{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,26]],"date-time":"2026-06-26T14:53:20Z","timestamp":1782485600118,"version":"3.54.5"},"reference-count":40,"publisher":"Public Library of Science (PLoS)","issue":"8","license":[{"start":{"date-parts":[[2021,8,20]],"date-time":"2021-08-20T00:00:00Z","timestamp":1629417600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"SIGA Technologies, Inc."},{"name":"SIGA Technologies, Inc."}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS ONE"],"abstract":"<jats:sec id=\"sec001\">\n                    <jats:title>Objectives<\/jats:title>\n                    <jats:p>Eradicated infectious diseases like smallpox can re-emerge through accident or the designs of bioterrorists, and cause heavy casualties. Presently, the populace is largely susceptible as only a small percentage is vaccinated, and their immunity is likely to have waned. 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 regarding whether to receive vaccines evolve over time through social exchanges via 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.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"sec002\">\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>We develop a computationally tractable metapopulation epidemiological model that captures the joint spatio-temporal evolution of an infectious disease (e.g., smallpox, COVID-19) and opinion dynamics.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"sec003\">\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Considering smallpox, the computations based on the model show that opinion dynamics have 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; 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 minimize the fatalities, and by itself, drugs reduce fatalities more than the vaccine. Accordingly, we assess the impact of increase in the supply of drugs and identify the most effective among a collection of policies for administering of drugs for various parameter combinations. Many of the observed patterns are stable to variations of a diverse set of parameters.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"sec004\">\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Our findings provide a quantitative foundation for various important elements of public health discourse that have largely been conducted qualitatively.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1371\/journal.pone.0256014","type":"journal-article","created":{"date-parts":[[2021,8,20]],"date-time":"2021-08-20T13:57:02Z","timestamp":1629467822000},"page":"e0256014","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":16,"title":["Countering the potential re-emergence of a deadly infectious disease\u2014Information warfare, identifying strategic threats, launching countermeasures"],"prefix":"10.1371","volume":"16","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9898-5749","authenticated-orcid":true,"given":"Rex N.","family":"Ali","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Harvey","family":"Rubin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Saswati","family":"Sarkar","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2021,8,20]]},"reference":[{"issue":"1","key":"pone.0256014.ref001","doi-asserted-by":"crossref","first-page":"59","DOI":"10.1089\/bsp.2012.0037","article-title":"The role of vaccination, antiorthopoxvirus drug, and social cooperativity in a mathematical model of smallpox control","volume":"11","author":"P Finin","year":"2013","journal-title":"Biosecurity and bioterrorism: biodefense strategy, practice, and science"},{"issue":"5","key":"pone.0256014.ref002","doi-asserted-by":"crossref","first-page":"648","DOI":"10.1177\/0272989X14561681","article-title":"Modeling the effect of herd immunity and contagiousness in mitigating a smallpox outbreak","volume":"35","author":"E Graeden","year":"2015","journal-title":"Medical Decision Making"},{"issue":"16","key":"pone.0256014.ref003","doi-asserted-by":"crossref","first-page":"10935","DOI":"10.1073\/pnas.162282799","article-title":"Emergency response to a smallpox attack: the case for mass vaccination","volume":"99","author":"EH Kaplan","year":"2002","journal-title":"Proceedings of the National Academy of Sciences"},{"issue":"1","key":"pone.0256014.ref004","doi-asserted-by":"crossref","DOI":"10.31646\/gbio.10","article-title":"Exercise Mataika: White Paper on response to a smallpox bioterrorism release in the Pacific","volume":"1","author":"C MacIntyre","year":"2019","journal-title":"Global Biosecurity"},{"key":"pone.0256014.ref005","unstructured":"The Children\u2019s Hospital of Philadelphia. A Look at Each Vaccine: Smallpox Vaccine. 2014 Aug. Available from: https:\/\/www.chop.edu\/centers-programs\/vaccine-education-center\/vaccine-details\/smallpox-vaccine"},{"key":"pone.0256014.ref006","unstructured":"Centers for Disease Control and Prevention (CDC). Bioterrorism Agents\/Diseases. 2018 Apr. Available from: https:\/\/emergency.cdc.gov\/agent\/agentlist-category.asp"},{"key":"pone.0256014.ref007","unstructured":"The spectre of smallpox lingers. Nature News. Nature Publishing Group; 2018. [cited 21 May 2020] Available: https:\/\/www.nature.com\/articles\/d41586-018-05936-x"},{"issue":"7524","key":"pone.0256014.ref008","doi-asserted-by":"crossref","first-page":"544","DOI":"10.1038\/514544a","article-title":"Forgotten NIH smallpox virus languishes on death row","volume":"514","author":"S Reardon","year":"2014","journal-title":"Nature News"},{"issue":"1","key":"pone.0256014.ref009","doi-asserted-by":"crossref","first-page":"e0188453","DOI":"10.1371\/journal.pone.0188453","article-title":"Construction of an infectious horsepox virus vaccine from chemically synthesized DNA fragments","volume":"13","author":"RS Noyce","year":"2018","journal-title":"PLOS ONE"},{"issue":"11","key":"pone.0256014.ref010","doi-asserted-by":"crossref","first-page":"1377","DOI":"10.1002\/hec.3937","article-title":"Vaccine hesitancy and (fake) news: Quasi-experimental evidence from Italy","volume":"28","author":"V Carrieri","year":"2019","journal-title":"Health economics"},{"issue":"5","key":"pone.0256014.ref011","doi-asserted-by":"crossref","first-page":"516","DOI":"10.3325\/cmj.2016.57.516","article-title":"Religious exception for vaccination or religious excuses for avoiding vaccination","volume":"57","author":"G Pel\u010di\u0107","year":"2016","journal-title":"Croatian medical journal"},{"key":"pone.0256014.ref012","unstructured":"Beard D. Poll shows 61 percent of Americans likely to take Covid-19 vaccine. 2021 Feb. Available from: https:\/\/www.nationalgeographic.com\/science\/article\/poll-shows-61-percent-americans-likely-to-take-coronavirus-vaccine"},{"key":"pone.0256014.ref013","unstructured":"Liebermann O, Kaufman E, Cole D. Nearly 40% of marines have declined Covid-19 vaccine. 2021 Apr. Available from: https:\/\/www.cnn.com\/2021\/04\/09\/politics\/marines-coronavirus-vaccines\/index.html"},{"key":"pone.0256014.ref014","doi-asserted-by":"crossref","DOI":"10.1177\/2333794X19862949","article-title":"Anti-vaccine decision-making and measles resurgence in the United States","volume":"6","author":"O Benecke","year":"2019","journal-title":"Global pediatric health"},{"key":"pone.0256014.ref015","unstructured":"Robeznieks A. Stopping the scourge of social media misinformation on vaccines. American Medication Association, Dec. 2019; Accessed: June 10, 2020. Available from: https:\/\/www.ama-assn.org\/delivering-care\/public-health\/stopping-scourge-social-media-misinformation-vaccines"},{"issue":"11","key":"pone.0256014.ref016","doi-asserted-by":"crossref","first-page":"2586","DOI":"10.1080\/21645515.2020.1780846","article-title":"Social media and vaccine hesitancy: new updates for the era of COVID-19 and globalized infectious diseases","volume":"16","author":"N Puri","year":"2020","journal-title":"Human vaccines & immunotherapeutics"},{"key":"pone.0256014.ref017","unstructured":"Centers for Disease Control and Prevention. Smallpox Prevention and Treatment. 2019 Jan. Available from: https:\/\/www.cdc.gov\/smallpox\/prevention-treatment\/index.html."},{"key":"pone.0256014.ref018","unstructured":"DailyMed. TPOXX\u2014Tecovirimat Monohydrate Capsule. U.S. National Library of Medicine. 2018 July. Available from: https:\/\/dailymed.nlm.nih.gov\/dailymed\/drugInfo.cfm?setid=fce826ab-4d6a-4139-a2ee-a304a913a253"},{"issue":"3","key":"pone.0256014.ref019","doi-asserted-by":"crossref","first-page":"259","DOI":"10.1257\/jep.32.3.259","article-title":"Social connectedness: Measurement, determinants, and effects","volume":"32","author":"M Bailey","year":"2018","journal-title":"Journal of Economic Perspectives"},{"key":"pone.0256014.ref020","unstructured":"Patacchini E. How does geographical distance affect social interactions? 2015 Jul. Available from: https:\/\/www.weforum.org\/agenda\/2015\/07\/how-does-geographical-distance-affect-social-interactions\/"},{"issue":"5597","key":"pone.0256014.ref021","doi-asserted-by":"crossref","first-page":"1428","DOI":"10.1126\/science.1074674","article-title":"Containing bioterrorist smallpox","volume":"298","author":"ME Halloran","year":"2002","journal-title":"Science"},{"issue":"1","key":"pone.0256014.ref022","doi-asserted-by":"crossref","first-page":"73","DOI":"10.1089\/bsp.2013.1211","article-title":"Smallpox epidemic models and response strategies","volume":"11","author":"DA Henderson","year":"2013","journal-title":"Biosecurity and bioterrorism: biodefense strategy, practice, and science"},{"issue":"1","key":"pone.0256014.ref023","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1186\/1471-2334-10-25","article-title":"Contingency planning for a deliberate release of smallpox in Great Britain\u2014the role of geographical scale and contact structure","volume":"10","author":"T House","year":"2010","journal-title":"BMC infectious diseases"},{"issue":"4","key":"pone.0256014.ref024","doi-asserted-by":"crossref","first-page":"646","DOI":"10.3201\/eid2404.171233","article-title":"Influence of population immunosuppression and past vaccination on smallpox reemergence","volume":"24","author":"CR Macintyre","year":"2018","journal-title":"Emerging infectious diseases"},{"issue":"6","key":"pone.0256014.ref025","doi-asserted-by":"crossref","first-page":"959","DOI":"10.3201\/eid0706.010607","article-title":"Modeling potential responses to smallpox as a bioterrorist weapon","volume":"7","author":"MI Meltzer","year":"2001","journal-title":"Emerging infectious diseases"},{"issue":"14","key":"pone.0256014.ref026","doi-asserted-by":"crossref","first-page":"7805","DOI":"10.1128\/JVI.03481-12","article-title":"Assessment of the protective effect of Imvamune and Acam2000 vaccines against aerosolized monkeypox virus in cynomolgus macaques","volume":"87","author":"GJ Hatch","year":"2013","journal-title":"Journal of virology"},{"key":"pone.0256014.ref027","unstructured":"Bavarian Nordic delivers 1 million doses of first vaccine developed under U.S. biopreparedness program to the Strategic National Stockpile. 2010 [cited 21 May 2020]. Available from: http:\/\/www.bavarian-nordic.com\/investor\/news\/news.aspx?news=2041"},{"issue":"2","key":"pone.0256014.ref028","article-title":"Expected adverse events in a mass smallpox vaccination campaign","volume":"5","author":"AR Kemper","year":"2002","journal-title":"Effective Clinical Practice"},{"issue":"1","key":"pone.0256014.ref029","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1186\/1742-4682-11-3","article-title":"Metapopulation epidemic models with heterogeneous mixing and travel behaviour","volume":"11","author":"A Apolloni","year":"2014","journal-title":"Theoretical Biology and Medical Modelling"},{"issue":"3","key":"pone.0256014.ref030","doi-asserted-by":"crossref","first-page":"450","DOI":"10.1016\/j.jtbi.2007.11.028","article-title":"Epidemic modeling in metapopulation systems with heterogeneous coupling pattern: Theory and simulations","volume":"251","author":"V Colizza","year":"2008","journal-title":"Journal of theoretical biology"},{"key":"pone.0256014.ref031","volume-title":"Smallpox and its eradication","author":"F Fenner","year":"1988"},{"issue":"7","key":"pone.0256014.ref032","doi-asserted-by":"crossref","first-page":"4296","DOI":"10.1128\/AAC.00208-15","article-title":"Treatment with the smallpox antiviral tecovirimat (ST-246) alone or in combination with ACAM2000 vaccination is effective as a postsymptomatic therapy for monkeypox virus infection","volume":"59","author":"A Berhanu","year":"2015","journal-title":"Antimicrobial agents and chemotherapy"},{"issue":"2","key":"pone.0256014.ref033","doi-asserted-by":"crossref","first-page":"750","DOI":"10.1109\/TNSE.2018.2873281","article-title":"Spread, then target, and advertise in waves: optimal budget allocation across advertising channels","volume":"7","author":"S Eshghi","year":"2018","journal-title":"IEEE Transactions on Network Science and Engineering"},{"key":"pone.0256014.ref034","doi-asserted-by":"crossref","first-page":"160","DOI":"10.1016\/j.trb.2019.11.004","article-title":"An epidemiological diffusion framework for vehicular messaging in general transportation networks","volume":"131","author":"J Kim","year":"2020","journal-title":"Transportation Research Part B: Methodological"},{"issue":"772","key":"pone.0256014.ref035","first-page":"700","article-title":"A contribution to the mathematical theory of epidemics","volume":"115","author":"WO Kermack","year":"1927","journal-title":"Proceedings of the royal society of london. Series A, Containing papers of a mathematical and physical character"},{"key":"pone.0256014.ref036","volume-title":"Mathematics of Epidemics on Networks: From Exact to Approximate Models","author":"Z Istvan","year":"2019"},{"key":"pone.0256014.ref037","volume-title":"Modelling disease ecology with mathematics","author":"R Smith","year":"2008"},{"issue":"2","key":"pone.0256014.ref038","doi-asserted-by":"crossref","first-page":"110","DOI":"10.1093\/aje\/kwg103","article-title":"Transmission potential of smallpox: estimates based on detailed data from an outbreak","volume":"158","author":"M Eichner","year":"2003","journal-title":"American journal of epidemiology"},{"key":"pone.0256014.ref039","unstructured":"U.S. Department of Health and Human Services (HHS). COVID-19 Treatments and Therapeutics. 2021 Feb. Available from: https:\/\/www.hhs.gov\/coronavirus\/covid-19-treatments-therapeutics\/index.html"},{"key":"pone.0256014.ref040","unstructured":"Centers for Disease Control and Prevention. What to Do if You Have an Allergic Reaction After Getting A COVID-19 Vaccine; 2021. 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