ACTION FOR BUILDING CAPACITY (ABC) AT UVA

Richard L Guerrant, Professor
University Of Virginia Charlottesville Box 400195 Charlottesville, Va 229044195

Grant 3D43TW001136-05S1 from Fogarty International Center, IRG: ZAI1

Project start date: 1999-07-01

Project end date: 2005-06-30

3D43TW001136-05S1 (2004): $100000

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EPIDEMIOLOGY, PREDISPOSING FACTORS, ETIOLOGIES OF PROLONGED DIARRHEA

Richard L Guerrant, Professor
University Of Virginia Charlottesville Box 400195 Charlottesville, Va 229044195

Grant 5U01AI026512-100001 from National Institute Of Allergy And Infectious Diseases, IRG:

Abstract: With the improved understanding and control of acute diarrheal illnesses, prolonged diarrheal illnesses and now emerging as a leading cause of morbidity and mortality. However, the epidemiology, etiology and pathogenesis of prolonged diarrheal remain very poorly understood. Several investigators have described bacterial overgrowth in the upper small bowel of patients with prolonged diarrhea or malnutrition; however, their specific nature and role in causing disease remain unknown. Based on studies with colonizing, non-toxigenic E. coli in piglets (19) and in human volunteers (20), we have recently demonstrated that the non-toxigenic, human colonizing E. coli strain 1392+ (CFA/II) but not the CFA/II negative derivative, colonizes the small intestine in large numbers and causes prolonged diarrhea in a rabbit model (17), establishing that colonization per se can cause prolonged small intestinal net secretion and diarrhea. We postulate that prolonged diarrhea is more common than generally recognized, has significant predisposing risk factors, and that combinations of specific infections (such as C. pylori gastritis with achlorhydria, and small bowel colonization with specific colonizing bacteria) derange small bowel electrolyte and nutrient absorption in susceptible hosts to cause prolonged diarrhea. Our overall objective is to determine the epidemiology, predisposing factors, etiologies, and pathogenesis of prolonged diarrhea in a highly endemic area, the tropical, developing Northeast of Brazil. We shall follow a cohort of infants born in an urban favela (slum) in Fortaleza, Ceara for frequency, risk factors, potential etiologies and the sequence of events leading to prolonged diarrhea (>14d). We shall conduct detailed fecal studies of 500 cases of all diarrhea and 100 cases of prolonged illness (to include 50 cases of sequential sampling of cases that become prolonged), then conduct intubation and balance studies of 50 children and 30 adults with prolonged diarrhea (>14, <30 days) and controls to examine potential etiologies (including quantitative cultures of adherent flora), host differences, and functional derangements. We shall determine the role and mechanisms by which colonizing Enterobacteriaciae either alone or in concert with other agents such as C. pylori or rotaviruses may contribute to prolonged intestinal dysfunction and malnourishing diarrhea. These studies will define potential risk factors and the sequence of events that lead to prolonged diarrhea, its etiologies and the key host factors and functional derangements that must be considered in controlling this important problem.

Keywords: Enterobacteriaceae, diarrhea, disease /disorder proneness /risk, epidemiology, tropical medicine, Escherichia coli, Helicobacter, achlorhydria, chronic disease /disorder, enteric bacteria, gastritis, gastrointestinal absorption /transport, infant human (0-1 year), malnutrition, microorganism growth, parasitic disease, preschool child (1-5), Bacillus, Brazil, Fungi, Retroviridae, Vibrionaceae, feces analysis, human subject, intubation, nutrition related tag

Tailoring Novel Therapeutics For Emerging Drug-Resistant C. Difficile Colitis

Richard L Guerrant, Professor
Medicineuniversity Of Virginia Charlottesville

Grant 5U01AI075526-02 from National Institute Of Allergy And Infectious Diseases, IRG: ZAI1

Abstract: Until recently, C. difficile associated diarrhea (CDAD) occurred as an opportunistic infection in older hospitalized patients on antibiotics. Currently, CDAD has become much more worrisome because of widespread increases in its frequency and severity throughout the US and Canada due to the emergence of hypertoxinogenic, binary toxin-producing, quinolone-resistant (Bl) strains. Furthermore, life threatening CDAD is now affecting healthy younger people in communities, even without recent antibiotic use. Even worse, current treatment consisting of more antibiotics is failing and often prolongs shedding or relapses. Hence we urgently need novel approaches that block toxin-induced colitis to prevent the progression of colitis produced by C. difficile toxin(s)) without further disruption of protective flora. This application from the University of Virginia brings together our experienced enterics laboratory team with basic science colleagues in toxin pathogenesis and in drug development, and a pharmaceutical partner (Adenosine Therapeutics, LLC). We shall address the emerging quinolone-resistant C. difficile colitis with an innovative antitoxic approach that is supported by pilot data demonstrating considerable promise. We propose to investigate three types of anti-inflammatory agents alone and in combination adenosine A2A receptor agonists that block leukocyte activation; A2B antagonists that block cytokine production by epithelial and mast cells, and the pro-absorptive injury repairing agent, alanyl-glutamine. The first three closely interrelated specific aims are designed to determine how these novel therapeutics regulate intestinal cell targets to block toxin-induced apoptosis, inflammation, and secretion. We plan to 1) use new human intestinal epithelial cell organoid and C57BL/6 murine models to define the targets of purified toxins A and B as well as B-variant and new Bl strain supernatants; 2) use C57BL/6 mice with adenosine receptor knockouts and Cre/loxp targeted cellular AaA receptor deletions to define the relevant adenosine targets to inhibition of toxin effects; and 3) use the information gained in aims 1 and 2 to test combinations of A2A agonists, A2B antagonists and alanyl-glutamine, alone and in combination, in animal models in order to prepare for clinical trials of these novel drug therapies for increasingly serious CDAD in humans. Our fourth aim involves discovery efforts towards developing more highly absorbed AaR agonists and the synthesis of the proposed A2A, agonists and A2B antagonists necessary to support this grant

Keywords: colitis, toxin Canada, Enterococcus, acid, actin, adenosine, aging, antibiotic, apoptosis, bacterial toxin, biology, bone marrow, cell, cell death, cell wall, chemotherapy, children, ciprofloxacin, clinical trial, colon surgery, community, concept, culture, cytokine, cytoskeleton, death, diarrhea, emotion, epithelium, experience, gene, genetics, glutamine, granulocyte, hamster, hospital, human, infection, inflammation, injury, lead, leukocyte activation /transformation, library, ligand, lymphocyte, macrophage, mast cell, metronidazole, model, neutralizing antibody, neutrophil, nursing home, opportunistic infection, organism, pathology, peptide, peptidoglycan, pharmacokinetics, pharmacology, pharyngitis, pregnancy, prodrug, purinergic receptor, quinoline, receptor, role, secretion, therapy, tissue /cell culture, tissue mosaicism, toll like receptor, transplantation, twin /multiplet, university, vancomycin, virulence, water

Project start date: 2007-08-01

Project end date: 2012-07-31

1U01AI075526-01 (2007): $697754

ENTERIC PATHOGENS

Richard L Guerrant, Professor
University Of Maryland Baltimore 660 W Redwood St, Rm 021 Baltimore, Md 21201

Grant 1U54AI057168-010005 from National Institute Of Allergy And Infectious Diseases, IRG: ZAI1

Abstract: Research Project V includes two Sub-Projects focused on key new aspects of the genomics, pathogenesis and vaccinology of the two leading Category B low-dose enteropathogens, and on their detection in clinical and environmental samples. These include the highly chlorine-resistant Cryptosporidium parvum, the most fearsome Shigella threat (S. dysenteriae 1) and the largely untreatable, Shiga toxin-producing enterohemorrhagic E. coli. These three pathogens all pose serious risks as low infectious dose agents of bioterrorism as well as major national and global health endemic and epidemic challenges. The team of investigators for this project has a very strong track record of working with these organisms. Led by experienced investigators with international reputations in enteric diseases, Richard L. Guerrant and James B. Kaper, this project builds upon highly productive expertise and upon longstanding and new cross-institutional synergies at UVa, UMd, VCU, VT, USUHS, UVt, and JHU. Our first Sub-Project V.1, on "Cryptosporidium genomics, pathogenesis and vaccinology" builds upon the near complete sequencing of the human (type 1) C. parvum genome by the VCU group, the published tissue culture, animal and field experience with Cryptosporidium by the UVa group, the plant-based production of mucosal vaccines at VT and on studies of the genetics of susceptibility at UVa, UVt, and JHU to identify and express type 1 (human) C. parvum candidate genes, define their roles in pathogenesis and immunity, express promising candidates and define genetic determinants of human susceptibility and thus optimal approaches to vaccine development. Sub-Project V.2 will engage UMd, USUHS and UVa colleagues to construct novel Shigella dysenteriae and enterohemorrhagic E. coli (EHEC) vaccines and develop novel therapeutics for EHEC disease.

Keywords: Enterobacteriaceae, bacterial vaccine, communicable disease control, drug screening /evaluation, nonhuman therapy evaluation, pharmacokinetics, protozoal vaccine, vaccine development, vaccine evaluation, Cryptosporidium, Escherichia coli, Shigella dysenteriae, Shigella vaccine, bioterrorism /chemical warfare, cooperative study, immunotherapy, live vaccine, pathologic process, shiga toxin, Macaca fascicularis, biotechnology, functional /structural genomics, high throughput technology, informatics, laboratory mouse, microarray technology, molecular cloning

Project start date: 2003-08-01

Project end date: 2008-07-31

Global Infectious Disease Research Training Grant At UVa

Richard L Guerrant, Professor
Medicineuniversity Of Virginia Charlottesville

Grant 2D43TW006578-06 from Fogarty International Center, IRG: ZRG1

Abstract: Our Global Infectious Diseases Research Training Program builds upon over 25 years of collaboration between the University of Virginia (UVa) and the Federal University of Ceara (UFC) in Fortaleza, Brazil. Together we have identified key needs and gaps in research capacity and have developed and pursued research opportunities through our findings on the long-term effects of endemic enteric and parasitic infections. The continuing goal of this training program is to build relevant laboratory, clinical trials, and genetic epidemiology expertise to strengthen the capacity of the Federal University of Ceara, in order to provide critical new data to instruct policy and practice on controlling endemic enteric and parasitic infections and their lasting consequences. The GIDRT training program at UVa focuses upon genetic epidemiology and clinical trials, areas of priority identified in our needs assessment. Carefully selected fellows from UFC train at UVa under the mentorship of dedicated faculty. Their programs are enriched by interaction and collaboration with other international trainees and by special activities such as courses and colloquia in microbial pathogenesis, immunology, genetics, and clinical trials, a research-in-progress series, and a journal club. Our model of sustained international training and collaboration has resulted in 100% of our fellows returning home after training. Their continued research alliances with UVa faculty result in shared discoveries, patents, grants, and publications (over 200 to date). All too often international training results in opportunities for overseas physicians and scientists to move permanently to the US (the "brain drain"). Our strongly articulated philosophy and documented track record is precisely the opposite to attract the brightest and most innovative researchers who are strongly committed to returning home after their training because the opportunities for further progress on their global infectious disease research priorities are greatest in their home countries

Project start date: 2003-09-05

Project end date: 2013-03-31

5D43TW006578-05 (2007): $133950

3D43TW006578-04S1 (2006): $113541

5D43TW006578-04 (2006): $142500

5D43TW006578-03 (2005): $150000

5D43TW006578-02 (2004): $150000

Global Infectious Disease Research Training Grant

Richard L Guerrant, Professor
University Of Virginia Charlottesville Box 400195 Charlottesville, Va 229044195

Grant 1D43TW006578-01 from Fogarty International Center, IRG: ZRG1

Abstract: Our Global Infectious Diseases Research Training Program builds upon our sustained 20 year collaborations at the University of Virginia with the Federal University of Ceara in Fortaleza, Brazil, and upon our identification of key needs and gaps in research capacity and opportunities raised by our findings of long-term effects of endemic enteric and parasitic infections there. The program goal is to build relevant laboratory, clinical trials and genetic epidemiology expertise to fill gaps and needs in these areas and to strengthen the capacity of the Federal University of Ceara, in order to provide key new data to instruct policy on controlling endemic enteric and parasitic infections and their lasting consequences. Our research themes will focus upon the key areas of need and opportunity genetic epidemiology and clinical trials. The training of carefully selected, competing postdoctoral fellows is enriched by special activities of this program, including an expanded 2 semester course on microbial pathogenesis, immunology, genetics and clinical trials courses and colloquia, a research-in-progress series, and a journal club, Our model of sustained international training and collaboration has resulted in a track record of 100% return of international trainees to become leaders in relevant research and excellence in centers in their home countries. All too often international training means providing opportunities for overseas physicians and scientists to be moved permanently to the U.S. (the typical problem of the "brain drain"). Our strongly articulated philosophy and documented track record is precisely the opposite to attract the brightest and most innovative researchers who are strongly committed and have positions to which they prepare to return because the global infectious diseases problems on which they work present greater opportunities in their home countries.

Keywords: clinical trial, communicable disease, genetic susceptibility, health science research support, training, Brazil, gastrointestinal infection, international cooperation, parasitic disease, postdoctoral investigator, human subject

Project start date: 2003-09-05

Project end date: 2008-03-31

1D43TW006578-01 (2003): $150000

APOE And The Effects Of Malnutrition On Cognitive And Intestinal Development

Richard L Guerrant, Professor
University Of Virginia Charlottesville Box 400195 Charlottesville, Va 229044195

Grant 5R01HD053131-02 from National Institute Of Child Health And Human Development, IRG: ZRG1

Abstract: In long-term studies, we have discovered important associations of impaired cognitive development, physical fitness, and growth with early childhood diarrhea and malnutrition in favela (shantytown) children in Northeast Brazil. Having found that an "Alzheimer s-like" deficit in higher executive function and semantic fluency were most affected, we then found a striking association of the "Alzheimer s gene," APOE4, with protection from the cognitive developmental impairments. Hence we postulate that early childhood diarrhea and its consequent malnutrition have their greatest impact via lasting impairment on cognitive development effects that are accentuated in individuals lacking the "protective" APOE4 allele and that specific micronutrient interventions can ameliorate this effect. In order to directly test our hypothesis that intestinal and cognitive impairments involve ApoE and that specific micronutrients can ameliorate these effects, and to examine potential mechanisms involved, we have established murine models of early malnutrition, growth, and cognitive development in both wild-type and APOE-knockout mice in our collaborations at the Federal University of Ceara (UFC) in Brazil and at the University of Virginia (UVa) respectively. Furthermore, with a synergistic new collaboration with colleagues at Duke University, we can specifically examine effects of APOE4 using human APOE4 targeted replacement "knock-in" mice to "close the loop" on our hypothesis and directly assess whether and how apoE4 is protective against intestinal and cognitive effects of malnutrition, studies that will have direct implications for the optimal health and development of children throughout developing areas. Hence our specific aims are to define the effects of malnutrition and specific micronutrients on intestinal, brain, and cognitive development in a murine model using outbred and inbred wild-type, ApoE knock-out (ko), and human ApoE4 targeted replacement "knock-in" C57BI mice. We will define the effects on intestinal and brain histology and maturation using immunohistochemical methods and studies of developmental milestones and behavioral ontogeny. We will seek to identify potential mechanisms of these effects in the intestine and brain including studies of IGF-1, and will examine the effects of glutamine, zinc, and arginine interventions.

Keywords: apolipoprotein E, cognition disorder, diarrhea, growth /development, intestine disorder, malnutrition, allele, biological signal transduction, disease /disorder model, executive function, physical fitness, semantics, behavior test, genetically modified animal, histology, immunocytochemistry, laboratory mouse

Project start date: 2006-09-22

Project end date: 2011-07-31

5R01HD053131-02 (2007): $256463

1R01HD053131-01 (2006): $272548

LONG-TERM IMPACT AND INTERVENTION FOR DIARRHEA IN BRAZIL

Richard L Guerrant, Professor
University Of Virginia Charlottesville Box 400195 Charlottesville, Va 229044195

Grant 3U01AI026512-15S3 from National Institute Of Allergy And Infectious Diseases, IRG: ZAI1

Abstract: Having defined the magnitude, major new etiologies, key novel mechanisms and short-term impact of persistent diarrheal illnesses and even certain "asymptomatic" enteric infections in a model collaboration and cohort of children born into active prospective surveillance in an urban shantytown in Northeast Brazil, we are now have a unique opportunity to define for the first time the long-term DALY (disability adjusted life years) impact of early childhood enteric infections on nutritional status defined by anthropometry, physical activity and fitness, and cognitive function over extended periods (even years later). We postulate, based on our short-term impact data, that the greatest long-term impact will occur in children with persistent diarrheal illnesses and in those with low height-for-age Z (HAZ) scores. Having also shown the potential short-term benefits of a new glutamine-based oral rehydration and nutrition therapy (ORNT) and of vitamin A (with studies of zinc pending) on speeding the repair of damaged intestinal barrier function, we can now determine the potential long-term benefits of glutamine-based ORNT, with vitamin A and zinc therapy (targeting children with persistent diarrhea or reduced HAZ, as noted above). We shall also examine the intermediate (ie 1- 6 months) and long-term (greater than 6 months) effects of specific emerging enteric infections we have found to be important, enteroaggregative E. coli, and Cryptosporidium parvum. Coupled with our new developments of stable glutamine derivatives, the above data on full long-term DALY impact of persistent diarrhea, enteric infections and malnutrition, and the data on benefits of glutamine-based ORNT with vitamin A and zinc will ultimately allow us to calculate a much more meaningful cost-effectiveness (in "dollars per DALY averted) of selected treatment of high risk children (ie any with a persistent diarrheal illness that extends greater than 14 days, or a height for age Z score of less than 0.5). This model, longstanding collaboration and prospective field cohort surveillance will also enable the use of molecular tools currently being developed to define the epidemiology and microbiology of such newly recognized major agents as enteroaggregative E. coli as well as opening new opportunities to train both US and international scientists in highly relevant bench and field investigation. This pioneering work builds on our unique opportunity to define for the first time the potentially huge (developmental and economic) burden of early childhood enteric infections, as well as holding promise for demonstrating a key intervention targeted at the most vulnerable subset of the population in greatest need.

Keywords: Enterobacteriaceae disease, child (0-11), child physical development, developmental nutrition, diarrhea, diet therapy, epidemiology, human therapy evaluation, tropical medicine, body water dehydration, chemoprevention, cooperative study, dietary mineral, dietary supplement, glutamine, longitudinal human study, malnutrition, retinoid, urban poverty area, zinc, Brazil, clinical research, human subject, nutrition related tag

Project start date: 1989-05-01

Project end date: 2007-04-30

3U01AI026512-15S3 (2006): $543413

3U01AI026512-15S2 (2005): $443305

3U01AI026512-15S1 (2004): $634082

5U01AI026512-15 (2003): $782748

3U01AI026512-14S1 (2002): $100547

5U01AI026512-14 (2002): $311947

5U01AI026512-13 (2001): $341036

5U01AI026512-12 (2000): $337741

2U01AI026512-11 (1999): $323889

APOE Genotype In Brazilian Children With Early Diarrhea

Richard L Guerrant, Professor
University Of Virginia Charlottesville Box 400195 Charlottesville, Va 229044195

Grant 3R21TW006713-02S1 from Fogarty International Center, IRG: ZNS1

Abstract: Having defined the magnitude, major new etiologies, key novel mechanisms and short-term and long-term impact of persistent and recurring diarrheal illnesses on cognitive development in a model collaboration and cohort of children born into active prospective surveillance in poor urban areas (shanty-towns) in Northeast Brazil, we now have a unique opportunity to better assign causal relationships by establishing the importance of genetic markers in defining risk, plan prevention strategies for future interventions, and build sustainable human genetic research together with environmental assessment. This proposal directly addresses potentially remediable mechanisms of long-term cognitive impairment, which we have calculated more than doubles the DALY impact of early childhood diarrheal illnesses worldwide. We postulate, based on our previous cognitive outcome data, that the greatest long-term impact will occur in children with persistent and recurring diarrheal illnesses carrying APOE4 alleles, a well-known genetic marker related to poor recovery following brain injury and sporadic, late-onset Alzheimer disease. Since APOE4 is associated with impaired recovery from brain injury, but not with cognitive function in healthy children, an association of APOE4 with impaired cognitive development that we see with heavy diarrhea burdens in favela (shanty-town) children will strongly suggest that these children endure a form of "brain injury" with their heavy diarrheal illness burdens in their most formative first two years of life. Hence, our longstanding collaboration and prospective field cohort surveillance will enable the use of new approaches and genetic technologies to define APOE allele distribution with impaired cognitive development, thus assessing the potential impact of early childhood diarrheal illnesses as a cause of "brain injury" at the critical formative first 2 years of life. This project will also open new opportunities to train both US and international scientists in highly relevant bench and field investigation, holding promise for demonstrating a key intervention targeted at the most vulnerable subset of children in greatest need.

Keywords: Brazil, apolipoprotein E, cognition disorder, developmental disease /disorder, diarrhea, early experience, epidemiology, gene expression, training, biomarker, brain injury, disease /disorder prevention /control, disease /disorder proneness /risk, genotype, health disparity, human population study, infant human (0-1 year), neuropsychology, urban poverty area, clinical research, human subject

Project start date: 2003-09-28

Project end date: 2006-02-28

3R21TW006713-02S1 (2005): $43217

5R21TW006713-02 (2004): $122752

Long-term Impact And Intervention For Diarrhea In Brazil

Richard L Guerrant, Professor
University Of Virginia Charlottesville

Grant 5U01AI026512-17 from National Institute Of Allergy And Infectious Diseases, IRG: ZAI1

Abstract: Having defined substantial lasting impacts of early childhood diarrhea on childhood physical and cognitive development and having launched a placebo-controlled trial in a cohort of favela children in whom informative long-term follow-up by an experienced surveillance team is now feasible, we are now poised to address the potential causality for these devastating effects that more than double the global diarrhea DALYs by assessing the impact of micronutrient interventions in long-term follow-up (work that complements our ongoing studies of their mechanisms in vitro and in an animal model) and by assessing the heritability and plausible genetic determinants of parasitic infections, overt symptoms, and their long-term impact on physical and cognitive development. Hence our broad, long-term objectives are to ameliorate the long-term developmental impact of early childhood diarrhea and parasitic infections by showing effective interventions and demonstrating potential genetic determinants of these enteric infections and their impact. Initial studies in vitro and in children suggest that zinc and potentially synergistic arginine are among key micronutrients for the repair of intestinal damage and absorptive function. Our specific aims are therefore to (1) Determine the effects of zinc (alone or in combination with vitamin A) on the long-term development of higher executive function in an ongoing randomized clinical trial and in a new intervention trial of arginine (with or without zinc or alanyl-glutamine) on diarrhea morbidity, nutritional status, cognitive development, and intestinal barrier function; and (2) Define plausible genetic determinants of genotype specific major enteric protozoan and enteroaggregative E. coli (EAEC) infections, overt diarrhea, intestinal inflammation, and long-term developmental sequelae using pedigree and candidate single nucleotide polymorphism analyses for which we already have seminal clues. Now that we are finding that the greatest impact is on semantic fluency in APOE4-negative individuals experiencing heavy diarrhea (and also knowing that APOE4 is associated with enhanced arginine transport in developing microglia), our most provocative unifying hypothesis is that zinc will improve cognitive function by improving absorption and nutritional status and that arginine may specifically protect the absorptive function, growth, and semantic fluency in APOE4-negative children experiencing heavy diarrhea burdens. This single project ICIDR renewal, focused upon our existing strengths and unique opportunities, will not only build clinical trial and molecular genetics tools at our collaborating site in Northeast Brazil (now in new expanded facilities), but it will also help further document causality and solutions that will drive policy to address the costly problem of diarrheal diseases, enteric parasitic infections, and their long-term sequelae.

Keywords: Enterobacteriaceae disease, child (0-11), child physical development, developmental nutrition, diarrhea, diet therapy, epidemiology, human therapy evaluation, tropical medicine, body water dehydration, chemoprevention, cooperative study, dietary mineral, dietary supplement, glutamine, longitudinal human study, malnutrition, retinoid, urban poverty area, zinc, Brazil, clinical research, human subject, nutrition related tag

Project start date: 1997-06-01

Project end date: 2010-04-30

2U01AI026512-16 (2007): $539735

UVa Framework Program In Global Health

Richard L Guerrant, Professor
University Of Virginia Charlottesville Box 400195 Charlottesville, Va 229044195

Grant 5R25TW007518-02 from Fogarty International Center, IRG: ZAI1

Abstract: Founded in 2001, the University of Virginia s Center for Global Health (CGH) builds on a 23-year program in Geographic Medicine. The CGH promotes the engagement of faculty and students in the development of multidisciplinary research and service projects that address global health issues. Through existing collaborations with international colleagues and institutions, CGH annually sponsors over 40 UVa students in mentored global health research and service projects abroad. In addition, 8-10 international research fellows, competitively selected from our collaborating institutions, come to UVa each year for training and research with UVa faculty mentors. Over 80 such fellows have now trained at UVa, and 100% have returned to their home countries to help build collaborative programs that include trans-university Centers for Global Health in Brazil, Philippines, Ghana, and South Africa. In the last four years, the number of global health-related courses and activities at UVa has exploded. Both undergraduate and professional students have formed interest groups related to global health, and student demand for information, career advice, and opportunities in global health has grown markedly. We therefore recognize the need for a Framework Program in Global Health to build a sustainable strategy to incorporate global health into curricular offerings across the university. We have seen how individual courses can develop and succeed. The Framework Program will reinforce links between existing courses and programs, institutionalize and formalize credit for work in global health, including the development of degree programs, and foster the creation of new opportunities for collaboration within the University and between our international partners. Our Framework Program will bring together three principal partners at UVa the Schools of Medicine and Nursing, and the College of Arts and Sciences. It will include 5 components 1) A Global Health Curriculum Working Group, coordinated by the Center for Global Health, to convene 8-10 faculty members from the Schools of Medicine, Nursing, and Arts and Sciences to plan and implement global health curricula and coordinate participation by their respective schools. 2) The Working Group will develop multidisciplinary global health curricula for undergraduate, graduate, and professional students across the university. 3) A University-wide conference schedule engaging UVa faculty, international fellows, and students in global health issues will invite visiting scholars from collaborating international institutions. 4) Expanded global health career planning services through website resources, internship placement, and mentoring from former global health scholars, fellows, and faculty contacts. 5) A coordinated, university-wide plan to raise funds to sustain global health programs at UVa.

Keywords: curriculum, education evaluation /planning, health care personnel education, health education, health science research support, career, meeting /conference /symposium, mentoring /mentor, organized financing, United States

Project start date: 2005-09-21

Project end date: 2008-07-31

5R25TW007518-02 (2006): $128250

1R25TW007518-01 (2005): $135000

5R25TW007518-03 (2007): $120555

Global Infectious Disease Research Training Grant At UVa

Richard L Guerrant, Professor
University Of Virginia Charlottesville Box 400195 Charlottesville, Va 229044195

Grant 3D43TW006578-05S1 from Fogarty International Center, IRG: ZRG1

Project start date: 2003-09-05

Project end date: 2008-03-31

3D43TW006578-05S1 (2007): $81447

3D43TW006578-05S2 (2007): $157262

INT´L TRAINING AND RESEARCH IN EMERGING INFECTIOUS DISEA

Richard L Guerrant, Professor
Medicineuniversity Of Virginia Charlottesville
box 400195
charlottesville, Va 229044195

Grant 5D43TW000909-05 from Fogarty International Center, IRG: ZAI1

Project start date: 1997-09-20

Project end date: 2005-07-31

5D43TW000909-05 (2001): $188413

ACTION FOR BUILDING CAPACITY (ABC) AT UVA

Richard L Guerrant, Professor
Medicineuniversity Of Virginia Charlottesville
box 400195
charlottesville, Va 229044195

Grant 5D43TW001136-03 from Fogarty International Center, IRG: ZAI1

Project start date: 1999-07-01

Project end date: 2004-06-30

5D43TW001136-03 (2001): $98389

5D43TW001136-02 (2000): $100000

INT´L TRAINING AND RESEARCH IN EMERGING INFECTIOUS DISEA

Richard L Guerrant, Professor
Medicineuniversity Of Virginia Charlottesville
box 400195
charlottesville, Va 229044195

Grant 5D43TW000909-04 from Fogarty International Center, IRG: ZAI1

Project start date: 1997-09-20

Project end date: 2002-07-31

5D43TW000909-04 (2000): $163801

5D43TW000909-03 (1999): $156275

ACTION FOR BUILDING CAPACITY (ABC) AT UVA

Richard L Guerrant, Professor
Medicineuniversity Of Virginia Charlottesville
box 400195
charlottesville, Va 229044195

Grant 1D43TW001136-01 from Fogarty International Center, IRG: ZAI1

Project start date: 1999-07-01

Project end date: 2004-06-30

1D43TW001136-01 (1999): $53316

RECOGNITION And EXPRESSION OF TROPICAL INFECTIOUS DISEASES

Richard L Guerrant, Professor
University Of Virginia Charlottesville Box 400195 Charlottesville, Va 229044195

Grant 5U01AI026512-10 from National Institute Of Allergy And Infectious Diseases, IRG: SRC

Keywords: diarrhea, tropical medicine, human subject

Project start date: 1989-05-01

Project end date: 1999-05-31

5U01AI026512-10 (1998): $187990

INT´L TRAINING AND RESEARCH IN EMERGING INFECTIOUS DISEA

Richard L Guerrant, Professor
Medicineuniversity Of Virginia Charlottesville
box 400195
charlottesville, Va 229044195

Grant 1D43TW000909-01 from Fogarty International Center, IRG: ZAI1

Project start date: 1997-09-20

Project end date: 2002-09-19

1D43TW000909-01 (1997): $150000

RECOGNITION & EXPRESSION OF TROPICAL INFECTIOUS DISEASES

Richard L Guerrant, Professor
Internal Medicineuniversity Of Virginia Charlottesville
box 400195
charlottesville, Va 229044195

Grant 5U01AI026512-09 from National Institute Of Allergy And Infectious Diseases, IRG: SRC

Keywords: diarrhea, tropical medicine human subject

Project start date: 1989-05-01

Project end date: 1999-05-31

5U01AI026512-09 (1997): $219692

EAGGEC INFECTION--EPIDEMIOLOGY AND PATHOPHYSIOLOGY

Richard L Guerrant, Professor
Medicineuniversity Of Virginia Charlottesville
box 400195
charlottesville, Va 229044195

Grant 3U01AI026512-09S1 from National Institute Of Allergy And Infectious Diseases, IRG: ZAI1

Project start date: 1989-05-01

Project end date: 1999-05-31

3U01AI026512-09S1 (1997): $193295

RECOGNITION & EXPRESSION OF TROPICAL INFECTIOUS DISEASES

Richard L Guerrant, Professor
Internal Medicineuniversity Of Virginia Charlottesville
box 400195
charlottesville, Va 229044195

Grant 5U01AI026512-08 from National Institute Of Allergy And Infectious Diseases, IRG: SRC

Project start date: 1989-05-01

Project end date: 1999-05-31

5U01AI026512-08 (1996): $288817

RECOGNITION & EXPRESSION OF TROPICAL INFECTIOUS DISEASE

Richard L Guerrant, Professor
Internal Medicineuniversity Of Virginia Charlottesville
box 400195
charlottesville, Va 229044195

Grant 3U01AI026512-08S1 from National Institute Of Allergy And Infectious Diseases, IRG: SRC

Project start date: 1989-05-01

Project end date: 1999-05-31

3U01AI026512-08S1 (1996): $30000

RECOGNITION And EXPRESSION OF TROPICAL INFECTIOUS DISEASES

Richard L Guerrant, Professor
University Of Virginia Charlottesville Box 400195 Charlottesville, Va 229044195

Grant 5U01AI026512-07 from National Institute Of Allergy And Infectious Diseases, IRG: SRC

Keywords: diarrhea, tropical medicine, human subject

Project start date: 1989-05-01

Project end date: 1999-05-31

5U01AI026512-07 (1995): $201867

RECOGNITION & EXPRESSION OF TROPICAL INFECTIOUS DISEASES

Richard L Guerrant, Professor
Internal Medicineuniversity Of Virginia Charlottesville
box 400195
charlottesville, Va 229044195

Grant 5P01AI026512-05 from National Institute Of Allergy And Infectious Diseases, IRG: SRC

Keywords: diarrhea, tropical medicine human subject

Project start date: 1989-05-01

Project end date: 1995-04-30

5P01AI026512-05 (1993): $362503

RECOGNITION & EXPRESSION OF TROPICAL INFECTIOUS DISEASES

Richard L Guerrant, Professor
University Of Virginia Charlottesville Box 400195 Charlottesville, Va 229044195

Grant 3P01AI026512-04S1 from National Institute Of Allergy And Infectious Diseases, IRG: SRC

Project start date: 1989-05-01

Project end date: 1994-04-30

3P01AI026512-04S1 (1992): $912