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The Global Economic And Health Burden Of Human Hookworm Infection., Sarah M Bartsch, Peter J. Hotez, Lindsey Asti, Kristina M Zapf, Maria Elena Bottazzi, David J. Diemert, Bruce Y Lee 2016 George Washington University

The Global Economic And Health Burden Of Human Hookworm Infection., Sarah M Bartsch, Peter J. Hotez, Lindsey Asti, Kristina M Zapf, Maria Elena Bottazzi, David J. Diemert, Bruce Y Lee

Microbiology, Immunology, and Tropical Medicine Faculty Publications

BACKGROUND: Even though human hookworm infection is highly endemic in many countries throughout the world, its global economic and health impact is not well known. Without a better understanding of hookworm's economic burden worldwide, it is difficult for decision makers such as funders, policy makers, disease control officials, and intervention manufacturers to determine how much time, energy, and resources to invest in hookworm control.

METHODOLOGY/PRINCIPLE FINDINGS: We developed a computational simulation model to estimate the economic and health burden of hookworm infection in every country, WHO region, and globally, in 2016 from the societal perspective. Globally, hookworm infection ...


Human Monoclonal Antibodies To Plasmodium Falciparum Circumsporozoite Protein For Transient Passive Protection Of Malaria Travelers To Endemic Areas, Stuart Nelson, Douglas Golenbock, Ann M. Moormann, Colby A. Souders, Lisa Cavacini 2016 University of Massachusettts Medical School

Human Monoclonal Antibodies To Plasmodium Falciparum Circumsporozoite Protein For Transient Passive Protection Of Malaria Travelers To Endemic Areas, Stuart Nelson, Douglas Golenbock, Ann M. Moormann, Colby A. Souders, Lisa Cavacini

Ann M. Moormann

Plasmodium falciparum, is a protozoa that causes over 214 million cases of Malaria worldwide and the World Health Organization reported an estimated 438,000 deaths attributed to malaria in 2015. Current prevention strategies have reduced malaria cases but they are either costly, have poor efficacy or resistance has begun to develop. There is a global need for an effective pre-exposure prophylaxis treatment.

The leading Malaria vaccine candidate is RTS,S which contains a monovalent Plasmodium falciparum circumsporozoite protein (CSP). The goal of this vaccine is to induce anti-CSP antibodies that would block sporozoite invasion of hepatocytes and thereby hinder parasite ...


The Immunomodulatory Role Of Adjuvants In Vaccines Formulated With The Recombinant Antigens Ov-103 And Ov-Ral-2 Against Onchocerca Volvulus In Mice., Jessica A. Hess Ligas, Bin Zhan, April R. Torigian, John B. Patton, Nikolai Petrovsky, Tingting Zhan, Maria Elena Bottazzi, Peter J. Hotez, Thomas R. Klei, Sara Lustigman, David Abraham 2016 Thomas Jefferson University

The Immunomodulatory Role Of Adjuvants In Vaccines Formulated With The Recombinant Antigens Ov-103 And Ov-Ral-2 Against Onchocerca Volvulus In Mice., Jessica A. Hess Ligas, Bin Zhan, April R. Torigian, John B. Patton, Nikolai Petrovsky, Tingting Zhan, Maria Elena Bottazzi, Peter J. Hotez, Thomas R. Klei, Sara Lustigman, David Abraham

Department of Microbiology and Immunology Faculty Papers

BACKGROUND: In some regions in Africa, elimination of onchocerciasis may be possible with mass drug administration, although there is concern based on several factors that onchocerciasis cannot be eliminated solely through this approach. A vaccine against Onchocerca volvulus would provide a critical tool for the ultimate elimination of this infection. Previous studies have demonstrated that immunization of mice with Ov-103 and Ov-RAL-2, when formulated with alum, induced protective immunity. It was hypothesized that the levels of protective immunity induced with the two recombinant antigens formulated with alum would be improved by formulation with other adjuvants known to enhance different types ...


Biliary Microbiota, Gallstone Disease And Infection With Opisthorchis Felineus., Irina V. Saltykova, Vjacheslav A Petrov, Maria D Logacheva, Polina G Ivanova, Nikolay V Merzlikin, Alexey E Sazonov, Ludmila M Ogorodova, Paul J. Brindley 2016 George Washington University

Biliary Microbiota, Gallstone Disease And Infection With Opisthorchis Felineus., Irina V. Saltykova, Vjacheslav A Petrov, Maria D Logacheva, Polina G Ivanova, Nikolay V Merzlikin, Alexey E Sazonov, Ludmila M Ogorodova, Paul J. Brindley

Microbiology, Immunology, and Tropical Medicine Faculty Publications

BACKGROUND: There is increasing interest in the microbiome of the hepatobiliary system. This study investigated the influence of infection with the fish-borne liver fluke, Opisthorchis felineus on the biliary microbiome of residents of the Tomsk region of western Siberia.

METHODOLOGY/PRINCIPAL FINDINGS: Samples of bile were provided by 56 study participants, half of who were infected with O. felineus, and all of who were diagnosed with gallstone disease. The microbiota of the bile was investigated using high throughput, Illumina-based sequencing targeting the prokaryotic 16S rRNA gene. About 2,797, discrete phylotypes of prokaryotes were detected. At the level of phylum ...


Global Assessment Of Schistosomiasis Control Over The Past Century Shows Targeting The Snail Intermediate Host Works Best., Susanne H Sokolow, Chelsea L Wood, Isabel J Jones, Scott J Swartz, Melina Lopez, Michael H. Hsieh, Kevin D Lafferty, Armand M Kuris, Chloe Rickards, Giulio A De Leo 2016 George Washington University

Global Assessment Of Schistosomiasis Control Over The Past Century Shows Targeting The Snail Intermediate Host Works Best., Susanne H Sokolow, Chelsea L Wood, Isabel J Jones, Scott J Swartz, Melina Lopez, Michael H. Hsieh, Kevin D Lafferty, Armand M Kuris, Chloe Rickards, Giulio A De Leo

Urology Faculty Publications

BACKGROUND: Despite control efforts, human schistosomiasis remains prevalent throughout Africa, Asia, and South America. The global schistosomiasis burden has changed little since the new anthelmintic drug, praziquantel, promised widespread control.

METHODOLOGY: We evaluated large-scale schistosomiasis control attempts over the past century and across the globe by identifying factors that predict control program success: snail control (e.g., molluscicides or biological control), mass drug administrations (MDA) with praziquantel, or a combined strategy using both. For data, we compiled historical information on control tactics and their quantitative outcomes for all 83 countries and territories in which: (i) schistosomiasis was allegedly endemic during ...


Lack Of Artemisinin Resistance In Plasmodium Falciparum In Uganda Based On Parasitological And Molecular Assays, Roland A. Cooper, Melissa D. Conrad, Quentin D. Watson, Stephanie J. Huezo, Harriet Ninsiima, Patrick Tumwebaze, Samuel L. Nsobya, Philip J. Rosenthal 2016 Department of Natural Sciences and Mathematics, Dominican University of California

Lack Of Artemisinin Resistance In Plasmodium Falciparum In Uganda Based On Parasitological And Molecular Assays, Roland A. Cooper, Melissa D. Conrad, Quentin D. Watson, Stephanie J. Huezo, Harriet Ninsiima, Patrick Tumwebaze, Samuel L. Nsobya, Philip J. Rosenthal

Roland A. Cooper

We evaluated markers of artemisinin resistance in Plasmodium falciparum isolated in Kampala in 2014. By standard in vitro assays, all isolates were highly sensitive to dihydroartemisinin (DHA). By the ring-stage survival assay, after a 6-h DHA pulse, parasitemia was undetectable in 40 of 43 cultures at 72 h. Two of 53 isolates had nonsynonymous K13-propeller gene polymorphisms but did not have the mutations associated with resistance in Asia. Thus, we did not see evidence for artemisinin resistance in Uganda.


Using Predator Carrying Capacity For A Pathogenic Vector-Dynamic Differential Model, Rosahn P. Bhattarai 2016 Georgia State University

Using Predator Carrying Capacity For A Pathogenic Vector-Dynamic Differential Model, Rosahn P. Bhattarai

Biology and Medicine Through Mathematics Conference

No abstract provided.


Anthelminthic Screening For Parasitic Nematodes, Elfawal A. Mostafa, Dan Lawler, Dirk Albrecht, Raffi V. Aroian 2016 University of Massachusetts Medical School

Anthelminthic Screening For Parasitic Nematodes, Elfawal A. Mostafa, Dan Lawler, Dirk Albrecht, Raffi V. Aroian

UMass Center for Clinical and Translational Science Research Retreat

For many parasitic diseases, high-throughput phenotypic screening is an important tool in finding new drugs. Some of the most important parasitic diseases are caused by nematodes. However, these parasitic nematodes are not typically amenable to high throughput screening. Due to the ease of its maintenance and suitability for high throughput assay, the nematode Caenorhabditis elegans is instead used. To address whether C. elegans is a good model for nematode drug discovery, we compared the drug susceptibility of C. elegans relative to the human hookworm nematode parasite Ancylostoma ceylanicum at several developmental stages using a library of FDA approved drugs. I ...


A Novel Population Of Natural Killer Cells Pplays A Critical Role In The Depletion Of Splenic B2 B Cells During Experimental Africian Trypanosomiasis, Deborah Frenkel, Samuel J. Black 2016 University of Massachusetts Amherst

A Novel Population Of Natural Killer Cells Pplays A Critical Role In The Depletion Of Splenic B2 B Cells During Experimental Africian Trypanosomiasis, Deborah Frenkel, Samuel J. Black

UMass Center for Clinical and Translational Science Research Retreat

Mice infected with Trypanosoma brucei, the causative agent of human sleeping sickness and a contributor to nagana in cattle, rapidly lose the capacity to mount VSG-specific antibody responses, and die with uncontrolled parasitemia. We have shown (Bockstal et al., 2011, PLOS Pathogens) that the loss of humoral immune competence in the infected mice results from depletion of developing and mature splenic B cells. We now report that T. brucei-induced splenic B cell depletion is dependent upon the presence of the pore forming molecule perforin which is present in the cytotoxic granules of cytotoxic T lymphocytes, natural killer T cells and ...


Crystal Protein Cry5b As A Novel And Powerful Anthelmintic, David Koch, Zeynep Mirza, Yan Hu, Thanh-thanh Nguyen, Gary R. Ostroff, Raffi V. Aroian 2016 University of Massachusetts Medical School

Crystal Protein Cry5b As A Novel And Powerful Anthelmintic, David Koch, Zeynep Mirza, Yan Hu, Thanh-Thanh Nguyen, Gary R. Ostroff, Raffi V. Aroian

UMass Center for Clinical and Translational Science Research Retreat

Soil-transmitted helminths (STHs), most notably, hookworms, whipworms, and Ascaris, are nematodes that infect more than 1.5 billion of the poorest people and are amongst the leading causes of morbidity worldwide. Only two classes of de-worming drugs (anthelmintics) are available for treatment, and only one is commonly used in mass drug administrations. New anthelmintics are urgently needed to overcome emerging resistance and to produce higher cure rates. Crystal (Cry) proteins, in particular Cry5B, made by Bacillus thuringiensis (Bt) are promising new candidates. Cry5B has excellent anthelmintic properties against many free-living and parasitic nematodes, including in vivo efficacy against multiple STH ...


Bioavailability Of The Antimalarial Drug Artemisinin Delivered Orally As Dried Leaves Of Artemisia Annua: The Role Of Solubility And Protein., Matthew Desrosiers, Pamela Weathers 2016 Worcester Polytechnic Institute

Bioavailability Of The Antimalarial Drug Artemisinin Delivered Orally As Dried Leaves Of Artemisia Annua: The Role Of Solubility And Protein., Matthew Desrosiers, Pamela Weathers

UMass Center for Clinical and Translational Science Research Retreat

Malaria treatment using orally consumed dried leaves of the artemisinin producing GRAS plant Artemisia annua has recently shown promise. Previously we showed, oral consumption of A. annua dried leaves (DLA) yielded >40 times more artemisinin in the blood of mice than treatment with pure artemisinin. Using the Caco-2 cell culture model of the human intestinal epithelium, we also showed that compared to pure artemisinin, digested DLA doubled the permeability (Papp). Here, using simulated human digestion, we show that artemisinin solubility is about seven times higher in digestates of DLA than in digestates of pure artemisinin, likely contributing to its enhanced ...


Terpenes As ‘Resistance-Busting” Anthelmintic Drug, Zeynep Mirza, David Koch, Thanh-thanh Nguyen, Yan Hu, Raffi V. Aroian, Gary R. Ostroff 2016 University of Massachusettts Medical School

Terpenes As ‘Resistance-Busting” Anthelmintic Drug, Zeynep Mirza, David Koch, Thanh-Thanh Nguyen, Yan Hu, Raffi V. Aroian, Gary R. Ostroff

UMass Center for Clinical and Translational Science Research Retreat

There is an urgent need for new therapies for parasitic helminthic diseases affecting 1.5-2 billion people worldwide due to the threat of wide-spread resistance development to existing treatments and due to problems of incomplete efficacies.

Terpenes are plant secondary metabolites and major essential oil constituents. Historically, the terpene thymol was successfully used to cure hookworm infections in the 1900’s. Although effective, large doses were needed and thymol treatment had significant side effects. Because free terpenes are absorbed in the stomach, less than 10% of oral terpenes entered the site where the parasites live. To overcome these problems we ...


Human Monoclonal Antibodies To Plasmodium Falciparum Circumsporozoite Protein For Transient Passive Protection Of Malaria Travelers To Endemic Areas, Stuart Nelson, Douglas Golenbock, Ann M. Moormann, Colby A. Souders, Lisa Cavacini 2016 University of Massachusettts Medical School

Human Monoclonal Antibodies To Plasmodium Falciparum Circumsporozoite Protein For Transient Passive Protection Of Malaria Travelers To Endemic Areas, Stuart Nelson, Douglas Golenbock, Ann M. Moormann, Colby A. Souders, Lisa Cavacini

UMass Center for Clinical and Translational Science Research Retreat

Plasmodium falciparum, is a protozoa that causes over 214 million cases of Malaria worldwide and the World Health Organization reported an estimated 438,000 deaths attributed to malaria in 2015. Current prevention strategies have reduced malaria cases but they are either costly, have poor efficacy or resistance has begun to develop. There is a global need for an effective pre-exposure prophylaxis treatment.

The leading Malaria vaccine candidate is RTS,S which contains a monovalent Plasmodium falciparum circumsporozoite protein (CSP). The goal of this vaccine is to induce anti-CSP antibodies that would block sporozoite invasion of hepatocytes and thereby hinder parasite ...


Impact Of Antimalarial Treatment And Chemoprevention On The Drug Sensitivity Of Malaria Parasites Isolated From Ugandan Children, Patrick Tumwebaze, Melisssa D. Conrad, Andrew Walakira, Norbert LeClair, Oswald Byaruhanga, Christine Nakazibwe, Benjamin Kozak, Jessica Bloome, Jaffer Okiring, Abel Kakuru, Victor Bigira, James Kapisi, Jennifer Legac, Jiri Gut, Roland A. Cooper, Moses R. Kamya, Diane V. Havlir, Grant Dorsey, Bryan Greenhouse, Samuel L. Nsobya, Philip J. Rosenthal 2016 Infectious Diseases Research Collaboration, Kampala, Uganda

Impact Of Antimalarial Treatment And Chemoprevention On The Drug Sensitivity Of Malaria Parasites Isolated From Ugandan Children, Patrick Tumwebaze, Melisssa D. Conrad, Andrew Walakira, Norbert Leclair, Oswald Byaruhanga, Christine Nakazibwe, Benjamin Kozak, Jessica Bloome, Jaffer Okiring, Abel Kakuru, Victor Bigira, James Kapisi, Jennifer Legac, Jiri Gut, Roland A. Cooper, Moses R. Kamya, Diane V. Havlir, Grant Dorsey, Bryan Greenhouse, Samuel L. Nsobya, Philip J. Rosenthal

Roland A. Cooper

Changing treatment practices may be selecting for changes in the drug sensitivity of malaria parasites. We characterized ex vivo drug sensitivity and parasite polymorphisms associated with sensitivity in 459 Plasmodium falciparum samples obtained from subjects enrolled in two clinical trials in Tororo, Uganda, from 2010 to 2013. Sensitivities to chloroquine and monodesethylamodiaquine varied widely; sensitivities to quinine, dihydroartemisinin, lumefantrine, and piperaquine were generally good. Associations between ex vivo drug sensitivity and parasite polymorphisms included decreased chloroquine and monodesethylamodiaquine sensitivity and increased lumefantrine and piperaquine sensitivity with pfcrt 76T, as well as increased lumefantrine sensitivity with pfmdr1 86Y, Y184, and 1246Y ...


Studies On The Prevalence And Control Of Parasitic Helminths In "Natural" Laying Hens, Brittany R. Weir 2016 University of Arkansas, Fayetteville

Studies On The Prevalence And Control Of Parasitic Helminths In "Natural" Laying Hens, Brittany R. Weir

Animal Science Undergraduate Honors Theses

One societal trend that has been gaining much traction and popularity since the 21st century began is “organic” and/or “natural” food products. In 1999, the global market accounted for $15.2 billion dollars worth of organic food and drink, compared to the market in 2014 where we consumed $80 billion dollars worth (Willer et. al, 2016). With “natural” production of food animals however, “natural” parasite transmission may be a consequence. To that end, this experiment examines the prevalence of helminths in 110 “natural” laying hens from three regional farms and the efficacies of fenbendazole, piperazine, and levamisole on ...


Novel Rnai-Mediated Approach To G Protein-Coupled Receptor Deorphanization: Proof Of Principle And Characterization Of A Planarian 5-Ht Receptor, Mostafa Zamanian, Prince Agbedanu, Nicholas Wheeler, Paul McVeigh, Michael Kimber, Timothy Day 2016 Iowa State University

Novel Rnai-Mediated Approach To G Protein-Coupled Receptor Deorphanization: Proof Of Principle And Characterization Of A Planarian 5-Ht Receptor, Mostafa Zamanian, Prince Agbedanu, Nicholas Wheeler, Paul Mcveigh, Michael Kimber, Timothy Day

Michael Kimber

G protein-coupled receptors (GPCRs) represent the largest known superfamily of membrane proteins extending throughout the Metazoa. There exists ample motivation to elucidate the functional properties of GPCRs given their role in signal transduction and their prominence as drug targets. In many target organisms, these efforts are hampered by the unreliable nature of heterologous receptor expression platforms. We validate and describe an alternative loss-of-function approach for ascertaining the ligand and G protein coupling properties of GPCRs in their native cell membrane environment. Our efforts are focused on the phylum Platyhelminthes, given the heavy health burden exacted by pathogenic flatworms, as well ...


Release Of Small Rna-Containing Exosome-Like Vesicles From The Human Filarial Parasite Brugia Malayi, Mostafa Zamanian, Lisa Fraser, Prince Agbedanu, Hiruni Harischandra, Andrew Moorhead, Tim Day, Lyric Bartholomay, Michael Kimber 2016 Iowa State University

Release Of Small Rna-Containing Exosome-Like Vesicles From The Human Filarial Parasite Brugia Malayi, Mostafa Zamanian, Lisa Fraser, Prince Agbedanu, Hiruni Harischandra, Andrew Moorhead, Tim Day, Lyric Bartholomay, Michael Kimber

Michael Kimber

Lymphatic filariasis (LF) is a socio-economically devastating mosquito-borne Neglected Tropical Disease caused by parasitic filarial nematodes. The interaction between the parasite and host, both mosquito and human, during infection, development and persistence is dynamic and delicately balanced. Manipulation of this interface to the detriment of the parasite is a promising potential avenue to develop disease therapies but is prevented by our very limited understanding of the host-parasite relationship. Exosomes are bioactive small vesicles (30–120 nm) secreted by a wide range of cell types and involved in a wide range of physiological processes. Here, we report the identification and partial ...


Functional Analysis Of Girardia Tigrina Transcriptome Seeds Pipeline For Anthelmintic Target Discovery, Nicholas Wheeler, Prince Agbedanu, Michael Kimber, Paula Ribeiro, Timothy Day, Mostafa Zamanian 2016 Iowa State University

Functional Analysis Of Girardia Tigrina Transcriptome Seeds Pipeline For Anthelmintic Target Discovery, Nicholas Wheeler, Prince Agbedanu, Michael Kimber, Paula Ribeiro, Timothy Day, Mostafa Zamanian

Michael Kimber

Background Neglected diseases caused by helminth infections impose a massive hindrance to progress in the developing world. While basic research on parasitic flatworms (platyhelminths) continues to expand, researchers have yet to broadly adopt a free-living model to complement the study of these important parasites. Methods We report the high-coverage sequencing (RNA-Seq) and assembly of the transcriptome of the planarian Girardia tigrina across a set of dynamic conditions. The assembly was annotated and extensive orthology analysis was used to seed a pipeline for the rational prioritization and validation of putative anthelmintic targets. A small number of targets conserved between parasitic and ...


Development Of An In Vivo Rnai Protocol To Investigate Gene Function In The Filarial Nematode, Brugia Malayi, Chuanzhe Song, Jack Gallup, Timothy Day, Lyric Bartholomay, Michael Kimber 2016 Iowa State University

Development Of An In Vivo Rnai Protocol To Investigate Gene Function In The Filarial Nematode, Brugia Malayi, Chuanzhe Song, Jack Gallup, Timothy Day, Lyric Bartholomay, Michael Kimber

Michael Kimber

Our ability to control diseases caused by parasitic nematodes is constrained by a limited portfolio of effective drugs and a paucity of robust tools to investigate parasitic nematode biology. RNA interference (RNAi) is a reverse-genetics tool with great potential to identify novel drug targets and interrogate parasite gene function, but present RNAi protocols for parasitic nematodes, which remove the parasite from the host and execute RNAi in vitro, are unreliable and inconsistent. We have established an alternative in vivo RNAi protocol targeting the filarial nematode Brugia malayi as it develops in an intermediate host, the mosquito Aedes aegypti. Injection of ...


Impact Of Plasmodium Falciparum Coinfection On Longitudinal Epstein-Barr Virus Kinetics In Kenyan Children, Arnold Reynaldi, Timothy Schlub, Kiprotich Chelimo, Peter Sumba, Erwan Piriou, Sidney Ogolla, Ann Moormann, Rosemary Rochford, Miles Davenport 2016 University of New South Wales

Impact Of Plasmodium Falciparum Coinfection On Longitudinal Epstein-Barr Virus Kinetics In Kenyan Children, Arnold Reynaldi, Timothy Schlub, Kiprotich Chelimo, Peter Sumba, Erwan Piriou, Sidney Ogolla, Ann Moormann, Rosemary Rochford, Miles Davenport

Ann M. Moormann

Endemic Burkitt lymphoma is associated with Epstein-Barr virus (EBV) and Plasmodium falciparum coinfection, although how P. falciparum exposure affects the dynamics of EBV infection is unclear. We have used a modeling approach to study EBV infection kinetics in a longitudinal cohort of children living in regions of high and low malaria transmission in Kenya. Residence in an area of high malaria transmission was associated with a higher rate of EBV expansion during primary EBV infection in infants and during subsequent episodes of EBV DNA detection, as well as with longer episodes of EBV DNA detection and shorter intervals between subsequent ...


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