Modeling studies show that combination strategies increase the effectiveness of individual strategies, guard against individual failures, and may reduce socio-economic impact. In the initial phases of an influenza pandemic, combination strategies provide the opportunity to contain the novel virus or delay its spread, allowing unaffected areas within a country and other countries to activate preventive strategies. During a pandemic, combination strategies allow for different strategies to have synergistic effect in reducing the impact of pandemic influenza, and the socio-economic impact of individual interventions. Finally, combination strategies protect against failure of individual interventions and should be considered in preparedness plans.  Let the sun shine in: effects of ultraviolet radiation on invasive pneumococcal disease risk in Philadelphia, Pennsylvania BACKGROUND: Streptococcus pneumoniae is a common cause of community acquired pneumonia and bacteremia. Excess wintertime mortality related to pneumonia has been noted for over a century, but the seasonality of invasive pneumococcal disease (IPD) has been described relatively recently and is poorly understood. Improved understanding of environmental influence on disease seasonality has taken on new urgency due to global climate change. METHODS: We evaluated 602 cases of IPD reported in Philadelphia County, Pennsylvania, from 2002 to 2007. Poisson regression models incorporating seasonal smoothers were used to identify associations between weekly weather patterns and case counts. Associations between acute (day-to-day) environmental fluctuations and IPD occurrence were evaluated using a case-crossover approach. Effect modification across age and sex strata was explored, and meta-regression models were created using stratum-specific estimates for effect. RESULTS: IPD incidence was greatest in the wintertime, and spectral decomposition revealed a peak at 51.0 weeks, consistent with annual periodicity. After adjustment for seasonality, yearly increases in reporting, and temperature, weekly incidence was found to be associated with clear-sky UV index (IRR per unit increase in index: 0.70 [95% CI 0.54-0.91]). The effect of UV index was highest among young strata and decreased with age. At shorter time scales, only an association with increases in ambient sulphur oxides was linked to disease risk (OR for highest tertile of exposure 0.75, 95% CI 0.60 to 0.93). CONCLUSION: We confirmed the wintertime predominance of IPD in a major urban center. The major predictor of IPD in Philadelphia is extended periods of low UV radiation, which may explain observed wintertime seasonality. The mechanism of action of diminished light exposure on disease occurrence may be due to direct effects on pathogen survival or host immune function via altered 1,25-(OH)(2)-vitamin-D metabolism. These findings may suggest less diminution in future IPD risk with climate change than would be expected if wintertime seasonality was driven by temperature. Many infectious diseases of public health importance exhibit predictable periodicity, with major increases in incidence during a specific season of the year [1] . Empirical evidence of such "seasonality" has been noted by physicians for centuries, and has been prominent enough to become a part of our vernacular (e.g., "cold and flu season") [1, 2] . Despite this wealth of experiential evidence, the mechanisms underlying seasonality are poorly understood, especially diseases characterized by person-to-person transmission [1] .