Animal Diseases Commons^™

Inhibiting Chikungunya Virus Protease Using Mtase-Like Domain Interactions For Novel Antiviral Therapies, Justin G. Julander

Funded Research Records

No abstract provided.

The Woah Global Wildlife Health Collaborating Centre Network (Woah-Wildnet): A Coordinated And Transformative Approach To Global Wildlife Health Challenges, David T.S. Hayman, Steve Unwin, Kelly Bateman, Casey Barton Behravesh, Charlotte Berg, Jemma Bergfeld, Cristina Casalone, Claire Cayol, Erin Davis, Sunday Ekesi, Johan Esterhuizen, Merid Getahun, Federica Giorda, Keith Hamilton, Damien O. Joly, Christa Kühn, Jean Claude Manuguerra, Daniel Masiga, Anita Michel, Paolo Mulatti, Misheck Mulumba, Annah Njui, Richard Paley, Antonio Fernández, Sascha Knauf, David P. Tchouassi, Youming Wang, Nathalie Vachiery, Jandouwe Villinger

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Introduction Wildlife health is integral to functioning, complex ecosystems [1], directly and indirectly influencing the health of people, animals, plants, and the environment [2–4]. Healthy wildlife populations are essential for ecosystem services and are at the heart of the One Health approach [3,4], which aims to sustainably balance and optimize the health of people, animals, and ecosystems through multisectoral and transdisciplinary collaboration [5]. Despite its importance, wildlife health initiatives often operate in silos, limiting capacity to address transboundary threats such as emerging diseases, pollution, and environmental changes. Anthropogenic changes, including habitat loss, degradation, fragmentation, and unsustainable harvesting, exacerbate wildlife health …

A Systematic Review And Meta-Analysis Of Mosquito Arboviral Infections Detected Through Xenosurveillance In Africa: A Focus On West Nile, Rift Valley Fever, And Chikungunya Virus Infections, Mxolisi Mgongoma, Armanda Bastos, Abel Ramoelo, David P. Tchouassi

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This systematic review and meta-analysis comprehensively evaluated the mosquito arboviral infections with West Nile virus (WNV), Rift Valley fever virus (RVFV), and chikungunya virus (CHIV), detected through xenosurveillance, reported in mosquito vectors across Africa in the last 25 years (2000–2024). The study analysed xenosurveillance data from 45 studies conducted with over 115,000 mosquito specimens, and incorporated moderator analyses to assess the influence of trap type, seasonality, regional location, settlement type, and screening methods on virus detection rates. The estimated pooled prevalence of WNV was 1.18% (95% CI: 0.60–3.43%), with higher rates observed in Culex quinquefasciatus and Culex pipiens, particularly in …

Roles Of Cytokines In Modulating Trypanosoma Brucei Rhodesiense Infection Outcomes In Vervet Monkeys, Clarah Jebet, John Kibuthu Thuita, Daniel Masiga, Benedict Owino Orindi, John Oidho, Mark C. Field, Enock Matovu, Vincent Owino Adung’A

All Peer-Reviewed Publications

Introduction:

Human African trypanosomiasis (HAT), caused by Trypanosoma brucei rhodesiense, is categorized as acute due to rapid disease progression but presents varying clinical outcomes. Although the mechanisms underpinning differential clinical progression are poorly understood, both host and parasite factors are implicated. Therefore, we sought to elucidate roles of primate host factors in mediating varying T. b. rhodesiense infection outcomes.

Methods:

Here, we assessed the roles of selected host cytokines in disease progression using a tsetse-mediated infection in a non-human primate (NHP) vervet monkey model that closely mimics HAT and natural infection. We quantified eight cytokines, including TNF-α, IFN-γ, IL-10, IL-6, …

Exploring The Microbiomes Of Camel Ticks To Infer Vector Competence: Insights From Tissue-Level Symbiont-Pathogen Relationships, Rua Khogali, Armanda Bastos, Dennis Getange, Joel L. Bargul, Shewit Kalayou, Nehemiah Ongeso, Joost Theo Petra Verhoeven, James Kabii, John Ngiela, Daniel Masiga, Jandouwe Villinger

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Ticks are blood-feeding ectoparasites that harbor diverse pathogens and endosymbionts. Their microbial communities vary based on tick species, stage, sex, geographical location, surrounding environment, and tissue type. Understanding tick microbiota at the tissue level is crucial for unraveling how microbiomes are distributed in tick tissues and influence pathogen transmission. We used V1-V2 16 S rRNA gene sequencing to analyze tissue-specific bacterial compositions (hemolymph, saliva, salivary glands, and midgut) of Amblyomma gemma, Rhipicephalus pulchellus, Hyalomma dromedarii, and Hyalomma rufipes ticks collected from camels in Marsabit County, northern Kenya. The V1-V2 region of the 16 S rRNA gene effectively differentiated 43 Rickettsia …

Climate-Driven Potential For Tularemia In East Africa: Skill Testing And Ecological Consistency Of A Transferred Risk Model, Komi Mensah Agboka, Allan Muohi Ngángá, Bonoukpoè Mawuko Sokame, Steve Soh Bernard Baleba, Tobias Landmann, Elfatih M. Abdel-Rahman, Chrysantus M. Tanga, Souleymane Diallo

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Tularemia, a neglected zoonosis, remains underreported in Africa despite growing concern over its climate-driven expansion. This study aims to quantify the specific contribution of climate to tularemia risk using a climate attribution framework. We trained a Least Squares Dummy Variable (LSDV) fixed-effects panel model on United States (U.S.) county-level tularemia incidence data from 2011–2020 (n = 500, R² = 0.90), incorporating only climatic predictors: cumulative temperature, cumulative precipitation, and their respective variabilities. The climate-only model explained 86% of variance in the training data, demonstrating strong climate influence on tularemia disease dynamics. We then applied the model to East Africa, using …

Host Genetics Role In Viral Disease Susceptibility, Christian Willis Eaton

Dissertations and Doctoral Documents, University of Nebraska-Lincoln, 2023–

Viruses and their hosts exist in an evolutionary arms race, with evolutionary promotion of host genetic-based defense mechanisms and evolution of virus genetic-based mechanisms to overcome host defenses. Viruses are capable of much more rapid evolution and adaptation than their hosts, often leading to the use of host cellular mechanisms to promote viral infection and replication. In this study, we describe the generation of a detection assay for atypical porcine pestivirus (APPV), designed to target the viral 5’ UTR, a region of the viral genome which sees less mutations than the protein coding regions. This assay was generated to be …

Stomoxys Flies (Diptera, Muscidae) Are Competent Vectors Of Trypanosoma Evansi, Trypanosoma Vivax, And Other Livestock Hemopathogens, Julia W. Muita, Joel L. Bargul, John Mark O. Makwatta, Ernest M. Ngatia, Simon K. Tawich, Daniel K. Masiga, Merid N. Getahun

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Stomoxys flies are widely distributed and economically significant vectors of various livestock pathogens of veterinary importance. However, the role of Stomoxys spp. in pathogen transmission is poorly understood. Therefore, we studied the feeding patterns of these blood feeders collected from specific locations in Kenya to identify various vertebrate hosts they fed on, the livestock hemopathogens they carried, and to elucidate their role in pathogens transmission. Our findings show that field-collected Stomoxys flies carried several pathogens, including Trypanosoma spp., Anaplasma spp., and Theileria spp., which were also detected in the blood of sampled livestock, namely camels and cattle. The findings on …

Emergence Of Transferable Daptomycin Resistance In Gram-Positive Bacteria, Tessa Marciniak, Lukas Kirchner, Silver A. Wolf, Birgit Walther, Thorsten Bischler, Justin Nyasinga, R Gunturu, Torsten Semmler, Tom Gräfenhan, Andrew Whitelaw

Pathology, East Africa

Daptomycin (DAP) is a last-resort antibiotic to treat infections by multiresistant Gram-positive pathogens, including methicillin-resistant Staphylococcus aureus (MRSA) and vancomycin-resistant enterococci. DAP resistance and clinical treatment failure has been associated with adaptive chromosomal mutations, but so far not with transmissible resistance traits. Here we report for the first time an acquired DAP-R determinant (named drc) that we detected in a livestock-associated Mammaliicoccus sciuri isolate. drc consists of a two-gene operon (drcAB) that is controlled by an adjacent two-component system (drcRS). The DrcAB proteins, which mediate DAP inactivation, are similar to BceAB-like antimicrobial peptide transporters of Gram-positives, but are distinct from …

Machine Learning Predicts Non-Preferred And Preferred Vertebrate Hosts Of Tsetse Flies (Glossina Spp.) Based On Skin Volatile Emission Profiles, Olabimpe Y. Orubuloye, David P. Tchouassi, Abdullahi A. Yusuf, Christian W.W. Pirk, Daniel K. Masiga, Edward Kariuki, Baldwyn Torto

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Tsetse fly vectors of African trypanosomosis preferentially feed on certain vertebrates largely determined by olfactory cues they emit. Previously, we established that three skin-derived ketones including 6-methyl-5-hepten-2-one, acetophenone and geranyl acetone accounted for avoidance of zebra by tsetse flies. Here, we tested the hypothesis that these three ketones serve as biomarkers for tsetse flies to distinguish between non-preferred- and preferred-vertebrate hosts. We used coupled gas chromatography/mass spectrometry to analyze and compare the skin volatile emissions of two non-preferred- (waterbuck and zebra) and four preferred- (buffalo, donkey, horse, warthog) vertebrate hosts in two wildlife parks in Kenya. We detected a total …

Applying Machine Learning Methods To Generate Understandings Of Differential Item Functioning In A Flu Knowledge Assessment, William L. Romine, Tanvi Banerjee, Derrick Cox

Computer Science and Engineering Faculty Publications

Current influenza trends, including the severity of the 2025 flu season and the prevalence of H5 bird flu in livestock, necessitate efforts to better understand how to educate students about its transmission. Although validated assessments of influenza knowledge exist, these have not been evaluated for affective and demographic biases. We explore differential item functioning (DIF) effects in four items focused on specific aspects of flu transmission derived from a validated influenza knowledge assessment. In doing so, we introduce and utilize a machine learning framework for exploration of DIF which offers greater flexibility than traditional statistical approaches in terms of studying …

Challenges And Lessons From A Vector Control Campaign Targeting Glossina Palpalis Palpalis In An Isolated Protected Forest Area In Abidjan, Côte D’Ivoire, Yao Jean Rodrigue Konan, Bi Tra Dieudonné Ta, Djakaridja Berté, Bamoro Coulibaly, Kinifo Donatien Coulibaly, Nick Steven Egnankon, Foungniguée Diarrassouba, Kouassi Albert Djabo, Stéphanie Watier-Grillot, Jean Paul Demoncheaux, Koffi Alain De Marie Kouadio, Louis N’Dri, Philippe Solano, Sophie Ravel, Guy Pacôme Adingra, Antoine Barreaux, Adeline Ségard, Dramane Kaba, Vincent Jamonneau, Thierry De Meeûs, Vincent Djohan

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Vector control (VC) is one of the strategies employed to manage African trypanosomoses. This study aimed at assessing the effectiveness of a VC campaign against Glossina palpalis palpalis using tiny targets (TTs) impregnated with insecticide in an isolated, protected forest in Abidjan, Côte d’Ivoire, while considering ecological, genetic, and operational factors. Between January 2020 and September 2022, 2,712 TTs were deployed at 684 sites, covering a total area of 1.7 km2. VC monitoring was conducted using Vavoua traps during 12 evaluation surveys, between June 2020 and March 2023. Five months after the initial TT deployment, tsetse fly density had decreased …

An Overview Of Tsetse Fly Repellents: Identification And Applications, Olabimpe Y. Orubuloye, Njelembo J. Mbewe, David P. Tchouassi, Abdullahi A. Yusuf, Christian W.W. Pirk, Baldwyn Torto

All Peer-Reviewed Publications

Tsetse flies are vectors of the parasite trypanosoma that cause the neglected tropical diseases human and animal African trypanosomosis. Semiochemicals play important roles in the biology and ecology of tsetse flies. Previous reviews have focused on olfactory-based attractants of tsetse flies. Here, we present an overview of the identification of repellents and their development into control tools for tsetse flies. Both natural and synthetic repellents have been successfully tested in laboratory and field assays against specific tsetse fly species. Thus, these repellents presented as innovative mobile tools offer opportunities for their use in integrated disease management strategies.

Exploring The Dynamic Adult Hard Ticks-Camel-Pathogens Interaction, John Mark O. Makwatta, Paul N. Ndegwa, Florence A. Oyieke, Peter Ahuya, Daniel K. Masiga, Merid N. Getahun

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The ability of ticks to interact and adapt to differentecologies and hosts determines their vectorial competence for various pathogens; however, ticks-livestock-pathogens interaction studies are limited. With our ticks-hosts-pathogens interface studies, we found 14 species of hard ticks feeding on various livestock. Ticks showed a strong preference for one-humped camels (Camelus dromedarius). The camel nostril was the most preferred predilection site. The most prevalent tick species on camels was Hyalomma rufipes. We found two novel Amblyomma gemma variants which are distinct both morphologically and genetically from previously described Amblyomma gemma. The signature odors from camel breath and body were attractive to …

Chronic Guillain-Barré Syndrome From Misdiagnosed Lyme Disease, Carlos H. Cisneros Jr, Alberto E. Almeida

MEDI 9331 Scholarly Activities Clinical Years

Lyme disease (borreliosis) is caused by transmission of Borrelia burgdorferi from deer ticks in the United States. Neurological symptoms can manifest in the early disseminated stage of the disease and have the worst involvement in the late dissemination stage. Few, but important case reports exist of patients experiencing disseminated Lyme with associated Guillain-Barre Syndrome (GBS). GBS manifests as an ascending flaccid paralysis with additional sensory deficits and is characterized as an immune-mediated polyneuropathy attacking the peripheral nervous system. A college-aged, wheelchair bound, quadriplegic female presented to the clinic to establish care in October 2023. She reported being bitten by a …

Immunoregulatory Properties Of Immune Cells That Associate With The Lens Capsule Surface During Acute And Resolution Phases Of Experimental Autoimmune Uveitis, Phuong M. Le, Mary J. Mattapallil, Rachel R. Caspi, Mary Ann Stepp, A. Sue Menko

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

Inflammation in the eye is tightly regulated to prevent vision impairment and irreversible blindness. Emerging evidence shows that immune cells are specifically recruited to the lens capsule in response to autoimmune uveitis, yet the potential that they have a role in regulating this inflammatory disease remained unexplored. Here, an immunolocalization approach combined with high-resolution confocal microscopy was used to investigate whether the immune cells that become stably associated with the lens capsule in the eyes of C57BL/6J mice with experimental autoimmune uveitis (EAU) have an immunoregulatory phenotype. These studies revealed that during the acute phase of uveitis, at day 18 …

The Role Of Southern Red-Backed Voles, Myodes Gapperi, And Peromyscus Mice In The Enzootic Maintenance Of Lyme Disease Spirochetes In North Dakota, Usa, Michael W. Dougherty, Nathan M. Russart, Robert A. Gaultney, Emily Marie Gisi, Haley M. Cooper, Lindsey R. Kallis, Catherine A. Brissette, Jefferson A. Vaughan

Biology Faculty Publications

Lyme disease has expanded into the Great Plains of the USA. To investigate local enzootic transmission, small mammals were trapped in two forested tracts in northeastern North Dakota during 2012 and 2013. Peromyscus mice and southern red-backed voles, Myodes gapperi, comprised over 90% of all mammals captured. One site was dominated by Peromyscus (79% of 100 mammals captured). At the other site, M. gapperi (59% of 107 mammals captured) was more abundant than Peromyscus (36%). Immature stages of two tick species parasitized small mammals: Dermacentor variabilis and Ixodes scapularis. Larval I. scapularis ectoparasitism was significantly higher on Peromyscus (81% …

Scaling Antimicrobial Resistance Surveillance Nationally: The Case Of The Fleming Fund In Kenya, Mitchelle Kasudi, Dishon Muloi, Murungi Maurice, Allan Azegele, Romona Ndanyi, Revathi Gunturu, Loice Ombajo, Emmanuel Tanui, Robert Onsare, Geoffrey Omuse

Pathology, East Africa

Rising levels of antimicrobial resistance (AMR) in both humans and animals have reached alarming levels and are being recognized as a serious incremental threat to global food security, animal health and public health. The One Health approach recognizes the interconnectedness of human, animal and environmental health, and that AMR can be spread between different species and environments. The Fleming Fund, a UK Overseas Development Aid program managed by the UK’s Department of Health and Social Care, aims to improve AMR and antimicrobial use (AMU) surveillance data in Africa and Asia by generating, sharing, and using data to improve antimicrobial use …

Analysis Of Antibiotic Sensitivity Patterns In Pasteurellaceae Family Isolates: A Microbial And Molecular Investigation, Jillian Barron

Honors Scholar Theses

Bacteria in the Pasteurellaceae family are known to cause disease in both human and animal species. Like all species of bacteria, the pathogens in the Pasteurellaceae family evolve and acquire antimicrobial-resistant traits. Antimicrobial resistance of bacteria is a significant public health concern, as treatment of resistant pathogens becomes more difficult, if not impossible, with current medical capabilities. In this project, phenotypic and genotypic analyses were performed on Pasteurellaceae family isolates sourced from the Connecticut Veterinary Medical Diagnostic Laboratory. Phenotypic antibiotic sensitivity patterns of each isolate were assessed against a panel of antibiotics through a Kirby-Bauer disk diffusion test. Disk diffusion …

Close Contacts Of Xenograft Recipients: Ethical Considerations Due To Risk Of Xenozoonosis, Daniel J Hurst, Luz Padilla, Daniel Rodger, Tamar Schiff, David K C Cooper

Rowan-Virtua School of Osteopathic Medicine Departmental Research

With decades of pre-clinical studies culminating in the recent clinical application of xenotransplantation, it would appear timely to provide recommendations for operationalizing oversight of xenotransplantation clinical trials. Ethical issues with clinical xenotransplantation have been described for decades, largely centering on animal welfare, the risks posed to the recipient, and public health risks posed by potential spread of xenozoonosis. Much less attention has been given to considerations relating to potentially elevated risks faced by those who may care for or otherwise have close contact with xenograft recipients. This paper examines the ethical and logistical issues raised by the potential exposure to …

Dual Suppression Of Glossina Pallidipes Using Entomopathogenic Fungal-Based Biopesticides And Sterile Insect Technique, Fidelis L.O. Ombura, Adly M.M. Abd-Alla, Komivi S. Akutse, Steven Runo, Paul O. Mireji, Rosemary Bateta, Joseck E. Otiwi, Inusa J. Ajene, Fathiya M. Khamis

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Tsetse flies and trypanosomosis significantly impact bovine production and human health in sub-Saharan Africa, exacerbating underdevelopment, malnutrition, and poverty. Despite various control strategies, long-term success has been limited. This study evaluates the combined use of entomopathogenic fungi (EPF) and the sterile insect technique (SIT) to combat tsetse flies. Eleven EPF isolates were tested against teneral males of Glossina pallidipes, focusing on mortality rates, radial growth, and impacts on fly fitness. Temperature effects on conidial growth, sporulation, and spore yield of SIT-compatible/tolerant strains were also assessed. The fungal isolates significantly influenced mortality rates in both unirradiated and irradiated (SIT-treated) males (p <  0.0001). Metarhizium anisopliae strains ICIPE 20, ICIPE 32, ICIPE 41, ICIPE 62, ICIPE 78, and Beauveria bassiana ICIPE 603 showed higher SIT compatibility/tolerance with LT50 values of 11–30 days, compared to other more virulent isolates with LT50 values of 4–9 days. Temperature significantly affected the radial growth of SIT-compatible EPF strains (p <  0.0001), with M. anisopliae ICIPE 78 exhibiting the fastest conidia growth at 25°C. Spore yield varied significantly across temperatures (15–40°C), and the thermal range for conidia germination of SIT-compatible strains was 8.1–45.4°C, with an optimal range of 26.7–31.1°C. Moreover, infected unirradiated females and irradiated males (donors) successfully transmitted conidia to untreated flies (receivers) without significant differences in survival rates (p = 0.6438) and no observed sex dimorphism. Our findings highlight the potential of combining EPF and SIT as a novel dual approach that could effectively and synergistically suppress tsetse fly populations.

Tissue-Specific Localization Of Tick-Borne Pathogens In Ticks Collected From Camels In Kenya: Insights Into Vector Competence, Rua Khogali, Armanda Bastos, Joel L. Bargul, Dennis Getange, James Kabii, Daniel Masiga, Jandouwe Villinger

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Background: Tick-borne pathogen (TBP) surveillance studies often use whole-tick homogenates when inferring tick-pathogen associations. However, localized TBP infections within tick tissues (saliva, hemolymph, salivary glands, and midgut) can inform pathogen transmission mechanisms and are key to disentangling pathogen detection from vector competence. Methods: We screened 278 camel blood samples and 504 tick tissue samples derived from 126 camel ticks sampled in two Kenyan counties (Laikipia and Marsabit) for Anaplasma, Ehrlichia, Coxiella, Rickettsia, Theileria, and Babesia by PCR-HRM analysis. Results: Candidatus Anaplasma camelii infections were common in camels (91%), but absent in all samples from Rhipicephalus pulchellus, Amblyomma gemma, Hyalomma dromedarii, …

Transferability Of Tsetse Habitat Models Between Different Regions In Kenya And Rwanda, Stella Gachoki, Anton Vrieling, Thomas A. Groen, Andrew Skidmore, Daniel Masiga

All Peer-Reviewed Publications

Accurate and reliable information on the distribution of tsetse habitats is crucial for the effective management of African Trypanosomiasis in sub-Saharan Africa. However, conducting large-scale surveillance of tsetse flies to develop distribution maps is impractical due to vast areas infested and limited resources available. To address this challenge, we evaluated the applicability of tsetse habitat models developed in the intensively sampled Shimba Hills National Reserve in Kenya for both the wet and the dry season, to two other regions in Kenya (Ruma National Park and Nguruman Conservancy) and one region in Rwanda (Akagera National Park). The models utilized satellite-based estimates …

Effect Of Use Of Tsetse Repellant Collar Technology On The Farm Performance And Household Welfare Of Small-Scale Livestock Farmers In Kenya, Beatrice W. Muriithi, Kassie Menale, Gracious M. Diiro, Michael N. Okal, Daniel K. Masiga

All Peer-Reviewed Publications

Tsetse-transmitted Animal African Trypanosomosis (AAT) is a disease of economic importance to livestock development in Sub-Saharan Africa. The disease is widely managed using trypanocides that are expensive for smallholders and associated with health risks due to drug residues in animal products and drug resistance. Developed recently by the International Centre of Insect Physiology and Ecology (icipe) and partners, the novel Tsetse repellent collar technology (TRCT) provides an effective alternative control measure that targets the tsetse fly vector of AAT. This study assessed the impact of TRCT on household welfare and food security by using ex-post non-experimental data obtained from 632 …

Whole Genome Sequencing Of West Nile Viruses From Animals Submitted To The Connecticut Veterinary Medical Diagnostic Laboratory (Cvmdl), Usa, 2021, Allison Appel

Honors Scholar Theses

West Nile Virus (WNV) causes a zoonotic disease. WNV was first isolated in Uganda in 1937 and has since become an endemic in countries such as North, South, and Central America [1]. According to the Connecticut Department of Public Health, an average of 8 cases of WNV in humans have been reported since the year 2000 [2]. In this study, we focused on the genetic characterization of the viral genomic RNA of WNVs circulating in birds and mammals in the New England region. Following that aim, the complete genome sequence of two WNVs was obtained via next-generation sequencing. One sample …

Characterizing Movement Patterns Of Nomadic Pastoralists And Their Exposure To Rift Valley Fever In Kenya, G. Mosomtai, J. L. Kasiiti, R. M. Murithi, P. Sandström, T. Landmann, O. W. Lwande, O. A. Hassan, C. Ahlm, R. Sang, M. Evander, Z. Szantoi, G. Ottavianelli

All Peer-Reviewed Publications

The role of animal movement in spreading infectious diseases is highly recognized by various legislations and institutions such as the World Organisation for Animal Health and the International Animal Health Code. The increased interactions at the nexus of human-animal-ecosystem interface have seen an unprecedented introduction and reintroduction of new zoonotic diseases with high socio-economic impacts such as the COVID-19 pandemic. Rift Valley fever (RVF) is a zoonotic disease that affects both humans and animals and is transmitted by Aedes mosquitoes or through contact with the body fluids of infected animals. This study seeks to characterize movement patterns of pastoralist and …

Circulating Plasma Exosomal Proteins Of Either Shiv-Infected Rhesus Macaque Or Hiv-Infected Patient Indicates A Link To Neuropathogenesis, Partha K. Chandra, Stephen E. Braun, Sudipa Maity, Jorge A. Castorena-Gonzalez, Hogyoung Kim, Jeffrey G. Shaffer, Sinisa Cikic, Ibolya Rutkai, Jia Fan, Jessie J. Guidry, David K. Worthylake, Chenzhong Li, Asim B. Abdel-Mageed, David W. Busija

School of Medicine Faculty Publications

Despite the suppression of human immunodeficiency virus (HIV) replication by combined antiretroviral therapy (cART), 50–60% of HIV-infected patients suffer from HIV-associated neurocognitive disorders (HAND). Studies are uncovering the role of extracellular vesicles (EVs), especially exosomes, in the central nervous system (CNS) due to HIV infection. We investigated links among circulating plasma exosomal (crExo) proteins and neuropathogenesis in simian/human immunodeficiency virus (SHIV)-infected rhesus macaques (RM) and HIV-infected and cART treated patients (Patient-Exo). Isolated EVs from SHIV-infected (SHIV-Exo) and uninfected (CTL-Exo) RM were predominantly exosomes (particle size < 150 nm). Proteomic analysis quantified 5654 proteins, of which 236 proteins (~4%) were significantly, differentially expressed (DE) between SHIV-/CTL-Exo. Interestingly, different CNS cell specific markers were abundantly expressed in crExo. Proteins involved in latent viral reactivation, neuroinflammation, neuropathology-associated interactive as well as signaling molecules were expressed at significantly higher levels in SHIV-Exo than CTL-Exo. However, proteins involved in mitochondrial biogenesis, ATP production, autophagy, endocytosis, exocytosis, and cytoskeleton organization were significantly less expressed in SHIV-Exo than CTL-Exo. Interestingly, proteins involved in oxidative stress, mitochondrial biogenesis, ATP production, and autophagy were significantly downregulated in primary human brain microvascular endothelial cells exposed with HIV+/cART+ Patient-Exo. We showed that Patient-Exo significantly increased blood–brain barrier permeability, possibly due to loss of platelet endothelial cell adhesion molecule-1 protein and actin cytoskeleton structure. Our novel findings suggest that circulating exosomal proteins expressed CNS cell markers—possibly associated with viral reactivation and neuropathogenesis—that may elucidate the etiology of HAND.

A Rodent Model For Dirofilaria Immitis, Canine Heartworm: Parasite Growth, Development, And Drug Sensitivity In Nsg Mice, Jessica A. Hess, Mark L. Eberhard, Marcelo Segura-Lepe, Kathrin Grundner-Culemann, Barbara Kracher, Jeffrey Shryock, John Harrington, David Abraham

Department of Microbiology and Immunology Faculty Papers

Heartworm disease, caused by Dirofilaria immitis, remains a significant threat to canines and felines. The development of parasites resistant to macrocyclic lactones (ML) has created a significant challenge to the control of the infection. The goal of this study was to determine if mice lacking a functional immune response would be susceptible to D. immitis. Immunodeficient NSG mice were susceptible to the infection, sustaining parasites for at least 15 weeks, with infective third-stage larvae molting and developing into the late fourth-stage larvae. Proteomic analysis of host responses to the infection revealed a complex pattern of changes after infection, with at …

Marineepi: A Gui-Based Matlab Toolbox To Simulate Marine Pathogen Transmission, Gorka Bidegain, Tal Ben-Horin, Eric N. Powell, John M. Klinck, Eileen E. Hofmann

CCPO Publications

The Graphical User Interface (GUI) MarineEpi is presented as a Matlab toolbox for easily (i) constructing disease transmission models for different marine host-pathogen systems, (ii) running simulations by specifying initial conditions and model parameters, and (iii) interpreting the resulting time series of the host and pathogen population dynamics. MarineEpi users can generate models for systems in which pathogen transmission occurs through contact with infected individuals (SI), contact with dead infected individuals (SID), contact with environmental pathogens released by infected individuals (SIP), and contact with environmental pathogens released by dead infected individuals (SIPD). MarineEpi is a freely available GUI that provides …

Characterizing The Cutaneous Microbiome Of Eurycea Lucifuga As A Potential Defense Against Chytridiomycosis, Madeline Key

Senior Honors Theses

Chytridiomycosis is an emerging infectious disease that is significantly reducing global amphibian populations. The disease is caused by Batrachochytrium dendrobatidis (Bd), a fungus that lethally modifies amphibian skin. Recent research has suggested that the cutaneous microbiome of individual amphibians may play a role in susceptibility to the pathogen. In this study, twelve cave salamanders (Eurycea lucifuga) were collected. Cutaneous bacteria from each salamander were isolated and identified using Sanger Sequencing. Additionally, a Bd-challenge assay was performed to determine each isolate’s antifungal activity. Results indicated many microbial isolates possessed inhibitory capabilities against Bd, which may …