Tropical Medicine Commons^™

Echinococcus Multilocularis Calreticulin Interferes With C1q-Mediated Complement Activation, Siqi Xian, Lujuan Chen, Yan Yan, Jianfang Chen, Guixia Yu, Yuxiao Shao, Bin Zhan, Yanhai Wang, Limei Zhao

Faculty, Staff and Students Publications

As a zoonotic disease caused by Echinococcus multilocularis larvae, alveolar echinococcosis (AE) is one of the most severe forms of parasitic infection. Over a long evolutional process E. multilocularis has developed complex strategies to escape host immune attack and survive within a host. However, the mechanisms underlying immune evasion remain unclear. Here we investigated the binding activity of E. multilocularis calreticulin (EmCRT), a highly conserved Ca2+-binding protein, to human complement C1q and its ability to inhibit classical complement activation. ELISA, Far Western blotting and immunoprecipitation results demonstrated that both recombinant and natural EmCRTs bound to human C1q, …

The Legacy Of The Covid-19 Pandemic For Childhood Vaccination In The Usa, Douglas J Opel, Noel T Brewer, Alison M Buttenheim, Timothy Callaghan, Richard M Carpiano, Chelsea Clinton, Jad A Elharake, Lisa C Flowers, Alison P Galvani, Peter J Hotez, Jason L Schwartz, Regina M Benjamin, Arthur Caplan, Renee Diresta, Rekha Lakshmanan, Yvonne A Maldonado, Michelle M Mello, Wendy E Parmet, Daniel A Salmon, Joshua M Sharfstein, Saad B Omer

Faculty, Staff and Students Publications

No abstract provided.

Editorial: Biological Drivers Of Vector-Pathogen Interactions – Vol Ii, Ryan O M Rego, Job E Lopez, Alejandro Cabesas-Cruz

Faculty, Staff and Students Publications

No abstract provided.

Editorial: The Regulatory Immune System As A Target To Improve Adjuvants And Novel Vaccines, Carlos Jiménez-Cortegana, Cristina Poveda, Gabriel Cabrera

Faculty, Staff and Students Publications

No abstract provided.

Editorial: Regeneration From Cells To Limbs: Past, Present, And Future, Pamela Imperadore, Kathryn Maxson Jones, Jennifer R Morgan, Fabio De Sio, Frank W Stahnisch

Faculty, Staff and Students Publications

No abstract provided.

Vaxi-Dl: An Artificial Intelligence-Enabled Platform For Vaccine Development, P Preeti, Swarsat Kaushik Nath, Nevidita Arambam, Trapti Sharma, Priyanka Ray Choudhury, Alakto Choudhury, Vrinda Khanna, Ulrich Strych, Peter J Hotez, Maria Elena Bottazzi, Kamal Rawal

Faculty, Staff and Students Publications

Vaccine development is a complex and long process. It involves several steps, including computational studies, experimental analyses, animal model system studies, and clinical trials. This process can be accelerated by using in silico antigen screening to identify potential vaccine candidates. In this chapter, we describe a deep learning-based technique which utilizes 18 biological and 9154 physicochemical properties of proteins for finding potential vaccine candidates. Using this technique, a new web-based system, named Vaxi-DL, was developed which helped in finding new vaccine candidates from bacteria, protozoa, viruses, and fungi. Vaxi-DL is available at: https://vac.kamalrawal.in/vaxidl/ .

Protocol Of Detection Of West Nile Virus In Clinical Samples, Hephzibah Nwanosike, Freedom M Green, Kristy O Murray, Jill E Weatherhead, Shannon E Ronca

Faculty, Staff and Students Publications

West Nile virus (WNV) is one of the leading causes of arboviral encephalitis in the United States but is often underdiagnosed. Despite the wide breadth of WNV-induced clinical disease syndromes, many of the symptoms associated with WNV are nonspecific at the time of presentation; thus, choosing the right diagnostic tool is essential to not only understand the true burden of disease but also provide pathogen-directed interventions for WNV-infected patients. In this chapter, we briefly discuss the three most common types of diagnostic methods for WNV in human clinical samples: nucleic acid detection, enzyme-linked immunoassay (ELISA), and plaque reduction neutralization test …

Vaccine-Linked Chemotherapy Improves Cardiac Structure And Function In A Mouse Model Of Chronic Chagas Disease, Kathryn M Jones, Elise N Mangin, Corey L Reynolds, Liliana E Villanueva, Julio Vladimir Cruz, Leroy Versteeg, Brian Keegan, April Kendricks, Jeroen Pollet, Fabian Gusovsky, Maria Elena Bottazzi, Peter J Hotez

Faculty, Staff and Students Publications

INTRODUCTION: Chagas disease, caused by chronic infection with the protozoan parasite Trypanosoma cruzi, affects 6-7 million people worldwide. The major clinical manifestation of Chagas disease is chronic Chagasic cardiomyopathy (CCC), which encompasses a spectrum of symptoms including arrhythmias, hypertrophy, dilated cardiomyopathy, heart failure, and sudden death. Current treatment is limited to two antiparasitic drugs, benznidazole (BNZ) and nifurtimox, but both have limited efficacy to halt the progression of CCC. We developed a vaccine-linked chemotherapy strategy using our vaccine consisting of recombinant Tc24-C4 protein and a TLR-4 agonist adjuvant in a stable squalene emulsion, in combination with low dose benznidazole treatment. …

Heterologous Mrna-Protein Vaccination With Tc24 Induces A Robust Cellular Immune Response Against Trypanosoma Cruzi, Characterized By An Increased Level Of Polyfunctional Cd8+ T-Cells, Cristina Poveda, Ana Carolina Leão, Chiara Mancino, Francesca Taraballi, Yi-Lin Chen, Rakesh Adhikari, Maria Jose Villar, Rakhi Kundu, Duc M Nguyen, Leroy Versteeg, Ulrich Strych, Peter J Hotez, Maria Elena Bottazzi, Jeroen Pollet, Kathryn M Jones

Faculty, Staff and Students Publications

Tc24 is a Trypanosoma cruzi-derived flagellar protein that, when formulated with a TLR-4 agonist adjuvant, induces a balanced immune response in mice, elevating IgG2a antibody titers and IFN-γ levels. Furthermore, vaccination with the recombinant Tc24 protein can reduce parasite levels and improve survival during acute infection. Although some mRNA vaccines have been proven to elicit a stronger immune response than some protein vaccines, they have not been used against T. cruzi. This work evaluates the immunogenicity of a heterologous prime/boost vaccination regimen using protein and mRNA-based Tc24 vaccines. Mice (C57BL/6) were vaccinated twice subcutaneously, three weeks apart, with …

Prevalence Of Trypanosoma Cruzi, The Etiologic Agent Of Chagas Disease, Infection In Texas Skunks (Mammalia: Mephitidae), Bonnie E Gulas-Wroblewski, Rodion Gorchakov, Rebecca B Kairis, Robert C Dowler, Kristy O Murray

Faculty, Staff and Students Publications

Background:

Chagas disease is one of the world's most neglected tropical diseases, infecting over six million people across the Americas. The hemoparasite Trypanosoma cruzi is the etiological agent for the disease, circulating in domestic, peridomestic, and sylvatic transmission cycles that are maintained by triatomine vectors and a diversity of wild and synanthropic hosts. Public health and wildlife management interventions targeting the interruption of T. cruzi transmission rely on an understanding of the dynamics driving the ecology of this zoonotic pathogen. One wildlife host that purportedly plays a role in the transmission of Chagas disease within the southern United States is …

Immunomodulatory Proteins From Hookworms Reduce Cardiac Inflammation And Modulate Regulatory Responses In A Mouse Model Of Chronic Trypanosoma Cruzi Infection, Kathryn M Jones, Bin Zhan, Keenan J Ernste, Maria Jose Villar, Nalini Bisht, Duc Nguyen, Li-Yen Chang, Cristina Poveda, Gonteria J Robinson, Akshar J Trivedi, Colby J Hofferek, William K Decker, Vanaja Konduri

Faculty, Staff and Students Publications

Introduction

Hookworms are parasitic helminths that secrete a variety of proteins that induce anti-inflammatory immune responses, stimulating increased CD4+Foxp3+ regulatory T cells and IL-10 production. Hookworm-derived recombinant proteins AIP-1 and AIP-2 have been shown to reduce inflammation in mouse models of inflammatory bowel disease and inflammatory airway disease by inducing CD4+Foxp3+ cells and IL-10 production. In contrast, chronic infection with the protozoal parasite Trypanosoma cruzi, the causative agent of Chagas disease, leads to chronic inflammation in tissues. Persistence of the parasites in tissues drives chronic low-grade inflammation, with increased infiltration of inflammatory cells into the heart, accompanied by increased …

Safety Procedures To Work With West Nile Virus In Biosafety Level 3 Facilities, Freedom M Green, Shannon E Ronca

Faculty, Staff and Students Publications

West Nile virus (WNV) can cause severe and sometimes fatal disease, but we do not have treatments or therapeutics to manage these outcomes. Since its introduction to the USA in 1999, WNV has been handled in a biosafety level 3 laboratory to decrease risk to researchers, requiring strict safety protocols and important considerations with planning experiments. Recent changes in US guidelines suggest that WNV can be handled at a lower biosafety level due to its endemicity in the USA and generally minor symptoms, but some research still requires the use of the agent at biosafety level 3. This chapter will …

Analysis Of Variable Major Protein Antigenic Variation In The Relapsing Fever Spirochete, Borrelia Miyamotoi, In Response To Polyclonal Antibody Selection Pressure, Robert D Gilmore, Brittany A Armstrong, Kevin S Brandt, Taylor J Van Gundy, Andrias Hojgaard, Job E Lopez, Alexander R Kneubehl

Faculty, Staff and Students Publications

Borrelia miyamotoi is a tick-transmitted spirochete that is genetically grouped with relapsing fever Borrelia and possesses multiple archived pseudogenes that encode variable major proteins (Vmps). Vmps are divided into two groups based on molecular size; variable large proteins (Vlps) and variable small proteins (Vsps). Relapsing fever Borrelia undergo Vmp gene conversion at a single expression locus to generate new serotypes by antigenic switching which is the basis for immune evasion that causes relapsing fever in patients. This study focused on B. miyamotoi vmp expression when spirochetes were subjected to antibody killing selection pressure. We incubated a low passage parent …

How I Approach Leishmaniasis: Diagnosis And Treatment In The United States, Tara E Ness, Rachel Martin-Blais, Jill E Weatherhead

Faculty, Staff and Students Publications

Leishmaniasis is a vector-borne disease caused by over 20 species of obligate intracellular protozoa belonging to the genus Leishmania. Leishmaniasis has a global distribution, including in the United States, and can cause a spectrum of clinical syndromes, including cutaneous, mucosal, and visceral diseases depending on host factors and the infecting Leishmania spp. Accurate diagnosis, including Leishmania species identification, is an important step to guide the most appropriate therapeutic intervention. Antileishmanial therapy is dependent on the Leishmania spp. identified, the clinical syndrome, and the child's immune system. However, many treatment regimens for children have been extrapolated from adult clinical trials, which …

Periprosthetic Knee Infection After Benign Tumor Excision Complicated By Carbapenem Resistant Enterobacteriaceae: A Case Report, Jennifer Adams, Daniel Habenicht, Duncan C. Ramsey

MEDI 9331 Scholarly Activities Clinical Years

Introduction

Periprosthetic joint infection (PJI) is a major complication after total knee arthroscopy. Enterobacter is a rare cause of PJI.

Case presentation

We present a 65 year old Caucasian man who presented with acute right knee PJI with Carbapenem-resistant Enterobacteriaceae (CRE) two months after undergoing right knee intra-articular mass removal with endoprosthetic reconstruction. The periprosthetic joint infection (PJI) was treated with revision with 1-stage static spacer and IV meropenem.

Discussion

CRE is an uncommon cause of PJI, but when it does occur, it commonly infects patients who are immunosuppressed or have specific risk factors. For an immunocompetent patient with CRE …

Regional Research-Practice-Policy Partnerships In Response To Climate-Related Disparities: Promoting Health Equity In The Pacific, Lawrence A. Palinkas, Meaghan O’Donnell, Susan Kemp, Jemaima Tiatia, Yvonette Duque, Michael Spencer, Rupa Basu, Kristine Idda Del Rosario, Kristin Diemer, Bonifacio Doma, David Forbes, Kari Gibson, Joshua Graff-Zivin, Bruce M. Harris, Nicola Hawley, Jill Johnston, Fay Lauraya, Nora Elizabeth F. Maniquiz, Jay Marlowe, Gordon C. Mccord, Imogen Nicholls, Smitha Rao, Angela Kim Saunders, Salvatore Sortino, Benjamin F. Springgate, David Takeuchi, Janette Ugsang, Vivien Villaverde

School of Medicine Faculty Publications

Although climate change poses a threat to health and well-being globally, a regional approach to addressing climate-related health equity may be more suitable, appropriate, and appealing to under-resourced communities and countries. In support of this argument, this commentary describes an approach by a network of researchers, practitioners, and policymakers dedicated to promoting climate-related health equity in Small Island Developing States and low- and middle-income countries in the Pacific. We identify three primary sets of needs related to developing a regional capacity to address physical and mental health disparities through research, training, and assistance in policy and practice implementation: (1) limited …

Rapid Assessment Of Opisthorchis Viverrini Igg Antibody In Serum: A Potential Diagnostic Biomarker To Predict Risk Of Cholangiocarcinoma In Regions Endemic For Opisthorchiasis., Rutchanee Rodpai, Vor Luvira, Lakkhana Sadaow, Wattana Sukeepaisarnjaroen, Amnat Kitkhuandee, Krisada Paonariang, Oranuch Sanpool, Wannaporn Ittiprasert, Victoria H. Mann, Pewpan M Intapan, Paul J. Brindley, Wanchai Maleewong

Microbiology, Immunology, and Tropical Medicine Faculty Publications

BACKGROUND: Opisthorchiasis is caused by an infection with fish-borne liver flukes of the genus Opisthorchis. Opisthorchiasis frequently leads to chronic inflammation in the biliary tract and is classified as a group 1 biological carcinogen by the International Agency for Research on Cancer: a definitive risk for cholangiocarcinoma (CCA).

METHODS: We used the rapid immunochromatographic test (ICT) to detect anti-Opisthorchis viverrini IgG and IgG4 subclass antibodies in sera of patients with CCA. The ICT kits were developed based on soluble antigens excreted and secreted by O. viverrini adult worms.

RESULTS: ICT indicated sera was positive for IgG and IgG4 antibodies, respectively, …

Chromosome-Level Genome Of Schistosoma Haematobium Underpins Genome-Wide Explorations Of Molecular Variation., Andreas J Stroehlein, Pasi K Korhonen, V Vern Lee, Stuart A Ralph, Margaret Mentink-Kane, Hong You, Donald P Mcmanus, Louis-Albert Tchuem Tchuenté, J Russell Stothard, Parwinder Kaur, Olga Dudchenko, Erez Lieberman Aiden, Bicheng Yang, Huanming Yang, Aidan M Emery, Bonnie L Webster, Paul J. Brindley, David Rollinson, Bill C H Chang, Robin B Gasser, Neil D Young

Microbiology, Immunology, and Tropical Medicine Faculty Publications

Urogenital schistosomiasis is caused by the blood fluke Schistosoma haematobium and is one of the most neglected tropical diseases worldwide, afflicting > 100 million people. It is characterised by granulomata, fibrosis and calcification in urogenital tissues, and can lead to increased susceptibility to HIV/AIDS and squamous cell carcinoma of the bladder. To complement available treatment programs and break the transmission of disease, sound knowledge and understanding of the biology and ecology of S. haematobium is required. Hybridisation/introgression events and molecular variation among members of the S. haematobium-group might effect important biological and/or disease traits as well as the morbidity of disease …

Rationalization Of The Laboratory Diagnosis For Good Management Of Malaria: Lessons From Transitional Methods, Neguemadji N. Ngaba, Imteyaz A. Khan, Namrata Hange, Maria Kezia Lourdes Ligsay Pormento, Manoj Kumar Reddy Somagutta, Ajay Kumar, Youssouf Abdelkerim, Alarangue Djindimadje, Samia Jahan

Ateneo School of Medicine and Public Health Publications

Introduction. Malaria is an endemic disease in sub-Saharan Africa. In clinical practice, the main concern is the overdiagnosis of malaria leading to inappropriate drug prescription without laboratory confirmation. Objective. This study aimed to evaluate clinical examination reliability compared with translational laboratory methods of malaria diagnosis. Methods. The study was conducted in Goundi Hospital among hospitalized patients over a seven-month period. Patients were interviewed, and malaria tests done included the Giemsa-stained thick and thin blood smears. Diagnostic accuracy was analysed by calculating sensitivity, specificity, and predictive values. Results. Among 1,874 participants, 674 (35.96%) patients had positive Giemsa-stained …

Health Disparities In Children And Adolescents Living In Lmic During Covid-19 Pandemic, Diane Nguyen, Satid Thammasitboon, Anna M Mandalakas

Faculty, Staff and Students Publications

PURPOSE OF REVIEW: The purpose of this editorial is to introduce the pediatric global health issue focusing on health disparities emerging from the COVID-19 pandemic on children and adolescents living in low- and middle-income countries (LMIC).

RECENT FINDINGS: As the COVID-19 pandemic ensues, children and adolescents living in LMIC have been disproportionately affected by socio-economic and mitigation practices, leading to widening disparities in health and the social determinants of health that influence their well-being.

SUMMARY: This pediatric global health issue brings to bare the extent, range, and nature of these health disparities, integrated with expert viewpoints, to prompt critical dialogue …