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25 records · Page 2

Predicting Future Disease Burden in a Rapidly Changing Climate

The interplay of a rapidly changing climate and infectious disease occurrence is emerging as a critical topic, requiring investigation of possible direct, as well as indirect, connections between disease processes and climate-related variation and phenomena. First, we introduce and overview three infectious disease exemplars (dengue, influenza, valley fever) representing different transmission classes (insect-vectored, human-to-human, environmentally-transmitted) to illuminate the complex and significant interplay between climate disease processes, as well as to motivate discussion of how Sandia can transform the field, and change our understanding of climate-driven infectious disease spread. We also review state-of-the-art epidemiological and climate modeling approaches, together with data analytics and machine learning methods, potentially relevant to climate and infectious disease studies. We synthesize the modeling and disease exemplars information, suggesting initial avenues for research and development (R&D) in this area, and propose potential sponsors for this work. Whether directly or indirectly, it is certain that a rapidly changing climate will alter global disease burden. The trajectory of climate change is an important control on this burden, from local, to regional and global scales. The efforts proposed herein respond to the National Research Councils call for the creation of a multidisciplinary institute that would address critical aspects of these interlocking, cascading crises.

54 ENVIRONMENTAL SCIENCES↗

Advocating for Coccidioidomycosis to Be a Reportable Disease Nationwide in the United States and Encouraging Disease Surveillance across North and South America

Coccidioidomycosis (Valley fever) has been a known health threat in the United States (US) since the 1930s, though not all states are currently required to report disease cases. Texas, one of the non-reporting states, is an example of where both historical and contemporary scientific evidence define the region as endemic, but we don’t know disease incidence in the state. Mandating coccidioidomycosis as a reportable disease across more US states would increase disease awareness, improve clinical outcomes, and help antifungal drug and vaccine development. It would also increase our understanding of where the disease is endemic and the relationships between environmental conditions and disease cases. This is true for other nations in North and South America that are also likely endemic for coccidioidomycosis, especially Mexico. This commentary advocates for US state and territory epidemiologists to define coccidioidomycosis as a reportable disease and encourages disease surveillance in other endemic regions across North and South America in order to protect human health and reduce disease burden.

54 ENVIRONMENTAL SCIENCES↗

Coccidioidomycosis Granulomas Informed by Other Diseases: Advancements, Gaps, and Challenges

Valley fever is a respiratory disease caused by a soil fungus, Coccidioides, that is inhaled upon soil disruption. One mechanism by which the host immune system attempts to control and eliminate Coccidioides is through granuloma formation. However, very little is known about granulomas during Coccidioides infection. Granulomas were first identified in tuberculosis (TB) lungs as early as 1679, and yet many gaps in our understanding of granuloma formation, maintenance, and regulation remain. Granulomas are best defined in TB, providing clues that may be leveraged to understand Coccidioides infections. Granulomas also form during several other infectious and spontaneous diseases including sarcoidosis, chronic granulomatous disease (CGD), and others. This review explores our current understanding of granulomas, as well as potential mechanisms, and applies this knowledge to unraveling coccidioidomycosis granulomas.

Miranda, Nadia (ORCID:0000000270038368)↗

Coccidioidomycosis Osteoarticular Dissemination

Valley fever or coccidioidomycosis is a pulmonary infection caused by species of Coccidioides fungi that are endemic to California and Arizona. Skeletal coccidioidomycosis accounts for about half of disseminated infections, with the vertebral spine being the preferred site of dissemination. Most cases of skeletal coccidioidomycosis progress to bone destruction or spread to adjacent structures such as joints, tendons, and other soft tissues, causing significant pain and restricting mobility. Manifestations of such cases are usually nonspecific, making diagnosis very challenging, especially in non-endemic areas. The lack of basic knowledge and research data on the mechanisms defining susceptibility to extrapulmonary infection, especially when it involves bones and joints, prompted us to survey available clinical and animal data to establish specific research questions that remain to be investigated. In this review, we explore published literature reviews, case reports, and case series on the dissemination of coccidioidomycosis to bones and/or joints. We highlight key differential features with other conditions and opportunities for mechanistic and basic research studies that can help develop novel diagnostic, prognostic, and treatment strategies.

59 BASIC BIOLOGICAL SCIENCES↗

Digital Biosurveillance for Zoonotic Disease Detection in Kenya

Infectious disease surveillance is crucial for early detection and situational awareness of disease outbreaks. Digital biosurveillance monitors large volumes of open-source data to flag potential health threats. This study investigates the potential of digital surveillance in the detection of the top five priority zoonotic diseases in Kenya: Rift Valley fever (RVF), anthrax, rabies, brucellosis, and trypanosomiasis. Open-source disease events reported between August 2016 and October 2020 were collected and key event-specific information was extracted using a newly developed disease event taxonomy. A total of 424 disease reports encompassing 55 unique events belonging to anthrax (43.6%), RVF (34.6%), and rabies (21.8%) were identified. Most events were first reported by news media (78.2%) followed by international health organizations (16.4%). News media reported the events 4.1 (±4.7) days faster than the official reports. There was a positive association between official reporting and RVF events (odds ratio (OR) 195.5, 95% confidence interval (CI); 24.01–4756.43, p < 0.001) and a negative association between official reporting and local media coverage of events (OR 0.03, 95% CI; 0.00–0.17, p = 0.030). This study highlights the usefulness of local news in the detection of potentially neglected zoonotic disease events and the importance of digital biosurveillance in resource-limited settings.

59 BASIC BIOLOGICAL SCIENCES↗

Small molecule inhibitors for treatment of alpha viruses

An in vitro assay was designed to measure the activity of the alphavirus non-structural protein 2 (nsP2), which is the viral protease and is required for viral replication. By taking advantage of fluorescence-resonance energy transfer between two proteins, a protease cleavage assay was generated. This was utilized for high-throughput screening of 40,000 small molecules. Inhibitors were validated using cell-based assays to measure alphavirus infection and cytotoxicity. Certain compounds were then characterized for anti-viral efficacy in various cell lines in numerous assays. Compounds were tested against Chikungunya virus, Venezuelan Equine Encephalitis virus, Rift Valley Fever virus, and Zika virus. Three compounds (compounds I, II, and III) showed pan-alphavirus anti-viral efficacy at concentrations that did not result in cell toxicity. An additional compound, structure IV, showed broad spectrum inhibition of all viruses tested. Pharmaceutical preparations and methods of treatment including these compounds are provided herein.

60 APPLIED LIFE SCIENCES↗

A Review of Coccidioides Research, Outstanding Questions in the Field, and Contributions by Women Scientists

Abstract Purpose of Review Coccidioidomycosis is an infectious disease that gained clinical significance in the early 20th century. Many of the foundational contributions to coccidioidomycosis research, including the discovery of the fungal disease agent, Coccidioides spp., were made by women. We review recent progress in Coccidioides research and big questions remaining in the field, while highlighting some of the contributions from women. Recent Findings New molecular-based techniques provide a promising method for detecting Coccidioides, which can help determine the dominate reservoir host and ideal environmental conditions for growth. Genetic and genomic analyses have allowed an understanding of population structure, species level diversity, and evolutionary histories. We present a current, comprehensive genome list, where women contributed many of these entries. Several efforts to develop a coccidioidomycosis vaccine are underway. Summary Women continue to pioneer research on Coccidioides, including the relationships between the fungi and the environment, genetics, and clinical observations. Significant questions remain in the field of Coccidioides, including the main host reservoir, the relationships between genotypic and phenotypic variation, and the underlying cause for chronic clinical coccidioidomycosis cases.

59 BASIC BIOLOGICAL SCIENCES↗