%PDF-1.3 1 0 obj << /Type /Catalog /Outlines 2 0 R /Pages 3 0 R >> endobj 2 0 obj << /Type /Outlines /Count 0 >> endobj 3 0 obj << /Type /Pages /Kids [6 0 R 141 0 R 203 0 R 225 0 R 248 0 R 258 0 R 296 0 R ] /Count 7 /Resources << /ProcSet 4 0 R /Font << /F1 8 0 R /F2 9 0 R /F3 10 0 R /F4 11 0 R /F5 12 0 R /F6 250 0 R >> /XObject << /I1 13 0 R /I2 14 0 R /I3 153 0 R /I4 154 0 R /I5 173 0 R /I6 174 0 R /I7 193 0 R /I8 194 0 R /I9 209 0 R /I10 212 0 R /I11 229 0 R /I12 232 0 R /I13 235 0 R /I14 253 0 R >> >> /MediaBox [0.000 0.000 612.000 792.000] >> endobj 4 0 obj [/PDF /Text /ImageC ] endobj 5 0 obj << /Creator (DOMPDF) /CreationDate (D:20180722220555+00'00') /ModDate (D:20180722220555+00'00') /Title (Early Epidemic Dynamics of the West African 2014 Ebola Outbreak: Estimates Derived with a Simple Two-Parameter Model PLOS Currents Outbreaks) >> endobj 6 0 obj << /Type /Page /Parent 3 0 R /Annots [ 15 0 R 17 0 R 19 0 R 21 0 R 23 0 R 25 0 R 27 0 R 29 0 R 31 0 R 33 0 R 35 0 R 37 0 R 39 0 R 41 0 R 43 0 R 45 0 R 47 0 R 49 0 R 51 0 R 53 0 R 55 0 R 57 0 R 59 0 R 61 0 R 63 0 R 65 0 R 67 0 R 69 0 R 71 0 R 73 0 R 75 0 R 77 0 R 79 0 R 81 0 R 83 0 R 85 0 R 87 0 R 89 0 R 91 0 R 93 0 R 95 0 R 97 0 R 99 0 R 101 0 R 103 0 R 105 0 R 107 0 R 109 0 R 111 0 R 113 0 R 115 0 R 117 0 R 119 0 R 121 0 R 123 0 R 125 0 R 127 0 R 129 0 R 131 0 R 133 0 R 135 0 R 137 0 R 139 0 R ] /Contents 7 0 R >> endobj 7 0 obj << /Length 27923 >> stream q 375.000 0 0 39.000 222.000 738.000 cm /I2 Do Q q 15.000 659.406 577.500 78.594 re W n 0.267 0.267 0.267 rg BT 15.000 718.042 Td /F2 21.0 Tf [(Early Epidemic Dynamics of the West African 2014 Ebola )] TJ ET BT 15.000 693.094 Td /F2 21.0 Tf [(Outbreak: Estimates Derived with a Simple Two-Parameter )] TJ ET BT 15.000 668.146 Td /F2 21.0 Tf [(Model)] TJ ET Q 0.271 0.267 0.267 rg BT 15.000 650.140 Td /F3 9.8 Tf [(September 8, 2014)] TJ ET BT 92.717 650.140 Td /F3 9.8 Tf [()] TJ ET 0.267 0.267 0.267 rg BT 97.592 650.140 Td /F3 9.8 Tf [(Research Article)] TJ ET BT 26.250 638.299 Td /F1 9.8 Tf [(David Fisman)] TJ ET 0.271 0.267 0.267 rg BT 85.842 638.299 Td /F1 9.8 Tf [(, )] TJ ET 0.267 0.267 0.267 rg BT 91.263 638.299 Td /F1 9.8 Tf [(Edwin Khoo)] TJ ET 0.271 0.267 0.267 rg BT 143.289 638.299 Td /F1 9.8 Tf [(, )] TJ ET 0.267 0.267 0.267 rg BT 148.710 638.299 Td /F1 9.8 Tf [(Ashleigh Tuite)] TJ ET 0.271 0.267 0.267 rg BT 26.250 626.394 Td /F1 9.8 Tf [(Fisman D, Khoo E, Tuite A. Early Epidemic Dynamics of the West African 2014 Ebola Outbreak: Estimates Derived with a )] TJ ET BT 26.250 614.490 Td /F1 9.8 Tf [(Simple Two-Parameter Model. PLOS Currents Outbreaks. 2014 Sep 8 . Edition 1. doi: )] TJ ET BT 26.250 602.585 Td /F1 9.8 Tf [(10.1371/currents.outbreaks.89c0d3783f36958d96ebbae97348d571.)] TJ ET q 15.000 42.082 577.500 558.122 re W n 0.271 0.267 0.267 rg BT 26.250 573.482 Td /F4 12.0 Tf [(Abstract)] TJ ET BT 26.250 553.528 Td /F1 9.8 Tf [(The 2014 West African Ebola virus outbreak, now more correctly referred to as an epidemic, is the largest ever to occur. As of )] TJ ET BT 26.250 541.623 Td /F1 9.8 Tf [(August 28, 2014, concerns have been raised that control efforts, particularly in Liberia, have been ineffective, as reported case )] TJ ET BT 26.250 529.719 Td /F1 9.8 Tf [(counts continue to increase. Limited data are available on the epidemiology of the outbreak. However, reported cumulative )] TJ ET BT 26.250 517.814 Td /F1 9.8 Tf [(incidence data as well as death counts are available for Guinea, Sierra Leone, Liberia and Nigeria. We utilized a simple, two )] TJ ET BT 26.250 505.909 Td /F1 9.8 Tf [(parameter mathematical model of epidemic growth and control, to characterize epidemic growth patterns in West Africa, to )] TJ ET BT 26.250 494.004 Td /F1 9.8 Tf [(evaluate the degree to which the epidemic is being controlled, and to assess the potential implications of growth patterns for )] TJ ET BT 26.250 482.100 Td /F1 9.8 Tf [(epidemic size. Models demonstrated good fits to data. Overall basic reproductive number \(R0\) for the epidemic was estimated )] TJ ET BT 26.250 470.195 Td /F1 9.8 Tf [(to be between 1.6 and 2.0, consistent with prior outbreaks. However, we identified only weak evidence for the occurrence of )] TJ ET BT 26.250 458.290 Td /F1 9.8 Tf [(epidemic control in West Africa as a whole, and essentially no evidence for control in Liberia \(though slowing of growth was )] TJ ET BT 26.250 446.385 Td /F1 9.8 Tf [(seen in Guinea and Sierra Leone\). It is projected that small reductions in transmission would prevent tens of thousands of future )] TJ ET BT 26.250 434.481 Td /F1 9.8 Tf [(infections. These findings suggest that there is an extraordinary need for improved control measures for the 2014 Ebola )] TJ ET BT 26.250 422.576 Td /F1 9.8 Tf [(epidemic, especially in Liberia, if catastrophe is to be averted.)] TJ ET BT 26.250 385.973 Td /F4 12.0 Tf [(Funding Statement)] TJ ET BT 26.250 366.019 Td /F1 9.8 Tf [(Ms. Tuite is funded by a Banting and Best Doctoral Award from the Canadian Institutes of Health Research. The funders had )] TJ ET BT 566.010 366.019 Td /F1 9.8 Tf [(no )] TJ ET BT 26.250 354.114 Td /F1 9.8 Tf [(role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.)] TJ ET BT 26.250 325.012 Td /F4 12.0 Tf [(Introduction)] TJ ET BT 26.250 305.058 Td /F1 9.8 Tf [(Ebola virus is a zoonotic filovirus that causes a hemorrhagic fever syndrome in humans, with a high case-fatality rate )] TJ ET 0.267 0.267 0.267 rg BT 531.281 306.565 Td /F4 8.7 Tf [(5)] TJ ET 0.271 0.267 0.267 rg BT 536.099 305.058 Td /F1 9.8 Tf [(. An )] TJ ET BT 26.250 293.153 Td /F1 9.8 Tf [(epidemic that started in December 2013 or early in 2014 )] TJ ET 0.267 0.267 0.267 rg BT 271.736 294.660 Td /F4 8.7 Tf [(6)] TJ ET 0.271 0.267 0.267 rg BT 276.554 293.153 Td /F1 9.8 Tf [( , and which has spread to four West African countries )] TJ ET BT 26.250 281.248 Td /F1 9.8 Tf [(\(Guinea,Liberia, Sierra Leone, and Nigeria\), has infected over 2000 individuals as of August 28 2014 )] TJ ET 0.267 0.267 0.267 rg BT 462.514 282.755 Td /F4 8.7 Tf [(8)] TJ ET 0.271 0.267 0.267 rg BT 467.332 281.248 Td /F1 9.8 Tf [( . While Ebola virus has )] TJ ET BT 26.250 269.343 Td /F1 9.8 Tf [(caused several prior outbreaks in Africa, this is the largest ever to occur )] TJ ET 0.267 0.267 0.267 rg BT 337.831 270.851 Td /F4 8.7 Tf [(7)] TJ ET 0.271 0.267 0.267 rg BT 342.649 269.343 Td /F1 9.8 Tf [( . Over half of all Ebola infections that have )] TJ ET BT 530.707 269.343 Td /F5 9.8 Tf [(ever)] TJ ET BT 549.671 269.343 Td /F1 9.8 Tf [( been )] TJ ET BT 26.250 257.439 Td /F1 9.8 Tf [(documented have occurred in the context of the current outbreak, which is ongoing.)] TJ ET BT 26.250 238.034 Td /F1 9.8 Tf [(In addition to a case-fatality rate greater than 50%, the current West African outbreak has proven difficult to control, has resulted )] TJ ET BT 26.250 226.129 Td /F1 9.8 Tf [(in international travel advisories, flight cancellations and border closures )] TJ ET 0.267 0.267 0.267 rg BT 339.459 227.636 Td /F4 8.7 Tf [(12)] TJ ET 0.271 0.267 0.267 rg BT 349.096 226.129 Td /F1 9.8 Tf [( , and has led to episodes of civil unrest, particularly )] TJ ET BT 26.250 214.224 Td /F1 9.8 Tf [(in Liberia )] TJ ET 0.267 0.267 0.267 rg BT 68.516 215.732 Td /F4 8.7 Tf [(11)] TJ ET 0.271 0.267 0.267 rg BT 78.154 218.113 Td /F1 8.7 Tf [(,)] TJ ET 0.267 0.267 0.267 rg BT 80.563 215.732 Td /F4 8.7 Tf [(10)] TJ ET 0.271 0.267 0.267 rg BT 90.200 214.224 Td /F1 9.8 Tf [( . The occurrence of cases in very large, well-connected urban centers \(including capitol cities of all affected )] TJ ET BT 26.250 202.320 Td /F1 9.8 Tf [(countries\) has fueled concerns about the international spread of disease via air travel, and on August 8, the World Health )] TJ ET BT 26.250 190.415 Td /F1 9.8 Tf [(Organization declared the outbreak to be a Public Health Emergency of International Concern )] TJ ET 0.267 0.267 0.267 rg BT 432.698 191.922 Td /F4 8.7 Tf [(9)] TJ ET 0.271 0.267 0.267 rg BT 437.517 190.415 Td /F1 9.8 Tf [(. This, again, contrasts with )] TJ ET BT 26.250 178.510 Td /F1 9.8 Tf [(earlier African Ebola outbreaks which have mostly occurred in smaller and less-connected cities, towns and rural areas )] TJ ET 0.267 0.267 0.267 rg BT 541.021 180.017 Td /F4 8.7 Tf [(7)] TJ ET 0.271 0.267 0.267 rg BT 545.839 178.510 Td /F1 9.8 Tf [( .)] TJ ET BT 26.250 159.105 Td /F1 9.8 Tf [(Mathematical models of infectious disease outbreaks and epidemics can be useful tools for synthesizing available information )] TJ ET BT 26.250 147.201 Td /F1 9.8 Tf [(on an infectious disease process, transforming data into useable knowledge, and defining and quantifying uncertainty about )] TJ ET BT 26.250 135.296 Td /F1 9.8 Tf [(infectious diseases)] TJ ET 0.267 0.267 0.267 rg BT 108.618 136.803 Td /F4 8.7 Tf [(13)] TJ ET 0.271 0.267 0.267 rg BT 118.255 139.184 Td /F1 8.7 Tf [(,)] TJ ET 0.267 0.267 0.267 rg BT 120.665 136.803 Td /F4 8.7 Tf [(14)] TJ ET 0.271 0.267 0.267 rg BT 130.302 135.296 Td /F1 9.8 Tf [(. Many models are explicitly mechanistic and represent epidemics as processes that result in transition )] TJ ET BT 26.250 123.391 Td /F1 9.8 Tf [(of individuals in the population between health states \(e.g., susceptible, infectious, and immune\) )] TJ ET 0.267 0.267 0.267 rg BT 442.458 124.898 Td /F4 8.7 Tf [(13)] TJ ET 0.271 0.267 0.267 rg BT 452.095 127.279 Td /F1 8.7 Tf [(,)] TJ ET 0.267 0.267 0.267 rg BT 454.505 124.898 Td /F4 8.7 Tf [(14)] TJ ET 0.271 0.267 0.267 rg BT 464.142 123.391 Td /F1 9.8 Tf [( . However, construction )] TJ ET BT 26.250 111.486 Td /F1 9.8 Tf [(of such models requires fairly detailed information on incidence, immune status in the population, and contact patterns for )] TJ ET BT 26.250 99.582 Td /F1 9.8 Tf [(correct parameterization. We have recently described a very simple mathematical model \(the Incidence Decay with Exponential )] TJ ET BT 26.250 87.677 Td /F1 9.8 Tf [(Adjustment, or IDEA, model\) that can be used as a descriptive and prognostic tool for epidemic processes when only limited )] TJ ET BT 26.250 75.772 Td /F1 9.8 Tf [(data \(e.g., cumulative incidence curves\) are available )] TJ ET 0.267 0.267 0.267 rg BT 258.719 77.279 Td /F4 8.7 Tf [(1)] TJ ET 0.271 0.267 0.267 rg BT 263.538 75.772 Td /F1 9.8 Tf [( . Here we apply this model to this epidemic; our objectives are to )] TJ ET BT 26.250 63.867 Td /F1 9.8 Tf [(reproduce, mathematically, observed patterns of epidemic growth, and to gain insights into the degree to which current control )] TJ ET BT 26.250 51.963 Td /F1 9.8 Tf [(efforts are likely to impact epidemic size and duration.)] TJ ET Q q 15.000 659.406 577.500 78.594 re W n 0.267 0.267 0.267 rg BT 15.000 718.042 Td /F2 21.0 Tf [(Early Epidemic Dynamics of the West African 2014 Ebola )] TJ ET BT 15.000 693.094 Td /F2 21.0 Tf [(Outbreak: Estimates Derived with a Simple Two-Parameter )] TJ ET BT 15.000 668.146 Td /F2 21.0 Tf [(Model)] TJ ET Q 0.271 0.267 0.267 rg BT 15.000 650.140 Td /F3 9.8 Tf [(September 8, 2014)] TJ ET BT 92.717 650.140 Td /F3 9.8 Tf [()] TJ ET 0.267 0.267 0.267 rg BT 97.592 650.140 Td /F3 9.8 Tf [(Research Article)] TJ ET BT 26.250 638.299 Td /F1 9.8 Tf [(David Fisman)] TJ ET 0.271 0.267 0.267 rg BT 85.842 638.299 Td /F1 9.8 Tf [(, )] TJ ET 0.267 0.267 0.267 rg BT 91.263 638.299 Td /F1 9.8 Tf [(Edwin Khoo)] TJ ET 0.271 0.267 0.267 rg BT 143.289 638.299 Td /F1 9.8 Tf [(, )] TJ ET 0.267 0.267 0.267 rg BT 148.710 638.299 Td /F1 9.8 Tf [(Ashleigh Tuite)] TJ ET 0.271 0.267 0.267 rg BT 26.250 626.394 Td /F1 9.8 Tf [(Fisman D, Khoo E, Tuite A. Early Epidemic Dynamics of the West African 2014 Ebola Outbreak: Estimates Derived with a )] TJ ET BT 26.250 614.490 Td /F1 9.8 Tf [(Simple Two-Parameter Model. PLOS Currents Outbreaks. 2014 Sep 8 . Edition 1. doi: )] TJ ET BT 26.250 602.585 Td /F1 9.8 Tf [(10.1371/currents.outbreaks.89c0d3783f36958d96ebbae97348d571.)] TJ ET q 15.000 42.082 577.500 558.122 re W n 0.271 0.267 0.267 rg BT 26.250 573.482 Td /F4 12.0 Tf [(Abstract)] TJ ET BT 26.250 553.528 Td /F1 9.8 Tf [(The 2014 West African Ebola virus outbreak, now more correctly referred to as an epidemic, is the largest ever to occur. As of )] TJ ET BT 26.250 541.623 Td /F1 9.8 Tf [(August 28, 2014, concerns have been raised that control efforts, particularly in Liberia, have been ineffective, as reported case )] TJ ET BT 26.250 529.719 Td /F1 9.8 Tf [(counts continue to increase. Limited data are available on the epidemiology of the outbreak. However, reported cumulative )] TJ ET BT 26.250 517.814 Td /F1 9.8 Tf [(incidence data as well as death counts are available for Guinea, Sierra Leone, Liberia and Nigeria. We utilized a simple, two )] TJ ET BT 26.250 505.909 Td /F1 9.8 Tf [(parameter mathematical model of epidemic growth and control, to characterize epidemic growth patterns in West Africa, to )] TJ ET BT 26.250 494.004 Td /F1 9.8 Tf [(evaluate the degree to which the epidemic is being controlled, and to assess the potential implications of growth patterns for )] TJ ET BT 26.250 482.100 Td /F1 9.8 Tf [(epidemic size. Models demonstrated good fits to data. Overall basic reproductive number \(R0\) for the epidemic was estimated )] TJ ET BT 26.250 470.195 Td /F1 9.8 Tf [(to be between 1.6 and 2.0, consistent with prior outbreaks. However, we identified only weak evidence for the occurrence of )] TJ ET BT 26.250 458.290 Td /F1 9.8 Tf [(epidemic control in West Africa as a whole, and essentially no evidence for control in Liberia \(though slowing of growth was )] TJ ET BT 26.250 446.385 Td /F1 9.8 Tf [(seen in Guinea and Sierra Leone\). It is projected that small reductions in transmission would prevent tens of thousands of future )] TJ ET BT 26.250 434.481 Td /F1 9.8 Tf [(infections. These findings suggest that there is an extraordinary need for improved control measures for the 2014 Ebola )] TJ ET BT 26.250 422.576 Td /F1 9.8 Tf [(epidemic, especially in Liberia, if catastrophe is to be averted.)] TJ ET BT 26.250 385.973 Td /F4 12.0 Tf [(Funding Statement)] TJ ET BT 26.250 366.019 Td /F1 9.8 Tf [(Ms. Tuite is funded by a Banting and Best Doctoral Award from the Canadian Institutes of Health Research. The funders had )] TJ ET BT 566.010 366.019 Td /F1 9.8 Tf [(no )] TJ ET BT 26.250 354.114 Td /F1 9.8 Tf [(role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.)] TJ ET BT 26.250 325.012 Td /F4 12.0 Tf [(Introduction)] TJ ET BT 26.250 305.058 Td /F1 9.8 Tf [(Ebola virus is a zoonotic filovirus that causes a hemorrhagic fever syndrome in humans, with a high case-fatality rate )] TJ ET 0.267 0.267 0.267 rg BT 531.281 306.565 Td /F4 8.7 Tf [(5)] TJ ET 0.271 0.267 0.267 rg BT 536.099 305.058 Td /F1 9.8 Tf [(. An )] TJ ET BT 26.250 293.153 Td /F1 9.8 Tf [(epidemic that started in December 2013 or early in 2014 )] TJ ET 0.267 0.267 0.267 rg BT 271.736 294.660 Td /F4 8.7 Tf [(6)] TJ ET 0.271 0.267 0.267 rg BT 276.554 293.153 Td /F1 9.8 Tf [( , and which has spread to four West African countries )] TJ ET BT 26.250 281.248 Td /F1 9.8 Tf [(\(Guinea,Liberia, Sierra Leone, and Nigeria\), has infected over 2000 individuals as of August 28 2014 )] TJ ET 0.267 0.267 0.267 rg BT 462.514 282.755 Td /F4 8.7 Tf [(8)] TJ ET 0.271 0.267 0.267 rg BT 467.332 281.248 Td /F1 9.8 Tf [( . While Ebola virus has )] TJ ET BT 26.250 269.343 Td /F1 9.8 Tf [(caused several prior outbreaks in Africa, this is the largest ever to occur )] TJ ET 0.267 0.267 0.267 rg BT 337.831 270.851 Td /F4 8.7 Tf [(7)] TJ ET 0.271 0.267 0.267 rg BT 342.649 269.343 Td /F1 9.8 Tf [( . Over half of all Ebola infections that have )] TJ ET BT 530.707 269.343 Td /F5 9.8 Tf [(ever)] TJ ET BT 549.671 269.343 Td /F1 9.8 Tf [( been )] TJ ET BT 26.250 257.439 Td /F1 9.8 Tf [(documented have occurred in the context of the current outbreak, which is ongoing.)] TJ ET BT 26.250 238.034 Td /F1 9.8 Tf [(In addition to a case-fatality rate greater than 50%, the current West African outbreak has proven difficult to control, has resulted )] TJ ET BT 26.250 226.129 Td /F1 9.8 Tf [(in international travel advisories, flight cancellations and border closures )] TJ ET 0.267 0.267 0.267 rg BT 339.459 227.636 Td /F4 8.7 Tf [(12)] TJ ET 0.271 0.267 0.267 rg BT 349.096 226.129 Td /F1 9.8 Tf [( , and has led to episodes of civil unrest, particularly )] TJ ET BT 26.250 214.224 Td /F1 9.8 Tf [(in Liberia )] TJ ET 0.267 0.267 0.267 rg BT 68.516 215.732 Td /F4 8.7 Tf [(11)] TJ ET 0.271 0.267 0.267 rg BT 78.154 218.113 Td /F1 8.7 Tf [(,)] TJ ET 0.267 0.267 0.267 rg BT 80.563 215.732 Td /F4 8.7 Tf [(10)] TJ ET 0.271 0.267 0.267 rg BT 90.200 214.224 Td /F1 9.8 Tf [( . The occurrence of cases in very large, well-connected urban centers \(including capitol cities of all affected )] TJ ET BT 26.250 202.320 Td /F1 9.8 Tf [(countries\) has fueled concerns about the international spread of disease via air travel, and on August 8, the World Health )] TJ ET BT 26.250 190.415 Td /F1 9.8 Tf [(Organization declared the outbreak to be a Public Health Emergency of International Concern )] TJ ET 0.267 0.267 0.267 rg BT 432.698 191.922 Td /F4 8.7 Tf [(9)] TJ ET 0.271 0.267 0.267 rg BT 437.517 190.415 Td /F1 9.8 Tf [(. This, again, contrasts with )] TJ ET BT 26.250 178.510 Td /F1 9.8 Tf [(earlier African Ebola outbreaks which have mostly occurred in smaller and less-connected cities, towns and rural areas )] TJ ET 0.267 0.267 0.267 rg BT 541.021 180.017 Td /F4 8.7 Tf [(7)] TJ ET 0.271 0.267 0.267 rg BT 545.839 178.510 Td /F1 9.8 Tf [( .)] TJ ET BT 26.250 159.105 Td /F1 9.8 Tf [(Mathematical models of infectious disease outbreaks and epidemics can be useful tools for synthesizing available information )] TJ ET BT 26.250 147.201 Td /F1 9.8 Tf [(on an infectious disease process, transforming data into useable knowledge, and defining and quantifying uncertainty about )] TJ ET BT 26.250 135.296 Td /F1 9.8 Tf [(infectious diseases)] TJ ET 0.267 0.267 0.267 rg BT 108.618 136.803 Td /F4 8.7 Tf [(13)] TJ ET 0.271 0.267 0.267 rg BT 118.255 139.184 Td /F1 8.7 Tf [(,)] TJ ET 0.267 0.267 0.267 rg BT 120.665 136.803 Td /F4 8.7 Tf [(14)] TJ ET 0.271 0.267 0.267 rg BT 130.302 135.296 Td /F1 9.8 Tf [(. Many models are explicitly mechanistic and represent epidemics as processes that result in transition )] TJ ET BT 26.250 123.391 Td /F1 9.8 Tf [(of individuals in the population between health states \(e.g., susceptible, infectious, and immune\) )] TJ ET 0.267 0.267 0.267 rg BT 442.458 124.898 Td /F4 8.7 Tf [(13)] TJ ET 0.271 0.267 0.267 rg BT 452.095 127.279 Td /F1 8.7 Tf [(,)] TJ ET 0.267 0.267 0.267 rg BT 454.505 124.898 Td /F4 8.7 Tf [(14)] TJ ET 0.271 0.267 0.267 rg BT 464.142 123.391 Td /F1 9.8 Tf [( . However, construction )] TJ ET BT 26.250 111.486 Td /F1 9.8 Tf [(of such models requires fairly detailed information on incidence, immune status in the population, and contact patterns for )] TJ ET BT 26.250 99.582 Td /F1 9.8 Tf [(correct parameterization. We have recently described a very simple mathematical model \(the Incidence Decay with Exponential )] TJ ET BT 26.250 87.677 Td /F1 9.8 Tf [(Adjustment, or IDEA, model\) that can be used as a descriptive and prognostic tool for epidemic processes when only limited )] TJ ET BT 26.250 75.772 Td /F1 9.8 Tf [(data \(e.g., cumulative incidence curves\) are available )] TJ ET 0.267 0.267 0.267 rg BT 258.719 77.279 Td /F4 8.7 Tf [(1)] TJ ET 0.271 0.267 0.267 rg BT 263.538 75.772 Td /F1 9.8 Tf [( . Here we apply this model to this epidemic; our objectives are to )] TJ ET BT 26.250 63.867 Td /F1 9.8 Tf [(reproduce, mathematically, observed patterns of epidemic growth, and to gain insights into the degree to which current control )] TJ ET BT 26.250 51.963 Td /F1 9.8 Tf [(efforts are likely to impact epidemic size and duration.)] TJ ET Q q 15.000 659.406 577.500 78.594 re W n 0.267 0.267 0.267 rg BT 15.000 718.042 Td /F2 21.0 Tf [(Early Epidemic Dynamics of the West African 2014 Ebola )] TJ ET BT 15.000 693.094 Td /F2 21.0 Tf [(Outbreak: Estimates Derived with a Simple Two-Parameter )] TJ ET BT 15.000 668.146 Td /F2 21.0 Tf [(Model)] TJ ET Q 0.271 0.267 0.267 rg BT 15.000 650.140 Td /F3 9.8 Tf [(September 8, 2014)] TJ ET BT 92.717 650.140 Td /F3 9.8 Tf [()] TJ ET 0.267 0.267 0.267 rg BT 97.592 650.140 Td /F3 9.8 Tf [(Research Article)] TJ ET BT 26.250 638.299 Td /F1 9.8 Tf [(David Fisman)] TJ ET 0.271 0.267 0.267 rg BT 85.842 638.299 Td /F1 9.8 Tf [(, )] TJ ET 0.267 0.267 0.267 rg BT 91.263 638.299 Td /F1 9.8 Tf [(Edwin Khoo)] TJ ET 0.271 0.267 0.267 rg BT 143.289 638.299 Td /F1 9.8 Tf [(, )] TJ ET 0.267 0.267 0.267 rg BT 148.710 638.299 Td /F1 9.8 Tf [(Ashleigh Tuite)] TJ ET 0.271 0.267 0.267 rg BT 26.250 626.394 Td /F1 9.8 Tf [(Fisman D, Khoo E, Tuite A. Early Epidemic Dynamics of the West African 2014 Ebola Outbreak: Estimates Derived with a )] TJ ET BT 26.250 614.490 Td /F1 9.8 Tf [(Simple Two-Parameter Model. PLOS Currents Outbreaks. 2014 Sep 8 . Edition 1. doi: )] TJ ET BT 26.250 602.585 Td /F1 9.8 Tf [(10.1371/currents.outbreaks.89c0d3783f36958d96ebbae97348d571.)] TJ ET q 15.000 42.082 577.500 558.122 re W n 0.271 0.267 0.267 rg BT 26.250 573.482 Td /F4 12.0 Tf [(Abstract)] TJ ET BT 26.250 553.528 Td /F1 9.8 Tf [(The 2014 West African Ebola virus outbreak, now more correctly referred to as an epidemic, is the largest ever to occur. As of )] TJ ET BT 26.250 541.623 Td /F1 9.8 Tf [(August 28, 2014, concerns have been raised that control efforts, particularly in Liberia, have been ineffective, as reported case )] TJ ET BT 26.250 529.719 Td /F1 9.8 Tf [(counts continue to increase. Limited data are available on the epidemiology of the outbreak. However, reported cumulative )] TJ ET BT 26.250 517.814 Td /F1 9.8 Tf [(incidence data as well as death counts are available for Guinea, Sierra Leone, Liberia and Nigeria. We utilized a simple, two )] TJ ET BT 26.250 505.909 Td /F1 9.8 Tf [(parameter mathematical model of epidemic growth and control, to characterize epidemic growth patterns in West Africa, to )] TJ ET BT 26.250 494.004 Td /F1 9.8 Tf [(evaluate the degree to which the epidemic is being controlled, and to assess the potential implications of growth patterns for )] TJ ET BT 26.250 482.100 Td /F1 9.8 Tf [(epidemic size. Models demonstrated good fits to data. Overall basic reproductive number \(R0\) for the epidemic was estimated )] TJ ET BT 26.250 470.195 Td /F1 9.8 Tf [(to be between 1.6 and 2.0, consistent with prior outbreaks. However, we identified only weak evidence for the occurrence of )] TJ ET BT 26.250 458.290 Td /F1 9.8 Tf [(epidemic control in West Africa as a whole, and essentially no evidence for control in Liberia \(though slowing of growth was )] TJ ET BT 26.250 446.385 Td /F1 9.8 Tf [(seen in Guinea and Sierra Leone\). It is projected that small reductions in transmission would prevent tens of thousands of future )] TJ ET BT 26.250 434.481 Td /F1 9.8 Tf [(infections. These findings suggest that there is an extraordinary need for improved control measures for the 2014 Ebola )] TJ ET BT 26.250 422.576 Td /F1 9.8 Tf [(epidemic, especially in Liberia, if catastrophe is to be averted.)] TJ ET BT 26.250 385.973 Td /F4 12.0 Tf [(Funding Statement)] TJ ET BT 26.250 366.019 Td /F1 9.8 Tf [(Ms. Tuite is funded by a Banting and Best Doctoral Award from the Canadian Institutes of Health Research. The funders had )] TJ ET BT 566.010 366.019 Td /F1 9.8 Tf [(no )] TJ ET BT 26.250 354.114 Td /F1 9.8 Tf [(role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.)] TJ ET BT 26.250 325.012 Td /F4 12.0 Tf [(Introduction)] TJ ET BT 26.250 305.058 Td /F1 9.8 Tf [(Ebola virus is a zoonotic filovirus that causes a hemorrhagic fever syndrome in humans, with a high case-fatality rate )] TJ ET 0.267 0.267 0.267 rg BT 531.281 306.565 Td /F4 8.7 Tf [(5)] TJ ET 0.271 0.267 0.267 rg BT 536.099 305.058 Td /F1 9.8 Tf [(. An )] TJ ET BT 26.250 293.153 Td /F1 9.8 Tf [(epidemic that started in December 2013 or early in 2014 )] TJ ET 0.267 0.267 0.267 rg BT 271.736 294.660 Td /F4 8.7 Tf [(6)] TJ ET 0.271 0.267 0.267 rg BT 276.554 293.153 Td /F1 9.8 Tf [( , and which has spread to four West African countries )] TJ ET BT 26.250 281.248 Td /F1 9.8 Tf [(\(Guinea,Liberia, Sierra Leone, and Nigeria\), has infected over 2000 individuals as of August 28 2014 )] TJ ET 0.267 0.267 0.267 rg BT 462.514 282.755 Td /F4 8.7 Tf [(8)] TJ ET 0.271 0.267 0.267 rg BT 467.332 281.248 Td /F1 9.8 Tf [( . While Ebola virus has )] TJ ET BT 26.250 269.343 Td /F1 9.8 Tf [(caused several prior outbreaks in Africa, this is the largest ever to occur )] TJ ET 0.267 0.267 0.267 rg BT 337.831 270.851 Td /F4 8.7 Tf [(7)] TJ ET 0.271 0.267 0.267 rg BT 342.649 269.343 Td /F1 9.8 Tf [( . Over half of all Ebola infections that have )] TJ ET BT 530.707 269.343 Td /F5 9.8 Tf [(ever)] TJ ET BT 549.671 269.343 Td /F1 9.8 Tf [( been )] TJ ET BT 26.250 257.439 Td /F1 9.8 Tf [(documented have occurred in the context of the current outbreak, which is ongoing.)] TJ ET BT 26.250 238.034 Td /F1 9.8 Tf [(In addition to a case-fatality rate greater than 50%, the current West African outbreak has proven difficult to control, has resulted )] TJ ET BT 26.250 226.129 Td /F1 9.8 Tf [(in international travel advisories, flight cancellations and border closures )] TJ ET 0.267 0.267 0.267 rg BT 339.459 227.636 Td /F4 8.7 Tf [(12)] TJ ET 0.271 0.267 0.267 rg BT 349.096 226.129 Td /F1 9.8 Tf [( , and has led to episodes of civil unrest, particularly )] TJ ET BT 26.250 214.224 Td /F1 9.8 Tf [(in Liberia )] TJ ET 0.267 0.267 0.267 rg BT 68.516 215.732 Td /F4 8.7 Tf [(11)] TJ ET 0.271 0.267 0.267 rg BT 78.154 218.113 Td /F1 8.7 Tf [(,)] TJ ET 0.267 0.267 0.267 rg BT 80.563 215.732 Td /F4 8.7 Tf [(10)] TJ ET 0.271 0.267 0.267 rg BT 90.200 214.224 Td /F1 9.8 Tf [( . The occurrence of cases in very large, well-connected urban centers \(including capitol cities of all affected )] TJ ET BT 26.250 202.320 Td /F1 9.8 Tf [(countries\) has fueled concerns about the international spread of disease via air travel, and on August 8, the World Health )] TJ ET BT 26.250 190.415 Td /F1 9.8 Tf [(Organization declared the outbreak to be a Public Health Emergency of International Concern )] TJ ET 0.267 0.267 0.267 rg BT 432.698 191.922 Td /F4 8.7 Tf [(9)] TJ ET 0.271 0.267 0.267 rg BT 437.517 190.415 Td /F1 9.8 Tf [(. This, again, contrasts with )] TJ ET BT 26.250 178.510 Td /F1 9.8 Tf [(earlier African Ebola outbreaks which have mostly occurred in smaller and less-connected cities, towns and rural areas )] TJ ET 0.267 0.267 0.267 rg BT 541.021 180.017 Td /F4 8.7 Tf [(7)] TJ ET 0.271 0.267 0.267 rg BT 545.839 178.510 Td /F1 9.8 Tf [( .)] TJ ET BT 26.250 159.105 Td /F1 9.8 Tf [(Mathematical models of infectious disease outbreaks and epidemics can be useful tools for synthesizing available information )] TJ ET BT 26.250 147.201 Td /F1 9.8 Tf [(on an infectious disease process, transforming data into useable knowledge, and defining and quantifying uncertainty about )] TJ ET BT 26.250 135.296 Td /F1 9.8 Tf [(infectious diseases)] TJ ET 0.267 0.267 0.267 rg BT 108.618 136.803 Td /F4 8.7 Tf [(13)] TJ ET 0.271 0.267 0.267 rg BT 118.255 139.184 Td /F1 8.7 Tf [(,)] TJ ET 0.267 0.267 0.267 rg BT 120.665 136.803 Td /F4 8.7 Tf [(14)] TJ ET 0.271 0.267 0.267 rg BT 130.302 135.296 Td /F1 9.8 Tf [(. Many models are explicitly mechanistic and represent epidemics as processes that result in transition )] TJ ET BT 26.250 123.391 Td /F1 9.8 Tf [(of individuals in the population between health states \(e.g., susceptible, infectious, and immune\) )] TJ ET 0.267 0.267 0.267 rg BT 442.458 124.898 Td /F4 8.7 Tf [(13)] TJ ET 0.271 0.267 0.267 rg BT 452.095 127.279 Td /F1 8.7 Tf [(,)] TJ ET 0.267 0.267 0.267 rg BT 454.505 124.898 Td /F4 8.7 Tf [(14)] TJ ET 0.271 0.267 0.267 rg BT 464.142 123.391 Td /F1 9.8 Tf [( . However, construction )] TJ ET BT 26.250 111.486 Td /F1 9.8 Tf [(of such models requires fairly detailed information on incidence, immune status in the population, and contact patterns for )] TJ ET BT 26.250 99.582 Td /F1 9.8 Tf [(correct parameterization. We have recently described a very simple mathematical model \(the Incidence Decay with Exponential )] TJ ET BT 26.250 87.677 Td /F1 9.8 Tf [(Adjustment, or IDEA, model\) that can be used as a descriptive and prognostic tool for epidemic processes when only limited )] TJ ET BT 26.250 75.772 Td /F1 9.8 Tf [(data \(e.g., cumulative incidence curves\) are available )] TJ ET 0.267 0.267 0.267 rg BT 258.719 77.279 Td /F4 8.7 Tf [(1)] TJ ET 0.271 0.267 0.267 rg BT 263.538 75.772 Td /F1 9.8 Tf [( . Here we apply this model to this epidemic; our objectives are to )] TJ ET BT 26.250 63.867 Td /F1 9.8 Tf [(reproduce, mathematically, observed patterns of epidemic growth, and to gain insights into the degree to which current control )] TJ ET BT 26.250 51.963 Td /F1 9.8 Tf [(efforts are likely to impact epidemic size and duration.)] TJ ET Q q 0.000 0.000 0.000 rg BT 291.710 19.825 Td /F1 11.0 Tf [(1)] TJ ET BT 25.000 19.825 Td /F1 11.0 Tf [(PLOS Currents Outbreaks)] TJ ET Q endstream endobj 8 0 obj << /Type /Font /Subtype /Type1 /Name /F1 /BaseFont /Helvetica /Encoding /WinAnsiEncoding >> endobj 9 0 obj << /Type /Font /Subtype /Type1 /Name /F2 /BaseFont /Times-Bold /Encoding /WinAnsiEncoding >> endobj 10 0 obj << /Type /Font /Subtype /Type1 /Name /F3 /BaseFont /Times-Italic /Encoding /WinAnsiEncoding >> endobj 11 0 obj << /Type /Font /Subtype /Type1 /Name /F4 /BaseFont /Helvetica-Bold /Encoding /WinAnsiEncoding >> endobj 12 0 obj << /Type /Font /Subtype /Type1 /Name /F5 /BaseFont 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26.250 710.919 Td /F1 9.8 Tf [(Case data, including cumulative incidence, and cumulative deaths, by date of report, for Liberia, Sierra Leone, Guinea, and )] TJ ET BT 26.250 699.015 Td /F1 9.8 Tf [(Nigeria were obtained from a public data repository maintained by Caitlin Rivers of Virginia Polytechnic Institute )] TJ ET BT 26.250 687.110 Td /F1 9.8 Tf [(\(https://github.com/cmrivers/ebola\). These data are derived from official case counts from the World Health Organization, but )] TJ ET BT 26.250 675.205 Td /F1 9.8 Tf [(have been aggregated and organized, making them an efficient resource for model fitting. Total case counts from this source do )] TJ ET BT 26.250 663.300 Td /F1 9.8 Tf [(not distinguish between suspect, probable and confirmed case counts, and consequently cumulative incidence may decrease )] TJ ET BT 26.250 651.396 Td /F1 9.8 Tf [(between measurements reflecting suspect cases who have been excluded through testing or other means. As only a fraction of )] TJ ET BT 26.250 639.491 Td /F1 9.8 Tf [(cases are subject to virological confirmation, we also obtained virologically-confirmed case counts, by date, from the Virology )] TJ ET BT 26.250 627.586 Td /F1 9.8 Tf [(Down Under blog, maintained by Dr. Ian Mackay \(http://virologydownunder.blogspot.com.au/\). These estimates are, again, )] TJ ET BT 26.250 615.681 Td /F1 9.8 Tf [(derived from World Health Organization reports. Dr. Mackays graphs are created in the Tableau application, and numerical )] TJ ET BT 26.250 603.777 Td /F1 9.8 Tf [(data can be obtained using Tableau \(http://www.tableausoftware.com\).)] TJ ET BT 26.250 584.372 Td /F5 9.8 Tf [(Model)] TJ ET BT 26.250 564.967 Td /F1 9.8 Tf [(We utilized the previously described incidence decay with exponential adjustment \(IDEA\) model to evaluate epidemic )] TJ ET BT 26.250 553.062 Td /F1 9.8 Tf [(dynamics )] TJ ET 0.267 0.267 0.267 rg BT 70.135 554.570 Td /F4 8.7 Tf [(1)] TJ ET 0.271 0.267 0.267 rg BT 74.953 553.062 Td /F1 9.8 Tf [( . This model describes epidemic processes both in terms of exponential growth \(a function of the basic reproductive )] TJ ET BT 26.250 541.158 Td /F1 9.8 Tf [(number, R)] TJ ET BT 71.763 539.093 Td /F1 8.7 Tf [(0)] TJ ET BT 76.582 541.158 Td /F1 9.8 Tf [(\) and in terms of simultaneous decay, brought about by behavioral change, public health interventions, increased )] TJ ET BT 26.250 529.253 Td /F1 9.8 Tf [(immunity in the population, or any other dynamic change that slows disease transmission; the model is descriptive and cannot )] TJ ET BT 26.250 517.348 Td /F1 9.8 Tf [(distinguish between putative controlling mechanisms, but has the advantage of allowing epidemic growth to slow even before )] TJ ET BT 26.250 505.443 Td /F1 9.8 Tf [(the critical fraction of susceptibles in the population is exhausted )] TJ ET 0.267 0.267 0.267 rg BT 306.426 506.951 Td /F4 8.7 Tf [(1)] TJ ET 0.271 0.267 0.267 rg BT 311.245 509.332 Td /F1 8.7 Tf [(,)] TJ ET 0.267 0.267 0.267 rg BT 313.654 506.951 Td /F4 8.7 Tf [(13)] TJ ET 0.271 0.267 0.267 rg BT 323.291 505.443 Td /F1 9.8 Tf [( . We have previously shown excellent agreement between )] TJ ET BT 26.250 493.539 Td /F1 9.8 Tf [(the IDEA model and a discrete-time susceptible-infectious-removed \(SIR\) compartmental model, when R)] TJ ET BT 477.607 491.474 Td /F1 8.7 Tf [(0)] TJ ET BT 482.425 493.539 Td /F1 9.8 Tf [( is low or moderate )] TJ ET 0.267 0.267 0.267 rg BT 567.494 495.046 Td /F4 8.7 Tf [(1)] TJ ET 0.271 0.267 0.267 rg BT 572.313 493.539 Td /F1 9.8 Tf [( . )] TJ ET BT 26.250 481.634 Td /F1 9.8 Tf [(The IDEA model has several attractive properties: it can be readily parameterized by fitting to either incidence or cumulative )] TJ ET BT 26.250 469.729 Td /F1 9.8 Tf [(incidence data, requires no assumptions regarding immune status in the population, and appears to provide reasonably )] TJ ET BT 26.250 457.824 Td /F1 9.8 Tf [(accurate projections about epidemic size and duration \(in the absence of change in control efforts\) based on pre-peak epidemic )] TJ ET BT 26.250 445.920 Td /F1 9.8 Tf [(data when R)] TJ ET BT 80.987 443.855 Td /F1 8.7 Tf [(0)] TJ ET BT 85.805 445.920 Td /F1 9.8 Tf [( is low or moderate. Furthermore, comparison with simulations suggests that the model can identify multi-wave )] TJ ET BT 26.250 434.015 Td /F1 9.8 Tf [(epidemics or abrupt changes in control based on sudden changes in the value of the control parameter )] TJ ET BT 472.274 434.015 Td /F5 9.8 Tf [(d )] TJ ET BT 480.405 434.015 Td /F1 9.8 Tf [(\(as described below\) )] TJ ET BT 26.250 422.110 Td /F1 9.8 Tf [(from generation to generation)] TJ ET 0.267 0.267 0.267 rg BT 154.150 423.617 Td /F4 8.7 Tf [(1)] TJ ET 0.271 0.267 0.267 rg BT 158.969 422.110 Td /F1 9.8 Tf [(.)] TJ ET BT 26.250 398.429 Td /F1 9.8 Tf [(The model utilizes the following functional form: )] TJ ET q 111.750 0 0 17.250 233.788 394.979 cm /I4 Do Q BT 345.538 398.429 Td /F1 9.8 Tf [(, where )] TJ ET BT 380.219 398.429 Td /F5 9.8 Tf [(t )] TJ ET BT 385.640 398.429 Td /F1 9.8 Tf [(is scaled in generation time, with R)] TJ ET BT 536.278 399.038 Td /F1 8.7 Tf [(0 )] TJ ET BT 543.506 398.429 Td /F1 9.8 Tf [(the )] TJ ET BT 26.250 385.455 Td /F1 9.8 Tf [(basic reproductive number, and )] TJ ET BT 165.519 385.455 Td /F5 9.8 Tf [(d)] TJ ET BT 170.940 385.455 Td /F1 9.8 Tf [( a control parameter that causes incidence to decay. I)] TJ ET BT 408.840 383.391 Td /F1 8.7 Tf [(t )] TJ ET BT 413.659 385.455 Td /F1 9.8 Tf [(represents incident cases in a given )] TJ ET BT 26.250 373.551 Td /F1 9.8 Tf [(generation. In the absence of control, incident case counts grow to the power of )] TJ ET BT 372.024 373.551 Td /F5 9.8 Tf [(t)] TJ ET BT 374.735 373.551 Td /F1 9.8 Tf [(. However, when control is present, the )] TJ ET BT 26.250 361.646 Td /F1 9.8 Tf [(effective reproduction number is reduced by a power of )] TJ ET BT 266.861 361.646 Td /F5 9.8 Tf [(t)] TJ ET BT 269.571 365.534 Td /F5 8.7 Tf [(2)] TJ ET BT 274.390 361.646 Td /F1 9.8 Tf [(, causing transmission to slow and stop even when the absolute value )] TJ ET BT 26.250 349.741 Td /F1 9.8 Tf [(of )] TJ ET BT 37.092 349.741 Td /F5 9.8 Tf [(d )] TJ ET BT 45.224 349.741 Td /F1 9.8 Tf [(is small. Best fit parameter values are estimated by fitting; we have generally identified preferred parameter values as those )] TJ ET BT 26.250 337.836 Td /F1 9.8 Tf [(that minimize the root-mean-squared distance between model estimates and empirical data, but other approaches \(e.g., )] TJ ET BT 26.250 325.932 Td /F1 9.8 Tf [(Bayesian maximum likelihood approaches\) are also possible.)] TJ ET BT 26.250 306.527 Td /F5 9.8 Tf [(Analyses)] TJ ET BT 26.250 287.122 Td /F1 9.8 Tf [(We utilized prior estimates of incubation period for Ebola virus infection \(mean approximately 13 days\) )] TJ ET 0.267 0.267 0.267 rg BT 468.959 288.629 Td /F4 8.7 Tf [(3)] TJ ET 0.271 0.267 0.267 rg BT 473.777 287.122 Td /F1 9.8 Tf [( and duration of )] TJ ET BT 26.250 275.217 Td /F1 9.8 Tf [(infectivity \(estimated at 3-5 days\) )] TJ ET 0.267 0.267 0.267 rg BT 171.466 276.725 Td /F4 8.7 Tf [(2)] TJ ET 0.271 0.267 0.267 rg BT 176.285 275.217 Td /F1 9.8 Tf [( to derive a generation time of 15 days for the outbreak, based on the heuristic )] TJ ET BT 516.638 275.217 Td /F5 9.8 Tf [(t)] TJ ET BT 519.349 275.217 Td /F1 9.8 Tf [( = incubation )] TJ ET BT 26.250 263.313 Td /F1 9.8 Tf [(+ 1/2 infective period, though this was varied \(from 12 days to 18 days\) in sensitivity analyses. We assumed incubation to be )] TJ ET BT 26.250 251.408 Td /F1 9.8 Tf [(equivalent to latency for this virus. The initial reported case count was 42 cases on March 22, 2014. Prior reports of R)] TJ ET BT 531.846 249.344 Td /F1 8.7 Tf [(0)] TJ ET BT 536.665 251.408 Td /F1 9.8 Tf [( for Ebola )] TJ ET BT 26.250 239.503 Td /F1 9.8 Tf [(virus have ranged from 1.5 to 2.7 )] TJ ET 0.267 0.267 0.267 rg BT 172.032 241.010 Td /F4 8.7 Tf [(2)] TJ ET 0.271 0.267 0.267 rg BT 176.851 243.391 Td /F1 8.7 Tf [(,)] TJ ET 0.267 0.267 0.267 rg BT 179.260 241.010 Td /F4 8.7 Tf [(4)] TJ ET 0.271 0.267 0.267 rg BT 184.079 239.503 Td /F1 9.8 Tf [( , and this cumulative case count would be consistent with that seen in approximately the )] TJ ET BT 26.250 227.598 Td /F1 9.8 Tf [(fifth generation of an epidemic process with R0 ~ 2; this was, again, varied from 3 generations to 7 generations in sensitivity )] TJ ET BT 26.250 215.694 Td /F1 9.8 Tf [(analyses.)] TJ ET BT 26.250 196.289 Td /F1 9.8 Tf [(In our base case analyses, we fit our model to time series data iteratively, using a progressively increasing number of outbreak )] TJ ET BT 26.250 184.384 Td /F1 9.8 Tf [(generations. Fits were performed using the Berkeley Madonna software package \(Berkeley, California, )] TJ ET BT 26.250 172.479 Td /F1 9.8 Tf [(http://www.berkeleymadonna.com/\), both using the built-in curve fit function, and also by evaluating root-mean-squared )] TJ ET BT 26.250 160.575 Td /F1 9.8 Tf [(distances between model estimates and observations for varying combinations of R)] TJ ET BT 386.610 158.510 Td /F1 8.7 Tf [(0)] TJ ET BT 391.429 160.575 Td /F1 9.8 Tf [( and )] TJ ET BT 413.113 160.575 Td /F5 9.8 Tf [(d)] TJ ET BT 418.534 160.575 Td /F1 9.8 Tf [(.)] TJ ET BT 26.250 141.170 Td /F1 9.8 Tf [(Model fits utilized epidemic time series available as of August 22, 2014. In addition to fitting models to overall epidemic )] TJ ET BT 26.250 129.265 Td /F1 9.8 Tf [(cumulative incidence curves, we fit models to country-specific data from Guinea, Liberia, and Sierra Leone. A separate model )] TJ ET BT 26.250 117.360 Td /F1 9.8 Tf [(was not fitted to data from Nigeria due to the low case count \(N = 15\) at the time of writing. For the purposes of fitting country-)] TJ ET BT 26.250 105.456 Td /F1 9.8 Tf [(level models, we used the same estimated start date for the Guinea epidemic as was used for the outbreak overall, while the )] TJ ET BT 26.250 93.551 Td /F1 9.8 Tf [(first generation of Liberias outbreak was dated to March 27, 2014, and Sierra Leones to May 27, 2014.)] TJ ET BT 26.250 56.948 Td /F4 12.0 Tf [(Results)] TJ ET Q q 15.000 27.113 577.500 749.887 re W n 0.271 0.267 0.267 rg BT 26.250 750.278 Td /F4 12.0 Tf [(Methods)] TJ ET BT 26.250 730.324 Td /F5 9.8 Tf [(Data Sources)] TJ ET BT 26.250 710.919 Td /F1 9.8 Tf [(Case data, including cumulative incidence, and cumulative deaths, by date of report, for Liberia, Sierra Leone, Guinea, and )] TJ ET BT 26.250 699.015 Td /F1 9.8 Tf [(Nigeria were obtained from a public data repository maintained by Caitlin Rivers of Virginia Polytechnic Institute )] TJ ET BT 26.250 687.110 Td /F1 9.8 Tf [(\(https://github.com/cmrivers/ebola\). These data are derived from official case counts from the World Health Organization, but )] TJ ET BT 26.250 675.205 Td /F1 9.8 Tf [(have been aggregated and organized, making them an efficient resource for model fitting. Total case counts from this source do )] TJ ET BT 26.250 663.300 Td /F1 9.8 Tf [(not distinguish between suspect, probable and confirmed case counts, and consequently cumulative incidence may decrease )] TJ ET BT 26.250 651.396 Td /F1 9.8 Tf [(between measurements reflecting suspect cases who have been excluded through testing or other means. As only a fraction of )] TJ ET BT 26.250 639.491 Td /F1 9.8 Tf [(cases are subject to virological confirmation, we also obtained virologically-confirmed case counts, by date, from the Virology )] TJ ET BT 26.250 627.586 Td /F1 9.8 Tf [(Down Under blog, maintained by Dr. Ian Mackay \(http://virologydownunder.blogspot.com.au/\). These estimates are, again, )] TJ ET BT 26.250 615.681 Td /F1 9.8 Tf [(derived from World Health Organization reports. Dr. Mackays graphs are created in the Tableau application, and numerical )] TJ ET BT 26.250 603.777 Td /F1 9.8 Tf [(data can be obtained using Tableau \(http://www.tableausoftware.com\).)] TJ ET BT 26.250 584.372 Td /F5 9.8 Tf [(Model)] TJ ET BT 26.250 564.967 Td /F1 9.8 Tf [(We utilized the previously described incidence decay with exponential adjustment \(IDEA\) model to evaluate epidemic )] TJ ET BT 26.250 553.062 Td /F1 9.8 Tf [(dynamics )] TJ ET 0.267 0.267 0.267 rg BT 70.135 554.570 Td /F4 8.7 Tf [(1)] TJ ET 0.271 0.267 0.267 rg BT 74.953 553.062 Td /F1 9.8 Tf [( . This model describes epidemic processes both in terms of exponential growth \(a function of the basic reproductive )] TJ ET BT 26.250 541.158 Td /F1 9.8 Tf [(number, R)] TJ ET BT 71.763 539.093 Td /F1 8.7 Tf [(0)] TJ ET BT 76.582 541.158 Td /F1 9.8 Tf [(\) and in terms of simultaneous decay, brought about by behavioral change, public health interventions, increased )] TJ ET BT 26.250 529.253 Td /F1 9.8 Tf [(immunity in the population, or any other dynamic change that slows disease transmission; the model is descriptive and cannot )] TJ ET BT 26.250 517.348 Td /F1 9.8 Tf [(distinguish between putative controlling mechanisms, but has the advantage of allowing epidemic growth to slow even before )] TJ ET BT 26.250 505.443 Td /F1 9.8 Tf [(the critical fraction of susceptibles in the population is exhausted )] TJ ET 0.267 0.267 0.267 rg BT 306.426 506.951 Td /F4 8.7 Tf [(1)] TJ ET 0.271 0.267 0.267 rg BT 311.245 509.332 Td /F1 8.7 Tf [(,)] TJ ET 0.267 0.267 0.267 rg BT 313.654 506.951 Td /F4 8.7 Tf [(13)] TJ ET 0.271 0.267 0.267 rg BT 323.291 505.443 Td /F1 9.8 Tf [( . We have previously shown excellent agreement between )] TJ ET BT 26.250 493.539 Td /F1 9.8 Tf [(the IDEA model and a discrete-time susceptible-infectious-removed \(SIR\) compartmental model, when R)] TJ ET BT 477.607 491.474 Td /F1 8.7 Tf [(0)] TJ ET BT 482.425 493.539 Td /F1 9.8 Tf [( is low or moderate )] TJ ET 0.267 0.267 0.267 rg BT 567.494 495.046 Td /F4 8.7 Tf [(1)] TJ ET 0.271 0.267 0.267 rg BT 572.313 493.539 Td /F1 9.8 Tf [( . )] TJ ET BT 26.250 481.634 Td /F1 9.8 Tf [(The IDEA model has several attractive properties: it can be readily parameterized by fitting to either incidence or cumulative )] TJ ET BT 26.250 469.729 Td /F1 9.8 Tf [(incidence data, requires no assumptions regarding immune status in the population, and appears to provide reasonably )] TJ ET BT 26.250 457.824 Td /F1 9.8 Tf [(accurate projections about epidemic size and duration \(in the absence of change in control efforts\) based on pre-peak epidemic )] TJ ET BT 26.250 445.920 Td /F1 9.8 Tf [(data when R)] TJ ET BT 80.987 443.855 Td /F1 8.7 Tf [(0)] TJ ET BT 85.805 445.920 Td /F1 9.8 Tf [( is low or moderate. Furthermore, comparison with simulations suggests that the model can identify multi-wave )] TJ ET BT 26.250 434.015 Td /F1 9.8 Tf [(epidemics or abrupt changes in control based on sudden changes in the value of the control parameter )] TJ ET BT 472.274 434.015 Td /F5 9.8 Tf [(d )] TJ ET BT 480.405 434.015 Td /F1 9.8 Tf [(\(as described below\) )] TJ ET BT 26.250 422.110 Td /F1 9.8 Tf [(from generation to generation)] TJ ET 0.267 0.267 0.267 rg BT 154.150 423.617 Td /F4 8.7 Tf [(1)] TJ ET 0.271 0.267 0.267 rg BT 158.969 422.110 Td /F1 9.8 Tf [(.)] TJ ET BT 26.250 398.429 Td /F1 9.8 Tf [(The model utilizes the following functional form: )] TJ ET q 111.750 0 0 17.250 233.788 394.979 cm /I6 Do Q BT 345.538 398.429 Td /F1 9.8 Tf [(, where )] TJ ET BT 380.219 398.429 Td /F5 9.8 Tf [(t )] TJ ET BT 385.640 398.429 Td /F1 9.8 Tf [(is scaled in generation time, with R)] TJ ET BT 536.278 399.038 Td /F1 8.7 Tf [(0 )] TJ ET BT 543.506 398.429 Td /F1 9.8 Tf [(the )] TJ ET BT 26.250 385.455 Td /F1 9.8 Tf [(basic reproductive number, and )] TJ ET BT 165.519 385.455 Td /F5 9.8 Tf [(d)] TJ ET BT 170.940 385.455 Td /F1 9.8 Tf [( a control parameter that causes incidence to decay. I)] TJ ET BT 408.840 383.391 Td /F1 8.7 Tf [(t )] TJ ET BT 413.659 385.455 Td /F1 9.8 Tf [(represents incident cases in a given )] TJ ET BT 26.250 373.551 Td /F1 9.8 Tf [(generation. In the absence of control, incident case counts grow to the power of )] TJ ET BT 372.024 373.551 Td /F5 9.8 Tf [(t)] TJ ET BT 374.735 373.551 Td /F1 9.8 Tf [(. However, when control is present, the )] TJ ET BT 26.250 361.646 Td /F1 9.8 Tf [(effective reproduction number is reduced by a power of )] TJ ET BT 266.861 361.646 Td /F5 9.8 Tf [(t)] TJ ET BT 269.571 365.534 Td /F5 8.7 Tf [(2)] TJ ET BT 274.390 361.646 Td /F1 9.8 Tf [(, causing transmission to slow and stop even when the absolute value )] TJ ET BT 26.250 349.741 Td /F1 9.8 Tf [(of )] TJ ET BT 37.092 349.741 Td /F5 9.8 Tf [(d )] TJ ET BT 45.224 349.741 Td /F1 9.8 Tf [(is small. Best fit parameter values are estimated by fitting; we have generally identified preferred parameter values as those )] TJ ET BT 26.250 337.836 Td /F1 9.8 Tf [(that minimize the root-mean-squared distance between model estimates and empirical data, but other approaches \(e.g., )] TJ ET BT 26.250 325.932 Td /F1 9.8 Tf [(Bayesian maximum likelihood approaches\) are also possible.)] TJ ET BT 26.250 306.527 Td /F5 9.8 Tf [(Analyses)] TJ ET BT 26.250 287.122 Td /F1 9.8 Tf [(We utilized prior estimates of incubation period for Ebola virus infection \(mean approximately 13 days\) )] TJ ET 0.267 0.267 0.267 rg BT 468.959 288.629 Td /F4 8.7 Tf [(3)] TJ ET 0.271 0.267 0.267 rg BT 473.777 287.122 Td /F1 9.8 Tf [( and duration of )] TJ ET BT 26.250 275.217 Td /F1 9.8 Tf [(infectivity \(estimated at 3-5 days\) )] TJ ET 0.267 0.267 0.267 rg BT 171.466 276.725 Td /F4 8.7 Tf [(2)] TJ ET 0.271 0.267 0.267 rg BT 176.285 275.217 Td /F1 9.8 Tf [( to derive a generation time of 15 days for the outbreak, based on the heuristic )] TJ ET BT 516.638 275.217 Td /F5 9.8 Tf [(t)] TJ ET BT 519.349 275.217 Td /F1 9.8 Tf [( = incubation )] TJ ET BT 26.250 263.313 Td /F1 9.8 Tf [(+ 1/2 infective period, though this was varied \(from 12 days to 18 days\) in sensitivity analyses. We assumed incubation to be )] TJ ET BT 26.250 251.408 Td /F1 9.8 Tf [(equivalent to latency for this virus. The initial reported case count was 42 cases on March 22, 2014. Prior reports of R)] TJ ET BT 531.846 249.344 Td /F1 8.7 Tf [(0)] TJ ET BT 536.665 251.408 Td /F1 9.8 Tf [( for Ebola )] TJ ET BT 26.250 239.503 Td /F1 9.8 Tf [(virus have ranged from 1.5 to 2.7 )] TJ ET 0.267 0.267 0.267 rg BT 172.032 241.010 Td /F4 8.7 Tf [(2)] TJ ET 0.271 0.267 0.267 rg BT 176.851 243.391 Td /F1 8.7 Tf [(,)] TJ ET 0.267 0.267 0.267 rg BT 179.260 241.010 Td /F4 8.7 Tf [(4)] TJ ET 0.271 0.267 0.267 rg BT 184.079 239.503 Td /F1 9.8 Tf [( , and this cumulative case count would be consistent with that seen in approximately the )] TJ ET BT 26.250 227.598 Td /F1 9.8 Tf [(fifth generation of an epidemic process with R0 ~ 2; this was, again, varied from 3 generations to 7 generations in sensitivity )] TJ ET BT 26.250 215.694 Td /F1 9.8 Tf [(analyses.)] TJ ET BT 26.250 196.289 Td /F1 9.8 Tf [(In our base case analyses, we fit our model to time series data iteratively, using a progressively increasing number of outbreak )] TJ ET BT 26.250 184.384 Td /F1 9.8 Tf [(generations. Fits were performed using the Berkeley Madonna software package \(Berkeley, California, )] TJ ET BT 26.250 172.479 Td /F1 9.8 Tf [(http://www.berkeleymadonna.com/\), both using the built-in curve fit function, and also by evaluating root-mean-squared )] TJ ET BT 26.250 160.575 Td /F1 9.8 Tf [(distances between model estimates and observations for varying combinations of R)] TJ ET BT 386.610 158.510 Td /F1 8.7 Tf [(0)] TJ ET BT 391.429 160.575 Td /F1 9.8 Tf [( and )] TJ ET BT 413.113 160.575 Td /F5 9.8 Tf [(d)] TJ ET BT 418.534 160.575 Td /F1 9.8 Tf [(.)] TJ ET BT 26.250 141.170 Td /F1 9.8 Tf [(Model fits utilized epidemic time series available as of August 22, 2014. In addition to fitting models to overall epidemic )] TJ ET BT 26.250 129.265 Td /F1 9.8 Tf [(cumulative incidence curves, we fit models to country-specific data from Guinea, Liberia, and Sierra Leone. A separate model )] TJ ET BT 26.250 117.360 Td /F1 9.8 Tf [(was not fitted to data from Nigeria due to the low case count \(N = 15\) at the time of writing. For the purposes of fitting country-)] TJ ET BT 26.250 105.456 Td /F1 9.8 Tf [(level models, we used the same estimated start date for the Guinea epidemic as was used for the outbreak overall, while the )] TJ ET BT 26.250 93.551 Td /F1 9.8 Tf [(first generation of Liberias outbreak was dated to March 27, 2014, and Sierra Leones to May 27, 2014.)] TJ ET BT 26.250 56.948 Td /F4 12.0 Tf [(Results)] TJ ET Q q 15.000 27.113 577.500 749.887 re W n 0.271 0.267 0.267 rg BT 26.250 750.278 Td /F4 12.0 Tf [(Methods)] TJ ET BT 26.250 730.324 Td /F5 9.8 Tf [(Data Sources)] TJ ET BT 26.250 710.919 Td /F1 9.8 Tf [(Case data, including cumulative incidence, and cumulative deaths, by date of report, for Liberia, Sierra Leone, Guinea, and )] TJ ET BT 26.250 699.015 Td /F1 9.8 Tf [(Nigeria were obtained from a public data repository maintained by Caitlin Rivers of Virginia Polytechnic Institute )] TJ ET BT 26.250 687.110 Td /F1 9.8 Tf [(\(https://github.com/cmrivers/ebola\). These data are derived from official case counts from the World Health Organization, but )] TJ ET BT 26.250 675.205 Td /F1 9.8 Tf [(have been aggregated and organized, making them an efficient resource for model fitting. Total case counts from this source do )] TJ ET BT 26.250 663.300 Td /F1 9.8 Tf [(not distinguish between suspect, probable and confirmed case counts, and consequently cumulative incidence may decrease )] TJ ET BT 26.250 651.396 Td /F1 9.8 Tf [(between measurements reflecting suspect cases who have been excluded through testing or other means. As only a fraction of )] TJ ET BT 26.250 639.491 Td /F1 9.8 Tf [(cases are subject to virological confirmation, we also obtained virologically-confirmed case counts, by date, from the Virology )] TJ ET BT 26.250 627.586 Td /F1 9.8 Tf [(Down Under blog, maintained by Dr. Ian Mackay \(http://virologydownunder.blogspot.com.au/\). These estimates are, again, )] TJ ET BT 26.250 615.681 Td /F1 9.8 Tf [(derived from World Health Organization reports. Dr. Mackays graphs are created in the Tableau application, and numerical )] TJ ET BT 26.250 603.777 Td /F1 9.8 Tf [(data can be obtained using Tableau \(http://www.tableausoftware.com\).)] TJ ET BT 26.250 584.372 Td /F5 9.8 Tf [(Model)] TJ ET BT 26.250 564.967 Td /F1 9.8 Tf [(We utilized the previously described incidence decay with exponential adjustment \(IDEA\) model to evaluate epidemic )] TJ ET BT 26.250 553.062 Td /F1 9.8 Tf [(dynamics )] TJ ET 0.267 0.267 0.267 rg BT 70.135 554.570 Td /F4 8.7 Tf [(1)] TJ ET 0.271 0.267 0.267 rg BT 74.953 553.062 Td /F1 9.8 Tf [( . This model describes epidemic processes both in terms of exponential growth \(a function of the basic reproductive )] TJ ET BT 26.250 541.158 Td /F1 9.8 Tf [(number, R)] TJ ET BT 71.763 539.093 Td /F1 8.7 Tf [(0)] TJ ET BT 76.582 541.158 Td /F1 9.8 Tf [(\) and in terms of simultaneous decay, brought about by behavioral change, public health interventions, increased )] TJ ET BT 26.250 529.253 Td /F1 9.8 Tf [(immunity in the population, or any other dynamic change that slows disease transmission; the model is descriptive and cannot )] TJ ET BT 26.250 517.348 Td /F1 9.8 Tf [(distinguish between putative controlling mechanisms, but has the advantage of allowing epidemic growth to slow even before )] TJ ET BT 26.250 505.443 Td /F1 9.8 Tf [(the critical fraction of susceptibles in the population is exhausted )] TJ ET 0.267 0.267 0.267 rg BT 306.426 506.951 Td /F4 8.7 Tf [(1)] TJ ET 0.271 0.267 0.267 rg BT 311.245 509.332 Td /F1 8.7 Tf [(,)] TJ ET 0.267 0.267 0.267 rg BT 313.654 506.951 Td /F4 8.7 Tf [(13)] TJ ET 0.271 0.267 0.267 rg BT 323.291 505.443 Td /F1 9.8 Tf [( . We have previously shown excellent agreement between )] TJ ET BT 26.250 493.539 Td /F1 9.8 Tf [(the IDEA model and a discrete-time susceptible-infectious-removed \(SIR\) compartmental model, when R)] TJ ET BT 477.607 491.474 Td /F1 8.7 Tf [(0)] TJ ET BT 482.425 493.539 Td /F1 9.8 Tf [( is low or moderate )] TJ ET 0.267 0.267 0.267 rg BT 567.494 495.046 Td /F4 8.7 Tf [(1)] TJ ET 0.271 0.267 0.267 rg BT 572.313 493.539 Td /F1 9.8 Tf [( . )] TJ ET BT 26.250 481.634 Td /F1 9.8 Tf [(The IDEA model has several attractive properties: it can be readily parameterized by fitting to either incidence or cumulative )] TJ ET BT 26.250 469.729 Td /F1 9.8 Tf [(incidence data, requires no assumptions regarding immune status in the population, and appears to provide reasonably )] TJ ET BT 26.250 457.824 Td /F1 9.8 Tf [(accurate projections about epidemic size and duration \(in the absence of change in control efforts\) based on pre-peak epidemic )] TJ ET BT 26.250 445.920 Td /F1 9.8 Tf [(data when R)] TJ ET BT 80.987 443.855 Td /F1 8.7 Tf [(0)] TJ ET BT 85.805 445.920 Td /F1 9.8 Tf [( is low or moderate. Furthermore, comparison with simulations suggests that the model can identify multi-wave )] TJ ET BT 26.250 434.015 Td /F1 9.8 Tf [(epidemics or abrupt changes in control based on sudden changes in the value of the control parameter )] TJ ET BT 472.274 434.015 Td /F5 9.8 Tf [(d )] TJ ET BT 480.405 434.015 Td /F1 9.8 Tf [(\(as described below\) )] TJ ET BT 26.250 422.110 Td /F1 9.8 Tf [(from generation to generation)] TJ ET 0.267 0.267 0.267 rg BT 154.150 423.617 Td /F4 8.7 Tf [(1)] TJ ET 0.271 0.267 0.267 rg BT 158.969 422.110 Td /F1 9.8 Tf [(.)] TJ ET BT 26.250 398.429 Td /F1 9.8 Tf [(The model utilizes the following functional form: )] TJ ET q 111.750 0 0 17.250 233.788 394.979 cm /I8 Do Q BT 345.538 398.429 Td /F1 9.8 Tf [(, where )] TJ ET BT 380.219 398.429 Td /F5 9.8 Tf [(t )] TJ ET BT 385.640 398.429 Td /F1 9.8 Tf [(is scaled in generation time, with R)] TJ ET BT 536.278 399.038 Td /F1 8.7 Tf [(0 )] TJ ET BT 543.506 398.429 Td /F1 9.8 Tf [(the )] TJ ET BT 26.250 385.455 Td /F1 9.8 Tf [(basic reproductive number, and )] TJ ET BT 165.519 385.455 Td /F5 9.8 Tf [(d)] TJ ET BT 170.940 385.455 Td /F1 9.8 Tf [( a control parameter that causes incidence to decay. I)] TJ ET BT 408.840 383.391 Td /F1 8.7 Tf [(t )] TJ ET BT 413.659 385.455 Td /F1 9.8 Tf [(represents incident cases in a given )] TJ ET BT 26.250 373.551 Td /F1 9.8 Tf [(generation. In the absence of control, incident case counts grow to the power of )] TJ ET BT 372.024 373.551 Td /F5 9.8 Tf [(t)] TJ ET BT 374.735 373.551 Td /F1 9.8 Tf [(. However, when control is present, the )] TJ ET BT 26.250 361.646 Td /F1 9.8 Tf [(effective reproduction number is reduced by a power of )] TJ ET BT 266.861 361.646 Td /F5 9.8 Tf [(t)] TJ ET BT 269.571 365.534 Td /F5 8.7 Tf [(2)] TJ ET BT 274.390 361.646 Td /F1 9.8 Tf [(, causing transmission to slow and stop even when the absolute value )] TJ ET BT 26.250 349.741 Td /F1 9.8 Tf [(of )] TJ ET BT 37.092 349.741 Td /F5 9.8 Tf [(d )] TJ ET BT 45.224 349.741 Td /F1 9.8 Tf [(is small. Best fit parameter values are estimated by fitting; we have generally identified preferred parameter values as those )] TJ ET BT 26.250 337.836 Td /F1 9.8 Tf [(that minimize the root-mean-squared distance between model estimates and empirical data, but other approaches \(e.g., )] TJ ET BT 26.250 325.932 Td /F1 9.8 Tf [(Bayesian maximum likelihood approaches\) are also possible.)] TJ ET BT 26.250 306.527 Td /F5 9.8 Tf [(Analyses)] TJ ET BT 26.250 287.122 Td /F1 9.8 Tf [(We utilized prior estimates of incubation period for Ebola virus infection \(mean approximately 13 days\) )] TJ ET 0.267 0.267 0.267 rg BT 468.959 288.629 Td /F4 8.7 Tf [(3)] TJ ET 0.271 0.267 0.267 rg BT 473.777 287.122 Td /F1 9.8 Tf [( and duration of )] TJ ET BT 26.250 275.217 Td /F1 9.8 Tf [(infectivity \(estimated at 3-5 days\) )] TJ ET 0.267 0.267 0.267 rg BT 171.466 276.725 Td /F4 8.7 Tf [(2)] TJ ET 0.271 0.267 0.267 rg BT 176.285 275.217 Td /F1 9.8 Tf [( to derive a generation time of 15 days for the outbreak, based on the heuristic )] TJ ET BT 516.638 275.217 Td /F5 9.8 Tf [(t)] TJ ET BT 519.349 275.217 Td /F1 9.8 Tf [( = incubation )] TJ ET BT 26.250 263.313 Td /F1 9.8 Tf [(+ 1/2 infective period, though this was varied \(from 12 days to 18 days\) in sensitivity analyses. We assumed incubation to be )] TJ ET BT 26.250 251.408 Td /F1 9.8 Tf [(equivalent to latency for this virus. The initial reported case count was 42 cases on March 22, 2014. Prior reports of R)] TJ ET BT 531.846 249.344 Td /F1 8.7 Tf [(0)] TJ ET BT 536.665 251.408 Td /F1 9.8 Tf [( for Ebola )] TJ ET BT 26.250 239.503 Td /F1 9.8 Tf [(virus have ranged from 1.5 to 2.7 )] TJ ET 0.267 0.267 0.267 rg BT 172.032 241.010 Td /F4 8.7 Tf [(2)] TJ ET 0.271 0.267 0.267 rg BT 176.851 243.391 Td /F1 8.7 Tf [(,)] TJ ET 0.267 0.267 0.267 rg BT 179.260 241.010 Td /F4 8.7 Tf [(4)] TJ ET 0.271 0.267 0.267 rg BT 184.079 239.503 Td /F1 9.8 Tf [( , and this cumulative case count would be consistent with that seen in approximately the )] TJ ET BT 26.250 227.598 Td /F1 9.8 Tf [(fifth generation of an epidemic process with R0 ~ 2; this was, again, varied from 3 generations to 7 generations in sensitivity )] TJ ET BT 26.250 215.694 Td /F1 9.8 Tf [(analyses.)] TJ ET BT 26.250 196.289 Td /F1 9.8 Tf [(In our base case analyses, we fit our model to time series data iteratively, using a progressively increasing number of outbreak )] TJ ET BT 26.250 184.384 Td /F1 9.8 Tf [(generations. Fits were performed using the Berkeley Madonna software package \(Berkeley, California, )] TJ ET BT 26.250 172.479 Td /F1 9.8 Tf [(http://www.berkeleymadonna.com/\), both using the built-in curve fit function, and also by evaluating root-mean-squared )] TJ ET BT 26.250 160.575 Td /F1 9.8 Tf [(distances between model estimates and observations for varying combinations of R)] TJ ET BT 386.610 158.510 Td /F1 8.7 Tf [(0)] TJ ET BT 391.429 160.575 Td /F1 9.8 Tf [( and )] TJ ET BT 413.113 160.575 Td /F5 9.8 Tf [(d)] TJ ET BT 418.534 160.575 Td /F1 9.8 Tf [(.)] TJ ET BT 26.250 141.170 Td /F1 9.8 Tf [(Model fits utilized epidemic time series available as of August 22, 2014. In addition to fitting models to overall epidemic )] TJ ET BT 26.250 129.265 Td /F1 9.8 Tf [(cumulative incidence curves, we fit models to country-specific data from Guinea, Liberia, and Sierra Leone. A separate model )] TJ ET BT 26.250 117.360 Td /F1 9.8 Tf [(was not fitted to data from Nigeria due to the low case count \(N = 15\) at the time of writing. For the purposes of fitting country-)] TJ ET BT 26.250 105.456 Td /F1 9.8 Tf [(level models, we used the same estimated start date for the Guinea epidemic as was used for the outbreak overall, while the )] TJ ET BT 26.250 93.551 Td /F1 9.8 Tf [(first generation of Liberias outbreak was dated to March 27, 2014, and Sierra Leones to May 27, 2014.)] TJ ET BT 26.250 56.948 Td /F4 12.0 Tf [(Results)] TJ ET Q q 0.000 0.000 0.000 rg BT 291.710 19.825 Td /F1 11.0 Tf [(2)] TJ ET BT 25.000 19.825 Td /F1 11.0 Tf [(PLOS Currents Outbreaks)] TJ ET Q endstream endobj 143 0 obj << /Type /Annot /Subtype /Link /A 144 0 R /Border [0 0 0] /H /I /Rect [ 70.1347 553.7679 74.9534 562.5862 ] >> endobj 144 0 obj << /Type /Action >> endobj 145 0 obj << /Type /Annot /Subtype /Link /A 146 0 R /Border [0 0 0] /H /I /Rect [ 306.4260 506.1489 311.2447 514.9672 ] >> endobj 146 0 obj << /Type /Action >> endobj 147 0 obj << /Type /Annot /Subtype /Link /A 148 0 R /Border [0 0 0] /H /I /Rect [ 313.6540 506.1489 323.2913 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HVg#OQ"*ĩ:uNUEUTEUUEE:QUU"FĊs9kEETEDTDDI7lvl_}?y33|vM7gň|30ݹw2$jμ#/Jtqꓡ[~{8SEp W<Y;MZQJmܱLO>O*L}C,=q?|'lg&i':f!YFh6I1}&{Y72Vy3UyO s:(3njB#u/Lwgn8dP6. sԱgK-mc gG|LBN}K2ҹpdT'U+-?ru<.!7*3߹pVUz*7>"rj|Tm*e- ֓ ݂m**;7ȵk]t:UoWj`GnFWʕ}Wm qtx7bp"Bb#7w93xz `4gPͦ>W123Cj])䑊©{9Yo.=Ƒ5˝RiαER$ϯ.6ڠR'>YHNGj1,>D:e.]_yS^m[FɚK48#*ܹ#CܘFNҁ_19M^{p*-ZVT_m[6[S> /ColorSpace /DeviceRGB /BitsPerComponent 8 /Length 32>> stream h nH@o(@ endstream endobj 195 0 obj << /Type /Annot /Subtype /Link /A 196 0 R /Border [0 0 0] /H /I /Rect [ 468.9585 287.8277 473.7772 296.6460 ] >> endobj 196 0 obj << /Type /Action >> endobj 197 0 obj << /Type /Annot /Subtype /Link /A 198 0 R /Border [0 0 0] /H /I /Rect [ 171.4665 275.9229 176.2852 284.7413 ] >> endobj 198 0 obj << /Type /Action >> endobj 199 0 obj << /Type /Annot /Subtype /Link /A 200 0 R /Border [0 0 0] /H /I /Rect [ 172.0320 240.2087 176.8507 249.0270 ] >> endobj 200 0 obj << /Type /Action >> endobj 201 0 obj << /Type /Annot /Subtype /Link /A 202 0 R /Border [0 0 0] /H /I /Rect [ 179.2600 240.2087 184.0787 249.0270 ] >> endobj 202 0 obj << /Type /Action >> endobj 203 0 obj << /Type /Page /Parent 3 0 R /Annots [ 205 0 R 207 0 R 210 0 R 213 0 R 215 0 R 217 0 R 219 0 R 221 0 R 223 0 R ] /Contents 204 0 R >> endobj 204 0 obj << /Length 18422 >> stream 0.271 0.267 0.267 rg q 15.000 17.563 577.500 759.437 re W n 0.271 0.267 0.267 rg BT 26.250 767.476 Td /F5 9.8 Tf [(Base Case Analysis)] TJ ET BT 26.250 748.071 Td /F1 9.8 Tf [(As increasing numbers of outbreak generations were used, best fit R)] TJ ET BT 322.133 746.007 Td /F1 8.7 Tf [(0)] TJ ET BT 326.952 748.071 Td /F1 9.8 Tf [( estimates and estimates of )] TJ ET BT 448.339 748.071 Td /F5 9.8 Tf [(d )] TJ ET BT 456.471 748.071 Td /F1 9.8 Tf [(declined \(Figure 1\). We )] TJ ET BT 26.250 736.167 Td /F1 9.8 Tf [(identified no abrupt surges in )] TJ ET BT 154.150 736.167 Td /F5 9.8 Tf [(d )] TJ ET BT 162.282 736.167 Td /F1 9.8 Tf [(that simulations suggest are indicative of multi-wave outbreaks )] TJ ET 0.267 0.267 0.267 rg BT 435.389 737.674 Td /F4 8.7 Tf [(1)] TJ ET 0.271 0.267 0.267 rg BT 440.208 736.167 Td /F1 9.8 Tf [( . There was a range of )] TJ ET BT 26.250 724.262 Td /F1 9.8 Tf [(combinations of R)] TJ ET BT 104.279 722.198 Td /F1 8.7 Tf [(0 )] TJ ET BT 111.507 724.262 Td /F1 9.8 Tf [(and d that provided approximate fits to observed case counts, but RMSD was lowest, by an order of )] TJ ET BT 26.250 712.357 Td /F1 9.8 Tf [(magnitude, for R)] TJ ET BT 98.322 710.293 Td /F1 8.7 Tf [(0 )] TJ ET BT 105.550 712.357 Td /F1 9.8 Tf [(values close to 1.8, and d values close to 0.01 \(Figure 2\). Our best fit model identified Ro as 1.78, and d as )] TJ ET BT 26.250 700.452 Td /F1 9.8 Tf [(0.009. Cumulative model case counts were projected to be 2435 as compared to 2473 observed cases \(Figure 3\).)] TJ ET BT 26.250 681.048 Td /F1 9.8 Tf [(Based on these parameter values, and in the absence of increase in )] TJ ET BT 323.245 681.048 Td /F5 9.8 Tf [(d)] TJ ET BT 328.666 681.048 Td /F1 9.8 Tf [( as a result of intervention, the outbreak would be )] TJ ET BT 26.250 669.143 Td /F1 9.8 Tf [(projected to have caused over 25,000 infections by the end of 2014. A peak in the epidemic would not occur until April 2015, )] TJ ET BT 26.250 657.238 Td /F1 9.8 Tf [(and continue until mid-2016, with a final size greater than 140,000 cases. However, epidemic size and duration are projected to )] TJ ET BT 26.250 645.333 Td /F1 9.8 Tf [(be extremely sensitive to incremental increases in the size of d. For example, a September 2014 increase in d by 0.005 \(to )] TJ ET BT 26.250 633.429 Td /F1 9.8 Tf [(0.014 rather than 0.009\) would diminish the projected epidemic size to < 10,000 cases, with incidence steadily diminishing )] TJ ET BT 26.250 621.524 Td /F1 9.8 Tf [(rather than increasing in the coming months.)] TJ ET BT 26.250 602.119 Td /F5 9.8 Tf [(Sensitivity Analyses and Alternate Approaches)] TJ ET BT 26.250 582.714 Td /F1 9.8 Tf [(We also fit separate models to epidemic curves derived from reported deaths, rather than cases, curves based only on )] TJ ET BT 26.250 570.810 Td /F1 9.8 Tf [(virologically confirmed cases, as well as curves based on varying assumptions about case-under-reporting, epidemic duration )] TJ ET BT 26.250 558.905 Td /F1 9.8 Tf [(prior to first reporting in March 2014, and generation times. None of these analyses provided estimates of R)] TJ ET BT 489.580 556.841 Td /F1 8.7 Tf [(0)] TJ ET BT 494.398 558.905 Td /F1 9.8 Tf [( and )] TJ ET BT 516.082 558.905 Td /F5 9.8 Tf [(d)] TJ ET BT 521.503 558.905 Td /F1 9.8 Tf [( that differed )] TJ ET BT 26.250 547.000 Td /F1 9.8 Tf [(markedly from those derived in the base case \(Table 1\), though it should be noted that the exponential nature of epidemic )] TJ ET BT 26.250 535.095 Td /F1 9.8 Tf [(growth means that even small changes in model parameters would result in large differences in final epidemic sizes.)] TJ ET BT 26.250 515.691 Td /F1 9.8 Tf [(In our base case we fitted IDEA models to overall cumulative epidemic curves, but fitting curves to individual country-level )] TJ ET BT 26.250 503.786 Td /F1 9.8 Tf [(epidemics \(Figure 5\), and summing these curves, also reproduced the overall epidemic curve well \(Figure 6\). However, the )] TJ ET BT 26.250 491.881 Td /F1 9.8 Tf [(epidemic dynamics of individual countries were quite distinct from one another. In Liberia, a low R)] TJ ET BT 446.748 489.817 Td /F1 8.7 Tf [(0 )] TJ ET BT 453.976 491.881 Td /F1 9.8 Tf [(with no control \()] TJ ET BT 522.792 491.881 Td /F5 9.8 Tf [(d)] TJ ET BT 528.212 491.881 Td /F1 9.8 Tf [( ~ 0\) )] TJ ET BT 26.250 479.976 Td /F1 9.8 Tf [(contrasted with a high R)] TJ ET BT 130.838 477.912 Td /F1 8.7 Tf [(0)] TJ ET BT 135.657 479.976 Td /F1 9.8 Tf [( and high control \()] TJ ET BT 213.696 479.976 Td /F5 9.8 Tf [(d)] TJ ET BT 219.117 479.976 Td /F1 9.8 Tf [( = 0.22\) in Sierra Leone. Model projections suggested that as of August 2014 )] TJ ET BT 26.250 468.072 Td /F1 9.8 Tf [(Sierra Leone and Guineas outbreaks are slowing, whereas the Liberian outbreak continues to grow in an exponential manner.)] TJ ET 0.965 0.965 0.965 rg 26.250 209.563 555.000 248.627 re f 0.267 0.267 0.267 rg 0.267 0.267 0.267 RG 26.250 458.191 m 581.250 458.191 l 581.250 457.441 l 26.250 457.441 l f 26.250 209.563 m 581.250 209.563 l 581.250 210.313 l 26.250 210.313 l f q 225.000 0 0 168.750 35.250 279.691 cm /I9 Do Q q 35.250 220.813 537.000 52.877 re W n 0.271 0.267 0.267 rg BT 35.250 264.167 Td /F4 9.8 Tf [(Fig. 1: Parameter Estimates by Generation of Epidemic)] TJ ET BT 35.250 244.797 Td /F1 9.8 Tf [(The graph plots best fit values of R)] TJ ET BT 185.907 243.648 Td /F1 8.7 Tf [(0)] TJ ET BT 190.726 244.797 Td /F1 9.8 Tf [( \(blue curve\) and )] TJ ET BT 266.590 244.797 Td /F5 9.8 Tf [(d)] TJ ET BT 272.011 244.797 Td /F1 9.8 Tf [( \(pink curve\) for the IDEA model obtained by utilizing progressively )] TJ ET BT 35.250 231.061 Td /F1 9.8 Tf [(increasing numbers of epidemic generations \(figure shows fits for generation 7 through 15\).)] TJ ET Q 0.965 0.965 0.965 rg 26.250 17.563 555.000 184.500 re f 0.267 0.267 0.267 rg 0.267 0.267 0.267 RG 26.250 202.063 m 581.250 202.063 l 581.250 201.313 l 26.250 201.313 l f q 225.000 0 0 168.750 35.250 23.563 cm /I10 Do Q q 35.250 17.563 537.000 0.000 re W n Q Q q 15.000 17.563 577.500 759.437 re W n 0.271 0.267 0.267 rg BT 26.250 767.476 Td /F5 9.8 Tf [(Base Case Analysis)] TJ ET BT 26.250 748.071 Td /F1 9.8 Tf [(As increasing numbers of outbreak generations were used, best fit R)] TJ ET BT 322.133 746.007 Td /F1 8.7 Tf [(0)] TJ ET BT 326.952 748.071 Td /F1 9.8 Tf [( estimates and estimates of )] TJ ET BT 448.339 748.071 Td /F5 9.8 Tf [(d )] TJ ET BT 456.471 748.071 Td /F1 9.8 Tf [(declined \(Figure 1\). We )] TJ ET BT 26.250 736.167 Td /F1 9.8 Tf [(identified no abrupt surges in )] TJ ET BT 154.150 736.167 Td /F5 9.8 Tf [(d )] TJ ET BT 162.282 736.167 Td /F1 9.8 Tf [(that simulations suggest are indicative of multi-wave outbreaks )] TJ ET 0.267 0.267 0.267 rg BT 435.389 737.674 Td /F4 8.7 Tf [(1)] TJ ET 0.271 0.267 0.267 rg BT 440.208 736.167 Td /F1 9.8 Tf [( . There was a range of )] TJ ET BT 26.250 724.262 Td /F1 9.8 Tf [(combinations of R)] TJ ET BT 104.279 722.198 Td /F1 8.7 Tf [(0 )] TJ ET BT 111.507 724.262 Td /F1 9.8 Tf [(and d that provided approximate fits to observed case counts, but RMSD was lowest, by an order of )] TJ ET BT 26.250 712.357 Td /F1 9.8 Tf [(magnitude, for R)] TJ ET BT 98.322 710.293 Td /F1 8.7 Tf [(0 )] TJ ET BT 105.550 712.357 Td /F1 9.8 Tf [(values close to 1.8, and d values close to 0.01 \(Figure 2\). Our best fit model identified Ro as 1.78, and d as )] TJ ET BT 26.250 700.452 Td /F1 9.8 Tf [(0.009. Cumulative model case counts were projected to be 2435 as compared to 2473 observed cases \(Figure 3\).)] TJ ET BT 26.250 681.048 Td /F1 9.8 Tf [(Based on these parameter values, and in the absence of increase in )] TJ ET BT 323.245 681.048 Td /F5 9.8 Tf [(d)] TJ ET BT 328.666 681.048 Td /F1 9.8 Tf [( as a result of intervention, the outbreak would be )] TJ ET BT 26.250 669.143 Td /F1 9.8 Tf [(projected to have caused over 25,000 infections by the end of 2014. A peak in the epidemic would not occur until April 2015, )] TJ ET BT 26.250 657.238 Td /F1 9.8 Tf [(and continue until mid-2016, with a final size greater than 140,000 cases. However, epidemic size and duration are projected to )] TJ ET BT 26.250 645.333 Td /F1 9.8 Tf [(be extremely sensitive to incremental increases in the size of d. For example, a September 2014 increase in d by 0.005 \(to )] TJ ET BT 26.250 633.429 Td /F1 9.8 Tf [(0.014 rather than 0.009\) would diminish the projected epidemic size to < 10,000 cases, with incidence steadily diminishing )] TJ ET BT 26.250 621.524 Td /F1 9.8 Tf [(rather than increasing in the coming months.)] TJ ET BT 26.250 602.119 Td /F5 9.8 Tf [(Sensitivity Analyses and Alternate Approaches)] TJ ET BT 26.250 582.714 Td /F1 9.8 Tf [(We also fit separate models to epidemic curves derived from reported deaths, rather than cases, curves based only on )] TJ ET BT 26.250 570.810 Td /F1 9.8 Tf [(virologically confirmed cases, as well as curves based on varying assumptions about case-under-reporting, epidemic duration )] TJ ET BT 26.250 558.905 Td /F1 9.8 Tf [(prior to first reporting in March 2014, and generation times. None of these analyses provided estimates of R)] TJ ET BT 489.580 556.841 Td /F1 8.7 Tf [(0)] TJ ET BT 494.398 558.905 Td /F1 9.8 Tf [( and )] TJ ET BT 516.082 558.905 Td /F5 9.8 Tf [(d)] TJ ET BT 521.503 558.905 Td /F1 9.8 Tf [( that differed )] TJ ET BT 26.250 547.000 Td /F1 9.8 Tf [(markedly from those derived in the base case \(Table 1\), though it should be noted that the exponential nature of epidemic )] TJ ET BT 26.250 535.095 Td /F1 9.8 Tf [(growth means that even small changes in model parameters would result in large differences in final epidemic sizes.)] TJ ET BT 26.250 515.691 Td /F1 9.8 Tf [(In our base case we fitted IDEA models to overall cumulative epidemic curves, but fitting curves to individual country-level )] TJ ET BT 26.250 503.786 Td /F1 9.8 Tf [(epidemics \(Figure 5\), and summing these curves, also reproduced the overall epidemic curve well \(Figure 6\). However, the )] TJ ET BT 26.250 491.881 Td /F1 9.8 Tf [(epidemic dynamics of individual countries were quite distinct from one another. In Liberia, a low R)] TJ ET BT 446.748 489.817 Td /F1 8.7 Tf [(0 )] TJ ET BT 453.976 491.881 Td /F1 9.8 Tf [(with no control \()] TJ ET BT 522.792 491.881 Td /F5 9.8 Tf [(d)] TJ ET BT 528.212 491.881 Td /F1 9.8 Tf [( ~ 0\) )] TJ ET BT 26.250 479.976 Td /F1 9.8 Tf [(contrasted with a high R)] TJ ET BT 130.838 477.912 Td /F1 8.7 Tf [(0)] TJ ET BT 135.657 479.976 Td /F1 9.8 Tf [( and high control \()] TJ ET BT 213.696 479.976 Td /F5 9.8 Tf [(d)] TJ ET BT 219.117 479.976 Td /F1 9.8 Tf [( = 0.22\) in Sierra Leone. Model projections suggested that as of August 2014 )] TJ ET BT 26.250 468.072 Td /F1 9.8 Tf [(Sierra Leone and Guineas outbreaks are slowing, whereas the Liberian outbreak continues to grow in an exponential manner.)] TJ ET 0.965 0.965 0.965 rg 26.250 209.563 555.000 248.627 re f 0.267 0.267 0.267 rg 0.267 0.267 0.267 RG 26.250 458.191 m 581.250 458.191 l 581.250 457.441 l 26.250 457.441 l f 26.250 209.563 m 581.250 209.563 l 581.250 210.313 l 26.250 210.313 l f q 225.000 0 0 168.750 35.250 279.691 cm /I9 Do Q q 35.250 220.813 537.000 52.877 re W n 0.271 0.267 0.267 rg BT 35.250 264.167 Td /F4 9.8 Tf [(Fig. 1: Parameter Estimates by Generation of Epidemic)] TJ ET BT 35.250 244.797 Td /F1 9.8 Tf [(The graph plots best fit values of R)] TJ ET BT 185.907 243.648 Td /F1 8.7 Tf [(0)] TJ ET BT 190.726 244.797 Td /F1 9.8 Tf [( \(blue curve\) and )] TJ ET BT 266.590 244.797 Td /F5 9.8 Tf [(d)] TJ ET BT 272.011 244.797 Td /F1 9.8 Tf [( \(pink curve\) for the IDEA model obtained by utilizing progressively )] TJ ET BT 35.250 231.061 Td /F1 9.8 Tf [(increasing numbers of epidemic generations \(figure shows fits for generation 7 through 15\).)] TJ ET Q 0.965 0.965 0.965 rg 26.250 17.563 555.000 184.500 re f 0.267 0.267 0.267 rg 0.267 0.267 0.267 RG 26.250 202.063 m 581.250 202.063 l 581.250 201.313 l 26.250 201.313 l f q 225.000 0 0 168.750 35.250 23.563 cm /I10 Do Q q 35.250 17.563 537.000 0.000 re W n Q Q q 15.000 17.563 577.500 759.437 re W n 0.271 0.267 0.267 rg BT 26.250 767.476 Td /F5 9.8 Tf [(Base Case Analysis)] TJ ET BT 26.250 748.071 Td /F1 9.8 Tf [(As increasing numbers of outbreak generations were used, best fit R)] TJ ET BT 322.133 746.007 Td /F1 8.7 Tf [(0)] TJ ET BT 326.952 748.071 Td /F1 9.8 Tf [( estimates and estimates of )] TJ ET BT 448.339 748.071 Td /F5 9.8 Tf [(d )] TJ ET BT 456.471 748.071 Td /F1 9.8 Tf [(declined \(Figure 1\). We )] TJ ET BT 26.250 736.167 Td /F1 9.8 Tf [(identified no abrupt surges in )] TJ ET BT 154.150 736.167 Td /F5 9.8 Tf [(d )] TJ ET BT 162.282 736.167 Td /F1 9.8 Tf [(that simulations suggest are indicative of multi-wave outbreaks )] TJ ET 0.267 0.267 0.267 rg BT 435.389 737.674 Td /F4 8.7 Tf [(1)] TJ ET 0.271 0.267 0.267 rg BT 440.208 736.167 Td /F1 9.8 Tf [( . There was a range of )] TJ ET BT 26.250 724.262 Td /F1 9.8 Tf [(combinations of R)] TJ ET BT 104.279 722.198 Td /F1 8.7 Tf [(0 )] TJ ET BT 111.507 724.262 Td /F1 9.8 Tf [(and d that provided approximate fits to observed case counts, but RMSD was lowest, by an order of )] TJ ET BT 26.250 712.357 Td /F1 9.8 Tf [(magnitude, for R)] TJ ET BT 98.322 710.293 Td /F1 8.7 Tf [(0 )] TJ ET BT 105.550 712.357 Td /F1 9.8 Tf [(values close to 1.8, and d values close to 0.01 \(Figure 2\). Our best fit model identified Ro as 1.78, and d as )] TJ ET BT 26.250 700.452 Td /F1 9.8 Tf [(0.009. Cumulative model case counts were projected to be 2435 as compared to 2473 observed cases \(Figure 3\).)] TJ ET BT 26.250 681.048 Td /F1 9.8 Tf [(Based on these parameter values, and in the absence of increase in )] TJ ET BT 323.245 681.048 Td /F5 9.8 Tf [(d)] TJ ET BT 328.666 681.048 Td /F1 9.8 Tf [( as a result of intervention, the outbreak would be )] TJ ET BT 26.250 669.143 Td /F1 9.8 Tf [(projected to have caused over 25,000 infections by the end of 2014. A peak in the epidemic would not occur until April 2015, )] TJ ET BT 26.250 657.238 Td /F1 9.8 Tf [(and continue until mid-2016, with a final size greater than 140,000 cases. However, epidemic size and duration are projected to )] TJ ET BT 26.250 645.333 Td /F1 9.8 Tf [(be extremely sensitive to incremental increases in the size of d. For example, a September 2014 increase in d by 0.005 \(to )] TJ ET BT 26.250 633.429 Td /F1 9.8 Tf [(0.014 rather than 0.009\) would diminish the projected epidemic size to < 10,000 cases, with incidence steadily diminishing )] TJ ET BT 26.250 621.524 Td /F1 9.8 Tf [(rather than increasing in the coming months.)] TJ ET BT 26.250 602.119 Td /F5 9.8 Tf [(Sensitivity Analyses and Alternate Approaches)] TJ ET BT 26.250 582.714 Td /F1 9.8 Tf [(We also fit separate models to epidemic curves derived from reported deaths, rather than cases, curves based only on )] TJ ET BT 26.250 570.810 Td /F1 9.8 Tf [(virologically confirmed cases, as well as curves based on varying assumptions about case-under-reporting, epidemic duration )] TJ ET BT 26.250 558.905 Td /F1 9.8 Tf [(prior to first reporting in March 2014, and generation times. None of these analyses provided estimates of R)] TJ ET BT 489.580 556.841 Td /F1 8.7 Tf [(0)] TJ ET BT 494.398 558.905 Td /F1 9.8 Tf [( and )] TJ ET BT 516.082 558.905 Td /F5 9.8 Tf [(d)] TJ ET BT 521.503 558.905 Td /F1 9.8 Tf [( that differed )] TJ ET BT 26.250 547.000 Td /F1 9.8 Tf [(markedly from those derived in the base case \(Table 1\), though it should be noted that the exponential nature of epidemic )] TJ ET BT 26.250 535.095 Td /F1 9.8 Tf [(growth means that even small changes in model parameters would result in large differences in final epidemic sizes.)] TJ ET BT 26.250 515.691 Td /F1 9.8 Tf [(In our base case we fitted IDEA models to overall cumulative epidemic curves, but fitting curves to individual country-level )] TJ ET BT 26.250 503.786 Td /F1 9.8 Tf [(epidemics \(Figure 5\), and summing these curves, also reproduced the overall epidemic curve well \(Figure 6\). However, the )] TJ ET BT 26.250 491.881 Td /F1 9.8 Tf [(epidemic dynamics of individual countries were quite distinct from one another. In Liberia, a low R)] TJ ET BT 446.748 489.817 Td /F1 8.7 Tf [(0 )] TJ ET BT 453.976 491.881 Td /F1 9.8 Tf [(with no control \()] TJ ET BT 522.792 491.881 Td /F5 9.8 Tf [(d)] TJ ET BT 528.212 491.881 Td /F1 9.8 Tf [( ~ 0\) )] TJ ET BT 26.250 479.976 Td /F1 9.8 Tf [(contrasted with a high R)] TJ ET BT 130.838 477.912 Td /F1 8.7 Tf [(0)] TJ ET BT 135.657 479.976 Td /F1 9.8 Tf [( and high control \()] TJ ET BT 213.696 479.976 Td /F5 9.8 Tf [(d)] TJ ET BT 219.117 479.976 Td /F1 9.8 Tf [( = 0.22\) in Sierra Leone. Model projections suggested that as of August 2014 )] TJ ET BT 26.250 468.072 Td /F1 9.8 Tf [(Sierra Leone and Guineas outbreaks are slowing, whereas the Liberian outbreak continues to grow in an exponential manner.)] TJ ET 0.965 0.965 0.965 rg 26.250 209.563 555.000 248.627 re f 0.267 0.267 0.267 rg 0.267 0.267 0.267 RG 26.250 458.191 m 581.250 458.191 l 581.250 457.441 l 26.250 457.441 l f 26.250 209.563 m 581.250 209.563 l 581.250 210.313 l 26.250 210.313 l f q 225.000 0 0 168.750 35.250 279.691 cm /I9 Do Q q 35.250 220.813 537.000 52.877 re W n 0.271 0.267 0.267 rg BT 35.250 264.167 Td /F4 9.8 Tf [(Fig. 1: Parameter Estimates by Generation of Epidemic)] TJ ET BT 35.250 244.797 Td /F1 9.8 Tf [(The graph plots best fit values of R)] TJ ET BT 185.907 243.648 Td /F1 8.7 Tf [(0)] TJ ET BT 190.726 244.797 Td /F1 9.8 Tf [( \(blue curve\) and )] TJ ET BT 266.590 244.797 Td /F5 9.8 Tf [(d)] TJ ET BT 272.011 244.797 Td /F1 9.8 Tf [( \(pink curve\) for the IDEA model obtained by utilizing progressively )] TJ ET BT 35.250 231.061 Td /F1 9.8 Tf [(increasing numbers of epidemic generations \(figure shows fits for generation 7 through 15\).)] TJ ET Q 0.965 0.965 0.965 rg 26.250 17.563 555.000 184.500 re f 0.267 0.267 0.267 rg 0.267 0.267 0.267 RG 26.250 202.063 m 581.250 202.063 l 581.250 201.313 l 26.250 201.313 l f q 225.000 0 0 168.750 35.250 23.563 cm /I10 Do Q q 35.250 17.563 537.000 0.000 re W n Q Q q 225.000 0 0 168.750 35.250 279.691 cm /I9 Do Q q 225.000 0 0 168.750 35.250 23.563 cm /I10 Do Q q 0.000 0.000 0.000 rg BT 291.710 19.825 Td /F1 11.0 Tf [(3)] TJ ET BT 25.000 19.825 Td /F1 11.0 Tf [(PLOS Currents Outbreaks)] TJ ET Q endstream endobj 205 0 obj << /Type /Annot /Subtype /Link /A 206 0 R /Border [0 0 0] /H /I /Rect [ 435.3893 736.8722 440.2079 745.6905 ] >> endobj 206 0 obj << /Type /Action >> endobj 207 0 obj << /Type /Annot /Subtype /Link /A 208 0 R /Border [0 0 0] /H /I /Rect [ 35.2500 279.6907 260.2500 448.4407 ] >> endobj 208 0 obj << /Type /Action /S /URI /URI (http://currents.plos.org/outbreaks/files/2014/08/Slide1.jpg) >> endobj 209 0 obj << /Type /XObject /Subtype /Image /Width 300 /Height 225 /ColorSpace /DeviceRGB /Filter /DCTDecode /BitsPerComponent 8 /Length 16167>> stream JFIF;CREATOR: gd-jpeg v1.0 (using IJG JPEG v62), quality = 90 C     C   ," }!1AQa"q2#BR$3br %&'()*456789:CDEFGHIJSTUVWXYZcdefghijstuvwxyz w!1AQaq"2B #3Rbr $4%&'()*56789:CDEFGHIJSTUVWXYZcdefghijstuvwxyz ?R J??(֗IEU5+}gMʹ'Mw#p@# 5gȣOƏƀ4dR~4~4dR~4~4Q|lŷ? {F!Ap (ـbݳ#q+߳k~mtAq%kJw$קW9#S`ю@‘qŽ(ր}((֎=h((Z? ? 8? ? 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Dark orange areas signifying lowest RMSD are seen with R0 in )] TJ ET BT 35.250 720.634 Td /F1 9.8 Tf [(the 1.75-1.90 range, and with )] TJ ET BT 164.788 720.634 Td /F5 9.8 Tf [(d)] TJ ET BT 170.209 720.634 Td /F1 9.8 Tf [( from 0.01 to 0.015.)] TJ ET Q 0.965 0.965 0.965 rg 26.250 443.009 555.000 248.627 re f 0.267 0.267 0.267 rg 0.267 0.267 0.267 RG 26.250 691.636 m 581.250 691.636 l 581.250 690.886 l 26.250 690.886 l f 26.250 443.009 m 581.250 443.009 l 581.250 443.759 l 26.250 443.759 l f q 225.000 0 0 168.750 35.250 513.136 cm /I11 Do Q q 35.250 454.259 537.000 52.877 re W n 0.271 0.267 0.267 rg BT 35.250 497.613 Td /F4 9.8 Tf [(Fig. 3: Overall Observed vs. Expected Cumulative Incidence)] TJ ET BT 35.250 478.243 Td /F1 9.8 Tf [(Best fit model \(dark curve\) \(R0 = 1.78, d = 0.009\) to observed cumulative incidence for West Africa by generation \(gray )] TJ ET BT 35.250 464.506 Td /F1 9.8 Tf [(bars\). A 15 day serial interval is assumed, and first reported cases are assumed to have been reported in generation 5.)] TJ ET Q 0.965 0.965 0.965 rg 26.250 159.409 555.000 276.100 re f 0.267 0.267 0.267 rg 0.267 0.267 0.267 RG 26.250 435.509 m 581.250 435.509 l 581.250 434.759 l 26.250 434.759 l f 26.250 159.409 m 581.250 159.409 l 581.250 160.159 l 26.250 160.159 l f q 225.000 0 0 168.750 35.250 257.009 cm /I12 Do Q q 35.250 170.659 537.000 80.350 re W n 0.271 0.267 0.267 rg BT 35.250 241.485 Td /F4 9.8 Tf [(Fig. 4: Projections of Incidence and Cumulative Incidence to January 1, 2015)] TJ ET BT 35.250 222.115 Td /F1 9.8 Tf [(The figure plots model-projected incidence \(per 15-day generation\) \(solid red curve, scale on left Y-axis\) and cumulative )] TJ ET BT 35.250 208.379 Td /F1 9.8 Tf [(incidence \(solid black curve, scale on right Y-axis\) against time \(X-axis\). Dashed curves show the potential impact of )] TJ ET BT 35.250 194.643 Td /F1 9.8 Tf [(intervention in September 2014 on incidence \(dashed red curve\) and cumulative incidence \(dashed black curve\), if )] TJ ET BT 35.250 180.907 Td /F1 9.8 Tf [(intervention resulted in an increase of d by 0.005.)] TJ ET Q 0.965 0.965 0.965 rg 26.250 -163.841 555.000 315.750 re f 0.267 0.267 0.267 rg 0.267 0.267 0.267 RG 26.250 151.909 m 581.250 151.909 l 581.250 151.159 l 26.250 151.159 l f q 225.000 0 0 300.000 35.250 -157.841 cm /I13 Do Q q 35.250 -163.841 537.000 0.000 re W n Q Q q 15.000 -163.841 577.500 940.841 re W n 0.965 0.965 0.965 rg 26.250 699.136 555.000 77.864 re f 0.267 0.267 0.267 rg 0.267 0.267 0.267 RG 26.250 699.136 m 581.250 699.136 l 581.250 699.886 l 26.250 699.886 l f q 35.250 710.386 537.000 66.614 re W n 0.271 0.267 0.267 rg BT 35.250 767.476 Td /F4 9.8 Tf [(Fig. 2: Contour Plot of Model Fit as a Function of R0 and d.)] TJ ET BT 35.250 748.106 Td /F1 9.8 Tf [(Figure plots root mean squared distance \(RMSD\) of model projected case counts from observed case counts in models )] TJ ET BT 35.250 734.370 Td /F1 9.8 Tf [(utilizing varying combinations of R0 \(X-axis\) and )] TJ ET BT 246.025 734.370 Td /F5 9.8 Tf [(d)] TJ ET BT 251.446 734.370 Td /F1 9.8 Tf [( \(Y-axis\). Dark orange areas signifying lowest RMSD are seen with R0 in )] TJ ET BT 35.250 720.634 Td /F1 9.8 Tf [(the 1.75-1.90 range, and with )] TJ ET BT 164.788 720.634 Td /F5 9.8 Tf [(d)] TJ ET BT 170.209 720.634 Td /F1 9.8 Tf [( from 0.01 to 0.015.)] TJ ET Q 0.965 0.965 0.965 rg 26.250 443.009 555.000 248.627 re f 0.267 0.267 0.267 rg 0.267 0.267 0.267 RG 26.250 691.636 m 581.250 691.636 l 581.250 690.886 l 26.250 690.886 l f 26.250 443.009 m 581.250 443.009 l 581.250 443.759 l 26.250 443.759 l f q 225.000 0 0 168.750 35.250 513.136 cm /I11 Do Q q 35.250 454.259 537.000 52.877 re W n 0.271 0.267 0.267 rg BT 35.250 497.613 Td /F4 9.8 Tf [(Fig. 3: Overall Observed vs. Expected Cumulative Incidence)] TJ ET BT 35.250 478.243 Td /F1 9.8 Tf [(Best fit model \(dark curve\) \(R0 = 1.78, d = 0.009\) to observed cumulative incidence for West Africa by generation \(gray )] TJ ET BT 35.250 464.506 Td /F1 9.8 Tf [(bars\). A 15 day serial interval is assumed, and first reported cases are assumed to have been reported in generation 5.)] TJ ET Q 0.965 0.965 0.965 rg 26.250 159.409 555.000 276.100 re f 0.267 0.267 0.267 rg 0.267 0.267 0.267 RG 26.250 435.509 m 581.250 435.509 l 581.250 434.759 l 26.250 434.759 l f 26.250 159.409 m 581.250 159.409 l 581.250 160.159 l 26.250 160.159 l f q 225.000 0 0 168.750 35.250 257.009 cm /I12 Do Q q 35.250 170.659 537.000 80.350 re W n 0.271 0.267 0.267 rg BT 35.250 241.485 Td /F4 9.8 Tf [(Fig. 4: Projections of Incidence and Cumulative Incidence to January 1, 2015)] TJ ET BT 35.250 222.115 Td /F1 9.8 Tf [(The figure plots model-projected incidence \(per 15-day generation\) \(solid red curve, scale on left Y-axis\) and cumulative )] TJ ET BT 35.250 208.379 Td /F1 9.8 Tf [(incidence \(solid black curve, scale on right Y-axis\) against time \(X-axis\). Dashed curves show the potential impact of )] TJ ET BT 35.250 194.643 Td /F1 9.8 Tf [(intervention in September 2014 on incidence \(dashed red curve\) and cumulative incidence \(dashed black curve\), if )] TJ ET BT 35.250 180.907 Td /F1 9.8 Tf [(intervention resulted in an increase of d by 0.005.)] TJ ET Q 0.965 0.965 0.965 rg 26.250 -163.841 555.000 315.750 re f 0.267 0.267 0.267 rg 0.267 0.267 0.267 RG 26.250 151.909 m 581.250 151.909 l 581.250 151.159 l 26.250 151.159 l f q 225.000 0 0 300.000 35.250 -157.841 cm /I13 Do Q q 35.250 -163.841 537.000 0.000 re W n Q Q q 15.000 -163.841 577.500 940.841 re W n 0.965 0.965 0.965 rg 26.250 699.136 555.000 77.864 re f 0.267 0.267 0.267 rg 0.267 0.267 0.267 RG 26.250 699.136 m 581.250 699.136 l 581.250 699.886 l 26.250 699.886 l f q 35.250 710.386 537.000 66.614 re W n 0.271 0.267 0.267 rg BT 35.250 767.476 Td /F4 9.8 Tf [(Fig. 2: Contour Plot of Model Fit as a Function of R0 and d.)] TJ ET BT 35.250 748.106 Td /F1 9.8 Tf [(Figure plots root mean squared distance \(RMSD\) of model projected case counts from observed case counts in models )] TJ ET BT 35.250 734.370 Td /F1 9.8 Tf [(utilizing varying combinations of R0 \(X-axis\) and )] TJ ET BT 246.025 734.370 Td /F5 9.8 Tf [(d)] TJ ET BT 251.446 734.370 Td /F1 9.8 Tf [( \(Y-axis\). Dark orange areas signifying lowest RMSD are seen with R0 in )] TJ ET BT 35.250 720.634 Td /F1 9.8 Tf [(the 1.75-1.90 range, and with )] TJ ET BT 164.788 720.634 Td /F5 9.8 Tf [(d)] TJ ET BT 170.209 720.634 Td /F1 9.8 Tf [( from 0.01 to 0.015.)] TJ ET Q 0.965 0.965 0.965 rg 26.250 443.009 555.000 248.627 re f 0.267 0.267 0.267 rg 0.267 0.267 0.267 RG 26.250 691.636 m 581.250 691.636 l 581.250 690.886 l 26.250 690.886 l f 26.250 443.009 m 581.250 443.009 l 581.250 443.759 l 26.250 443.759 l f q 225.000 0 0 168.750 35.250 513.136 cm /I11 Do Q q 35.250 454.259 537.000 52.877 re W n 0.271 0.267 0.267 rg BT 35.250 497.613 Td /F4 9.8 Tf [(Fig. 3: Overall Observed vs. Expected Cumulative Incidence)] TJ ET BT 35.250 478.243 Td /F1 9.8 Tf [(Best fit model \(dark curve\) \(R0 = 1.78, d = 0.009\) to observed cumulative incidence for West Africa by generation \(gray )] TJ ET BT 35.250 464.506 Td /F1 9.8 Tf [(bars\). A 15 day serial interval is assumed, and first reported cases are assumed to have been reported in generation 5.)] TJ ET Q 0.965 0.965 0.965 rg 26.250 159.409 555.000 276.100 re f 0.267 0.267 0.267 rg 0.267 0.267 0.267 RG 26.250 435.509 m 581.250 435.509 l 581.250 434.759 l 26.250 434.759 l f 26.250 159.409 m 581.250 159.409 l 581.250 160.159 l 26.250 160.159 l f q 225.000 0 0 168.750 35.250 257.009 cm /I12 Do Q q 35.250 170.659 537.000 80.350 re W n 0.271 0.267 0.267 rg BT 35.250 241.485 Td /F4 9.8 Tf [(Fig. 4: Projections of Incidence and Cumulative Incidence to January 1, 2015)] TJ ET BT 35.250 222.115 Td /F1 9.8 Tf [(The figure plots model-projected incidence \(per 15-day generation\) \(solid red curve, scale on left Y-axis\) and cumulative )] TJ ET BT 35.250 208.379 Td /F1 9.8 Tf [(incidence \(solid black curve, scale on right Y-axis\) against time \(X-axis\). Dashed curves show the potential impact of )] TJ ET BT 35.250 194.643 Td /F1 9.8 Tf [(intervention in September 2014 on incidence \(dashed red curve\) and cumulative incidence \(dashed black curve\), if )] TJ ET BT 35.250 180.907 Td /F1 9.8 Tf [(intervention resulted in an increase of d by 0.005.)] TJ ET Q 0.965 0.965 0.965 rg 26.250 -163.841 555.000 315.750 re f 0.267 0.267 0.267 rg 0.267 0.267 0.267 RG 26.250 151.909 m 581.250 151.909 l 581.250 151.159 l 26.250 151.159 l f q 225.000 0 0 300.000 35.250 -157.841 cm /I13 Do Q q 35.250 -163.841 537.000 0.000 re W n Q Q q 225.000 0 0 168.750 35.250 513.136 cm /I11 Do Q q 225.000 0 0 168.750 35.250 257.009 cm /I12 Do Q q 225.000 0 0 300.000 35.250 -157.841 cm /I13 Do Q q 0.000 0.000 0.000 rg BT 291.710 19.825 Td /F1 11.0 Tf [(4)] TJ ET BT 25.000 19.825 Td /F1 11.0 Tf [(PLOS Currents Outbreaks)] TJ ET Q endstream endobj 227 0 obj << /Type /Annot /Subtype /Link /A 228 0 R /Border [0 0 0] /H /I /Rect [ 35.2500 513.1365 260.2500 681.8865 ] >> endobj 228 0 obj << /Type /Action /S /URI /URI (http://currents.plos.org/outbreaks/files/2014/08/Slide21.jpg) >> endobj 229 0 obj << /Type /XObject /Subtype /Image /Width 300 /Height 225 /ColorSpace /DeviceRGB /Filter /DCTDecode /BitsPerComponent 8 /Length 13174>> stream JFIF;CREATOR: gd-jpeg v1.0 (using IJG JPEG v62), quality = 90 C     C   ," }!1AQa"q2#BR$3br %&'()*456789:CDEFGHIJSTUVWXYZcdefghijstuvwxyz w!1AQaq"2B #3Rbr $4%&'()*56789:CDEFGHIJSTUVWXYZcdefghijstuvwxyz ?R J??(֗#|>|s\}}6H $CJ.8;~)u B%լ[KgC )EdB>~|#p`JĽ O,edRVF"2:v`M_ ^;_N*~=nk'+}:բ H7l3.TE}/hsz} -$`3~52(xfKhD@,z޽ 0ů E"MYYOpeȠCW_ 'B߈kS_}I ¿*8o]:Y]:[\G)l0\+bB]*0~b~Ӵ5Og]i2,7y-)IDt{KWxᏅ[%Dmd*@GgM0RLȎZFF {;cwFȠ R>Ykz=&ZVfWUA?¡aP~_֬ȉ-Cۺ4̊CV I ץAZ_,DhF6Tj! $%֥Տ,Po0\,EEeqc' oᯏ4."򵕶y  :KkYZI\ܪnvjxÿaƕOv\ uWlX[ co{vh^pxKꚍjL{om2<1hAʓJ?[/'W S:VɶTkXg]5]_L-SOsil]XO (A@ BjEؿ(!W¿׿AE/  x*?^x"o XhwV7vѡ ͈|UӴ=2k=XKGg5*M9.]dB$_W64¾A4|gF~$>]W1]MlJ'a$Y򌠈?_kRQW ^ҿ;z'e3E/  F~~9wgsI"d>EQEQEQERqKG4RR'RG|7e[*!V8X=$s&ݴ#x^_|?2_޿ 4gnd+ooSVWOKx^~ZO1d/ m5u_f I4 4?]vHC Xh_ KWypBURE!֏Ə^hjjQpm]GgqiyqrWG*(8ː9"'Xbo YbEҦӖQ>qwiw9$c~vQ|mum"SЮ$$KxE}=G3"˻$>1k!4]M"IO.K ~`1)$>K$.@#ik} G{-F&%9% ѣ/pH׌]~Ϟ5~,V[;:=*YVIk27>d_\g_Qh3ivw6zŕRQO:EP'X[ʆF[ S"UoIf>B`\go ¯zׂDj3cgo{ki<;x./:(FLgg9OWZ?=[PKj>u("Vz\W|o {˫(FYY'%f|+ۇ^quo~9VS-uA^{sdP~~~4~4QQEQ@~4PE~4QEQEQ@'KR~kN?]A|^yzIrCgd/ |[~,tPQFe?rSǀܜH~7ƯMMhOxؘ(ݸg%?>~4^4,>#MًD儁t9`&y?ֱE#_O5F-ywo86Һ<4^?夿k#m?WCCdž-t?AU| ۟m/]@ QGK_ZCGy&&&}7|y`n@ 3X_ٟ+=7&yגV|oP w':݅7P^^Ziy1I졉hY0`N3r0cvo|KPh0\8Wx7C؈pI iֺQwoqʓ́ȌЫA@5wOd{ʯe?<-mkx'cm9ĺTnB^ecI2 T>4MOQ4.P`*I;H.eY=؞/(~;Z8'׀|CjWz֮aTi"o홤ym%xr>i o{?66yLImqӟj/Š((? 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F $I(Tg$?ƒ??(i)h)}hGj;v%㻼;XktPE62F|4D1J!9漗Ҿ]:tOq4w4,r 8 ^|6Ro#JdPaéxׁ^=?K^BEʖ`|BW2{.خ4?tͲͼ,@!$pN~i y~eZG[1I[WeŪGۙ E&Er0G|qpW;mPݩcO,?ր9)cgʲ}UV6q H漇ž&|[O}O#ڬL6๞FݟzwZ?|i$q## g=_s(U>&w`}&s7T>F;^GUVlT}h#<c9dpAR#PAkڊ((QT5{N{jאimM5̋qH}k _&l~ x}.tJIG$:d~(hFfuk[.oXazW^-b|:<~iIְ>g'ZQ#=꒖€ (((ZZ(IڀO{o2is[^Cyb$2HA9V"jA`p>޼ KY[xtU[?$bz}kG{);Ҋ=h;QE 2C, uMQq/,,QFݰROa^>n4FsĐ$U6q~[3@Ң]A;l-ȵQG@QW~!^&g>o"VmYQOOթD/ڲ2Ȣɨŭ?/󯨫_?ƀ<~iIְ>g'ZQ#=_ƒ )?J)?J(h֒ր ;Qގw 'ux^=3G].^VUMECE(JJLx$kӊſ>&-}ͩcl1~^1ҼGZD Yϲ1 H5GxL/u}2;m>2Sn)  [h~!|B-:g}W,]ыr~`>kнkͯI3MsRtx5Yvrj%8bԖ^k.mnIciJlVX'?N~aMּCSiY/?h?Z%0h y}]=a+~k1I}Hx[^_KB 셁* 9'}E|k=MXwY*W2+[ 0`{6G<'6]|Pټ3iH !}3xS YtT`F3mgW: 6fi:mQ@}y ^-bwu 4veKS_$SՇKԒiu3h1A Zy^gm%̑Tr05W^_פ|_?( j;"%)0Y9Z煠F4Hlb#}i 냎^!^&g+.N_,-tӕkm"fGQ9W:Vy2QQ6K@;N<`@"=Z_edE??VMn*;02Ci$2 pi5 ŐM|I_8Rtkvo`__Q׌Z|[oJU,2GhC2 kz{KTY|O"ċۣ6lnVTL,A9}8G5;Y'k{[ලD*4 gbJZ4eIn#Af&>^h)+{y/dEq(739 A+(()i)hր'jZ(i=)h/ĞҼ[j-H$-?uq$'i*Ys)A5O 5}Ud \pvs]/qp|!vm4\٥[2F T`8jKMTfy^FW\cjڃk0€2z'@o/Btwh+%ǺaP8\ u1 @XNEv` e[8@1t{M[G>Eq,oXVI$1ֳtO^%"p%:( (}hjχS^RڒX 2Tߩ5u|WvR`TnSPխ+2In4Lד\t72Nc$d@v^4{jb@vϖ7(=8ɪW <3^]\lP&+sN:q]O'柪[Xo5;"R> endobj 237 0 obj << /Type /Action /S /URI /URI (http://currents.plos.org/outbreaks/files/2014/08/Slide21.jpg) >> endobj 238 0 obj << /Type /Annot /Subtype /Link /A 239 0 R /Border [0 0 0] /H /I /Rect [ 35.2500 257.0092 260.2500 425.7592 ] >> endobj 239 0 obj << /Type /Action /S /URI /URI (http://currents.plos.org/outbreaks/files/2014/08/Slide31.jpg) >> endobj 240 0 obj << /Type /Annot /Subtype /Link /A 241 0 R /Border [0 0 0] /H /I /Rect [ 35.2500 -157.8405 260.2500 142.1595 ] >> endobj 241 0 obj << /Type /Action /S /URI /URI (http://currents.plos.org/outbreaks/files/2014/08/Slide12.jpg) >> endobj 242 0 obj << /Type /Annot /Subtype /Link /A 243 0 R /Border [0 0 0] /H /I /Rect [ 35.2500 513.1365 260.2500 681.8865 ] >> endobj 243 0 obj << /Type /Action /S /URI /URI (http://currents.plos.org/outbreaks/files/2014/08/Slide21.jpg) >> endobj 244 0 obj << /Type /Annot /Subtype /Link /A 245 0 R /Border [0 0 0] /H /I /Rect [ 35.2500 257.0092 260.2500 425.7592 ] >> endobj 245 0 obj << /Type /Action /S /URI /URI (http://currents.plos.org/outbreaks/files/2014/08/Slide31.jpg) >> endobj 246 0 obj << /Type /Annot /Subtype /Link /A 247 0 R /Border [0 0 0] /H /I /Rect [ 35.2500 -157.8405 260.2500 142.1595 ] >> endobj 247 0 obj << /Type /Action /S /URI /URI (http://currents.plos.org/outbreaks/files/2014/08/Slide12.jpg) >> endobj 248 0 obj << /Type /Page /Parent 3 0 R /Annots [ 251 0 R 254 0 R 256 0 R ] /Contents 249 0 R >> endobj 249 0 obj << /Length 27238 >> stream q 15.000 36.933 577.500 740.067 re W n 0.965 0.965 0.965 rg 26.250 712.873 555.000 64.127 re f 0.267 0.267 0.267 rg 0.267 0.267 0.267 RG 26.250 712.873 m 581.250 712.873 l 581.250 713.623 l 26.250 713.623 l f q 35.250 724.123 537.000 52.877 re W n 0.271 0.267 0.267 rg BT 35.250 767.476 Td /F4 9.8 Tf [(Fig. 5: Country Specific Model Fits, Observed vs. Expected Cumulative Incidence)] TJ ET BT 35.250 748.106 Td /F1 9.8 Tf [(Graphs demonstrate good model fits \(dark curves\) to observed generation by generation cumulative incidence of infection )] TJ ET BT 35.250 734.370 Td /F1 9.8 Tf [(in Guinea \(top panel\), Liberia \(middle panel\), and Sierra Leone \(bottom panel\).)] TJ ET Q 0.965 0.965 0.965 rg 26.250 443.009 555.000 262.364 re f 0.267 0.267 0.267 rg 0.267 0.267 0.267 RG 26.250 705.373 m 581.250 705.373 l 581.250 704.623 l 26.250 704.623 l f 26.250 443.009 m 581.250 443.009 l 581.250 443.759 l 26.250 443.759 l f q 225.000 0 0 168.750 35.250 526.873 cm /I14 Do Q q 35.250 454.259 537.000 66.614 re W n 0.271 0.267 0.267 rg BT 35.250 511.349 Td /F4 9.8 Tf [(Fig. 6: Overall vs. Country-Level Model Fits)] TJ ET BT 35.250 491.979 Td /F1 9.8 Tf [(Graphs show good agreement between the base-case model, fit to overall cumulative incidence data \(all countries )] TJ ET BT 35.250 478.243 Td /F1 9.8 Tf [(combined, solid gray curve\) vs. summed outputs \(solid black curve\) from models fit to country-level data from Guinea )] TJ ET BT 35.250 464.506 Td /F1 9.8 Tf [(\(dashed black curve\), Liberia \(thin black curve\), and Sierra Leone \(dashed gray curve\).)] TJ ET Q q 26.250 421.773 555.000 13.736 re W n 0.271 0.267 0.267 rg BT 26.250 424.520 Td /F1 9.8 Tf [(Table 1. Sensitivity of Model Estimates to Alternate Approaches and Assumption)] TJ ET Q 1.000 1.000 1.000 rg 26.250 209.918 555.000 204.355 re f 0.965 0.965 0.965 rg 27.000 401.243 369.113 12.280 re f 0.267 0.267 0.267 rg 26.625 413.148 369.488 0.750 re f 26.625 400.868 0.750 13.030 re f 0.271 0.267 0.267 rg BT 31.500 403.999 Td /F4 9.8 Tf [(Alternate Assumption)] TJ ET 0.965 0.965 0.965 rg 396.113 401.243 84.244 12.280 re f 0.267 0.267 0.267 rg 396.113 413.148 84.244 0.750 re f 0.271 0.267 0.267 rg BT 400.613 403.999 Td /F6 9.8 Tf [(R)] TJ ET BT 407.653 403.999 Td /F6 8.7 Tf [(0)] TJ ET 0.965 0.965 0.965 rg 480.357 401.243 100.143 12.280 re f 0.267 0.267 0.267 rg 480.357 413.148 100.518 0.750 re f 580.125 400.868 0.750 13.030 re f 0.271 0.267 0.267 rg BT 484.857 403.999 Td /F6 9.8 Tf [(d)] TJ ET 0.267 0.267 0.267 rg 26.625 400.868 369.863 0.750 re f 26.625 384.987 0.750 16.631 re f 0.271 0.267 0.267 rg BT 31.875 391.013 Td /F1 9.8 Tf [(Base case)] TJ ET 0.267 0.267 0.267 rg 395.738 400.868 84.994 0.750 re f 395.738 384.987 0.750 16.631 re f 0.271 0.267 0.267 rg BT 400.988 391.013 Td /F1 9.8 Tf [(1.78)] TJ ET 0.267 0.267 0.267 rg 479.982 400.868 100.893 0.750 re f 479.982 384.987 0.750 16.631 re f 580.125 384.987 0.750 16.631 re f 0.271 0.267 0.267 rg BT 485.232 391.013 Td /F1 9.8 Tf [(0.009)] TJ ET 0.267 0.267 0.267 rg 26.625 384.987 369.863 0.750 re f 26.625 369.106 0.750 16.631 re f 0.271 0.267 0.267 rg BT 31.875 375.132 Td /F1 9.8 Tf [(12 day generation time)] TJ ET 0.267 0.267 0.267 rg 395.738 384.987 84.994 0.750 re f 395.738 369.106 0.750 16.631 re f 0.271 0.267 0.267 rg BT 400.988 375.132 Td /F1 9.8 Tf [(1.68)] TJ ET 0.267 0.267 0.267 rg 479.982 384.987 100.893 0.750 re f 479.982 369.106 0.750 16.631 re f 580.125 369.106 0.750 16.631 re f 0.271 0.267 0.267 rg BT 485.232 375.132 Td /F1 9.8 Tf [(0.009)] TJ ET 0.267 0.267 0.267 rg 26.625 369.106 369.863 0.750 re f 26.625 353.224 0.750 16.631 re f 0.271 0.267 0.267 rg BT 31.875 359.251 Td /F1 9.8 Tf [(18 day generation time)] TJ ET 0.267 0.267 0.267 rg 395.738 369.106 84.994 0.750 re f 395.738 353.224 0.750 16.631 re f 0.271 0.267 0.267 rg BT 400.988 359.251 Td /F1 9.8 Tf [(1.94)] TJ ET 0.267 0.267 0.267 rg 479.982 369.106 100.893 0.750 re f 479.982 353.224 0.750 16.631 re f 580.125 353.224 0.750 16.631 re f 0.271 0.267 0.267 rg BT 485.232 359.251 Td /F1 9.8 Tf [(0.013)] TJ ET 0.267 0.267 0.267 rg 26.625 353.224 369.863 0.750 re f 26.625 337.343 0.750 16.631 re f 0.271 0.267 0.267 rg BT 31.875 343.369 Td /F1 9.8 Tf [(Outbreak recognized generation 3)] TJ ET 0.267 0.267 0.267 rg 395.738 353.224 84.994 0.750 re f 395.738 337.343 0.750 16.631 re f 0.271 0.267 0.267 rg BT 400.988 343.369 Td /F1 9.8 Tf [(2.19)] TJ ET 0.267 0.267 0.267 rg 479.982 353.224 100.893 0.750 re f 479.982 337.343 0.750 16.631 re f 580.125 337.343 0.750 16.631 re f 0.271 0.267 0.267 rg BT 485.232 343.369 Td /F1 9.8 Tf [(0.022)] TJ ET 0.267 0.267 0.267 rg 26.625 337.343 369.863 0.750 re f 26.625 321.462 0.750 16.631 re f 0.271 0.267 0.267 rg BT 31.875 327.488 Td /F1 9.8 Tf [(Outbreak recognized generation 7)] TJ ET 0.267 0.267 0.267 rg 395.738 337.343 84.994 0.750 re f 395.738 321.462 0.750 16.631 re f 0.271 0.267 0.267 rg BT 400.988 327.488 Td /F1 9.8 Tf [(1.70)] TJ ET 0.267 0.267 0.267 rg 479.982 337.343 100.893 0.750 re f 479.982 321.462 0.750 16.631 re f 580.125 321.462 0.750 16.631 re f 0.271 0.267 0.267 rg BT 485.232 327.488 Td /F1 9.8 Tf [(0.011)] TJ ET 0.267 0.267 0.267 rg 26.625 321.462 369.863 0.750 re f 26.625 305.581 0.750 16.631 re f 0.271 0.267 0.267 rg BT 31.875 311.607 Td /F1 9.8 Tf [(Outbreak 50% under-reported)] TJ ET 0.267 0.267 0.267 rg 395.738 321.462 84.994 0.750 re f 395.738 305.581 0.750 16.631 re f 0.271 0.267 0.267 rg BT 400.988 311.607 Td /F1 9.8 Tf [(1.92)] TJ ET 0.267 0.267 0.267 rg 479.982 321.462 100.893 0.750 re f 479.982 305.581 0.750 16.631 re f 580.125 305.581 0.750 16.631 re f 0.271 0.267 0.267 rg BT 485.232 311.607 Td /F1 9.8 Tf [(0.013)] TJ ET 0.267 0.267 0.267 rg 26.625 305.581 369.863 0.750 re f 26.625 289.699 0.750 16.631 re f 0.271 0.267 0.267 rg BT 31.875 295.726 Td /F1 9.8 Tf [(Outbreak 100% under-reported)] TJ ET 0.267 0.267 0.267 rg 395.738 305.581 84.994 0.750 re f 395.738 289.699 0.750 16.631 re f 0.271 0.267 0.267 rg BT 400.988 295.726 Td /F1 9.8 Tf [(2.02)] TJ ET 0.267 0.267 0.267 rg 479.982 305.581 100.893 0.750 re f 479.982 289.699 0.750 16.631 re f 580.125 289.699 0.750 16.631 re f 0.271 0.267 0.267 rg BT 485.232 295.726 Td /F1 9.8 Tf [(0.015)] TJ ET 0.267 0.267 0.267 rg 26.625 289.699 369.863 0.750 re f 26.625 273.818 0.750 16.631 re f 0.271 0.267 0.267 rg BT 31.875 279.844 Td /F1 9.8 Tf [(Virologically confirmed cases only)] TJ ET 0.267 0.267 0.267 rg 395.738 289.699 84.994 0.750 re f 395.738 273.818 0.750 16.631 re f 0.271 0.267 0.267 rg BT 400.988 279.844 Td /F1 9.8 Tf [(1.74)] TJ ET 0.267 0.267 0.267 rg 479.982 289.699 100.893 0.750 re f 479.982 273.818 0.750 16.631 re f 580.125 273.818 0.750 16.631 re f 0.271 0.267 0.267 rg BT 485.232 279.844 Td /F1 9.8 Tf [(0.011)] TJ ET 0.267 0.267 0.267 rg 26.625 273.818 369.863 0.750 re f 26.625 257.937 0.750 16.631 re f 0.271 0.267 0.267 rg BT 31.875 263.963 Td /F1 9.8 Tf [(Deaths only)] TJ ET 0.267 0.267 0.267 rg 395.738 273.818 84.994 0.750 re f 395.738 257.937 0.750 16.631 re f 0.271 0.267 0.267 rg BT 400.988 263.963 Td /F1 9.8 Tf [(1.66)] TJ ET 0.267 0.267 0.267 rg 479.982 273.818 100.893 0.750 re f 479.982 257.937 0.750 16.631 re f 580.125 257.937 0.750 16.631 re f 0.271 0.267 0.267 rg BT 485.232 263.963 Td /F1 9.8 Tf [(0.008)] TJ ET 0.267 0.267 0.267 rg 26.625 257.937 369.863 0.750 re f 26.625 242.056 0.750 16.631 re f 0.271 0.267 0.267 rg BT 31.875 248.082 Td /F1 9.8 Tf [(Guinea cases only)] TJ ET 0.267 0.267 0.267 rg 395.738 257.937 84.994 0.750 re f 395.738 242.056 0.750 16.631 re f 0.271 0.267 0.267 rg BT 400.988 248.082 Td /F1 9.8 Tf [(2.46)] TJ ET 0.267 0.267 0.267 rg 479.982 257.937 100.893 0.750 re f 479.982 242.056 0.750 16.631 re f 580.125 242.056 0.750 16.631 re f 0.271 0.267 0.267 rg BT 485.232 248.082 Td /F1 9.8 Tf [(0.050)] TJ ET 0.267 0.267 0.267 rg 26.625 242.056 369.863 0.750 re f 26.625 226.174 0.750 16.631 re f 0.271 0.267 0.267 rg BT 31.875 232.201 Td /F1 9.8 Tf [(Liberia cases only)] TJ ET 0.267 0.267 0.267 rg 395.738 242.056 84.994 0.750 re f 395.738 226.174 0.750 16.631 re f 0.271 0.267 0.267 rg BT 400.988 232.201 Td /F1 9.8 Tf [(1.72)] TJ ET 0.267 0.267 0.267 rg 479.982 242.056 100.893 0.750 re f 479.982 226.174 0.750 16.631 re f 580.125 226.174 0.750 16.631 re f 0.271 0.267 0.267 rg BT 485.232 232.201 Td /F1 9.8 Tf [(0)] TJ ET 0.267 0.267 0.267 rg 26.625 226.174 369.863 0.750 re f 26.625 210.293 369.863 0.750 re f 26.625 210.293 0.750 16.631 re f 0.271 0.267 0.267 rg BT 31.875 216.319 Td /F1 9.8 Tf [(Sierra Leone cases only)] TJ ET 0.267 0.267 0.267 rg 395.738 226.174 84.994 0.750 re f 395.738 210.293 84.994 0.750 re f 395.738 210.293 0.750 16.631 re f 0.271 0.267 0.267 rg BT 400.988 216.319 Td /F1 9.8 Tf [(8.33)] TJ ET 0.267 0.267 0.267 rg 479.982 226.174 100.893 0.750 re f 479.982 210.293 100.893 0.750 re f 479.982 210.293 0.750 16.631 re f 580.125 210.293 0.750 16.631 re f 0.271 0.267 0.267 rg BT 485.232 216.319 Td /F1 9.8 Tf [(0.22)] TJ ET BT 26.250 138.197 Td /F4 12.0 Tf [(Discussion)] TJ ET Q q 15.000 36.933 577.500 740.067 re W n 0.965 0.965 0.965 rg 26.250 712.873 555.000 64.127 re f 0.267 0.267 0.267 rg 0.267 0.267 0.267 RG 26.250 712.873 m 581.250 712.873 l 581.250 713.623 l 26.250 713.623 l f q 35.250 724.123 537.000 52.877 re W n 0.271 0.267 0.267 rg BT 35.250 767.476 Td /F4 9.8 Tf [(Fig. 5: Country Specific Model Fits, Observed vs. Expected Cumulative Incidence)] TJ ET BT 35.250 748.106 Td /F1 9.8 Tf [(Graphs demonstrate good model fits \(dark curves\) to observed generation by generation cumulative incidence of infection )] TJ ET BT 35.250 734.370 Td /F1 9.8 Tf [(in Guinea \(top panel\), Liberia \(middle panel\), and Sierra Leone \(bottom panel\).)] TJ ET Q 0.965 0.965 0.965 rg 26.250 443.009 555.000 262.364 re f 0.267 0.267 0.267 rg 0.267 0.267 0.267 RG 26.250 705.373 m 581.250 705.373 l 581.250 704.623 l 26.250 704.623 l f 26.250 443.009 m 581.250 443.009 l 581.250 443.759 l 26.250 443.759 l f q 225.000 0 0 168.750 35.250 526.873 cm /I14 Do Q q 35.250 454.259 537.000 66.614 re W n 0.271 0.267 0.267 rg BT 35.250 511.349 Td /F4 9.8 Tf [(Fig. 6: Overall vs. Country-Level Model Fits)] TJ ET BT 35.250 491.979 Td /F1 9.8 Tf [(Graphs show good agreement between the base-case model, fit to overall cumulative incidence data \(all countries )] TJ ET BT 35.250 478.243 Td /F1 9.8 Tf [(combined, solid gray curve\) vs. summed outputs \(solid black curve\) from models fit to country-level data from Guinea )] TJ ET BT 35.250 464.506 Td /F1 9.8 Tf [(\(dashed black curve\), Liberia \(thin black curve\), and Sierra Leone \(dashed gray curve\).)] TJ ET Q q 26.250 421.773 555.000 13.736 re W n 0.271 0.267 0.267 rg BT 26.250 424.520 Td /F1 9.8 Tf [(Table 1. Sensitivity of Model Estimates to Alternate Approaches and Assumption)] TJ ET Q 1.000 1.000 1.000 rg 26.250 209.918 555.000 204.355 re f 0.965 0.965 0.965 rg 27.000 401.243 369.113 12.280 re f 0.267 0.267 0.267 rg 26.625 413.148 369.488 0.750 re f 26.625 400.868 0.750 13.030 re f 0.271 0.267 0.267 rg BT 31.500 403.999 Td /F4 9.8 Tf [(Alternate Assumption)] TJ ET 0.965 0.965 0.965 rg 396.113 401.243 84.244 12.280 re f 0.267 0.267 0.267 rg 396.113 413.148 84.244 0.750 re f 0.271 0.267 0.267 rg BT 400.613 403.999 Td /F6 9.8 Tf [(R)] TJ ET BT 407.653 403.999 Td /F6 8.7 Tf [(0)] TJ ET 0.965 0.965 0.965 rg 480.357 401.243 100.143 12.280 re f 0.267 0.267 0.267 rg 480.357 413.148 100.518 0.750 re f 580.125 400.868 0.750 13.030 re f 0.271 0.267 0.267 rg BT 484.857 403.999 Td /F6 9.8 Tf [(d)] TJ ET 0.267 0.267 0.267 rg 26.625 400.868 369.863 0.750 re f 26.625 384.987 0.750 16.631 re f 0.271 0.267 0.267 rg BT 31.875 391.013 Td /F1 9.8 Tf [(Base case)] TJ ET 0.267 0.267 0.267 rg 395.738 400.868 84.994 0.750 re f 395.738 384.987 0.750 16.631 re f 0.271 0.267 0.267 rg BT 400.988 391.013 Td /F1 9.8 Tf [(1.78)] TJ ET 0.267 0.267 0.267 rg 479.982 400.868 100.893 0.750 re f 479.982 384.987 0.750 16.631 re f 580.125 384.987 0.750 16.631 re f 0.271 0.267 0.267 rg BT 485.232 391.013 Td /F1 9.8 Tf [(0.009)] TJ ET 0.267 0.267 0.267 rg 26.625 384.987 369.863 0.750 re f 26.625 369.106 0.750 16.631 re f 0.271 0.267 0.267 rg BT 31.875 375.132 Td /F1 9.8 Tf [(12 day generation time)] TJ ET 0.267 0.267 0.267 rg 395.738 384.987 84.994 0.750 re f 395.738 369.106 0.750 16.631 re f 0.271 0.267 0.267 rg BT 400.988 375.132 Td /F1 9.8 Tf [(1.68)] TJ ET 0.267 0.267 0.267 rg 479.982 384.987 100.893 0.750 re f 479.982 369.106 0.750 16.631 re f 580.125 369.106 0.750 16.631 re f 0.271 0.267 0.267 rg BT 485.232 375.132 Td /F1 9.8 Tf [(0.009)] TJ ET 0.267 0.267 0.267 rg 26.625 369.106 369.863 0.750 re f 26.625 353.224 0.750 16.631 re f 0.271 0.267 0.267 rg BT 31.875 359.251 Td /F1 9.8 Tf [(18 day generation time)] TJ ET 0.267 0.267 0.267 rg 395.738 369.106 84.994 0.750 re f 395.738 353.224 0.750 16.631 re f 0.271 0.267 0.267 rg BT 400.988 359.251 Td /F1 9.8 Tf [(1.94)] TJ ET 0.267 0.267 0.267 rg 479.982 369.106 100.893 0.750 re f 479.982 353.224 0.750 16.631 re f 580.125 353.224 0.750 16.631 re f 0.271 0.267 0.267 rg BT 485.232 359.251 Td /F1 9.8 Tf [(0.013)] TJ ET 0.267 0.267 0.267 rg 26.625 353.224 369.863 0.750 re f 26.625 337.343 0.750 16.631 re f 0.271 0.267 0.267 rg BT 31.875 343.369 Td /F1 9.8 Tf [(Outbreak recognized generation 3)] TJ ET 0.267 0.267 0.267 rg 395.738 353.224 84.994 0.750 re f 395.738 337.343 0.750 16.631 re f 0.271 0.267 0.267 rg BT 400.988 343.369 Td /F1 9.8 Tf [(2.19)] TJ ET 0.267 0.267 0.267 rg 479.982 353.224 100.893 0.750 re f 479.982 337.343 0.750 16.631 re f 580.125 337.343 0.750 16.631 re f 0.271 0.267 0.267 rg BT 485.232 343.369 Td /F1 9.8 Tf [(0.022)] TJ ET 0.267 0.267 0.267 rg 26.625 337.343 369.863 0.750 re f 26.625 321.462 0.750 16.631 re f 0.271 0.267 0.267 rg BT 31.875 327.488 Td /F1 9.8 Tf [(Outbreak recognized generation 7)] TJ ET 0.267 0.267 0.267 rg 395.738 337.343 84.994 0.750 re f 395.738 321.462 0.750 16.631 re f 0.271 0.267 0.267 rg BT 400.988 327.488 Td /F1 9.8 Tf [(1.70)] TJ ET 0.267 0.267 0.267 rg 479.982 337.343 100.893 0.750 re f 479.982 321.462 0.750 16.631 re f 580.125 321.462 0.750 16.631 re f 0.271 0.267 0.267 rg BT 485.232 327.488 Td /F1 9.8 Tf [(0.011)] TJ ET 0.267 0.267 0.267 rg 26.625 321.462 369.863 0.750 re f 26.625 305.581 0.750 16.631 re f 0.271 0.267 0.267 rg BT 31.875 311.607 Td /F1 9.8 Tf [(Outbreak 50% under-reported)] TJ ET 0.267 0.267 0.267 rg 395.738 321.462 84.994 0.750 re f 395.738 305.581 0.750 16.631 re f 0.271 0.267 0.267 rg BT 400.988 311.607 Td /F1 9.8 Tf [(1.92)] TJ ET 0.267 0.267 0.267 rg 479.982 321.462 100.893 0.750 re f 479.982 305.581 0.750 16.631 re f 580.125 305.581 0.750 16.631 re f 0.271 0.267 0.267 rg BT 485.232 311.607 Td /F1 9.8 Tf [(0.013)] TJ ET 0.267 0.267 0.267 rg 26.625 305.581 369.863 0.750 re f 26.625 289.699 0.750 16.631 re f 0.271 0.267 0.267 rg BT 31.875 295.726 Td /F1 9.8 Tf [(Outbreak 100% under-reported)] TJ ET 0.267 0.267 0.267 rg 395.738 305.581 84.994 0.750 re f 395.738 289.699 0.750 16.631 re f 0.271 0.267 0.267 rg BT 400.988 295.726 Td /F1 9.8 Tf [(2.02)] TJ ET 0.267 0.267 0.267 rg 479.982 305.581 100.893 0.750 re f 479.982 289.699 0.750 16.631 re f 580.125 289.699 0.750 16.631 re f 0.271 0.267 0.267 rg BT 485.232 295.726 Td /F1 9.8 Tf [(0.015)] TJ ET 0.267 0.267 0.267 rg 26.625 289.699 369.863 0.750 re f 26.625 273.818 0.750 16.631 re f 0.271 0.267 0.267 rg BT 31.875 279.844 Td /F1 9.8 Tf [(Virologically confirmed cases only)] TJ ET 0.267 0.267 0.267 rg 395.738 289.699 84.994 0.750 re f 395.738 273.818 0.750 16.631 re f 0.271 0.267 0.267 rg BT 400.988 279.844 Td /F1 9.8 Tf [(1.74)] TJ ET 0.267 0.267 0.267 rg 479.982 289.699 100.893 0.750 re f 479.982 273.818 0.750 16.631 re f 580.125 273.818 0.750 16.631 re f 0.271 0.267 0.267 rg BT 485.232 279.844 Td /F1 9.8 Tf [(0.011)] TJ ET 0.267 0.267 0.267 rg 26.625 273.818 369.863 0.750 re f 26.625 257.937 0.750 16.631 re f 0.271 0.267 0.267 rg BT 31.875 263.963 Td /F1 9.8 Tf [(Deaths only)] TJ ET 0.267 0.267 0.267 rg 395.738 273.818 84.994 0.750 re f 395.738 257.937 0.750 16.631 re f 0.271 0.267 0.267 rg BT 400.988 263.963 Td /F1 9.8 Tf [(1.66)] TJ ET 0.267 0.267 0.267 rg 479.982 273.818 100.893 0.750 re f 479.982 257.937 0.750 16.631 re f 580.125 257.937 0.750 16.631 re f 0.271 0.267 0.267 rg BT 485.232 263.963 Td /F1 9.8 Tf [(0.008)] TJ ET 0.267 0.267 0.267 rg 26.625 257.937 369.863 0.750 re f 26.625 242.056 0.750 16.631 re f 0.271 0.267 0.267 rg BT 31.875 248.082 Td /F1 9.8 Tf [(Guinea cases only)] TJ ET 0.267 0.267 0.267 rg 395.738 257.937 84.994 0.750 re f 395.738 242.056 0.750 16.631 re f 0.271 0.267 0.267 rg BT 400.988 248.082 Td /F1 9.8 Tf [(2.46)] TJ ET 0.267 0.267 0.267 rg 479.982 257.937 100.893 0.750 re f 479.982 242.056 0.750 16.631 re f 580.125 242.056 0.750 16.631 re f 0.271 0.267 0.267 rg BT 485.232 248.082 Td /F1 9.8 Tf [(0.050)] TJ ET 0.267 0.267 0.267 rg 26.625 242.056 369.863 0.750 re f 26.625 226.174 0.750 16.631 re f 0.271 0.267 0.267 rg BT 31.875 232.201 Td /F1 9.8 Tf [(Liberia cases only)] TJ ET 0.267 0.267 0.267 rg 395.738 242.056 84.994 0.750 re f 395.738 226.174 0.750 16.631 re f 0.271 0.267 0.267 rg BT 400.988 232.201 Td /F1 9.8 Tf [(1.72)] TJ ET 0.267 0.267 0.267 rg 479.982 242.056 100.893 0.750 re f 479.982 226.174 0.750 16.631 re f 580.125 226.174 0.750 16.631 re f 0.271 0.267 0.267 rg BT 485.232 232.201 Td /F1 9.8 Tf [(0)] TJ ET 0.267 0.267 0.267 rg 26.625 226.174 369.863 0.750 re f 26.625 210.293 369.863 0.750 re f 26.625 210.293 0.750 16.631 re f 0.271 0.267 0.267 rg BT 31.875 216.319 Td /F1 9.8 Tf [(Sierra Leone cases only)] TJ ET 0.267 0.267 0.267 rg 395.738 226.174 84.994 0.750 re f 395.738 210.293 84.994 0.750 re f 395.738 210.293 0.750 16.631 re f 0.271 0.267 0.267 rg BT 400.988 216.319 Td /F1 9.8 Tf [(8.33)] TJ ET 0.267 0.267 0.267 rg 479.982 226.174 100.893 0.750 re f 479.982 210.293 100.893 0.750 re f 479.982 210.293 0.750 16.631 re f 580.125 210.293 0.750 16.631 re f 0.271 0.267 0.267 rg BT 485.232 216.319 Td /F1 9.8 Tf [(0.22)] TJ ET BT 26.250 138.197 Td /F4 12.0 Tf [(Discussion)] TJ ET Q q 15.000 36.933 577.500 740.067 re W n 0.965 0.965 0.965 rg 26.250 712.873 555.000 64.127 re f 0.267 0.267 0.267 rg 0.267 0.267 0.267 RG 26.250 712.873 m 581.250 712.873 l 581.250 713.623 l 26.250 713.623 l f q 35.250 724.123 537.000 52.877 re W n 0.271 0.267 0.267 rg BT 35.250 767.476 Td /F4 9.8 Tf [(Fig. 5: Country Specific Model Fits, Observed vs. Expected Cumulative Incidence)] TJ ET BT 35.250 748.106 Td /F1 9.8 Tf [(Graphs demonstrate good model fits \(dark curves\) to observed generation by generation cumulative incidence of infection )] TJ ET BT 35.250 734.370 Td /F1 9.8 Tf [(in Guinea \(top panel\), Liberia \(middle panel\), and Sierra Leone \(bottom panel\).)] TJ ET Q 0.965 0.965 0.965 rg 26.250 443.009 555.000 262.364 re f 0.267 0.267 0.267 rg 0.267 0.267 0.267 RG 26.250 705.373 m 581.250 705.373 l 581.250 704.623 l 26.250 704.623 l f 26.250 443.009 m 581.250 443.009 l 581.250 443.759 l 26.250 443.759 l f q 225.000 0 0 168.750 35.250 526.873 cm /I14 Do Q q 35.250 454.259 537.000 66.614 re W n 0.271 0.267 0.267 rg BT 35.250 511.349 Td /F4 9.8 Tf [(Fig. 6: Overall vs. Country-Level Model Fits)] TJ ET BT 35.250 491.979 Td /F1 9.8 Tf [(Graphs show good agreement between the base-case model, fit to overall cumulative incidence data \(all countries )] TJ ET BT 35.250 478.243 Td /F1 9.8 Tf [(combined, solid gray curve\) vs. summed outputs \(solid black curve\) from models fit to country-level data from Guinea )] TJ ET BT 35.250 464.506 Td /F1 9.8 Tf [(\(dashed black curve\), Liberia \(thin black curve\), and Sierra Leone \(dashed gray curve\).)] TJ ET Q q 26.250 421.773 555.000 13.736 re W n 0.271 0.267 0.267 rg BT 26.250 424.520 Td /F1 9.8 Tf [(Table 1. Sensitivity of Model Estimates to Alternate Approaches and Assumption)] TJ ET Q 1.000 1.000 1.000 rg 26.250 209.918 555.000 204.355 re f 0.965 0.965 0.965 rg 27.000 401.243 369.113 12.280 re f 0.267 0.267 0.267 rg 26.625 413.148 369.488 0.750 re f 26.625 400.868 0.750 13.030 re f 0.271 0.267 0.267 rg BT 31.500 403.999 Td /F4 9.8 Tf [(Alternate Assumption)] TJ ET 0.965 0.965 0.965 rg 396.113 401.243 84.244 12.280 re f 0.267 0.267 0.267 rg 396.113 413.148 84.244 0.750 re f 0.271 0.267 0.267 rg BT 400.613 403.999 Td /F6 9.8 Tf [(R)] TJ ET BT 407.653 403.999 Td /F6 8.7 Tf [(0)] TJ ET 0.965 0.965 0.965 rg 480.357 401.243 100.143 12.280 re f 0.267 0.267 0.267 rg 480.357 413.148 100.518 0.750 re f 580.125 400.868 0.750 13.030 re f 0.271 0.267 0.267 rg BT 484.857 403.999 Td /F6 9.8 Tf [(d)] TJ ET 0.267 0.267 0.267 rg 26.625 400.868 369.863 0.750 re f 26.625 384.987 0.750 16.631 re f 0.271 0.267 0.267 rg BT 31.875 391.013 Td /F1 9.8 Tf [(Base case)] TJ ET 0.267 0.267 0.267 rg 395.738 400.868 84.994 0.750 re f 395.738 384.987 0.750 16.631 re f 0.271 0.267 0.267 rg BT 400.988 391.013 Td /F1 9.8 Tf [(1.78)] TJ ET 0.267 0.267 0.267 rg 479.982 400.868 100.893 0.750 re f 479.982 384.987 0.750 16.631 re f 580.125 384.987 0.750 16.631 re f 0.271 0.267 0.267 rg BT 485.232 391.013 Td /F1 9.8 Tf [(0.009)] TJ ET 0.267 0.267 0.267 rg 26.625 384.987 369.863 0.750 re f 26.625 369.106 0.750 16.631 re f 0.271 0.267 0.267 rg BT 31.875 375.132 Td /F1 9.8 Tf [(12 day generation time)] TJ ET 0.267 0.267 0.267 rg 395.738 384.987 84.994 0.750 re f 395.738 369.106 0.750 16.631 re f 0.271 0.267 0.267 rg BT 400.988 375.132 Td /F1 9.8 Tf [(1.68)] TJ ET 0.267 0.267 0.267 rg 479.982 384.987 100.893 0.750 re f 479.982 369.106 0.750 16.631 re f 580.125 369.106 0.750 16.631 re f 0.271 0.267 0.267 rg BT 485.232 375.132 Td /F1 9.8 Tf [(0.009)] TJ ET 0.267 0.267 0.267 rg 26.625 369.106 369.863 0.750 re f 26.625 353.224 0.750 16.631 re f 0.271 0.267 0.267 rg BT 31.875 359.251 Td /F1 9.8 Tf [(18 day generation time)] TJ ET 0.267 0.267 0.267 rg 395.738 369.106 84.994 0.750 re f 395.738 353.224 0.750 16.631 re f 0.271 0.267 0.267 rg BT 400.988 359.251 Td /F1 9.8 Tf [(1.94)] TJ ET 0.267 0.267 0.267 rg 479.982 369.106 100.893 0.750 re f 479.982 353.224 0.750 16.631 re f 580.125 353.224 0.750 16.631 re f 0.271 0.267 0.267 rg BT 485.232 359.251 Td /F1 9.8 Tf [(0.013)] TJ ET 0.267 0.267 0.267 rg 26.625 353.224 369.863 0.750 re f 26.625 337.343 0.750 16.631 re f 0.271 0.267 0.267 rg BT 31.875 343.369 Td /F1 9.8 Tf [(Outbreak recognized generation 3)] TJ ET 0.267 0.267 0.267 rg 395.738 353.224 84.994 0.750 re f 395.738 337.343 0.750 16.631 re f 0.271 0.267 0.267 rg BT 400.988 343.369 Td /F1 9.8 Tf [(2.19)] TJ ET 0.267 0.267 0.267 rg 479.982 353.224 100.893 0.750 re f 479.982 337.343 0.750 16.631 re f 580.125 337.343 0.750 16.631 re f 0.271 0.267 0.267 rg BT 485.232 343.369 Td /F1 9.8 Tf [(0.022)] TJ ET 0.267 0.267 0.267 rg 26.625 337.343 369.863 0.750 re f 26.625 321.462 0.750 16.631 re f 0.271 0.267 0.267 rg BT 31.875 327.488 Td /F1 9.8 Tf [(Outbreak recognized generation 7)] TJ ET 0.267 0.267 0.267 rg 395.738 337.343 84.994 0.750 re f 395.738 321.462 0.750 16.631 re f 0.271 0.267 0.267 rg BT 400.988 327.488 Td /F1 9.8 Tf [(1.70)] TJ ET 0.267 0.267 0.267 rg 479.982 337.343 100.893 0.750 re f 479.982 321.462 0.750 16.631 re f 580.125 321.462 0.750 16.631 re f 0.271 0.267 0.267 rg BT 485.232 327.488 Td /F1 9.8 Tf [(0.011)] TJ ET 0.267 0.267 0.267 rg 26.625 321.462 369.863 0.750 re f 26.625 305.581 0.750 16.631 re f 0.271 0.267 0.267 rg BT 31.875 311.607 Td /F1 9.8 Tf [(Outbreak 50% under-reported)] TJ ET 0.267 0.267 0.267 rg 395.738 321.462 84.994 0.750 re f 395.738 305.581 0.750 16.631 re f 0.271 0.267 0.267 rg BT 400.988 311.607 Td /F1 9.8 Tf [(1.92)] TJ ET 0.267 0.267 0.267 rg 479.982 321.462 100.893 0.750 re f 479.982 305.581 0.750 16.631 re f 580.125 305.581 0.750 16.631 re f 0.271 0.267 0.267 rg BT 485.232 311.607 Td /F1 9.8 Tf [(0.013)] TJ ET 0.267 0.267 0.267 rg 26.625 305.581 369.863 0.750 re f 26.625 289.699 0.750 16.631 re f 0.271 0.267 0.267 rg BT 31.875 295.726 Td /F1 9.8 Tf [(Outbreak 100% under-reported)] TJ ET 0.267 0.267 0.267 rg 395.738 305.581 84.994 0.750 re f 395.738 289.699 0.750 16.631 re f 0.271 0.267 0.267 rg BT 400.988 295.726 Td /F1 9.8 Tf [(2.02)] TJ ET 0.267 0.267 0.267 rg 479.982 305.581 100.893 0.750 re f 479.982 289.699 0.750 16.631 re f 580.125 289.699 0.750 16.631 re f 0.271 0.267 0.267 rg BT 485.232 295.726 Td /F1 9.8 Tf [(0.015)] TJ ET 0.267 0.267 0.267 rg 26.625 289.699 369.863 0.750 re f 26.625 273.818 0.750 16.631 re f 0.271 0.267 0.267 rg BT 31.875 279.844 Td /F1 9.8 Tf [(Virologically confirmed cases only)] TJ ET 0.267 0.267 0.267 rg 395.738 289.699 84.994 0.750 re f 395.738 273.818 0.750 16.631 re f 0.271 0.267 0.267 rg BT 400.988 279.844 Td /F1 9.8 Tf [(1.74)] TJ ET 0.267 0.267 0.267 rg 479.982 289.699 100.893 0.750 re f 479.982 273.818 0.750 16.631 re f 580.125 273.818 0.750 16.631 re f 0.271 0.267 0.267 rg BT 485.232 279.844 Td /F1 9.8 Tf [(0.011)] TJ ET 0.267 0.267 0.267 rg 26.625 273.818 369.863 0.750 re f 26.625 257.937 0.750 16.631 re f 0.271 0.267 0.267 rg BT 31.875 263.963 Td /F1 9.8 Tf [(Deaths only)] TJ ET 0.267 0.267 0.267 rg 395.738 273.818 84.994 0.750 re f 395.738 257.937 0.750 16.631 re f 0.271 0.267 0.267 rg BT 400.988 263.963 Td /F1 9.8 Tf [(1.66)] TJ ET 0.267 0.267 0.267 rg 479.982 273.818 100.893 0.750 re f 479.982 257.937 0.750 16.631 re f 580.125 257.937 0.750 16.631 re f 0.271 0.267 0.267 rg BT 485.232 263.963 Td /F1 9.8 Tf [(0.008)] TJ ET 0.267 0.267 0.267 rg 26.625 257.937 369.863 0.750 re f 26.625 242.056 0.750 16.631 re f 0.271 0.267 0.267 rg BT 31.875 248.082 Td /F1 9.8 Tf [(Guinea cases only)] TJ ET 0.267 0.267 0.267 rg 395.738 257.937 84.994 0.750 re f 395.738 242.056 0.750 16.631 re f 0.271 0.267 0.267 rg BT 400.988 248.082 Td /F1 9.8 Tf [(2.46)] TJ ET 0.267 0.267 0.267 rg 479.982 257.937 100.893 0.750 re f 479.982 242.056 0.750 16.631 re f 580.125 242.056 0.750 16.631 re f 0.271 0.267 0.267 rg BT 485.232 248.082 Td /F1 9.8 Tf [(0.050)] TJ ET 0.267 0.267 0.267 rg 26.625 242.056 369.863 0.750 re f 26.625 226.174 0.750 16.631 re f 0.271 0.267 0.267 rg BT 31.875 232.201 Td /F1 9.8 Tf [(Liberia cases only)] TJ ET 0.267 0.267 0.267 rg 395.738 242.056 84.994 0.750 re f 395.738 226.174 0.750 16.631 re f 0.271 0.267 0.267 rg BT 400.988 232.201 Td /F1 9.8 Tf [(1.72)] TJ ET 0.267 0.267 0.267 rg 479.982 242.056 100.893 0.750 re f 479.982 226.174 0.750 16.631 re f 580.125 226.174 0.750 16.631 re f 0.271 0.267 0.267 rg BT 485.232 232.201 Td /F1 9.8 Tf [(0)] TJ ET 0.267 0.267 0.267 rg 26.625 226.174 369.863 0.750 re f 26.625 210.293 369.863 0.750 re f 26.625 210.293 0.750 16.631 re f 0.271 0.267 0.267 rg BT 31.875 216.319 Td /F1 9.8 Tf [(Sierra Leone cases only)] TJ ET 0.267 0.267 0.267 rg 395.738 226.174 84.994 0.750 re f 395.738 210.293 84.994 0.750 re f 395.738 210.293 0.750 16.631 re f 0.271 0.267 0.267 rg BT 400.988 216.319 Td /F1 9.8 Tf [(8.33)] TJ ET 0.267 0.267 0.267 rg 479.982 226.174 100.893 0.750 re f 479.982 210.293 100.893 0.750 re f 479.982 210.293 0.750 16.631 re f 580.125 210.293 0.750 16.631 re f 0.271 0.267 0.267 rg BT 485.232 216.319 Td /F1 9.8 Tf [(0.22)] TJ ET BT 26.250 138.197 Td /F4 12.0 Tf [(Discussion)] TJ ET Q q 225.000 0 0 168.750 35.250 526.873 cm /I14 Do Q q 0.000 0.000 0.000 rg BT 291.710 19.825 Td /F1 11.0 Tf [(5)] TJ ET BT 25.000 19.825 Td /F1 11.0 Tf [(PLOS Currents Outbreaks)] TJ ET Q endstream endobj 250 0 obj << /Type /Font /Subtype /Type1 /Name /F6 /BaseFont /Helvetica-BoldOblique /Encoding /WinAnsiEncoding >> endobj 251 0 obj << /Type /Annot /Subtype /Link /A 252 0 R /Border [0 0 0] /H /I /Rect [ 35.2500 526.8727 260.2500 695.6227 ] >> endobj 252 0 obj << /Type /Action /S /URI /URI (http://currents.plos.org/outbreaks/files/2014/08/Slide3.jpg) >> endobj 253 0 obj << /Type /XObject /Subtype /Image /Width 300 /Height 225 /ColorSpace /DeviceRGB /Filter /DCTDecode /BitsPerComponent 8 /Length 9234>> 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Based on models fit to available cumulative incidence data from August 2014, we )] TJ ET BT 26.250 743.667 Td /F1 9.8 Tf [(project that in the absence of more effective control interventions, this epidemic will increase to affect tens, and possibly )] TJ ET BT 26.250 731.762 Td /F1 9.8 Tf [(hundreds, of thousands of individuals. Given the high case fatality ratio associated with Ebola virus infection, such an )] TJ ET BT 26.250 719.857 Td /F1 9.8 Tf [(occurrence would be nothing short of catastrophic. Based on data currently available to us, it appears that this threat is currently )] TJ ET BT 26.250 707.952 Td /F1 9.8 Tf [(centered on the Liberian component of the epidemic, which can be characterized as a simple exponential growth process, with )] TJ ET BT 26.250 696.048 Td /F1 9.8 Tf [(little evidence for slowing of transmission. This contrasts with outbreaks in Guinea and Sierra Leone.)] TJ ET BT 26.250 676.643 Td /F1 9.8 Tf [(The IDEA model is descriptive, and consequently it is not possible to attribute mechanisms to the decay parameter \(d\) which )] TJ ET BT 26.250 664.738 Td /F1 9.8 Tf [(defines slowing of growth. In more complex and explicit models, the effects that occur via )] TJ ET BT 412.623 664.738 Td /F5 9.8 Tf [(d)] TJ ET BT 418.044 664.738 Td /F1 9.8 Tf [( could occur with decreased rates of )] TJ ET BT 26.250 652.833 Td /F1 9.8 Tf [(contact with infectious individuals, greater availability of personal protective items, behavioral change, depletion of susceptibles, )] TJ ET BT 26.250 640.929 Td /F1 9.8 Tf [(or any other factor that impacts the effective reproductive number or force of infection of an epidemic process )] TJ ET 0.267 0.267 0.267 rg BT 499.339 642.436 Td /F4 8.7 Tf [(13)] TJ ET 0.271 0.267 0.267 rg BT 508.977 644.817 Td /F1 8.7 Tf [(,)] TJ ET 0.267 0.267 0.267 rg BT 511.386 642.436 Td /F4 8.7 Tf [(14)] TJ ET 0.271 0.267 0.267 rg BT 521.024 640.929 Td /F1 9.8 Tf [(. )] TJ ET BT 26.250 629.024 Td /F1 9.8 Tf [(Nonetheless, this parameter describes the observed tendency of epidemics and outbreaks to end before the critical density of )] TJ ET BT 26.250 617.119 Td /F1 9.8 Tf [(susceptibles is exhausted )] TJ ET 0.267 0.267 0.267 rg BT 140.052 618.626 Td /F4 8.7 Tf [(1)] TJ ET 0.271 0.267 0.267 rg BT 144.871 617.119 Td /F1 9.8 Tf [(. In our published )] TJ ET 0.267 0.267 0.267 rg BT 222.373 618.626 Td /F4 8.7 Tf [(1)] TJ ET 0.271 0.267 0.267 rg BT 227.192 617.119 Td /F1 9.8 Tf [( , and as yet unpublished applications of this modeling approach to influenza and )] TJ ET BT 26.250 605.214 Td /F1 9.8 Tf [(MERS coronavirus epidemics and outbreaks, negligible values for )] TJ ET BT 312.900 605.214 Td /F5 9.8 Tf [(d)] TJ ET BT 318.321 605.214 Td /F1 9.8 Tf [(, as observed in Liberia, have been distinctly unusual. )] TJ ET BT 26.250 593.310 Td /F1 9.8 Tf [(However, uninterrupted exponential growth of an epidemic, as we observe in Liberia, is consistent with media reports and )] TJ ET BT 26.250 581.405 Td /F1 9.8 Tf [(communication from colleagues in the field. We project that even small, incremental near-term increases in control \(as defined )] TJ ET BT 26.250 569.500 Td /F1 9.8 Tf [(by )] TJ ET BT 39.257 569.500 Td /F5 9.8 Tf [(d)] TJ ET BT 44.678 569.500 Td /F1 9.8 Tf [(\) would result in thousands or tens of thousands of infections prevented. The value of 0.005 used in our analysis is arbitrary; )] TJ ET BT 26.250 557.595 Td /F1 9.8 Tf [(unfortunately, the novelty of the IDEA approach means that we have very limited understanding of the empiric size of real-world )] TJ ET BT 26.250 545.691 Td /F1 9.8 Tf [(control factors that would translate to a given change in )] TJ ET BT 267.416 545.691 Td /F5 9.8 Tf [(d.)] TJ ET BT 275.548 545.691 Td /F1 9.8 Tf [( However, our experiment confers a control factor on Liberia less than )] TJ ET BT 26.250 533.786 Td /F1 9.8 Tf [(that that appears to be operative in Guinea, so we believe this is likely to represent an attainable increase in control.)] TJ ET BT 26.250 514.381 Td /F1 9.8 Tf [(As with any mathematical model, ours is limited by the quality of data used for model calibration. Numerous factors, including )] TJ ET BT 26.250 502.476 Td /F1 9.8 Tf [(limited resources, understandable concerns for personal safety among healthcare and public health personnel, civil unrest, and )] TJ ET BT 26.250 490.572 Td /F1 9.8 Tf [(limited virological resources, are likely to combine to make accurate enumeration of cases difficult. We performed numerous )] TJ ET BT 26.250 478.667 Td /F1 9.8 Tf [(sensitivity analyses, and found that use of deaths or virologically confirmed case numbers, variation in plausible starting date or )] TJ ET BT 26.250 466.762 Td /F1 9.8 Tf [(generation time, and varying assumptions about \(constant\) under-reporting resulted in very little change in best-fit model )] TJ ET BT 26.250 454.857 Td /F1 9.8 Tf [(parameters. That said, factors such as abrupt decreases or surges in case reporting \(as opposed to occurrence\) would be likely )] TJ ET BT 26.250 442.953 Td /F1 9.8 Tf [(to result in distortion of model-based estimates.)] TJ ET BT 26.250 423.548 Td /F1 9.8 Tf [(For almost all scenarios evaluated, and for all countries except for Sierra Leone evaluated by single-country models, we found )] TJ ET BT 26.250 411.643 Td /F1 9.8 Tf [(estimates of R)] TJ ET BT 88.562 409.579 Td /F1 8.7 Tf [(0 )] TJ ET BT 95.790 411.643 Td /F1 9.8 Tf [(similar to those that have been reported previously for Ebola outbreaks )] TJ ET 0.267 0.267 0.267 rg BT 404.144 413.150 Td /F4 8.7 Tf [(2)] TJ ET 0.271 0.267 0.267 rg BT 408.962 415.531 Td /F1 8.7 Tf [(,)] TJ ET 0.267 0.267 0.267 rg BT 411.372 413.150 Td /F4 8.7 Tf [(4)] TJ ET 0.271 0.267 0.267 rg BT 416.190 411.643 Td /F1 9.8 Tf [( . For Sierra Leone, we found an )] TJ ET BT 26.250 399.738 Td /F1 9.8 Tf [(outbreak that appeared to explode extremely rapidly, and then be controlled with similar rapidity. Whether this reflects actual )] TJ ET BT 26.250 387.834 Td /F1 9.8 Tf [(disease dynamics or artifacts of disease surveillance and reporting remains to be seen.)] TJ ET BT 26.250 351.231 Td /F4 12.0 Tf [(Conclusion)] TJ ET BT 26.250 331.277 Td /F1 9.8 Tf [(Using a simple, two-parameter mathematical model, we find that the initial growth characteristics of the 2014 West African )] TJ ET BT 26.250 319.372 Td /F1 9.8 Tf [(Ebola epidemic to be similar to those associated with prior Ebola outbreaks. Concerning is the lack of control evident, with )] TJ ET BT 26.250 307.467 Td /F1 9.8 Tf [(epidemic processes growing in an essentially uncontrolled exponential manner, particularly in Liberia. While further data will )] TJ ET BT 26.250 295.563 Td /F1 9.8 Tf [(permit model validation or re-calibration in the coming months, our findings indicate that this epidemic represents a public health )] TJ ET BT 26.250 283.658 Td /F1 9.8 Tf [(emergency which has the potential to grow to extraordinarily destructive dimensions. We hope our model will add support to )] TJ ET BT 26.250 271.753 Td /F1 9.8 Tf [(those voices already calling for an extraordinary international cooperative effort to control this epidemic.)] TJ ET BT 26.250 235.151 Td /F4 12.0 Tf [(Competing Interests)] TJ ET BT 26.250 215.196 Td /F1 9.8 Tf [(The authors have declared that no competing interests exist.)] TJ ET BT 26.250 178.594 Td /F4 12.0 Tf [(Acknowledgements)] TJ ET BT 26.250 158.640 Td /F1 9.8 Tf [(The authors thank Maimuna S. Majumdar, Stephane Helleringer, John Brownstein, Ian Mackay, Caitlin Rivers, and Christian )] TJ ET BT 26.250 146.735 Td /F1 9.8 Tf [(Althus for comments, suggestions, and guidance regarding data sources. In particular, Caitlin Riverss data repository )] TJ ET BT 26.250 134.830 Td /F1 9.8 Tf [(\(https://github.com/cmrivers/ebola\), and Ian Mackays Virology Down Under blog \(http://virologydownunder.blogspot.com.au/\), )] TJ ET BT 26.250 122.925 Td /F1 9.8 Tf [(were invaluable as sources for Ebola epidemic data.)] TJ ET BT 26.250 93.823 Td /F4 12.0 Tf [(References)] TJ ET BT 26.250 66.369 Td /F1 9.8 Tf [(1.)] TJ ET BT 38.132 66.369 Td /F1 9.8 Tf [(Fisman DN, Hauck TS, Tuite AR, Greer AL. An IDEA for short term outbreak projection: nearcasting using the basic )] TJ ET BT 26.250 54.464 Td /F1 9.8 Tf [(reproduction number. PLoS One. 2013;8\(12\):e83622. PubMed PMID:24391797.)] TJ ET Q q 15.000 44.583 577.500 732.417 re W n 0.271 0.267 0.267 rg BT 26.250 767.476 Td /F1 9.8 Tf [(The 2014 Ebola epidemic now stands as the largest ever recorded, and threatens not only health and healthcare institutions, )] TJ ET BT 26.250 755.571 Td /F1 9.8 Tf [(but civil institutions, in affected countries. Based on models fit to available cumulative incidence data from August 2014, we )] TJ ET BT 26.250 743.667 Td /F1 9.8 Tf [(project that in the absence of more effective control interventions, this epidemic will increase to affect tens, and possibly )] TJ ET BT 26.250 731.762 Td /F1 9.8 Tf [(hundreds, of thousands of individuals. Given the high case fatality ratio associated with Ebola virus infection, such an )] TJ ET BT 26.250 719.857 Td /F1 9.8 Tf [(occurrence would be nothing short of catastrophic. Based on data currently available to us, it appears that this threat is currently )] TJ ET BT 26.250 707.952 Td /F1 9.8 Tf [(centered on the Liberian component of the epidemic, which can be characterized as a simple exponential growth process, with )] TJ ET BT 26.250 696.048 Td /F1 9.8 Tf [(little evidence for slowing of transmission. This contrasts with outbreaks in Guinea and Sierra Leone.)] TJ ET BT 26.250 676.643 Td /F1 9.8 Tf [(The IDEA model is descriptive, and consequently it is not possible to attribute mechanisms to the decay parameter \(d\) which )] TJ ET BT 26.250 664.738 Td /F1 9.8 Tf [(defines slowing of growth. In more complex and explicit models, the effects that occur via )] TJ ET BT 412.623 664.738 Td /F5 9.8 Tf [(d)] TJ ET BT 418.044 664.738 Td /F1 9.8 Tf [( could occur with decreased rates of )] TJ ET BT 26.250 652.833 Td /F1 9.8 Tf [(contact with infectious individuals, greater availability of personal protective items, behavioral change, depletion of susceptibles, )] TJ ET BT 26.250 640.929 Td /F1 9.8 Tf [(or any other factor that impacts the effective reproductive number or force of infection of an epidemic process )] TJ ET 0.267 0.267 0.267 rg BT 499.339 642.436 Td /F4 8.7 Tf [(13)] TJ ET 0.271 0.267 0.267 rg BT 508.977 644.817 Td /F1 8.7 Tf [(,)] TJ ET 0.267 0.267 0.267 rg BT 511.386 642.436 Td /F4 8.7 Tf [(14)] TJ ET 0.271 0.267 0.267 rg BT 521.024 640.929 Td /F1 9.8 Tf [(. )] TJ ET BT 26.250 629.024 Td /F1 9.8 Tf [(Nonetheless, this parameter describes the observed tendency of epidemics and outbreaks to end before the critical density of )] TJ ET BT 26.250 617.119 Td /F1 9.8 Tf [(susceptibles is exhausted )] TJ ET 0.267 0.267 0.267 rg BT 140.052 618.626 Td /F4 8.7 Tf [(1)] TJ ET 0.271 0.267 0.267 rg BT 144.871 617.119 Td /F1 9.8 Tf [(. In our published )] TJ ET 0.267 0.267 0.267 rg BT 222.373 618.626 Td /F4 8.7 Tf [(1)] TJ ET 0.271 0.267 0.267 rg BT 227.192 617.119 Td /F1 9.8 Tf [( , and as yet unpublished applications of this modeling approach to influenza and )] TJ ET BT 26.250 605.214 Td /F1 9.8 Tf [(MERS coronavirus epidemics and outbreaks, negligible values for )] TJ ET BT 312.900 605.214 Td /F5 9.8 Tf [(d)] TJ ET BT 318.321 605.214 Td /F1 9.8 Tf [(, as observed in Liberia, have been distinctly unusual. )] TJ ET BT 26.250 593.310 Td /F1 9.8 Tf [(However, uninterrupted exponential growth of an epidemic, as we observe in Liberia, is consistent with media reports and )] TJ ET BT 26.250 581.405 Td /F1 9.8 Tf [(communication from colleagues in the field. We project that even small, incremental near-term increases in control \(as defined )] TJ ET BT 26.250 569.500 Td /F1 9.8 Tf [(by )] TJ ET BT 39.257 569.500 Td /F5 9.8 Tf [(d)] TJ ET BT 44.678 569.500 Td /F1 9.8 Tf [(\) would result in thousands or tens of thousands of infections prevented. The value of 0.005 used in our analysis is arbitrary; )] TJ ET BT 26.250 557.595 Td /F1 9.8 Tf [(unfortunately, the novelty of the IDEA approach means that we have very limited understanding of the empiric size of real-world )] TJ ET BT 26.250 545.691 Td /F1 9.8 Tf [(control factors that would translate to a given change in )] TJ ET BT 267.416 545.691 Td /F5 9.8 Tf [(d.)] TJ ET BT 275.548 545.691 Td /F1 9.8 Tf [( However, our experiment confers a control factor on Liberia less than )] TJ ET BT 26.250 533.786 Td /F1 9.8 Tf [(that that appears to be operative in Guinea, so we believe this is likely to represent an attainable increase in control.)] TJ ET BT 26.250 514.381 Td /F1 9.8 Tf [(As with any mathematical model, ours is limited by the quality of data used for model calibration. Numerous factors, including )] TJ ET BT 26.250 502.476 Td /F1 9.8 Tf [(limited resources, understandable concerns for personal safety among healthcare and public health personnel, civil unrest, and )] TJ ET BT 26.250 490.572 Td /F1 9.8 Tf [(limited virological resources, are likely to combine to make accurate enumeration of cases difficult. We performed numerous )] TJ ET BT 26.250 478.667 Td /F1 9.8 Tf [(sensitivity analyses, and found that use of deaths or virologically confirmed case numbers, variation in plausible starting date or )] TJ ET BT 26.250 466.762 Td /F1 9.8 Tf [(generation time, and varying assumptions about \(constant\) under-reporting resulted in very little change in best-fit model )] TJ ET BT 26.250 454.857 Td /F1 9.8 Tf [(parameters. That said, factors such as abrupt decreases or surges in case reporting \(as opposed to occurrence\) would be likely )] TJ ET BT 26.250 442.953 Td /F1 9.8 Tf [(to result in distortion of model-based estimates.)] TJ ET BT 26.250 423.548 Td /F1 9.8 Tf [(For almost all scenarios evaluated, and for all countries except for Sierra Leone evaluated by single-country models, we found )] TJ ET BT 26.250 411.643 Td /F1 9.8 Tf [(estimates of R)] TJ ET BT 88.562 409.579 Td /F1 8.7 Tf [(0 )] TJ ET BT 95.790 411.643 Td /F1 9.8 Tf [(similar to those that have been reported previously for Ebola outbreaks )] TJ ET 0.267 0.267 0.267 rg BT 404.144 413.150 Td /F4 8.7 Tf [(2)] TJ ET 0.271 0.267 0.267 rg BT 408.962 415.531 Td /F1 8.7 Tf [(,)] TJ ET 0.267 0.267 0.267 rg BT 411.372 413.150 Td /F4 8.7 Tf [(4)] TJ ET 0.271 0.267 0.267 rg BT 416.190 411.643 Td /F1 9.8 Tf [( . For Sierra Leone, we found an )] TJ ET BT 26.250 399.738 Td /F1 9.8 Tf [(outbreak that appeared to explode extremely rapidly, and then be controlled with similar rapidity. Whether this reflects actual )] TJ ET BT 26.250 387.834 Td /F1 9.8 Tf [(disease dynamics or artifacts of disease surveillance and reporting remains to be seen.)] TJ ET BT 26.250 351.231 Td /F4 12.0 Tf [(Conclusion)] TJ ET BT 26.250 331.277 Td /F1 9.8 Tf [(Using a simple, two-parameter mathematical model, we find that the initial growth characteristics of the 2014 West African )] TJ ET BT 26.250 319.372 Td /F1 9.8 Tf [(Ebola epidemic to be similar to those associated with prior Ebola outbreaks. Concerning is the lack of control evident, with )] TJ ET BT 26.250 307.467 Td /F1 9.8 Tf [(epidemic processes growing in an essentially uncontrolled exponential manner, particularly in Liberia. While further data will )] TJ ET BT 26.250 295.563 Td /F1 9.8 Tf [(permit model validation or re-calibration in the coming months, our findings indicate that this epidemic represents a public health )] TJ ET BT 26.250 283.658 Td /F1 9.8 Tf [(emergency which has the potential to grow to extraordinarily destructive dimensions. We hope our model will add support to )] TJ ET BT 26.250 271.753 Td /F1 9.8 Tf [(those voices already calling for an extraordinary international cooperative effort to control this epidemic.)] TJ ET BT 26.250 235.151 Td /F4 12.0 Tf [(Competing Interests)] TJ ET BT 26.250 215.196 Td /F1 9.8 Tf [(The authors have declared that no competing interests exist.)] TJ ET BT 26.250 178.594 Td /F4 12.0 Tf [(Acknowledgements)] TJ ET BT 26.250 158.640 Td /F1 9.8 Tf [(The authors thank Maimuna S. Majumdar, Stephane Helleringer, John Brownstein, Ian Mackay, Caitlin Rivers, and Christian )] TJ ET BT 26.250 146.735 Td /F1 9.8 Tf [(Althus for comments, suggestions, and guidance regarding data sources. In particular, Caitlin Riverss data repository )] TJ ET BT 26.250 134.830 Td /F1 9.8 Tf [(\(https://github.com/cmrivers/ebola\), and Ian Mackays Virology Down Under blog \(http://virologydownunder.blogspot.com.au/\), )] TJ ET BT 26.250 122.925 Td /F1 9.8 Tf [(were invaluable as sources for Ebola epidemic data.)] TJ ET BT 26.250 93.823 Td /F4 12.0 Tf [(References)] TJ ET BT 26.250 66.369 Td /F1 9.8 Tf [(1.)] TJ ET BT 38.132 66.369 Td /F1 9.8 Tf [(Fisman DN, Hauck TS, Tuite AR, Greer AL. An IDEA for short term outbreak projection: nearcasting using the basic )] TJ ET BT 26.250 54.464 Td /F1 9.8 Tf [(reproduction number. PLoS One. 2013;8\(12\):e83622. PubMed PMID:24391797.)] TJ ET Q q 15.000 44.583 577.500 732.417 re W n 0.271 0.267 0.267 rg BT 26.250 767.476 Td /F1 9.8 Tf [(The 2014 Ebola epidemic now stands as the largest ever recorded, and threatens not only health and healthcare institutions, )] TJ ET BT 26.250 755.571 Td /F1 9.8 Tf [(but civil institutions, in affected countries. Based on models fit to available cumulative incidence data from August 2014, we )] TJ ET BT 26.250 743.667 Td /F1 9.8 Tf [(project that in the absence of more effective control interventions, this epidemic will increase to affect tens, and possibly )] TJ ET BT 26.250 731.762 Td /F1 9.8 Tf [(hundreds, of thousands of individuals. Given the high case fatality ratio associated with Ebola virus infection, such an )] TJ ET BT 26.250 719.857 Td /F1 9.8 Tf [(occurrence would be nothing short of catastrophic. Based on data currently available to us, it appears that this threat is currently )] TJ ET BT 26.250 707.952 Td /F1 9.8 Tf [(centered on the Liberian component of the epidemic, which can be characterized as a simple exponential growth process, with )] TJ ET BT 26.250 696.048 Td /F1 9.8 Tf [(little evidence for slowing of transmission. This contrasts with outbreaks in Guinea and Sierra Leone.)] TJ ET BT 26.250 676.643 Td /F1 9.8 Tf [(The IDEA model is descriptive, and consequently it is not possible to attribute mechanisms to the decay parameter \(d\) which )] TJ ET BT 26.250 664.738 Td /F1 9.8 Tf [(defines slowing of growth. In more complex and explicit models, the effects that occur via )] TJ ET BT 412.623 664.738 Td /F5 9.8 Tf [(d)] TJ ET BT 418.044 664.738 Td /F1 9.8 Tf [( could occur with decreased rates of )] TJ ET BT 26.250 652.833 Td /F1 9.8 Tf [(contact with infectious individuals, greater availability of personal protective items, behavioral change, depletion of susceptibles, )] TJ ET BT 26.250 640.929 Td /F1 9.8 Tf [(or any other factor that impacts the effective reproductive number or force of infection of an epidemic process )] TJ ET 0.267 0.267 0.267 rg BT 499.339 642.436 Td /F4 8.7 Tf [(13)] TJ ET 0.271 0.267 0.267 rg BT 508.977 644.817 Td /F1 8.7 Tf [(,)] TJ ET 0.267 0.267 0.267 rg BT 511.386 642.436 Td /F4 8.7 Tf [(14)] TJ ET 0.271 0.267 0.267 rg BT 521.024 640.929 Td /F1 9.8 Tf [(. )] TJ ET BT 26.250 629.024 Td /F1 9.8 Tf [(Nonetheless, this parameter describes the observed tendency of epidemics and outbreaks to end before the critical density of )] TJ ET BT 26.250 617.119 Td /F1 9.8 Tf [(susceptibles is exhausted )] TJ ET 0.267 0.267 0.267 rg BT 140.052 618.626 Td /F4 8.7 Tf [(1)] TJ ET 0.271 0.267 0.267 rg BT 144.871 617.119 Td /F1 9.8 Tf [(. In our published )] TJ ET 0.267 0.267 0.267 rg BT 222.373 618.626 Td /F4 8.7 Tf [(1)] TJ ET 0.271 0.267 0.267 rg BT 227.192 617.119 Td /F1 9.8 Tf [( , and as yet unpublished applications of this modeling approach to influenza and )] TJ ET BT 26.250 605.214 Td /F1 9.8 Tf [(MERS coronavirus epidemics and outbreaks, negligible values for )] TJ ET BT 312.900 605.214 Td /F5 9.8 Tf [(d)] TJ ET BT 318.321 605.214 Td /F1 9.8 Tf [(, as observed in Liberia, have been distinctly unusual. )] TJ ET BT 26.250 593.310 Td /F1 9.8 Tf [(However, uninterrupted exponential growth of an epidemic, as we observe in Liberia, is consistent with media reports and )] TJ ET BT 26.250 581.405 Td /F1 9.8 Tf [(communication from colleagues in the field. We project that even small, incremental near-term increases in control \(as defined )] TJ ET BT 26.250 569.500 Td /F1 9.8 Tf [(by )] TJ ET BT 39.257 569.500 Td /F5 9.8 Tf [(d)] TJ ET BT 44.678 569.500 Td /F1 9.8 Tf [(\) would result in thousands or tens of thousands of infections prevented. The value of 0.005 used in our analysis is arbitrary; )] TJ ET BT 26.250 557.595 Td /F1 9.8 Tf [(unfortunately, the novelty of the IDEA approach means that we have very limited understanding of the empiric size of real-world )] TJ ET BT 26.250 545.691 Td /F1 9.8 Tf [(control factors that would translate to a given change in )] TJ ET BT 267.416 545.691 Td /F5 9.8 Tf [(d.)] TJ ET BT 275.548 545.691 Td /F1 9.8 Tf [( However, our experiment confers a control factor on Liberia less than )] TJ ET BT 26.250 533.786 Td /F1 9.8 Tf [(that that appears to be operative in Guinea, so we believe this is likely to represent an attainable increase in control.)] TJ ET BT 26.250 514.381 Td /F1 9.8 Tf [(As with any mathematical model, ours is limited by the quality of data used for model calibration. Numerous factors, including )] TJ ET BT 26.250 502.476 Td /F1 9.8 Tf [(limited resources, understandable concerns for personal safety among healthcare and public health personnel, civil unrest, and )] TJ ET BT 26.250 490.572 Td /F1 9.8 Tf [(limited virological resources, are likely to combine to make accurate enumeration of cases difficult. We performed numerous )] TJ ET BT 26.250 478.667 Td /F1 9.8 Tf [(sensitivity analyses, and found that use of deaths or virologically confirmed case numbers, variation in plausible starting date or )] TJ ET BT 26.250 466.762 Td /F1 9.8 Tf [(generation time, and varying assumptions about \(constant\) under-reporting resulted in very little change in best-fit model )] TJ ET BT 26.250 454.857 Td /F1 9.8 Tf [(parameters. That said, factors such as abrupt decreases or surges in case reporting \(as opposed to occurrence\) would be likely )] TJ ET BT 26.250 442.953 Td /F1 9.8 Tf [(to result in distortion of model-based estimates.)] TJ ET BT 26.250 423.548 Td /F1 9.8 Tf [(For almost all scenarios evaluated, and for all countries except for Sierra Leone evaluated by single-country models, we found )] TJ ET BT 26.250 411.643 Td /F1 9.8 Tf [(estimates of R)] TJ ET BT 88.562 409.579 Td /F1 8.7 Tf [(0 )] TJ ET BT 95.790 411.643 Td /F1 9.8 Tf [(similar to those that have been reported previously for Ebola outbreaks )] TJ ET 0.267 0.267 0.267 rg BT 404.144 413.150 Td /F4 8.7 Tf [(2)] TJ ET 0.271 0.267 0.267 rg BT 408.962 415.531 Td /F1 8.7 Tf [(,)] TJ ET 0.267 0.267 0.267 rg BT 411.372 413.150 Td /F4 8.7 Tf [(4)] TJ ET 0.271 0.267 0.267 rg BT 416.190 411.643 Td /F1 9.8 Tf [( . For Sierra Leone, we found an )] TJ ET BT 26.250 399.738 Td /F1 9.8 Tf [(outbreak that appeared to explode extremely rapidly, and then be controlled with similar rapidity. Whether this reflects actual )] TJ ET BT 26.250 387.834 Td /F1 9.8 Tf [(disease dynamics or artifacts of disease surveillance and reporting remains to be seen.)] TJ ET BT 26.250 351.231 Td /F4 12.0 Tf [(Conclusion)] TJ ET BT 26.250 331.277 Td /F1 9.8 Tf [(Using a simple, two-parameter mathematical model, we find that the initial growth characteristics of the 2014 West African )] TJ ET BT 26.250 319.372 Td /F1 9.8 Tf [(Ebola epidemic to be similar to those associated with prior Ebola outbreaks. Concerning is the lack of control evident, with )] TJ ET BT 26.250 307.467 Td /F1 9.8 Tf [(epidemic processes growing in an essentially uncontrolled exponential manner, particularly in Liberia. While further data will )] TJ ET BT 26.250 295.563 Td /F1 9.8 Tf [(permit model validation or re-calibration in the coming months, our findings indicate that this epidemic represents a public health )] TJ ET BT 26.250 283.658 Td /F1 9.8 Tf [(emergency which has the potential to grow to extraordinarily destructive dimensions. We hope our model will add support to )] TJ ET BT 26.250 271.753 Td /F1 9.8 Tf [(those voices already calling for an extraordinary international cooperative effort to control this epidemic.)] TJ ET BT 26.250 235.151 Td /F4 12.0 Tf [(Competing Interests)] TJ ET BT 26.250 215.196 Td /F1 9.8 Tf [(The authors have declared that no competing interests exist.)] TJ ET BT 26.250 178.594 Td /F4 12.0 Tf [(Acknowledgements)] TJ ET BT 26.250 158.640 Td /F1 9.8 Tf [(The authors thank Maimuna S. Majumdar, Stephane Helleringer, John Brownstein, Ian Mackay, Caitlin Rivers, and Christian )] TJ ET BT 26.250 146.735 Td /F1 9.8 Tf [(Althus for comments, suggestions, and guidance regarding data sources. In particular, Caitlin Riverss data repository )] TJ ET BT 26.250 134.830 Td /F1 9.8 Tf [(\(https://github.com/cmrivers/ebola\), and Ian Mackays Virology Down Under blog \(http://virologydownunder.blogspot.com.au/\), )] TJ ET BT 26.250 122.925 Td /F1 9.8 Tf [(were invaluable as sources for Ebola epidemic data.)] TJ ET BT 26.250 93.823 Td /F4 12.0 Tf [(References)] TJ ET BT 26.250 66.369 Td /F1 9.8 Tf [(1.)] TJ ET BT 38.132 66.369 Td /F1 9.8 Tf [(Fisman DN, Hauck TS, Tuite AR, Greer AL. An IDEA for short term outbreak projection: nearcasting using the basic )] TJ ET BT 26.250 54.464 Td /F1 9.8 Tf [(reproduction number. PLoS One. 2013;8\(12\):e83622. PubMed PMID:24391797.)] TJ ET Q q 0.000 0.000 0.000 rg BT 291.710 19.825 Td /F1 11.0 Tf [(6)] TJ ET BT 25.000 19.825 Td /F1 11.0 Tf [(PLOS Currents Outbreaks)] TJ ET Q endstream endobj 260 0 obj << /Type /Annot /Subtype /Link /A 261 0 R /Border [0 0 0] /H /I /Rect [ 499.3395 641.6342 508.9768 650.4525 ] >> endobj 261 0 obj << /Type /Action >> endobj 262 0 obj << /Type /Annot /Subtype /Link /A 263 0 R /Border [0 0 0] /H /I /Rect [ 511.3862 641.6342 521.0235 650.4525 ] >> endobj 263 0 obj << /Type /Action >> endobj 264 0 obj << /Type /Annot /Subtype /Link /A 265 0 R /Border [0 0 0] /H /I /Rect [ 140.0520 617.8247 144.8707 626.6430 ] >> endobj 265 0 obj << /Type /Action >> endobj 266 0 obj << /Type /Annot /Subtype /Link /A 267 0 R /Border [0 0 0] /H /I /Rect [ 222.3734 617.8247 227.1921 626.6430 ] >> endobj 267 0 obj << /Type /Action >> endobj 268 0 obj << /Type /Annot /Subtype /Link /A 269 0 R /Border [0 0 0] /H /I /Rect [ 404.1438 412.3487 408.9624 421.1670 ] >> endobj 269 0 obj << /Type /Action >> endobj 270 0 obj << /Type /Annot /Subtype /Link /A 271 0 R /Border [0 0 0] /H /I /Rect [ 411.3718 412.3487 416.1904 421.1670 ] >> endobj 271 0 obj << /Type /Action >> endobj 272 0 obj << /Type /Annot /Subtype /Link /A 273 0 R /Border [0 0 0] /H /I /Rect [ 499.3395 641.6342 508.9768 650.4525 ] >> endobj 273 0 obj << /Type /Action >> endobj 274 0 obj << /Type /Annot /Subtype /Link /A 275 0 R /Border [0 0 0] /H /I /Rect [ 511.3862 641.6342 521.0235 650.4525 ] >> endobj 275 0 obj << /Type /Action >> endobj 276 0 obj << /Type /Annot /Subtype /Link /A 277 0 R /Border [0 0 0] /H /I /Rect [ 140.0520 617.8247 144.8707 626.6430 ] >> endobj 277 0 obj << /Type /Action >> endobj 278 0 obj << /Type /Annot /Subtype /Link /A 279 0 R /Border [0 0 0] /H /I /Rect [ 222.3734 617.8247 227.1921 626.6430 ] >> endobj 279 0 obj << /Type /Action >> endobj 280 0 obj << /Type /Annot /Subtype /Link /A 281 0 R /Border [0 0 0] /H /I /Rect [ 404.1438 412.3487 408.9624 421.1670 ] >> endobj 281 0 obj << /Type /Action >> endobj 282 0 obj << /Type /Annot /Subtype /Link /A 283 0 R /Border [0 0 0] /H /I /Rect [ 411.3718 412.3487 416.1904 421.1670 ] >> endobj 283 0 obj << /Type /Action >> endobj 284 0 obj << /Type /Annot /Subtype /Link /A 285 0 R /Border [0 0 0] /H /I /Rect [ 499.3395 641.6342 508.9768 650.4525 ] >> endobj 285 0 obj << /Type /Action >> endobj 286 0 obj << /Type /Annot /Subtype /Link /A 287 0 R /Border [0 0 0] /H /I /Rect [ 511.3862 641.6342 521.0235 650.4525 ] >> endobj 287 0 obj << /Type /Action >> endobj 288 0 obj << /Type /Annot /Subtype /Link /A 289 0 R /Border [0 0 0] /H /I /Rect [ 140.0520 617.8247 144.8707 626.6430 ] >> endobj 289 0 obj << /Type /Action >> endobj 290 0 obj << /Type /Annot /Subtype /Link /A 291 0 R /Border [0 0 0] /H /I /Rect [ 222.3734 617.8247 227.1921 626.6430 ] >> endobj 291 0 obj << /Type /Action >> endobj 292 0 obj << /Type /Annot /Subtype /Link /A 293 0 R /Border [0 0 0] /H /I /Rect [ 404.1438 412.3487 408.9624 421.1670 ] >> endobj 293 0 obj << /Type /Action >> endobj 294 0 obj << /Type /Annot /Subtype /Link /A 295 0 R /Border [0 0 0] /H /I /Rect [ 411.3718 412.3487 416.1904 421.1670 ] >> endobj 295 0 obj << /Type /Action >> endobj 296 0 obj << /Type /Page /Parent 3 0 R /Annots [ 298 0 R 300 0 R 302 0 R 304 0 R 306 0 R 308 0 R 310 0 R 312 0 R 314 0 R 316 0 R 318 0 R 320 0 R 322 0 R 324 0 R 326 0 R ] /Contents 297 0 R >> endobj 297 0 obj << /Length 14599 >> stream 0.271 0.267 0.267 rg q 15.000 293.011 577.500 483.989 re W n 0.271 0.267 0.267 rg BT 26.250 759.976 Td /F1 9.8 Tf [(2.)] TJ ET BT 38.132 759.976 Td /F1 9.8 Tf [(Chowell G, Hengartner NW, Castillo-Chavez C, Fenimore PW, Hyman JM. The basic reproductive number of Ebola and the )] TJ ET BT 26.250 748.071 Td /F1 9.8 Tf [(effects of public health measures: the cases of Congo and Uganda. J Theor Biol. 2004 Jul 7;229\(1\):119-26. PubMed )] TJ ET BT 26.250 736.167 Td /F1 9.8 Tf [(PMID:15178190.)] TJ ET BT 26.250 716.762 Td /F1 9.8 Tf [(3.)] TJ ET BT 38.132 716.762 Td /F1 9.8 Tf [(Eichner M, Dowell SF, Firese N. Incubation period of ebola hemorrhagic virus subtype zaire. Osong Public Health Res )] TJ ET BT 26.250 704.857 Td /F1 9.8 Tf [(Perspect. 2011 Jun;2\(1\):3-7. PubMed PMID:24159443.)] TJ ET BT 26.250 685.452 Td /F1 9.8 Tf [(4.)] TJ ET BT 38.132 685.452 Td /F1 9.8 Tf [(Legrand J, Grais RF, Boelle PY, Valleron AJ, Flahault A. Understanding the dynamics of Ebola epidemics. Epidemiol Infect. )] TJ ET BT 26.250 673.548 Td /F1 9.8 Tf [(2007 May;135\(4\):610-21. PubMed PMID:16999875.)] TJ ET BT 26.250 654.143 Td /F1 9.8 Tf [(5.)] TJ ET BT 38.132 654.143 Td /F1 9.8 Tf [(Kortepeter MG, Bausch DG, Bray M. Basic clinical and laboratory features of filoviral hemorrhagic fever. J Infect Dis. 2011 )] TJ ET BT 26.250 642.238 Td /F1 9.8 Tf [(Nov;204 Suppl 3:S810-6. PubMed PMID:21987756.)] TJ ET BT 26.250 622.833 Td /F1 9.8 Tf [(6.)] TJ ET BT 38.132 622.833 Td /F1 9.8 Tf [(Donnelly, P. Ebola outbreak sweeping West Africa started with two-year-old boy infected by a fruit bat, say researchers. )] TJ ET BT 26.250 610.929 Td /F1 9.8 Tf [(MailOnline. 10:00 EST, 24 August 2014. Available via the Internet, last accessed August 27, 2014.)] TJ ET 0.267 0.267 0.267 rg BT 26.250 602.443 Td /F1 7.5 Tf [(REFERENCE LINK)] TJ ET 0.271 0.267 0.267 rg BT 26.250 583.893 Td /F1 9.8 Tf [(7.)] TJ ET BT 38.132 583.893 Td /F1 9.8 Tf [(Dixon MG, Schafer IJ. Ebola viral disease outbreak--West Africa, 2014. MMWR Morb Mortal Wkly Rep. 2014 Jun )] TJ ET BT 26.250 571.988 Td /F1 9.8 Tf [(27;63\(25\):548-51. PubMed PMID:24964881.)] TJ ET BT 26.250 552.583 Td /F1 9.8 Tf [(8.)] TJ ET BT 38.132 552.583 Td /F1 9.8 Tf [(Roos R. As Ebola outbreak grows, WHO notes case-count difficulties. CIDRAP Center for Infectious Disease Research and )] TJ ET BT 26.250 540.678 Td /F1 9.8 Tf [(Policy. August 22, 2014. Available via the Internet, last accessed August 27, 2014. )] TJ ET 0.267 0.267 0.267 rg BT 26.250 532.192 Td /F1 7.5 Tf [(REFERENCE LINK)] TJ ET 0.271 0.267 0.267 rg BT 26.250 513.642 Td /F1 9.8 Tf [(9.)] TJ ET BT 38.132 513.642 Td /F1 9.8 Tf [(Briand S, Bertherat E, Cox P, Formenty P, Kieny MP, Myhre JK, Roth C, Shindo N, Dye C. The International Ebola )] TJ ET BT 26.250 501.738 Td /F1 9.8 Tf [(Emergency. N Engl J Med. 2014 Aug 20. PubMed PMID:25140855.)] TJ ET BT 26.250 482.333 Td /F1 9.8 Tf [(10.)] TJ ET BT 43.553 482.333 Td /F1 9.8 Tf [(French M. Ebola Center Run by Americans Closed After Disturbances. Bloomberg News Jul 29, 2014 7:05 PM ET. )] TJ ET BT 26.250 470.428 Td /F1 9.8 Tf [(Available via the Internet, last accessed August 27, 2014.)] TJ ET 0.267 0.267 0.267 rg BT 26.250 461.942 Td /F1 7.5 Tf [(REFERENCE LINK)] TJ ET 0.271 0.267 0.267 rg BT 26.250 443.392 Td /F1 9.8 Tf [(11.)] TJ ET BT 43.553 443.392 Td /F1 9.8 Tf [(Greene D, Aizenman N. Liberia Blocks Off Neighborhood In Ebola Quarantine, Sparking Riot. National Public Radio News. )] TJ ET BT 26.250 431.487 Td /F1 9.8 Tf [(August 20, 201411:30 AM ET. Available via the Internet, last accessed August 27, 2014. )] TJ ET 0.267 0.267 0.267 rg BT 26.250 423.001 Td /F1 7.5 Tf [(REFERENCE LINK)] TJ ET 0.271 0.267 0.267 rg BT 26.250 404.451 Td /F1 9.8 Tf [(12.)] TJ ET BT 43.553 404.451 Td /F1 9.8 Tf [(Frankel TC. Alarm grows as Ebola outbreak spurs more flight cancellations, border closures. Washington Post, August 25, )] TJ ET BT 26.250 392.547 Td /F1 9.8 Tf [(2014. Available via the Internet, last accessed August 27, 2014.)] TJ ET 0.267 0.267 0.267 rg BT 26.250 384.061 Td /F1 7.5 Tf [(REFERENCE LINK)] TJ ET 0.271 0.267 0.267 rg BT 26.250 365.511 Td /F1 9.8 Tf [(13.)] TJ ET BT 43.553 365.511 Td /F1 9.8 Tf [(Fisman D. Modelling an influenza pandemic: A guide for the perplexed. CMAJ. 2009 Aug 4;181\(3-4\):171-3. PubMed )] TJ ET BT 26.250 353.606 Td /F1 9.8 Tf [(PMID:19620267.)] TJ ET BT 26.250 334.201 Td /F1 9.8 Tf [(14.)] TJ ET BT 43.553 334.201 Td /F1 9.8 Tf [(Pitman R, Fisman D, Zaric GS, Postma M, Kretzschmar M, Edmunds J, Brisson M. Dynamic transmission modeling: a )] TJ ET BT 26.250 322.296 Td /F1 9.8 Tf [(report of the ISPOR-SMDM Modeling Good Research Practices Task Force--5. Value Health. 2012 Sep-Oct;15\(6\):828-34. )] TJ ET BT 26.250 310.392 Td /F1 9.8 Tf [(PubMed PMID:22999132.)] TJ ET Q q 15.000 293.011 577.500 483.989 re W n 0.271 0.267 0.267 rg BT 26.250 759.976 Td /F1 9.8 Tf [(2.)] TJ ET BT 38.132 759.976 Td /F1 9.8 Tf [(Chowell G, Hengartner NW, Castillo-Chavez C, Fenimore PW, Hyman JM. The basic reproductive number of Ebola and the )] TJ ET BT 26.250 748.071 Td /F1 9.8 Tf [(effects of public health measures: the cases of Congo and Uganda. J Theor Biol. 2004 Jul 7;229\(1\):119-26. PubMed )] TJ ET BT 26.250 736.167 Td /F1 9.8 Tf [(PMID:15178190.)] TJ ET BT 26.250 716.762 Td /F1 9.8 Tf [(3.)] TJ ET BT 38.132 716.762 Td /F1 9.8 Tf [(Eichner M, Dowell SF, Firese N. Incubation period of ebola hemorrhagic virus subtype zaire. Osong Public Health Res )] TJ ET BT 26.250 704.857 Td /F1 9.8 Tf [(Perspect. 2011 Jun;2\(1\):3-7. PubMed PMID:24159443.)] TJ ET BT 26.250 685.452 Td /F1 9.8 Tf [(4.)] TJ ET BT 38.132 685.452 Td /F1 9.8 Tf [(Legrand J, Grais RF, Boelle PY, Valleron AJ, Flahault A. Understanding the dynamics of Ebola epidemics. Epidemiol Infect. )] TJ ET BT 26.250 673.548 Td /F1 9.8 Tf [(2007 May;135\(4\):610-21. PubMed PMID:16999875.)] TJ ET BT 26.250 654.143 Td /F1 9.8 Tf [(5.)] TJ ET BT 38.132 654.143 Td /F1 9.8 Tf [(Kortepeter MG, Bausch DG, Bray M. Basic clinical and laboratory features of filoviral hemorrhagic fever. J Infect Dis. 2011 )] TJ ET BT 26.250 642.238 Td /F1 9.8 Tf [(Nov;204 Suppl 3:S810-6. PubMed PMID:21987756.)] TJ ET BT 26.250 622.833 Td /F1 9.8 Tf [(6.)] TJ ET BT 38.132 622.833 Td /F1 9.8 Tf [(Donnelly, P. Ebola outbreak sweeping West Africa started with two-year-old boy infected by a fruit bat, say researchers. )] TJ ET BT 26.250 610.929 Td /F1 9.8 Tf [(MailOnline. 10:00 EST, 24 August 2014. 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