, may lead to increased demand. When a “CBC” still means to a lot of consumers, The Canadian Broadcast Company?  if it means anything at all, there’s a limit to the market. When everyone, or their apps knows what a CBC that could seriously disrupt testing markets.

It’s too early to tell the impact of direct-to-consumer testing though on the extreme end of prediction, the stakes are high.  The entire clinical lab services market is premised on patients visiting doctors at a normal rate and physicians ordering tests as needed.  There never seemed to be a reason to think that would change, until now.  An additional volume of tests from consumers bypassing the doctors office visit, likely fueled by technology that facilitates the origination and interpretation of tests, and generally, greater knowledge of tests by informed consumers could push clinical lab services markets (market opportunity/demand for the performance of tests) beyond previous estimates.  This also means the markets for in vitro diagnostic instruments and reagents could be augmented in a similar fashion.  Time will tell; it has been Kalorama’s practice to be conservative on such forecasts.

HIV remains a deadly disease, but fortunately, in vitro diagnostic solutions abound for its detection and progress-tracking of treatments.  In this article, we chronicle the developments in HIV IVD – more information can be found in our Worldwide Market for In Vitro Diagnostics Tests, 11th Edition: https://www.kaloramainformation.com/Worldwide-In-Vitro-Diagnostic-Tests-11th-Edition-11723890/

Many of the 35.3 million people infected with HIV worldwide are unaware of their condition, as symptoms may not always be apparent.  A few weeks occur between contamination and the appearance of the first anti-HIV serum antibodies. This makes early detection of seroconversions a focus for healthcare providers and the IVD vendors that serve them.  Fortunately, there are an array of in vitro diagnostic solutions to the detection, identification and prognosis assessment of HIV:

New Small-Hospital Analyzer HIV Test: Ortho Clinical Diagnostics announced that its VITROS® Immunodiagnostic Products HIV Combo Reagent Pack and Calibrator (VITROS® HIV Combo test) received approval from the U.S. Food and Drug Administration for use on Ortho’s VITROS® ECi/ECiQ Immunodiagnostic Systems. The product is aimed at the small hospital market and is sold in and outside the U.S. The VITROS® HIV Combo test was previously approved for use on Ortho’s VITROS® 5600 Integrated System and Ortho’s VITROS® 3600 Immunodiagnostic System. VITROS® HIV Combo, a fourth-generation test, detects both HIV-1 and HIV-2 antibodies (Ab) and the p24 antigen (Ag), enabling detection of acute HIV-1 infection earlier than third-generation tests, according to the company.

Roche’s Plasma Separation Card: In January 2018, Roche announced the launch of its cobas Plasma Separation Card, a simple and stable device for the collection of plasma for HIV viral load testing, with Roche’s cobas AmpliPrep, cobas TaqMan, and cobas 6800/8800 HIV tests. The device requires only a small volume of blood taken the patient’s fingertip, and can be transported with the need for cold storage, making the Plasma Separation Card ideal for use in remote areas and those of extreme temperature and humidity.

Recent Use: In August 2018, Roche installed the system at the Kenya Medical Research Institute (Kemri). for testing in remote areas months after it launched its Cobas Plasma Separation Card. The easy-to-use sample collection device will make it possible to transport plasma for testing in far-flung regions without the use of refrigeration. The machine can handle up to 960 samples within an eight-hour shift compared to the one-month span it traditionally took patients to get results. The Cobas 8800 instrument installed at the Kemri has a capacity to test more than 300,000 Kenyans living with HIV annually.

Using Dentists for HIV Screening: Dental clinics may provide expanded opportunities for oral HIV rapid testing and conversations about HIV prevention in high HIV prevalence communities. A recent study assessed HIV testing in dental clinics in South Florida, an urban area with the highest rates of HIV diagnoses in the United States in 2015. During 2014 and 2015, dentists and hygienists at two federally qualified health center (FQHC) dental clinics who serve racial/ethnic minority patient populations in South Florida were trained to administer oral HIV rapid tests as a part of a routine dental visit.   Expanding HIV screening for populations at risk necessitates testing in nontraditional settings. Patients presenting for dental services were offered a rapid HIV test and brief survey regarding their demographics, HIV testing history and behaviors. Most (85%) accepted oral HIV rapid testing (none tested HIV-positive); 14% had never been tested for HIV.

Latent HIV Quantification: A latent HIV reservoir is a group of immune cells in the body that are infected with HIV but are not actively producing new HIV. Latent HIV reservoirs can hide cells for years, and they can “wake up” and start making more HIV. If someone with HIV is not taking HIV medicines when this happens, the level of HIV in their body (called the viral load) will start to increase. The University of North Carolina at Chapel Hill (UNC) HIV Cure Center and Cell Microsystems, a provider of instruments for the sorting and isolation of single cells, have received an approximately $283,000, 12-month Phase I Small Business Innovation and Research contract from the National Institutes of Health to develop an automated platform to quantify the latent HIV reservoir. As researchers develop therapies to reverse HIV latency—a step toward clearing the virus from the body—an accompanying diagnostic test is also needed to accurately measure the viral reservoir and judge the efficacy of these new latency reversal agents. The collaboration between UNC and Cell Microsystems aims to fill this need by using Cell Microsystems automated images analysis tools, the CytoSort Array and CellRaft AIR system, to screen and isolate thousands of patient-derived cells to detect emergence of HIV after exposure to potential therapeutics.

Mobile HIV-1/2 Test: Arkansas-based start-up NOWDiagnostics is working on a handheld device for fingerstick blood tests called the Lateral Flow Reader that “can be adapted for almost any qualitative or quantitative rapid test.” The company’s ADEXUSDx hCG pregnancy test received 501(k) FDA clearance in 2015. The company’s HIV-1/2 Antibody Test has received CE mark in Europe. The test is an immunochromatographic assay used for the qualitative detection of antibodies against human immunodeficiency virus (HIV) in human whole blood, plasma or serum samples. Each cartridge takes a single drop of blood and returns a result in minutes. There are other tests that are used to measure the severity or monitor therapy of HIV infection such as CD4 count and the viral load test. HIV antibody detection based rapid test is the most appropriate test for routine diagnosis of HIV infection among adults.

Nanophone Technology: Investigators at Brigham and Women’s Hospital have designed a portable and affordable mobile diagnostic tool, utilizing a cellphone and nanotechnology, with the ability to detect HIV viruses and monitor its management in resource-limited regions. The novel platform was described in a paper published recently in Nature Communications. Utilizing nanotechnology, a microchip, a cellphone and a 3D-printed phone attachment, the researchers created a platform that can detect the RNA nucleic acids of the virus from a single drop of blood.

Rapids: Rapid (point-of-care) tests can be conducted away from laboratory facilities and give results in less than 30 minutes. A reactive results from a rapid should be followed up with a lab based test. Among marketed rapids:
• Alere Determine HIV–1/2 Ag/Ab Combo
• Chembio HIV 1/2 STAT-PAK® tests
• Uni-Gold™ Recombigen® HIV-1/2
• OraQuick® HIV Self-Test (HIVST)

Other HIV Testing Systems: There are scores of HIV IVD tests on the market. Besides the tests mentioned, other significant marketed tests include:
• Hologic Aptima HIV-1 RNA Qualitative Assay
• Abbott ARCHITECT HIV Ag/Ab Combo Assay
• Siemens ADVIA Centaur HIV Ag/Ab Combo (CHIV) Assay
• Roche Elecys HIV combi PT
• Bio-Rad GS HIV Combo Ag/Ab EIA
• bioMérieux VIDAS HIV DUO Ultra

Poor Trending with Youth Testing: Testing for HIV is at a crossroads as the youngest and most exposed population seems to be trending against getting tested for AIDs. According to a study published by the CDC in 2018, In the United States, 38.8% of women and 53.8% of men aged 15 to 44 reported they had never been tested for HIV outside of donating blood or blood products. Yet among those 15 to 24, the percentage who reported they had never been tested soared to 63.9% of women and 73.7% of men.
The most common reason reported by women and men for having never been tested was that they thought they were “unlikely to have been exposed to HIV,” or “never offered a test,” which indicates both This roughly matches a previous study, conducted by CDC researchers and published in the journal Pediatrics in 2016, found that the percentage of young adults aged 18 to 24 who reported they have never been tested for HIV remained steady among young men, and increased significantly among young women between 2011 and 2013. Specifically, among all young women, a significant decrease in the prevalence of HIV testing was detected overall, from 42.4% ever being tested in 2011 to 39.5% in 2013, according to that previous study, which was based on data from the national Youth Risk Behavior Survey and Behavioral Risk Factor Surveillance System.

Opt-Out HIV Testing and Other Solutions: The results have surprised experts given the amount of public education and the many HIV testing options available to the public, from at-home HIV testing kits to community health events that involve HIV testing. The decline of AIDs as a large scale national public health issue is a problem, or its status as an episodic event are possible factors. There are some calls for HIV testing to be added to common tests and conducted every year or every six months, at least for certain age groups. Other arrangements for opt-out type testing in certain areas. Opt-out HIV screening is performing an HIV test after notifying the patient that the test will be done; consent is inferred unless the patient declines. A study in San Francisco found that opt-out testing greatly increases test acceptance (https://www.jwatch.org/na40265/2016/02/04/opt-and-opt-out-hiv-testing-revisited).

Kalorama’s market forecasts for multiple types of clinical testing, including HIV testing, can be found in its Worldwide Market for In Vitro Diagnostics Tests, 11th Edition: https://www.kaloramainformation.com/Worldwide-In-Vitro-Diagnostic-Tests-11th-Edition-11723890/

When Columbia University posted a press release in February 2018 about a promising new proof-of-concept study of the Tick-Borne Disease Serochip (TBD Serochip), the press office soon had to amend the announcement with an update for the public: no, the test is not available yet; no, you can’t enroll in a clinical trial or send specimens; and no, they don’t know when it will be ready.

Has the university received a lot of public inquiries about the TBD serochip?

“Indeed we have!” said Tim Paul, editorial director of communications, via email.

The excitement around the TBD Serochip is just one sign of how eager the public is for a better tick-borne disease test.

Lyme disease and other tickborne diseases are on the rise in the United States. As the geographic range of ticks expands, perhaps due to climate change, infections are occurring in new locations. The number of reported tickborne diseases more than doubled in the United States between 2004 and 2016, according to the U.S. Centers for Disease Control and Prevention.

Lyme disease treatment – an oral antibiotic against the Borreliaburgdorferi bacterium — is most effective when administered in the early stages of infection. Delayed treatment can lead to long term damage to the nervous system or joints, and many patients fear the disease will become chronic if diagnosed late (although the CDC maintains that most people respond well to treatment even in later stages of the disease).

Yet diagnosing Lyme disease early can be tricky. Many patients do not notice the initial tick bite and early symptoms of Lyme disease may be vague. Only 70 to 80 percent of infected individuals develop a telltale erythema migrans rash. Meanwhile, current tests, which measure Lyme disease indirectly through the antibodies a person’s body creates to fight the disease, tend to perform poorly in the early weeks of an infection because it takes time for antibody production to rise to detectable levels. By some estimates, traditional serology-based test methods identify fewer than 40% of patients with early disease.

Kalorama estimates and forecasts Lyme Disease testing markets in our latest worldwide IVD market study.

For Lyme disease, the most common tick-borne disease in the United States, the CDC has recommended the same testing process since 1995: a serology-based two-tiered algorithm. The first tier is an immunoassay, then if the immunoassay results are positive or equivocal, it is followed by the second tier, a Western blot. To address the issue of false negatives for early-stage infections, the CDC suggests a provider consider treatment based on clinical presentation alone if the patient has had symptoms for less than 30 days, and offer a repeat immunoassay a few weeks later to confirm the diagnosis.

Serology has remained the only technique employed by all of the FDA-approved Lyme disease tests, according to a 2016 review in the Journal of Clinical Microbiology (DOI: 10.1128/JCM.03394-15), even while molecular and “-omics” methods have transformed other realms of clinical microbiology diagnostics.

Enzyme-linked immunosorbent assays (ELISA), which are typically used as the first step in the two-tier algorithm, have improved over the years, with targets that are more specific to Borreliaburgdorferi and less likely to cross react with other infectious agents. Yet their performance is still best when they are paired with Western blots, and Western blot testing has many limitations, including low sensitivity for early stage infections and a labor-intensive, somewhat subjective process.

Some researchers are now advocating for new testing algorithms, in particular a two-ELISA algorithm, where an initial positive or equivocal ELISA result is followed by a second ELISA assay that has slightly different targets. They find this method effective and also 27.1% to 44.0% cheaper than the two-tier algorithm with Western blot. A 2018 study comparing three variations of immunoassay-only algorithms found them all accurate, and in some cases even better than the traditional two-tier algorithm. However, the CDC still recommends the traditional two-tier algorithm.

For the other tick-borne diseases, the diagnostic options are limited. Immunofluorescent assays are available for BabesiaAnaplasmaEhrlichia and Rickettsia, although accuracy varies by laboratory. Some tick-borne viruses can be detected by specialty labs. For other tick-borne diseases, such as Southern tick-associated rash illness (STARI), there are no immunoassays available. There are no commercially available tests that simultaneously detect multiple tick-borne disease agents.

New tests on the horizon

That explains why the TBD Serochip has gotten so much attention this year and piqued the interest of the public. U.S. National Institutes of Health director Francis Collins even highlighted the February TBD Serochip study in a blog post in June, noting that it was developed by NIH-funded researchers.  The TBD Serochip is a serological test, like the commercially available tests today. However, it detects multiple targets based on a variety of newly identified antigenic proteins, so it has the potential to be more specific to Borrelia than other than previous tests. Also, it can detect antibodies to multiple tick-borne pathogens simultaneously. The first version of the TBD Serochip can detect Lyme disease, babesiosis, and anaplasmosis, as well as human monocytic ehrlichiosis, Rocky Mountain spotted fever, Heartland virus, and Powasan virus. New pathogens can be added to the assay as new targets are discovered, in a process that the researchers say would take only about 4 weeks.

The lead author of the TBD Serochip journal article, Rafal Tokarz, PhD, told Infectious Disease Advisor in March 2018 that the challenge now is to improve the test and make a simpler version that can be used by clinical laboratories.

“Although our test works quite well, we are still validating it and are trying to make it even more comprehensive by including additional agents that we did not include in the first version of the test,” Tokarz said.

Tokarz told Clinical Laboratory News in July 2018 that the TBD Serochip in its current form would still be useable by specialty labs only, but the goal is to make it a point of care test. He predicted the test would be available for clinical use within the next two years.

The TBD Serochip is just one possible approach to better tick-borne disease testing.

Researchers at the CDC and elsewhere are working to develop tests for tick-borne diseases based on metabolomics, which is the technique of finding a unique signature of metabolites in a person’s blood that corresponds with a certain disease.

A promising proof-of-concept study was published in 2015 showing that liquid chromatography-mass spectrometry could be used to detect a biosignature of 44 “molecular features” that correctly classify early Lyme disease patients versus healthy controls. A follow-up study in 2017 showed that the same technique could distinguish between early Lyme disease and STARI, which is a tick-borne illness that causes a rash similar to Lyme disease. There is currently no diagnostic blood test for STARI because the causative agent is unknown.

Meanwhile, other researcher groups are searching for molecular diagnostic techniques to identify tick-borne diseases. A non-for profit organization called Translational Genomics Research Institute (TGen) announced in 2017 it had raised hundreds of thousands of dollars from patient advocacy groups to develop LymeSeq, a DNA-based test to detect “multiple strains of Lyme bacteria.” Their goal, as of 2016, was to use next generation DNA amplicon sequencing to detect “over 22 strains of Lyme bacteria, all major co-infections and non-Lyme causes of disease like influenza or staph in a single blood test.”

Some reference laboratories already offer polymerase chain reaction (PCR) blood tests for Lyme disease, but with the caveat that they may be used as an aid to diagnosis but are not diagnostic alone. In general, direct detection of the spirochete bacteria that cause Lyme disease bacteria has not worked clinically because there are so few bacterial cells in the body. As a result, the sensitivity of PCR to B. burgdorferi DNA in blood, plasma, or serum samples from patients with Lyme disease is low.

While academic researchers pursue these new directions, in vitro diagnostics developers appear to be focusing on improving on serology-based tests that are already available, making them faster and easier to use.

For example, Quidel announced in August 2018 that its Sofia 2 Lyme fluorescent immunoassay received FDA 510(k) clearance and a CLIA waiver. The assay, which runs on the 2-pound benchtop Sofia 2 Fluorescent Immunoassay Analyzer, requires only a fingerstick whole blood sample. It detects IgM and IgG antibodies to Borrelia burgdorferi, returning a result in 3 to 15 minutes. With its new CLIA waiver, the assay can now be used in physician offices or clinics.

The current developments, product launches and company plans in IVD testing on smartphone platforms has been detailed by Kalorama Information in a recent report by Kalorama’s Rob Camp: https://www.kaloramainformation.com/Smartphone-Based-IVD-Products-Trends-Potential-12019398/

We summarize some of the findings of our study here.  This represents a fraction of the findings of the report:

The techniques that can most successfully harness mobile phone technology look to be lateral flow immunoassay-based tests, ELISAs, and spectrophotometry, as they are methodologies that use a tool that has become ubiquitous in the developed world and is on the rise globally, the smartphone camera. In recent years, researchers have been developing algorithms and machine learning systems that can scan and analyze colorimetric tests as accurately as a sophisticated piece of laboratory machinery, but at a fraction of the cost. While the technology appears yet to be in its nascent stages, there are quite a few examples of devices under development that employ these techniques

According to the GSM Association, two-thirds of the world’s population have a mobile phone service plan, but growth is slowing as the market matures; it took four years to go from 4 to 5 billion subscribers. It is projected to take even longer to reach another billion; estimates are 5.7 billion unique subscribers by 2020, representing 72% total market penetration. However, the number of subscriptions per person is widely distributed. On average, there are 1.04 subscriptions for every person worldwide, ranging from only 0.08 per capita in Eritrea to nearly 2.5 in Hong Kong and over three in nearby Macau. The table below highlights the growth of mobile services in twenty-four selected countries, and the map illustrates the overall global distribution of subscriptions in 2017.

Formed out of the University of Colorado-Boulder, Mobile Assay is a startup that produces a smartphone-compatible lateral flow assay reader that is stated to be able to read test strips of any type; the mReader imaging system transforms qualitative tests into highly sensitive quantitative tests. The company’s universal Lab-on Mobile-Device (LMD) platform uses Mobile Image Radiometry (MIR), an image analysis algorithm that converts the analog visual signals of a rapid diagnostic test into a normalized and calibrated digital signal.

The platform improves the quantification of RDTs by increasing sensitivity over a hundredfold, comparable to ELISA. Mobile Assay has partnered with companies like Alere/Abbott and Rapid Medical Diagnostics to validate a number of tests for their platform, focusing primarily on insect-borne tropical diseases, including lymphatic filariasis, malaria, onchocerciasis, and schistosomiasis.

Novarum (Cardiff, Wales, UK) develops smartphone-based mobile POCT platforms customized to users’ specifications and made to work for any number of applications. Users work with Novarum to develop an app designed for specific testing needs; the app is then used to scan a code to identify the type of test to be conducted, then to scan the test results. Results can be sent to a database of the user’s choosing via email, SMS, web, Bluetooth, or USB.

iXensor’s Eveline ovulation test also uses a dipstick test, but is instead a single-use LH-detecting colorimetric test unit that attaches to a clip set over the front camera of a
smartphone. The included app uses iXensor’s adaptive algorithm to present data in a three-tiered snapshot of the user’s fertility, and stores the information in a Fertility Calendar that gives the dates the user will likely be at her most fertile. Reminders can be set to take tests to more accurately pinpoint peak fertility.

Fertility Tech (Las Vegas, NV) takes a different approach to ovulation testing: the company’s Ovatel is a saliva-based test that functions more as a microscope than a lateral flow assay analyzer. Users place a saliva sample on a lens that attaches to the smartphone camera, which analyzes the image for a certain fern-like physical pattern, formed by salt crystals, that appears in the sample due to spikes in a woman’s estrogen levels during her cycle. No basal body temperature measures or urine samples are necessary, nor are additional purchases, as Ovatel is reusable.

BACtrack released the BACtrack Mobile Smartphone Breathalyzer in April 2013. The device uses Xtend Fuel Cell Sensor technology offered in their professional-grade
analyzers, which detect the electrochemical process that oxidizes the alcohol in a breath sample and produces an electrical current, which is then relayed back to the analyzer’s sensor to determine the user’s BAC; the device also features a mini solenoid pump to ensure the most accurate and efficient breath capture for testing.

The BACtrack Mobile breathalyzer is compatible with most Apple devices running iOS 8.0 or newer, including iPod Touch, as well as most Android smartphones by Samsung and Google. The device connects wirelessly to the phone via Bluetooth and operates through the BACtrack Companion App, which features the company’s ZeroLine technology, which estimates when the user’s BAC will return to 0.00%. The app also helps the user to call a ride sharing service when necessary.

For more information on smartphone IVD combinations, Kalorama’s recent report is available here: https://www.kaloramainformation.com/Smartphone-Based-IVD-Products-Trends-Potential-12019398/