Digital Commons Network^™

Zika Virus-Like Particle (Vlp) Based Vaccine, Héléne Boigard, Alexandra Alimova, George R. Martin, Al Katz, Paul Gottlieb, Jose M. Galarza

Publications and Research

The newly emerged mosquito-borne Zika virus poses a major public challenge due to its ability to cause significant birth defects and neurological disorders. The impact of sexual transmission is unclear but raises further concerns about virus dissemination. No specific treatment or vaccine is currently available, thus the development of a safe and effective vaccine is paramount. Here we describe a novel strategy to assemble Zika virus-like particles (VLPs) by co-expressing the structural (CprME) and non-structural (NS2B/NS3) proteins, and demonstrate their effectiveness as vaccines. VLPs are produced in a suspension culture of mammalian cells and self-assembled into particles closely resembling Zika …

Worldwide Use Of Triclosan: Can Dentistry Do Without This Antimicrobial?, Diana V. Macri

Publications and Research

No abstract provided.

Rseqrep: Rna-Seq Reports, An Open-Source Cloud-Enabled Framework For Reproducible Rna-Seq Data Processing, Analysis, And Result Reporting, Travis L. Jensen, Michael Frasketi, Kevin Conway, Leigh Villarroel, Heather Hill, Konstantinos Krampis, Johannes B. Goll

Publications and Research

RNA-Seq is increasingly being used to measure human RNA expression on a genome-wide scale. Expression profiles can be interrogated to identify and functionally characterize treatment-responsive genes. Ultimately, such controlled studies promise to reveal insights into molecular mechanisms of treatment effects, identify biomarkers, and realize personalized medicine. RNA-Seq Reports (RSEQREP) is a new open-source cloud-enabled framework that allows users to execute start-to-end gene-level RNA-Seq analysis on a preconfigured RSEQREP Amazon Virtual Machine Image (AMI) hosted by AWS or on their own Ubuntu Linux machine. The framework works with unstranded, stranded, and paired-end sequence FASTQ files stored locally, on Amazon Simple Storage …

Demographic Transition And The Dynamics Of Measles In Six Provinces In China: A Modeling Study, Sheng Li, Chao Ma, Lixin Hao, Qiru Su, Zhijie An, Fubao Ma, Shuyun Xie, Aiqiang Xu, Yangyang Zhang, Zhengrong Ding, Hui Li, Lisa Cairns, Huaqing Wang, Huiming Luo, Ning Wang, Li Li, Matthew J. Ferrari

Publications and Research

Background Industrialization and demographic transition generate nonstationary dynamics in human populations that can affect the transmission and persistence of infectious diseases. Decades of increasing vaccination and development have led to dramatic declines in the global burden of measles, but the virus remains persistent in much of the world. Here we show that a combination of demographic transition, as a result of declining birth rates, and reduced measles prevalence, due to improved vaccination, has shifted the age distribution of susceptibility to measles throughout China.

Methods and findings We fit a novel time-varying catalytic model to three decades of age-specific measles case …

How History As Mystery Reveals Historical Thinking: A Look At Two Accounts Of Finding Typhoid Mary, Myra Zarnowski, Susan Turkel

Publications and Research

While the words clue, evidence, and detective might not be the first words you associate with history, the idea of history as a mystery to be solved by historian-detectives has a substantial and lively past. That is because the analogy of a historian to a detective solving a mystery is a strong one. Both historians and detectives try to answer the same question: What happened? Both work with evidence from the past to create a plausible narrative using only fragments left behind. Both engage in inferencing as a means of learning from evidence. Both are problem solvers.

In this article, …

Developing Local Health Policy: Profiling Needs And Opportunities In The Municipality Of Quito, Ecuador, Maria Isabel Roldós, Claudia Hopenhyan, Fernando Sacoto, Kathy Bustamante

Publications and Research

We describe the steps taken and analysis applied in developing a local health policy agenda for the city of Quito, in Ecuador. In 2014, the Health Commissioner’s Office of the Municipality of Quito analyzed the city’s epidemiological health profiles, social determinants of health, the legal authority of the Municipality, and relevant literature to understand the city’s health burden and develop a Ten-Year Health Plan (2015–2025). Results revealed that Quito’s population suffered from noncommunicable chronic diseases (diabetes and hypertension) and identified the primary risk factors (poor nutrition, physical inactivity, and resulting overweight or obesity). Other common conditions included respiratory diseases, mental …

Hepatitis C Serosorting Among People Who Inject Drugs In Rural Puerto Rico, Ian Duncan, Ric Curtis, Juan Carlos Reyes, Roberto Abadie, Bilal Khan, Kirk Dombrowski

Publications and Research

Due to the high cost of treatment, preventative measures to limit Hepatitis C (HCV) transmission among people who inject drugs (PWID) are encouraged by many public health officials. A key one of these is serosorting, where PWID select risk partners based on concordant HCV status. Research on the general U.S. population bySmith et al. (2013) found that knowledge of one's own HCV status facilitated serosorting behaviors among PWID, such that respondents with knowledge of their own status were more likely to ask potential partners about their status prior to sharing risk. Our objective was to see if this held true …

Characteristics Of Hiv-Infected Children At Enrollment Into Care And At Antiretroviral Therapy Initiation In Central Africa, Adebola Adedimeji, Andrew Edmonds, Donald Hoover, Qiuhu Shi, Jean D'Amour Sinayobye, Martin Nduwinmana, Patricia Lelo, Denis Nash, Kathryn Anastos, Marcel Yotebieng

Publications and Research

Background Despite the World Health Organization (WHO) regularly updating guidelines to recommend earlier initiation of antiretroviral therapy (ART) in children, timely enrollment into care and initiation of ART in sub-Saharan Africa in children lags behind that of adults. The impact of implementing increasingly less restrictive ART guidelines on ART initiation in Central Africa has not been described.

Materials and Methods Data are from the Central Africa International Epidemiologic Databases to Evaluate AIDS (IeDEA) pediatric cohort of 3,426 children (0±15 years) entering HIV care at 15 sites in Burundi, DRC, and Rwanda. Measures include CD4 count, WHO clinical stage, age, and …

A Cost-Effectiveness Study Of The Quadrivalent Hpv6/11/16/18 Vaccination In A Two-Dose Scheme In Girls Of 9-11 Years Old Compared To Bivalent Hpv 16/18 Vaccination In Ecuador And Challenges For Public Health And Screening, Maria-Isabel Roldos, Isabel Espinosa, Amit Kulkarni, Matthew Pillsbury, Andrew Pavelyev, Homero A. Monsanto, Diego Guarin, Miguel Cashat-Cruz

Publications and Research

Abstract

Aims: Assess the incremental cost-effectiveness of the quadrivalent HPV6/11/16/18 vaccination as administered in a two-dose scheme to girls between 9 and 11 years old, as compared to the bivalent HPV 16/18 vaccination administered in Ecuador, and to estimate the cost-saving of preventing GW while preventing cervical cancer with both vaccines.

Study Design: We used a previously developed transmission dynamic mathematical model to evaluate the impact of routine vaccination of 9-11 year-old females. The model assumed coverage of 90% for two doses of HPV6/11/16/18 vaccine at international price rates versus HPV16/18 vaccine and costs for genital warts treatment. Other simulation …

All-Cause Mortality In Hiv-Positive Adults Starting Combination Antiretroviral Therapy: Correcting For Loss To Follow-Up, Nanina Anderegg, Leigh F. Johnson, Elizabeth Zaniewski, Keri N. Althoff, Eric Balestre, Matthew Law, Denis Nash, Bryan E. Shepherd, Constantin T. Yiannoutsos, Matthias Egger

Publications and Research

Objective: To estimate mortality in HIV-positive patients starting combination antiretroviral therapy (ART) and to discuss different approaches to calculating correction factors to account for loss to follow-up.

Methods: A total of 222 096 adult HIV-positive patients who started ART 2009–2014 in clinics participating in the International epidemiology Databases to Evaluate AIDS collaboration in 43 countries in sub-Saharan Africa, Asia Pacific, Latin America, and North America were included. To allow for underascertainment of deaths due to loss to follow-up, two correction factors (one for the period 0–6 months on ART and one for later periods) or 168 correction factors (combinations of …

Predicting Initiator And Near Repeat Events In Spatiotemporal Crime Patterns: An Analysis Of Residential Burglary And Motor Vehicle Theft, Eric L. Piza, Jeremy G. Carter

Publications and Research

Near repeat analysis has been increasingly used to measure the spatiotemporal clustering of crime in contemporary criminology. Despite its predictive capacity, the typically short time frame of near repeat crime patterns can negatively affect the crime prevention utility of near repeat analysis. Thus, recent research has argued for a greater understanding of the types of places that are most likely to generate near repeat crime patterns. The current study contributes to the literature through a spatiotemporal analysis of residential burglary and motor vehicle theft in Indianapolis, IN. Near Repeat analyses were followed by multinomial logistic regression models to identify covariates …

The King And The Land: A Geography Of Royal Power In The Biblical World, Stephen C. Russell

Publications and Research

The King and the Land offers an innovative history of space and power in the biblical world. Stephen C. Russell shows how the monarchies in ancient Israel and Judah asserted their power over strategically important spaces such as privately-held lands, religious buildings, collectively-governed towns, and urban water systems. Among the case studies examined are Solomon's use of foreign architecture, David's dedication of land to Yahweh, Jehu's decommissioning of Baal's temple, Absalom's navigation of the collective politics of Levantine towns, and Hezekiah's reshaping of the tunnels that supplied Jerusalem with water.

By treating the full range of archaeological and textual evidence …

The Replication Initiator Of The Cholera Pathogen’S Second Chromosome Shows Structural Similarity To Plasmid Initiators, Natalia Orlova, Matthew Gerding, Olha Ivashkiv, Paul Dominic B. Olinares, Brian T. Chait, Matthew K. Waldor, David Jeruzalmi

Publications and Research

The conserved DnaA-oriC system is used to initiate replication of primary chromosomes throughout the bacterial kingdom; however, bacteria with multipartite genomes evolved distinct systems to initiate replication of secondary chromosomes. In the cholera pathogen, Vibrio cholerae, and in related species, secondary chromosome replication requires the RctB initiator protein. Here, we show that RctB consists of four domains. The structure of its central two domains resembles that of several plasmid replication initiators. RctB contains at least three DNA binding winged-helix-turn-helix motifs, and mutations within any of these severely compromise biological activity. In the structure, RctB adopts a headto- head dimeric configuration …

The Vibrio Cholerae Minor Pilin Tcpb Initiates Assembly And Retraction Of The Toxin- Coregulated Pilus, Dixon Ng, Tony Harn, Tuba Altindal, Subramania Kolappan, Jarrad M. Marles, Rajan Lala, Ingrid Spielman, Yang Gao, Caitlyn A. Hauke, Gabriela Kovacikova, Zia Verjee, Ronald K. Taylor, Nicolas Biais, Lisa Craig

Publications and Research

Type IV pilus (T4P) systems are complex molecular machines that polymerize major pilin proteins into thin filaments displayed on bacterial surfaces. Pilus functions require rapid extension and depolymerization of the pilus, powered by the assembly and retraction ATPases, respectively. A set of low abundance minor pilins influences pilus dynamics by unknown mechanisms. The Vibrio cholerae toxin-coregulated pilus (TCP) is among the simplest of the T4P systems, having a single minor pilin TcpB and lacking a retraction ATPase. Here we show that TcpB, like its homolog CofB, initiates pilus assembly. TcpB co-localizes with the pili but at extremely low levels, equivalent …

Street By Street: Cross-Site Evaluation Of The Ojjdp Community-Based Violence Prevention Demonstration Program, Kathleen A. Tomberg, Jeffrey A. Butts

Publications and Research

In 2010, the U.S. Department of Justice’s Office of Juvenile Justice and Delinquency Prevention (OJJDP) launched the Community-Based Violence Prevention (CBVP) program to reduce youth violence through targeted community-level initiatives. The program offered grants to cities for implementing evidence-based strategies, such as Cure Violence and the Boston Gun Project, to address high-risk youth involvement in violence. The John Jay College Research and Evaluation Center evaluated the program’s impact on five recipient cities: Brooklyn, NY; Denver, CO; Newark, NJ; Oakland, CA; and Washington, DC. The evaluation focused on the effectiveness of these interventions in reducing violence among youth and young adults.

Regional Variation In Ascaris Lumbricoides And Trichuris Trichiura Infections By Age Cohort And Sex: Effects Of Market Integration Among The Indigenous Shuar Of Amazonian Ecuador, Theresa E. Gildner, Tara J. Cepon-Robins, Melissa A. Liebert, Samuel S. Urlacher, Felicia C. Madimenos, J. Josh Snodgross, Lawrence S. Sugiyama

Publications and Research

Background: Soil-transmitted helminth (STH) infection peaks during childhood and varies by sex. The impact of market integration (MI) (increasing production for and consumption from a market-based economy) on these infection patterns, however, is unclear. In this study, STH infection is examined by sex and age among indigenous Shuar inhabiting two regions of Amazonian Ecuador: (1) the modestly market-integrated Upano Valley (UV) and (2) the more traditional Cross-Cutucú (CC) region.

Methods: Kato-Katz fecal smears were examined for parasite presence and infection intensity. Factorial ANOVAs and post hoc simple effects analyses were performed by sex to compare infection intensity between regions and …

Hiv Glycoprotein Gp120 Impairs Fast Axonal Transport By Activating Tak1 Signaling Pathways, Sarah H. Berth, Nichole Mesnard-Hoaglin, Bin Wang, Hajwa Kim, Yuyu Song, Maria Sapar, Gerardo Morfini, Scott T. Brady

Publications and Research

Sensory neuropathies are the most common neurological complication of HIV. Of these, distal sensory polyneuropathy (DSP) is directly caused by HIV infection and characterized by length-dependent axonal degeneration of dorsal root ganglion (DRG) neurons. Mechanisms for axonal degeneration in DSP remain unclear, but recent experiments revealed that the HIV glycoprotein gp120 is internalized and localized within axons of DRG neurons. Based on these findings, we investigated whether intra-axonal gp120 might impair fast axonal transport (FAT), a cellular process critical for appropriate maintenance of the axonal compartment. Significantly, we found that gp120 severely impaired both anterograde and retrograde FAT. Providing a …

Towards An Integrated Primary And Secondary Hiv Prevention Continuum For The United States: A Cyclical Process Model, Tim Horn, Jennifer Sherwood, Robert H. Remien, Denis Nash, Judith D. Auerbach

Publications and Research

Introduction: Every new HIV infection is preventable and every HIV-related death is avoidable. As many jurisdictions around the world endeavour to end HIV as an epidemic, missed HIV prevention and treatment opportunities must be regarded as public health emergencies, and efforts to quickly fill gaps in service provision for all people living with and vulnerable to HIV infection must be prioritized.

Discussion: We present a novel, comprehensive, primary and secondary HIV prevention continuum model for the United States as a conceptual framework to identify key steps in reducing HIV incidence and improving health outcomes among those vulnerable to, as well …

Airborne Infectious Agents And Other Pollutants In Automobiles For Domestic Use: Potential Health Impacts And Approaches To Risk Mitigation, Syed A. Sattar, Kathryn E. Wright, Bahram Zargar, Joseph R. Rubino, M. Khalid Ijaz

Publications and Research

Theworld total of passenger cars is expected to go fromthe current one billion to >2.5 billion by 2050. Cars for domestic use account for ∼74% of the world’s yearly production ofmotorized vehicles. In North America, ∼80% of the commuters use their own car with another 5.6% travelling as passengers.With the current life-expectancy of 78.6 years, the average North American spends 4.3 years driving a car! This equates to driving 101 minutes/day with a lifetime driving distance of nearly 1.3 million km inside the confined and often shared space of the car with exposure to a mix of potentially harmful pathogens, …

Immediate Blood Draw For Cd4+ Cell Count Is Associated With Linkage To Care In Durban, South Africa: Findings From Pathways To Engagement In Hiv Care, Susie Hoffman, Theresa M. Exner, Naomi Lince-Deroche, Cheng-Shiun Leu, Jessica L. Phillip, Elizabeth A. Kelvin, Anisha D. Gandhi, Bruce Levin, Dinesh Singh, Joanne E. Mantell, Kelly Blanchard, Gita Ramjee

Publications and Research

Background Timely linkage to care by newly-diagnosed HIV+ individuals remains a significant challenge to achieving UNAIDS 90-90-90 goals. Current World Health Organization (WHO) guidelines recommend initiating anti-retroviral treatment (ART) regardless of CD4+ count, with priority given to those with CD4+/μl. We evaluated the impact of not having a day-of-diagnosis CD4+ count blood draw, as recommended by South African guidelines, on time to linkage, using data from a prospective cohort study.

Methods Individuals (N = 2773) were interviewed prior to HIV counseling and testing at three public sector primary care clinics in the greater Durban area; 785 were newly-diagnosed and eligible …

Ifn-G Induces Histone 3 Lysine 27 Trimethylation In A Small Subset Of Promoters To Stably Silence Gene Expression In Human Macrophages, Yu Qiao, Kyuho Kang, Eugenia Giannopoulou, Celeste Fang, Lionel B. Ivashkiv

Publications and Research

The mechanisms by which IFN-g activates expression of interferon-stimulated genes that have inflammatory and host defense functions are well understood. In contrast, little is known about how IFN-g represses gene expression. By using transcriptomic and epigenomic analysis, we found that stable repression of a small group of genes by IFN-g is associated with recruitment of the histone methyltransferase EZH2 and deposition of the negative mark histone 3 lysine 27 trimethylation (H3K27me3) at their promoters. Repressed genes included MERTK, PPARG, and RANK, which have anti-inflammatory functions and promote osteoclast differentiation. Gene repression and H3K27me3 persisted after IFN-g signaling was terminated, and …

Receptor-Type Guanylyl Cyclase At 76c (Gyc76c) Regulates De Novo Lumen Formation During Drosophila Tracheal Development, Monn Monn Myat, Unisha Patel

Publications and Research

Lumen formation and maintenance are important for the development and function of essential organs such as the lung, kidney and vasculature. In the Drosophila embryonic trachea, lumena formde novo to connect the different tracheal branches into an interconnected network of tubes. Here, we identify a novel role for the receptor type guanylyl cyclase at 76C (Gyc76C) in de novo lumen formation in the Drosophila trachea.We show that in embryosmutant for gyc76C or its downsteam effector protein kinase G (PKG) 1, tracheal lumena are disconnected. Dorsal trunk (DT) cells of gyc76C mutant embryos migrate to contact each other and complete the …

Polycations. 23. Antimicrobial Surfaces For Prevention Of Pathogen Transmission, Robert Engel, Karin Melkonian, Jay Ho, Jaime Lee Iolani Rizzo

Publications and Research

The continued evolution of bacterial and fungal species poses a significant difficulty for the treatment of disease of microbial origin. Given this situation, the prevention of transmission of such microbial diseases becomes of increasing importance. Efforts of this laboratory have been directed toward the destruction of microbial species on environmental surfaces as a prophylaxis toward infection, and we herein report on the efficacy of a system that demonstrates activity against both Gram-positive and Gram-negative bacteria, as well as fungi. We report specifically herein on the use of fabric materials so activated for the destruction of these microbial species, useful for …

Anomaly Detection In Host Signaling Pathways For The Early Prognosis Of Acute Infection, Kun Wang, Stanley Langevin, Corey S. O'Hern, Mark D. Shattuck, Serenity Ogle, Adriana Forero, Juliet Morrison, Richard Slayden, Michael G. Katze, Michael Kirby

Publications and Research

Clinical diagnosis of acute infectious diseases during the early stages of infection is critical to administering the appropriate treatment to improve the disease outcome. We present a data driven analysis of the human cellular response to respiratory viruses including influenza, respiratory syncytia virus, and human rhinovirus, and compared this with the response to the bacterial endotoxin, Lipopolysaccharides (LPS). Using an anomaly detection framework we identified pathways that clearly distinguish between asymptomatic and symptomatic patients infected with the four different respiratory viruses and that accurately diagnosed patients exposed to a bacterial infection. Connectivity pathway analysis comparing the viral and bacterial diagnostic …

Associations Between Mental Health And Ebola-Related Health Behaviors: A Regionally Representative Cross-Sectional Survey In Post-Conflict Sierra Leone, Theresa S. Betancourt, Robert T. Brennan, Patrick Vinck, Tyler J. Vanderweele, Dayo Spencer-Walters, Joshua Jeong, Adeyinka M. Akinsulure-Smith, Phuong Pham

Publications and Research

Background

Little attention has been paid to potential relationships between mental health, trauma, and personal exposures to Ebola virus disease (EVD) and health behaviors in post-conflict West Africa. We tested a conceptual model linking mental health and trauma to EVD risk behaviors and EVD prevention behaviors.

Methods and Findings

Using survey data from a representative sample in the Western Urban and Western Rural districts of Sierra Leone, this study examines associations between war exposures, post-traumatic stress disorder (PTSD) symptoms, depression, anxiety, and personal EVD exposure (e.g., having family members or friends diagnosed with EVD) and EVD-related health behaviors among 1,008 …

Prophylactic Bacteriophage Administration More Effective Than Post-Infection Administration In Reducing Salmonella Enterica Serovar Enteritidis Shedding In Quail, Mosab Ahmadi, M. Amir Karimi Torshizi, Shaban Rahimi, John J. Dennehy

Publications and Research

Infections caused by Salmonella bacteria, often through poultry products, are a serious public health issue. Because of drawbacks associated with antibiotic prophylaxis, alternative treatments are sought. Bacterial viruses (bacteriophages) may provide an effective alternative, but concerns remain with respect to bacteriophage stability and effectiveness. To this end, we assessed the stability of a novel bacteriophage isolated from poultry excreta, siphovirus PSE, and its effectiveness in reducing Salmonella enterica serovar Enteritidis colonization in vitro and in vivo. Moreover, we sought to determine how the timing (prophylactic or therapeutic) and route (oral gavage or vent lip) of PSE administration impacted its effectiveness. …

Cultivating Minority Scientists: Undergraduate Research Increases Self-Efficacy And Career Ambitions For Underrepresented Students In Stem, Anthony Carpi, Darcy M. Ronan, Heather M. Falconer, Nathan H. Lents

Publications and Research

In this study, Social Cognitive Career Theory (SCCT) is used to explore changes in the career intentions of students in an undergraduate research experience (URE) program at a large public minority-serving college. Our URE model addresses the challenges of establishing an undergraduate research program within an urban, commuter, underfunded, Minority-Serving Institution (MSI). However, our model reaches beyond a focus on retention and remediation toward scholarly contributions and shifted career aspirations. From a student’s first days at the College to beyond their graduation, we have encouraged them to explore their own potential as scientists in a coordinated, sequential, and self-reflective process. …

Machine Learning Meta-Analysis Of Large Metagenomic Datasets: Tools And Biological Insight, Edoardo Pasolli, Duy Tin Truong, Faizan Malik, Levi Waldron, Nicola Segata

Publications and Research

Shotgun metagenomic analysis of the human associated microbiome provides a rich set of microbial features for prediction and biomarker discovery in the context of human diseases and health conditions. However, the use of such high-resolution microbial features presents new challenges, and validated computational tools for learning tasks are lacking. Moreover, classification rules have scarcely been validated in independent studies, posing questions about the generality and generalization of disease-predictive models across cohorts. In this paper, we comprehensively assess approaches to metagenomics-based prediction tasks and for quantitative assessment of the strength of potential microbiome-phenotype associations. We develop a computational framework for prediction …

Untangling The Relationship Between Antiretroviral Therapy Use And Incident Pregnancy: A Marginal Structural Model Analysis Using Data From 47,313 Hiv-Positive Women In East Africa, Batya Elul, Kara K. Wools-Kaloustian, Yingfeng Wu, Beverly S. Musick, Harriet Nuwagaba-Biribonwoha, Denis Nash, Samuel Ayaya, Elizabeth Bukusi, Pius Okong, Juliana Otieno, Deo Wabwire, Andrew Kambugu, Constantin T. Yiannoutsos

Publications and Research

Background: Scale-up of triple-drug antiretroviral therapy (ART) in Africa has transformed the context of childbearing for HIV-positive women and may impact pregnancy incidence in HIV programs.

Methods: Using observational data from 47,313 HIV-positive women enrolled at 26 HIV clinics in Kenya and Uganda between 2001 and 2009, we calculated the crude cumulative incidence of pregnancy for the pre-ART and on-ART periods. The causal effect of ART use on incident pregnancy was assessed using inverse probability weighted marginal structural models, and the relationship was further explored in multivariable Cox models.

Results: Crude cumulative pregnancy incidence at 1 year after enrollment/ART initiation …

Pharmacologic Inhibition Of Host Phosphodiesterase-4 Improves Isoniazid-Mediated Clearance Of Mycobacterium Tuberculosis, Selvakumar Subbian, Mi-Sun Koo, Liana Tsenova, Vikram Khetani, Jerome B. Zeldis, Dorothy Fallows, Gilla Kaplan

Publications and Research

The lengthy duration of multidrug therapy needed to cure tuberculosis (TB) poses significant challenges for global control of the disease. Moreover, chronic inflammation associated with TB leads to pulmonary damage that can remain even after successful cure. Thus, there is a great need for the development of effective shorter drug regimens to improve clinical outcome and strengthen TB control. Host-directed therapy (HDT) is emerging as a novel adjunctive strategy to enhance the efficacy and shorten the duration of TB treatment. Previously, we showed that the administration of CC-3052, a phosphodiesterase-4 inhibitor (PDE4i), reduced the host inflammatory response during Mycobacterium tuberculosis …