Novel molecular technologies are evolving at a rapid pace, cutting the time it takes to diagnose infectious disease, to individualize treatment, and to optimize outcomes for patients. For the first time, a full track dedicated to the development of Molecular Diagnostics for Infectious Disease will take place at Molecular Medicine Tri-Conference. This track will highlight several emerging technologies, including NGS and other emerging tools, and discuss challenges in integrating these tests into clinical practice. We will examine the challenges in diagnosing sepsis and GI infectious diseases specifically, and discuss the topic of antimicrobial resistance and stewardship, outcome studies, and, new this year, the human microbiome. Join esteemed colleagues Jennifer Dien Bard, Keck School of Medicine of the University of Southern California; Steve Miller, University of San Francisco; Chris Polage, UC Davis Medical Center; Nathan Ledeboer, Medical College of Wisconsin; Susan Butler-Wu, University of Washington; Purvesh Khatri, Stanford School of Medicine; and others to discuss these topics and more.
Final Agenda
Monday, March 7
10:30 am Conference Program Registration Open
11:50 Chairperson’s Opening Remarks
Stephen Salipante, M.D., Ph.D., Assistant Professor, Director, Next-Generation Sequencing Analytics Laboratory; Assistant Director, Molecular Diagnosis Section, University of Washington
12:00 pm NGS Assays for Diagnosis of Infectious Diseases
Charles Chiu, M.D., Ph.D., Associate Professor, Lab Medicine and Infectious Diseases; Director, UCSF-Abbott Viral Diagnostics and Discovery Center; Associate Director, UCSF Clinical Microbiology Laboratory
There is great interest and potential in the use of metagenomic next-generation sequencing (NGS) for diagnosis of infectious diseases in clinical settings. We will discuss assay development, clinical validation, bioinformatics analysis, and regulatory considerations involved when developing such NGS-based assays in CLIA-certified laboratories. We will also discuss emerging rapid, point-of-care sequencing technologies and host-based approaches for infectious disease diagnosis.
12:30 Ingredients for a CLIA-Approved Clinical 16S rRNA Gene Assay for Mixed Bacterial Populations by Next-Generation Sequencing
Noah Hoffman, M.D., Ph.D., Associate Professor, University of Washington, Department of Laboratory Medicine, Associate Director, Informatics Division, University of Washington Medical Center
Development of software tools for species-level classification of bacteria using next-generation sequencing, as well as processes for rapid and confident clinical sign out have been particularly challenging in the clinical laboratory setting. In this talk, I will present the development of one of the first NGS 16S gene sequencing assays to be offered by a clinical laboratory, discuss bioinformatic challenges and solutions, and present applications for this assay using case studies.
1:00 Session Break
1:15 Luncheon Presentation (Sponsorship Opportunity Available) or Enjoy Lunch on Your Own
2:15 Session Break
2:30 Chairperson’s Remarks
Weian Zhao, Ph.D., Assistant Professor, Department of Pharmaceutical Sciences, Sue and Bill Gross Stem Cell Research Center, Chao Family Comprehensive Cancer Center, Edwards Lifesciences Center for Advanced Cardiovascular Technology, Department of Biomedical Engineering, University of California–Irvine
2:40 Large-Scale Whole Genome Sequencing in Microbiology
Stephen Salipante, M.D., Ph.D., Assistant Professor, Director, Next-Generation Sequencing Analytics Laboratory; Assistant Director, Molecular Diagnosis Section, University of Washington
Next-generation sequencing is making it increasingly feasible to generate whole genome sequence data from large numbers of microorganisms. This session will examine what kinds of information can be obtained from performing large-scale genomic sequencing of bacteria originating directly from the clinical laboratory.
3:10 Assuring the Quality of Next-Generation Sequencing in Clinical Microbiology and Public Health Laboratories
Amy Gargis, PhD, Laboratory Preparedness and Response Branch, Division of Preparedness and Emerging Infections, National Center for Emerging and Zoonotic Infectious Diseases, Centers for Disease Control and Prevention
The Centers for Disease Control and Prevention published practice recommendations developed by multidisciplinary workgroups for clinical next-generation sequencing of human genomic DNA. To follow up, CDC began an effort to consider quality issues and guidance for NGS infectious disease testing. The similarities and differences applicable to NGS testing of human and infectious disease samples will be discussed, including considerations for NGS test validation, quality control procedures, proficiency testing, and reference materials.
3:40 Regulatory Perspective on Infectious Disease NGS Dx Devices
Heike Sichtig, Ph.D., Medical Countermeasures/Multiplex, Microbiology Devices, Center for Devices (CDRH), FDA
The presentation will outline studies to evaluate the use of NGS-based devices as an aid in infectious disease diagnostics, and to gain a better understanding of potential NGS clinical implementation strategies. Focus will be on the possible approaches to validation studies and data for the evaluation of infectious disease NGS-based diagnostics for potential regulatory clearance/approval, and the use of sequence outputs from infectious disease NGS-based devices to evaluate performance.
4:10 Clinical Testing Using an NGS-Based HIV-1 Genotyping Assay (DEEPGEN™ HIV): The Importance of Utilizing a Stringent Quality Control
Miguel E. Quinones-Mateu, Ph.D., Associate Professor & Scientific Director, University Hospitals Case Medical Center/Case Western Reserve University
A robust validation and implementation process is essential to guarantee the success of NGS-based lab-developed tests (LDTs) in a CLIA-certified environment, including the use of appropriate controls, standards and reference materials. This presentation will describe the development and implementation of an ultrasensitive NGS HIV-1 genotyping assay (DEEPGENTM HIV) designed to detect minority drug-resistant HIV-1 variants and the use of novel recombinant RNA viral technology ‘full process’ reference material to monitor the detection of HIV-1 drug resistant targets.
4:25 Utility of Rapid Real-Time PCR Using a Novel Random-Access 20-Minute Real-Time PCR System
Christopher Connelly, Ph.D., Research and Development Scientific Manager, Molecular Technology, Streck
This talk will focus on PCR-based applications for the Philisa® Real-Time PCR System that serve to accelerate workflow for molecular diagnostic analysis. Critical assays for infectious disease testing, such as detection of antibiotic resistant bacteria and RT-PCR-based identification of viruses will benefit from the versatility and performance of the Philisa Real-Time PCR System.
4:40 Refreshment Break and Transition to Plenary Session
5:00 Plenary Keynote Session
6:00 Grand Opening Reception in the Exhibit Hall with Poster Viewing
7:30 Close of Day
Tuesday, March 8
7:00 am Registration Open and Morning Coffee
8:00 Plenary Keynote Session
9:00 Refreshment Break in the Exhibit Hall with Poster Viewing
10:05 Chairperson’s Remarks
Nathan A. Ledeboer, Ph.D., D(ABMM), Assistant Professor, Medical Director, Clinical Microbiology, Medical College of Wisconsin
10:15 Syndrome-Specific Infectious Disease Panels: More Answers, More Questions
Elizabeth M. Marlowe, Ph.D., D(ABMM), Technical Director, Microbiology, Kaiser Permanente, The Permanente Medical Group Regional Laboratories
In this talk, we will explore trends in US healthcare in the Era of Consumerism and discuss what is driving the design and implementation of panels. You will understand the role of syndrome-specific panels in the practice of infectious disease testing.
10:45 Nanomaterial Integrated Platforms for Infectious Disease Diagnosis
Siyang Zheng, Ph.D., Associate Professor, Biomedical Engineering, Pennsylvania State University
Infectious diseases can erupt unpredictably, propagate rapidly, affect large population and have potential for explosive global effects. Prompt surveillance on large human or animal population requires high-performance portable tools. Nanomaterial integrated platforms promise to deliver the platform for future infectious disease diagnosis.
11:15 Integrated Comprehensive Droplet Digital Detection Technology (IC 3D) for Rapid and Sensitive Detection of Infectious Diseases
Weian Zhao, Ph.D., Assistant Professor, Department of Pharmaceutical Sciences, Sue and Bill Gross Stem Cell Research Center, Chao Family Comprehensive Cancer Center, Edwards Lifesciences Center for Advanced Cardiovascular Technology, Department of Biomedical Engineering, University of California–Irvine
Rapid and sensitive detection of pathogens for infectious diseases remains a major challenge in medical sciences and healthcare systems. With the capability and versatility, our IC 3D technology has the potential to introduce a new paradigm in rapid detection of low abundance infectious pathogens from complex media. The significant shortened assay time allows timely and effective intervention to reduce mortality and financial costs with patient care.
11:45 Will Point-of-Care Molecular Testing Displace Laboratory-Based Testing?
Nathan A. Ledeboer, Ph.D., D(ABMM), Assistant Professor, Medical Director, Clinical Microbiology, Medical College of Wisconsin
Development of point-of-care molecular assays for the detection of infectious diseases is rapidly expanding. The assays being released have exhibited variable sensitivity and specificity, leaving providers to understand the limitations of point-of-care testing. This session will explore the clinical outcomes of point-of-care testing from an antimicrobial stewardship perspective, particularly focusing on Streptococcal pharyngitis and influenza testing.
12:15 pm Session Break
12:25 Luncheon Presentation (Sponsorship Opportunity Available) or Enjoy Lunch on Your Own
1:25 Refreshment Break in the Exhibit Hall with Poster Viewing
2:00 Chairperson’s Remarks
Raymond J. Langley, Ph.D., Assistant Professor, Department of Pharmacology, University of South Alabama
2:10 SPOTLIGHT SESSION: Resolving Molecular Diagnostics Need for Ebola, Advancing Point of Care Testing for the West
Sterghios Moschos, Ph.D., Associate Professor, Biomedical Sciences, University of Westminster
The West African Ebola outbreak galvanized academics and biotech internationally to innovate solutions for mass point of need testing for category 4 biological agents. The international public-private EbolaCheck consortium has addressed this need by developing a 5-step, <30 min, portable system that can quantify Ebola virus in as little as 5 ul of crude biofluids for under US$12 per test. Engineered for West Africa, the technology is now expanding to address differential diagnosis need for future infectious disease outbreaks and beyond.
2:40 Novel Approaches to the Laboratory Diagnosis of Sepsis
Jennifer Dien Bard, Director, Clinical Microbiology Laboratory; Assistant Professor of Clinical Pathology, Keck School of Medicine of the University of Southern California
Sepsis is associated with high morbidity and mortality. Prompt microbiological workup that guide appropriate antimicrobial therapy is essential for the optimization of patient outcome. Novel, innovative technologies have revolutionized the detection and identification of bloodstream pathogens in the laboratory. This session will discuss approaches to rapid laboratory diagnosis of sepsis.
3:10 Integrative -Omics Analysis of Sepsis: Biomarkers for Improved Patient Management
Raymond J. Langley, Ph.D., Assistant Professor, Department of Pharmacology, University of South Alabama
Infection-induced severe sepsis patients who do not receive early therapy have a high mortality rate (55%). However, current diagnostics are fairly non-specific. We used an integrative -omics approach to develop a clinico-metabolomic classifier to predict sepsis and the probability of death at the time of presentation.
3:40 T2 Magnetic Resonance (T2MR) a Revolutionary Breakthrough in Sepsis Diagnostics
Tom Lowery, Ph.D., Chief Scientific Officer, T2 Biosystems
T2MR is the first and only sepsis diagnostic that identifies pathogens directly from whole blood without reliance on insensitive blood cultures. T2MR technology provides faster, easier and more accurate results in 3-5 hours.
3:55 Isothermal Amplification: an Innovative Tool for Infection Diseases Detection
Roberto Spricigo, Manager, Strategic Alliances & OEM PON, QIAGEN Lake Constance
The presentation gives an overview on isothermal amplification technologies and on the new dedicated solutions provided by QIAGEN Lake Constance GmbH, which could be particularly useful in the detection of Infection Diseases.
4:10 St. Patrick’s Day Celebration in the Exhibit Hall with Poster Viewing
5:00 Breakout Discussions in the Exhibit Hall
Challenges of Diagnosing Sepsis
Jennifer Dien Bard, Director of the Clinical Microbiology Laboratory, Assistant Professor of Clinical Pathology, Keck School of Medicine of the University of Southern California
- What factors impact the diagnosis of sepsis in the laboratory?
- What are the most ground-breaking and innovative tests available to diagnose sepsis?
- How useful is rapid identification if susceptibility is still delayed?
Rapid Detection Methods for Infectious Diseases
Weian Zhao, PhD, Assistant Professor, Department of Pharmaceutical Sciences, Sue and Bill Gross Stem Cell Research Center, Chao Family Comprehensive Cancer Center, Edwards Lifesciences Center for Advanced Cardiovascular Technology, Department of Biomedical Engineering, University of California–Irvine
- What do you think are the biggest problems remaining in the field?
- How do the rapid infectious disease test and monitoring fit into the new digital health paradigm?
- Discussions on rapid test of antibiotic resistance and precision medicine
Challenges in Antimicrobial Resistance
Susan Butler-Wu, Ph.D., D(ABMM), Associate Professor of Clinical Pathology, Keck School of Medicine of the University of Southern California, Director of Clinical Microbiology, LAC+USC Medical Center
- What diagnostic opportunities in antimicrobial resistance can be explored further?
- What are the most important factors in detecting antimicrobial resistance?
- How can this knowledge be applied to antimicrobial stewardship?
6:00 Close of Day
Wednesday, March 9
7:00 am Registration Open
7:00 am Breakfast Presentation (Sponsorship Opportunity Available) or Morning Coffee
8:00 Plenary Keynote Session Panel
10:00 Refreshment Break and Poster Competition Winner Announced in the Exhibit Hall
10:50 Chairperson’s Remarks
Romney M. Humphries, Ph.D., D(ABMM), Assistant Professor, UCLA Pathology & Laboratory Medicine, Section Chief of Clinical Microbiology, David Geffen School of Medicine, University of California, Los Angeles
11:00 Identification of CRE Outbreak through Use of Next-Generation Sequencing
Romney M. Humphries, Ph.D., D(ABMM), Assistant Professor, UCLA Pathology & Laboratory Medicine, Section Chief of Clinical Microbiology, David Geffen School of Medicine, University of California, Los Angeles
Antimicrobial resistance among Gram negative bacteria is continually evolving. We identified a novel carbapenem antimicrobial resistance mechanism among Klebsiella spp. present in patients at our institution through whole microbial genome sequencing, and tracked this to a large outbreak of carbapenem-resistant Klebsiella among patients at our facility, associated with duodenoscopes.
11:30 Rapid Molecular Diagnostics – Role of Antimicrobial Stewardship
Graeme Forrest, M.B.B.S., Associate Professor of Medicine, VA Portland Healthcare System, Division of Infectious Diseases
Rapid molecular testing of blood cultures, respiratory viral and stool specimens has grown rapidly in last few years. How treating providers utilize these results is a great unknown. I will discuss the role of antimicrobial stewardship programs and how they bridge the gap between results and action with these new technologies.
12:00 pm Determination of Antimicrobial Susceptibility by Mass Spectrometry: Where Are We Now and Where Are We Going?
Susan Butler-Wu, Ph.D., D(ABMM), Associate Professor of Clinical Pathology, Keck School of Medicine of the University of Southern California; Director, Clinical Microbiology, LAC+USC Medical Center
MALDI-TOF Mass Spectrometry is increasingly becoming the standard of practice for microorganism identification in clinical microbiology laboratories. There have recently been a variety of efforts to apply this technology to the detection of antimicrobial resistance. In this session, we will discuss the status of the determination of antimicrobial susceptibility testing by MALDI-TOF as well as other forms of mass spectrometry
12:30 Session Break
12:40 Luncheon Presentation: TB Testing at a Diverse Inner-City Population, an Overview of Testing Platforms from One Institute's Experience.
Diane Hirigoyen, M.S., Lead Molecular Specialist, Hennepin County Medical Center, Univ of Minnesota
The incidence of active TB has increased amongst certain US populations, resulting in increased detection of multi-drug resistant (MDR) and extreme resistant (XDR) strains of TB as a result. Here we share the experience of The Mycobacteriology Laboratory at HCMC and results on the emergence of TB and TB-like disease in an inner-city and active immigrant community.
1:10 Refreshment Break in the Exhibit Hall and Last Chance for Poster Viewing
1:50 Chairperson’s Remarks
Purvesh Khatri, Ph.D., Assistant Professor, Stanford Institute for Immunity, Transplantation and Infection (ITI), Stanford Center for Biomedical Informatics Research (BMIR), Department of Medicine, Stanford University
2:00 Metagenomic Analysis of the Microbiome in Infectious Disease
George M. Weinstock, Ph.D., Professor and Associate Director, Jackson Laboratory for Genomic Medicine, Farmington
Metagenomic analysis of the microbiome can help determine the normal bacteria found in a healthy person versus the bacteria that causes an infectious disease. This talk will discuss the role of next-generation sequencing for metagenomics as well as how examination and metagenomic analysis of the microbiome can lead to new diagnostic approaches.
2:30 Using Heterogeneous Data for Infectious Disease Diagnostic Markers and Therapies
Purvesh Khatri, Ph.D., Assistant Professor, Stanford Institute for Immunity, Transplantation and Infection (ITI), Stanford Center for Biomedical Informatics Research (BMIR), Department of Medicine, Stanford University
Large amounts of publicly available data present novel unprecedented opportunities to carry out integrated, multi-cohort analyses of infectious diseases that are better representatives of heterogeneity observed in the real-world patient population. However, the presence of biological and technical heterogeneity in these data also present significant challenges in their integration. I will discuss a novel computational framework for addressing these challenges while leveraging heterogeneity present in these data. I will demonstrate applications of this framework to various infectious diseases by identifying novel robust and reproducible diagnostic signatures and therapies.
3:00 Decentralized Diagnostics in Low Resource Settings: Innovations in Technology, Linkage to Care, Access, and Impact
Peter J. Dailey, Ph.D., MPH, Senior Technical Officer, FIND (Foundation for Innovative New Diagnostics)
Decentralized diagnostics are playing an increasing role in patient care, disease surveillance, and control in low resource settings with infectious diseases such as Tuberculosis, Malaria, HIV, and Human African Trypanosomiasis. Key gaps remain. Further innovations in decentralized diagnostics are needed to reach the UNAIDS HIV/AIDS 90-90-90 goal, enable the global expansion of Hepatitis C treatment, combat antimicrobial resistance, and support the global elimination of neglected tropical diseases.
3:30 Sample Prep Challenges for Bloodstream Infection Assays
Gregory Richmond, Ph.D., Principal Scientist, Ibis Biosciences, Abbott
We describe a sample preparation system that provides for the rapid detection and identification of bacterial and Candidal nucleic acid directly in whole blood specimens from patients with suspected bloodstream infections. A cellular lysis method and DNA purification system were designed for processing 5 ml of whole blood. A novel sample prep approach removed high levels of inhibiting human DNA prior to target detection. The system provides for rapid and sensitive molecular detection of diverse agents of these clinically important infections in approximately 6h.
4:00 Session Break
4:10 Chairperson’s Remarks
Steve Miller, Associate Professor and Director, UCSF Clinical Microbiology Laboratory, University of California, San Francisco
4:15 Critical Role of Clinical and Healthcare Outcome Data in the Evaluation of Molecular Diagnostic Tests for Infectious Diseases
Chris Polage, Director, Clinical Microbiology Laboratory, Department of Pathology and Laboratory Medicine, University of California Davis Medical Center
The clinical significance of positive molecular test results and effect of molecular testing on clinical and healthcare outcomes are rarely evaluated. This presentation will review selected studies that confirm and question the value of molecular diagnostic tests for infectious diseases with two main goals: 1) highlight pitfalls in molecular diagnostic test application and interpretation as pertains to infectious diseases; 2) promote more widespread evaluation of clinical and healthcare outcomes associated with molecular diagnostic test use.
4:45 Respiratory Pathogen Molecular Testing – Inpatient Outcome Study in the Hospital Setting
Susan Novak-Weekley, Ph.D., D(ABMM), Director or Microbiology, Molecular Infectious Disease & Serology Testing, Southern California Permanente Medical Group
Along with the implementation of sophisticated molecular tools in the clinical laboratory, outcome data is needed to substantiate the use and placement of tests. Outcome data will be presented from the pediatric inpatient hospital setting related to quicker result turn-around time for respiratory pathogen testing in patients seen in the hospital or emergency room.
5:15 Utility of Viral Monitoring Tests in Transplant Recipients
Steve Miller, Associate Professor and Director, UCSF Clinical Microbiology Laboratory, University of California, San Francisco
Transplant recipients are at high risk for viral infection, and a variety of testing strategies are available for monitoring. This talk will discuss the clinical utility and approach to testing these patients for CMV, EBV, BK and adenovirus, and illustrate how these tests can be used to improve patient management and outcomes.
5:45 Close of Conference Program