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Didelot X.,Imperial College London | Gardy J.,British Columbia Center for Disease Control | Gardy J.,University of British Columbia | Colijn C.,Imperial College London
Molecular Biology and Evolution | Year: 2014

Genomics is increasingly being used to investigate disease outbreaks, but an important question remains unanswered - how well do genomic data capture known transmission events, particularly for pathogens with long carriage periods or large within-host population sizes? Here we present a novel Bayesian approach to reconstruct densely sampled outbreaks from genomic data while considering within-host diversity. We infer a time-labeled phylogeny using Bayesian evolutionary analysis by sampling trees (BEAST), and then infer a transmission network via a Monte Carlo Markov chain. We find that under a realistic model of within-host evolution, reconstructions of simulated outbreaks contain substantial uncertainty even when genomic data reflect a high substitution rate. Reconstruction of a real-world tuberculosis outbreak displayed similar uncertainty, although the correct source case and several clusters of epidemiologically linked cases were identified. We conclude that genomics cannot wholly replace traditional epidemiology but that Bayesian reconstructions derived from sequence data may form a useful starting point for a genomic epidemiology investigation. © The Author 2014.


Skowronski D.M.,British Columbia Center for Disease Control
BMJ (Clinical research ed.) | Year: 2011

To assess the effectiveness of the pandemic influenza A/H1N1 vaccine used in Canada during autumn 2009. Test negative incident case-control study based on sentinel physician surveillance system. Community based clinics contributing to sentinel networks in British Columbia, Alberta, Ontario, and Quebec, Canada. 552 patients who presented to a sentinel site within seven days of onset of influenza-like illness during the primary analysis period between 8 November and 5 December 2009; participants were mostly (>80%) children and adults under 50 years old. Monovalent AS03 adjuvanted pandemic influenza A/H1N1 vaccine as the predominant formulation (>95%) distributed in Canada. Vaccine effectiveness calculated as 1-(odds ratio for influenza in vaccinated (received pandemic H1N1 vaccine at least two weeks before onset of influenza-like illness) versus unvaccinated participants), with adjustment for age, comorbidity, province, timeliness of specimen collection, and week of illness onset. Sensitivity analyses explored the influence of varying analysis periods between 1 November and 31 December, receipt of trivalent seasonal influenza vaccine, and restriction to participants without comorbidity. During the primary analysis period, pandemic H1N1 was detected by reverse transcription polymerase chain reaction in 209/552 (38%) participants; rates were highest in children and young adults (40%) and lowest in people aged 65 or over (9%). Among the 209 cases, 35 (17%) reported comorbidity compared with 80/343 (23%) controls. Two (1%) cases had received pandemic H1N1 vaccine at least two weeks before the onset of illness, compared with 58/343 (17%) controls, all single dose. Adjusted vaccine effectiveness overall was 93% (95% confidence interval 69% to 98%). High estimates of vaccine protection-generally at least 90%-were maintained across most sensitivity analyses. Although limited by a small number of vaccine failures, this study suggests that the monovalent AS03 adjuvanted vaccine used in Canada during autumn 2009 was highly effective in preventing medically attended, laboratory confirmed pandemic H1N1 illness, with reference in particular to a single dose in children and young adults.


De Serres G.,Laval University | Skowronski D.M.,British Columbia Center for Disease Control | Wu X.W.,MedImmune | Ambrose C.S.,MedImmune
Eurosurveillance | Year: 2013

The test-negative design (TND) is an efficient form of case-control study commonly applied to influenza vaccine effectiveness (VE) estimation. TND validity is predicated on the core assumption that the intervention (vaccine) has no effect on other non-targeted aetiologies resulting in similar illness/disease. Here we verify this core assumption and compare efficacy estimates derived by the TND versus classical per-protocol analysis of four datasets obtained from randomised placebo-controlled clinical trials (RCT) of the live attenuated influenza vaccine (LAIV) in children ≤7 years-old and the elderly ≥60 years-old. We further assess generalisability of the TND approach in two other RCT datasets to evaluate monoclonal antibody in the prevention of respiratory syncytial virus (RSV) hospitalisation. Efficacy estimates and their confidence intervals were virtually identical for per-protocol RCT versus TND analyses of LAIV and also for RSV monoclonal antibody. Neither LAIV nor monoclonal antibodies affected the risk of disease aetiologies that were not specifically targeted by the respective interventions (e.g. other respiratory viruses). This study validates the core assumption of the TND approach for influenza vaccine efficacy estimation and confirms the accuracy and precision of its estimates compared to the gold standard of classic per-protocol RCT analysis of the same data sets. The TND approach is generalisable for other conditions such as RSV for which the core assumption is also met. However, when used in observational studies, the TND, like all designs, still requires assessment for bias and confounding that may exist in the absence of randomised participation and blinded follow-up.


Henderson S.B.,British Columbia Center for Disease Control | Henderson S.B.,University of British Columbia | Johnston F.H.,Menzies Research Institute
Current Opinion in Allergy and Clinical Immunology | Year: 2012

Purpose of Review: Exposure to forest fire smoke is episodic, which makes its health effects challenging to study. We review the newest contributions to a growing literature on acute respiratory outcomes. Recent Findings: Smoke exposure was associated with increases in self-reported symptoms, medication use, outpatient physician visits, emergency room visits, hospital admissions, and mortality. The associations were strongest for the outcomes most specific to asthma. Summary: Studies with varied approaches to exposure assessment and varied measures of respiratory outcomes were consistent among themselves, and consistent with most previous work. © 2012 Wolters Kluwer Health | Lippincott Williams & Wilkins.


Gottlieb S.L.,Centers for Disease Control and Prevention | Xu F.,Centers for Disease Control and Prevention | Brunham R.C.,British Columbia Center for Disease Control
Sexually Transmitted Diseases | Year: 2013

We critically reviewed randomized controlled trials evaluating chlamydia screening to prevent pelvic inflammatory disease (PID) and explored factors affecting interpretation and translation of trial data into public health prevention. Taken together, data from these trials offer evidence that chlamydia screening and treatment is an important and useful intervention to reduce the risk of PID among young women. However, the magnitude of benefit to be expected from screening may have been overestimated based on the earliest trials. It is likely that chlamydia screening programs have contributed to declines in PID incidence through shortening prevalent infections, although the magnitude of their contribution remains unclear. Program factors such as screening coverage as well as natural history factors such as risk of PID after repeat chlamydia infection can be important in determining the impact of chlamydia screening on PID incidence in a population. Uptake of chlamydia screening is currently suboptimal, and expansion of screening among young, sexually active women remains a priority. To reduce transmission and repeat infections, implementation of efficient strategies to treat partners of infected women is also essential. Results of ongoing randomized evaluations of the effect of screening on community-wide chlamydia prevalence and PID will also be valuable. Copyright © 2013 American Sexually Transmitted Diseases Association All rights reserved.

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