Parasitology Commons^™

Advancing Trypanosoma Cruzi N-Myristoyltransferase As A Drug Target For Chagas Disease Through In Silico Discovery And Biochemical Evaluation, Diana Citlali González García

Open Access Theses & Dissertations

Chagas disease remains one of the most persistent and neglected parasitic infections in the Americas, advancing silently through the intracellular replication of Trypanosoma cruzi amastigotes and the invasive spread of trypomastigotes. The survival of the parasite is critically reliant on protein N-myristoylation, a lipid modification catalyzed by N-myristoyltransferase (NMT). This dissertation aims to advance beyond prior studies by systematically investigating NMT inhibition across multiple biological levels, spanning from the characterization of the purified enzyme, through cellular infection models, to the global proteomic remodeling induced within the parasite, thereby evaluating TcNMT as a potential therapeutic vulnerability in T.cruzi.Recombinant TcNMT was expressed, …

Bibliometric Analysis Of Congenital Toxoplasmosis: A Ten-Year (2013-2023) Review Of Research Publications, Festus Mulakoli, Horatius Musembi, Ann Kimani

School of Nursing & Midwifery, East Africa

Background:Toxoplasma gondii, an obligate intracellular protozoan, infects more than one-third of the global population and causes toxoplasmosis, which can lead to severe fetal complications in pregnant women. The global prevalence of latent toxoplasmosis in pregnant women is 33.8%, with regional variations and risk factors, including the consumption of undercooked meat, exposure to cat feces, and consumption of contaminated water. Pregnant women lack sufficient awareness of these risk factors, necessitating enhanced education, regular screening, and counseling during antenatal care for early detection and management.

Aim: This study performed a comprehensive bibliometric analysis of research on congenital toxoplasmosis published between 2013 …

Characterization Of Vaccine-Enhanced Humoral Immune Responses Against Emergent Sars-Cov-2 Variants In A Convalescent Cohort, Jared Sheehan, Amber J. Trauth, Michael E. Hagensee, Alistair J. Ramsay

School of Graduate Studies Faculty Publications

Vaccination of COVID-19–convalescent individuals may generate ‘hybrid’ immunity of enhanced magnitude, durability, and cross-reactive breadth. Our primary goal was to characterize hybrid antibody (Ab) responses in a patient cohort infected with ancestral Wuhan-Hu-1 virus and vaccinated between 6 and 10 months later with the Wuhan-Hu-1–based BNT162b2 mRNA vaccine. We were particularly interested in determining the efficacy of neutralizing Ab responses against subsequently emergent SARS-CoV-2 variants. Sera collected at 3-monthly intervals over a period of 12 months were analyzed by ELISA for SARS-CoV-2 RBD–specific Ab responses, and also for neutralizing Ab activity using pseudovirus-based neutralization assays. We found that convalescent RBD-reactive …

Novel Therapuetic Approaches For Chagas Disease, Juan Carlos Silva

Open Access Theses & Dissertations

Chagas disease (CD) is caused by the hemoflagellate protozoan Trypanosoma cruzi. This disease is considered one of the 20 neglected tropical diseases (NTD), and it is estimated that 6 to 8 million people worldwide are diagnosed with CD. In the United States, Chagas infection is not reported in all states; however, most reported CD cases are chronic infections. Chagas infection is characterized by two phases: an acute and a chronic phase. Until this present moment, no prophylactic or therapeutic human vaccine is available. However, in a recent study in a murine model, our group showed that the synthetic 20-merpeptide (DAENPGGEVFNDNKKGLSRV) …

Limosilactobacillus Reuteri Ameliorates Maternal Separation Stress In Newborn Mice And Alters Subsequent Adult Behaviour, Z. M. Saleh, B. Okeugo, V. R. Venna, F. W. Blixt, V. A. Quaicoe, E. S. Park, S. Giorgberidze, Meng Luo, Christopher M. Taylor, J. M. Rhoads, Y. Liu

School of Medicine Faculty Publications

Maternal separation (MS) in mice results in behavioral deficits and gut microbiota dysbiosis that all persist into adulthood. Limosilactobacillus reuteri DSM 17938 modulates gut microbiota, alters systemic metabolites, and facilitates immune regulation. To assess the effect of DSM 17938 on biochemical and behavioural stress-associated changes, newborn mice were exposed to unpredictable MS (MSU) daily from day 7 to day 20 of life, with intragastric administration of DSM 17938 or PBS as control. Body weight, brain levels of cholecystokinin (CCK), glial fibrillary acidic protein (GFAP), corticosterone, and stool microbiota were assessed at day 21. Behaviour tests including Y-maze (YMT), Tail Suspension …

Low Prevalence Of Soil Transmitted Helminth Infection In Ugandan Children Hospitalized With Severe Malaria, Drew Capone, Nuzrath Jahan, Ruth Namazzi, Robert Opoka, Chandy John

Paediatrics and Child Health, East Africa

Co-infection by intestinal helminths and Plasmodium spp. may be common in endemic communities. Several studies have identified a relationship between helminth infection, Plasmodium spp. infection and malaria severity. However, the relationship is not well defined, and results are inconclusive. We analyzed stool samples from a cohort of children with severe malaria enrolled in two hospitals in Uganda from 2014-2017 and asymptomatic community children from the same household or neighborhood and enrolled at the same time, all 6 months to 48 months of age. We investigated if intestinal helminth infection modified risk of severe malaria. We extracted nucleic acids from stool …

Characterization Of High-Risk-Other Human Papillomavirus Genotypes In Papanicolaou Tests, High-Grade Squamous Intraepithelial Lesions, And Cervical Cancer, Caitlin E. Witt, Elizabeth F. Sutton, Ashley M. Stansbury, Ashley N. Winters, Luke C. Konur, Meng Luo, Jennifer E. Cameron, Beverly Ogden

School of Medicine Faculty Publications

Background: The objective of this study was to determine the human papillomavirus (HPV) genotypes of high-risk-other HPV Papanicolaou (Pap) tests and of biopsy tissues from patients with high-grade squamous intraepithelial lesion (HGSIL) or cervical cancer. High-risk-other HPV status was determined with the cobas HPV Test (Roche Diagnostics, North America) that identifies 12 high-risk, non-16/18 HPV genotypes. We hypothesized that we would find genotypes of HPV in our population that are not covered by the 9-valent HPV vaccine. Methods: For this retrospective cohort study, we randomly selected 50 high-risk-other HPV Pap test samples from 2018 from our pathology department registries for …

Concepts In Animal Parasitology, Scott L. Gardner, Sue Ann Gardner

Zea E-Books Collection

Note that this version of the textbook has been superceded by the one updated in 2026, available at the UNL Pressbooks site.

The hard copy version that is for sale at lulu.com is the old version.

"This is a textbook covering concepts in animal parasitology. It is meant to be used by students, teachers, professors, researchers, and members of the public who are interested in learning about animal parasite biology, systematics, taxonomy, zoogeography, and ecology. The primary intended audience is upper-level undergraduate or graduate university students who have knowledge of basic biology and, particularly, basic animal biology. (863 pages, …

Tailoring T Fh Profiles Enhances Antibody Persistence To A Clade C Hiv-1 Vaccine In Rhesus Macaques, Anil Verma, Chase E. Hawes, Sonny R. Elizaldi, Justin C. Smith, Dhivyaa Rajasundaram, Gabriel Kristian Pedersen, Xiaoying Shen, La Tonya D. Williams, Georgia D. Tomaras, Pamela A. Kozlowski, Rama R. Amara, Smita S. Iyer

School of Medicine Faculty Publications

CD4 T follicular helper cells (Tfh) are essential for establishing serological memory and have distinct helper attributes that impact both the quantity and quality of the antibody response. Insights into Tfh subsets that promote antibody persistence and functional capacity can critically inform vaccine design. Based on the Tfh profiles evoked by the live attenuated measles virus vaccine, renowned for its ability to establish durable humoral immunity, we investigated the potential of a Tfh1/17 recall response during the boost phase to enhance persistence of HIV-1 Envelope (Env) antibodies in rhesus macaques. Using a DNA-prime encoding gp160 antigen and Tfh polarizing cytokines …

Probiotic Limosilactobacillus Reuteri Dsm 17938 Changes Foxp3 Deficiency-Induced Dyslipidemia And Chronic Hepatitis In Mice, Erini Nessim Kostandy, Ji Ho Suh, Xiangjun Tian, Beanna Okeugo, Erin Rubin, Sara Shirai, Meng Luo, Christopher M. Taylor, Kang Ho Kim, J. Marc Rhoads, Yuying Liu

School of Medicine Faculty Publications

The probiotic Limosilactobacillus reuteri DSM 17938 produces anti-inflammatory effects in scurfy (SF) mice, a model characterized by immune dysregulation, polyendocrinopathy, enteropathy, and X-linked inheritance (called IPEX syndrome in humans), caused by regulatory T cell (Treg) deficiency and is due to a Foxp3 gene mutation. Considering the pivotal role of lipids in autoimmune inflammatory processes, we investigated alterations in the relative abundance of lipid profiles in SF mice (± treatment with DSM 17938) compared to normal WT mice. We also examined the correlation between plasma lipids and gut microbiota and circulating inflammatory markers. We noted a significant upregulation of plasma lipids …

Microbial Interactions Among Gardnerella, Prevotella And Fannyhessea Prior To Incident Bacterial Vaginosis: Protocol For A Prospective, Observational Study, Christina A. Muzny, Jacob H. Elnaggar, Lúcia G.V. Sousa, Ângela Lima, Kristal J. Aaron, Isaac C. Eastlund, Keonte J. Graves, Chaoling Dong, Olivia T. Van Gerwen, Meng Luo, Ashutosh Tamhane, Dustin Long, Nuno Cerca, Christopher M. Taylor

School of Graduate Studies Faculty Publications

Introduction The aetiology of bacterial vaginosis (BV), a biofilm-associated vaginal infection, remains unknown. Epidemiologic data suggest that it is sexually transmitted. BV is characterised by loss of lactic acid-producing lactobacilli and an increase in facultative and strict anaerobic bacteria. Gardnerella spp are present in 95%–100% of cases; Gardnerella vaginalis has been found to be more virulent than other BV-associated bacteria (BVAB) in vitro. However, G. vaginalis is found in women with normal vaginal microbiota and colonisation is not sufficient for BV development. We hypothesise that Gardnerella spp initiate BV biofilm formation, but incident BV (iBV) requires incorporation of other key …

Targeted Repression Of Topa By Crispri Reveals A Critical Function For Balanced Dna Topoisomerase I Activity In The Chlamydia Trachomatis Developmental Cycle, Li Shen, Leiqiong Gao, Abigail R. Swoboda, Scot P. Ouellette

School of Medicine Faculty Publications

Chlamydia trachomatis is an obligate intracellular bacterium that is responsible for the most prevalent bacterial sexually transmitted infection. Changes in DNA topology in this pathogen have been linked to its pathogenicity-associated developmental cycle. Here, evidence is provided that the balanced activity of DNA topoisomerases contributes to controlling Chlamydia developmental processes. Utilizing catalytically inactivated Cas12 (dCas12)-based clustered regularly interspaced short palindromic repeats interference (CRISPRi) technology, we demonstrate targeted knockdown of chromosomal topA transcription in C. trachomatis without detected toxicity of dCas12. Repression of topA impaired the developmental cycle of C. trachomatis mostly through disruption of its differentiation from a replicative form …

Interplay Between Acetylation And Ubiquitination Of Imitation Switch Chromatin Remodeler Isw1 Confers Multidrug Resistance In Cryptococcus Neoformans, Yang Meng, Yue Ni, Zhuoran Li, Tianhang Jiang, Tianshu Sun, Yanjian Li, Xindi Gao, Hailong Li, Chenhao Suo, Chao Li, Sheng Yang, Tian Lan, Guojian Liao, Tongbao Liu, Ping Wang, Chen Ding

School of Medicine Faculty Publications

Cryptococcus neoformans poses a threat to human health, but anticryptococcal therapy is hampered by the emergence of drug resistance, whose underlying mechanisms remain poorly understood. Herein, we discovered that Isw1, an imitation switch chromatin remodeling ATPase, functions as a master modulator of genes responsible for in vivo and in vitro multidrug resistance in C. neoformans. Cells with the disrupted ISW1 gene exhibited profound resistance to multiple antifungal drugs. Mass spectrometry analysis revealed that Isw1 is both acetylated and ubiquitinated, suggesting that an interplay between these two modification events exists to govern Isw1 function. Mutagenesis studies of acetylation and ubiquitination sites …

Genital Tract Infections, The Vaginal Microbiome And Gestational Age At Birth Among Pregnant Women In South Africa: A Cohort Study Protocol, Ranjana M.S. Gigi, Mandisa M. Mdingi, Hyunsul Jung, Shantelle Claassen-Weitz, Lukas Bütikofer, Jeffrey D. Klausner, Christina A. Muzny, Christopher M. Taylor, Janneke H.H.M. Van De Wijgert, Remco P.H. Peters, Nicola Low

School of Medicine Faculty Publications

Introduction Preterm birth complications are the most common cause of death in children under 5 years. The presence of multiple microorganisms and genital tract inflammation could be the common mechanism driving early onset of labour. South Africa has high levels of preterm birth, genital tract infections and HIV infection among pregnant women. We plan to investigate associations between the presence of multiple lower genital tract microorganisms in pregnancy and gestational age at birth. Methods and analysis This cohort study enrols around 600 pregnant women at one public healthcare facility in East London, South Africa. Eligible women are ≥18 years and …

Association Of Chlamydia Trachomatis Burden With The Vaginal Microbiota, Bacterial Vaginosis, And Metronidazole Treatment, Caleb M. Ardizzone, Christopher M. Taylor, Evelyn Toh, Rebecca A. Lillis, Jacob H. Elnaggar, John W. Lammons, Patricia Dehon Mott, Emily L. Duffy, Li Shen, Alison J. Quayle

School of Graduate Studies Faculty Publications

Bacterial vaginosis (BV), a dysbiosis of the vaginal microbiota, is a common coinfection with Chlamydia trachomatis (Ct), and BV-associated bacteria (BVAB) and their products have been implicated in aiding Ct evade natural immunity. Here, we determined if a non-optimal vaginal microbiota was associated with a higher genital Ct burden and if metronidazole, a standard treatment for BV, would reduce Ct burden or aid in natural clearance of Ct infection. Cervicovaginal samples were collected from women at enrollment and, if testing positive for Ct infection, at a follow-up visit approximately one week later. Cervical Ct burden was assessed by inclusion forming …

Exploration Of The Implementation Of An Integrated Electronic Laboratory Information Management System On Quality Diagnostics Service Indicators At A County Level Public Hospital In Western Kenya., Kelly Allen

Capstone Collection

Underinvestment in pathology and laboratory capacity caused by low visibility in research and in prioritization by public health leaders results in limited effective healthcare coverage and an estimated 1.1 million premature deaths annually in Low-and-Middle-Income Countries. Kenya’s public health laboratories provide a median 41% of the Essential Diagnostic List to their patients and in Kisumu County, as much as 44.2% of the population has little to no access to essential diagnostics. The government of Kisumu implemented the county Health Laboratory Strategic Plan 2018-2022 to address this public health challenge. Little information exists on the effectiveness of these initiatives and the …

Impact Of Testosterone Use On The Vaginal Microbiota Of Transgender Men, Including Susceptibility To Bacterial Vaginosis: Study Protocol For A Prospective, Observational Study, Christina A. Muzny, Olivia T. Van Gerwen, Julia A. Schroeder, Emma Sophia Kay-Duncan, Krishmita Siwakoti, Kristal J. Aaron, Isaac C. Eastlund, Keonte J. Graves, Jacob H. Elnaggar, Ashutosh Tamhane, Dustin Long, Nicholas Van Wagoner, Evelyn Toh, Christopher M. Taylor

School of Graduate Studies Faculty Publications

Introduction The effect of testosterone (T) therapy on the vaginal microbiota of transgender men (TGM) is not well characterised, although one cross-sectional study comparing the vaginal microbiota of cisgender women to TGM on T≥1 year found that, in 71% of the TGM, the vaginal microbiota was less likely to be Lactobacillus-dominated and more likely to be enriched with >30 other bacterial species, many associated with bacterial vaginosis (BV). This prospective study aims to investigate changes in the composition of the vaginal microbiota over time in TGM who retain their natal genitalia (ie, vagina) and initiate T. In addition, we will …

Anti-Tick Vaccine Candidate Subolesin Is Important For Blood Feeding And Innate Immune Gene Expression In Soft Ticks, Krittika Nandy, Comfort Tamakloe, Daniel E. Sonenshine, Hameeda Sultana, Girish Neelakanta

Biological Sciences Faculty Publications

Subolesin is a conserved molecule in both hard and soft ticks and is considered as an effective candidate molecule for the development of anti-tick vaccine. Previous studies have reported the role of subolesin in blood feeding, reproduction, development, and gene expression in hard ticks. However, studies addressing the role of subolesin in soft ticks are limited. In this study, we report that subolesin is not only important in soft tick Ornithodoros turicata americanus blood feeding but also in the regulation of innate immune gene expression in these ticks. We identified and characterized several putative innate immune genes including Toll, Lysozyme …

Tick Extracellular Vesicles Enable Arthropod Feeding And Promote Distinct Outcomes Of Bacterial Infection, Adela S. Oliva Chávez, Xiaowei Wang, Liron Marnin, Nathan K. Archer, Holly L. Hammond, Erin E. Mcclure Carroll, Dana K. Shaw, Brenden G. Tully, Amanda D. Buskirk, Shelby L. Ford, L. Rainer Butler, Preeti Shahi, Kateryna Morozova, Cristina C. Clement, Lauren Lawres, Anya J. O'Neal, Choukri Ben Mamoun, Kathleen L. Mason, Brandi E. Hobbs, Glen A. Scoles, Eileen M. Barry, Daniel E. Sonenshine, Utpal Pal, Jesus G. Valenzuela, Marcelo B. Sztein, Marcela F. Pasetti, Michael L. Levin, Michail Kotsyfakis, Steven M. Jay, Jason F. Huntley, Lloyd S. Miller, Laura Santambrogio, Joao H.F. Pedra

Biological Sciences Faculty Publications

Extracellular vesicles are thought to facilitate pathogen transmission from arthropods to humans and other animals. Here, we reveal that pathogen spreading from arthropods to the mammalian host is multifaceted. Extracellular vesicles from Ixodes scapularis enable tick feeding and promote infection of the mildly virulent rickettsial agent Anaplasma phagocytophilum through the SNARE proteins Vamp33 and Synaptobrevin 2 and dendritic epidermal T cells. However, extracellular vesicles from the tick Dermacentor andersoni mitigate microbial spreading caused by the lethal pathogen Francisella tularensis. Collectively, we establish that tick extracellular vesicles foster distinct outcomes of bacterial infection and assist in vector feeding by acting …

Plasmodium Impairs Antibacterial Innate Immunity To Systemic Infections In Part Through Hemozoin-Bound Bioactive Molecules., Christopher Lynn Harding

Electronic Theses and Dissertations

Despite efforts to decrease the global health burden of malaria, infections with Plasmodium species continue to cause over 200 million episodes of malaria each year which resulted in 405,000 deaths in 2018 [1]. One complication of malaria is increased susceptibility to invasive bacterial infections. Plasmodium infections impair host immunity to non-Typhoid Salmonella (NTS) through activities of heme oxygenase I (HO-I) )-induced release of immature granulocytes and myeloid cell-derived IL-10. Yet, it is not known if these mechanisms are specific to NTS. We show here, that Plasmodium yoelii 17XNL (Py) infected mice had impaired clearance of systemic Listeria monocytogenes (Lm) during …

Expression And Functional Sialome Of Triatomines, Insect Vectors Of Chagas Disease, Maria Tays Mendes

Open Access Theses & Dissertations

Triatomines are blood-sucking arthropods that transmit Trypanosoma cruzi, the etiologic agent of Chagas disease (ChD). Triatomines use bioactive molecules in the saliva for successful blood feeding and to evade the hemostatic and immune defense system of the hosts. Knowing the saliva composition could be useful for a better understanding which and how insect-derived molecules might influence host-parasite interactions. Previous studies have shown that some saliva-derived proteins and lipids can modulate the host immune system and increase T. cruzi infection. We hypothesize that the triatomine saliva contains a great diversity of lipids and proteins that can modulate the mammalian host immune …

Molecular Investigation And Phylogeny Of Species Of The Anaplasmataceae Infecting Animals And Ticks In Senegal, Mustapha Dahmani, Bernard Davoust, Masse Sambou, Hubert Bassene, Pierre Scandola, Tinhinene Ameur, Didier Raoult, Florence Feenollar, Oleg Mediannikov

Biological Sciences Faculty Publications

Background: Our study aimed to assess the diversity of the species of Anaplasmataceae in Senegal that infect animals and ticks in three areas: near Keur Momar Sarr (northern region), Dielmo and Diop (Sine Saloum, central region of Senegal), and in Casamance (southern region of Senegal).

Methods: A total of 204 ticks and 433 blood samples were collected from ruminants, horses, donkeys and dogs. Ticks were identified morphologically and by molecular characterization targeting the 12S rRNA gene. Molecular characterization of species of Anaplasmataceae infecting Senegalese ticks and animals was conducted using the 23S rRNA, 16S rRNA, rpoB and groEL genes.

Results: …

Dynamics Of Two Pathogens In A Single Tick Population, Alexis White, Elsa Schaefer, Chelsea Wright-Thompson, Christopher M. Kribs, Holly Gaff

Biological Sciences Faculty Publications

A mathematical model for a two-pathogen, one-tick, one-host system is presented and explored. The goal of this model is to determine how long an invading pathogen persists within a tick population in which a resident pathogen is already established. The numerical simulations of the model demonstrate the parameter ranges that allow for coexistence of the two pathogens. Sensitivity analysis highlights the importance of vector-borne, tick-to-host, transmission rates on the invasion reproductive number and persistence of the pathogens over time. The model is then applied to a case study based on a reclaimed swampland field site in southeastern Virginia using field …

Trypanosoma Cruzi Trypomastigote Glycosylphosphatidylinositol-Anchored Mucins And A Synthetic Alpha-Gal-Containing Neoglycoprotein As Potential Biomarkers And Vaccines For Chagas Disease, Igor Leandro Estevao

Open Access Theses & Dissertations

Chagas disease (CD), caused by the protozoan Trypanosoma cruzi, is a neglected tropical disease that kills or permanently disable thousands of people annually. About 6-8 million people are estimated to be infected worldwide. Although many efforts have been made for the development of an effective immunotherapy, currently there is no vaccine to prevent or treat CD in humans. Despite their toxicity, the two current drugs for CD, benznidazole (BZN) and nifurtimox (NFX), have medium-to-high efficacy in the chronic stage of the disease and could save or improve the lives of thousands of patients. However, negative seroconversion in treated patients, as …

The Small Rna Complement Of Adult Schistosoma Haematobium., Andreas J Stroehlein, Neil D Young, Pasi K Korhonen, Ross S Hall, Aaron R Jex, Bonnie L Webster, David Rollinson, Paul J Brindley, Robin B Gasser

Microbiology, Immunology, and Tropical Medicine Faculty Publications

BACKGROUND: Blood flukes of the genus Schistosoma cause schistosomiasis-a neglected tropical disease (NTD) that affects more than 200 million people worldwide. Studies of schistosome genomes have improved our understanding of the molecular biology of flatworms, but most of them have focused largely on protein-coding genes. Small non-coding RNAs (sncRNAs) have been explored in selected schistosome species and are suggested to play essential roles in the post-transcriptional regulation of genes, and in modulating flatworm-host interactions. However, genome-wide small RNA data are currently lacking for key schistosomes including Schistosoma haematobium-the causative agent of urogenital schistosomiasis of humans.

METHODOLOGY: MicroRNAs (miRNAs) and other …

Drug Repurposing For Schistosomiasis: Combinations Of Drugs Or Biomolecules., Maria João Gouveia, Paul J Brindley, Fátima Gärtner, José M Correia Da Costa, Nuno Vale

Microbiology, Immunology, and Tropical Medicine Faculty Publications

Schistosomiasis is a major neglected tropical disease. Control of schistosomiasis currently relies on a single drug, praziquantel, and despite its efficacy against the all schistosome species that parasitize humans, it displays some problematic drawbacks and alone is ineffective in counteracting adverse pathologies associated with infection. Moreover, due to the development of the potential emergence of PZQ-resistant strains, the search for additional or alternative antischistosomal drugs have become a public health priority. The current drug discovery for schistosomiasis has been slow and uninspiring. By contrast, repurposing of existing approved drugs may offer a safe, rapid and cost-effective alternative. Combined treatment with …

Sertraline, Paroxetine, And Chlorpromazine Are Rapidly Acting Anthelmintic Drugs Capable Of Clinical Repurposing., Janis C Weeks, William M Roberts, Caitlyn Leasure, Brian M Suzuki, Kristin J Robinson, John M Hawdon, +Several Additional Authors

Microbiology, Immunology, and Tropical Medicine Faculty Publications

Parasitic helminths infect over 1 billion people worldwide, while current treatments rely on a limited arsenal of drugs. To expedite drug discovery, we screened a small-molecule library of compounds with histories of use in human clinical trials for anthelmintic activity against the soil nematode Caenorhabditis elegans. From this screen, we found that the neuromodulatory drugs sertraline, paroxetine, and chlorpromazine kill C. elegans at multiple life stages including embryos, developing larvae and gravid adults. These drugs act rapidly to inhibit C. elegans feeding within minutes of exposure. Sertraline, paroxetine, and chlorpromazine also decrease motility of adult Trichuris muris whipworms, prevent hatching …

Granulin Secreted By The Food-Borne Liver Fluke, Brandon Haugen, Shannon E Karinshak, Victoria H Mann, Anastas Popratiloff, Alex Loukas, Paul J Brindley, Michael J Smout

Microbiology, Immunology, and Tropical Medicine Faculty Publications

The liver fluke Opisthorchis viverrini is a food-borne, zoonotic pathogen endemic to Thailand and adjacent countries in Southeast Asia. The adult developmental stage of the O. viverrini parasite excretes and secretes numerous proteins within the biliary tract including the gall bladder. Lesions caused by the feeding activities of the liver fluke represent wounds that undergo protracted cycles of healing and re-injury during chronic infection, which can last for decades. Components of the excretory/secretory (ES) complement released by the worms capably drive proliferation of bile duct epithelial cells and are implicated in establishing the oncogenic milieu that leads to bile duct …

Granulin Secreted By The Food-Borne Liver Fluke Opisthorchis Viverrini Promotes Angiogenesis In Human Endothelial Cells, Brandon Haugen, Shannon Karinshak, Victoria H. Mann, Anastas Popratiloff, Alex Loukas, Paul J. Brindley, Michael J. Smout

Microbiology, Immunology, and Tropical Medicine Faculty Publications

The liver fluke Opisthorchis viverrini is a food-borne, zoonotic pathogen endemic to Thailand and adjacent countries in Southeast Asia. The adult developmental stage of the O. viverrini parasite excretes and secretes numerous proteins within the biliary tract including the gall bladder. Lesions caused by the feeding activities of the liver fluke represent wounds that undergo protracted cycles of healing and re-injury during chronic infection, which can last for decades. Components of the excretory/secretory (ES) complement released by the worms capably drive proliferation of bile duct epithelial cells and are implicated in establishing the oncogenic milieu that leads to bile duct …

Controlled Human Hookworm Infection: Accelerating Human Hookworm Vaccine Development, David Diemert, Doreen Campbell, Jill Brelsford, Caitlyn Leasure, Guangzhao Li, Naji Younes, +Several Additional Authors

Microbiology, Immunology, and Tropical Medicine Faculty Publications

Background

Controlled human hookworm infection (CHHI) is a central component of a proposed hookworm vaccination-challenge model (HVCM) to test the efficacy of candidate vaccines. Critical to CHHI is the manufacture of Necator americanus infective larvae (NaL3) according to current Good Manufacturing Practice (cGMP) and the determination of an inoculum of NaL3 that is safe and reliably induces patent infection. Methods

cGMP-grade NaL3 were produced for a phase 1 trial in 20 healthy, hookworm-naïve adults in the United States, who received either 25 or 50 NaL3. Participants were monitored for 12–18 weeks postinfection for safety, tolerability, …