Population-based estimate of hepatitis C virus prevalence in Ontario, Canada.

BACKGROUND: Hepatitis C virus (HCV) is the most burdensome infectious illness in Canada. Current screening strategies miss a significant proportion of cases, leaving many undiagnosed. Elevated HCV prevalence in those born between 1945 and 1965 has prompted calls for birth-cohort screening in this group. However, Canada lacks population-level data to support this recommendation. We performed a serosurvey to obtain population-based HCV prevalence estimates in Ontario residents born between 1945-1974, to generate evidence for birth-cohort screening recommendations. METHODS: We tested anonymized residual sera in five-year age-sex bands from Ontario for anti-HCV antibody. We performed descriptive epidemiological analysis and used a logistic regression model to determine HCV risk-factors. RESULTS: Of 10,006 sera analyzed, 155 (1.55%, 95% confidence interval (CI) 1.32, 1.81) were positive for HCV antibody. Individuals born between 1950-1964 had a significantly higher combined prevalence of 1.92% (95% CI 1.56, 2.34) compared to 1.14% (95% CI 0.69, 1.77) (p = 0.04) for those born between 1970-1974. For males, comprising 107/155 (69.03%) of positive samples, the highest prevalence was 3.00% (95% CI 1.95, 4.39) for the 1960-1964 birth-cohort. For females, the highest prevalence was 1.56% (95% CI 0.83, 2.65) for those born between 1955-1959. Male sex was significantly associated with positive HCV serostatus. INTERPRETATION: HCV prevalence in Ontario is highest among those in this birth cohort, and higher than previous estimates. The prevalence estimates presented in our study provide important data to underpin birth-cohort screening recommendations.

Early impact of Ontario's human papillomavirus (HPV) vaccination program on anogenital warts (AGWs): A population-based assessment.

INTRODUCTION: This study aimed to evaluate the early population impact of Ontario's school-based human papillomavirus (HPV) vaccination program, implemented in September 2007 for grade 8 females, by comparing anogenital wart (AGW) health care utilization before and after vaccine program implementation, in program-eligible and program-ineligible cohorts, focusing on 15-26year olds. METHODS: Using a retrospective longitudinal population-based study design, health administrative data were used to identify incident AGWs and total health service utilization (HSU) for AGWs for Ontario residents 15years and older between April 1 2004 and March 31 2014. The study period was divided into two eras: the pre-vaccine program era and the vaccine program era. Negative binomial models were generated to analyze trends across time by age group and sex. We adjusted female rates for routine Papanicolaou (Pap) testing to address spillover effects of Pap smear policy changes on AGW diagnosis. RESULTS: Between fiscal years 2004 and 2013, AGW incidence decreased 2.6% on average per year in 15-17year old females, and total HSU for AGWs decreased an average of 4.8% and 2.2% per year in 15-17 and 18-20year old females. Comparing the vaccine era to the pre-vaccine era, AGW incidence decreased 6.5% in 18-20year old females, and AGW HSU decreased 13.8%, 11.1%, and 10.0% in 15-17, 18-20, and 21-23year old females respectively. In contrast, male AGW incidence rates increased an average of 4.1%, 2.8%, and 0.9% per year in 15-17, 21-23, and 24-26year old males respectively. AGW incidence rates increased 12.2% in 15-17year old males from the pre-vaccine to vaccine era. CONCLUSION: The decline in AGW incidence and HSU in program-eligible females suggests the school-based HPV vaccination program has had an early population impact in Ontario. The increasing AGW incidence in males suggests no early evidence of herd effects in males.

Health service utilisation for anogenital warts in Ontario, Canada prior to the human papillomavirus (HPV) vaccine programme introduction: a retrospective longitudinal population-based study.

OBJECTIVE: Trends in occurrence of anogenital warts (AGWs) can provide early evidence of human papillomavirus (HPV) vaccination programme impact on preventing HPV infection and HPV-induced lesions. The objective of this study was to provide a baseline of AGW epidemiology in Ontario prior to the introduction of the publicly-funded school-based HPV vaccination programme in September 2007. SETTING AND PARTICIPANTS: As a retrospective longitudinal population-based study, we used health administrative data as a proxy to estimate incident AGWs and total health service utilisation (HSU) for AGWs for all Ontario residents 15 years and older with valid health cards between 1 April 2003 and 31 March 2007. OUTCOME MEASURES: The outcome of interest was AGW healthcare utilisation identified using the International Classification of Diseases, 10th revision (ICD-10) diagnostic code for AGWs, as well as an algorithm for identifying AGW physician office visits in a database with a unique system of diagnostic and procedural codes. An AGW case was considered incident if preceded by 12 months without HSU for AGWs. Time trends by age group and sex were analysed. RESULTS: Between fiscal years 2003 and 2006, we identified 123,247 health service visits for AGWs by 51,436 Ontario residents 15 years and older. Incident AGWs peaked in females and males in the 21-23 year age group, at 3.74 per 1000 and 2.81 per 1000, respectively. HSU for AGWs peaked in females and males within the 21-23 year age group, at 9.34 per 1000 and 7.22 per 1000, respectively. CONCLUSIONS: To the best of our knowledge, this is the first population-based study of AGW incidence and HSU in Ontario. The sex and age distribution of individuals with incident and prevalent AGWs in Ontario was similar to that of other provinces before HPV vaccine programme implementation in Canada.

Homeodomain-interacting protein kinase (HIPK)-1 is required for splenic B cell homeostasis and optimal T-independent type 2 humoral response.

The homeodomain-interacting protein kinase (HIPK) family is comprised of four highly related serine/threonine kinases originally identified as co-repressors for various homeodomain-containing transcription factors. The HIPKs have been shown to be involved in growth regulation and apoptosis, with numerous studies highlighting HIPK regulation of the tumor suppressor p53. In this study, we have discovered a B cell homeostatic defect in HIPK1-deficient (HIPK1(-/-)) mice. Lymphopoietic populations within the thymus and bone marrow of HIPK1(-/-) mice appeared normal based upon FACS analysis; however, the spleen exhibited a reduced number of total B cells with a significant loss of transitional-1 and follicular B cell populations. Interestingly, the marginal zone B cell population was expanded in HIPK1(-/-) mice, yielding an increased frequency of these cells. HIPK1(-/-) B cells exhibited impaired cell division in response to B cell receptor cross-linking in vitro based upon thymidine incorporation or CFSE dilution; however, the addition of CD40L rescued HIPK1(-/-) proliferation to wild-type levels. Despite the expanded MZ B cell population in the HIPK1(-/-) mice, the T-independent type 2 humoral response was impaired. These data identify HIPK1 as a novel kinase required for optimal B cell function in mice.

Putting out the fire: coordinated suppression of the innate and adaptive immune systems by SOCS1 and SOCS3 proteins.

The mounting of an effective immune response requires the coordinated function of both the innate and the adaptive arm of the immune system. Cells from both types of immunity respond to antigenic stimuli through a variety of surface and intracellular receptors and produce cytokines that tightly orchestrate the inflammatory response. The operation of feedback control mechanisms that regulate the duration and the amplitude of antigenic and cytokine receptor signaling is therefore required to prevent hyper-activation of the immune system that could lead to tissue destruction or autoimmunity. Suppressor of cytokine signaling (SOCS) proteins have been identified as a negative feedback loop to cytokine signaling. Recently, the generation of genetically engineered mouse models permitted the evaluation of their function in different processes of the immune responses. In this article, we review new insights into the modular structure of SOCS proteins and the function of SOCS1 and SOCS3 to negatively regulate activation and/or differentiation pathways in macrophages, dendritic cells, and T lymphocytes. Thus, SOCS family proteins are components of an emerging immunoregulatory mechanism that maintains the coordinated balance of both innate and adaptive immune responses.