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Global Burden Of Disease Study 2010: Interpretation And Implications For The Neglected Tropical Diseases, Peter J. Hotez, Miriam Alvarado, Maria Gloria Basanez, Ian Bolliger, et al. 2014 Baylor College of Medicine

Global Burden Of Disease Study 2010: Interpretation And Implications For The Neglected Tropical Diseases, Peter J. Hotez, Miriam Alvarado, Maria Gloria Basanez, Ian Bolliger, Et Al.

Baylor Faculty Publications

No abstract provided.


Induction Of Il-12 Production In Human Peripheral Monocytes By Trypanosoma Cruzi Is Mediated By Glycosylphosphatidylinositol-Anchored Mucin-Like Glycoproteins And Potentiated By Ifn- Gamma And Cd40-Cd40l Interactions, Lucia Cristina Abel Jamli, Ludmila Rodrigues Ferreira Pinto, Isabela Cunha Navarro, Monique Andrade Baron, Jorge Kalil, Ricardo T. Gazzinelli, Luiz Vicente Rizzo, Edecio Cunha-Neto 2014 University of Sao Paulo

Induction Of Il-12 Production In Human Peripheral Monocytes By Trypanosoma Cruzi Is Mediated By Glycosylphosphatidylinositol-Anchored Mucin-Like Glycoproteins And Potentiated By Ifn- Gamma And Cd40-Cd40l Interactions, Lucia Cristina Abel Jamli, Ludmila Rodrigues Ferreira Pinto, Isabela Cunha Navarro, Monique Andrade Baron, Jorge Kalil, Ricardo T. Gazzinelli, Luiz Vicente Rizzo, Edecio Cunha-Neto

Open Access Articles

Chagas disease, caused by the protozoan parasite Trypanosoma cruzi (T. cruzi), is characterized by immunopathology driven by IFN-gamma secreting Th1-like T cells. T. cruzi has a thick coat of mucin-like glycoproteins covering its surface, which plays an important role in parasite invasion and host immunomodulation. It has been extensively described that T. cruzi or its products-like GPI anchors isolated from GPI-anchored mucins from the trypomastigote life cycle stage (tGPI-mucins)-are potent inducers of proinflammatory responses (i.e., cytokines and NO production) by IFN-gamma primed murine macrophages. However, little is known about whether T. cruzi or GPI-mucins exert a similar action ...


An Unstable Th Epitope Of P. Falciparum Fosters Central Memory T Cells And Anti-Cs Antibody Responses, Carlos A. Parra-Lopez, David Bernal -Estevez, Luis Eduardo Eduardo Vargas, Carolina Pulido -Calixto, Luz Mary Salazar, J. Mauricio Calvo-Calle, Lawrence J. Stern 2014 Universidad Nacional de Colombia

An Unstable Th Epitope Of P. Falciparum Fosters Central Memory T Cells And Anti-Cs Antibody Responses, Carlos A. Parra-Lopez, David Bernal -Estevez, Luis Eduardo Eduardo Vargas, Carolina Pulido -Calixto, Luz Mary Salazar, J. Mauricio Calvo-Calle, Lawrence J. Stern

University of Massachusetts Medical School Faculty Publications

Malaria is transmitted by Plasmodium-infected anopheles mosquitoes. Widespread resistance of mosquitoes to insecticides and resistance of parasites to drugs highlight the urgent need for malaria vaccines. The most advanced malaria vaccines target sporozoites, the infective form of the parasite. A major target of the antibody response to sporozoites are the repeat epitopes of the circumsporozoite (CS) protein, which span almost one half of the protein. Antibodies to these repeats can neutralize sporozoite infectivity. Generation of protective antibody responses to the CS protein (anti-CS Ab) requires help by CD4 T cells. A CD4 T cell epitope from the CS protein designated ...


Genetic Vaccination Against Experimental Infection With Myotropic Parasite Strains Of Trypanosoma Cruzi, Adriano Fernando Araujo, Gabriel de Oliveira, Juliana Fraga Vasconcelos, Jonatan Ersching, Mariana Ribeiro Dominguez, Jose Ronnie Vasconcelos, Alexandre Vieira Machado, Ricardo T. Gazzinelli, Oscar Bruna-Romero, Milena Botelho Soares, Mauricio Martins Rodrigues 2014 Universidade Federal de Sao Paulo

Genetic Vaccination Against Experimental Infection With Myotropic Parasite Strains Of Trypanosoma Cruzi, Adriano Fernando Araujo, Gabriel De Oliveira, Juliana Fraga Vasconcelos, Jonatan Ersching, Mariana Ribeiro Dominguez, Jose Ronnie Vasconcelos, Alexandre Vieira Machado, Ricardo T. Gazzinelli, Oscar Bruna-Romero, Milena Botelho Soares, Mauricio Martins Rodrigues

Open Access Articles

In earlier studies, we reported that a heterologous prime-boost regimen using recombinant plasmid DNA followed by replication-defective adenovirus vector, both containing Trypanosoma cruzi genes encoding trans-sialidase (TS) and amastigote surface protein (ASP) 2, provided protective immunity against experimental infection with a reticulotropic strain of this human protozoan parasite. Herein, we tested the outcome of genetic vaccination of F1 (CB10XBALB/c) mice challenged with myotropic parasite strains (Brazil and Colombian). Initially, we determined that the coadministration during priming of a DNA plasmid containing the murine IL-12 gene improved the immune response and was essential for protective immunity elicited by the heterologous ...


Functional Characterization Of A Novel Family Of Acetylcholine-Gated Chloride Channels In Schistosoma Mansoni, Kevin MacDonald, Samuel Buxton, Michael J. Kimber, Timothy A. Day, Alan P. Robertson, Paula Ribeiro 2014 McGill University

Functional Characterization Of A Novel Family Of Acetylcholine-Gated Chloride Channels In Schistosoma Mansoni, Kevin Macdonald, Samuel Buxton, Michael J. Kimber, Timothy A. Day, Alan P. Robertson, Paula Ribeiro

Biomedical Sciences Publications

Acetylcholine is the canonical excitatory neurotransmitter of the mammalian neuromuscular system. However, in the trematode parasite Schistosoma mansoni, cholinergic stimulation leads to muscle relaxation and a flaccid paralysis, suggesting an inhibitory mode of action. Information about the pharmacological mechanism of this inhibition is lacking. Here, we used a combination of techniques to assess the role of cholinergic receptors in schistosome motor function. The neuromuscular effects of acetylcholine are typically mediated by gated cation channels of the nicotinic receptor (nAChR) family. Bioinformatics analyses identified numerous nAChR subunits in the S. mansoni genome but, interestingly, nearly half of these subunits carried a ...


Primary Amoebic Meningoencephalitis: Amoebicidal Effects Of Clinically Approved Drugs Against Naegleria Fowleri, Abdul Baig, Huma Kulsoom, Naveed Khan 2014 Aga Khan University

Primary Amoebic Meningoencephalitis: Amoebicidal Effects Of Clinically Approved Drugs Against Naegleria Fowleri, Abdul Baig, Huma Kulsoom, Naveed Khan

Abdul Mannan Baig

Here we tested the effects of clinically approved drugs targeting vital cellular receptors and biochemical pathways against Naegleria fowleri. For the first time, our findings revealed that digoxin and procyclidine showed potent amoebicidal effects as no viable trophozoites were observed (>95% kill rate). In view of the devastating nature of this disease and the problems associated with chemotherapy, the present findings offer promising drug-leads for clinical practice. Drugs tested in the present study are FDA approved and should be of potential value in the management of primary amoebic meningoencephalitis.


New Insights Into The Flpergic Complements Of Parasitic Nematodes: Informing Deorphanisation Approaches, Ciaran J. McCoy, Louise E. Atkinson, Mostafa Zamanian, Paul McVeigh, Timothy A. Day, Michael J. Kimber, Nikki J. Marks, Aaron G. Maule, Angela Mousley 2014 Queen's University Belfast

New Insights Into The Flpergic Complements Of Parasitic Nematodes: Informing Deorphanisation Approaches, Ciaran J. Mccoy, Louise E. Atkinson, Mostafa Zamanian, Paul Mcveigh, Timothy A. Day, Michael J. Kimber, Nikki J. Marks, Aaron G. Maule, Angela Mousley

Biomedical Sciences Publications

FMRFamide-like peptide (FLP) receptors are appealing as putative anthelmintic targets. To date, 31 flp-encoding genes have been identified in Caenorhabditis elegans and thirteen FLP-activated G-protein coupled receptors (FLP-GPCRs) have been reported. The lack of knowledge on FLPs and FLP-GPCRs in parasites impedes their functional characterisation and chemotherapeutic exploitation. Using homology-based BLAST searches and phylogenetic analyses this study describes the identification of putative flpand flp-GPCR gene homologues in 17 nematode parasites providing the first pan-phylum genome-based overview of the FLPergic complement. These data will facilitate FLP-receptor deorphanisation efforts in the quest for novel control targets for nematode parasites.


Cytokine Changes In Colonic Mucosa Associated With Blastocystis Spp. Subtypes 1 And 3 In Diarrhoea-Predominant Irritable Bowel Syndrome, Javed Yakoob, Zaigham Abbas, Muhammad Waqas Usman, Aisha Sultana, Muhammad Islam, Safia Awan, Zubair Ahmad, Saeed Hamid, Wasim Jafri 2014 Aga Khan University

Cytokine Changes In Colonic Mucosa Associated With Blastocystis Spp. Subtypes 1 And 3 In Diarrhoea-Predominant Irritable Bowel Syndrome, Javed Yakoob, Zaigham Abbas, Muhammad Waqas Usman, Aisha Sultana, Muhammad Islam, Safia Awan, Zubair Ahmad, Saeed Hamid, Wasim Jafri

Section of Gastroenterology

We determined cytokines (e.g. interleukin-8, 10, 12 and TNF-α) expression by peripheral blood mononuclear cells (PBMCs) and in rectal mucosa in diarrhoea-predominant irritable bowel syndrome (D-IBS) with Blastocystis spp. Eighty patients with D-IBS and Blastocystis spp. infection were classified as 'cases' and 80 with D-IBS without Blastocystis spp. infection were classified as 'control'. Cases were subdivided into D-IBS and Blastocystis sp. defined type 1 (subtype-specific primer SB83) and type 3 (SB227). Stool microscopy and culture were performed. Rectal biopsies were obtained for histology and cytokines by real-time PCR for mRNA expression of cytokines. PBMCs IL-8 was similar in different ...


Laboratory Testing Of Clinically Approved Drugs Against Balamuthia Mandrillaris., Abdul Baig 2014 Aga Khan University

Laboratory Testing Of Clinically Approved Drugs Against Balamuthia Mandrillaris., Abdul Baig

Abdul Mannan Baig

Balamuthia mandrillaris is a free-living protist pathogen that can cause life-threatening granulomatous amoebic encephalitis. Given the lack of effective available drugs against B. mandrillaris encephalitis with a mortality rate of more than 90 %, here we screened drugs, targeting vital cellular receptors and biochemical pathways, that are already in approved clinical use for their potential clinical usefulness. Amoebicidal assays were performed by incubating B. mandrillaris with drugs (3 × 105 cells/0.5 mL/well) in phosphate buffered saline for 24 h and viability was determined using Trypan blue exclusion staining. For controls, amoebae were incubated with the solvent alone. To determine ...


A Multifactorial Role For P. Falciparum Malaria In Endemic Burkitt's Lymphoma Pathogenesis, Charles Torgbor, Peter Awuah, Kirk Deitsch, Parisa Kalantari, Karen A. Duca, David A Thorley-Lawson 2014 Tufts University School of Medicine

A Multifactorial Role For P. Falciparum Malaria In Endemic Burkitt's Lymphoma Pathogenesis, Charles Torgbor, Peter Awuah, Kirk Deitsch, Parisa Kalantari, Karen A. Duca, David A Thorley-Lawson

University of Massachusetts Medical School Faculty Publications

Endemic Burkitt's lymphoma (eBL) arises from the germinal center (GC). It is a common tumor of young children in tropical Africa and its occurrence is closely linked geographically with the incidence of P. falciparum malaria. This association was noted more than 50 years ago. Since then we have learned that eBL contains the oncogenic herpes virus Epstein-Barr virus (EBV) and a defining translocation that activates the c-myc oncogene. However the link to malaria has never been explained. Here we provide evidence for a mechanism arising in the GC to explain this association. Accumulated evidence suggests that eBL arises in ...


Bedbugs Biting Back? A Multifactorial Consideration Of Bedbug Resurgence, Vanessa L. Abejuela-Matt 2014 Department of Family Medicine, Aurora St. Luke's Medical Center, Aurora Health Care

Bedbugs Biting Back? A Multifactorial Consideration Of Bedbug Resurgence, Vanessa L. Abejuela-Matt

Journal of Patient-Centered Research and Reviews

Bedbugs, previously thought to be eradicated during the mid-20th century, have reemerged in the new millennium with unforeseen furor. Affected patients and families frequently present in primary care settings, not only with complaints of pruritus or rash, but with anxiety and shame regarding the condition. Changes in eradication techniques and resistance, as well as lack of reporting – from both patients and lodging institutions – have hindered control. The increased mobility of goods and the human population has provided further avenues for bedbug spread. While current literature thoroughly describes the clinical presentation of bedbugs and the increasingly problematic effects on society, less ...


Urinary Estrogen Metabolites And Self-Reported Infertility In Women Infected With Schistosoma Haematobium, Julio Santos, Maria Joao Gouveia, Nuno Vale, Maria de Lurdes Delgado, Ana Goncalves, Gabriel Rinaldi, Paul J. Brindley, +10 additional authors 2014 Clínica da Sagrada Esperança, Luanda, Angola

Urinary Estrogen Metabolites And Self-Reported Infertility In Women Infected With Schistosoma Haematobium, Julio Santos, Maria Joao Gouveia, Nuno Vale, Maria De Lurdes Delgado, Ana Goncalves, Gabriel Rinaldi, Paul J. Brindley, +10 Additional Authors

Microbiology, Immunology, and Tropical Medicine Faculty Publications

Background

Schistosomiasis is a neglected tropical disease, endemic in 76 countries, that afflicts more than 240 million people. The impact of schistosomiasis on infertility may be underestimated according to recent literature. Extracts of Schistosoma haematobium include estrogen-like metabolites termed catechol-estrogens that down regulate estrogen receptors alpha and beta in estrogen responsive cells. In addition, schistosome derived catechol-estrogens induce genotoxicity that result in estrogen-DNA adducts. These catechol estrogens and the catechol-estrogen-DNA adducts can be isolated from sera of people infected with S. haematobium. The aim of this study was to study infertility in females infected with S. haematobium and its association ...


Utilization Of Molecular Inversion Probes In Malaria Sequencing, Ozkan Aydemir, Alice Tran, Yasin Kaymaz, Nicholas J. Hathaway, Jeffrey A. Bailey 2014 University of Massachusetts Medical School

Utilization Of Molecular Inversion Probes In Malaria Sequencing, Ozkan Aydemir, Alice Tran, Yasin Kaymaz, Nicholas J. Hathaway, Jeffrey A. Bailey

UMass Center for Clinical and Translational Science Research Retreat

While massively parallel sequencing of whole genomes shed light on many previously puzzling genetic questions, the high costs associated with this approach makes its use impractical when large cohorts need to be sequenced at high coverage. Available capture technologies reduces the sequencing costs by enriching template material for the regions of interest. However, these technologies are also prohibitively costly at high sample numbers. Capture methods utilizing molecular inversion probes (MIPs) offer a flexible alternative to enrich template material that multiplex well for thousands of samples and require minimal resources. Here, for our work in malaria, we extend the utility of ...


Developing A Whole Plant Artemisia Annua Antimalarial Therapeutic: Pact, Pamela Weathers, Nicole Jordan, Praphapan Lasin, Melissa Towler, Douglas T. Golenbock, Mostafa Elfawal, Nicholas Reich, George Acquaah-Mensah, Stephen Rich 2014 Worcester Polytechnic Institute

Developing A Whole Plant Artemisia Annua Antimalarial Therapeutic: Pact, Pamela Weathers, Nicole Jordan, Praphapan Lasin, Melissa Towler, Douglas T. Golenbock, Mostafa Elfawal, Nicholas Reich, George Acquaah-Mensah, Stephen Rich

UMass Center for Clinical and Translational Science Research Retreat

The GRAS plant Artemisia annua L. produces the sesquiterpene lactone, artemisinin. The current therapy for malaria is artemisinin + an older drug: artemisinin combination therapy (ACT). In Plasmodium chabaudi-infected mice, dried leaves of A. annua are more potent than equal amounts of pure artemisinin and may also prevent artemisinin drug resistance from emerging. This whole plant therapy is pACT: plant-based artemisinin combination therapy. Pharmacokinetics in healthy and infected mice given either pure artemisinin or pACT is different and showed that > 40 fold more artemisinin enters the blood when plant material is present; plant matrix enhanced bioavailability into serum. Dried leaves as ...


Diversity And Expression Of Micrornas In The Filarial Parasite, Brugia Malayi, Catherine B. Poole, Weifeng Gu, Sanjay Kumar, Jingmin Jin, Paul J. Davis, David Bauche, Larry A. McReynolds 2014 New England Biolabs

Diversity And Expression Of Micrornas In The Filarial Parasite, Brugia Malayi, Catherine B. Poole, Weifeng Gu, Sanjay Kumar, Jingmin Jin, Paul J. Davis, David Bauche, Larry A. Mcreynolds

University of Massachusetts Medical School Faculty Publications

Human filarial parasites infect an estimated 120 million people in 80 countries worldwide causing blindness and the gross disfigurement of limbs and genitals. An understanding of RNA-mediated regulatory pathways in these parasites may open new avenues for treatment. Toward this goal, small RNAs from Brugia malayi adult females, males and microfilariae were cloned for deep-sequencing. From approximately 30 million sequencing reads, 145 miRNAs were identified in the B. malayi genome. Some microRNAs were validated using the p19 RNA binding protein and qPCR. B. malayi miRNAs segregate into 99 families each defined by a unique seed sequence. Sixty-one of the miRNA ...


Suppression Of Basophil Histamine-Release And Other Ige-Dependent Responses In Childhood Schistosoma Mansoni Hookworm Co-Infection, Angela Pinot de Moira, Colin M. Fitzsimmons, Frances M. Jones, Shona Wilson, Pierre Cahen, Edridah Tukahebwa, Harriet Mpairwe, Joseph K. Mwatha, Jeffrey M. Bethony, Per S. Skov, Narcis B. Kabatereine, David W. Dunne 2014 University of Cambridge, Cambridge, UK

Suppression Of Basophil Histamine-Release And Other Ige-Dependent Responses In Childhood Schistosoma Mansoni Hookworm Co-Infection, Angela Pinot De Moira, Colin M. Fitzsimmons, Frances M. Jones, Shona Wilson, Pierre Cahen, Edridah Tukahebwa, Harriet Mpairwe, Joseph K. Mwatha, Jeffrey M. Bethony, Per S. Skov, Narcis B. Kabatereine, David W. Dunne

Microbiology, Immunology, and Tropical Medicine Faculty Publications

Background. The poor correlation between allergen-specific-IgE (asIgE) and clinical signs of allergy in helminth infected populations suggests that helminth infections could protect against allergy by uncoupling asIgE from its effector mechanisms. We investigated this hypothesis in Ugandan schoolchildren coinfected with Schistosoma mansoni and hookworm.

Methods. Skin prick test (SPT) sensitivity to house dust mite allergen (HDM) and current wheeze were assessed pre-anthelmintic treatment. Non-specific (anti-IgE), helminth-specific and HDM-allergen-specific basophil histamine release (HR), plus helminth- and HDM-specific IgE and IgG4 responses were measured pre- and post-treatment.

Results.Non-specific- and helminth-specific-HR, and associations between helminth-specific-IgE and helminth-specific-HR increased post-treatment. Hookworm infection appeared ...


Differing Patterns Of Selection And Geospatial Genetic Diversity Within Two Leading Plasmodium Vivax Candidate Vaccine Antigens, Christian M. Parobek, Jeffrey A. Bailey, Nicholas J. Hathaway, Duong Socheat, William O. Rogers, Jonathan J. Juliano 2014 University of North Carolina at Chapel Hill

Differing Patterns Of Selection And Geospatial Genetic Diversity Within Two Leading Plasmodium Vivax Candidate Vaccine Antigens, Christian M. Parobek, Jeffrey A. Bailey, Nicholas J. Hathaway, Duong Socheat, William O. Rogers, Jonathan J. Juliano

UMass Center for Clinical and Translational Science Supported Publications

Although Plasmodium vivax is a leading cause of malaria around the world, only a handful of vivax antigens are being studied for vaccine development. Here, we investigated genetic signatures of selection and geospatial genetic diversity of two leading vivax vaccine antigens--Plasmodium vivax merozoite surface protein 1 (pvmsp-1) and Plasmodium vivax circumsporozoite protein (pvcsp). Using scalable next-generation sequencing, we deep-sequenced amplicons of the 42 kDa region of pvmsp-1 (n = 44) and the complete gene of pvcsp (n = 47) from Cambodian isolates. These sequences were then compared with global parasite populations obtained from GenBank. Using a combination of statistical and phylogenetic methods ...


Combined Drug Therapy In The Management Of Granulomatous Amoebic Encephalitis Due To Acanthamoeba Spp., And Balamuthia Mandrillaris, Abdul Baig 2014 Aga Khan University

Combined Drug Therapy In The Management Of Granulomatous Amoebic Encephalitis Due To Acanthamoeba Spp., And Balamuthia Mandrillaris, Abdul Baig

Abdul Mannan Baig

Granulomatous amoebic encephalitis (GAE) is caused by two protist pathogens, Acanthamoeba spp., and Balamuthia mandrillaris. Although rare, it almost always results in death. In the present study, amoebae were treated with various combinations of clinically-approved drugs, targeting vital cellular receptors and biochemical pathways. The results revealed that among the seven different combinations tested, three proved highly effective against both Acanthamoeba castellanii as well as B. mandrillaris at a concentration of 100μM. These combinations included (i) prochlorperazine plus loperamide; (ii) prochlorperazine plus apomorphine; and (iii) procyclidine plus loperamide. In viability assays, none of the drug-treated amoebae emerged as viable trophozoites, suggesting ...


The Genome Of Anopheles Darlingi, The Main Neotropical Malaria Vector, Osvaldo Marinotti, Adam R. Wespiser, Daniel R. Caffrey, Douglas T. Golenbock, Neal S. Silverman 2014 University of California Irvine

The Genome Of Anopheles Darlingi, The Main Neotropical Malaria Vector, Osvaldo Marinotti, Adam R. Wespiser, Daniel R. Caffrey, Douglas T. Golenbock, Neal S. Silverman

Neal Silverman

Anopheles darlingi is the principal neotropical malaria vector, responsible for more than a million cases of malaria per year on the American continent. Anopheles darlingi diverged from the African and Asian malaria vectors approximately 100 million years ago (mya) and successfully adapted to the New World environment. Here we present an annotated reference A. darlingi genome, sequenced from a wild population of males and females collected in the Brazilian Amazon. A total of 10 481 predicted protein-coding genes were annotated, 72% of which have their closest counterpart in Anopheles gambiae and 21% have highest similarity with other mosquito species. In ...


Babesiosis: An Under-Recognized Tick Bourne Illness, Michael N. Daniels DO, Katie Mastoris DO, Mark Knouse MD, Stacey Smith MD, FACP 2014 Lehigh Valley Health Network

Babesiosis: An Under-Recognized Tick Bourne Illness, Michael N. Daniels Do, Katie Mastoris Do, Mark Knouse Md, Stacey Smith Md, Facp

Department of Medicine

No abstract provided.


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