Urogenital schistosomiasis remains a major global challenge. Optimal management of this infection depends upon imaging-based assessment of sequelae. Although established imaging modalities such as ultrasonography, plain radiography, magnetic resonance imaging (MRI), narrow band imaging, and computerized tomography (CT) have been used to determine tissue involvement by urogenital schistosomiasis, newer refinements in associated technologies may lead to improvements in patient care.
View Article and Find Full Text PDFSensing and responding to environmental signals is critical for bacterial pathogens to successfully infect and persist within hosts. Many bacterial pathogens sense temperature as an indication they have entered a new host and must alter their virulence factor expression to evade immune detection. Using secondary structure prediction, we identified an RNA thermosensor (RNAT) in the 5' untranslated region (UTR) of tviA encoded by the typhoid fever-causing bacterium Salmonella enterica serovar Typhi (S.
View Article and Find Full Text PDFThe various sub-species of Salmonella enterica cause a range of disease in human hosts. The human-adapted Salmonella enterica serovar Typhi enters the gastrointestinal tract and invades systemic sites to cause enteric (typhoid) fever. In contrast, most non-typhoidal serovars of Salmonella are primarily restricted to gut tissues.
View Article and Find Full Text PDFAdenoviral vectors are being developed as vaccines against infectious agents and tumour-associated antigens, because of their ability to induce cellular immunity. However, the protection afforded in animal models has not easily translated into primates and clinical trials, underlying the need for improving adenoviral vaccines-induced immunogenicity. A Toll-like receptor signalling molecule, TRAM, was assessed for its ability to modify the immune responses induced by an adenovirus-based vaccine.
View Article and Find Full Text PDFMany intracellular bacteria can establish chronic infection and persist in tissues within granulomas composed of macrophages. Granuloma macrophages exhibit heterogeneous polarization states, or phenotypes, that may be functionally distinct. Here, we elucidate a host-pathogen interaction that controls granuloma macrophage polarization and long-term pathogen persistence during Salmonella Typhimurium (STm) infection.
View Article and Find Full Text PDFSalmonella Typhimurium sequence type (ST) 313 causes invasive nontyphoidal Salmonella (iNTS) disease in sub-Saharan Africa, targeting susceptible HIV+, malarial, or malnourished individuals. An in-depth genomic comparison between the ST313 isolate D23580 and the well-characterized ST19 isolate 4/74 that causes gastroenteritis across the globe revealed extensive synteny. To understand how the 856 nucleotide variations generated phenotypic differences, we devised a large-scale experimental approach that involved the global gene expression analysis of strains D23580 and 4/74 grown in 16 infection-relevant growth conditions.
View Article and Find Full Text PDFThe intestinal microbiota provides colonization resistance against pathogens, limiting pathogen expansion and transmission. These microbiota-mediated mechanisms were previously identified by observing loss of colonization resistance after antibiotic treatment or dietary changes, which severely disrupt microbiota communities. We identify a microbiota-mediated mechanism of colonization resistance against Salmonella enterica serovar Typhimurium (S.
View Article and Find Full Text PDFGenome degradation correlates with host adaptation and systemic disease in Salmonella. Most lineages of the S. enterica subspecies Typhimurium cause gastroenteritis in humans; however, the recently emerged ST313 lineage II pathovar commonly causes systemic bacteremia in sub-Saharan Africa.
View Article and Find Full Text PDFIntroduction And Objective: The bladder urothelium changes dramatically during Schistosoma haematobium infection (urogenital schistosomiasis). These alterations include hyperplasia, ulceration, dysplasia, squamous metaplasia and frank carcinogenesis. Defining the pathways underpinning these urothelial responses will contribute to a deeper understanding of how S.
View Article and Find Full Text PDFApproximately 200,000,000 people have schistosomiasis (schistosome infection). Among the schistosomes, Schistosoma haematobium is responsible for the most infections, which are present in 110 million people globally, mostly in sub-Saharan Africa. This pathogen causes an astonishing breadth of sequelae: hematuria, anemia, dysuria, stunting, uremia, bladder cancer, urosepsis, and human immunodeficiency virus coinfection.
View Article and Find Full Text PDFT cells play a central role in the immune response to many of the world's major infectious diseases. In this study we investigated the tumour necrosis factor receptor superfamily costimulatory molecule, 4-1BBL (CD137L, TNFSF9), for its ability to increase T cell immunogenicity induced by a variety of recombinant vectored vaccines. To efficiently test this hypothesis, we assessed a number of promoters and developed a stable bi-cistronic vector expressing both the antigen and adjuvant.
View Article and Find Full Text PDFUrogenital schistosomiasis, infection with Schistosoma haematobium, is linked to increased risk for the development of bladder cancer, but the importance of various mechanisms responsible for this association remains unclear, in part, owing to lack of sufficient and appropriate animal models. New advances in the study of this parasite, bladder regenerative processes, and human schistosomal bladder cancers may shed new light on the complex biological processes that connect S. haematobium infection to bladder carcinogenesis.
View Article and Find Full Text PDFBackground: Over 112 million people worldwide are infected with Schistosoma haematobium, one of the most prevalent schistosome species affecting humans. Female genital schistosomiasis (FGS) occurs when S. haematobium eggs are deposited into the female reproductive tract by adult worms, which can lead to pelvic pain, vaginal bleeding, genital disfigurement and infertility.
View Article and Find Full Text PDFUnderstanding how malignancies arise within normal tissues requires identification of the cancer cell of origin and knowledge of the cellular and tissue dynamics of tumour progression. Here we examine bladder cancer in a chemical carcinogenesis model that mimics muscle-invasive human bladder cancer. With no prior bias regarding genetic pathways or cell types, we prospectively mark or ablate cells to show that muscle-invasive bladder carcinomas arise exclusively from Sonic hedgehog (Shh)-expressing stem cells in basal urothelium.
View Article and Find Full Text PDFMost subunit vaccines require adjuvants in order to induce protective immune responses to the targeted pathogen. However, many of the potent immunogenic adjuvants display unacceptable local or systemic reactogenicity. Liposomes are spherical vesicles consisting of single (unilamellar) or multiple (multilamellar) phospholipid bi-layers.
View Article and Find Full Text PDFTo prevent important infectious diseases such as tuberculosis, malaria and HIV, vaccines inducing greater T cell responses are required. In this study, we investigated whether fusion of the M. tuberculosis antigen 85A to recently described adjuvant IMX313, a hybrid avian C4bp oligomerization domain, could increase T cell responses in pre-clinical vaccine model species.
View Article and Find Full Text PDFLive recombinant viral vectors based on adenoviruses and poxviruses are among the most promising platforms for development of new vaccines against diseases such as malaria, tuberculosis, and HIV-AIDS. Vaccines based on live viruses must remain infectious to be effective, so therefore need continuous refrigeration to maintain stability and viability, a requirement that can be costly and difficult, especially in developing countries. The sugars sucrose and trehalose are commonly used as stabilizing agents and cryoprotectants for biological products.
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