CDC Seed Projects - Abstracts

Development of Hydrogel Microarrays for Multiplex Detection of Pathogens by Nucleic Acid Hybridization

L. Andrew Lyon, PhD (Georgia Tech) and Jonas M. Winchell, PhD, MS (CDC)

DESCRIPTION: This proposal is aimed at developing a novel detection technology employing responsive hydrogel microlens arrays that can detect many different pathogens. Bioterrorism threats and the emergence of novel pathogens underscore the need for the development of rapid, sensitive, and robust diagnostic technologies. Although many detection methods exist, none meets all of the needs described above; each has its own intrinsic advantages and limitations. The proposed project is an attempt to develop a reliable and novel detection system that requires less expertise and expense than current systems, but takes advantage of the sensitivity and specificity of nucleic acid hybridization. The research, which encompasses the complimentary expertise of the Co-PI’s, has three specific objectives. The first objective is to demonstrate a proof of concept for the application of hydrogel microlens arrays that are responsive to nucleic acid hybridization events. Model oligonucleotide DNA probes will be selected and incorporated in microlenses using standard coupling chemistry. The performance of the assay with known DNA sequences from Mycoplasma pneumoniae will be tested to identify critical parameters and optimal conditions for hydrogel microlens based detection. The second objective is to optimize DNA probe molecules to enhance stringent binding specificity to DNA targets. A stringency clamp approach will be employed to design DNA probes that will discriminate perfectly matched target sequences from imperfectly paired sequences that may occur in multiplex hybridization environments. The third objective is to build a secondary confirmatory reporting signal into the biosensor design.  This approach will increase accuracy in reported results and enable greater sensitivity.  

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Exploring the use of social media and mobile technologies for diabetes management

Beth Mynatt, PhD (Georgia Tech) and Scott Mullins (CDC)

DESCRIPTION: We propose initiating a new collaboration integrating three complementary research activities all aimed at improving chronic disease management.  Our complementary goals include (a) understanding the potential of mobile monitoring technologies for connecting relevant moments of monitoring with opportunities for learning about chronic disease management, (b) understanding the potential of web-based discussions to model reflection and to improve disease understanding, and (c) understanding the hoped-for connection between increased understanding and subsequent behavior change.

Specifically the team will iteratively review the data of an on-going pilot study, assess its potential impact, and design a subsequent study.  This initial study involves adults (ages 40-65) newly diagnosed with diabetes.  The on-going pilot study examines the use a glucometer integrated with a cell phone that prompts for questions and concerns when a person takes a glucose reading.   The captured data is then available on a collaborative website for discussion by the person with diabetes and a diabetes educator.  Preliminary results indicate that participants improve in their ability to effectively reflect about disease management in contrast to the control group.

Specific outcomes of this proposed project include collaborative review of the pilot study data, subsequent technology design, and the collaborative design, implementation and analysis of a follow-on study.  Possible follow-on study topics include (a) investigating social media techniques to further motivate diabetes management and (b) understanding potential barriers of this approach with older adults (aged 65-80) by assessing the difficulty of using the mobile device and enabling direct interaction via the website.

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Emergence of Vibrio parahaemolyticus Pathogens: Novel Genotypes Promoting Disease

Patricia Sobecky, PhD (Georgia Tech) and Cheryl Bopp, MS (CD)

DESCRIPTION: The incidence of gastrointestinal illnesses, wound infections, and septicemia caused by species of the genus Vibrio is rising dramatically. Among the ubiquitous Vibrio species occurring in coastal marine and estuarine environments is Vibrio parahaemolyticus, an opportunistic human pathogen. V. parahaemolyticus presently accounts for the majority of Vibrio infections in the United States. The emergence of the serotype O3:K6 in 1996 is now the first documented V. parahaemolyticus serotype to cause global, pandemic disease. Unlike the more extensively studied pathogens, V. cholerae and V. vulnificus, little is known about the evolutionary and environmental dynamics of V. parahaemolyticus. Increases in V. parahaemolyticus-associated outbreaks may be due to the emergence and evolution of novel genotypes that promote the organism's expansion to new niches, host populations or enhance its ability to cause disease. The molecular mechanisms and associated mobile genetic elements facilitating the emergence of V. parahaemolyticus pathogens need to be elucidated to better address the threat of this emerging pathogen. The central hypothesis of this proposal is that rapid evolution of emerging pathogenic Vibrio parahaemolyticus strains is due to horizontal gene transfer interactions between pathogenic (i.e., clinical strains) and metapopulations of environmental V. parahaemolyticus isolates. This study will establish a better understanding of the differences in the genomes and mobile genetic elements that promote HGT between clinical and environmental V. parahaemolyticus populations. Understanding molecular processes that promote rapid genome evolution will yield insights into the evolution of V. parahaemolyticus pathogenicity and the emergence of new serotypes of this opportunistic human pathogen.

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Preventing Childhood Maltreatment in the Wake of a Disaster: What do States do?

Page Anderson, PhD (GSU) and Janet Saul, PhD (CDC)

DESCRIPTION: Child Maltreatment (CM) is identified as a significant public health problem by the CDC and research has indicated that risk for CM increases following disasters.  Little information is available on state level plans for CM prevention in the aftermath of disaster.  This proposal delineates a pilot project that would examine state planning for such efforts post-disaster in two southeastern states, one with relatively more disaster response experience in recent years (LA) and one with relatively less (GA).  Specifically, researchers propose to engage in a 5-step process which includes:  developing an interview instrument that will examine disaster response plans and CM issues related to disaster in LA and GA, interviewing  relevant LA and GA agencies about CM prevention in the aftermath of a disaster, developing a preliminary summary report of findings, conducting focus groups in LA and GA to review findings with representatives of agency participants to obtain feedback, and finalizing/disseminating summary report.  The proposed project will enhance our knowledge base regarding state plans for child maltreatment prevention following catastrophic events, with the ultimate goal of informing the development, implementation, dissemination, and evaluation of future prevention programs to target this specific issue. 

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Toward a Better Understanding of Non-addicted, Methamphetamine-using Men who have Sex with Men (MSM)

Brian J. Dew, PhD (GSU) and Gordon Mansergh, PhD (CDC)

DESCRIPTION: Methamphetamine use and its association with sexual risk behavior are linked to increases in new HIV infections among men who have sex with men (MSM). Although effective treatment programs for addicted MSM have been developed, little is known about how to reduce methamphetamine use and sexual risk among non-addicted MSM. The purpose of this proposal is to learn more about the motivations, contextual influences, and other factors facilitating methamphetamine use among non-addicted MSM users, and to determine culturally appropriate and effective program methods and materials that ultimately work to reduce methamphetamine use and sexual risk behavior among MSM. The formative stage of this project includes focus groups consisting of non-addicted, methamphetamine-using MSM, public and private substance abuse treatment providers, and HIV risk-reduction experts. A quantitative assessment will also be collected using ACASI with focus group participants prior to the groups. Based on formative work, an intervention method and related materials will be developed and preliminarily tested in a second set of focus groups. Subsequent funding will be pursued to systematically test the efficacy of a full intervention.

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The Effects of a High Fructose Diet on Brain and Behavior

Marise B. Parent, PhD (GSU) and Joel Kimmons, PhD (CDC)

DESCRIPTION:Over the past 30 years, there has been an alarming increase in the consumption of fructose from sweeteners in the North American diet.  In humans and rodents, extensive intake of fructose is associated with a variety of pathological changes, including insulin insensitivity, obesity, cardiovascular disease, and type II diabetes. In rodents, some of the pathological changes are observed as soon as two weeks after consumption of a high fructose diet.  The findings of a study conducted by our collaborator demonstrated for the first time that the damaging effects of a high fructose diet extend to the brain.  Specifically, fructose feeding produces hippocampal insulin resistance and impairs hippocampal synaptic plasticity in hamsters.  These findings raise the possibility that a high fructose diet influences cognition and behavior, because the hippocampus plays a pivotal role in memory.  Moreover, there is an association between peripheral insulin resistance and deficits in hippocampal-dependent behavior.  As a result, the research proposed in the present application will test the hypothesis that a diet high in fructose impairs hippocampal-dependent memory and that it does so by producing hippocampal insulin resistance. Moreover, this research will test the hypothesis that the deleterious effects of fructose increase as a function of the percent of dietary kilocalories (kcal) from fructose and duration of fructose intake. Different groups of young male rats will be given 30% or 60% fructose in their chow (or vegetable starch as a control) for 40, 84, or 140 days. We will determine 1) whether the diet affects performance in the spatial water maze, which is a behavioral task that is dependent on the integrity of the hippocampus, 2) whether deficits in insulin-mediated phosphorylation of the insulin receptor and associated downstream signaling molecules in the brain are correlated with behavioral deficits, and 3) and whether the deleterious effects of fructose are more pronounced in rats given higher concentrations of fructose for longer periods.  Collectively, the research outlined in this proposal meets the objectives of the Healthy People in Every Stage of Life CDC Health Protection Theme.  Specifically, this research will identify how a prevalent lifestyle choice (i.e. excessive fructose consumption) produces health disparities that can limit optimal health throughout the lifespan. The information gained from these findings can be used to demonstrate the need for human studies in this area and assist in developing appropriate recommendations regarding the consumption of fructose to optimize wellness.  Such strategies will likely serve to increase the number of people who are able to participate in life fully and live longer.

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Determining the Prevalence of Autism Spectrum Disorders in Young Children

Diana Robins, PhD (GSU) and Marshalyn Yeargin-Allsopp, MD (CDC)

DESCRIPTION: Current surveillance methodology for autism spectrum disorders (ASD) at the Centers for Disease Control and Prevention (CDC) involves the review of educational and health records of 8-year-old children in a given study year. Due to a growing interest in understanding the prevalence of ASDs in young children, CDC funded three external sites in 2006 to develop protocols that could be used to determine the prevalence of ASDs in children younger than four years of age (RFA DD06-001). All of the funded sites proposed a direct-screening approach to identify children with ASDs, which involves administering a clinical evaluation to children who fail an ASD screen; a similar approach is employed by an ongoing screening study at Georgia State University (GSU). To date, no study has examined the feasibility of using a record-review methodology or compared a direct-screening approach to a record-review approach in younger cohorts. Therefore, the goals of this proposal are to: 1) determine the feasibility of using a record-review methodology in determining the prevalence of ASDs in young children and 2) compare a direct-screening approach and record-review approach in determining the prevalence of ASDs in young children. Approximately 60 children younger than four years of age will be identified from the ongoing direct-screening study at GSU. The GSU study involves administering a comprehensive clinical evaluation to children who fail an ASD screen and subsequent telephone interview, and a random sample of children who do not fail an ASD screen. Educational and health records of all children who receive a GSU clinical evaluation and agree to participate in the proposed study will be reviewed and abstracted by CDC personnel; only records prior to the GSU evaluation will be included. Information abstracted from records will be sent to CDC clinician reviewers who will apply a standardized coding scheme to determine surveillance case status. CDC case status (i.e., ASD or nonASD) will be compared to the results of the GSU evaluation (i.e., ASD or nonASD). Results will yield valuable information on the feasibility of using a record-review methodology in younger cohorts and how well a record-review approach compares to a direct-screening approach. This proposal brings together experienced researchers from both CDC and GSU who have been approaching the question of ASD identification through different methodologies; this collaboration will be the first study to directly compare ASD surveillance from record review with direct screening in a young sample of children. Additionally, this proposal addresses the CDC Health Protection goal of “Healthy People in Every Stage of Life” and specific areas of interest outlined by the seed grant program announcement. Results of this seed grant may also provide pilot data for funding proposals for a larger collaborative study.

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An Assessment of the Attitudes and Program Preferences about Pre-exposure Prophylaxis (PrEP) among Inner City Young Adults at Risk for HIV/AIDS

Richard Rothenberg, MD (GSU) and Dawn K. Smith, MD, MS, MPH (CDC)

DESCRIPTION:Pre-exposure prophylaxis (PrEP), as currently being tested in trials,  is the daily administration of a single dose of antiretroviral medication to uninfected persons whose behavior and social context places them at high risk of acquiring HIV. Efficacy and safety trials of PrEP are currently underway, mostly in Asia, Africa, and Latin America among populations with high HIV incidence. A small trial among MSM in the United States is focusing on behavioral and clinical safety as well as acceptability.  Because of the biological plausibility of this approach and previous demonstration that oral chemoprophylaxis is effective for other infectious diseases (e.g., malaria), for the prevention of mother-to-child HIV transmission, and in animal models has been shown to block mucosal transmission of HIV-related viruses, we have reason to believe that the trials may soon confirm both safety and efficacy of PrEP. However, building effective, safe, and accessible PrEP intervention programs for socially and economically disadvantaged populations at high risk of HIV acquisition in the US will be complex. An early assessment of the perspective of intended users is critical to this planning process. We propose an initial ethnographic evaluation in the first year of the project that will include conducting 20 focus groups in high-risk areas of Atlanta GA.  Building on this information, in the second year, we will conduct in-depth, open-ended ethnographic interviews with 50 persons from these same areas.  These results, though not generalizable to all such participants, will provide preliminary information on the potential ways of designing and introducing PrEP intervention programs in these communities.

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Ecological and Anthropogenic Drivers of Vampire Bat-Transmitted Rabies Outbreaks

Sonia P. Altizer, PhD (UGA) and Charles E. Rupprecht, VMD, PhD (CDC)

In an era of human expansion, intensifying land use and globalization, newly emerging infectious diseases, especially those that cross species barriers, are a principle threat to human health, wildlife conservation and sustainable economic growth. Our research focuses on interactions between vampire bats (Desmodus rotundus) and rabies to explore how shifts in animal behavior and population dynamics in response to human activities influence viral persistence in wildlife and risk of human disease emergence. We will combine field studies of wild bats in Peru, laboratory investigations at the CDC and mathematical modeling at UGA to address key mechanisms in rabies transmission. First, serological surveys in bats and phylogenetic analysis of Rabies viruses will test the prediction that large-scale livestock rearing supplements vampire bat feeding, increases bat populations, and hence allows enzootic persistence of rabies. Next, genetic identification of the species origin of vampire bat blood meals, together with human survey data, will test the prediction that anthropogenic declines in native wildlife increase human rabies risk by forcing vampire bats to feed on humans. The proposed research represents a unique, multi-disciplinary effort among an experienced team of researchers to simultaneously understand the intrinsic dynamics of viral transmission within natural populations and the drivers of human outbreaks. We expect this research to lead to a minimum of 3 publications that make significant contributions to the fields of public health and ecology. Importantly, data collected through this seed grant are crucial to provide a strong basis for collaborative proposals to panels such as the NSF/NIH Ecology of Infectious Diseases Initiative.

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Development of Simple, Field-Usable Molecular Tools for the Diagnosis of Malaria

Jessica Kissinger, PhD (UGA) and Venkatachalam Udhayakumar, PhD (CDC)

Plasmodium, the causative agent of malaria is a major contributor to global morbidity and mortality. The clinical diagnosis of malaria largely depends on microscopy. Recently, rapid tests for malaria diagnosis have become valuable alternative tools, especially in developing countries. Both these methods are limited by species misidentification and a lack of sensitivity. More sensitive PCR-based tests have been developed. These are based on the small subunit ribosomal RNA genes, targets that were identified prior to the completion of any genome projects. However, these PCR-based assays are less than ideal and are expensive for field implementation. Therefore, there is a need for more sensitive tests for detecting sub-clinical infection and species identification and for simpler field useable tools. Genome sequence data are now available for 8 Plasmodium species (three human-infecting), and a dozen additional sequences are in progress. These data are available at the Plasmodium genome database. However, little advantage has been taken of this database to improve the diagnosis of malaria. This proposal will apply comparative genomic approaches to identify novel molecular targets that can be tested for their applicability for the diagnosis of malaria and evaluated for their potential use in field applications. We propose to simplify current PCR methods by using isothermal amplification and novel portable equipment amicable to use even in remote field settings. Results generated from this proposal will help us develop and optimize a complementary, more sensitive, and field usable molecular-based tool for the diagnosis of malaria under field conditions in resource limited countries.

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Ecosystem Health and Human Health: Understanding the Ecological Effects of Prescribed Fire Regimes on the Distribution and Population Dynamics of Tick-Borne Zoonoses

Michael J. Yabsley, PhD (UGA) and Michael R. Levin, PhD (CDC)

Compromise of ecosystem health, often measured as biodiversity loss, community composition shifts, pollution, alien species invasions, and increase in frequency/emergence of disease events, is increasingly being recognized as relevant to human, domestic animal, and wildlife health. Despite growing knowledge of connections between ecosystem change and diseases, the ecological effects of prescribed fire (commonly used to maintain biodiversity and habitat quality) on zoonotic diseases remain largely unstudied. Although a few studies have examined fire impacts on ticks our understanding of the ecological processes that influence recovery of tick populations after fire or how the influences of fires translate into infection rates and disease transmission risk are limited. We aim to test novel hypotheses about the relationships between prescribed fire and tick-borne disease through a large-scale field experiment which examines the responses of tick density and pathogen prevalence to time since fire, fuelbed type and host availability and density. We will also examine how the spatial pattern of unburned source habitats interacts with host movements to affect recolonization and recovery of tick populations following fire. This integrated, multilevel approach will result in significant new insights into how fire interacts with tick and pathogen dynamics at a local level, but should have considerable implications across broader geographic areas. We hypothesize that maintenance of natural fires regimes can lead to a decrease in tick-borne zoonoses. This project will develop new and strengthen previous collaborations between UGA and CDC researchers and partially support one graduate student who has a strong dedication to public health zoonotic diseases.

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Aerosol Delivery of a Virus-Like-Particle Vaccine Against H5N1 Avian Influenza in Poultry

Egbert Mundt, DVM, PhD; Holly Sellers, PhD (UGA) and Mark Papania, MD, MPH; Ruben Donis, PhD (CDC)

The lack of a vaccine against Highly Pathogenic Avian Influenza (HPAI) which could be delivered rapidly to billions of chickens in the event of an HPAI outbreak is a major threat to public health and a major concern of the poultry industry. In the United States, over 8 billion boiler chickens and 70.8 billion table eggs are produced annually. In addition, current human influenza vaccine production requires fertile eggs. Most poultry are bath vaccinated against diseases using living attenuated vaccines delivered by aerosol. However, currently available HPAI vaccines would have to be delivered by injection to each chicken, which would severely limit vaccination capacity. Influenza virus-like-particle (VLP) vaccines have been successfully delivered to the respiratory tract in mice by intranasal application. We propose to assess delivery of HPAI-VLP vaccines by aerosol to poultry. Our research objectives are: 1) Assess the immune response to HPAI-VLP aerosol vaccination in chickens, including serum and mucosal antibodies and cellular immune responses, 2) Determine the effects of dose and adjuvants on the immune response, 3) Assess protection from homologous (same clade) H5 HPAI challenge, 4) Assess protection from challenge with a heterologous (different clade) H5 HPAI. The unique expertise in aerosol delivery and influenza vaccines at CDC combines with the world class poultry research facilities and expertise at PDRC/UGA and VLP vaccine expertise at Novavax, Inc. to assure high caliber research to address these challenges. The expected project outcome is proof of the principle of aerosol delivery of HPAI-VLP vaccines in poultry. If successful, aerosol VLP vaccines would be a powerful vaccine delivery platform for humans as well as chickens.

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High Sensitivity Nano-Optical Method to Detect Measles Virus in Clinical Samples

Richard Dluhy, PhD (UGA) and Paul Rota, PhD (CDC)

Laboratory surveillance for measles is based on detection of virus-specific antibodies and detection of viral proteins or viral RNA. Detection of viral RNA by RT-PCR requires nucleic acid extraction and amplification, while the sensitivity of viral antigen detection is limited by the low levels of virus typically found in a clinical sample. The objective of this study is to determine the feasibility of using a highly sensitive nanophotonics method, i.e. surface enhanced Raman spectroscopy (SERS), to directly detect low levels of measles virus in clinical samples. We have already shown that SERS is extremely sensitive and requires no virus-specific reagents for detection; therefore specimens can be tested directly without prior nucleic acid extraction or amplification. Preliminary work between UGA and CDC has shown that SERS is able to identify and classify different measles strains with 90-100% specificity and sensitivity. The current project would extend our previous laboratory-based studies to more clinically relevant samples. If successful, this method would benefit surveillance in highly vaccinated populations where serologic markers are sometimes unreliable, as well as lead to the development of a point-of-care diagnostic assay for multiple virus species that could be used in various epidemiologic settings. The SERS methods described here provide a platform enabling technology with applications to all viral pathogens. This work directly addresses current state of Georgia and GRA focus areas in nanotechnology, detection and diagnostics.

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