Infectious Disease

Leadership

Danielle Zerr, MD
Professor
Interim Division Chief

Overview

The Division of Infectious Disease is committed to providing quality care at Seattle Children's in the area of infectious diseases.

Clinical Programs

The Infectious Disease division provides diagnostic and therapeutic services for children with proven or suspected infectious diseases and treats complicated, chronic or recurrent infections.

Research Programs

Serge Barcy, PhD
Research Assistant Professor of Pediatrics, University of Washington School of Medicine, Seattle Children’s Research Institute
Dr. Barcy's research focuses on characterizing the effector mechanisms involved in the immune control of chronic viral infection. As an immunologist, he has acquired significant expertise and research experience with the immune defenses against viral chronic infections in humans. Dr. Barcy had a unique opportunity as a junior faculty to be part of a successfully funded program project entitled, "Oral pathogenesis and host interactions of KSHV infection." The main goal of the subproject he supervises, with Dr. Soren Gantt, is to identify the immune correlates in the oral mucosa involved with control of KSHV infection and define the impact of HIV infection. This subproject is based upon Dr. Barcy’s original observation that gamma/delta T cells are involved in the cellular immune response against infection with KSHV. He also supervises the core facility that provides titered virus stocks, KSHV relevant primary and immortalized cell cultures and primary tissue for all of the projects involved in the program project.

Marta Bull, PhD
Research Assistant Professor of Pediatrics, University of Washington School of Medicine, Seattle Children’s Research Institute.
Dr. Bull’s primary research interest includes HIV at mucosal sites, primarily but not limited to the female genital tract. My interest in the genital tract is threefold: (1) To better define immunological milieu at mucosal sites and how this pertains to HIV persistence at these sites, (2) to better define the viral dynamics and exchange between the genital tract, blood and other tissues, and (3) to evaluate the role of other chronic viruses—such as herpes simplex virus (HSV) 1, HSV-2, cytomegalovirus (CMV), and Epstein Barr virus—in HIV persistence. Specific areas currently under study include the cellular populations associated with HIV shedding from the female genital tract and immune mechanisms that promote HIV persistence at tissue sites as a barrier to a cure for HIV.

Jane L. Burns, MD
Professor of Pediatrics, University of Washington School of Medicine, Seattle Children's
Dr. Burns’ primary area of research for many years has been cystic fibrosis (CF) microbiology, including antibiotic resistance and bacterial pathogenesis. Her studies have used both in vitro and in vivo models of infection. Novel methods of in vitro susceptibility testing have been established, including testing drug activity against bacteria grown in biofilms and examining drug bioactivity in the presence of CF sputum. She has worked with both primary CF cells and immortalized cell lines in tissue culture to examine bacterial pathogenesis including attachment, invasion and apoptosis. In vivo experiments use a mouse model of chronic bacterial infections with Pseudomonas aeruginosa and Burkholderia cepacia complex. Recent work is examining the phenotypic and genotypic adaptations of both organisms to growth within the CF airway. Dr. Burns frequently collaborates with clinical and basic science CF researchers at Seattle Children’s Hospital and the University of Washington. In addition, she directs the Center for CF Microbiology at Seattle Children’s Hospital, which is a core laboratory for the CF Foundation Therapeutics Development Network.

Angela Campbell, MD, MPH
Assistant Professor of Pediatrics, University of Washington School of Medicine, Seattle Children's. Associate in Clinical Research, Vaccine and Infectious Disease Division, Clinical Research Division, Fred Hutchinson Cancer Research Center.
Dr. Campbell's research focuses on factors that influence the acquisition of respiratory virus infection and disease progression among immunocompromised children and adults, with the goal to facilitate new diagnostic, preventive, and treatment strategies for respiratory virus infections. She was recently a co-investigator for a large prospective study of respiratory virus infections in hematopoietic stem cell transplant recipients, with an emphasis on parainfluenza virus (PIV) infections. PIVs are ubiquitous respiratory viruses that are second only to respiratory syncytial virus (RSV) as important viral causes of lower respiratory infection in children and immunocompromised patients. Unlike RSV, there are no specific antiviral therapies to prevent or treat PIVs. These viruses are important sources of morbidity and mortality in adult and pediatric immunocompromised patients, especially hematopoietic cell transplant (HCT) recipients. Among HCT recipients, PIVs are the most common serious respiratory viruses, with high rates of pneumonia and increased risk of mortality even with upper respiratory tract disease alone. The spectrum of PIV infection can range from asymptomatic infection to pneumonia and death in the HCT population. Prolonged viral shedding, increased risk of long-term airflow obstruction, and high rates of nosocomial transmission accompany PIV infection in HCT recipients. Her studies will be important to document rates of asymptomatic PIV infection in a large cohort of HCT recipients, to determine if asymptomatic infection leads to progression of respiratory disease, to clearly define the presence of persistent subclinical shedding, and to analyze whether humoral immunity is protective against symptomatic infection or disease progression. She is also interested in developing a method by which patients can collect their own respiratory samples for respiratory virus testing and was the principal investigator for a recent study of self-collected swabs from patients with cystic fibrosis, as well as an ongoing study of self-collected swabs from hematopoietic stem cell transplant recipients.

Lawrence Corey, MD
Professor, Laboratory Medicine and Medicine
Adjunct Professor of Pediatrics
Co-Director, Vaccine & Infectious Disease Institute
President and Director, FHCRC 
Dr. Corey’s research areas include studies of the immunobiology of HSV, infection and vaccine development for HSV-2, HIV, infections in the bone marrow transplant patient, and the interactions between HSV-2 and HIV-1.  Dr. Corey’s major laboratory program involves understanding host responses that influence HSV reactivation and acquisition, with the ultimate goal of developing an effective HSV vaccine. The clinical program in genital herpes includes studies looking at the natural history of subclinical shedding, the transmission of HSV to sexual partners and infants, and the relationship between the host response and viral reactivation of infection.  His laboratory also specializes in the detection of antigen specific T cells in mucosal tissues.

Dr. Corey directs a molecular diagnostic laboratory studying novel viral infections, especially in immunocompromised patients. One area of focus is the relationship between viral infection and mortality and graft rejection in transplant patients. Studies examining the relationship between Kaposi’s sarcoma and the acquisition, transmission, and effect of viral replication of HHV-8 are also underway. These studies are performed in collaboration with Dr. Corey Casper and are largely based at the Uganda Cancer Center in Kampala, Uganda.

Dr. Corey is the PI of the NIAID-supported HIV Vaccine Trials Network (HVTN). This is a multi-center, international program for developing and testing candidate HIV vaccines that includes Phase I through Phase III studies.

Janet Englund, MD
Professor of Pediatrics, University of Washington School of Medicine, Seattle Children's.
Dr. Englund's research interests include the study of vaccine-preventable diseases and viral respiratory diseases in young children and immunocompromised hosts, as well as the evaluation of antiviral therapy for the prevention and treatment of viral diseases. As a Clinical Associate at Fred Hutchinson Cancer Research Center, she is actively involved in transplant-related protocols in the prevention and treatment of disease in the immunocompromised host. She also studies the development of antiviral resistance and novel methods of antiviral therapy for various respiratory viruses. Dr. Englund and her research team are involved in research studies of new respiratory vaccines, partnering with Dr. Ruth Karron/Johns Hopkins University and Dr. Peter Collins/NIAID/NIH, to study live attenuated vaccines against RSV, parainfluenza virus, and human metapneumovirus. Her research group is also involved in new methods of enhanced diagnosis of respiratory diseases in collaboration with Dr. Paul Yager, Dept. of Bioengineering, UW. She is currently involved with the study of maternal immunization with influenza virus vaccines in Nepal in a large placebo-controlled clinical trial directed by Drs. Mark Steinhoff, Cincinnati Children’s Hospital, and James Tielsch/Joanne Katz at Johns Hopkins University School of Medicine. Dr. Englund is also interested in vaccine policy and implementation and is actively involved in vaccine issues with the Pediatric Infectious Diseases Society, the American Academy of Pediatrics, the ACIP (American Committee on Immunization Practices) and the WHO (World Health Organization).

Lisa M. Frenkel, MD
Associate Director of the Center for Childhood Infections & Prematurity Research; Professor of Pediatrics, Laboratory Medicine and Global Health, University of Washington School of Medicine.
Dr. Frenkel's research focuses on understanding HIV-1-drug-resistance, prevention of mother-to-child-transmission, and mechanisms that allow HIV-1 infection to persist despite suppressive antiretroviral therapy, including defining viruses that persist to form reservoirs, and viruses that are shed from the genital tract of adults when blood tests show that HIV-1 replication is suppressed by antiretroviral treatment. Her group also is working to develop and transfer practical and economical assays to facilitate HIV-1 diagnosis in infants and to monitor antiretroviral treatment and drug-resistant mutants in resource-poor communities. Their projects include collaborative studies with colleagues in Kenya, Peru, Thailand, South Africa, the USA and Zimbabwe.

Soren Gantt, MD, PhD, MPH
Assistant Professor of Pediatrics, University of Washington School of Medicine, Seattle Children's.
Dr. Gantt’s research focuses on the pathogenesis and immunology of human herpesvirus (HHV) infections, including HHV-8, herpes simplex virus (HSV), and cytomegalovirus (CMV). Several studies are ongoing to understand how HHV-8 causes Kaposi sarcoma (KS). KS is the most common cancer in many parts of Africa, including Uganda, where nearly everyone is infected with HHV-8 during childhood. Dr. Gantt, along with Dr. Corey Casper and colleagues at the Fred Hutchinson Cancer Research Center and the Uganda Cancer Institute, is following Ugandan children from birth to characterize clinical manifestations and antiviral immune responses at the time HHV-8 infection is acquired. In collaboration with Dr. Serge Barcy and others, Dr. Gantt is conducting studies to identify the HHV-8-specific immune responses that are dysregulated by HIV infection. In addition, Dr. Gantt has identified that nelfinavir, an HIV protease inhibitor, has previously unrecognized inhibitory activity against HHV-8 and other HHVs. As such, Dr. Gantt is investigating nelfinavir’s novel antiviral mechanism of action in the laboratory, as well as developing clinical trial protocols to evaluate nelfinavir-containing antiretroviral therapy regimens to prevent and treat diseases due to herpesviruses in people co-infected with HIV. Additional studies, in collaboration with Dr. Helen Horton, are underway to determine the role of immune suppressor cell populations in immune maturation and control of HSV and CMV infections during early infancy.

Sara Healy, MD, MPH
Clinical Trials Investigator, Malaria Clinical Trials Center at Seattle Biomedical Research Institute; Clinical Assistant Professor of Pediatrics, University of Washington School of Medicine, Seattle Children's.
Dr. Healy’s primary area of research is in malaria clinical trials, specifically conducting Phase I/II malaria vaccine trials at the Malaria Clinical Trials Center and designing and conducting experimental medicine clinical trials to explore malaria stage-specific immunity and attempt to identify novel antigens for future vaccine development. In addition, Dr. Healy has clinical interest in travel medicine, vaccinations, and adoption medicine.

Matthew "Boots" Kronman, MD, MSCE
Assistant Professor of Pediatrics, University of Washington School of Medicine, Seattle Children's.
Dr. Kronman’s primary research area of interest is antimicrobial stewardship, using the tools of pharmacoepidemiology to understand current patterns of antimicrobial use, identify the unintended consequences of antimicrobial overuse, and ultimately find ways to improve the overall quality of antimicrobial prescribing for various conditions. His clinical time is split between inpatient Infectious Diseases consultations and the outpatient Infectious Diseases Clinic. In addition, he serves as a consultant to the Seattle Children's Hospital Clinical Effectiveness Program, assisting with the development and implementation of clinical pathways of care for inpatients at Seattle Children's Hospital.

Ann Melvin, MD
Associate Professor of Pediatrics, University of Washington School of Medicine, Seattle Children's.
Dr. Melvin is co-director of the Pediatric HIV program at SCH. Her research interests are in the antiretroviral management of HIV disease in children and prevention and management of complications of HIV treatment. Dr. Melvin is co-principle investigator of the International Maternal Pediatric Adolescent Clinical Trials unit at the University of Washington, sponsored by the NIH, through which she is also chair or co-chair of several national and international research trials. She is also the co-director of the Regulatory Support and Bioethics Core of the Institute for Translational Health Sciences of the University of Washington. She collaborates with Drs. Englund, Frenkel, Corey, and Zerr.

Lakshmi Rajagopal, PhD
Associate Professor of Pediatrics, Adjunct Associate Professor of Microbiology and Global Health, University of Washington School of Medicine, Seattle Children’s Research Institute
Dr. Rajagopal's research interest is to understand signaling events that occur during bacterial disease pathogenesis. The human pathogens that she and her lab study are Group B Streptococcus (GBS) and Staphylococcus aureus. Although both GBS and S. aureus are commensal organisms, these bacteria can also become disease-causing pathogens. GBS are commonly found in the recto-vaginal tract of healthy women but can cause severe invasive disease in human newborns and adults that include elderly, immunocompromised and diabetic individuals. Their studies on GBS are focused on understanding how these bacteria adapt to the environmental niches encountered during their life cycle. Studies from their research have shown that GBS encodes signaling factors such as a serine/threonine kinase; these proteins were previously thought only to exist in higher forms such as eukaryotic organisms. Their research showed that the kinase regulates the expression of the GBS toxin known as hemolysin/cytolysin and also enables the bacteria to adapt to nutrient starvation. In recent studies, they demonstrated that the kinase affects toxin expression based upon its interaction with a DNA-binding response regulator known as CovR. The interaction between the kinase and CovR represents novel findings in bacterial environmental adaptation. Current research is focused toward identifying the environmental cues/signals that are sensed by these bacteria for regulation of toxin expression and virulence. Like GBS, S. aureus are also Gram-positive bacteria that can cause severe invasive disease in humans. They have recently identified a number of novel genes/signaling factors that regulate toxin expression in S. aureus. Current studies are focused on elucidating how these signaling factors regulate toxin expression and S. aureus virulence. The ultimate goal is to use the information gathered from their research to identify novel compounds that can be used to treat these bacterial infections.

Timothy Rose, PhD
Professor of Pediatrics, Adjunct Professor in the Department of Epidemiology and Institute of Public Health Genetics, School of Public Health and Community Medicine, Departments of Oral Biology, School of Dentistry, Epidemiology, and Microbiology, University of Washington School of Medicine, Seattle Children's Research Institute.
Dr. Rose's and his lab's research is focused on herpesviruses implicated in cellular transformation and tumor induction, and in the study of host and viral proteins that mediate these effects. In particular, they are studying the viral etiology of Kaposi's sarcoma (KS) and other AIDS-related malignancies with regards to the interactions between viruses (retroviruses and herpesviruses) and cytokines in virus activation and tumor induction. Their research focuses on the Kaposi's sarcoma-associated herpesvirus (KSHV) and its homologs in non-human primates. They discovered the macaque homolog of KSHV and are studying its association with a Kaposi’s sarcoma-like malignancy in macaques, called retroperitoneal fibromatosis (RF), which like AIDS-KS is associated with a retrovirus infection. RF occurs in conjunction with simian AIDS (SAIDS) caused by infection with simian retrovirus 2 (SRV2) or SIV, the simian homolog of HIV. They have identified a second lineage of KSHV-like rhadinoviruses in macaques and are studying its role in RF and other macaque tumors. Ongoing projects include the cloning and sequence of the genome of the new macaque herpesvirus, the identification and characterization of cellular receptors mediating infection by KSHV, the comparative analysis of KSHV and its simian homologs and their role in tumor induction in association with HIV-induced immunosuppression, the characterization of latency and the activating switch to herpesvirus replication, and the development of diagnostic tests for novel viruses.

Arnold L. Smith, MD
Professor of Pediatrics, Adjunct Professor of the Departments of Microbiology and Global Health, University of Washington School of Medicine, Seattle Children’s Research Institute.
The Smith lab seeks to understand the biology of Haemophilus influenzae, a ubiquitous bacterium, in humans and the mechanisms it uses in producing mucosal disease of the respiratory tract and sporadic invasive disease. The current focus is on regulation of gene expression, which differs from strain-to-strain and is both stochastic and directed; the role of intermediary metabolism in virulence is emphasized. A wide variety of model systems and techniques is used to gain insight into this bacterium. An additional pilot project is seeking to derive temperature stable protein vaccine to be used in the construction of protein-polysaccharide conjugates. The strategies used by Thermophiles is being used as a template for vaccine development.

Sherilyn Smith, MD
Professor of Pediatrics, Pediatric Infectious Disease Fellowship Director, Pediatric Clerkship Associate Director, University of Washington School of Medicine, Seattle Children’s.
Dr. Smith’s interests are in medical education, teaching and curriculum development. She is currently the Director of the Infectious Disease Fellowship. Her primary responsibilities are curriculum development for the fellowship, coordination of teaching activities of infectious disease fellows, general mentoring of fellows, monitoring programmatic compliance with requirements necessary for board certification in Pediatric Infectious Disease, and implementing all requirements for continued certification of the fellowship program by the ACGME (Accreditation Council for Graduate Medical Education). She works closely with the Research Director and Training Grant Principle Investigator (Dr. Frenkel) to coordinate all aspects of the training of our fellows.

Kevin Urdahl, MD, PhD
Assistant Member, Seattle Biomedical Research Institute, Clinical Assistant Professor of Pediatrics, Affiliate Assistant Professor of Immunology, University of Washington School of Medicine, Seattle Children's.
Dr. Urdahl's research is focused on understanding T cell mediated immunity during Mycobacterium tuberculosis (Mtb) infection, including understanding the factors that promote vs. restrict immune protection. His laboratory has recently discovered that antigen-specific natural regulatory T cells expand during early tuberculosis and impair immunity by inhibiting the priming of effector T cells in the lung draining lymph node. Currently, they are studying how these cells are induced, how they affect T cell priming, and also how they impact and are impacted by vaccination. The lab is also studying how protective CD4 T cell responses are maintained throughout chronic infection with Mtb. They have acquired a wide array of reagents and methodologies for tracking Mtb-specific T cell responses, including the use of Mtb-specific MHC class I and class II tetramers, advanced tetramer-based enrichment techniques for tracking rare populations of antigen-specific T cells, and adoptive transfer of CD4+ T cells from Mtb-specific, T cell receptor transgenic mice. They believe that enhanced understanding of the basic biology of the immune response to Mtb will be critical for the development of an effective vaccine strategy. In the future, they plan to confirm and advance the discoveries they have elucidated in the mouse model in human populations immunized against and/or infected with Mtb.

Thor Wagner, MD
Assistant Professor of Pediatrics, University of Washington School of Medicine, Seattle Children’s.
Dr. Wagner’s research is focused on pediatric HIV, which accounts for 15% of all HIV deaths. His primary interest is understanding chronic HIV infection during antiretroviral therapy. Specifically, why doesn't antiretroviral therapy eradicate HIV infection? Is there ongoing viral replication? Is there proliferation of cells with viable proviral HIV? Can we identify the remaining infected cells? Is immune tolerance to HIV a barrier to an HIV cure? Answers to these questions should help design new treatment strategies more likely to cure HIV. Dr. Wagner’s other research interest is improving infectious disease diagnostics in low resource settings. Specifically, he is working to develop a point-of-care diagnostic test for infant HIV. Currently there is no simple test to diagnose infants with HIV, and 50% of HIV-infected children die before they can be diagnosed. To accomplish this, he is utilizing state-of-the-art monoclonal antibody screening technology to optimize the sensitivity of immunoassays to detect HIV antigens.

Scott Weissman, MD
Assistant Professor of Pediatrics, University of Washington School of Medicine, Seattle Children’s.
Despite being one of the most exhaustively studied free-living organisms in biology, the Escherichia coli bacterium continues to produce a massive burden of disease, including extraintestinal syndromes such as urinary tract infections (UTI) and bloodstream infections. Since the initiation of intrapartum antimicrobial prophylaxis for group B streptococcus during pregnancy, E. coli has become the leading bacterial cause of early-onset sepsis (EOS) in newborns. Now, with ampicillin-resistant rates >80% among E. coli isolates, it remains unclear whether contemporary EOS isolates represent antibiotic-resistant derivatives of the traditional K1-encapsulated clones described in the 1970’s (which would facilitate rapid point-of-care screening tests) or a more diverse array of novel antibiotic-resistant clones like those that have complicated empiric treatment of community-acquired UTI (e.g., Bactrim-resistant ‘clonal group A’). Dr. Weissman and his lab use PCR- and sequence-based molecular typing techniques to characterize clinical isolate collections gathered through active and passive surveillance by the NICHD Neonatal Research Network and the Minnesota Department of Health. With the appearance of EOS-associated clones resistant to standard ampicillin/gentamicin combination therapy, this project will inform guidelines for the empiric treatment of early-onset sepsis. His lab is also using molecular techniques to characterize the spread of plasmid-borne extended-spectrum beta-lactamase (ESBL) enzymes among Enterobacteriaceae. Since 2000, they have witnessed the worldwide emergence of Gram-negative 'superbugs' such as E. coli ST131 and Klebsiella pneumonia ST258—which not only encode multiple virulence factors associated with extraintestinal disease, but also Class A enzymes that hydrolyze third-generation cephalosporins and carbapenem antibiotics (CTX-M-15 and KPC, respectively). Their molecular typing methods will characterize the dynamics of antibiotic resistance, to distinguish epidemics of resistance genes that spread between plasmids, plasmids that spread between strains, and strains that spread across continents.

Danielle Zerr, MD, MPH
Interim Division Chief, Professor of Pediatrics, University of Washington School of Medicine, Seattle Children’s, Affiliate Investigator at the Fred Hutchinson Cancer Research Center, Medical Director of Infection Prevention at Seattle Children’s Hospital.
Dr. Zerr’s research has focused on two main areas: (1) Defining the epidemiology of viral pathogens in healthy children and immunocompromised hosts and (2) describing the epidemiology and defining prevention strategies for healthcare-associated infections. Recent work includes studies investigating the epidemiology of human herpesvirus 6 (HHV-6) in hematopoietic stem cell transplant recipients. This work has involved the application of neuropsychiatric and neuropsychological tools in order to better understand the impact HHV-6 has on the central nervous system in these patients. In addition, Dr. Zerr collaborates with Dr. Weissman in investigating the molecular epidemiology of broad-spectrum beta-lactam resistance in pediatric Enterobacteriaceae infections. Currently, they lead a multi-center surveillance study that will result in integrative analyses of patient characteristics, bacterial phylogenetics, and molecular resistance mechanisms in order to better target prevention strategies. She collaborates with Drs. Corey, Boeckh, Englund, and Weissman.

Training Programs

The overall goal of our training programs is to train individuals for careers in academic pediatrics who will be skilled investigators and clinical subspecialists. Clinical training is intensive during the first year; our institutions have large patient bases, providing a rich clinical exposure over the six-twelve months of intensive clinical training. Subsequent years are devoted primarily to investigation, with clinics at sufficient frequency to develop a longitudinal perspective on patient management and to maintain clinical skills.

For more information, please visit the Pediatrics Infectious Disease Fellowship webpage.