RESEARCH PROJECTS JULY 1, 2005 – JUNE 30, 2006
Project Title: Animal models of TSEs
PI: S. Booth
Collaborators: S.Czub, M. Coulthart, G. Telling, K. Qingzhong
Project Description: This project is to establish the infrastructure and expertise within Canada to perform transmission and characterization studies of TSEs in rodent models. A number of different mouse models, including BSE and CJD that require level III containment, are being established in our laboratory. The study will include primary transmission of Canada’s BSE, CWD and vCJD cases into mice. Transgenic mice containing human, bovine, and elk genes have been previously constructed and reported to show increased sensitivity and short incubation times for transmission.
Duration: 2003 onwards
Funding: Health Canada
Project Title: Antibiotic PK/PD determinants of outcome in human septic shock
PI: Anand Kumar
Project Description: As above
Funding Source(s): University of Manitoba Research Grant
Total Funding Amount: $7500
Duration: 2005
Project Title: Antibodies to Burkholderia Type III Secretion System
PI: Cangene Corporation (W. Johnson department member)
Co-investigators: Defence R&D Canada; Los Alamos National Laboratory – Dr. Paul Jackson
Project description: The primary objectives of the project are: 1) Development of mAbs with utility in diagnosing and treating B.(pseudo)mallei and other Burkholderia species, including B.cepacia; 2)Improved understanding of the pathogenicity of B.(pseudo)mallei as a basis for potential vaccine development.
Duration: September 2003 to February 2006
Funding: NIH Grant # 1U10A156383-01; $1,372,000 USD
Project Title: Antiretroviral Therapy Delivery in Two Long-Standing Research Cohorts in Nairobi
PI: Lawrence Gelmon
Collaborators: P. Thottinghal, S. Barasa, C. Wachihi
Project Description: The purpose of this project is to provide antiretroviral delivery and care to the research subjects in the long-standing Pumwani and Majengo research cohorts in Nairobi Kenya. These women, their children and partners have been the subjects of research for over twenty years, and this project provides the opportunity for the delivery of antiretroviral care to those members of the cohorts who require it. Besides providing antiretroviral care to several hundred members of the research cohort and their families, the project will also provide basic HIV/AIDS treatment as well as promotion of prevention programmes, including peer support, voluntary counseling, testing and risk reduction counseling.
Funding Source(s): United States Government – PEPFAR program
Total Funding Amount: US$ 105,000 per year
Duration: until March 29, 2010
Project Title: “Antiviral development on Hepatitis B Virus”
PI: Runtao He
Co-PI: John Cullen (State University of North Carolina)
Project Description: as above
Funding Source(s): PHAC/NML
Total Funding Amount: N/A
Duration: 2005-2007
Project Title: API-1292 activity against MRSA
PI: George Zhanel
Project Description: As above
Funding Source(s): Affinium
Total Funding Amount: $15,000
Duration: Ongoing
Project Title: The Appearance of Blastomycosis of the Lungs on Computed Axial Tomographic Scans
Principle Investigator: John M. Embil
Co- Principle Investigators: Michael Meyers
Collaborators: Suzanne Ronald
Project Description: A review of computed axial tomographic scans of the chest will be undertaken to try and establish patterns observed in pulmonary blastomycosis.
Funding Source(s): Unfunded
Duration: 2 years
Project Title: Assay Development and Production team (ADAPT) for the development, validation, production, and distribution of assays for the identification of BT agents.
Co-PI: Jody Berry
Project Description: As above
Duration: Ongoing
Funding: CRTI-DRDC Project; $3,790,000 over 3 years.
Project Title: Assessment of Moxifloxacin ability to eradicate and prevent development of Streptococcus pneumoniae resistance: Clinical simulation and Monte Carlo analysis
PI: Ayman Noreddin
Co-PI: Virginia Haynes
Collaborators: Johan Baken
Project Description: Pharmacokinetic and pharmacodynamic analysis of Moxifloxacin use in Community Acquired Pneumonia. Monte carlo simulation of potential bacterial eradication and preventing of resistance is conducted
Funding Source(s): Whiteside institute of Clinical Research
Total Funding Amount: $10,000
Duration: 2 years
Project Title: Assessment of antimicrobial administration delay as a cause of excessive mortality in fungal septic shock
PI: Anand Kumar
Project Description: As above
Funding Source(s): Astellas Canada Unrestricted Research Grant & Astellas US Unrestricted Research Grant
Total Funding Amount: $10,000 (Canada) $15,000 (US)
Duration: 2005
Project Title: Assessment of antimicrobial determinants of outcome in human septic shock
PI: Anand Kumar
Project Description: As above
Funding Source(s): Pfizer Unrestricted Research Grant
Total Funding Amount: $12,500
Duration: 2006
Project Title: Assessment of therapeutic determinants of outcome in septic shock
PI: Anand Kumar
Project Description: As above
Funding Source(s): Pfizer Unrestricted Research Grant; Bayer Unrestricted Grant
Total Funding Amount: $15,000 (Pfizer); $10,000 (Bayer)
Duration: 2005
Project Title: Association of Campylobacter porA gene sequences with the Guillain-Barré Syndrome
PI: Clifford Clark
Collaborators: Gehua Wang
Project Description:Thirty-nine porA genes have been sequenced from reference isolates, clinical isolates, and GBS isolates of C. jejuni. Sixty-six previously completed DNA sequences available on GenBank were also included in the analysis. These sequences comprised three distinct groups and showed no recombination between groups. The 11 GBS isolates tested so far are associated with group 1 only. Restriction fragment polymorphism (RFLP) assays have been developed to distinguish among the Campylobacter porA sequence groups.
A collaboration with Dr. Ed Taboada (Laboratory for Foodborne Zoonoses, PHAC, Guelph) and Dr. John Nash (NRC, Ottawa) will allow the analysis of porA genes from 40 additional GBS isolates and 20 more reference strains by DNA sequencing and RFLP analysis.
Funding Source(s): not specifically funded
Duration: continuing
Project Title: Bacterial Genomics
PI: Michael Mulvey
Study description: As above
Duration: Ongoing
Funding: Canadian Biotechnology Strategy, Health Canada; $650,000
Project Title: Best management practices to improve sustainability and productivity of forage-based beef cattle production systems
PI: Ominski, K., Wittenberg, K. M., Krause, D. O., and Holley, R.
Project Description: As above
Funding Source(s): Agriculture and Agri-food Canada
Total Funding Amount: $500,000
Duration: 2005-2008
Project Title: Biology of Cancer: Follicular Lymphoma as a Model of Cancer Progression
PI: Joseph Connors
Co-PI: Marco Marra, Randy Gascoyne, Doug Horsman
Collaborators: Collaborators: Jacquie Schien, Steven Jones, Martin Krzywinski, Robert Holt
Project Description: High resolution analysis of follicular lymphoma genomes by large-scale high-throughput BAC clone fingerprinting: To discover the genomic rearrangements contributing to development of follicular lymphoma and the additional rearrangements contributing to the progression from follicular lymphoma to diffuse large B cell lymphoma using BAC fingerprinting.
Funding Source(s): NCIC
Total Funding Amount: $3,540,067 CAD
Duration: 07/2005 to 06/2008
Project Title: Campylobacter temperate phages: biology, importance in typing methods and virulence
PI: Clifford Clark
Project Description: Southern blot experiments showed that temperate phages affect Campylobacter PFGE patterns on a short timescale. Temperate phages with DNA sequence homology to one of the bacteriophages found in C. jejuni strain RM1221 have variable carriage within C. jejuni isolates studied to date, including a panel of multi-locus sequence typing (MLST) reference isolates representing the variation within the global C. jejuni population. Partial DNA sequencing of twelve temperate phages has shown sequence variation suggesting that these phages have a modular structure similar to temperate bacteriophages infecting other genera. Further studies will be aimed at examining the variability of these temperate bacteriophages and the roles of temperate phages in bacterial virulence and adaptability.
Funding Source(s): not specifically funded
Duration: ongoing
Project Title: Canadian Azole Resistance Study (CARS)
Co-PI: George Zhanel and Daryl Hoban
Project Description: Eighteen hospital sites representing tertiary care hospitals in Canada are recruited to provide fungemic Candida spp. isolates from blood cultures (1 per patient) plus Candida spp. isolates from the lower respiratory tract and skin and soft tissue infections. Isolates sent to the reference lab (HSC, Microbiology) for antifungal susceptibility testing. Data analysis to include all susceptibility data plus species prevalence data.
Duration: Ongoing
Funding: Pharmaceutical Industry; $50,000/year
Project Title: Canadian Community Etiology Study; etiologic agents of diarrheal disease in Canada
PI: Rita Finley (Project Co-ordinator)
Co-PI: Paul Sockett, Lai-King Ng
Collaborators: for lab component: Jody Berry, Clifford Clark, Helen Tabor, Tim Booth; for epidemiological component: André Ravel, Nadia Ciampa, James Flint, Angela Cook, Frank Pollari, Barbara Marshall, Shannon Majowicz
Project Description: Core Objective
The overarching aim this study is to determine how representative what we see in national surveillance is of what is truly happening in the population, since policy is based on the findings of these surveillance data. Thus, the core objective of this study is to comprehensively determine the pathogen-specific incidences and microbial features (using published laboratory methods), and epidemiological risk factors related to acute gastrointestinal illness in a the Canadian population for an a priori list pathogens, which will include (a) all nationally reportable enteric pathogens, and (b) other pathogens considered important. For nationally reportable enteric pathogens, pathogen-specific under-reporting ratios will be generated by comparing the pathogen-specific community incidence rate to the reported rate for the same time frame. This will enable us to determine how the relative incidence reported at the national level (e.g. fraction of illness observed to be due to Salmonella spp.) compares to the relative incidence as it occurs in the community (e.g. fraction of illness actually due to Salmonella spp.). For those pathogens that are not nationally reportable, pathogen-specific community incidence rates will be determined. This will enable us to determine (a) how the relative incidence of these non-reportable pathogens compares to the relative incidence of reportable pathogens at the community level, and (b) what proportion of the “unknown” fraction these pathogens account for. This will also help guide future national surveillance activities. Additionally, incidence rates generated from this study will be combined with economic information from the Office of Public Health Practice’s Policy Research Unit (disability weights, etc.) to generate burden of disease estimates (disability-adjusted life years; DALY’s) for Canada. These DALY’s will feed into the World Health Organization’s Burden of Disease project .
Secondary Objectives
· Secondary objectives, subject to resource availability, may include:
· Detailed burden of illness and cost
· Specific investigation of Campylobacter concisus
· Methodologic investigations (e.g. research into new laboratory methods, retrospective versus prospective survey methods)
· Further investigation of the “other” fraction (i.e. those that test negative for our final panel of pathogens)
· Further investigation of viral infections
· Risk factors
· Asymptomatic carriage rates
The proposed approach is a community-based, prospective longitudinal study. A randomly selected group of people from the community (representative of all ages) would be followed for a pre–determined period of time to determine how many develop AGI and which pathogens caused the illnesses. When a participant met the case definition, a stool sample would be requested and tested for a specific group of enteric pathogens. A pilot study will be conducted to ensure the methodologies are viable.
Bacteriological laboratory component: Helen Tabor, Clifford Clark, Jody Berry
All stool samples will be tested for enteric bacterial pathogens using culture methods and single-plex PCR. Multiplex PCR methods currently in development will be evaluated on a subset of samples. Novel antibody-based detection methods will be developed and compared with existing (commercial) methods.
Funding Source(s): internal
Total Funding Amount: $1 million for laboratory equipment and supplies (overall) for 2006-2007 government fiscal year; equal amount for 2006-2007 fiscal year (?) for personnel and supplies
Duration: to be determined
Project Title: Canadian Integrated Program for Antimicrobial Resistance Surveillance (CIPARS).
Collaborators: Matthew Gilmour
Project Description: Molecular characterization of multi-drug resistant Salmonella enterica serovar Heidelberg strains isolated from agricultural and clinical samples; plasmid gene characterization; comparative microarray genomics. This project has policy implications on the use of antibiotics in the agricultural sector.
Duration: 2005-present
Project Title: Canadian National – Intensive Care Unit (CAN-ICU) Surveillance Study
PI: George G. Zhanel
Co-PI: Daryl J. Hoban
Project Description: To examine, in depth, the level and extent of resistance to pathogens isolated from ICU patients in Canada as well as the activity of commonly used antimicrobials and comparators against these organisms.
Funding Source(s): Wyeth Pharmaceuticals, AstrZeneca, Pfizer
Total Funding Amount: $382,000 (Wyeth); $125,000 (AstraZeneca); $50,000 (Pfizer)
Duration: 1 year – January 1-December 31, 2005
Project Title: Canadian Network for Public Health Intelligence
Co-PI: Amin Kabani
Project description: as above
Duration: 2002 onwards
Funding: CRTI $7,908,234
Project Title: Canadian Nosocomial Surveillance Program Studies
PI: Various: Co-Investigators J Embil, J Embree, M Mulvey et al
Project descriptions:
1) Nosocomial Cerebral spinal Fluid Shunt-Associated Infections within Acute-Care Institutions: Prospective study of nosocomial CSF shunt infections in participating hospitals across Canada of shunts placed between January 15th 2000 to January 14th, 2002 to determine the incidence, risk factors and outcomes
2) Vancomycin Resistant Enterococci Suveillance in CHEC/CNISP Health Care Facilities: An ongoing surveillance since 1998 of the incidence and changing trends of vancomycin resistance among Enterococci in Canadian sentininel hospitals. MRSA Suveillance in CHEC/CNISP Health Care Facilities:
3) An ongoing surveillance since 1995 of the incidence, changing trends and associated risk factors of MRSA in Canadian sentininel hospitals.
Duration: Ongoing
Funding: Health Canada
Project Title: Canadian Paediatric Surveillance Program – Estimating the Incidence of Severe Combined Iimmunodeficiency (SCID) in Canada (2004-March 2006)
PI: Ramsingh R,
Project Team: Pelletier L, Probert A, Yacoub W, Junker A, Schultz K, Champagne MA, Long R, Langley J, Embree J
Project description: A prospective two year study to estimate the incidence of SCID in Canadian children and, in particular, Aboriginal children in Canada to determine the basic demographics, clinical features and outcomes of children diagnosed with SCID in Canada.
Duration: April 2004-March 2006
Funding: Health Canada
Project Title: Canadian Respiratory Organism Susceptibility Study (CROSS)
Co-PI: Daryl Hoban and George Zhanel
Project Description: Twenty-five labs in Canada are recruited to collect, identify and ship to the reference centre (HSC, Microbiology) S. pneumoniae, H. influenzae, M. catarrhalis, S. pyogenes plus all bacteremic S. pneumoniae. At the reference site microbroth MIC testing is performed using carbapenems, ß-lactams, fluoroquinolones plus other comparators, and data analysis conducted.
Duration: Ongoing, Currently completing 8th year of study
Funding: Pharmaceutical Industry; $400,000/year
Project Title: Can-Ward study
PI: George Zhanel
Project Description: To examine, in depth, the level and extent of resistance to pathogens isolated from patients in Canadian hospitals as well as the activity of commonly used antimicrobials against these organisms.
Funding Source(s): Wyeth
Total Funding Amount: $304,000
Duration: Ongoing
Project Title: Case-Control Genetic Analysis Study of Risk Factors for Acquisition of Endemic Blastomycosis
PI: John Embil
Co-PI: Stephen Chanock
Project Description: North American blastomycosis is an uncommon granulomatous fungal infection caused by Blastomyces dermatitidis. This fungus is endemic in Canada, specifically in northwestern Ontario and southeastern Manitoba. The exact reservoir of B. dermatitidis is not known, but it is presumed to be the soil. Inhalation of aerosols containing conidia is believed to be the cause of infection in humans and animals. Much of the information that is available about acquisition of B. dermatitidis has been determined from epidemics. Unfortunately, little is known about risk factors for the acquisition of endemic blastomycosis. It is important to note that in our endemic region, it is endemic B. dermatitidis infection which is prevalent. A recently published retrospective review of the epidemiology and clinical spectrum of blastomycosis diagnosed at Manitoba hospitals has revealed that the annual incidence rate of blastomycosis in Manitoba is 0.6 cases per 100, 000 population compared with 7.11 cases per 100,000 population in the Kenora, Ontario district. It is presumed that a genetic predisposition may exist for the acquisition of B. dermatitidis disease, however, this has never been confirmed. It is also not known why some persons who develop B. dermatitidis disease have a self-limited benign course while others have a more significant invasive and progressive infection.