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.