The Forever War: Malaria versus the World

The Forever War: Malaria versus the World

Wednesday, November 16, 2011

The New York Academy of Sciences

Presented By

Presented by The New York Academy of Sciences and The Johns Hopkins Bloomberg School of Public Health

 

The Johns Hopkins Bloomberg School of Public Health is celebrating the tenth anniversary of the founding of the Johns Hopkins Malaria Research Institute by hosting a half-day symposium at the New York Academy of Sciences. The goal of the symposium is to call attention to the enormous burden imposed by this devilishly resistant disease, and highlight the groundbreaking research conducted by Johns Hopkins researchers as well as other scientists aligned in the battle against malaria.

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By: 10/14/2011After: 10/14/2011Onsite: 11/16/2011
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Presented by

Agenda

* Presentation times are subject to change.


Wednesday, November 16, 2011

12:15 PM

Registration

1:00 PM

Welcome Remarks
Ellis Rubinstein, The New York Academy of Sciences
Michael J. Klag, MD, MPH, Johns Hopkins Bloomberg School of Public Health

1:05 PM

Malaria Video

1:10 PM


Welcome Address
The Honorable Michael E. Bloomberg, Mayor of the City of New York

1:30 PM

The Founding of Johns Hopkins Malaria Research Institute
Alfred Sommer, MD, MHS, Johns Hopkins Bloomberg School of Public Health

Johns Hopkins Malaria Research Institute: An Opportune Time to Invest
Diane E. Griffin, MD, PhD, Johns Hopkins Bloomberg School of Public Health

1:45 PM

Conquering Malaria: Community Involvement Can Make the Difference
Phil E. Thuma, MD, Malaria Institute at Macha

 

Tussle with a Thinking Parasite: Surprises from the Field
Sungano Mharakurwa, PhD, MSc, Johns Hopkins Center for Global Health

2:30 PM

Getting a Grip: How Malaria Parasite Establish Infection
Photini Sinnis, MD, New York University Langone Medical Center

3:00 PM

Stopping Malaria in the Mosquito Belly
George Dimopoulos, PhD, MBA, Johns Hopkins Bloomberg School of Public Health

3:30 PM

How to Lose this Battle Against Malaria
David Smith, PhD, University of Florida

4:00 PM

Coffee Break

4:30 PM

Keynote Address
Jeffrey D. Sachs, PhD, The Earth Institute, Columbia University

5:15 PM

Q&A (Moderated by Peter Agre, MD, Johns Hopkins Malaria Research Institute)

5:30 PM

Cocktail Reception

6:30 PM

Meeting Adjourns

Speakers

Keynote Speaker

Jeffrey D. Sachs, PhD

The Earth Institute, Columbia University

Jeffrey D. Sachs is the Director of The Earth Institute, Quetelet Professor of Sustainable Development, and Professor of Health Policy and Management at Columbia University. He is Special Advisor to United Nations Secretary-General Ban Ki-moon. From 2002 to 2006, he was Director of the UN Millennium Project and Special Advisor to United Nations Secretary-General Kofi Annan on the Millennium Development Goals. Sachs is also President and Co-Founder of Millennium Promise Alliance. For more than 20 years Professor Sachs has been in the forefront of the challenges of economic development, poverty alleviation, and enlightened globalization, promoting policies to help all parts of the world to benefit from expanding economic opportunities and wellbeing. He is author of hundreds of scholarly articles and many books, including the New York Times bestsellers Common Wealth: Economics for a Crowded Planet (Penguin, 2008) and The End of Poverty (Penguin, 2005).

Speakers

Peter Agre, MD

Johns Hopkins Malaria Research Institute

A native Minnesotan, Peter Agre studied chemistry at Augsburg College (BA 1970) and medicine at Johns Hopkins (MD 1974). Following Internal Medicine Residency at Case Western Reserve University Hospitals of Cleveland and Hematology–Oncology Fellowship at the University of North Carolina at Chapel Hill, Agre joined the faculty at the Johns Hopkins School of Medicine where his laboratory became widely recognized for discovering the aquaporins, a family of water channel proteins found throughout nature and responsible for numerous physiological processes as well as multiple clinical disorders. Following a term as Vice Chancellor at Duke Medical Center, Agre joined the Johns Hopkins Bloomberg School of Public Health in 2008, where he is University Professor and Director of the Malaria Research Institute and Program Director of the NIH International Center of Excellence in Malaria Research for Zambia and Zimbabwe.

Agre shared the 2003 Nobel Prize in Chemistry with Roderick MacKinnon "for discoveries concerning channels in cell membranes." Agre has received additional honors including the Distinguished Eagle Scout Award from the Boy Scouts of America. Agre is a member of the National Academy of Sciences and the Institute of Medicine; he is past-Chair and member of the Committee on Human Rights of the National Academies.

From 2009–11, Agre served as President and Chair of the Board of Directors of the American Association for the Advancement of Sciences and led scientific diplomacy visits to Cuba, Democratic Republic of Korea (North Korea), and Myanmar (Burma). Agre and his wife Mary, a teacher, have been married 36 years and have four grown children.

George Dimopoulos, PhD, MBA

Johns Hopkins Bloomberg School of Public Health

George Dimopoulos received his BSc in microbiology at Stockholm University and his PhD from the University of Crete where he studies population biology and gene expression of malaria transmitting mosquitoes. He was a Marie Curie postdoctoral fellow with Prof Fotis Kafatos at the European Molecular Biology Laboratory where he studied mosquito immunity to Plasmodium. He became a Senior Lecturer at Imperial College London in 2001 and was recruited as an Assistant Professor at the Johns Hopkins University Malaria Research Institute in 2003. Dr. Dimopoulos also received his MBA in 2008 from Johns Hopkins Carey Business School. Dr. Dimopoulos research focuses on the innate immune system of mosquitoes that transmit malaria parasites and dengue virus. Dr. Dimopoulos' research is funded by the NIH and he is a recipient of the Ellison Medical Foundation Young Investigator Award and an editorial board member of a variety of scientific Journals.

Diane E. Griffin, MD, PhD

Johns Hopkins Bloomberg School of Public Health

Dr. Griffin earned her BA at Augustana College in Rock Island, Ill and her MD, and PhD at Stanford University School of Medicine. She received clinical training in Internal Medicine at Stanford University Hospital and postdoctoral training in infectious diseases and virology at Johns Hopkins University School of Medicine. Her research interests are in the area of pathogenesis of viral diseases with a particular focus on measles and alphavirus encephalitis. These studies address issues related to virulence and the role of immune responses in protection from infection and in clearance of infection. She is currently Distinguished University Service Professor and Alfred and Jill Sommer Chair of the W. Harry Feinstone Department of Molecular Microbiology and Immunology at the Johns Hopkins Bloomberg School of Public Health. She is an editor for Field's Virology, has published more than 300 scientific papers, serves on several editorial and advisory boards and has been President of the American Society for Microbiology, the American Society for Virology and the Association of Microbiology and Immunology Chairs. She is a fellow of the American Association for the Advancement of Science and member of the National Academy of Sciences, American Academy of Microbiology and the Institute of Medicine.

Michael J. Klag, MD, MPH

Johns Hopkins Bloomberg School of Public Health

Dr. Klag is Dean of the Johns Hopkins Bloomberg School of Public Health, the oldest and largest independent graduate school of public health in the world. He is chair of the Association of Schools of Public Health and chair of the NIH Advisory Board on Clinical Research.

Dr. Klag is a world renowned kidney disease epidemiologist whose scientific contributions have been in the prevention and epidemiology of kidney disease, hypertension and cardiovascular disease. He was one of the earliest investigators to apply epidemiologic methods to the study of kidney disease. He directs one of the longest running longitudinal studies in existence, the Precursors Study, which began in 1946. Dr. Klag is the author of over 200 publications and was the Editor-in-Chief of the Johns Hopkins Family Health Book.

Dr. Klag earned his medical degree at the University of Pennsylvania and his MPH degree from the Johns Hopkins School of Hygiene and Public Health. For eight years, he was Director of the Division of General Internal Medicine and was the first Vice Dean for Clinical Investigation at the Johns Hopkins School of Medicine.

Sungano Mharakurwa, PhD, MSc

Johns Hopkins Center for Global Health

Sungano Mharakurwa earned his BSc. from the University of Zimbabwe in 1991. He was trained for MSc. (medical parasitology) at the London School of Hygiene and Tropical Medicine, awarded in 1993. Mharakurwa undertook his PhD studies at Oxford University, completing in 2001. He was a Beit Memorial postdoctoral fellow at the Peter Medawar Building for Pathogen Research, Oxford University, under leadership of geneticist Professor Karen Day. Mharakurwa joined the Johns Hopkins Malaria Research Institute for posting at the Malaria Institute at Macha field research station during its inception in November 2003. He is currently Malaria Institute at Macha Scientific Director and Johns Hopkins Bloomberg School of Public Health Senior Research Associate. Mharakurwa and others were the first to show proof of concept for the detection of malaria infection using human saliva samples in lieu of blood. His research interests include malaria non-invasive diagnosis and strategies for containment of drug resistance.

Photini Sinnis, MD

New York University Langone Medical Center

Photini Sinnis received a BA from Swarthmore College and attended medical school at Dartmouth. Following this she did postdoctoral training in the laboratory of Victor Nussenzweig at New York University where she studied the molecular events leading to hepatocyte recognition by malaria sporozoites. She joined the faculty at NYU School of Medicine where she continued her work on the pre-erythrocytic stages of the malaria parasite. This Fall, Dr. Sinnis relocated to the Johns Hopkins School of Public Health where she is an Associate Professor. She serves on the editorial boards of PLoS Neglected Tropical Diseases and PLoS ONE.

David Smith, PhD

University of Florida

David L. Smith earned BS and MS degrees in mathematics from Brigham Young University in Provo, Utah where he was also elected President of the Honors Student Council. He attended graduate school at Princeton University where he earned his MA and PhD in Ecology and Evolutionary Biology working with Simon A. Levin. He is currently Professor of the Department of Epidemiology (JHBSPH), member of the JHMRI, and Senior Fellow and Associate Director for Research at the Center for Disease Dynamics, Economics & Policy. Professor Smith has worked in departments of biology, global health, economics, and epidemiology, and his research questions are at the confluence of infectious disease ecology, epidemiology, economics, and policy. He has worked extensively on the epidemiology and control of malaria, strategic planning for malaria elimination, and the evolution of resistance to antimalarial drugs and antibiotics, and he has also published on the spatio-temporal dynamics or bioeconomics of human and avian flu, cholera, rabies, hospital-acquired infections, agricultural antibiotic use, and MRSA. Professor Smith is currently a member of the Malaria Atlas Project (MAP), the Malaria Elimination Group (MEG), the Malaria Eradication Research Agenda (MalERA), Extending the Cure (ETC), the Global Antibiotic Resistance Partnership (GARP), and The Human Mobility Mapping Project (THUMMP). He recently collaborated with the Zanzibar Minister of Health and the Zanzibar Malaria Control Progamme to write Malaria Elimination in Zanzibar, A Feasibility Assessment. Methodology from the report was recently adopted by the Global Malaria Programme at the W.H.O. His current research is funded by the Johns Hopkins Malaria Research Institute, the Bill & Melinda Gates Foundation, the National Institutes of Allergies and Infectious Diseases, and the RAPIDD program of the Science & Technology Directorate, Department of Homeland Security, and the Fogarty International Center, National Institutes of Health. He serves on the editorial boards of Advances in Parasitology and Malaria Journal.

Alfred Sommer, MD, MHS

Johns Hopkins Bloomberg School of Public Health

Dr. Sommer is a Gilman Scholar and University Distinguished Service Professor at Johns Hopkins University; Johns Hopkins Professor of Epidemiology, Ophthalmology, and International Health; and Dean Emeritus of the Bloomberg School of Public Health. He received his MD from Harvard Medical School (1967) and his Master of Health Science in Epidemiology from the Johns Hopkins School of Public Health (1973). He has published 5 books and over 300 scientific articles; has received numerous awards including the Albert Lasker Award for Clinical Research, the Warren Alpert Foundation Prize, and the Duke Elder International Gold Medal for Contributions to Ophthalmology; has delivered over 30 named lectureships, including the Jackson Memorial Lecture (American Academy of Ophthalmology), Duke Elder Oration (Royal College of Ophthalmologists), De Schweinitz Lecture (College of Physicians, Philadelphia), Dohlman Lecture (Harvard Medical School), Doyne Lecture (Oxford Ophthalmologic Congress), and the Kimura Lecture (University of California, San Francisco), among others; and is a member of both the National Academy of Sciences and its Institute of Medicine. His current research interests include child survival and blindness prevention strategies, micronutrient interventions, and the interface between public health and clinical medicine.

Phil E. Thuma, MD

Malaria Institute at Macha

Phil Thuma completed his undergraduate degree in Chemistry at Messiah College, Grantham, Pennsylvania and his medical degree at Temple University Medical School in Philadelphia. He subsequently completed a pediatric residency at Johns Hopkins Hospital, including an additional year as Chief Resident in Pediatrics. Other than a seven year period as a faculty member at Penn State University Hershey Medical Center in the 90's, he has spent most of his life and medical career working in rural Zambia as a medical doctor and researcher, concentrating on malaria as it presents in children. This work has led to over 45 publications in peer reviewed journals. In 2003 he began collaborating with the Johns Hopkins Malaria Research Institute to develop a malaria research field site at Macha Hospital in southern Zambia, and continues to work with the Johns Hopkins Bloomberg School of Public Health as a Senior Research Associate. Over the last 8 years these efforts have witnessed a marked decrease in malaria prevalence in the area around the hospital. Phil is active at the national level in Zambia serving on various committees, including the National Health Ethics Research Committee, of which he is currently vice chair.

Abstracts

The Founding of JHMRI
Alfred Sommer, MD, MHS, Johns Hopkins Bloomberg School of Public Health

Major new institutions arise from the unique intersection between individuals with insight and passion for a new undertaking, and individuals with insight and passion to fund it, and thereby make a difference. These are not random events.
 

Johns Hopkins Malaria Research Institute: An Opportune Time to Invest
Diane E. Griffin, MD, PhD, Johns Hopkins Bloomberg School of Public Health

In 2001, the war on malaria needed a better understanding of all aspects of this complicated disease and its transmission. New knowledge was necessary to provide the basis for the development of new tools for control at a time of increasing drug resistance and insecticide resistance. The first sequence information on the human genome had just become available and the Anopheles gambiae and Plasmodium falciparum genomes were almost complete, but there was little funding for basic research in malaria. The vision for JHMRI included recruitment of new faculty to form a critical mass of malaria investigators covering all aspects of the life cycle, construction of new laboratory space and core facilities, development of an endemic area field site and a pilot grant program to attract new investigators into malaria research.
 

Conquering Malaria: Community Involvement Can Make the Difference
Philip E. Thuma, MD, Malaria Institute at Macha, Zambia; Johns Hopkins Malaria Research Institute, Baltimore

Malaria has been endemic in sub-Saharan Africa for centuries, and only recently has there been hope that this disease can be conquered in that part of the world. Our experience with more than a 95% decline in malaria cases over the past ten years in the rural community around Macha Hospital in southern Zambia, has led us to analyze the various factors that may have contributed to this dramatic decrease. We will present evidence to suggest that a key factor in making the difference was the community involvement at the grass roots level. Without such involvement, we doubt that malaria can be conquered, despite using all the current modalities. Whether such community involvement can be reproduced in other parts of Africa to bring about the same dramatic decrease in malaria is open to question, but understanding the necessary elements in obtaining and maintaining community support for a concerted effort to conquer malaria, may be beneficial.
 
Coauthors: Sungano Mharakurwa1,2, Janneke van Dijk1, and Harry Hamapumbu1.
 
1. Macha Research Trust, Zambia.
2. Johns Hopkins Malaria Research Institute, Baltimore.
 

Tussle with a Thinking Parasite: Surprises from the Field
Sungano Mharakurwa, PhD, MSc, Johns Hopkins Bloomberg School of Public Health; Malaria Institute at Macha, Zambia

One of the key obstacles for control and elimination of malaria the emergence of drug resistance in the parasite, especially Plasmodium falciparum. Monitoring against spread of resistant parasites is therefore critical. However, current surveillance is mostly based on typing microscopy-positive human malaria infections. The infections in vector mosquitoes are seldom considered, despite the insects being the definitive host, where parasite genetic recombination occurs. Here we report unanticipated contrasts in the repertoire of P. falciparum resistance alleles in humans compared to those in local vector Anopheles arabiensis mosquitoes from sleeping huts in rural Zambia. DNA encoding P. falciparum dihydrofolate reductase (DHFR, EC 1.5.1.3) was genotyped by polymerase chain reaction (PCR) and allele-specific restriction enzyme digestion, with confirmatory DNA sequencing. Highly prevalent pyrimethamine resistance mutants were evident in human P. falciparum infections—S108N (91%), N51I (82%), C59R (59%) and 108N+51I+59R triple mutants (46%). This was expected from selection pressure due to decades of sulfadoxine/pyrimethamine use in the region. Surprisingly, these same mutants were up to 100-fold less prevalent in the vector mosquitoes. Instead, strikingly high cycloguanil resistance mutants were observed in mosquitoes—S108T (90%), A16V (57%) and the 108T+16V double mutant (49%)—despite absence of prior cycloguanil use in the area. We conclude that P. falciparum can exhibit highly host-specific drug resistance polymorphisms, most likely reflecting different selective pressures found in humans and mosquitoes. Thus, it may be essential to sample both human and mosquito vector infections to accurately monitor the epidemiological emergence of drug resistance alleles.
 
Coauthors: Mwiche Siame1, Mtawa A.P. Mkulama1, Sandra Chishimba1, Clive J. Shiff2, and Philip E. Thuma1,2.
 
1. Malaria Institute at Macha, Zambia.
2. Johns Hopkins Bloomberg School of Public Health.
 

How to Lose this Battle Against Malaria
David L. Smith, PhD, Johns Hopkins Bloomberg School of Public Health; Center for Disease Dynamics Economics and Policy, Washington, DC

Malaria kills hundreds of thousands of people each year, so a secondary function of malaria research has been advocacy. Scientists can exert a powerful influence for good or ill as their "expert opinion" influences the chatter among technocrats and shapes policy. The optimistic and pessimistic messages being sent by scientists about eradication, however, are sometimes supported by their own evidence, and they are often at odds with or unsupported by evidence, including the following four myths: 1) malaria transmission can't be interrupted in Africa; 2) the evolution of resistance caused malaria eradication to fail; 3) because of the loss of malaria immunity, most places were worst off when eradication failed; and 4) climate change poses a major threat to malaria eradication. The main conclusions to be drawn from the past are instead: 1) malaria can be eliminated from anywhere, but it is likely to take longer and cost more than anticipated; 2) the greatest threat to success is the loss of public interest, political will, and international financing; and 3) existing problems can be overcome with leadership.
 

Getting a Grip: How Malaria Parasites Establish Infection
Photini Sinnis, MD, New York University School of Medicine

Plasmodium sporozoites begin their life on the midgut wall of the mosquito and must successfully reach the liver of the mammalian host in order to establish malaria infection. Our work has focused on better understanding the interactions between sporozoites and their mosquito and mammalian hosts, that make this journey possible. We have performed studies of two important sporozoite proteins, CSP and TRAP, and have found that sporozoite proteases regulate the exposure and release of adhesive domains of these proteins. This in turn, regulates the overall adhesiveness of the sporozoite and enables it to either continue on its journey or change course to invade and develop into the next life cycle stage. These data suggest that proteases perform critical functions in sporozoites and may be good targets for future drug design.
 

Stopping Malaria in the Mosquito Belly
George Dimopoulos, PhD, MBA, Johns Hopkins Bloomberg School of Public Health

We are interested in understanding the role and mechanisms of the mosquito's immune system, and its intestinal bacterial flora (microflora), in stopping the malaria parasite Plasmodium development in the mosquito intestine. We have shown that the mosquito IMD (immune deficiency) pathway mediate anti-Plasmodium defense in the major malaria vector mosquitoes of sub-Saharan Africa, Central and South America, and Asia. Based on this knowledge we have generated the first genetically modified super-immune mosquitoes that turn on this defense system earlier and stronger than normal, when a mosquito feed on blood, thereby resulting in resistance to malaria parasite infection. In a separate study we have also shown that the intestinal microflora can both directly and indirectly influence the ability of the malaria parasite to infect the mosquito. Our studies revealed that the intestinal microflora induces the mosquito's immune system (basal immune activity) that, in turn, is acting against the malaria parasite. We have also identified a bacterium from the intestines of field-caught mosquitoes in Southern Zambia that exert direct anti-parasitic activity. The Enterobacter sp_Z bacterium produces reactive oxygen species that mediate the blocking of Plasmodium development in the mosquito intestine. We are currently exploring translational aspect of these discoveries that may lead to novel malaria control strategies.
 

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