Scholars@Duke
Ephraim Tsalik

Ephraim Tsalik

Adjunct Associate Professor in the Department of Medicine
Medicine, Infectious Diseases
e.t@duke.edu
Box 102359 DUMC, Durham, NC 27710
Room 157 Hanes House Trent DRI, Box 102359, Durham, NC 27710
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Selected Publications

Plasma Microbial Cell-Free DNA Sequencing in Immunocompromised Patients With Pneumonia: A Prospective Observational Study.

Journal Article Clin Infect Dis · March 20, 2024 BACKGROUND: Pneumonia is a common cause of morbidity and mortality, yet a causative pathogen is identified in a minority of cases. Plasma microbial cell-free DNA sequencing may improve diagnostic yield in immunocompromised patients with pneumonia. METHODS: ... Full text Link to item Cite

Implementation of a Prospective Index-Cluster Sampling Strategy for the Detection of Presymptomatic Viral Respiratory Infection in Undergraduate Students.

Journal Article Open Forum Infect Dis · March 2024 BACKGROUND: Index-cluster studies may help characterize the spread of communicable infections in the presymptomatic state. We describe a prospective index-cluster sampling strategy (ICSS) to detect presymptomatic respiratory viral illness and its implement ... Full text Link to item Cite

Moving Beyond Mortality: Development and Application of a Desirability of Outcome Ranking (DOOR) Endpoint for Hospital-Acquired Bacterial Pneumonia and Ventilator-Associated Bacterial Pneumonia.

Journal Article Clin Infect Dis · February 17, 2024 BACKGROUND: Hospital-acquired and ventilator-associated bacterial pneumonia (HABP/VABP) are frequently caused by multidrug-resistant organisms. Patient-centered endpoints in clinical trials are needed to develop new antibiotics for HABP/VABP. Desirability ... Full text Link to item Cite

Epigenetic and transcriptional responses in circulating leukocytes are associated with future decompensation during SARS-CoV-2 infection.

Journal Article iScience · January 19, 2024 To elucidate host response elements that define impending decompensation during SARS-CoV-2 infection, we enrolled subjects hospitalized with COVID-19 who were matched for disease severity and comorbidities at the time of admission. We performed combined si ... Full text Link to item Cite

Host-response transcriptional biomarkers accurately discriminate bacterial and viral infections of global relevance.

Journal Article Sci Rep · December 18, 2023 Diagnostic limitations challenge management of clinically indistinguishable acute infectious illness globally. Gene expression classification models show great promise distinguishing causes of fever. We generated transcriptional data for a 294-participant ... Full text Link to item Cite

Peripheral Transcriptomics in Acute and Long-Term Kidney Dysfunction in SARS-CoV2 Infection.

Journal Article medRxiv · October 27, 2023 BACKGROUND: Acute kidney injury (AKI) is common in hospitalized patients with SARS-CoV2 infection despite vaccination and leads to long-term kidney dysfunction. However, peripheral blood molecular signatures in AKI from COVID-19 and their association with ... Full text Link to item Cite

RADx-UP Testing Core: Access to COVID-19 Diagnostics in Community-Engaged Research with Underserved Populations.

Journal Article J Clin Microbiol · August 23, 2023 Research on the COVID-19 pandemic revealed a disproportionate burden of COVID-19 infection and death among underserved populations and exposed low rates of SARS-CoV-2 testing in these communities. A landmark National Institutes of Health (NIH) funding init ... Full text Open Access Link to item Cite

Viewing both sides of the coin for infectious disease diagnosis.

Journal Article J Clin Invest · April 17, 2023 Optimal management of lower respiratory tract infection relies on distinguishing infectious from noninfectious etiologies and identifying the microbiologic cause if applicable. This process is complicated by overlapping clinical symptoms and the colonizing ... Full text Link to item Cite

Efficacy and safety of azithromycin versus placebo to treat lower respiratory tract infections associated with low procalcitonin: a randomised, placebo-controlled, double-blind, non-inferiority trial.

Journal Article Lancet Infect Dis · April 2023 BACKGROUND: Lower respiratory tract infections are frequently treated with antibiotics, despite a viral cause in many cases. It remains unknown whether low procalcitonin concentrations can identify patients with lower respiratory tract infection who are un ... Full text Open Access Link to item Cite

Clinically Adjudicated Reference Standards for Evaluation of Infectious Diseases Diagnostics.

Journal Article Clin Infect Dis · March 4, 2023 Lack of a gold standard can present a challenge for evaluation of diagnostic test accuracy of some infectious diseases tests, particularly when the test's accuracy potentially exceeds that of its predecessors. This approach may measure agreement with an im ... Full text Open Access Link to item Cite

Blood RNA alternative splicing events as diagnostic biomarkers for infectious disease.

Journal Article Cell Rep Methods · February 27, 2023 Assays detecting blood transcriptome changes are studied for infectious disease diagnosis. Blood-based RNA alternative splicing (AS) events, which have not been well characterized in pathogen infection, have potential normalization and assay platform stabi ... Full text Open Access Link to item Cite

Screening tools for predicting mortality of adults with suspected sepsis: an international sepsis cohort validation study.

Journal Article BMJ Open · February 20, 2023 OBJECTIVES: We evaluated the performance of commonly used sepsis screening tools across prospective sepsis cohorts in the USA, Cambodia and Ghana. DESIGN: Prospective cohort studies. SETTING AND PARTICIPANTS: From 2014 to 2021, participants with two or mor ... Full text Open Access Link to item Cite

Murine Host Response to Typical and Atypical Pneumonia

Conference AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE · 2023 Cite

Access to COVID-19 testing by individuals with housing insecurity during the early days of the COVID-19 pandemic in the United States: a scoping review.

Journal Article Front Public Health · 2023 INTRODUCTION: The COVID-19 pandemic focused attention on healthcare disparities and inequities faced by individuals within marginalized and structurally disadvantaged groups in the United States. These individuals bore the heaviest burden across this pande ... Full text Open Access Link to item Cite

Omic approaches to infectious disease testing

Chapter · January 1, 2023 A pathogen-based approach to infectious disease diagnosis has long been the gold standard, despite poor sensitivity, specificity, or long time to result with this method. The host response offers a robust and complementary approach to infectious disease di ... Full text Cite

Multi-objective optimization identifies a specific and interpretable COVID-19 host response signature.

Journal Article Cell Syst · December 21, 2022 The identification of a COVID-19 host response signature in blood can increase the understanding of SARS-CoV-2 pathogenesis and improve diagnostic tools. Applying a multi-objective optimization framework to both massive public and new multi-omics data, we ... Full text Link to item Cite

Host Gene Expression to Predict Sepsis Progression.

Journal Article Crit Care Med · December 1, 2022 OBJECTIVES: Sepsis causes significant mortality. However, most patients who die of sepsis do not present with severe infection, hampering efforts to deliver early, aggressive therapy. It is also known that the host gene expression response to infection pre ... Full text Link to item Cite

Plasma Microbial Cell-Free DNA Sequencing in Immunocompromised Patients With Pneumonia: A Prospective Observational Study.

Journal Article Clin Infect Dis · March 20, 2024 BACKGROUND: Pneumonia is a common cause of morbidity and mortality, yet a causative pathogen is identified in a minority of cases. Plasma microbial cell-free DNA sequencing may improve diagnostic yield in immunocompromised patients with pneumonia. METHODS: ... Full text Link to item Cite

Implementation of a Prospective Index-Cluster Sampling Strategy for the Detection of Presymptomatic Viral Respiratory Infection in Undergraduate Students.

Journal Article Open Forum Infect Dis · March 2024 BACKGROUND: Index-cluster studies may help characterize the spread of communicable infections in the presymptomatic state. We describe a prospective index-cluster sampling strategy (ICSS) to detect presymptomatic respiratory viral illness and its implement ... Full text Link to item Cite

Moving Beyond Mortality: Development and Application of a Desirability of Outcome Ranking (DOOR) Endpoint for Hospital-Acquired Bacterial Pneumonia and Ventilator-Associated Bacterial Pneumonia.

Journal Article Clin Infect Dis · February 17, 2024 BACKGROUND: Hospital-acquired and ventilator-associated bacterial pneumonia (HABP/VABP) are frequently caused by multidrug-resistant organisms. Patient-centered endpoints in clinical trials are needed to develop new antibiotics for HABP/VABP. Desirability ... Full text Link to item Cite

Epigenetic and transcriptional responses in circulating leukocytes are associated with future decompensation during SARS-CoV-2 infection.

Journal Article iScience · January 19, 2024 To elucidate host response elements that define impending decompensation during SARS-CoV-2 infection, we enrolled subjects hospitalized with COVID-19 who were matched for disease severity and comorbidities at the time of admission. We performed combined si ... Full text Link to item Cite

Host-response transcriptional biomarkers accurately discriminate bacterial and viral infections of global relevance.

Journal Article Sci Rep · December 18, 2023 Diagnostic limitations challenge management of clinically indistinguishable acute infectious illness globally. Gene expression classification models show great promise distinguishing causes of fever. We generated transcriptional data for a 294-participant ... Full text Link to item Cite

Peripheral Transcriptomics in Acute and Long-Term Kidney Dysfunction in SARS-CoV2 Infection.

Journal Article medRxiv · October 27, 2023 BACKGROUND: Acute kidney injury (AKI) is common in hospitalized patients with SARS-CoV2 infection despite vaccination and leads to long-term kidney dysfunction. However, peripheral blood molecular signatures in AKI from COVID-19 and their association with ... Full text Link to item Cite

RADx-UP Testing Core: Access to COVID-19 Diagnostics in Community-Engaged Research with Underserved Populations.

Journal Article J Clin Microbiol · August 23, 2023 Research on the COVID-19 pandemic revealed a disproportionate burden of COVID-19 infection and death among underserved populations and exposed low rates of SARS-CoV-2 testing in these communities. A landmark National Institutes of Health (NIH) funding init ... Full text Open Access Link to item Cite

Viewing both sides of the coin for infectious disease diagnosis.

Journal Article J Clin Invest · April 17, 2023 Optimal management of lower respiratory tract infection relies on distinguishing infectious from noninfectious etiologies and identifying the microbiologic cause if applicable. This process is complicated by overlapping clinical symptoms and the colonizing ... Full text Link to item Cite

Efficacy and safety of azithromycin versus placebo to treat lower respiratory tract infections associated with low procalcitonin: a randomised, placebo-controlled, double-blind, non-inferiority trial.

Journal Article Lancet Infect Dis · April 2023 BACKGROUND: Lower respiratory tract infections are frequently treated with antibiotics, despite a viral cause in many cases. It remains unknown whether low procalcitonin concentrations can identify patients with lower respiratory tract infection who are un ... Full text Open Access Link to item Cite

Clinically Adjudicated Reference Standards for Evaluation of Infectious Diseases Diagnostics.

Journal Article Clin Infect Dis · March 4, 2023 Lack of a gold standard can present a challenge for evaluation of diagnostic test accuracy of some infectious diseases tests, particularly when the test's accuracy potentially exceeds that of its predecessors. This approach may measure agreement with an im ... Full text Open Access Link to item Cite

Blood RNA alternative splicing events as diagnostic biomarkers for infectious disease.

Journal Article Cell Rep Methods · February 27, 2023 Assays detecting blood transcriptome changes are studied for infectious disease diagnosis. Blood-based RNA alternative splicing (AS) events, which have not been well characterized in pathogen infection, have potential normalization and assay platform stabi ... Full text Open Access Link to item Cite

Screening tools for predicting mortality of adults with suspected sepsis: an international sepsis cohort validation study.

Journal Article BMJ Open · February 20, 2023 OBJECTIVES: We evaluated the performance of commonly used sepsis screening tools across prospective sepsis cohorts in the USA, Cambodia and Ghana. DESIGN: Prospective cohort studies. SETTING AND PARTICIPANTS: From 2014 to 2021, participants with two or mor ... Full text Open Access Link to item Cite

Murine Host Response to Typical and Atypical Pneumonia

Conference AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE · 2023 Cite

Access to COVID-19 testing by individuals with housing insecurity during the early days of the COVID-19 pandemic in the United States: a scoping review.

Journal Article Front Public Health · 2023 INTRODUCTION: The COVID-19 pandemic focused attention on healthcare disparities and inequities faced by individuals within marginalized and structurally disadvantaged groups in the United States. These individuals bore the heaviest burden across this pande ... Full text Open Access Link to item Cite

Omic approaches to infectious disease testing

Chapter · January 1, 2023 A pathogen-based approach to infectious disease diagnosis has long been the gold standard, despite poor sensitivity, specificity, or long time to result with this method. The host response offers a robust and complementary approach to infectious disease di ... Full text Cite

Multi-objective optimization identifies a specific and interpretable COVID-19 host response signature.

Journal Article Cell Syst · December 21, 2022 The identification of a COVID-19 host response signature in blood can increase the understanding of SARS-CoV-2 pathogenesis and improve diagnostic tools. Applying a multi-objective optimization framework to both massive public and new multi-omics data, we ... Full text Link to item Cite

Host Gene Expression to Predict Sepsis Progression.

Journal Article Crit Care Med · December 1, 2022 OBJECTIVES: Sepsis causes significant mortality. However, most patients who die of sepsis do not present with severe infection, hampering efforts to deliver early, aggressive therapy. It is also known that the host gene expression response to infection pre ... Full text Link to item Cite

Differential chromatin accessibility in peripheral blood mononuclear cells underlies COVID-19 disease severity prior to seroconversion.

Journal Article Sci Rep · July 9, 2022 SARS-CoV-2 infection triggers profound and variable immune responses in human hosts. Chromatin remodeling has been observed in individuals severely ill or convalescing with COVID-19, but chromatin remodeling early in disease prior to anti-spike protein IgG ... Full text Open Access Link to item Cite

SARS-CoV-2 reinfection across a spectrum of immunological states.

Journal Article Health Sci Rep · July 2022 PURPOSE: Several cases of symptomatic reinfection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) after full recovery from a prior episode have been reported. As reinfection has become an increasingly common phenomenon, an improved unders ... Full text Open Access Link to item Cite

Envisioning Future Urinary Tract Infection Diagnostics.

Journal Article Clin Infect Dis · April 9, 2022 Urinary tract infections (UTIs) are among the most common bacterial infections in the United States and are a major driver of antibiotic use, both appropriate and inappropriate, across healthcare settings. Novel UTI diagnostics are a strategy that might en ... Full text Open Access Link to item Cite

Prospective Validation of a Rapid Host Gene Expression Test to Discriminate Bacterial From Viral Respiratory Infection.

Journal Article JAMA Netw Open · April 1, 2022 IMPORTANCE: Bacterial and viral causes of acute respiratory illness (ARI) are difficult to clinically distinguish, resulting in the inappropriate use of antibacterial therapy. The use of a host gene expression-based test that is able to discriminate bacter ... Full text Open Access Link to item Cite

Systematic comparison of published host gene expression signatures for bacterial/viral discrimination.

Journal Article Genome Med · February 21, 2022 BACKGROUND: Measuring host gene expression is a promising diagnostic strategy to discriminate bacterial and viral infections. Multiple signatures of varying size, complexity, and target populations have been described. However, there is little information ... Full text Open Access Link to item Cite

Comparing the Diagnostic Accuracy of Clinician Judgment to a Novel Host Response Diagnostic for Acute Respiratory Illness.

Journal Article Open Forum Infect Dis · December 2021 BACKGROUND: Difficulty discriminating bacterial from viral infections drives antibacterial misuse. Host gene expression tests discriminate bacterial and viral etiologies, but their clinical utility has not been evaluated. METHODS: Host gene expression and ... Full text Open Access Link to item Cite

Discriminating Bacterial and Viral Infection Using a Rapid Host Gene Expression Test.

Journal Article Crit Care Med · October 1, 2021 OBJECTIVES: Host gene expression signatures discriminate bacterial and viral infection but have not been translated to a clinical test platform. This study enrolled an independent cohort of patients to describe and validate a first-in-class host response b ... Full text Open Access Link to item Cite

Assessment of the Feasibility of Using Noninvasive Wearable Biometric Monitoring Sensors to Detect Influenza and the Common Cold Before Symptom Onset.

Journal Article JAMA Netw Open · September 1, 2021 IMPORTANCE: Currently, there are no presymptomatic screening methods to identify individuals infected with a respiratory virus to prevent disease spread and to predict their trajectory for resource allocation. OBJECTIVE: To evaluate the feasibility of usin ... Full text Open Access Link to item Cite

Validation of a Host Gene Expression Test for Bacterial/Viral Discrimination in Immunocompromised Hosts.

Journal Article Clin Infect Dis · August 16, 2021 BACKGROUND: Host gene expression has emerged as a complementary strategy to pathogen detection tests for the discrimination of bacterial and viral infection. The impact of immunocompromise on host-response tests remains unknown. We evaluated a host-respons ... Full text Open Access Link to item Cite

Antibacterial Resistance Leadership Group 2.0: Back to Business.

Journal Article Clin Infect Dis · August 16, 2021 In December 2019, the Antibacterial Resistance Leadership Group (ARLG) was awarded funding for another 7-year cycle to support a clinical research network on antibacterial resistance. ARLG 2.0 has 3 overarching research priorities: infections caused by ant ... Full text Open Access Link to item Cite

Heparin-based blood purification attenuates organ injury in baboons with Streptococcus pneumoniae pneumonia.

Journal Article Am J Physiol Lung Cell Mol Physiol · August 1, 2021 Bacterial pneumonia is a major cause of morbidity and mortality worldwide despite the use of antibiotics, and novel therapies are urgently needed. Building on previous work, we aimed to 1) develop a baboon model of severe pneumococcal pneumonia and sepsis ... Full text Link to item Cite

The host transcriptional response to Candidemia is dominated by neutrophil activation and heme biosynthesis and supports novel diagnostic approaches.

Journal Article Genome Med · July 5, 2021 BACKGROUND: Candidemia is one of the most common nosocomial bloodstream infections in the United States, causing significant morbidity and mortality in hospitalized patients, but the breadth of the host response to Candida infections in human patients rema ... Full text Open Access Link to item Cite

Leveraging Existing and Soon-to-Be-Available Novel Diagnostics for Optimizing Outpatient Antibiotic Stewardship in Patients With Respiratory Tract Infections.

Journal Article Clin Infect Dis · June 15, 2021 Respiratory tract infections (RTIs) drive many outpatient encounters and, despite being predominantly viral, are associated with high rates of antibiotic prescriptions. With rising antibacterial resistance, optimization of prescribing of antibiotics in out ... Full text Link to item Cite

Mucosal-associated invariant T cell responses differ by sex in COVID-19.

Journal Article Med · June 11, 2021 BACKGROUND: Sexual dimorphisms in immune responses contribute to coronavirus disease 2019 (COVID-19) outcomes, but the mechanisms governing this disparity remain incompletely understood. METHODS: We carried out sex-balanced sampling of peripheral blood mon ... Full text Open Access Link to item Cite

An atlas connecting shared genetic architecture of human diseases and molecular phenotypes provides insight into COVID-19 susceptibility.

Journal Article Genome Med · May 17, 2021 BACKGROUND: While genome-wide associations studies (GWAS) have successfully elucidated the genetic architecture of complex human traits and diseases, understanding mechanisms that lead from genetic variation to pathophysiology remains an important challeng ... Full text Open Access Link to item Cite

Sepsis Subclasses: A Framework for Development and Interpretation.

Journal Article Crit Care Med · May 1, 2021 Sepsis is defined as a dysregulated host response to infection that leads to life-threatening acute organ dysfunction. It afflicts approximately 50 million people worldwide annually and is often deadly, even when evidence-based guidelines are applied promp ... Full text Open Access Link to item Cite

A blood-based host gene expression assay for early detection of respiratory viral infection: an index-cluster prospective cohort study.

Journal Article Lancet Infect Dis · March 2021 BACKGROUND: Early and accurate identification of individuals with viral infections is crucial for clinical management and public health interventions. We aimed to assess the ability of transcriptomic biomarkers to identify naturally acquired respiratory vi ... Full text Open Access Link to item Cite

Dysregulated transcriptional responses to SARS-CoV-2 in the periphery.

Journal Article Nat Commun · February 17, 2021 SARS-CoV-2 infection has been shown to trigger a wide spectrum of immune responses and clinical manifestations in human hosts. Here, we sought to elucidate novel aspects of the host response to SARS-CoV-2 infection through RNA sequencing of peripheral bloo ... Full text Open Access Link to item Cite

The Host Response to Viral Infections Reveals Common and Virus-Specific Signatures in the Peripheral Blood.

Journal Article Front Immunol · 2021 Viruses cause a wide spectrum of clinical disease, the majority being acute respiratory infections (ARI). In most cases, ARI symptoms are similar for different viruses although severity can be variable. The objective of this study was to understand the sha ... Full text Open Access Link to item Cite

A comparison of host response strategies to distinguish bacterial and viral infection.

Journal Article PLoS One · 2021 OBJECTIVES: Compare three host response strategies to distinguish bacterial and viral etiologies of acute respiratory illness (ARI). METHODS: In this observational cohort study, procalcitonin, a 3-protein panel (CRP, IP-10, TRAIL), and a host gene expressi ... Full text Open Access Link to item Cite

Simultaneous Evaluation of Diagnostic Assays for Pharyngeal and Rectal Neisseria gonorrhoeae and Chlamydia trachomatis Using a Master Protocol.

Journal Article Clin Infect Dis · December 3, 2020 BACKGROUND: Pharyngeal and rectal Neisseria gonorrhoeae and Chlamydia trachomatis play important roles in infection and antibacterial resistance transmission, but no US Food and Drug Administration (FDA)-cleared assays for detection at these sites existed ... Full text Open Access Link to item Cite

Average Weighted Accuracy: Pragmatic Analysis for a Rapid Diagnostics in Categorizing Acute Lung Infections (RADICAL) Study.

Journal Article Clin Infect Dis · June 10, 2020 Patient management relies on diagnostic information to identify appropriate treatment. Standard evaluations of diagnostic tests consist of estimating sensitivity, specificity, positive/negative predictive values, likelihood ratios, and accuracy. Although u ... Full text Open Access Link to item Cite

Analytical Evaluation of the Abbott RealTime CT/NG Assay for Detection of Chlamydia trachomatis and Neisseria gonorrhoeae in Rectal and Pharyngeal Swabs.

Journal Article J Mol Diagn · June 2020 Chlamydia trachomatis and Neisseria gonorrhoeae infections in the rectum and pharynx are important extragenital reservoirs of infection. Few assays approved by the US Food and Drug Administration are commercially available to diagnose pharyngeal or rectal ... Full text Open Access Link to item Cite

Previously Derived Host Gene Expression Classifiers Identify Bacterial and Viral Etiologies of Acute Febrile Respiratory Illness in a South Asian Population.

Journal Article Open Forum Infect Dis · June 2020 BACKGROUND: Pathogen-based diagnostics for acute respiratory infection (ARI) have limited ability to detect etiology of illness. We previously showed that peripheral blood-based host gene expression classifiers accurately identify bacterial and viral ARI i ... Full text Open Access Link to item Cite

Serum Procalcitonin Trends in Hospital-Acquired Infections: A Prospective Multi-Center Observational Cohort

Conference AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE · 2020 Cite

Rapid, Sample-to-Answer Host Gene Expression Test to Diagnose Viral Infection.

Journal Article Open Forum Infect Dis · November 2019 OBJECTIVE: Distinguishing bacterial, viral, or other etiologies of acute illness is diagnostically challenging with significant implications for appropriate antimicrobial use. Host gene expression offers a promising approach, although no clinically useful ... Full text Open Access Link to item Cite

Direct-from-blood RNA sequencing identifies the cause of post-bronchoscopy fever.

Journal Article BMC Infect Dis · October 28, 2019 BACKGROUND: Antibiotic resistance is rising at disturbing rates and contributes to the deaths of millions of people yearly. Antibiotic resistant infections disproportionately affect those with immunocompromising conditions, chronic colonization, and freque ... Full text Open Access Link to item Cite

Host-Based Diagnostics for Acute Respiratory Infections.

Journal Article Clin Ther · October 2019 PURPOSE: The inappropriate use of antimicrobials, especially in acute respiratory infections (ARIs), is largely driven by difficulty distinguishing bacterial, viral, and noninfectious etiologies of illness. A new frontier in infectious disease diagnostics ... Full text Open Access Link to item Cite

Validation of a host response test to distinguish bacterial and viral respiratory infection.

Journal Article EBioMedicine · October 2019 BACKGROUND: Distinguishing bacterial and viral respiratory infections is challenging. Novel diagnostics based on differential host gene expression patterns are promising but have not been translated to a clinical platform nor extensively tested. Here, we v ... Full text Open Access Link to item Cite

Biologic Differences Between Type 1 and 2 Lupus

Conference ARTHRITIS & RHEUMATOLOGY · October 1, 2019 Link to item Cite

A Decade On: Systematic Review of ClinicalTrials.gov Infectious Disease Trials, 2007-2017.

Journal Article Open Forum Infect Dis · June 2019 BACKGROUND: Registration of interventional trials of Food and Drug Administration-regulated drug and biological products and devices became a legal requirement in 2007; the vast majority of these trials are registered in ClinicalTrials.gov. An analysis of ... Full text Open Access Link to item Cite

Pilot study of myocardial ischemia-induced metabolomic changes in emergency department patients undergoing stress testing.

Journal Article PLoS One · 2019 BACKGROUND: The heart is a metabolically active organ, and plasma acylcarnitines are associated with long-term risk for myocardial infarction. We hypothesized that myocardial ischemia from cardiac stress testing will produce dynamic changes in acylcarnitin ... Full text Open Access Link to item Cite

A host gene expression approach for identifying triggers of asthma exacerbations.

Journal Article PLoS One · 2019 RATIONALE: Asthma exacerbations often occur due to infectious triggers, but determining whether infection is present and whether it is bacterial or viral remains clinically challenging. A diagnostic strategy that clarifies these uncertainties could enable ... Full text Open Access Link to item Cite

HOST GENES ARE DIFFERENTIALLY EXPRESSED IN DENGUE COMPARED TO INFLUENZA INFECTIONS

Conference AMERICAN JOURNAL OF TROPICAL MEDICINE AND HYGIENE · January 1, 2019 Link to item Cite

MOLECULAR PROFILING OF SEPSIS PATIENTS FROM AUSTERE ENVIRONMENTS USING TOPOLOGICAL DATA ANALYSIS

Conference AMERICAN JOURNAL OF TROPICAL MEDICINE AND HYGIENE · January 1, 2019 Link to item Cite

Overview: Genomic and precision medicine for infectious and inflammatory disease

Chapter · January 1, 2019 A century of advances in infectious disease diagnosis, treatment, and prevention changed the face of medicine and global health. However, challenges persist including high mortality from sepsis, emerging antimicrobial resistance, and globalization that inc ... Full text Cite

Genomic and precision medicine: Infectious and inflammatory disease

Book · January 1, 2019 Genomic and Precision Medicine: Infectious and Inflammatory Disease, Third Edition, provides current clinical solutions on the application of genome discovery on a broad spectrum of disease categories in IMD - including asthma, obesity and multiple scleros ... Full text Cite

A crowdsourced analysis to identify ab initio molecular signatures predictive of susceptibility to viral infection.

Journal Article Nat Commun · October 24, 2018 The response to respiratory viruses varies substantially between individuals, and there are currently no known molecular predictors from the early stages of infection. Here we conduct a community-based analysis to determine whether pre- or early post-expos ... Full text Open Access Link to item Cite

Pediatric Antibacterial and Antifungal Trials From 2007 to 2017.

Journal Article Pediatrics · September 2018 BACKGROUND AND OBJECTIVES: The impact of the Best Pharmaceuticals for Children Act (BPCA) and the Pediatric Research Equity Act (PREA) on pediatric antibacterial or antifungal drug trials is unknown. Our objective was to identify and characterize trials co ... Full text Open Access Link to item Cite

The host response as a tool for infectious disease diagnosis and management.

Journal Article Expert Rev Mol Diagn · August 2018 A century of advances in infectious disease diagnosis and treatment changed the face of medicine. However, challenges continue to develop including multi-drug resistance, globalization that increases pandemic risks, and high mortality from severe infection ... Full text Open Access Link to item Cite

Future Research Directions in Pneumonia. NHLBI Working Group Report.

Conference Am J Respir Crit Care Med · July 15, 2018 Pneumonia is a complex pulmonary disease in need of new clinical approaches. Although triggered by a pathogen, pneumonia often results from dysregulations of host defense that likely precede infection. The coordinated activities of immune resistance and ti ... Full text Link to item Cite

Unsupervised Analysis of Transcriptomics in Bacterial Sepsis Across Multiple Datasets Reveals Three Robust Clusters.

Journal Article Crit Care Med · June 2018 OBJECTIVES: To find and validate generalizable sepsis subtypes using data-driven clustering. DESIGN: We used advanced informatics techniques to pool data from 14 bacterial sepsis transcriptomic datasets from eight different countries (n = 700). SETTING: Re ... Full text Link to item Cite

A community approach to mortality prediction in sepsis via gene expression analysis.

Journal Article Nat Commun · February 15, 2018 Improved risk stratification and prognosis prediction in sepsis is a critical unmet need. Clinical severity scores and available assays such as blood lactate reflect global illness severity with suboptimal performance, and do not specifically reveal the un ... Full text Open Access Link to item Cite

New Molecular Diagnostic Approaches to Bacterial Infections and Antibacterial Resistance.

Journal Article Annu Rev Med · January 29, 2018 Recent advances in the field of infectious disease diagnostics have given rise to a number of host- and pathogen-centered diagnostic approaches. Most diagnostic approaches in contemporary infectious disease focus on pathogen detection and characterization. ... Full text Link to item Cite

Evaluating the discriminating capacity of cell death (apoptotic) biomarkers in sepsis.

Journal Article J Intensive Care · 2018 BACKGROUND: Sepsis biomarker panels that provide diagnostic and prognostic discrimination in sepsis patients would be transformative to patient care. We assessed the mortality prediction and diagnostic discriminatory accuracy of two biomarkers reflective o ... Full text Open Access Link to item Cite

A miRNA Host Response Signature Accurately Discriminates Acute Respiratory Infection Etiologies.

Journal Article Front Microbiol · 2018 Background: Acute respiratory infections (ARIs) are the leading indication for antibacterial prescriptions despite a viral etiology in the majority of cases. The lack of available diagnostics to discriminate viral and bacterial etiologies contributes to th ... Full text Open Access Link to item Cite

Transcriptomic Techniques in Diagnostic Microbiology

Chapter · January 1, 2018 Traditional pathogen detection methods have long been the standard diagnostic approach to infectious diseases. While undoubtedly useful, pathogen detection is hampered by low sensitivity and specificity or prolonged turnaround times. A novel concept that a ... Full text Cite

Advancing Diagnostics to Address Antibacterial Resistance: The Diagnostics and Devices Committee of the Antibacterial Resistance Leadership Group.

Journal Article Clin Infect Dis · March 15, 2017 Diagnostics are a cornerstone of the practice of infectious diseases. However, various limitations frequently lead to unmet clinical needs. In most other domains, diagnostics focus on narrowly defined questions, provide readily interpretable answers, and u ... Full text Link to item Cite

Nasopharyngeal Protein Biomarkers of Acute Respiratory Virus Infection.

Journal Article EBioMedicine · March 2017 Infection of respiratory mucosa with viral pathogens triggers complex immunologic events in the affected host. We sought to characterize this response through proteomic analysis of nasopharyngeal lavage in human subjects experimentally challenged with infl ... Full text Open Access Link to item Cite

Human genetic and metabolite variation reveals that methylthioadenosine is a prognostic biomarker and an inflammatory regulator in sepsis.

Journal Article Sci Adv · March 2017 Sepsis is a deleterious inflammatory response to infection with high mortality. Reliable sepsis biomarkers could improve diagnosis, prognosis, and treatment. Integration of human genetics, patient metabolite and cytokine measurements, and testing in a mous ... Full text Open Access Link to item Cite

Host-Based Peripheral Blood Gene Expression Analysis for Diagnosis of Infectious Diseases.

Journal Article J Clin Microbiol · February 2017 Emerging pandemic infectious threats, inappropriate antibacterial use contributing to multidrug resistance, and increased morbidity and mortality from diagnostic delays all contribute to a need for improved diagnostics in the field of infectious diseases. ... Full text Link to item Cite

MASTERMIND: Bringing Microbial Diagnostics to the Clinic.

Journal Article Clin Infect Dis · February 1, 2017 New diagnostics are urgently needed to address emerging antimicrobial resistance. The Antibacterial Resistance Leadership Group proposes a strategy called MASTERMIND (Master Protocol for Evaluating Multiple Infection Diagnostics) for advancement of infecti ... Full text Open Access Link to item Cite

Candidate genes on murine chromosome 8 are associated with susceptibility to Staphylococcus aureus infection in mice and are involved with Staphylococcus aureus septicemia in humans.

Journal Article PLoS One · 2017 We previously showed that chromosome 8 of A/J mice was associated with susceptibility to S. aureus infection. However, the specific genes responsible for this susceptibility are unknown. Chromosome substitution strain 8 (CSS8) mice, which have chromosome 8 ... Full text Open Access Link to item Cite

Federated Gene Expression Analysis Of Mortality Prediction In Sepsis

Conference AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE · January 1, 2017 Link to item Cite

Systematic Molecular Phenotyping: A Path Toward Precision Emergency Medicine?

Journal Article Acad Emerg Med · October 2016 Precision medicine is an emerging approach to disease treatment and prevention that considers variability in patient genes, environment, and lifestyle. However, little has been written about how such research impacts emergency care. Recent advances in anal ... Full text Open Access Link to item Cite

Transcriptomic Analysis of the Host Response and Innate Resilience to Enterotoxigenic Escherichia coli Infection in Humans.

Journal Article J Infect Dis · May 1, 2016 BACKGROUND: Enterotoxigenic Escherichia coli (ETEC) is a globally prevalent cause of diarrhea. Though usually self-limited, it can be severe and debilitating. Little is known about the host transcriptional response to infection. We report the first gene ex ... Full text Open Access Link to item Cite

Differential evolution of peripheral cytokine levels in symptomatic and asymptomatic responses to experimental influenza virus challenge.

Journal Article Clin Exp Immunol · March 2016 Exposure to influenza virus triggers a complex cascade of events in the human host. In order to understand more clearly the evolution of this intricate response over time, human volunteers were inoculated with influenza A/Wisconsin/67/2005 (H3N2), and then ... Full text Link to item Cite

Potential Cost-effectiveness of Early Identification of Hospital-acquired Infection in Critically Ill Patients.

Journal Article Ann Am Thorac Soc · March 2016 RATIONALE: Limitations in methods for the rapid diagnosis of hospital-acquired infections often delay initiation of effective antimicrobial therapy. New diagnostic approaches offer potential clinical and cost-related improvements in the management of these ... Full text Open Access Link to item Cite

Host gene expression classifiers diagnose acute respiratory illness etiology.

Journal Article Sci Transl Med · January 20, 2016 Acute respiratory infections caused by bacterial or viral pathogens are among the most common reasons for seeking medical care. Despite improvements in pathogen-based diagnostics, most patients receive inappropriate antibiotics. Host response biomarkers of ... Full text Open Access Link to item Cite

A Genomic Signature of Influenza Infection Shows Potential for Presymptomatic Detection, Guiding Early Therapy, and Monitoring Clinical Responses.

Journal Article Open Forum Infect Dis · January 2016 Early, presymptomatic intervention with oseltamivir (corresponding to the onset of a published host-based genomic signature of influenza infection) resulted in decreased overall influenza symptoms (aggregate symptom scores of 23.5 vs 46.3), more rapid reso ... Full text Open Access Link to item Cite

Respiratory Tract Infection Clinical Trials from 2007 to 2012. A Systematic Review of ClinicalTrials.gov.

Journal Article Ann Am Thorac Soc · December 2015 RATIONALE: Respiratory tract infections are highly prevalent and variable, and confer considerable morbidity and mortality. There is a growing need for new treatments for such infections, particularly in the setting of worsening antibacterial resistance. O ... Full text Link to item Cite

Renal systems biology of patients with systemic inflammatory response syndrome.

Journal Article Kidney Int · October 2015 A systems biology approach was used to comprehensively examine the impact of renal disease and hemodialysis (HD) on patient response during critical illness. To achieve this, we examined the metabolome, proteome, and transcriptome of 150 patients with crit ... Full text Open Access Link to item Cite

Beauty is only skin deep

Journal Article Science Translational Medicine · April 8, 2015 Full text Cite

Seq and the city

Journal Article Science Translational Medicine · February 25, 2015 Full text Cite

Fear as a cardiovascular risk factor

Journal Article Science Translational Medicine · January 1, 2015 Full text Cite

Non-Gaussian discriminative factor models via the max-margin rank-likelihood

Journal Article 32nd International Conference on Machine Learning, ICML 2015 · January 1, 2015 We consider the problem of discriminative factor analysis for data that are in general non-Gaussian. A Bayesian model based on the ranks of the data is proposed. We first introduce a new max-margin version of the rank-likelihood. A discriminative factor mo ... Open Access Cite

What was old is new again: using the host response to diagnose infectious disease.

Journal Article Expert Rev Mol Diagn · 2015 A century of advances in infectious disease diagnosis and treatment changed the face of medicine. However, challenges continue to develop including multi-drug resistance, globalization that increases pandemic risks and high mortality from severe infections ... Full text Link to item Cite

Host-based diagnostics for detection and prognosis of infectious diseases

Journal Article · January 1, 2015 The field of infectious diseases is witnessing the rapid evolution of molecular diagnostics, mostly focused on pathogen detection. However, targeting the host response for diagnostic and prognostic purposes has been described as a paradigm shift (Ramilo & ... Full text Cite

Crowdsourcing disease prognosis

Journal Article Science Translational Medicine · November 26, 2014 Full text Cite

Sequence-specific antibiotics

Journal Article Science Translational Medicine · October 22, 2014 Full text Cite

The current epidemiology and clinical decisions surrounding acute respiratory infections.

Journal Article Trends Mol Med · October 2014 Acute respiratory infection (ARI) is a common diagnosis in outpatient and emergent care settings. Currently available diagnostics are limited, creating uncertainty in the use of antibacterial, antiviral, or supportive care. Up to 72% of ambulatory care pat ... Full text Link to item Cite

The microbial origins of obesity

Journal Article Science Translational Medicine · September 3, 2014 Full text Cite

Integrative "omic" analysis of experimental bacteremia identifies a metabolic signature that distinguishes human sepsis from systemic inflammatory response syndromes.

Journal Article Am J Respir Crit Care Med · August 15, 2014 RATIONALE: Sepsis is a leading cause of morbidity and mortality. Currently, early diagnosis and the progression of the disease are difficult to make. The integration of metabolomic and transcriptomic data in a primate model of sepsis may provide a novel mo ... Full text Link to item Cite

Cardiovascular genetics: All systems point to TREML4

Journal Article Science Translational Medicine · July 23, 2014 Full text Cite

Antimicrobial drug resistance in all four corners of the earth

Journal Article Science Translational Medicine · June 11, 2014 Full text Cite

Dusp3 and Psme3 are associated with murine susceptibility to Staphylococcus aureus infection and human sepsis.

Journal Article PLoS Pathog · June 2014 Using A/J mice, which are susceptible to Staphylococcus aureus, we sought to identify genetic determinants of susceptibility to S. aureus, and evaluate their function with regard to S. aureus infection. One QTL region on chromosome 11 containing 422 genes ... Full text Open Access Link to item Cite

The sum of one's parts? What our microbiomes say about us

Journal Article Science Translational Medicine · April 30, 2014 Full text Cite

A cross-sectional analysis of HIV and hepatitis C clinical trials 2007 to 2010: the relationship between industry sponsorship and randomized study design.

Journal Article Trials · January 22, 2014 Featured Publication BACKGROUND: The proportion of clinical research sponsored by industry will likely continue to expand as federal funds for academic research decreases, particularly in the fields of HIV/AIDS and hepatitis C (HCV). While HIV and HCV continue to burden the US ... Full text Open Access Link to item Cite

An integrated transcriptome and expressed variant analysis of sepsis survival and death.

Journal Article Genome Med · 2014 BACKGROUND: Sepsis, a leading cause of morbidity and mortality, is not a homogeneous disease but rather a syndrome encompassing many heterogeneous pathophysiologies. Patient factors including genetics predispose to poor outcomes, though current clinical ch ... Full text Open Access Link to item Cite

Integrative Analysis Of The Metabolome, Proteome, And Transcriptome In Systemic Inflammatory Response Syndrome

Journal Article AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE · January 1, 2014 Link to item Cite

Plasma microRNA signature as a noninvasive biomarker for acute graft-versus-host disease.

Journal Article Blood · November 7, 2013 Featured Publication Acute graft-versus-host disease (aGVHD) is the leading cause of morbidity and mortality after allogeneic hematopoietic cell transplantation (HCT). Approximately 35% to 50% of HCT recipients develop aGVHD; however, there are no validated diagnostic and pred ... Full text Link to item Cite

A host-based RT-PCR gene expression signature to identify acute respiratory viral infection.

Journal Article Sci Transl Med · September 18, 2013 Featured Publication Improved ways to diagnose acute respiratory viral infections could decrease inappropriate antibacterial use and serve as a vital triage mechanism in the event of a potential viral pandemic. Measurement of the host response to infection is an alternative to ... Full text Link to item Cite

An integrated clinico-metabolomic model improves prediction of death in sepsis.

Journal Article Sci Transl Med · July 24, 2013 Featured Publication Sepsis is a common cause of death, but outcomes in individual patients are difficult to predict. Elucidating the molecular processes that differ between sepsis patients who survive and those who die may permit more appropriate treatments to be deployed. We ... Full text Link to item Cite

Gene expression-based classifiers identify Staphylococcus aureus infection in mice and humans.

Journal Article PLoS One · 2013 Featured Publication Staphylococcus aureus causes a spectrum of human infection. Diagnostic delays and uncertainty lead to treatment delays and inappropriate antibiotic use. A growing literature suggests the host's inflammatory response to the pathogen represents a potential t ... Full text Open Access Link to item Cite

The state of infectious diseases clinical trials: a systematic review of ClinicalTrials.gov.

Journal Article PLoS One · 2013 Featured Publication BACKGROUND: There is a paucity of clinical trials informing specific questions faced by infectious diseases (ID) specialists. The ClinicalTrials.gov registry offers an opportunity to evaluate the ID clinical trials portfolio. METHODS: We examined 40,970 in ... Full text Open Access Link to item Cite

Discriminative value of inflammatory biomarkers for suspected sepsis.

Journal Article J Emerg Med · July 2012 Featured Publication BACKGROUND: Circulating biomarkers can facilitate sepsis diagnosis, enabling early management and improved outcomes. Procalcitonin (PCT) has been suggested to have superior diagnostic utility compared to other biomarkers. STUDY OBJECTIVES: To define the di ... Full text Link to item Cite

An Infection Control Program for a 2009 influenza A H1N1 outbreak in a university-based summer camp.

Journal Article J Am Coll Health · 2011 Featured Publication OBJECTIVES: Describe two 2009-H1N1 influenza outbreaks in university-based summer camps and the implementation of an infection control program. PARTICIPANTS: 7,906 campers across 73 residential camps from May 21-August 2, 2009. METHODS: Influenza-like-illn ... Full text Link to item Cite

Life-threatening asymptomatic incidentaloma: a case report of idiopathic CD4 lymphocytopenia and opportunistic infections.

Journal Article Am J Med Sci · August 2010 Featured Publication Incidental lung nodules can be due to a variety of etiologies. Management is guided by the most likely or urgent pathology, which is frequently malignancy in an elderly smoker. We present the case of a 62-year-old, long-time smoker, with an incidental lung ... Full text Link to item Cite

Disease progression in hemodynamically stable patients presenting to the emergency department with sepsis.

Journal Article Acad Emerg Med · April 2010 Featured Publication BACKGROUND: Aggressive diagnosis and treatment of patients presenting to the emergency department (ED) with septic shock has been shown to reduce mortality. To enhance the ability to intervene in patients with lesser illness severity, a better understandin ... Full text Link to item Cite

Clinical presentation and response to treatment of novel influenza A H1N1 in a university-based summer camp population.

Journal Article J Clin Virol · March 2010 Featured Publication BACKGROUND: Little is known about the clinical presentation and course of novel H1N1 influenza in summer camps. OBJECTIVES: To describe the clinical course and evaluate the effect of influenza treatment in a summer camp population. STUDY DESIGN: Two large ... Full text Link to item Cite

Multiplex PCR to diagnose bloodstream infections in patients admitted from the emergency department with sepsis.

Journal Article J Clin Microbiol · January 2010 Featured Publication Sepsis is caused by a heterogeneous group of infectious etiologies. Early diagnosis and the provision of appropriate antimicrobial therapy correlate with positive clinical outcomes. Current microbiological techniques are limited in their diagnostic capacit ... Full text Link to item Cite

Sepsis redefined: the search for surrogate markers.

Journal Article Int J Antimicrob Agents · 2009 Featured Publication Sepsis is a common and severe medical condition with substantial associated morbidity, mortality and cost. Furthermore, the incidence of sepsis has been rising annually over the past three decades, and morbidity and mortality remain high. The management of ... Full text Link to item Cite

DNA-based immunotherapy to treat atopic disease.

Journal Article Ann Allergy Asthma Immunol · November 2005 OBJECTIVE: To review the current literature regarding DNA-based immunotherapy with respect to signaling mechanisms, cytokine profiles, and the applicability and success of this strategy to treat allergic disease. DATA SOURCES: English-language articles wer ... Full text Link to item Cite

LIM homeobox gene-dependent expression of biogenic amine receptors in restricted regions of the C. elegans nervous system.

Journal Article Dev Biol · November 1, 2003 Biogenic amines regulate a variety of behaviors. Their functions are predominantly mediated through G-protein-coupled 7-transmembrane domain receptors (GPCR), 16 of which are predicted to exist in the genome sequence of the nematode Caenorhabditis elegans. ... Full text Link to item Cite

Functional mapping of neurons that control locomotory behavior in Caenorhabditis elegans.

Journal Article J Neurobiol · August 2003 One approach to understanding behavior is to define the cellular components of neuronal circuits that control behavior. In the nematode Caenorhabditis elegans, neuronal circuits have been delineated based on patterns of synaptic connectivity derived from u ... Full text Link to item Cite

A regulatory cascade of three homeobox genes, ceh-10, ttx-3 and ceh-23, controls cell fate specification of a defined interneuron class in C. elegans.

Journal Article Development · June 2001 The development of the nervous system requires the coordinated activity of a variety of regulatory factors that define the individual properties of specific neuronal subtypes. We report a regulatory cascade composed of three homeodomain proteins that act t ... Full text Link to item Cite

Curing Saccharomyces cerevisiae of the 2 micron plasmid by targeted DNA damage.

Journal Article Yeast · June 30, 1998 Powerful mutagenic screens of yeast Saccharomyces cerevisiae have recently been developed which require strains that lack the endogenous 2 micron plasmid (Burns et al., 1994). Here, we describe a simple and reliable method for curing yeast of the highly st ... Full text Link to item Cite