Our results show that a combination of a novel strategy of finding and immunizing highly connected individuals with case isolation and contact tracing can prevent a large smallpox outbreak, with the advantage of vaccinating only about 10% of the population (Figure 2 ). This low vaccination coverage considerably reduces the number of severe side effects and deaths due to vaccination [2, 3, 18] . In the case of smallpox vaccines this is of paramount importance, as reported by Casey et al. 2006 , "after the inoculation of 37,901 people in the United States, three deaths, two permanent disabilities, and ten life-threatening illnesses were attributed to vaccination during 2003" [6] .