234 ABSTRACT: Although diagnosed infrequently, hantavirus infections do occur in British Columbia. Hantavirus pulmonary syndrome has a crude mortality rate of approximately 40% to 50% and is typically characterized by fever, chills, and myalgias followed by an abrupt onset of respiratory distress and hypotension, often requiring ventilation. In 2002, a case of hantavirus pulmonary syndrome with uncharacteristic presentation was diagnosed in a 46-year-old male from the Okanagan region. This case highlights the need for physicians to be aware of such atypical case histories, the epidemiological and laboratory investigations required, and the epidemiology of hantavirus infection in British Columbia, including modes of transmission and common risk factors for disease. Physicians should also be aware of the national and BC case definition, specimen collection procedure, differential diagnoses, clinical management, and the importance of case reporting. Case history In early July 2002, a 46-year-old male presented to an emergency department complaining of epigastric discomfort followed by significant vomiting and intense right upper quadrant pain. He was admitted to hospital and within 2 days developed drenching night sweats and mild breathlessness, headache, but no diarrhea. Initial Xrays indicated interstitial pneumonitis with bilateral effusions; oxygen saturation was 84% on room air but improved with administration of supplemental oxygen (94% on 4 L O2). The patient developed a cough by his fourth day in hospital and fine course crackles were present throughout both lung fields. Some bilateral chest pain was present but this was not typical of pleuritic pain. The patient’s highest recorded temperature was 38.1°C on day 2, with fluctuation between 36°C and 38°C. His BUN and creatinine levels were initially normal, but he went into transient renal failure (maximum creatinine 260). His liver function studies were normal except for a GGT of 160 (normal range 12–50 U/L). His WBC count was normal at 6.18, with 3.40 polymorphonuclear leukocytes and 0.19 bands, but the smear showed rare nucleated red cells and immature granulocytes, which were considered to be abnormal. Similarly, many of the lymphocytes were abnormal in appearance. His initial hemoglobin count was 166 but on rehydration fell to 115. His platelet count was 90 000 at presentation, fell to 65 000 2 days later, and then slowly recovered. His chest X-ray ultimately revealed interstitial edema with small pleural effusions. L. MacDougall, MSc, M. Fyfe, MD, MSc, William R. Bowie, MD, FRCPC, K. Cooper, CPHI(C), G.D. McCauley, MD, FRCPC, M. Morshed, PhD

a Department of Food, Agricultural and Resource Economics, University of Guelph, Guelph, Ontario, Canada N1G 2W1 b Foodborne, Waterborne and Zoonotic Infections Division, Public Health Agency of Canada, Guelph, Ontario, Canada N1H 8J1 c Department of Population Medicine, University of Guelph, Guelph, Ontario, Canada N1G 2W1 d British Columbia Centre for Diseases Control, Vancouver, British Columbia, Canada V5Z 4R4 e Faculty of Medicine, Memorial University of Newfoundland, St Johns, Newfoundland, Canada NL A1C 5S7

The costs associated with gastrointestinal infection (GI) in the province of British Columbia, Canada. were estimated using data from a population-based survey in three health service delivery areas, namely Vancouver, East Kootenay and Northern Interior. The number of cases of disease, consequent expenditure of resources and associated economic costs were modeled as probability distributions in a stochastic model. Using 2004 prices, the estimated mean annual cost per capita of gastrointestinal infection was CAN$128.61 ("sic"207.96), with a mean annual cost per case of CAN$1,342.57 ("sic"2,170.99). The mean estimate of the overall economic burden to British Columbia was CAN$14.2 million ("sic"831.5 million) (95% CFI CAN$161.0 million to CAN$5.8 billion: "sic"260.3 million to "sic"9.38 billion). The major element of this cost was the loss of productivity associated with time away from paid employment by both the sick and their caregivers. Sensitivity analysis suggested that the uncertainty associated with the base model assumptions did not significantly affect the estimates. The results are comparable to those obtained in an earlier study using a similar analytical framework and data from the city of Hamilton, Ontario, Canada. (C) 2008 Elsevier B. V. All rights reserved.

BACKGROUND:Cryptococcus gattii causes disease among immunocompetent individuals in the tropics and subtropics. We document the appearance of C. gattii infections on Vancouver Island (VI), a temperate region, and discuss reasons for this emergence.METHODS:Data on Cryptococcus hospitalizations for the calendar years 1995 through 2004 were reviewed. Viable historic isolates stored at the provincial public health laboratory between 1987 and 2000 were serotyped. Human cases were mapped by place of residence.RESULTS:Cryptococcosis among HIV negative individuals diagnosed on VI increased sharply after 1999. C. gattii was not detected in stored isolates prior to 1999. C. gattii cases lived in a specific biogeoclimatic zone on VI. Higher rates of illness were associated with exposure to the central region of VI.CONCLUSIONS:The emergence of C. gattii in a temperate region is unprecedented. Clinicians should consider C. gattii in the differential diagnosis of individuals who travelled to certain areas in British Columbia.

Under-reporting of infectious gastrointestinal illness (IGI) in British Columbia, Canada was calculated using simulation modelling, accounting for the uncertainty and variability of input parameters. Factors affecting under-reporting were assessed during a cross-sectional randomized telephone survey. For every case of IGI reported to the province, a mean of 347 community cases occurred (5th and 95th percentile estimates ranged from 181 to 611 community cases, respectively). Vomiting [odds ratio (OR) 2.15, 95 % confidence interval (CI) 1.03-4.49] and antibiotic use in the previous 28 days (OR 3.59, 95 % CI 1.17-10.97) significantly predicted health-care visits in a logistic regression model. In bivariate analyses, physicians were significantly less likely to request stool samples from patients with vomiting (RR 0.09, 95 % CI 0.01-0.65) and patients of North American as opposed to non-North American cultural groups (RR 0.38, 95 % CI 0.15-0.96). Physicians were more likely to request stool samples from older patients (P=0.003), patients with fewer household members (P=0.002) and those who reported anti-diarrhoeal use following illness (RR 3.33, 95 % CI 1.32-8.45). People with symptoms of vomiting were under-represented in provincial communicable disease statistics. Differential degrees of under-reporting must be understood before biased surveillance data can be adjusted.

A cross-sectional telephone survey was performed in the province of British Columbia, Canada, to investigate drinking water consumption patterns and their associations with various demographic characteristics and acute gastrointestinal illness (AGI). Water consumption included plain water and water used in the preparation of cold beverages. The median amount of water consumed daily was four-250 mL servings (1.0 L), although responses were highly variable (0 to 9.0 L). Alternative water use was common: bottled water was the primary source of drinking water (i.e. >= 75% of the total daily water intake) for 23% of respondents and 47% of households used in-home water treatment methods. Approximately 10% of respondents reported an episode of AGI (vomiting or diarrhea) in the previous 4-week period. Such illness was associated with age (continuous variable in years, OR=-0.98), sex (male vs. female, OR=0.8) and the amount of water consumed (continuous variable in 250-mL servings, OR= 1.06); however, a causal relationship with water consumption cannot be established based on this study alone. Overall, the associations of drinking water patterns with age, sex, education, and household income serve as important reminders to researchers and public health professionals of the non-uniform nature of drinking water consumption, and indicate potential differences in exposure to waterborne hazards in this population. (c) 2007 Elsevier B. V. All rights reserved.

1 Foodborne, Waterborne and Zoonotic Infections Division, Public Health Agency of Canada, Guelph and Ottawa, Ontario, Canada 2 British Columbia Centre for Disease Control and Prevention, Vancouver, British Columbia, Canada 3 Vancouver Island Health Authority, Victoria, British Columbia, Canada 4 Department of Agricultural Economics and Business, University of Guelph, Guelph, Ontario, Canada 5 Western University of Health Sciences, Pomona, California, USA 6 Division of Community Health Faculty of Medicine, Memorial University of Newfoundland, St. John’s, Newfoundland and Labrador, Canada

Hematide is a PEGylated synthetic peptidic ESA that binds to and activates the erythropoietin (EPO) receptor. It has demonstrated potent and sustained dose dependent erythropoietic activity in healthy volunteers (HV).

A total of 184 methicillin-resistant Staphylococcus aureus (MRSA) strains were collected from patients who sought treatment primarily for skin and soft tissue infections from January 1, 1999, to March 31, 2002, in east-central Saskatchewan, Canada. Molecular subtyping analysis using pulsed-field gel electrophoresis showed 2 major clusters. Cluster A (n = 55) was composed of a multidrug-resistant MRSA strain associated with a long-term care facility and was similar to the previously reported nosocomial Canadian epidemic strain labeled CMRSA-2. Cluster B (n = 125) was associated with cases identified at community health centers and was indistinguishable from a community-associated (CA)-MRSA strain identified previously in the United States (USA400). Cluster B remained susceptible to a number of classes of antimicrobial agents and harbored the lukF-PV and lukS-PV toxin genes. Over 50% of both clonal groups displayed high-level resistance to mupirocin. This is the first report of the USA400 strain harboring the lukF-PV and lukS-PV toxin genes in Canada.

A case-control study was conducted from 1 January to 31 May 2003 to identify risk factors for S . Heidelberg infection in Canada. Controls were pair-matched by age group and telephone exchange to 95 cases. Exposures in the 7 days before illness/interview were assessed using multivariate conditional logistic regression. Consumption of home-prepared chicken nuggets and/or strips [matched odds ratio (mOR) 4.0, 95% confidence interval (CI) 1.4-13.8], and undercooked eggs (mOR 7.5, 95% CI 1.5-75.5) increased the risk of illness. Exposure to a farm setting lowered the risk (mOR 0.22, 95% CI 0.03-1.00). The population-attributable fraction associated with chicken nuggets/strips was 34% and with undercooked eggs was 16%. One-third of study participants did not perceive, handle or prepare chicken nuggets and strips as high-risk products, although the majority of the products on the Canadian market are raw. These findings have prompted changes in product-labelling policy and consumer education.

Petting zoos have been associated with E. coli O157:H7 outbreaks. Given the epidemiologic link between all cases and the farm, the hypothesis under joint investigation by the BCCDC and local health units was that the infections resulted from contact with the petting zoo animals. The purposes of this investigation were to verify the cause of the outbreak, determine the outbreak’s scope, and identify activities or behaviours that influenced the risk of infection.

Cryptococcus gattii causes life-threatening infection of the pulmonary and central nervous systems in hosts with normal immunity and traditionally has been considered to be restricted geographically to tropical and subtropical climates. The recent outbreak of C. gattii in the temperate climate of Vancouver Island, BC, Canada, led to a collaborative investigation. The objectives of the current study were to ascertain the environmental source of the outbreak infections, survey the molecular types of the outbreak and environmental cryptococcal isolates, and determine the extent of genetic diversity among the isolates. PCR-fingerprinting and amplified fragment length polymorphism (AFLP) were used to examine the genotypes, and mating assays were performed to determine the mating type of the isolates. All outbreak and environmental isolates belonged to C. gattii. Concordant results were obtained by using PCR-fingerprinting and AFLP analysis. The vast majority of clinical and veterinary infections were caused by isolates of the molecular type VGII/AFLP6, but two were caused by molecular type VGI/AFLP4. All environmental isolates belonged to molecular type VGII/AFLP6. Two or three subtypes were observed within VGII/AFLP6 among outbreak and environmental isolates. All mating-competent isolates were of the alpha-mating type. The emergence of this usually tropical pathogen on Vancouver Island highlights the changing distribution of this genotype and emphasizes the importance of an ongoing collaborative effort to monitor the global epidemiology of this yeast.

The ovaries of 12 mature wapiti hinds were studied by transrectal ultrasonography during the anovulatory season to characterize follicular dynamics and to test the hypothesis that follicle development occurs in a wave-like fashion. The hinds were examined daily, standing without sedation. Follicle size and numbers were recorded, and individual follicles were identified serially. Follicle development was considered wave-like if periodic changes in follicle numbers could be associated temporally with the development of a dominant follicle. There were non-random changes (P<0.01) in the number of follicles ≥4 mm in diameter detected per day. Each peak in follicle numbers was associated with the development of a single dominant follicle. The dominant follicle of the cohort was larger (P<0.05) than the other follicles 1 day after its emergence. Intervals between successive peaks (6.8±0.4 day) and troughs (6.8±0.4 day) in follicle numbers, and emergence of sequential dominant follicles (7.1±0.5 day) were not different (P=0.86). Results confirmed the hypothesis that ovarian follicles develop in a wave-like fashion in wapiti during the anovulatory season.

We investigated personal protective behaviors against West Nile virus infection. Barriers to adopting these behaviors were identified, including the perception that DEET (N,N-diethyl-m-toluamide and related compounds) is a health and environmental hazard. Televised public health messages and knowing that family or friends practiced protective behaviors were important cues to action.

Phosphoinositide 3-kinases (PI3-kinases) have been shown to be recruited to cell surface receptor signal complexes whose formation is triggered by growth factors, cytokines and other ligands. PI3-kinases are also involved in protein sorting phenomena. A number of PI3-kinase isotypes have been characterised in several laboratories. Here the relations between the PI3-kinases, PI4-kinases and PI5-kinases and other potential phosphoinositide kinases are analysed. A study of the relation of structure to function for sequence motifs defined through the use of homology searches and protein modelling techniques is described and used to assign the family of phosphoinositide kinases to subgroups.

Phosphoinositide (PI) 3‐kinases have been characterized as enzymes involved in receptor signal transduction in mammalian cells and in a complex which mediates protein trafficking in yeast. PI 3‐kinases linked to receptors with intrinsic or associated tyrosine kinase activity are heterodimeric proteins, consisting of p85 adaptor and p110 catalytic subunits, which can generate the 3‐phosphorylated forms of phosphatidylinositol (PtdIns), PtdIns4P and PtdIns(4,5)P2 as potential second messengers. Yeast Vps34p kinase, however, has a substrate specificity restricted to PtdIns and is a PtdIns 3‐kinase. Here the molecular characterization of a new human PtdIns 3‐kinase with extensive sequence homology to Vps34p is described. PtdIns 3‐kinase does not associate with p85 and phosphorylates PtdIns, but not PtdIns4P or PtdIns(4,5)P2. In vivo PtdIns 3‐kinase is in a complex with a cellular protein of 150 kDa, as detected by immunoprecipitation from human cells. Protein sequence analysis and cDNA cloning show that this 150 kDa protein is highly homologous to Vps15p, a 160 kDa protein serine/threonine kinase associated with yeast Vps34p. These results suggest that the major components of the yeast Vps intracellular trafficking complex are conserved in humans.