Identification of SNPs Associated with Variola Virus Virulence

Background: Decades after the eradication of smallpox, its etiological agent, variola virus (VARV), remains a threat as a potential bioweapon. Outbreaks of smallpox around the time of the global eradication effort exhibited variable case fatality rates (CFRs), likely attributable in part to complex viral genetic determinants of smallpox virulence. We aimed to identify genome-wide single nucleotide polymorphisms associated with CFR. We evaluated unadjusted and outbreak geographic location-adjusted models of single SNPs and two- and three-way interactions between SNPs. Findings: Using the data mining approach multifactor dimensionality reduction (MDR), we identified five VARV SNPs in models significantly associated with CFR. The topper forming unadjusted model and adjusted models both revealed the same two-way gene-gene interaction. We discuss the biological plausibility of the influence of the SNPs identified these and other significant models on the strain-specific virulence of VARV. Conclusions: We have identified genetic loci in the VARV genome that are statistically associated with VARV virulence as measured by CFR. While our ability to infer a causal relationship between the specific SNPs identified in our analysis and VARV virulence is limited, our results suggest that smallpox severity is in part associated with VARV strain variation and that VARV virulence may be determined by multiple genetic loci. This study represents the first application of MDR to the identification of pathogen gene-gene interactions for predicting infectious disease outbreak severity

Multi-Criteria Decision Analysis as an Innovative Approach to Managing Zoonoses: Results from a Study on Lyme Disease in Canada

ackground: Zoonoses are a growing international threat interacting at the human-animal-environment interface and call for transdisciplinary and multi-sectoral approaches in order to achieve effective disease management. The recent emergence of Lyme disease in Quebec, Canada is a good example of a complex health issue for which the public health sector must find protective interventions. Traditional preventive and control interventions can have important environmental, social and economic impacts and as a result, decision-making requires a systems approach capable of integrating these multiple aspects of interventions. This paper presents the results from a study of a multi-criteria decision analysis (MCDA) approach for the management of Lyme disease in Quebec, Canada. MCDA methods allow a comparison of interventions or alternatives based on multiple criteria. Methods: MCDA models were developed to assess various prevention and control decision criteria pertinent to a comprehensive management of Lyme disease: a first model was developed for surveillance interventions and a second was developed for control interventions. Multi-criteria analyses were conducted under two epidemiological scenarios: a disease emergence scenario and an epidemic scenario. Results: In general, we observed a good level of agreement between stakeholders. For the surveillance model, the three preferred interventions were: active surveillance of vectors by flagging or dragging, active surveillance of vectors by trapping of small rodents and passive surveillance of vectors of human origin. For the control interventions model, basic preventive communications, human vaccination and small scale landscaping were the three preferred interventions. Scenarios were found to only have a small effect on the group ranking of interventions in the control model. Conclusions: MCDA was used to structure key decision criteria and capture the complexity of Lyme disease management. This facilitated the identification of gaps in the scientific literature and enabled a clear identification of complementary interventions that could be used to improve the relevance and acceptability of proposed prevention and control strategy. Overall, MCDA presents itself as an interesting systematic approach for public health planning and zoonoses management with a “One Health” perspective

Evidence-based Tool for Triggering School Closures during Influenza Outbreaks, Japan

Guidelines available to school administrators to support school closure decisions during influenza outbreaks are usually not evidence-based. Using empirical data on absentee rates of elementary school students in Japan, we developed a simple and practical algorithm for determining the optimal timing of school closures for control of influenza outbreaks

Characteristics of US public schools with reported cases of novel influenza A (H1N1)

Objective The 2009 pandemic of influenza A (H1N1) has disproportionately affected children and young adults, resulting in attention by public health officials and the news media on schools as important settings for disease transmission and spread. We aimed to characterize US schools affected by novel influenza A (H1N1) relative to other schools in the same communities. Methods A database of US school-related cases was obtained by electronic news media monitoring for early reports of novel H1N1 influenza between April 23 and June 8, 2009. We performed a matched case–control study of 32 public primary and secondary schools that had one or more confirmed cases of H1N1 influenza and 6815 control schools located in the same 23 counties as case schools. Results Compared with controls from the same county, schools with reports of confirmed cases of H1N1 influenza were less likely to have a high proportion of economically disadvantaged students (adjusted odds ratio (aOR) 0.385; 95% confidence interval (CI) 0.166–0.894) and less likely to have older students (aOR 0.792; 95% CI 0.670–0.938). Conclusions We conclude that public schools with younger, more affluent students may be considered sentinels of the epidemic and may have played a role in its initial spread.National Institute of Allergy and Infectious Diseases (U.S.) (R21AI073591-01)National Institutes of Health (U.S.)Canadian Institutes of Health Research (PAN-83152)Canadian Institutes of Health Research (CAT-86857)Google (Firm) (Research Grant

Whole genome capture of vector-borne pathogens from mixed DNA samples: a case study of Borrelia burgdorferi

Background: Rapid and accurate retrieval of whole genome sequences of human pathogens from disease vectors or animal reservoirs will enable fine-resolution studies of pathogen epidemiological and evolutionary dynamics. However, next generation sequencing technologies have not yet been fully harnessed for the study of vector-borne and zoonotic pathogens, due to the difficulty of obtaining high-quality pathogen sequence data directly from field specimens with a high ratio of host to pathogen DNA. Results: We addressed this challenge by using custom probes for multiplexed hybrid capture to enrich for and sequence 30 Borrelia burgdorferi genomes from field samples of its arthropod vector. Hybrid capture enabled sequencing of nearly the complete genome (~99.5 %) of the Borrelia burgdorferi pathogen with 132-fold coverage, and identification of up to 12,291 single nucleotide polymorphisms per genome. Conclusions: The proprosed culture-independent method enables efficient whole genome capture and sequencing of pathogens directly from arthropod vectors, thus making population genomic study of vector-borne and zoonotic infectious diseases economically feasible and scalable. Furthermore, given the similarities of invertebrate field specimens to other mixed DNA templates characterized by a high ratio of host to pathogen DNA, we discuss the potential applicabilty of hybrid capture for genomic study across diverse study systems. Keywords: Hybrid capture Whole-genome sequencing SNPs Tick-borne pathogens Lyme diseas

Population Biology of Lyme Borreliosis Spirochetes

Klaus Kurtenbach, Anne Gatewood, Stephen J. Bent, Stephanie A. Vollmer, Nicholas H. Ogden and Gabriele Margoshttp://trove.nla.gov.au/work/3645207