Influenza increases invasive meningococcal disease risk in temperate countries.

OBJECTIVES: Invasive meningococcal disease (IMD) is a severe bacterial infection that displays wintertime seasonality in temperate countries. Mechanisms driving seasonality are poorly understood and may include environmental conditions and/or respiratory virus infections. We evaluated the contribution of influenza and environmental conditions to IMD risk, using standardized methodology, across multiple geographical regions. METHODS: We evaluated 3276 IMD cases occurring between January 1999 and December 2011 in 11 jurisdictions in Australia, Canada, France and the United States. Effects of environmental exposures and normalized weekly influenza activity on IMD risk were evaluated using a case-crossover design. Meta-analytic methods were used to evaluate homogeneity of effects and to identify sources of between-region heterogeneity. RESULTS: After adjustment for environmental factors, elevated influenza activity at a 2-week lag was associated with increased IMD risk (adjusted odds ratio (OR) per standard deviation increase 1.29; 95% confidence interval, 1.04-1.59). This increase was homogeneous across the jurisdictions studied. By contrast, although associations between environmental exposures and IMD were identified in individual jurisdictions, none was generalizable. CONCLUSIONS: Using a self-matched design that adjusts for both coseasonality and case characteristics, we found that surges in influenza activity result in an acute increase in population-level IMD risk. This effect is seen across diverse geographic regions in North America, France and Australia. The impact of influenza infection on downstream meningococcal risk should be considered a potential benefit of influenza immunization programmes.

Epidemiological evaluation of spatiotemporal and genotypic clustering of Mycobacterium tuberculosis in Ontario, Canada.

BACKGROUND: In Canada, tuberculosis (TB) rates are at a historic low, with the remaining risk concentrated in a few vulnerable population subgroups. OBJECTIVES: To describe the epidemiology of TB in the Canadian province of Ontario and to characterise risk factors associated with transmission events, identified using genetic typing techniques. DESIGN: Retrospective analysis of 2186 culture-positive TB cases between August 2007 and December 2011. Temporal trends and risk of spatiotemporal and genotypic clustering were evaluated using Poisson and logistic regression models. RESULTS: Being in a spatiotemporal cluster was associated with Aboriginal status (odds ratio [OR] 3.63, 95% confidence interval [CI] 1.23-10.71). Cases in genotypic clusters were more likely to report homelessness as a risk factor (adjusted OR [aOR] 2.92, 95%CI 1.74-4.90) or be male (aOR 1.35, 95%CI 1.09-1.68), and were less likely to be aged ≥ 65 years (aOR 0.63, 95%CI 0.49-0.82), foreign-born (aOR 0.32, 95%CI 0.24-0.43) or Aboriginal (aOR 0.40, 95%CI 0.16-0.99). The Beijing lineage had an annual rate of increase of almost 10% (P = 0.047), and was associated with genotypic clustering (aOR 2.84, 95%CI 2.19-3.67). CONCLUSION: Genotypic data suggest that disease clusters are smaller, but far more common, than would be estimated using spatiotemporal clustering.

Age, influenza pandemics and disease dynamics.

The world is currently confronting the first influenza pandemic of the 21st century [caused by a novel pandemic influenza A (H1N1) virus]. Earlier pandemics have been characterized by age distributions that are distinct from those observed with seasonal influenza epidemics, with higher attack rates (and correspondingly increased proportionate or relative mortality) in younger individuals. While the genesis of protection against infection in older individuals during a pandemic is uncertain, differential vulnerability to infection by age has important implications for disease dynamics and control, and for choice of optimal vaccination strategies. Age-related vulnerability to infection may explain differences between school- and community-derived estimates of the reproductive number (R) for a newly emerged pandemic strain, and may also help explain the failure of a newly emerged influenza A (H1N1) virus strain to cause a pandemic in 1977. Age-related factors may also help explain variability in attack rates, and the size and impact of influenza epidemics across jurisdictions and between populations. In Canada, such effects have been observed in the apparently increased severity of outbreaks on Indigenous peoples' reserves. The implications of these patterns for vaccine allocation necessitate targeted research to understand age-related vulnerabilities early in an influenza pandemic.

Genetic control of susceptibility to Candida albicans in susceptible A/J and resistant C57BL/6J mice.

The importance of host factors in determining susceptibility to systemic Candida albicans infections is evident in both humans and mice. We have used a mouse model to study the genetic basis of susceptibility, using the inbred strains A/J and C57BL/6J, which are susceptible and resistant, respectively, based on different parameters of the response to infection. To identify genes responsible for this differential host response, brain and kidney fungal load were measured in 128 [A/J x C57BL/6J] F(2) mice 48 h after infection with 5 x 10(4) C. albicans blastospores. Segregation analysis in this informative population identified complement component 5 (C5/Hc) as the major gene responsible for this differential susceptibility (LOD of 22.7 for kidney, 19.0 for brain), with a naturally occurring mutation that causes C5 deficiency leading to enhanced susceptibility. C5 was also found to control heart fungal load, survival time, and serum TNF-alpha levels during infection. Investigation of the response to C. albicans challenge in a series of AcB/BcA recombinant congenic strains validated the importance of C5 in determining the host response. However, the strains BcA67 and BcA72 showed discordant phenotypes with respect to their C5 status, suggesting additional complexity in the genetic control of the inter-strain difference in susceptibility observed in A/J and C57BL/6J following systemic infection with C. albicans.

Genetic analysis of innate immunity in resistance to Candida albicans.

Systemic candidiasis is a significant cause of nosocomial infections and the mechanisms of defense against Candida albicans in humans remain poorly understood. Studies in animal models have demonstrated the importance of innate immunity in controlling the response to infection. Although Th1 cytokines have been shown to direct the overall outcome of infection, the precise role of the Th1/Th2 response and, more generally, the adaptive immune response as a whole, in systemic candidiasis, appears to apply mainly to the development of resistance to reinfection. A genetic approach to the identification of host factors regulating pathogenesis and susceptibility to C. albicans infection has been used in humans and in mouse models of infection. Mouse mutants bearing experimentally induced mutations in specific genes have provided a systematic tool for directly assessing the role of individual proteins in C. albicans susceptibility. Inbred mouse strains have been valuable in showcasing the spectrum of naturally occurring variations in initial susceptibility to infection, and type of disease developed. Crosses between resistant and susceptible strains have led to the detection of additional gene effects affecting innate immunity. Of particular interest is the major effect of a naturally occurring loss-of-function mutation in the C5 complement component that has become fixed in many inbred strains. These and other studies have shown that both a functional complement pathway and robust inflammatory response are critical for resistance to C. albicans.

Falls prevention: partnering occupational therapy and general practitioners.

The Falls STOP project was a partnership between general practitioners (GPs) and occupational therapists with the common goal to reduce accidental falls in the elderly. A home visiting service was implemented that included the organisation of home modifications, education on falls prevention strategies and referral to other community services. The pilot demonstrated some valuable benefits to sixty-eight clients referred to the program by twenty GPs. A number of resources were developed such as a falls risk questionnaire completed by patients while waiting to see the doctor, and a falls prevention educational booklet. A significant challenge for future preventative programs is rousing the interest of a larger group of referring doctors, and promoting the benefits of shared care arrangements with occupational therapists that target specific health issues such as falls in the elderly.