Global Health and Infectious Disease Conference

March 31, 2017
8:30 a.m. - 5 p.m.
Eric P. Newman Education Ctr, Medical Campus

March 31, 2017
8:30 am – 5:00 pm
Eric P. Newman Education Center,
Washington University Medical Campus

The event includes presentations, a poster session and an opportunity to have lunch with a speaker.

All students, postdoctoral fellows, and faculty from Washington University and elsewhere working in global health are encouraged to submit a poster abstract by Tuesday, February 1, 2017. 

Free and open to all. Registration is required; deadline is March 24, 2017.

Agenda

8:00 am Registration and Poster Session
8:30 am Provost Holden Thorp, Washington University – Welcome
8:33 am William Powderly, MD, Washington University – The Latest in Global Health
8:45 am Ernesto Ruiz-Tiben, MD, the Carter Institute – Progress Towards the Eradication of Guinea Worm Disease
9:20 am Thaddeus Stappenbeck, MD, PhD, Washington University –  Implication of Host Microbial Interactions on Global Health
9:55 am Break and Poster Session
10:25 am Flaminia Catteruccia, PhD, Harvard UniversityMalaria Transmission by the Mosquito Vector: Studying Basic Biology to Find New Solutions to an Old Problem
11:00 am Mary Wilson, MD, University of Iowa – Strategies to Control Leishmaniasis in India and Brazil: Intersection of Global Health, Immunology and Genetics
11:35 am Lunch
12:30 pm Poster Session
1:30 pm Stephen Beverley, PhD, Washington University – Endogenous RNA Viral Elements as Virulence Factors in Parasitic Protozoa
2:05 pm Albert Ko, MD, FACP, FIDSA, Yale University– Emergence of Zika Congenital Syndrome
2:40 pm Jennifer Philips, MD, PhD, Washington University – Immune Evasion Strategies of Mycobacterium tuberculosis
3:15 pm Break
3:30 pm Ellyn Ogden, MPH, USAID – The Science of Political and Financial Support for Disease Eradication
4:05 pm Awards & Closing Remarks – Gary Weil, MD

Topics

  • Malaria Control
  • Zika Congenital Syndrome
  • Polio Eradication
  • Pathogenesis of TB
  • Guinea Worm
  • Intestinal Host-Microbial Interactions

Speaker Bios

Stephen Beverley, PhD

Chair of the Department of Molecular Microbiology
Washington University

Robert J. Boston Photographs
Steven Beverley
Washington University
Lab PI

Biography
Dr. Beverley’s laboratory studies the biology of the protozoan parasite Leishmania, including virulence factors, host response and basic metabolic functions. His laboratory has focused on the development of genetic tools and their applications to diverse questions in Leishmania biology, more recently incorporating genomic approaches. Recent foci include the study of the RNAi interference pathway, as a tool and also the forces contributing to its loss during evolution in some Leishmania species. These studies have led his laboratory into the study of Leishmania RNA viruses and their role in parasite virulence. Translational interests include the identification of chemotherapeutic targets and live vaccination strategies. Dr. Beverley earned his PhD in biochemistry from University of California, Berkeley, and did postdoctoral research at Stanford University. In 1983 he moved to Harvard Medical School and went on to become Professor and Interim Chair of the Department of Biological Chemistry & Molecular Pharmacology. In 1997 he joined the faculty at Washington University School of Medicine in St. Louis as Head of the Dept. of Molecular Microbiology. Beverley is a Burroughs-Welcome Scholar in Molecular Parasitology, and a member of the US National Academy of Sciences and American Academy of Microbiology, and a AAAS Fellow.

Title – Endogenous RNA Viral Elements as Virulence Factors in Parasitic Protozoa

Abstract – Virus-like elements occur in many parasitic protozoans, but previously were seen largely as molecular curiosities of uncertain importance.  Leishmania in South America often bear the dsRNA Leishmaniavirus (LRV1).  Like most Totiviruses, LRV1 is neither shed nor infectious, and thus may be viewed as a persistent endobiont.   Perspectives on the importance of these elements changed upon discovery that L. guyanensis LRV1 is associated with hypervirulence and increased metastasis, the latter being a hallmark of the more severe forms of leishmaniasis (Ives et al. Science 2011).  We have been pursuing this observation intensively as a new paradigm of protozoal virulence.  For Leishmania we developed tools for reproducibly generating isogenic lines lacking LRV1s.  This has allowed extension of findings with L.guyanensis to L. braziliensis, the predominant agent of mucocutaneous leishmaniasis (MCL).  Transcriptomic analysis of infected macrophages shows an elevated ‘hyperinflammatory’ response including stimulation of many Type I interferon-inducible genes.   Recent data suggest that viral coinfections may similarly provide the Type I interferon response leading to hypervirulence.   Another question is the contribution of LRV1 with Leishmania pathogenicity in human infections, where disease manifestations differ greatly from those seen in murine models, which is complicated by several factors.  Recently we showed that the presence of LRV1 was associated with increased relapse and/or treatment failures in human L.braziliensis-infected patients treated with pentavalent antimonials in Peru and Bolivia, as well as in L.guyanensis infections treated with pentamidine (Adauai et al & Bourreau et al. J. Inf. Dis 2016).  The association of LRV1 with clinical drug treatment failure could serve to guide more effective treatment of tegumentary disease caused by Leishmania sp.  Current studies are directed towards discovery of additional Leishmania viruses as well as extension of the protozoal virus paradigm into other parasites including Trichomonas, Toxoplasma and Cryptosporidium.

Flaminia Catteruccia, PhD

Associate Professor, Department of Immunology and Infectious Diseases
Harvard T.H. Chan School of Public Health

Biography
Dr. Flaminia Catteruccia is Associate Professor at the Department of Immunology and Infectious Diseases in the Harvard T.H. Chan School of Public Health. Her lab studies the biology of mosquitoes that transmit malaria, a disease that kills half a million people each year. In particular, her research focuses on how mosquitoes reproduce and transmit the disease to humans. Her goal is to reduce the malaria burden by identifying where we can interfere with the mosquito’s ability to transmit deadly malaria parasites. Flaminia trained as a molecular entomologist at Imperial College London, where she achieved the first genetic manipulation of Anopheles mosquitoes. She has since contributed numerous molecular and genetic studies that have expanded our understanding of mosquito biology and mosquito-parasite interactions. Her work includes field studies in a number of African countries to bridge laboratory findings to the implementation of novel strategies for malaria elimination.

Title – Malaria Transmission by the Mosquito Vector: Studying Basic Biology to Find New Solutions to an Old Problem

Abstract – Nearly 200 million people are infected every year by malaria parasites, and more than 10 million people have already died because of malaria infections since the turn of this century, mostly young children in sub-Saharan Africa. According to the World Health Organization, “mosquito control is the only intervention that can reduce malaria transmission from very high levels to close to zero”. Consistently, extraordinary efforts are being made to control Plasmodium transmission by the Anopheles mosquito using long lasting insecticide treated nets (LLINs) and indoor residual spraying (IRS). The increased application of both interventions over the last decade, however, has inevitably led to the emergence and spread of insecticide resistance in natural mosquito populations, making the generation of alternative strategies that can reduce disease transmission a high priority.

Here we present studies on the molecular and genetic mechanisms that shape the interplay between reproductive biology and Plasmodium development in Anopheles mosquitoes. Specifically, we show how the malaria parasite exploits the physiological environment created by mating and blood feeding in the female Anopheles to achieve its own transmission. Increasing knowledge of mosquito biology and mosquito-Plasmodium interactions will contribute novel tools and concepts for malaria control.

Albert Icksang Ko, MD, FACP, FIDSA

Chair, Department of Epidemiology of Microbial Diseases
Yale University

Biography
Dr. Albert Icksang Ko, an infectious disease physician, is a Professor and Chair of the Department of Epidemiology of Microbial Diseases at Yale School of Public Health and Collaborating Researcher at the Oswaldo Cruz Foundation, Brazilian Ministry of Health. His research centers on the health problems that have emerged as a consequence of rapid urbanization and social inequity. Dr. Ko coordinates a research and training program on urban slum health in Brazil and is conducting prospective studies on rat-borne leptospirosis, dengue, meningitis and respiratory infections. His research particularly focuses on understanding the transmission dynamics and natural history of leptospirosis, which is as a model for an infectious disease that has emerged in slum environments due to the interaction of climate, urban ecology and social marginalization. Current research combines multidisciplinary epidemiology, ecology and translational research-based approaches to identify prevention and control strategies that can be implemented in slum communities. Dr. Ko is also Program Director at Yale for the Fogarty Global Health Equity Scholars Program which provides research training opportunities for US and LMIC post and pre-doctoral fellows at collaborating international sites. Since December 2016, the research and training program in the city of Salvador, Brazil has mobilized their efforts to investigate the on-going outbreak of Zika virus infection and microcephaly.

Title – Emergence of Zika Congenital Syndrome

Abstract – TBD

Ellyn Ogden, MPH

Worldwide Polio Eradication Coordinator
USAID

Biography
Ellyn W. Ogden, MPH, has been the Worldwide Polio Eradication Coordinator and Technical Director for the US Agency for International Development (USAID) and a Senior Technical Advisor for Health and Child Survival since 1997.  She is responsible for the USAID’s $59 million annual polio eradication that works in over 25 countries in Africa, South Asia, and the Near East. Recognizing the need for equity and access to health services for all children, Ms. Ogden has directed special attention to children in conflict countries and among marginalized or under-served communities.  A graduate of the Tulane (B.A. International Relations) and the Tulane School of Public Health and Tropical Medicine (MPH Epidemiology and Infectious Disease Control), Ellyn has nearly 30 years of international public health experience in the areas of child survival, disease prevention and control, health communication, and health and human rights. During her career, Ms Ogden has served as a Peace Corps volunteer in Papua New Guinea and as a John’s Hopkins University Health and Child Survival Fellow with USAID’s Latin America Bureau.  Ms. Ogden is a Member of the Polio Eradication Regional Certification Committee for Europe. In 2008, Ms. Ogden received USAID’s Award for Heroism for her successful efforts to negotiate “Ceasefires and Days of Tranquility” in several conflict countries in Africa and Asia. She is also the recipient of Rotary International’s prestigious “Paul Harris Fellows Award” for Humanitarian Service.

Title – The Science of Political and Financial Support for Disease Eradication

Abstract – The Science of Disease Elimination Eradication of disease is the aspirational goal of global public health efforts, and yet only one infectious disease of humans — smallpox — has been eradicated to date. There are ongoing efforts to eradicate poliomyelitis, dracunculiasis, yaws and malaria, and five more infectious diseases have been identified as potentially eradicable, including measles. Diseases that are potentially eradicable share a number of critical features, including the absence of a non-human reservoir or environmental amplification, availability of diagnostics, and an efficient and effective intervention. Additional factors such as financial support to implement interventions and political commitment are crucial to mount a successful eradication campaign.  A trend analysis of the polio eradication budget over nearly 20 years, tells an important story of early optimism, the cost of underestimating the social context and complexity of field operations, the challenges of building coalitions at the international level down to every household as well as resource mobilization.  These lessons are instructive as the world contemplates future elimination and eradication initiatives.

Jennifer Philips, MD, PhD

Assistant Professor, Department of Medicine, Division of Infectious Diseases
Washington University

Biography
Jennifer A. Philips received her medical and graduate training at the University of California, San Francisco, followed by training in Internal Medicine and Infectious Diseases at Brigham and Women’s Hospital and Massachusetts General Hospital. She worked in Translational Medicine at Novartis before starting her laboratory at NYU School of Medicine. Her laboratory, which moved to Washington University School of Medicine in 2015, investigates how Mycobacterium tuberculosis impairs lysosomal trafficking and evades immune eradication. She is a recipient of awards from the Infectious Disease Society of America, the Doris Duke Charitable Foundation, and the Edward Mallinckrodt, Jr. Foundation.

Title – Immune Evasion Strategies of Mycobacterium tuberculosis

Abstract – Mycobacterium tuberculosis (Mtb), the causative agent of tuberculosis, has infected one third of the world’s population and kills more people than any other infectious disease. Mtb is able to evade immune eradication by surviving in macrophages and inhibiting MHC II antigen presentation. The focus of the Philips’ laboratory is to understand the molecular basis by which Mtb undermines the innate and adaptive immune response. In order to survive in macrophages, Mtb has to inhibit the antimicrobial arsenal of macrophages, including production of reactive oxygen and degradation by phagolysosomes. Mtb also has to compete with the host for nutrients, and it alters host fatty acid metabolism. We are interested in identifying and characterizing bacterial effectors that Mtb uses to alter the physiology of innate immune cells. We focus on several important bacterial effectors, including CpsA and EsxH, and host molecules, such as the NADPH oxidase, the endosomal sorting complex required for transport (ESCRT), and miR-33. We have shown that these factors play a central role in the ability of Mtb to evade the host immune system. In elucidating the molecular basis by which Mtb undermines the immune response, we hope to inform the development of much needed novel therapies and vaccines.

Ernesto Ruiz-Tiben, PhD

Director, Guinea Worm Eradication Program
The Carter Center

Biography
Dr. Ernesto Ruiz-Tiben joined The Carter Center in 1992 after more than 27 years of service as a commissioned officer of the U.S. Public Health Service at the Centers for Disease Control and Prevention. Since 1998, Dr. Ruiz-Tiben has served as director of the Carter Center’s Guinea Worm (Dracunculiasis) Eradication Program. In this capacity, he works in conjunction with the World Health Organization Collaborating Center for Research, Training, and Eradication of Dracunculiasis at the CDC, monitoring and disseminating information about the status of the global campaign and providing technical assistance to national eradication programs.

During his tenure at CDC, Dr. Ruiz-Tiben headed the Helminthic Disease Branch, Division of Parasitic Disease, National Center for Infectious Diseases. He has worked to control the disease schistosomiasis in Puerto Rico, the Dominican Republic, Suriname, Brazil, Egypt, and Liberia and dengue fever in the Caribbean area. For this outstanding work, he received special commendations from the U.S. Public Health Service. Additionally, in recognition of his contributions to the global initiative to eradicate dracunculiasis, the CDC in 1990 awarded him the U.S. Public Health Service’s Outstanding Service Medal.

Dr. Ruiz-Tiben received the Bachelor of Science degree from Catholic University in Puerto Rico. He holds a Master of Science degree from the University of Puerto Rico School of Public Health and a doctorate in epidemiology from the University of Texas School of Public Health at Houston.

Title – Progress Towards the Eradication of Guinea Worm Disease

Abstract – Caused by the parasitic nematode Dracunculus medinensis endemic transmission of Guinea worm disease (GWD) is a consequence of extreme poverty among residents of remote and marginalized communities in sub-Saharan Africa, negatively affecting health, agricultural productivity, school attendance and overall quality of life.

The idea of eradicating GWD had its genesis at the Centers for Disease Control and Prevention in 1980.  Experts believed then that the parasite could be driven to extinction by preventing contamination of sources of stagnant water by infected residents. 3.5 million cases of GWD were estimated to occur in 1986, in 18 sub-Saharan countries and India and Pakistan in Asia. That year former US President Jimmy Carter agreed to become the chief advocate for eradication of GWD and allow The Carter Center to become the lead non-governmental organization providing technical and financial assistance to national eradication programs. This presentation will review the history of the global campaign, including the strategies, and program management methods used to interrupt disease transmission, and reduce incidence to only 25 cases from 19 villages as of the end of 2016. Recent new challenges to the global eradication campaign will be discussed, including how these are currently being addressed.

Thaddeus Stappenbeck, MD, PhD

Professor, Pathology and Immunology and Co-Director, Laboratory and Genomic Medicine
Washington University

Biography
Dr. Thaddeus Stappenbeck is currently the Conan Professor of Pathology & Immunology and Co-Chief of the Division of Laboratory and Genomic Medicine at the Washington University School of Medicine. He received a B.A. degree in the Integrated Science Program from Northwestern University. He obtained an MD/PhD from Northwestern University. He trained in anatomic pathology at Washington University School of Medicine and conducted postdoctoral research with Jeffrey Gordon also at Washington University.

Dr. Stappenbeck’s research program has focused on the response of intestinal epithelial cells to injury using several mouse models including chemical and physical damage as well as genetic modulation of the immune system and epithelial function. His lab has found epithelial repair is directed by intestinal microbes, specific cells of the immune system and the stromal cells that support the epithelium. Within the intestinal epithelium, the process of autophagy is required within specific secretory cells to support intestinal homeostasis. His lab has been supported by the National Institute of Health, the Crohn’s Colitis Foundation of America, The Broad Medical Research Program, the Pew Foundation, among others.

Topic – Host-microbial interactions that modulate repair in the intestine and the impact of these studies on global health and what the major gaps are and how we can use basic and translational studies to address these limitations.

Title – Implication of Host Microbial Interactions on Global Health

Abstract – We and others are beginning to decipher specific mechanisms of host microbial interactions that control physiologic and pathophysiologic conditions. The latter includes both inciting damage and subsequent repair processes. The microbial contribution includes diverse collections of bacteria, viruses and parasites that not only interact with the host by also with each other. Focusing on bacteria, we are learning that in many cases small molecules or small fragments of bacterial membranes can readily penetrate host defenses (specifically the mucus and epithelial barriers) and engage components of the  host immune system. I will describe progress in model systems and focus on outer membrane vesicle engagement with the host and screens for metabolites that impact function of the epithelium and stromal cells. I will also show that we are now able to model these interactions in vitro using primary human cells. I will also address the challenges of applying these paradigms to world-wide health issues that impact the intestine.

Mary Wilson, MD

Professor, Department of Internal Medicine
University of Iowa Carver College of Medicine

Biography
Dr. Wilson obtained her BS degree from Carleton College and MD from the University of Rochester in New York. She did a residency in Internal Medicine at the University of Michigan, and postdoctoral fellowship Infectious Diseases fellowship at the University of Virginia in Charlottesville. At UVA she worked with Richard Pearson studying the immunobiology of leishmaniasis.  She then joined the faculty at the University of Iowa in Internal Medicine, Division of Infectious Diseases, and later obtained a joint appointment in the Department of Microbiology. She holds a secondary appointment in the Department of Epidemiology, and is a member of the Interdisciplinary graduate programs in Immunology, Genetics and Molecular & Cellular Biology. Dr. Wilson’s international research began in 1996 when she initiated a study of the human genetic susceptibility to leishmaniasis in endemic neighborhoods outside of Natal, northeast Brazil in collaboration with Dr. Selma Jeronimo of the Federal University of Rio Grande do Norte in Natal.  This has developed into a collaborative program with two universities in northeast Brazil, headed by Dr. Edgar Carvalho of the Federal University of Bahia and Dr. Selma Jeronimo, with studies funded through a Tropical Medicine Research Center from the NIH.  Dr. Wilson began studies of leishmaniasis in India in collaboration with Dr. Shyam Sundar of Banaras Hindu University, funded through a second Tropical Medicine Research Center to that university.  Dr. Wilson’s studies at the University of Iowa focus on the innate and adaptive immune response to Leishmania spp. in rodent models and in models of human skin. Her studies in India and Brazil have focused on development of techniques to detect and quantify parasites in asymptomatic and symptomatic infection, the genetics of human susceptibility to leishmaniasis, the effects of divergent parasite strains on the outcome of infection, and the importance of insect microbiomes in transmission of infection.

Title – Strategies to Control Leishmaniasis in India and Brazil: Intersection of Global Health, Immunology and Genetics

Abstract – Leishmaniasis is a group of vector-borne parasitic diseases caused by the obligate intracellular Leishmania spp. protozoa. It is highly prevalent worldwide, and has been called a “neglected tropical disease” due to disproportionate funding for research and prevention compared to the burden of disease.  Similar to other NTDs, leishmaniasis is most common in lower income countries, and within these it affects primarily the more impoverished members of the population.  The severest form, visceral leishmaniasis (VL), is usually fatal if untreated. Treatment of leishmaniasis is troubled by drug resistance of the parasite, and toxic side effects from most available agents. Most agents require parenteral administration of drugs over a 3-4 week period of time, a task that is complex in many endemic regions.  Even though there are currently no proven effective human vaccines preventing any parasitic infection, a preventive vaccine for leishmaniasis would be tremendously useful. More efficient therapeutic approaches and development of a protective vaccine are high priorities for research investigators.

Clinical observations suggest that drug-induced cure of leishmaniasis leads to at least partial resistance to re-infection.  However many unusual features of the disease show that vaccine development is not straightforward. Most infected animals (and likely humans) retain persistent parasites that no longer cause symptoms after disease cure. It is unclear whether persistent parasites are required for long-term protective immunity. Human infection is associated with dysregulated lipid metabolism, exaggerated innate inflammatory responses, and dys-regulated adaptive immunity that must be overcome by preventive or therapeutic management strategies.  The complex genetic and antigenic characteristics of the parasite lead to questions whether vaccine development will be feasible.

Our investigations in endemic regions of India and northeast Brazil are addressing questions relevant to improved diagnosis, treatment and prevention of leishmaniasis. Despite the fact that studies often highlight obstacles rather than dissolve them, work in endemic populations often raises awareness and decreases disease incidence merely by improved knowledge of risks and early recognition of disease. The goals of international research include not only the development of improved methods for disease management, but also education of the people in endemic regions about the disease.  Cooperative work with scientists and health professionals in the country, and work with people in endemic situations is needed if effective strategies are to be designed.

Event Sponsors: Center for Global Health and Infectious Disease at the Institute for Public Health, and the Departments of Medicine, Molecular Microbiology, and Pediatrics in the School of Medicine

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