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Background: Changes in microbiota composition as a result of antibiotics use in early life has been proposed as a possible contributor in the aetiology of autism spectrum disorders (ASD). We aimed to examine the association between early life antibiotic exposure and risk of ASD.Methods: This was a population-based cohort study which included all live births in Manitoba, Canada, between 1 April 1998 and 31 March 2016. We used administrative health data from the Manitoba Population Research Data Repository. Exposure was defined as having filled one or more antibiotic prescription during the first year of life. The main outcome was ASD diagnosis. Cox proportional hazards regression models were used to estimate the risk of developing ASD in the overall population and in a sibling cohort.Results: Of all subjects in the cohort (n = 214 834), 94 024 (43.8%) filled an antibiotic prescription during the first year of life. During follow-up, 2965 children received an ASD diagnosis. Compared with children who did not use antibiotics during the first year of life, those who received antibiotics had a reduced risk of ASD [adjusted hazardz ratio (HR) 0.91, 95% confidence interval (CI) 0.84-0.99). Number of treatment courses and cumulative duration of antibiotic exposure were not associated with ASD. In the sibling-controlled analysis, early life antibiotic exposure was not associated with ASD (adjusted HR 1.03, 95% CI 0.86-1.23).Conclusions: Our findings suggested no clinically significant association between early life antibiotics exposure and risk of autism spectrum disorders, and should provide reassurance to concerned prescribers and parents. [ABSTRACT FROM AUTHOR]

Preclinical studies suggest statins may help prevent prostate cancer (PC), but epidemiologic results are mixed. Many epidemiological studies have relatively short prediagnosis drug exposure data, which may miss some statin use. We completed a nested case–control study investigating the impact of statin use on PC diagnosis and clinically significant PC using data from men aged ≥40 years in the Canadian province of Saskatchewan between 1990 and 2010. Drug exposure histories were derived from a population‐based prescription drug database. We used conditional logistic regression to model use of statins as a class and stratified analyses for groups defined by lipophilicity. Clinically significant PC was defined as Gleason score 8–10 OR stage C or D or III or IV at diagnosis. 12,745 cases of PC were risk‐set matched on age and geographic location to 50,979 controls. Greater than 90% of subjects had prediagnosis drug exposure histories >15 years. 2,064 (16.2%) cases and 7,956 (15.6%) controls were dispensed one or more statin prescriptions. In multivariable models, ever prescription of statins was not associated with PC diagnosis (OR 0.97; 95% CI 0.90–1.05). Neither lipophilic statins (OR 0.96, 95% CI 0.88–1.04) nor hydrophilic statins (OR 1.06, 95% CI 0.95–1.20) impacted PC diagnosis. There was no effect of the dose or duration of statin use. Diagnosis of clinically significant PC decreased with statin use (OR 0.84, 95% CI 0.73–0.97). Statin use is not associated with overall PC risk, regardless of duration or dose of statin exposure. Statin use is associated with a decreased risk of clinically significant PC. [ABSTRACT FROM AUTHOR]

Introduction: Under-reporting of pertussis cases is a longstanding challenge. We estimated the true number of pertussis cases in Ontario using multiple data sources, and evaluated the completeness of each source. Methods: We linked data from multiple sources for the period 2009 to 2015: public health reportable disease surveillance data, public health laboratory data, and health administrative data (hospitalizations, emergency department visits, and physician office visits). To estimate the total number of pertussis cases in Ontario, we used a three-source capture-recapture analysis stratified by age (infants, or aged one year and older) and adjusting for dependency between sources. We used the Bayesian Information Criterion to compare models. Results: Using probable and confirmed reported cases, laboratory data, and combined hospitalizations/emergency department visits, the estimated total number of cases during the six-year period amongst infants was 924, compared with 545 unique observed cases from all sources. Using the same sources, the estimated total for those aged 1 year and older was 12,883, compared with 3,304 observed cases from all sources. Only 37% of infants and 11% for those aged 1 year and over admitted to hospital or seen in an emergency department for pertussis were reported to public health. Public health reporting sensitivity varied from 2% to 68% depending on age group and the combination of data sources included. Sensitivity of combined hospitalizations and emergency department visits varied from 37% to 49% and of laboratory data from 1% to 50%. Conclusions: All data sources contribute cases and are complementary, suggesting that the incidence of pertussis is substantially higher than suggested by routine reports. The sensitivity of different data sources varies. Better case identification is required to improve pertussis control in Ontario. [ABSTRACT FROM AUTHOR]

Background. Canada's Sentinel Physician Surveillance Network links genetic, antigenic, and vaccine effectiveness (VE) measures in an integrated platform of influenza monitoring, described here for the 2013-2014 influenza season of resurgent A(H1N1)pdm09 and late-season type B activity. Methods. VE was estimated as [1 - odds ratio] × 100% and compared vaccination status between individuals who tested positive (cases) and those who tested negative (controls) for influenza virus. Vaccine-virus relatedness was assessed by genomic sequence analysis and hemagglutination inhibition assays. Results. Analyses included 1037 controls (of whom 33% were vaccinated) and 663 cases (of whom 14% were vaccinated). A total of 415 cases tested positive for A(H1N1)pdm09 virus, 15 tested positive for A(H3N2) virus, 191 tested positive for B/Yamagata-lineage virus, 6 tested positive for B/Victoria-lineage virus, and 36 tested positive for viruses of unknown subtype or lineage. A(H1N1)pdm09 viruses belonged to clade 6B, distinguished by a K163Q substitution, but remained antigenically similar to the A/California/07/2009-like vaccine strain, with an adjusted VE of 71% (95% confidence interval [CI], 58%-80%). Most B/Yamagata-lineage viruses (83%) clustered phylogenetically with the prior (ie, 2012-2013) season's B/Wisconsin/01/2010-like clade 3 vaccine strain, while only 17% clustered with the current (ie, 2013-2014) season's B/Massachusetts/02/2012-like clade 2 vaccine strain. The adjusted VE for B/Yamagata-lineage virus was 73% (95% CI, 57%-84%), with a lower VE obtained after partial calendar-time adjustment for clade-mismatched B/Wisconsin/01/2010-like virus (VE, 63%; 95% CI, 41%-77%), compared with that for clade-matched B/Massachusetts/02/2012-like virus (VE, 88%; 95% CI, 48%-97%). No A(H3N2) viruses clustered with the A/Texas/50/2012-like clade 3C.1 vaccine strain, and more than half were antigenically mismatched, but sparse data did not support VE estimation. Conclusions. VE corresponded with antigenically conserved A(H1N1)pdm09 and lineage-matched B/Yamagata viruses with clade-level variation. Surveillance linking genotypic, phenotypic, and epidemiologicmeasures of vaccine-virus relatedness and effectiveness could better inform predictions of vaccine performance and reformulation. [ABSTRACT FROM AUTHOR]

Background: Despite the public health significance of annual influenza outbreaks, the literature comparing the epidemiology of influenza A and B infections is limited and dated and may not reflect recent trends. In Canada, the relative contribution of influenza A and B to the burden of morbidity is not well understood. We examined rates of laboratory-confirmed cases of influenza A and B (LCI-A and LCI-B) in the Canadian province of Manitoba between 1993 and 2008 and compared cases of the two types in terms of socio-demographic and clinical characteristics. Methods: Laboratory-confirmed cases of influenza A and B in Manitoba between 1993 and 2008 were identified from the Cadham Provincial Laboratory (CPL) Database and linked to de-identified provincial administrative health records. Crude and age-adjusted incidence rates of LCI-A and LCI-B were calculated. Demographic characteristics, health status, health service use, and vaccination history were compared by influenza type. Results: Over the study period, 1,404 of LCI-A and 445 cases of LCI-B were diagnosed, corresponding to an annual age-standardized rate of 7.2 (95% CI: 6.5-7.9) for LCI-A and 2.2 (CI: 1.5 - 3.0) per 100,000 person-years for LCI-B. Annual rates fluctuated widely but there was less variation in the LCI-B rates. For LCI-A, but not LCI-B, incidence was inversely related to household income. Older age, urban residence and past hospitalization were associated with increased detection of LCI-A whereas receipt of the influenza vaccine was associated with decreased LCI-A detection. Once socio-demographic variables were controlled, having a pre-existing chronic disease or immune suppression was not related to influenza type. Conclusion: Influenza A and B affected different segments of the population. Older age was associated with increased LCI-A detection, but not with pre-existing chronic diseases. This information may be useful to public health professionals in planning and evaluating new and existing seasonal influenza vaccines. [ABSTRACT FROM AUTHOR]

Background: Influenza vaccine effectiveness (VE) is generally interpreted in the context of vaccine match/mismatch to circulating strains with evolutionary drift in the latter invoked to explain reduced protection. During the 2012–13 season, however, detailed genotypic and phenotypic characterization shows that low VE was instead related to mutations in the egg-adapted H3N2 vaccine strain rather than antigenic drift in circulating viruses. Methods/Findings: Component-specific VE against medically-attended, PCR-confirmed influenza was estimated in Canada by test-negative case-control design. Influenza A viruses were characterized genotypically by amino acid (AA) sequencing of established haemagglutinin (HA) antigenic sites and phenotypically through haemagglutination inhibition (HI) assay. H3N2 viruses were characterized in relation to the WHO-recommended, cell-passaged vaccine prototype (A/Victoria/361/2011) as well as the egg-adapted strain as per actually used in vaccine production. Among the total of 1501 participants, influenza virus was detected in 652 (43%). Nearly two-thirds of viruses typed/subtyped were A(H3N2) (394/626; 63%); the remainder were A(H1N1)pdm09 (79/626; 13%), B/Yamagata (98/626; 16%) or B/Victoria (54/626; 9%). Suboptimal VE of 50% (95%CI: 33–63%) overall was driven by predominant H3N2 activity for which VE was 41% (95%CI: 17–59%). All H3N2 field isolates were HI-characterized as well-matched to the WHO-recommended A/Victoria/361/2011 prototype whereas all but one were antigenically distinct from the egg-adapted strain as per actually used in vaccine production. The egg-adapted strain was itself antigenically distinct from the WHO-recommended prototype, and bore three AA mutations at antigenic sites B [H156Q, G186V] and D [S219Y]. Conversely, circulating viruses were identical to the WHO-recommended prototype at these positions with other genetic variation that did not affect antigenicity. VE was 59% (95%CI:16–80%) against A(H1N1)pdm09, 67% (95%CI: 30–85%) against B/Yamagata (vaccine-lineage) and 75% (95%CI: 29–91%) against B/Victoria (non-vaccine-lineage) viruses. Conclusions: These findings underscore the need to monitor vaccine viruses as well as circulating strains to explain vaccine performance. Evolutionary drift in circulating viruses cannot be regulated, but influential mutations introduced as part of egg-based vaccine production may be amenable to improvements. [ABSTRACT FROM AUTHOR]

Please cite this paper as: Mahmud et al. (2012) Outbreaks of influenza-like illness in long-term care facilities in Winnipeg, Canada. Influenza and Other Respiratory Viruses 10.1111/irv.12052 Background Outbreaks of influenza-like illness (ILI) are common in long-term care facilities (LTCFs) and result in significant morbidity and mortality among residents. Objectives We describe patterns of reported ILI outbreaks in LTCFs in Winnipeg, Canada, and examine LTCF and outbreak characteristics that influence the clinical outcomes of these outbreaks. Methods We analyzed the electronic records of all ILI outbreaks reported by LTCFs in Winnipeg from 2003 to 2011. Outbreak duration, ILI attack rates among staff and residents, and residents' death rates were calculated by presumed viral etiology, staff vaccination rates, type of influenza chemoprophylaxis used, and time to notification to public health. Results Of a total of 154 reported outbreaks, most ( N = 80) were attributed to influenza, and these outbreaks tended to have higher attack and death rates among LTCF residents compared with outbreaks caused by other respiratory viruses (12) or those of unknown etiology (62). About 92% of residents and 38% of staff of the average LTCFs were vaccinated. Chemoprophylaxis was used in 57·5% of influenza outbreaks. Regardless of presumed viral etiology, outbreaks reported within 3 days of onset ended sooner and had lower attack and mortality rates among residents. Conclusions Influenza-like illness outbreaks still occur among highly immunized LTCF residents, so in addition to vaccination of staff and residents, it is important to maintain competent infection control practices. Early identification and notification to public health authorities and possibly early initiation of control measures could improve clinical outcomes of ILI outbreaks. [ABSTRACT FROM AUTHOR]

In 1960, it was discovered that Simian Virus 40 (SV40) contaminated up to 30% of the poliovirus vaccines in the US. This contamination arose because the vaccines were produced in monkey kidney cell cultures harboring SV40 between 1955 and 1963. During this period, approximately 90% of children and 60% of adults in the USA were inoculated for polio and possibly exposed to SV40. Many epidemiologic and molecular pathogenesis studies have been conducted in order to identify potential cancer risks since this ‘natural’ experiment began. Productive SV40 infection has the potential to initiate malignancy in a variety of target tissues. Epidemiological studies that investigated the relationship between SV40 infection and cancer risks have yielded mixed results. Studies can be grouped into three categories based on their exposure definition of SV40 infection: (1) use of vaccination or birth cohorts as proxy variables for infection, (2) follow-up of children of pregnant women who received polio vaccines, and (3) direct molecular detection of the virus or serologic detection of anti-SV40 antibody responses. A meta-analysis of five published studies did not support the hypothesis that SV40 exposure increases the overall risk of cancer incidence or cancer mortality. The analysis of specific cancer sites is largely inconclusive because of substantial problems that most studies have had in reliably defining exposure, defining latency effects, or dealing with confounding and other biases. A new generation of molecular epidemiologic studies is necessary to properly address these issues.Oncogene (2004) 23, 6535-6540. doi:10.1038/sj.onc.1207877 [ABSTRACT FROM AUTHOR]

• Acellular vaccine provides moderate protection in the years following vaccination. • Young children who follow the vaccine schedule are well protected from pertussis. • The decrease in protection after 5 years is consistent with waning immunity. Pertussis is still frequently reported in Canada. In Alberta, pertussis incidence ranged from 1.8 to 20.5 cases per 100,000 persons for 2004–2015. Most cases occurred in those aged <15 years. In Alberta, acellular formulations replaced whole-cell in 1997. We investigated pertussis vaccine effectiveness (VE) using a test-negative design (TND) study. We included all persons who had a real-time PCR laboratory test for Bordetella pertussis between January 1, 2010 and August 31, 2015, in the province of Alberta, Canada. Vaccination history was obtained from Alberta's immunization repository. Vaccination status was classified as complete, incomplete, or unvaccinated, based on the province's vaccination schedule. Persons who had received ≥one dose of whole cell vaccine were excluded from analysis. Multivariable logistic regression models were used to estimate adjusted odds ratios (aOR) and 95% confidence intervals (95% CI) for pertussis infection by time since last vaccination. We adjusted for vaccination status, age, sex, neighbourhood income, urban/rural status, and the presence of a co-morbid condition. VE was calculated as [(1 − aOR) * 100]. Of the 12,149 tests available, 936 (7.7%) were positive for Bordetella pertussis. Among the full cohort, VE was 90% (95% CI 87–92%) at 1 year, 81% (95% CI 77–85%) at 1–3 years, 76% (95% CI 68–82%) at 4–7 years, and 37% (95% CI 11–56%) at 8 or more years since a last dose of acellular pertussis vaccine. Pertussis VE was highest in the first year after vaccination, then declined noticeably as years since a last vaccination increased. Our results suggest that a large number of adolescents and adults are susceptible to infection with Bordetella pertussis. Regular boosters throughout childhood, adolescence, and during pregnancy may be needed. [ABSTRACT FROM AUTHOR]

Background Few studies in North America have quantified the risks of second malignant neoplasms (SMNs) among survivors of childhood non-central nervous system (non-CNS) embryonal tumours due to their rarity. We aimed to investigate these risks by combining population-based data from the United States of America and Canada. Methods We evaluated patients with childhood non-CNS embryonal tumours reported to the Surveillance Epidemiology and End Results program and eight Canadian cancer registries from 1969 to 2010. Standardised incidence ratio (SIR) and cumulative incidence of SMNs were calculated. Subgroup analyses were conducted by the type of first primary cancer, age at first primary diagnosis and follow-up duration. Findings Of the 13,107 survivors, 190 SMNs were reported over 134,548 person-years of follow-up. The SIR for all SMNs combined was 6.4 (95% confidence interval [CI]: 5.5–7.4). Most site-specific SIRs were significantly increased, ranging from 36 (95% CI: 26–49) for bone and joint cancer to 3.1 (95% CI: 1.5–5.2) for brain tumour. The risk for second malignancies declined as the time elapsed from the first primary diagnosis and was less prominent for patients first diagnosed at age 1–4 years. Notably, rhabdomyosarcoma survivors had a higher risk for SMNs than those with other first primaries. The overall cumulative incidence of SMNs was 1.0% at 10 years, increasing to 2.2% at 20 years and 4.1% at 30 years. Interpretation Survivors with childhood non-CNS embryonal tumours faced an increased risk for SMNs compared to the general population. The risk variations observed in different patient categories may help target prevention strategies in high-risk subgroups. [ABSTRACT FROM AUTHOR]