Mel Krajden | University of British Columbia (original) (raw)

Papers by Mel Krajden

Research paper thumbnail of Immunogenicity of 2 vs 3 Doses of the Quadrivalent Human Papillomavirus Vaccine in Girls Aged 9 to 13 Years After 60 Months

JAMA, Apr 25, 2017

Human papillomavirus (HPV) vaccines were originally approved with 3-dose schedules. However, 2 do... more Human papillomavirus (HPV) vaccines were originally approved with 3-dose schedules. However, 2 doses of HPV vaccine have been recommended 1 for girls younger than 15 years based on antibody response at 36 months, 2,3 although continued research on the duration of antibody persistence was advised. We report antibody response at 60 months after 2 doses of quadrivalent HPV vaccine.

Research paper thumbnail of Assessment of HPV 16 and HPV 18 antibody responses by pseudovirus neutralization, Merck cLIA and Merck total IgG LIA immunoassays in a reduced dosage quadrivalent HPV vaccine trial

Research paper thumbnail of Human Illness From Avian Influenza H7N3, British Columbia

Emerging infectious …, 2004

Avian influenza that infects poultry in close proximity to humans is a concern because of its pan... 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 ...

Research paper thumbnail of Is pre-treatment liver biopsy necessary for all hepatitis C genotypes?

Annals of hepatology: official journal of the Mexican Association of Hepatology

Current practice guidelines recommend liver biopsy prior to treatment of hepatitis C genotype-1 b... 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...

Research paper thumbnail of Projected Impact of HPV and LBC Primary Testing on Rates of Referral for Colposcopy in a Canadian Cervical Cancer Screening Program

Journal of obstetrics and gynaecology Canada : JOGC = Journal d'obstétrique et gynécologie du Canada : JOGC, 2015

To estimate the impact of implementing primary human papilloma virus liquid-based cytology (LBC) ... 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...

Research paper thumbnail of Self-Collected versus Clinician-Collected Sampling for Chlamydia and Gonorrhea Screening: A Systemic Review and Meta-Analysis

PLOS ONE, 2015

The increases in STI rates since the late 1990s in Canada have occurred despite widespread primar... 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.

Research paper thumbnail of Whole-Genome Sequencing of Measles Virus Genotypes H1 and D8 During Outbreaks of Infection Following the 2010 Olympic Winter Games Reveals Viral Transmission Routes

Journal of Infectious Diseases, 2015

Research paper thumbnail of Decreasing Hepatitis C Incidence Among a Population With Repeated Tests: British Columbia, Canada, 1993-2011

American journal of public health, Jan 11, 2015

We estimated HCV incidence among individuals who repeatedly underwent anti-HCV testing. We studie... more We estimated HCV incidence among individuals who repeatedly underwent anti-HCV testing. We studied HCV-negative individuals who had at least 2 tests between April 1992 and September 2012 in British Columbia, Canada. We calculated incidence as the number of new infections per 100 person-years at risk. From 1992 to 2012, 323 598 individuals who persistently tested negative and 7490 HCV seroconverters contributed 1 774 262 person-years of observation time. Incidence rates ranged from 2.66 infections per 100 person-years (95% confidence interval [CI] = 2.07, 3.35) in 1993 to 0.25 infections per 100 person-years (95% CI = 0.21, 0.29) in 2011. Rates declined sharply in the 1990s and declined more gradually in the 2000s. Incidence declined with age; highest incidence rates were among those aged 15 to 24 years. Incidence among male repeat testers exceeded that of female repeat testers across all years, although the gap narrowed over time. Addictions treatment, harm reduction, prevention edu...

Research paper thumbnail of Methamphetamine injecting is associated with phylogenetic clustering of hepatitis C virus infection among street-involved youth in Vancouver, Canada

Drug and Alcohol Dependence, 2015

Please cite this article in press as: Cunningham, E.B., et al., Methamphetamine injecting is asso... more Please cite this article in press as: Cunningham, E.B., et al., Methamphetamine injecting is associated with phylogenetic clustering of hepatitis C virus infection among street-involved youth in Vancouver, Canada. Drug Alcohol Depend. (2015), http://dx.a b s t r a c t Background: Among prospective cohorts of people who inject drugs (PWID), phylogenetic clustering of HCV infection has been observed. However, the majority of studies have included older PWID, representing distant transmission events. The aim of this study was to investigate phylogenetic clustering of HCV infection among a cohort of street-involved youth. Methods: Data were derived from a prospective cohort of street-involved youth aged 14-26 recruited between 2005 and 2012 in Vancouver, Canada (At Risk Youth Study, ARYS). HCV RNA testing and sequencing (Core-E2) were performed on HCV positive participants. Phylogenetic trees were inferred using maximum likelihood methods and clusters were identified using ClusterPicker (Core-E2 without HVR1, 90% bootstrap threshold, 0.05 genetic distance threshold). Results: Among 945 individuals enrolled in ARYS, 16% (n = 149, 100% recent injectors) were HCV antibody positive at baseline interview (n = 86) or seroconverted during follow-up (n = 63). Among HCV antibody positive participants with available samples (n = 131), 75% (n = 98) had detectable HCV RNA and 66% (n = 65, mean age 23, 58% with recent methamphetamine injection, 31% female, 3% HIV+) had available Core-E2 sequences. Of those with Core-E2 sequence, 14% (n = 9) were in a cluster (one cluster of three) or pair (two pairs), with all reporting recent methamphetamine injection. Recent methamphetamine injection was associated with membership in a cluster or pair (P = 0.009). Conclusion: In this study of street-involved youth with HCV infection and recent injecting, 14% demonstrated phylogenetic clustering. Phylogenetic clustering was associated with recent methamphetamine injection, suggesting that methamphetamine drug injection may play an important role in networks of HCV transmission.

Research paper thumbnail of A molecular phylogenetics-based approach for identifying recent hepatitis C virus transmission events

Infection, Genetics and Evolution, 2015

a b s t r a c t 35 Improved surveillance methods are needed to better understand the current hepa... more a b s t r a c t 35 Improved surveillance methods are needed to better understand the current hepatitis C virus (HCV) dis-36 ease burden and to monitor the impact of prevention and treatment interventions on HCV transmission 37 dynamics. Sanger sequencing (HCV NS5B, HVR1 and Core-E1-HVR1) and phylogenetics were applied to 38 samples from individuals diagnosed with HCV in British Columbia, Canada in 2011. This included individ-39 uals with two or three sequential samples collected <1 year apart. Patristic distances between sequential 40 samples were used to set cutoffs to identify recent transmission clusters. Factors associated with trans-41 mission clustering were analyzed using logistic regression. From 618 individuals, 646 sequences were 42 obtained. Depending on the cutoff used, 63 (10%) to 92 (15%) unique individuals were identified within 43 transmission clusters of predicted recent origin. Clustered individuals were more likely to be <40 years 44 old (Adjusted Odds Ratio (AOR) 2.12, 95% CI 1.21-3.73), infected with genotype 1a (AOR 6.60, 95% CI 45 1.98-41.0), and to be seroconverters with estimated infection duration of <1 year (AOR 3.13, 95% CI 46 1.29-7.36) or >1 year (AOR 2.19, 95% CI 1.22-3.97). 47 Conclusion: Systematic application of molecular phylogenetics may be used to enhance traditional 48 surveillance methods through identification of recent transmission clusters.

Research paper thumbnail of Integrated sentinel surveillance linking genetic, antigenic and epidemiologic monitoring of influenza vaccine-virus relatedness and effectiveness, 2013-14 season

The Journal of infectious diseases, Jan 17, 2015

Canada's Sentinel Physician Surveillance Network (SPSN) links genetic, antigenic and vaccine... 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'...

Research paper thumbnail of Obstetrical and neonatal outcomes among women infected with hepatitis C and their infants

Journal of obstetrics and gynaecology Canada : JOGC = Journal d'obstétrique et gynécologie du Canada : JOGC, 2014

(1) To describe obstetrical and neonatal outcomes among a cohort of hepatitis C virus (HCV) infec... more (1) To describe obstetrical and neonatal outcomes among a cohort of hepatitis C virus (HCV) infected women, comparing HCV RNA positive to HCV RNA negative women; (2) to characterize virologic and hepatic parameters associated with HCV infection during pregnancy; and (3) to describe the rate of HCV vertical transmission. We prospectively enrolled 145 HCV-positive pregnant women across British Columbia between 2000 and 2003. Participating women were monitored during pregnancy and their infants were followed to assess them for HCV infection. Maternal HCV RNA was assessed close to delivery. Seventy percent of women reported injection drug use as their primary risk factor for HCV acquisition. Observed rates of intrauterine fetal death, preterm delivery, small for gestational age, and low birth weight infants were 3.4%, 17.9%, 11.3%, and 12.5%, respectively, without a significant association with maternal HCV RNA status. The rate of cholestasis was 5.6% in the HCV RNA-positive group (6/108) and 2.8% in the HCV RNA-negative group (1/37) (P = 0.496). Serum alanine aminotransferase levels decreased significantly through pregnancy, and were significantly higher in HCV RNA-positive women than in HCV RNA-negative women after controlling for cholestasis, co-infections, and alcohol consumption. Among the HCV RNA-positive women, the median FIB-4 score was 0.67 (IQR 0.56 to 0.76) in the first trimester, 0.74 (IQR 0.52 to 1.18) in the second trimester, and 0.89 (IQR 0.52 to 1.09) in the third trimester (P = 0.02). The median HCV viral load at delivery was 424 561 IU/mL. The vertical transmission rate was 4.7% in HCV RNA-positive women, with no cases in HCV RNA-negative women. Because of the high rates of poor obstetrical outcomes found in this prospective cohort, population-level screening for HCV in pregnancy should be considered.

Research paper thumbnail of Hepatitis C and HIV prevalence using oral mucosal transudate, and reported drug use and sexual behaviours of youth in custody in British Columbia

Canadian journal of public health = Revue canadienne de santé publique

Youth in custody have high-risk drug use and sexual behaviours. HIV prevalence in this population... 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 paper thumbnail of The laboratory diagnosis of hepatitis B virus

The Canadian journal of infectious diseases & medical microbiology = Journal canadien des maladies infectieuses et de la microbiologie médicale / AMMI Canada, 2005

Hepatitis B virus (HBV) chronically infects approximately 250,000 Canadians and 350 million peopl... 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 ...

Research paper thumbnail of Clinical practice guidelines: prevention of cytomegalovirus disease after renal transplantation

Journal of the American Society of Nephrology : JASN, 1998

To develop a set of comprehensive, standardized, evidence-based guidelines for the use of antivir... 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 paper thumbnail of Long-term predictive value of a single cytomegalovirus (CMV) DNA PCR assay for CMV disease in human immunodeficiency virus-infected patients

Journal of clinical microbiology, 1998

Universal prophylaxis with oral ganciclovir is not cost-effective for the prevention of cytomegal... 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.

Research paper thumbnail of Evaluation of Roche Amplicor PCR assay for Mycobacterium tuberculosis

Journal of clinical microbiology, 1996

The Roche Amplicor Mycobacterium tuberculosis PCR test (RMtb-PCR) was compared with mycobacterial... 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 paper thumbnail of Mortality in a large community-based cohort of inner-city residents in Vancouver, Canada

CMAJ open, 2013

The Downtown Eastside is a robust and densely populated neighbourhood in Vancouver, Canada, that ... 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...

Research paper thumbnail of Reduction in cervical dysplasia in young women in British Columbia after introduction of the HPV vaccine: An ecological analysis

International Journal of Cancer, 2015

We report on the rates of cervical dysplasia in young women aged 15 to 22 years of age in British... more We report on the rates of cervical dysplasia in young women aged 15 to 22 years of age in British Columbia before and after the introduction of an HPV vaccine program. Rates of cervical intraepithelial neoplasia (CIN) 2+ for each age stratum (15-22) in the calendar years 2004-2012 for the province of British Columbia were obtained from the BC Cancer Agency&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;#39;s population-based cervical cancer program. Incidence rate ratios (IRR) of CIN2+ were described and compared before and after HPV vaccine program introduction in cohorts born in vaccine eligible years, and in non-vaccine eligible years using piece-wise Poisson regression analysis, and adjusted for age. Between 2004 and 2012, rates of CIN2 and CIN2+ in young women aged 15 to 22 in the province of British Columbia have decreased overall. After the introduction of the HPV vaccine program, the age adjusted IRR for CIN2+ for girls aged 15-17 decreased significantly from 0.91 (95%CI: 0.86; 0.98 p&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt;0.01) to 0.36 (95%CI: 0.18; 0.73 p&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt;0.01). During the same time period, no similar reduction was found in young women 18 to 22. After introduction of HPV vaccine program, IRR for CIN2+ in girls 15-17 was significantly reduced for CIN2+ (0.14; 95%CI 0.04, 0.47; p&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt;0.01) and CIN2 (0.1; 95% CI 0.02, 0.54; p&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt;0.01). This ecological analysis shows a significant reduction in CIN2+ lesions in young women aged 15 to 17 in British Columbia after the introduction of the HPV vaccine in girls despite vaccine uptake levels below 70%. This article is protected by copyright. All rights reserved.

Research paper thumbnail of Pre- and postpandemic estimates of 2009 pandemic influenza A(H1N1) seroprotection to inform surveillance-based incidence, by age, during the 2013-2014 epidemic in Canada

The Journal of infectious diseases, 2015

To understand the epidemic resurgence of influenza due to the 2009 pandemic influenza A(H1N1) str... 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...

Research paper thumbnail of Immunogenicity of 2 vs 3 Doses of the Quadrivalent Human Papillomavirus Vaccine in Girls Aged 9 to 13 Years After 60 Months

JAMA, Apr 25, 2017

Human papillomavirus (HPV) vaccines were originally approved with 3-dose schedules. However, 2 do... more Human papillomavirus (HPV) vaccines were originally approved with 3-dose schedules. However, 2 doses of HPV vaccine have been recommended 1 for girls younger than 15 years based on antibody response at 36 months, 2,3 although continued research on the duration of antibody persistence was advised. We report antibody response at 60 months after 2 doses of quadrivalent HPV vaccine.

Research paper thumbnail of Assessment of HPV 16 and HPV 18 antibody responses by pseudovirus neutralization, Merck cLIA and Merck total IgG LIA immunoassays in a reduced dosage quadrivalent HPV vaccine trial

Research paper thumbnail of Human Illness From Avian Influenza H7N3, British Columbia

Emerging infectious …, 2004

Avian influenza that infects poultry in close proximity to humans is a concern because of its pan... 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 ...

Research paper thumbnail of Is pre-treatment liver biopsy necessary for all hepatitis C genotypes?

Annals of hepatology: official journal of the Mexican Association of Hepatology

Current practice guidelines recommend liver biopsy prior to treatment of hepatitis C genotype-1 b... 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...

Research paper thumbnail of Projected Impact of HPV and LBC Primary Testing on Rates of Referral for Colposcopy in a Canadian Cervical Cancer Screening Program

Journal of obstetrics and gynaecology Canada : JOGC = Journal d'obstétrique et gynécologie du Canada : JOGC, 2015

To estimate the impact of implementing primary human papilloma virus liquid-based cytology (LBC) ... 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...

Research paper thumbnail of Self-Collected versus Clinician-Collected Sampling for Chlamydia and Gonorrhea Screening: A Systemic Review and Meta-Analysis

PLOS ONE, 2015

The increases in STI rates since the late 1990s in Canada have occurred despite widespread primar... 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.

Research paper thumbnail of Whole-Genome Sequencing of Measles Virus Genotypes H1 and D8 During Outbreaks of Infection Following the 2010 Olympic Winter Games Reveals Viral Transmission Routes

Journal of Infectious Diseases, 2015

Research paper thumbnail of Decreasing Hepatitis C Incidence Among a Population With Repeated Tests: British Columbia, Canada, 1993-2011

American journal of public health, Jan 11, 2015

We estimated HCV incidence among individuals who repeatedly underwent anti-HCV testing. We studie... more We estimated HCV incidence among individuals who repeatedly underwent anti-HCV testing. We studied HCV-negative individuals who had at least 2 tests between April 1992 and September 2012 in British Columbia, Canada. We calculated incidence as the number of new infections per 100 person-years at risk. From 1992 to 2012, 323 598 individuals who persistently tested negative and 7490 HCV seroconverters contributed 1 774 262 person-years of observation time. Incidence rates ranged from 2.66 infections per 100 person-years (95% confidence interval [CI] = 2.07, 3.35) in 1993 to 0.25 infections per 100 person-years (95% CI = 0.21, 0.29) in 2011. Rates declined sharply in the 1990s and declined more gradually in the 2000s. Incidence declined with age; highest incidence rates were among those aged 15 to 24 years. Incidence among male repeat testers exceeded that of female repeat testers across all years, although the gap narrowed over time. Addictions treatment, harm reduction, prevention edu...

Research paper thumbnail of Methamphetamine injecting is associated with phylogenetic clustering of hepatitis C virus infection among street-involved youth in Vancouver, Canada

Drug and Alcohol Dependence, 2015

Please cite this article in press as: Cunningham, E.B., et al., Methamphetamine injecting is asso... more Please cite this article in press as: Cunningham, E.B., et al., Methamphetamine injecting is associated with phylogenetic clustering of hepatitis C virus infection among street-involved youth in Vancouver, Canada. Drug Alcohol Depend. (2015), http://dx.a b s t r a c t Background: Among prospective cohorts of people who inject drugs (PWID), phylogenetic clustering of HCV infection has been observed. However, the majority of studies have included older PWID, representing distant transmission events. The aim of this study was to investigate phylogenetic clustering of HCV infection among a cohort of street-involved youth. Methods: Data were derived from a prospective cohort of street-involved youth aged 14-26 recruited between 2005 and 2012 in Vancouver, Canada (At Risk Youth Study, ARYS). HCV RNA testing and sequencing (Core-E2) were performed on HCV positive participants. Phylogenetic trees were inferred using maximum likelihood methods and clusters were identified using ClusterPicker (Core-E2 without HVR1, 90% bootstrap threshold, 0.05 genetic distance threshold). Results: Among 945 individuals enrolled in ARYS, 16% (n = 149, 100% recent injectors) were HCV antibody positive at baseline interview (n = 86) or seroconverted during follow-up (n = 63). Among HCV antibody positive participants with available samples (n = 131), 75% (n = 98) had detectable HCV RNA and 66% (n = 65, mean age 23, 58% with recent methamphetamine injection, 31% female, 3% HIV+) had available Core-E2 sequences. Of those with Core-E2 sequence, 14% (n = 9) were in a cluster (one cluster of three) or pair (two pairs), with all reporting recent methamphetamine injection. Recent methamphetamine injection was associated with membership in a cluster or pair (P = 0.009). Conclusion: In this study of street-involved youth with HCV infection and recent injecting, 14% demonstrated phylogenetic clustering. Phylogenetic clustering was associated with recent methamphetamine injection, suggesting that methamphetamine drug injection may play an important role in networks of HCV transmission.

Research paper thumbnail of A molecular phylogenetics-based approach for identifying recent hepatitis C virus transmission events

Infection, Genetics and Evolution, 2015

a b s t r a c t 35 Improved surveillance methods are needed to better understand the current hepa... more a b s t r a c t 35 Improved surveillance methods are needed to better understand the current hepatitis C virus (HCV) dis-36 ease burden and to monitor the impact of prevention and treatment interventions on HCV transmission 37 dynamics. Sanger sequencing (HCV NS5B, HVR1 and Core-E1-HVR1) and phylogenetics were applied to 38 samples from individuals diagnosed with HCV in British Columbia, Canada in 2011. This included individ-39 uals with two or three sequential samples collected <1 year apart. Patristic distances between sequential 40 samples were used to set cutoffs to identify recent transmission clusters. Factors associated with trans-41 mission clustering were analyzed using logistic regression. From 618 individuals, 646 sequences were 42 obtained. Depending on the cutoff used, 63 (10%) to 92 (15%) unique individuals were identified within 43 transmission clusters of predicted recent origin. Clustered individuals were more likely to be <40 years 44 old (Adjusted Odds Ratio (AOR) 2.12, 95% CI 1.21-3.73), infected with genotype 1a (AOR 6.60, 95% CI 45 1.98-41.0), and to be seroconverters with estimated infection duration of <1 year (AOR 3.13, 95% CI 46 1.29-7.36) or >1 year (AOR 2.19, 95% CI 1.22-3.97). 47 Conclusion: Systematic application of molecular phylogenetics may be used to enhance traditional 48 surveillance methods through identification of recent transmission clusters.

Research paper thumbnail of Integrated sentinel surveillance linking genetic, antigenic and epidemiologic monitoring of influenza vaccine-virus relatedness and effectiveness, 2013-14 season

The Journal of infectious diseases, Jan 17, 2015

Canada's Sentinel Physician Surveillance Network (SPSN) links genetic, antigenic and vaccine... 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'...

Research paper thumbnail of Obstetrical and neonatal outcomes among women infected with hepatitis C and their infants

Journal of obstetrics and gynaecology Canada : JOGC = Journal d'obstétrique et gynécologie du Canada : JOGC, 2014

(1) To describe obstetrical and neonatal outcomes among a cohort of hepatitis C virus (HCV) infec... more (1) To describe obstetrical and neonatal outcomes among a cohort of hepatitis C virus (HCV) infected women, comparing HCV RNA positive to HCV RNA negative women; (2) to characterize virologic and hepatic parameters associated with HCV infection during pregnancy; and (3) to describe the rate of HCV vertical transmission. We prospectively enrolled 145 HCV-positive pregnant women across British Columbia between 2000 and 2003. Participating women were monitored during pregnancy and their infants were followed to assess them for HCV infection. Maternal HCV RNA was assessed close to delivery. Seventy percent of women reported injection drug use as their primary risk factor for HCV acquisition. Observed rates of intrauterine fetal death, preterm delivery, small for gestational age, and low birth weight infants were 3.4%, 17.9%, 11.3%, and 12.5%, respectively, without a significant association with maternal HCV RNA status. The rate of cholestasis was 5.6% in the HCV RNA-positive group (6/108) and 2.8% in the HCV RNA-negative group (1/37) (P = 0.496). Serum alanine aminotransferase levels decreased significantly through pregnancy, and were significantly higher in HCV RNA-positive women than in HCV RNA-negative women after controlling for cholestasis, co-infections, and alcohol consumption. Among the HCV RNA-positive women, the median FIB-4 score was 0.67 (IQR 0.56 to 0.76) in the first trimester, 0.74 (IQR 0.52 to 1.18) in the second trimester, and 0.89 (IQR 0.52 to 1.09) in the third trimester (P = 0.02). The median HCV viral load at delivery was 424 561 IU/mL. The vertical transmission rate was 4.7% in HCV RNA-positive women, with no cases in HCV RNA-negative women. Because of the high rates of poor obstetrical outcomes found in this prospective cohort, population-level screening for HCV in pregnancy should be considered.

Research paper thumbnail of Hepatitis C and HIV prevalence using oral mucosal transudate, and reported drug use and sexual behaviours of youth in custody in British Columbia

Canadian journal of public health = Revue canadienne de santé publique

Youth in custody have high-risk drug use and sexual behaviours. HIV prevalence in this population... 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 paper thumbnail of The laboratory diagnosis of hepatitis B virus

The Canadian journal of infectious diseases & medical microbiology = Journal canadien des maladies infectieuses et de la microbiologie médicale / AMMI Canada, 2005

Hepatitis B virus (HBV) chronically infects approximately 250,000 Canadians and 350 million peopl... 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 ...

Research paper thumbnail of Clinical practice guidelines: prevention of cytomegalovirus disease after renal transplantation

Journal of the American Society of Nephrology : JASN, 1998

To develop a set of comprehensive, standardized, evidence-based guidelines for the use of antivir... 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 paper thumbnail of Long-term predictive value of a single cytomegalovirus (CMV) DNA PCR assay for CMV disease in human immunodeficiency virus-infected patients

Journal of clinical microbiology, 1998

Universal prophylaxis with oral ganciclovir is not cost-effective for the prevention of cytomegal... 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.

Research paper thumbnail of Evaluation of Roche Amplicor PCR assay for Mycobacterium tuberculosis

Journal of clinical microbiology, 1996

The Roche Amplicor Mycobacterium tuberculosis PCR test (RMtb-PCR) was compared with mycobacterial... 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 paper thumbnail of Mortality in a large community-based cohort of inner-city residents in Vancouver, Canada

CMAJ open, 2013

The Downtown Eastside is a robust and densely populated neighbourhood in Vancouver, Canada, that ... 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...

Research paper thumbnail of Reduction in cervical dysplasia in young women in British Columbia after introduction of the HPV vaccine: An ecological analysis

International Journal of Cancer, 2015

We report on the rates of cervical dysplasia in young women aged 15 to 22 years of age in British... more We report on the rates of cervical dysplasia in young women aged 15 to 22 years of age in British Columbia before and after the introduction of an HPV vaccine program. Rates of cervical intraepithelial neoplasia (CIN) 2+ for each age stratum (15-22) in the calendar years 2004-2012 for the province of British Columbia were obtained from the BC Cancer Agency&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;#39;s population-based cervical cancer program. Incidence rate ratios (IRR) of CIN2+ were described and compared before and after HPV vaccine program introduction in cohorts born in vaccine eligible years, and in non-vaccine eligible years using piece-wise Poisson regression analysis, and adjusted for age. Between 2004 and 2012, rates of CIN2 and CIN2+ in young women aged 15 to 22 in the province of British Columbia have decreased overall. After the introduction of the HPV vaccine program, the age adjusted IRR for CIN2+ for girls aged 15-17 decreased significantly from 0.91 (95%CI: 0.86; 0.98 p&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt;0.01) to 0.36 (95%CI: 0.18; 0.73 p&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt;0.01). During the same time period, no similar reduction was found in young women 18 to 22. After introduction of HPV vaccine program, IRR for CIN2+ in girls 15-17 was significantly reduced for CIN2+ (0.14; 95%CI 0.04, 0.47; p&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt;0.01) and CIN2 (0.1; 95% CI 0.02, 0.54; p&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt;0.01). This ecological analysis shows a significant reduction in CIN2+ lesions in young women aged 15 to 17 in British Columbia after the introduction of the HPV vaccine in girls despite vaccine uptake levels below 70%. This article is protected by copyright. All rights reserved.

Research paper thumbnail of Pre- and postpandemic estimates of 2009 pandemic influenza A(H1N1) seroprotection to inform surveillance-based incidence, by age, during the 2013-2014 epidemic in Canada

The Journal of infectious diseases, 2015

To understand the epidemic resurgence of influenza due to the 2009 pandemic influenza A(H1N1) str... 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...