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Avian influenza that infects poultry in close proximity to humans is a concern because of its pandemic potential. In 2004, an outbreak of highly pathogenic avian influenza H7N3 occurred in poultry in British Columbia, Canada. Surveillance... more
Avian influenza that infects poultry in close proximity to humans is a concern because of its pandemic potential. In 2004, an outbreak of highly pathogenic avian influenza H7N3 occurred in poultry in British Columbia, Canada. Surveillance identified two persons with ...
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Current practice guidelines recommend liver biopsy prior to treatment of hepatitis C genotype-1 but not for genotype-2/3; this is based on expert opinion, not on published evidence. In retrospective analysis of a large trial database... more
Current practice guidelines recommend liver biopsy prior to treatment of hepatitis C genotype-1 but not for genotype-2/3; this is based on expert opinion, not on published evidence. In retrospective analysis of a large trial database prior to the publication of recent guidelines, we compared outcomes in 985 treatment-naïve patients with hepatitis C who did or did not undergo liver biopsy before starting peginterferon alfa-2a plus ribavirin. Physicians elected to treat 141/654 (21.6%) genotype-1 patients and 126/331 (38.1%) genotype-2/3 patients without liver biopsy. There were no differences in baseline characteristics among those with or without pre-treatment liver biopsy, except for female preponderance in genotype-1 patients with liver biopsy. The sustained viral response (SVR) rate was no different amongst genotype-2/3 patients who had a biopsy before treatment with 66.3% SVR vs. 69.8% of those treated without biopsy (p = 0.546), but significantly higher among genotype-1 patient...
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To estimate the impact of implementing primary human papilloma virus liquid-based cytology (LBC) screening on four-year rates of referral for colposcopy in the British Columbia screening program. We used data on referral for colposcopy... more
To estimate the impact of implementing primary human papilloma virus liquid-based cytology (LBC) screening on four-year rates of referral for colposcopy in the British Columbia screening program. We used data on referral for colposcopy from an RCT (HPV FOCAL) comparing HPV testing every four years with LBC testing every two years. We also used data from population screening with conventional cytology among women aged 25 to 69. The predicted effect of adoption of either trial protocol on rates of referral for colposcopy was estimated using trial age-specific result and screening result-specific rates weighted by their screening program distribution. The cumulative age-specific rates of referral for colposcopy over four years were calculated. Use of HPV testing initially increased rates of referral for colposcopy in the trial, but over four years the cumulative rates of referral were similar to those for LBC except in women aged 25 to 29, in whom a substantial excess persisted. Four-y...
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The increases in STI rates since the late 1990s in Canada have occurred despite widespread primary care and targeted public health programs and in the setting of universal health care. More innovative interventions are required that would... more
The increases in STI rates since the late 1990s in Canada have occurred despite widespread primary care and targeted public health programs and in the setting of universal health care. More innovative interventions are required that would eliminate barriers to STI testing such as internet-based or mail-in home and community service testing for patients that are hard to reach, who refuse to go for clinician-based testing, or who decline an examination. Jurisdictions such as New Zealand and some American states currently use self-collected sampling, but without the required evidence to determine whether self-collected specimens are as accurate as clinician-collected specimens in terms of chlamydia and gonorrhea diagnostic accuracy. The objective of the review is to compare self-collected vaginal, urine, pharyngeal and rectal samples to our reference standard - clinician-collected cervical, urethral, pharyngeal and rectal sampling techniques to identify a positive specimen using nucleic acid amplification test assays. The hierarchical summary receiver operating characteristic and the fixed effect models were used to assess the accuracy of comparable specimens that were collected by patients compared to clinicians. Sensitivity and specificity estimates with 95% confidence intervals (CI) were reported as our main outcome measures. We included 21 studies based on over 6100 paired samples. Fourteen included studies examined chlamydia only, 6 compared both gonorrhea and chlamydia separately in the same study, and one examined gonorrhea. The six chlamydia studies comparing self-collection by vaginal swab to a clinician-collected cervical swab had the highest sensitivity (92%, 95% CI 87-95) and specificity (98%, 95% CI 97-99), compared to other specimen-types (urine/urethra or urine/cervix). Six studies compared urine self-samples to urethra clinician-collected samples in males and produced a sensitivity of 88% (95% CI 83-93) and a specificity of 99% (95% CI 0.94-0.99). Taking into account that urine samples may be less sensitive than cervical samples, eight chlamydia studies that compared urine self-collected verses clinician-collected cervical samples had a sensitivity of 87% (95% CI 81-91) and high specificity of 99% (95% CI 0.98-1.00). For gonorrhea testing, self-collected urine samples compared to clinician-collected urethra samples in males produced a sensitivity of 92% (95% CI 83-97) and specificity of 99% (95% CI 0.98-1.00). The sensitivity and specificity of vaginal self-collected swabs compared to swabs collected by clinicians supports the use of vaginal swab as the recommended specimen of choice in home-based screening for chlamydia and gonorrhea. Urine samples for gonorrhea collected by men had comparably high sensitivity and specificity, so could be recommended as they can be left at room temperature for several days, allowing for the possibility of mail-in home-based testing. In populations that may not go for testing at all, do not have the option of clinical testing, or who refuse a clinical examination, self-collected screening would be a good alternative. We recommend that guidelines on how to self-collect gonorrhea and chlamydia urine, vaginal, rectal and pharyngeal specimens be published.
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Research Interests: Genetics, Epidemiology, Phylogenetics, Hepatitis C, Phylogeny, and 17 moreSequencing, Humans, Female, Male, OR, Cluster Analysis, Iu, Young Adult, Risk factors, British Columbia, Middle Aged, Genotype, Adult, cDNA, RT PCR, Risk Factors, and HVR
Canada's Sentinel Physician Surveillance Network (SPSN) links genetic, antigenic and vaccine effectiveness (VE) measures in an integrated platform of influenza monitoring, described here for the 2013-14 season of resurgent... more
Canada's Sentinel Physician Surveillance Network (SPSN) links genetic, antigenic and vaccine effectiveness (VE) measures in an integrated platform of influenza monitoring, described here for the 2013-14 season of resurgent A(H1N1)pdm09 and late-season influenza B activity. VE was estimated as [1-OddsRatio]x100% comparing vaccination status between influenza test-positive cases and test-negative controls. Vaccine-virus relatedness was assessed by genomic sequence analysis and hemagglutination-inhibition assay. Analyses included 1037 controls (33%vaccinated) and 663 cases (15%vaccinated): 415 A(H1N1)pdm09, 15 A(H3N2), 191 B/Yamagata-lineage, 6 B/Victoria-lineage, 36 unknown subtype/lineage. A(H1N1)pdm09 viruses belonged to clade-6B, distinguished by a K163Q substitution, but remained antigenically-similar to A/California/07/2009-like vaccine with adjusted-VE of 71%(95%CI=58-80%). Most (83%) B/Yamagata-lineage viruses clustered phylogenetically with the prior 2012-13 season'...
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Youth in custody have high-risk drug use and sexual behaviours. HIV prevalence in this population was assessed in British Columbia (BC) in 1994 but hepatitis C virus (HCV) prevalence has never been measured. We sought to determine: 1) the... more
Youth in custody have high-risk drug use and sexual behaviours. HIV prevalence in this population was assessed in British Columbia (BC) in 1994 but hepatitis C virus (HCV) prevalence has never been measured. We sought to determine: 1) the performance of the OraSure, a non-invasive device for oral mucosal transudate (OMT) specimen collection, to detect HCV and HIV antibodies; 2) the prevalence of HCV and HIV among youth in custody; and 3) the factors associated with intravenous drug use and sex for trade. OraSure was validated in 110 adults with known HIV and HCV sero-status. Nurses administered an anonymous survey and collected OMT samples from youth aged 14-19 years in BC youth custody centres. Antibody detection in OMT had 96.4% sensitivity for HIV and 94.6% for HCV. 417 youth were enrolled; 22% were female; 48% reported Aboriginal ethnicity. Although 98.3% reported ever using drugs, <8% reported injection drug use (IDU). IDU was independently associated with age of first sexua...
Research Interests: Risk Taking, Adolescent, Hepatitis C, HIV, Harm Reduction, and 20 moreHumans, Prostitution, Female, Male, Sexual Behavior, Young Adult, Risk factors, British Columbia, Prisoners, Saliva, Mouth mucosa, Public health systems and services research, Odds ratio, Curriculum and Pedagogy, Age Factors, Health surveys, Hiv seropositivity, Risk Factors, Sensitivity and Specificity, and Substance-Related Disorders
Hepatitis B virus (HBV) chronically infects approximately 250,000 Canadians and 350 million people worldwide. Without intervention, approximately 15% to 40% of chronically infected individuals will eventually develop cirrhosis, end-stage... more
Hepatitis B virus (HBV) chronically infects approximately 250,000 Canadians and 350 million people worldwide. Without intervention, approximately 15% to 40% of chronically infected individuals will eventually develop cirrhosis, end-stage liver disease or hepatocellular carcinoma, or require liver transplantation. The availability and extensive use of the HBV vaccine has dramatically reduced the number of incident infections in Canada and worldwide. Effective therapeutic agents have been and continue to be developed to treat chronic infection. The present review provides a comprehensive overview of diagnostic tests for HBV infection and immunity, and elaborates on HBV risk factors, vaccine prevention and therapeutic monitoring. HBV diagnosis is accomplished by testing for a series of serological markers of HBV and by additional testing to exclude alternative etiological agents such as hepatitis A and C viruses. Serological tests are used to distinguish acute, self-limited infections ...
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To develop a set of comprehensive, standardized, evidence-based guidelines for the use of antiviral therapy to prevent cytomegalovirus disease in adult patients having undergone renal transplantation. The use of medication, at the time of... more
To develop a set of comprehensive, standardized, evidence-based guidelines for the use of antiviral therapy to prevent cytomegalovirus disease in adult patients having undergone renal transplantation. The use of medication, at the time of induction therapy or at the earliest sign of viremia. Treatments were evaluated by patient and donor serologic groups and the induction regimen used. The control of symptoms and features of cytomegalovirus disease over the first 6 mo to 1 yr after transplantation. Articles, compiled using a MEDLINE search from 1976 to July 1997, were reviewed by representatives of nephrology, microbiology, pharmacy, and epidemiology. Additional information was obtained from recent review articles and conference abstracts, and from experts in the field. The evidence-based methods and values of the Canadian Task Force on the Periodic Health Examinations were used. High value was placed on studies with a randomized controlled design and blinded outcome observers. Stud...
Research Interests: Microbiology, Forecasting, Kidney transplantation, Controller Design, Canada, and 18 moreRenal transplantation, Humans, Female, Male, Cytomegalovirus, The, Clinical Sciences, Adult, Cost Benefit Analysis, Drug Costs, Prognosis, Cytomegalovirus Infections, Graft Rejection, Observational Study, Chronic Kidney Failure, Antiviral Agents, Acyclovir, and Ganciclovir
Universal prophylaxis with oral ganciclovir is not cost-effective for the prevention of cytomegalovirus (CMV) disease in human immunodeficiency virus infection. For a preemptive strategy to be considered, patients at highest risk for CMV... more
Universal prophylaxis with oral ganciclovir is not cost-effective for the prevention of cytomegalovirus (CMV) disease in human immunodeficiency virus infection. For a preemptive strategy to be considered, patients at highest risk for CMV disease need to be easily and accurately identified. In this study, the sensitivity, specificity, positive predictive value, and negative predictive value of a single CMV DNA PCR assay for the subsequent development of CMV disease were 0.75, 0.89, 0.75, and 0.89, respectively.
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The Roche Amplicor Mycobacterium tuberculosis PCR test (RMtb-PCR) was compared with mycobacterial culture, with the BACTEC 460 system and inoculation on Lowenstein-Jensen media. Results were interpreted with an adjusted "gold... more
The Roche Amplicor Mycobacterium tuberculosis PCR test (RMtb-PCR) was compared with mycobacterial culture, with the BACTEC 460 system and inoculation on Lowenstein-Jensen media. Results were interpreted with an adjusted "gold standard" incorporating clinical diagnosis. A total of 1,480 clinical specimens from 1,155 patients, including tissues and fluids, as well as 141 specimens which demonstrated a positive growth index on the BACTEC 460 system were assessed. The sensitivity, specificity, and positive and negative predictive values of RMtb-PCR compared with the adjusted gold standard for clinical specimens were 79, 99, 93, and 98%, respectively. In smear-positive specimens, the sensitivity of RMtb-PCR was 98% versus 53% for smear-negative specimens. When RMtb-PCR was performed two times per week, PCR results were available an average of 21 days before the culture results. For specimens demonstrating a positive growth index on the BACTEC 460 system, RMtb-PCR had a sensitiv...
Research Interests: Clinical Microbiology, Biological Sciences, Tuberculosis, Humans, Mycobacterium tuberculosis, and 10 moreMycobacterium, Clinical, Polymerase Chain Reaction, Gold Standard, Time Factors, Lowenstein Jensen, Species Specificity, Sensitivity and Specificity, Pulmonary Tuberculosis, and Clinical Diagnosis
The Downtown Eastside is a robust and densely populated neighbourhood in Vancouver, Canada, that is characterized by low-income housing and drug use and a high prevalence of HIV infection. We evaluated mortality and excess mortality among... more
The Downtown Eastside is a robust and densely populated neighbourhood in Vancouver, Canada, that is characterized by low-income housing and drug use and a high prevalence of HIV infection. We evaluated mortality and excess mortality among the broader community of individuals living in this neighbourhood. The Community Health and Safety Evaluation is a community-based study of inner-city residents in the Downtown Eastside who were recruited in 2003 and 2004. Participants' data were linked with data in provincial virology and mortality databases retrospectively and prospectively for the period 1991-2009. Mortality and standardized mortality ratios (SMRs) were calculated for the period 2003-2009 to compare death rates in the study population with rates in the population of Vancouver. Among 2913 participants, 374 deaths occurred, for an all-cause mortality of 223 per 10 000 person-years (95% confidence interval [CI] 201-247 per 10 000 person-years). Compared with the population of V...
To understand the epidemic resurgence of influenza due to the 2009 pandemic influenza A(H1N1) strain (A[H1N1]pdm09) during the 2013-2014 influenza season, we compared age-related cross-sectional estimates of seroprotection before the... more
To understand the epidemic resurgence of influenza due to the 2009 pandemic influenza A(H1N1) strain (A[H1N1]pdm09) during the 2013-2014 influenza season, we compared age-related cross-sectional estimates of seroprotection before the pandemic (during 2009) and after the pandemic (during 2010 and 2013) to subsequent surveillance-based, laboratory-confirmed incidence of influenza due to A(H1N1)pdm09 in British Columbia, Canada. Prepandemic seroprotection was negligible except for very old adults (defined as adults aged ≥ 80 years), among whom 80% had seroprotection. Conversely, postpandemic seroprotection followed a U-shaped distribution, with detection in approximately 35%-45% of working-aged adults but in ≥ 70% of very old adults and young children, excluding children aged <5 years in 2013, among whom seroprotection again decreased to <20%. The incidence was 5-fold higher during 2013-2014, compared with 2010-2011, and was highest among children aged <5 years and working-age...
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Crack use is prevalent amongst street drug users in Canadian cities, and associated with severe drug use, health and social problems. Whilst few targeted interventions are available for crack use, the common use and sharing of hazardous... more
Crack use is prevalent amongst street drug users in Canadian cities, and associated with severe drug use, health and social problems. Whilst few targeted interventions are available for crack use, the common use and sharing of hazardous makeshift paraphernalia are a key concern, as these risks may be associated with oral injury and blood-borne virus (BBV)--e.g., hepatitis C virus (HCV)--transmission amongst users. Recently, distribution programmes of so-called 'safer crack use kits' (SCUKs) have been initiated in select Canadian cities, primarily to reduce the use of unsafe materials and paraphernalia sharing amongst crack users. This study explored uptake and benefits of, barriers to, and possible improvements to two recently implemented SCUK distribution programme in Victoria, Canada. N=31 regular crack smokers were recruited through community-based efforts between June and August 2010, and assessed via an interviewer-administered protocol involving quantitative and qualit...
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A multi-organ donor seronegative for hepatitis C virus (HCV) by 1st generation enzyme immunoassay (EIA) supplied 5 solid organs and 2 corneas to 7 recipients. This donor was retrospectively shown to be 2nd generation HCV EIA-positive and... more
A multi-organ donor seronegative for hepatitis C virus (HCV) by 1st generation enzyme immunoassay (EIA) supplied 5 solid organs and 2 corneas to 7 recipients. This donor was retrospectively shown to be 2nd generation HCV EIA-positive and polymerase chain reaction (PCR)-positive. All 5 solid organ recipients but none of the corneal recipients developed HCV infection. To demonstrate the discordance between serological and PCR-based HCV detection in solid organ transplant recipients and the lack of transmission of HCV to the two corneal transplant recipients. All 5 solid organ recipients were retrospectively shown to be HCV PCR-negative and -seronegative pre-transplant and HCV PCR-positive post-transplant. Serial serum samples on 3 recipients were evaluated by 2nd generation EIA, a prototypic structural and non-structural dual bead assay (EIA-SA, Abbott), the Chiron Recombinant Immunoblot Assay, 2nd generation (RIBA-2), and the Chiron RIBA HCV Test System Strip Immunoblot Assay 3.0 (RIBA-3, Chiron). The dual bead EIA-SA and RIBA-3 were able to detect HCV seroconversion approximately 6 months earlier than the 2nd generation EIA in 2 recipients, and in 1 recipient only PCR detected infection within the first 10 months. There was no evidence of HCV transmission to the corneal recipients. Although third generation assays such as the RIBA-3 and EIA-SA narrowed the window of HCV seronegativity in transplant recipients compared with the 2nd generation EIA, PCR was the most sensitive method of detecting acute HCV infection. Despite transmission of HCV to all of the solid organ recipients HCV was not transmitted to the corneal transplant recipients.
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Research Interests: Hepatology, Humans, Female, Male, Young Adult, and 6 moreIncidence, British Columbia, Clinical Sciences, Aged, Middle Aged, and Adult
Effectively controlling infectious diseases requires quantitative comparisons of quarantine, infection control precautions, case identification and isolation, and immu- nization interventions. We used contact network epidemiol- ogy to... more
Effectively controlling infectious diseases requires quantitative comparisons of quarantine, infection control precautions, case identification and isolation, and immu- nization interventions. We used contact network epidemiol- ogy to predict the effect of various control policies for a mildly contagious disease, such as severe acute respira- tory syndrome, and a moderately contagious disease, such as smallpox. The success of an intervention depends
Research Interests: Medical Microbiology, Public Health, Emerging Infectious Diseases, Disease Outbreaks, Masks, and 11 moreHumans, Infection Control, Infectious Disease, Quarantine, British Columbia, Clinical Sciences, Spectrum, Public health systems and services research, Control Strategy, Respiratory Tract Infections, and Urban Population
Research Interests: Hepatitis C, Multidisciplinary, Canada, Humans, Female, and 7 moreMale, Incidence, Risk factors, PLoS one, Questionnaires, Adult, and Risk Factors
Hepatitis C virus (HCV) has a naturally occurring polymorphism, Q80K, in the nonstructural protein 3 (NS3) gene encoding the viral protease, which has been associated with reduced susceptibility to the direct-acting antiviral inhibitor... more
Hepatitis C virus (HCV) has a naturally occurring polymorphism, Q80K, in the nonstructural protein 3 (NS3) gene encoding the viral protease, which has been associated with reduced susceptibility to the direct-acting antiviral inhibitor simeprevir. Q80K is observed predominantly in HCV genotype 1a and seldom in other HCV genotypes; moreover, it has a markedly high prevalence in the United States. Here, we reconstruct the evolutionary history of this polymorphism to investigate why it is so highly localized in prevalence and whether it is stably transmitted between hosts. We found that the majority (96%) of HCV infections carrying Q80K were descended from a single lineage in which a Q80K substitution occurred around the 1940s in the United States, which implies that this polymorphism is likely highly transmissible. Furthermore, we identified 2 other substitutions in NS3 that may interact with Q80K and contribute to its stability. Our results imply that the current distribution and prevalence of Q80K are unlikely to change significantly in the short term.
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Twenty-four isolated double lung transplants (LTXs) have been performed in 22 patients with cystic fibrosis, with a follow-up of 4 to 47 months. Prior to LTX, all patients were colonized with Pseudomonas aeruginosa, and ten patients were... more
Twenty-four isolated double lung transplants (LTXs) have been performed in 22 patients with cystic fibrosis, with a follow-up of 4 to 47 months. Prior to LTX, all patients were colonized with Pseudomonas aeruginosa, and ten patients were also colonized with Pseudomonas cepacia. Both organisms were specifically sought before LTX. All patients who grew P cepacia before LTX did so after LTX. Five additional patients only grew this bacterium after LTX. There was no difference between those who grew P cepacia and those who did not in terms of data before LTX for age, weight, pulmonary function, and 6-min walk. After LTX, 7 of the 15 patients who had ever grown P cepacia died. No patient who grew only P aeruginosa died. The median survival in the subgroup with P cepacia was 28 days. Five of the seven died as a direct result of P cepacia pneumonia and sepsis. One died of cyclosporin A (cyclosporine) neurotoxicity with concurrent P cepacia pneumonia, and one died at the time of a retransplant for graft failure (associated with three bouts of P cepacia pneumonia and cytomegalovirus). Four of seven had not grown this bacterium before LTX. There were no perioperative factors, including antibiotic choices, that distinguished survivors and nonsurvivors. Overall 1-year survival is about 70 percent (15/22). Fourteen bouts of P cepacia pneumonia occurred in 12 patients. Four empyemas, one lung abscess, one suppurative pericarditis, and five cases of sinusitis were also due to this bacterium. In conclusion, P cepacia is responsible for excess morbidity and mortality after LTX. This organism is particularly lethal if isolated for the first time after LTX. Factors predicting its acquisition in this setting are unknown. While it is possible that the facial sinuses may act as an unrecognized reservoir or that patients or equipment provide a source, further study into the epidemiology of this organism is necessary to improve the survival of colonized patients undergoing LTX.
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Ribavirin is a guanosine analogue that normalizes serum liver enzymes in most nontransplant patients with chronic hepatitis C virus (HCV) infection. We conducted an uncontrolled pilot study of ribavirin in 9 liver transplantation... more
Ribavirin is a guanosine analogue that normalizes serum liver enzymes in most nontransplant patients with chronic hepatitis C virus (HCV) infection. We conducted an uncontrolled pilot study of ribavirin in 9 liver transplantation recipients that had persistently elevated liver enzymes, active hepatitis by liver biopsy, and HCV RNA in serum by polymerase chain reaction. Ribavirin was given orally at dosages of 800-1200 mg per day for 3 mo. All 9 patients promptly responded to ribavirin: mean (+/- SD) ALT decreased from 392 +/- 377 IU/L immediately before treatment to 199 +/- 185 and 68 +/- 37 IU/L after 1 and 12 weeks of treatment, respectively, complete normalization of enzymes occurred in 4 patients. None of the patients cleared the virus from their serum during therapy, and biochemical relapse occurred in all patients 4 +/- 4.2 weeks after cessation of therapy. The hepatitis activity index of liver biopsy specimens obtained before and at the cessation of therapy was similar. Ribavirin treatment was resumed in 4 patients because of increasing fatigue (2 patients), rising bilirubin (3), or increasing necroinflammation on liver biopsy (2); the biochemical response to the second course of therapy was similar to the first course in all 4 patients. Ribavirin caused reversible hemolysis in all patients, including symptomatic anemia in 3 patients that resolved after reduction of drug dosage. These results suggest that ribavirin may be of benefit in the treatment of HCV infection after liver transplantation. Further studies are needed to determine the optimal dosage and duration of therapy.