Eradicated infectious diseases like smallpox can re-emerge through accident or designs of bioterrorists, and perpetrate heavy casualties. Currently, only a small percentage of the populace is vaccinated, and their protection is likely to have waned. Most therefore are susceptible today. And when the disease re-emerges the susceptible individuals may be manipulated by disinformation on Social Media to refuse vaccines. Thus, a combination of countermeasures consisting of antiviral drugs and vaccines and a range of policies for their application need to be investigated. Opinions as to receptivity of vaccines evolve with time through social exchanges over networks that overlap with but are not identical to the disease propagation networks. These couple the spread of the biological and information contagion and necessitate a joint investigation of the two. Towards these, we develop a computationally tractable metapopulation epidemiological model that captures the joint spatio-temporal evolution of smallpox and opinion dynamics. The computations based on the model show that opinion dynamics has a substantial impact on the fatality count. Towards understanding how perpetrators are likely to seed the infection we identify a) the initial distribution of infected individuals that maximize the overall fatality count regardless of mobility patterns, and b) which habitation structures are more vulnerable to outbreaks. We assess the relative efficacy of different countermeasures and conclude that a combination of vaccines and drugs minimizes the fatalities, and by itself, for smallpox, drugs reduce fatalities more than the vaccine. Accordingly, we assess the efficacies of three separate policies for administering the drugs and identify the best among them for various parameter combinations. When the availability of the drug is finite, we show that increase in its supply substantially reduces the overall fatality. Our findings lead to policy recommendations for public health and urban design authorities towards thwarting smallpox and other infectious disease outbreaks.