Parasitic Diseases Commons^™

Elevated Plasma Il-6 Associates With Increased Risk Of Advanced Fibrosis And Cholangiocarcinoma In Individuals Infected By Opisthorchis Viverrini, Banchob Sripa, Bandit Thinkhamrop, Eimorn Mairiang, Thewarach Laha, Sasithorn Kaewkes, Paiboon Sithithaworn, Maria V. Periago, Vajarabhongsa Bhudhisawasdi, Ponlapat Yonglitthipagon, Jason Mulvenna, Paul J. Brindley, Alex Loukas, Jeffrey M. Bethony

Microbiology, Immunology, and Tropical Medicine Faculty Publications

Opisthorchis viverrini is considered among the most important of the food-borne trematodes due to its strong association with advanced periductal fibrosis and bile duct cancer (cholangiocarcinoma). We investigated the relationship between plasma levels of Interleukin (IL)-6 and the risk of developing advanced fibrosis and bile duct cancer from chronic Opisthorchis infection. We show that IL-6 circulates in plasma at concentrations 58 times higher in individuals with advanced fibrosis than age, sex, and nearest-neighbor matched controls and 221 times higher in individuals with bile duct cancer than controls. We also observed a dose-response relationship between increasing levels of plasma IL-6 and …

Five-Year Longitudinal Assessment Of The Downstream Impact On Schistosomiasis Transmission Following Closure Of The Three Gorges Dam., Darren J. Gray, Aaron P. Thrift, Gail M. Williams, Feng Zheng, Yue-Sheng Li, Jiagang Guo, Honggen Chen, Tianping Wang, Xin J. Xu, Rong Zhu, Hongqing Zhu, Chun Li Cao, Dan D. Lin, Zhen Y. Zhao, Robert S. Li, George M. Davis, Donald P. Mcmanus

Microbiology, Immunology, and Tropical Medicine Faculty Publications

Background

Schistosoma japonicum is a major public health concern in the Peoples' Republic of China (PRC), with about 800,000 people infected and another 50 million living in areas at risk of infection. Based on ecological, environmental, population genetic and molecular factors, schistosomiasis transmission in PRC can be categorised into four discrete ecosystems or transmission modes. It is predicted that, long-term, the Three Gorges Dam (TGD) will impact upon the transmission of schistosomiasis in the PRC, with varying degree across the four transmission modes.

Methodology/Principal Findings

We undertook longitudinal surveillance from 2002 to 2006 in sentinel villages of the three transmission …

Enhanced Protective Efficacy Of A Chimeric Form Of The Schistosomiasis Vaccine Antigen Sm-Tsp-2, Mark S. Pearson, Darren A. Pickering, Henry J. Mcsorley, Jeffrey M. Bethony, Leon Tribolet, Annette M. Dougall, Peter J. Hotez, Alex Loukas

Microbiology, Immunology, and Tropical Medicine Faculty Publications

The large extracellular loop of the Schistosoma mansoni tetraspanin, Sm-TSP-2, when fused to a thioredoxin partner and formulated with Freund's adjuvants, has been shown to be an efficacious vaccine against murine schistosomiasis. Moreover, Sm-TSP-2 is uniquely recognised by IgG1 and IgG3 from putatively resistant individuals resident in S. mansoniendemic areas in Brazil. In the present study, we expressed Sm-TSP-2 at high yield and in soluble form in E. coli without the need for a solubility enhancing fusion partner. We also expressed in E. coli a chimera called Sm-TSP-2/5B, which consisted of Sm-TSP-2 fused to …

Characterising The Mucosal And Systemic Immune Responses To Experimental Human Hookworm Infection., Soraya Gaze, Henry J. Mcsorley, James Daveson, Di Jones, Jeffrey M. Bethony, Luciana M. Oliveira, Richard Speare, James S. Mccarthy, Christian R. Engwerda, John Croese, Alex Loukas

Microbiology, Immunology, and Tropical Medicine Faculty Publications

The mucosal cytokine response of healthy humans to parasitic helminths has never been reported. We investigated the systemic and mucosal cytokine responses to hookworm infection in experimentally infected, previously hookworm naive individuals from non-endemic areas. We collected both peripheral blood and duodenal biopsies to assess the systemic immune response, as well as the response at the site of adult worm establishment. Our results show that experimental hookworm infection leads to a strong systemic and mucosal Th2 (IL-4, IL-5, IL-9 and IL-13) and regulatory (IL-10 and TGF-β) response, with some evidence of a Th1 (IFN-γ and IL-2) response. Despite upregulation after …

Redefining Chronic Toxoplasmosis: A T Cell Exhaustion Perspective, Rajarshi Bhadra, Imtiaz A. Khan

Microbiology, Immunology, and Tropical Medicine Faculty Publications

No abstract provided.

Natural Antiparasitic Coumarins: An In Silico Study, William R. Erwin

Summer Community of Scholars Posters (RCEU and HCR Combined Programs)

No abstract provided.

Zoonotic And Human Parasites Of Inhabitants Of Cueva De Los Muertos Chiquitos, Rio Zape Valley, Durango, Mexico, F. Agustín Jiménez-Ruiz, Scott Lyell Gardner, Adauto Araújo, Martín Horacio Fugassa, Richard H. Brooks, Elizabeth Racz, Karl J. Reinhard

Harold W. Manter Laboratory of Parasitology: Faculty Publications

We present the first reconstruction of the parasitoses among the people of the Loma San Gabriel culture, as represented by 36 coprolites excavated from the Cueva de los Muertos Chiquitos in Durango, Mexico. The coprolites date to approximately 1,400-yr ago. Species identified based on eggs recovered include the trematode Echinostoma sp., the tapeworms Hymenolepis sp. and Dipylidium caninum, and the nematodes Ancylostoma duodenale, Enterobius vermicularis, and Trichuris trichiura. After rehydration and screening, 2 methods were used to recover eggs from these samples including spontaneous sedimentation and flotation. Samples were analyzed by 3 different laboratories for independent …

Comparative Immunogenicity Of Na-Gst-1 Human Hookworm Vaccine With Synthetic Glucopyranosyl Lipid Adjuvant (Gla) In Balb/C Mice, Amar R. Jariwala, Brian Keegan, Jordan L. Plieskatt, Maria Elena Bottazzi, Peter J. Hotez, Jeffrey M. Bethony

Microbiology, Immunology, and Tropical Medicine Posters and Presentations

More than 740 million people worldwide are infected with Hookworm. Hookworm infection is most prevalent in the poorest of the poor populations of the world, and has serious health effects. Hookworm infection causes blood loss leading to iron deficiency anemia and protein energy malnutrition, which results in a compromised immune response. Consequently, the target human population suffers from an increased susceptibility to infectious diseases including hookworm infection. We have developed recombinant adult hookworm vaccines against hookworm infection to break this vicious cycle. Toll-like receptor (TLR) 4 agonist are known to boost immune response in healthy and immunocompromised individuals. We believe …

Transgenic C. Elegans Dauer Larvae Expressing Hookworm Phospho Null Daf-16/Foxo Exit Dauer, Verena Gelmedin, Thomas Brodigan, Xin Gao, Michael Krause, Zhu Wang, John M. Hawdon

Research Center for Neglected Diseases of Poverty

Parasitic hookworms and the free-living model nematode Caenorhabtidis elegans share a developmental arrested stage, called the dauer stage in C. elegans and the infective third-stage larva (L3) in hookworms. One of the key transcription factors that regulate entrance to and exit from developmental arrest is the forkhead transcription factor DAF-16/FoxO. During the dauer stage, DAF-16 is activated and localized in the nucleus. DAF-16 is negatively regulated by phosphorylation by the upstream kinase AKT, which causes DAF-16 to localize out of the nucleus and the worm to exit from dauer. DAF-16 is conserved in hookworms, and hypothesized to control recovery from …

Preventive Zinc Supplementation In Developing Countries: Impact On Mortality And Morbidity Due To Diarrhea, Pneumonia And Malaria, Mohammad Yawar Yakoob, Evropi Theodoratou, Afshan Jabeen, Aamer Imdad, Thomas P. Eisele, Joy Ferguson, Arnoupe Jhass, Igor Rudan, Harry Campbell, Robert E. Black, Zulfiqar Ahmed Bhutta

Woman and Child Health

Background:Zinc deficiency is commonly prevalent in children in developing countries and plays a role in decreased immunity and increased risk of infection. Preventive zinc supplementation in healthy children can reduce mortality due to common causes like diarrhea, pneumonia and malaria. The main objective was to determine all-cause mortality and cause-specific mortality and morbidity in children under five in developing countries for preventive zinc supplementation. Data sources/review methods: A literature search was carried out on PubMed, the Cochrane Library and the WHO regional databases to identify RCTs on zinc supplementation for greater than 3 months in children less than 5 …

Screening Of Metal-Based Azole Derivatives Antiparasitic Activity On Trypanosoma Cruzi And Leishmania Major, Teresia A. Carreon^, Linda Herrera, Miguel Vasquez, Roberto A. Sanchez-Delgado, Rosa A. Maldonado*

COURI Symposium Abstracts, Spring 2011

The trypanosomatids Leishmania major and Trypanosoma cruzi are parasites that affect millions of people worldwide. Leishmaniasis is naturally transmitted via sandflies while T. cruzi is transmitted by kissing bugs. Due to immigration and deployment to endemic regions, lack of screening in blood banks and climatic changes these neglected diseases have become a growing health concern in the United States. The lack of vaccines to prevent/treat the diseases and the toxicity of current treatments supports the need for new drug treatments. Azole compounds inhibit the sterol synthesis pathway of these parasites, which has been validated as a drug target. T.cruzi epimastigote …

Efficacy And Safety Of Quinine Loading Dose In Patients With Severe Falciparum Malaria At A Tertiary Care Hospital In Pakistan, M. Tariq, Taimur Saleem, Hamid Ullah, Vikram Mehraj, Abdul Jawwad Samdani, Syeda Hena Kazmi, Syed Imran Ayaz, Mehmood Riaz, Muhammad Junaid Patel, Mohammed Asim Beg

Section of Internal Medicine

OBJECTIVE: To compare the clinical outcomes of a loading dose regimen of quinine with a uniform dose regimen in patients with severe falciparum malaria.

METHODS: A retrospective chart review of 315 patients admitted with severe falciparum malaria and treated with quinine at a tertiary care teaching hospital of Karachi, Pakistan during 1999-2006 was conducted. Group A with 103 patients (32.7%) was given an initial loading dose of quinine while group B with 212 patients (67.3%) did not receive the loading dose. The two groups were compared in terms of reduction of parasite load, resolution of fever, recovery of consciousness and …

Infection Rate Of Dactylogyrus Parasites On Etheostoma Duryi And Etheostoma Zonale, Kara Million

Summer Community of Scholars Posters (RCEU and HCR Combined Programs)

No abstract provided.

Campylobacter Ureolyticus: An Emerging Gastrointestinal Pathogen?, Susan Bullman, Daniel Corcoran, James O'Leary, Brigid Lucey, Deirdre Byrne, Roy D. Sleator

Department of Biological Sciences Publications

A total of 7194 faecal samples collected over a 1-year period from patients presenting with diarrhoea were screened for Campylobacter spp. using EntericBios, a multiplex-PCR system. Of 349 Campylobacter-positive samples, 23.8% were shown to be Campylobacter ureolyticus, using a combination of 16S rRNA gene analysis and highly specific primers targeting the HSP60 gene of this organism. This is, to the best of our knowledge, the first report of C. ureolyticus in the faeces of patients presenting with gastroenteritis and may suggest a role for this organism as an emerging enteric pathogen.

Chloroquine Susceptibility And Reversibility In A Plasmodium Falciparum Genetic Cross, Jigar J. Patel, Drew Thacker, Jon C. Tan, Perri Pleeter, Lisa Checkley, Joseph M. Gonzales, Bingbing Deng, Paul D. Roepe, Roland A. Cooper, Michael T. Ferdig

Collected Faculty Scholarship

Mutations in the Plasmodium falciparum chloroquine (CQ) resistance transporter (PfCRT), are major determinants of verapamil (VP)-reversible CQ resistance (CQR). In the presence of mutant PfCRT, additional genes contribute to the wide range of CQ susceptibilities observed. It is not known if these genes influence mechanisms of chemosensitization by CQR reversal agents. Using quantitative trait locus (QTL) mapping of progeny clones from the HB3 × Dd2 cross, we show that the P. falciparum multidrug resistance gene 1 (pfmdr1) interacts with the Southeast Asiaderived mutant pfcrt haplotype to modulate CQR levels. A novel chromosome 7 locus is predicted to contribute with the …

The Role Of Unrealistic Optimism In Explaining Preventive Behaviors In High Versus Low Endemic Malaria Settings In Belize, Daniel G. Handysides

Loma Linda University Electronic Theses, Dissertations & Projects

Background: Of all the diseases an individual can encounter in the world, malaria is one of the most destructive. Simple measures like sleeping under a bednet would greatly reduce the burden (Abeku, 2007). When people estimate their risk relative to others, they are most often unrealistically optimistic, which may explain why those at risk often fail to perform behaviors, such as using a bednet that will reduce their risk. However, one study showed that people at high risk for malaria held pessimistic perceptions of their risk for the disease, but the reasons for this finding are unclear (Morrison, Ager, & …

Knowledge, Attitudes And Practices Regarding Dengue Fever Among Adults Of High And Low Socioeconomic Groups, Madiha Syed, Taimur Saleem, Umme-Rubab Syeda, Manal Habib, Rehan Zahid, Atif Bashir, Madiha Rabbani, Madiha Khalid, Asif Iqbal, Ehsen Zawwar Rao, Shujja-Ur-Rehman, Sarah Saleem

Community Health Sciences

OBJECTIVE: To ascertain the knowledge, attitudes and practices of selected adult population in Pakistan regarding Dengue Fever.METHODS: A cross sectional survey was conducted among selected communities with different socio-economic backgrounds in Karachi, Pakistan. A sample size of 440 adults (aged 18 years and above) were interviewed using a pre-tested questionnaire regarding their knowledge, attitude and practices about dengue fever. A composite scoring system, based on the answers given in the questionnaire, was used to establish the level of awareness in the population. The division of the higher and lower socio-economic groups was based on their income and locality; both these …

Intravenous Artesunate For Severe Malaria, Karl M. Hess, Jeffery A. Goad, Paul M. Arguin

Pharmacy Faculty Articles and Research

OBJECTIVE: To review the pharmacodynamics and pharmacotherapeutic use of intravenous artesunate for the treatment of severe malaria.

DATA SOURCES: Literature was retrieved through PubMed (1999 March 2010), MEDLINE (1996 March 2010), and the Centers for Disease Control and Prevention (CDC), using the search terms artemisinin, artesunate, malaria, and severe malaria. In addition, reference citations from publications identified were reviewed.

STUDY SELECTION AND DATA EXTRACTION: All articles in English that were identified from the data sources were reviewed. Focus was placed on post-marketing trials examining the safety and efficacy of artesunate in comparison with other regimens.

DATA SYNTHESIS …

Common Regional Pests Of Western Australia, Department Of Agriculture And Food, Western Australia

Bulletins 4000 -

Western Australia is free from many exotic animal and plant pests, diseases and weeds that are present elsewhere in Australia. However, the state does have some unwanted intruders. Of these, many are declared plants or declared animals which, for the sake of convenience, we collectively call declared pests.

Inhibition Of Yeast Hexokinase By The Antimalarial Drug Artemisinin: Probing Mechanism Of Action With A Model Enzyme, Jennifer S. Spence

Biological Sciences Theses & Dissertations

A leading infectious cause of death, malaria threatens approximately half of the world's population, and drug-resistant strains of Plasmodium falciparum have created immense difficulty in chemotherapy of the disease. The artemisinin (ART) class of antimalarials may represent a powerful solution. In addition to their safety, effectiveness, and moderate cost, they are the only drugs in use for which there has been no widespread evidence of clinical resistance. The exact parasiticidal mechanism of ART is highly contested, but evidence suggests that protein alkylation may play a role in cytotoxicity. in vitro essays were performed using yeast hexokinase (HK) to demonstrate a …

Accumulation Of Artemisinin Trioxane Derivatives Within Neutral Lipids Of Plasmodium Falciparum Malaria Parasites Is Endoperoxide-Dependent, Carmony L. Hartwig, Andrew S. Rosenthal, John D'Angelo, Carol E. Griffin, Gary H. Posner, Roland A. Cooper

Collected Faculty Scholarship

The antimalarial trioxanes, exemplified by the naturally occurring sesquiterpene lactone artemisinin and its semi-synthetic derivatives, contain an endoperoxide pharmacophore that lends tremendous potency against Plasmodium parasites. Despite decades of research, their mechanism of action remains unresolved. A leading model of anti-plasmodial activity hypothesizes that iron-mediated cleavage of the endoperoxide bridge generates cytotoxic drug metabolites capable of damaging cellular macromolecules. To probe the malarial targets of the endoperoxide drugs, we studied the distribution of fluorescent dansyl trioxane derivatives in living, intraerythrocytic-stage Plasmodium falciparum parasites using microscopic imaging. The fluorescent trioxanes rapidly accumulated in parasitized erythrocytes, localizing within digestive vacuole-associated neutral lipid …

Antitumour And Antimalarial Activity Of Artemisinin–Acridine Hybrids, Michael Jones, Amy Mercer, Paul Stocks, Louise La Pensee, Rick Cosstick, B. Kevin Park, Miriam Kennedy, Ivo Piantanida, Stephen Ward, Jill Davies, Patrick Bray, Sarah Rawe, Jonathon Baird, Tafadzwa Charidza, Omar Janneh, Paul O'Neill

Articles

Artemisinin–acridine hybrids were prepared and evaluated for their in vitro activity against tumour cell lines and a chloroquine sensitive strain of Plasmodium falciparum. They showed a 2–4-fold increase in activity against HL60, MDA-MB-231 and MCF-7 cells in comparison with dihydroartemisinin (DHA) and moderate antimalarial activity. Strong evidence that the compounds induce apoptosis in HL60 cells was obtained by flow cytometry, which indicated accumulation of cells in the G1 phase of the cell cycle.

Genome-Wide Compensatory Changes Accompany Drug Selected Mutations In The Plasmodium Falciparum Crt Gene, Hongying Jiang, Jigar J. Patel, Ming Yi, Jianbing Mu, Jinhui Ding, Robert Stephens, Roland Cooper, Michael T. Ferdig, Xin-Zhuan Su

Collected Faculty Scholarship

Mutations in PfCRT (Plasmodium falciparum chloroquine-resistant transporter), particularly the substitution at amino acid position 76, confer chloroquine (CQ) resistance in P. falciparum. Point mutations in the homolog of the mammalian multidrug resistance gene (pfmdr1) can also modulate the levels of CQ response. Moreover, parasites with the same pfcrt and pfmdr1 alleles exhibit a wide range of drug sensitivity, suggesting that additional genes contribute to levels of CQ resistance (CQR). Reemergence of CQ sensitive parasites after cessation of CQ use indicates that changes in PfCRT are deleterious to the parasite. Some CQR parasites, however, persist in the field and grow well …

Evaluation Of The Efficacy Of Chloroplast-Derived Antigensagainst Malaria, Melissa Schreiber

Electronic Theses and Dissertations

Malaria is the most prevalent vector-borne parasitic disease worldwide and a major cause of death from infections. There is a great need to develop a low cost vaccine for malaria to control transmission of infection and impact of disease, due to the emergence of anti-malarial resistance. Two leading blood stage malarial vaccine candidates are the apical membrane antigen-1 (AMA-1) and the merozoite surface protein-1 (MSP-1). The aim of this project is to express malarial antigens in tobacco plants via plastid transformation and deliver them by subcutaneous or oral gavage of minimally processed transplastomic tissue to evaluate their efficacy to elicit …

The Potential For Sustainability Of Malaria In Pregnancy Initiatives In East And Southern Africa: Kenya And Malawi, Washington Onyango-Ouma, Sam Agatre Okuonzi, Doreen Ali, Harriet Birungi, Annie Mwangi

Reproductive Health

This study assesses the sustainability of initiatives to improve maternal and child health survival by preventing and treating illness from malaria, and documents best practices for promoting sustainability and lessons for replication in countries where malaria is endemic. The study applied the Child Survival Sustainability Assessment framework to initiatives in Kenya and Malawi to analyze progress toward sustainability, including not only a biomedical perspective but also the human, social, and organizational processes that influence sustainability of health projects. The report concludes that Malaria in Pregnancy (MIP) interventions were sustained within and beyond the project districts in both countries. Furthermore, both …

An Epidemiological Model Of Rift Valley Fever, Holly D. Gaff, David M. Hartley, Nicole P. Leahy

Biological Sciences Faculty Publications

We present and explore a novel mathematical model of the epidemiology of Rift Valley Fever (RVF). RVF is an Old World, mosquito-borne disease affecting both livestock and humans. The model is an ordinary differential equation model for two populations of mosquito species, those that can transmit vertically and those that cannot, and for one livestock population. We analyze the model to find the stability of the disease-free equlibrium and test which model parameters affect this stability most significantly. This model is the basis for future research into the predication of future outbreaks in the Old World and the assessment of …

Lack Of Il-15 Results In The Suboptimal Priming Of Cd4+ T Cell Response Against An Intracellular Parasite, Crescent L. Combe, Magali M. Moretto, Joseph D. Schwartzman, Jason P. Gigley, David J. Bzik, Imtiaz A. Khan

Dartmouth Scholarship

IFN-gamma-producing CD4+ T cells, although important for protection against acute Toxoplasma gondii infection, can cause gut pathology, which may prove to be detrimental for host survival. Here we show that mice lacking IL-15 gene develop a down-regulated IFN-gamma-producing CD4+ T cell response against the parasite, which leads to a reduction in gut necrosis and increased level of survival against infection. Moreover, transfer of immune CD4+ T cells from WT to IL-15-/- mice reversed inhibition of gut pathology and caused mortality equivalent to levels of parental WT mice. Down-regulated CD4+ T cell response in the absence of IL-15, manifested as reduced …

Diet Affects Immunologically Relevant Gene Expression In Brains Of Toxoplasma Gondii Infected, Lydia Kullman

Mahurin Honors College Capstone Experience/Thesis Projects

No abstract provided.

A Monkey’S Tale: The Origin Of Plasmodium Vivax As A Human Malaria Parasite, Ananias A. Escalante, Omar E. Cornejo, Denise E. Freeland, Amanda C. Poe, Ester Durrego, William E. Collins, Altaf A. Lal

Harold W. Manter Laboratory of Parasitology: Library Materials

The high prevalence of Duffy negativity (lack of the Duffy blood group antigen) among human populations in sub-Saharan Africa has been used to argue that Plasmodium vivax originated on that continent. Here, we investigate the phylogenetic relationships among 10 species of Plasmodium that infect primates by using three genes, two nuclear (β-tubulin and cell division cycle 2) and a gene from the plastid genome (the elongation factor Tu). We find compelling evidence that P. vivax is derived from a species that inhabited macaques in Southeast Asia. Specifically, those phylogenies that include P. vivax as an ancient lineage from …

Interleukin-17/Interleukin-17 Receptor-Mediated Signaling Is Important For Generation Of An Optimal Polymorphonuclear Response Against Toxoplasma Gondii Infection, Michelle N. Kelly, Jay K. Kolls, Kyle Happel, Joseph D. Schwartzman

Dartmouth Scholarship

We investigated the role of interleukin-17 (IL-17)/IL-17 receptor (IL-17R)-mediated signaling in the protective immunity against Toxoplasma gondii. IL-17R−/− mice developed a normal adaptive immunity against the parasite. However, increased mortality in the knockout animals can be attributed to a defect in the migration of polymorphonuclear leukocytes to infected sites during early infection.