PMC:2854337 / 21436-31562
Annnotations
{"target":"http://pubannotation.org/docs/sourcedb/PMC/sourceid/2854337","sourcedb":"PMC","sourceid":"2854337","source_url":"https://www.ncbi.nlm.nih.gov/pmc/2854337","text":"Results\nWe carried out simulations of a novel influenza epidemic in Sapporo city to estimate the suppressive effectiveness of the following interventions against an influenza attack: TAP, STAP, school closure, restraint, and various combinations thereof. In each scenario, the initial patient, an 18-year-old high school student with symptoms, was introduced into Chuo ward of Sapporo city, which has the highest day-time population of any of the other city's wards [28].\n\nBaseline\nThe baseline scenario was the situation with no intervention. The number of patients reached a peak at about 100 days after introduction of the initial patient; thereafter, the number decreased gradually, and the epidemic was eradicated after about 7 months (Fig. 2a). The effective reproductive number (R t) for 90 days after introduction of the initial patient, which was calculated following the formula of Germann et al. [12], was estimated to be 2.0 in the beginning and 1.6 about 10 days after the introduction (Fig. 2b). Infection spread throughout Sapporo city from Chuo ward for 1 month, decreasing just after the peak of the epidemic in the Kita and Higashi wards, which have a greater residential population than the other wards in Sapporo city, 4 months following its introduction [28] (Fig. 3). The infected cases and deaths in the entire population were assessed to be, on average, 58 and 0.2%, respectively, in 100-trial simulations.\nFig. 2 Baseline scenario. a Epidemic curves for the baseline scenario in 100-trial simulations (grey lines) and in the profile of the average (black line). b Changes in the effective reproductive number (R t) over a 90-day period\nFig. 3 State of a novel influenza infection spreading among wards in Sapporo city for the baseline scenario. a–f Graphic illustration of the sequence in which the epidemic develops and spreads from 30 to 180 days after the introduction of the initial patient. Patterns of brightness show the number of patients per wards (see legend)\n\nSingle intervention\nFour intervention measures were examined: medication of antiviral drugs by TAP and STAP, school closure, and restraint.\n\nTargeted antiviral prophylaxis\nThe impact of changing the necessary tracing period and the actual coverage of tracing persons in contact with a patient for the TAP intervention were investigated (Fig. 4). The mean numbers of total patients and persons treated with antiviral drugs for prophylaxis with 95% confidence intervals (CIs) for 90 days after the introduction of the initial patient and also the numbers of cases prevented per person treated with antiviral drugs for prophylaxis are shown in Table 4. For situations with a necessary tracing period of 6 days with 30% coverage and 2 days with 70%, the mean number of total patients for 90 days would be decreased to 4.0 and 1.2%, respectively, compared with the baseline. The ripple effect of the administration of antiviral drugs in TAP on the reduction in patient numbers was estimated to be 27.6- and 37.5-fold, respectively, for these situations, indicating that the TAP intervention would have a substantial effect in suppressing the spread of the infection.\nFig. 4 Comparison of the total number of patients (a) and the number treated with antiviral drugs (b) for 90 days with a tracing coverage of 30, 50, and 70%, respectively, and a necessary tracing period of 2, 4, and 6 days, respectively, for the targeted antiviral prophylaxis (TAP) intervention. The squares show the mean value for 100-trial simulations with error bars showing the 95% confidence interval (CI). Grey, light grey, and white squares show the situations for necessary tracing periods of 2, 4, and 6 days, respectively\nTable 4 Summary of results for TAP and STAP\nIntervention Coverage (%) Necessary tracing period Total number of patients Number of treated persons Number of cases prevented/no. of treated persons\n(days) Mean (95% CI) Mean (95% CI)\nTAP 30 2 5,244 (3,738, 6,750) 5,018 (4,081, 5,955) 38.1\n4 7,299 (5,398, 9,201) 6,612 (5,643, 7,581) 28.6\n6 7,790 (5,600, 9,980) 6,824 (5,716, 7,931) 27.6\n50 2 3,093 (2,039, 4,147) 4,923 (3,897, 5,949) 39.2\n4 4,643 (3,446, 5,841) 7,258 (6,052, 8,464) 26.4\n6 7,274 (5,234, 9,314) 10,050 (8,238, 11,861) 18.8\n70 2 2,299 (1,586, 3,013) 5,167 (4,091, 6,242) 37.5\n4 3,618 (2,529, 4,707) 7,206 (5,704, 8,708) 26.7\n6 6,492 (4,376, 8,608) 10,637 (8,511, 12,763) 17.8\nSTAP 30 2 2,681 (2,215, 3,148) 17,094 (15,083, 19,106) 11.3\n4 2,723 (2,238, 3,209) 19,339 (16,717, 21,960) 10.0\n6 2,984 (2,575, 3,392) 18,925 (16,687, 21,162) 10.2\n50 2 2,473 (2,103, 2,844) 25,494 (22,067, 28,921) 7.6\n4 2,758 (2,361, 3,156) 24,451 (21,502, 27,400) 7.9\n6 2,893 (2,462, 3,324) 22,971 (20,319, 25,623) 8.4\n70 2 2,496 (2,117, 2,874) 31,638 (27,647, 35,628) 6.1\n4 2,538 (2,079, 2,996) 31,260 (27,163, 35,357) 6.2\n6 2,698 (2,245, 3,151) 27,938 (24,276, 31,601) 6.9\nCI Confidence interval\n\nSchool-age TAP\nThe impact of changes in the necessary tracing period and the actual coverage for the STAP intervention were investigated (Fig. 5). The mean numbers of total patients and persons treated with antiviral drugs for prophylaxis with 95% CIs for 90 days after the introduction of the initial patient and also the numbers of cases prevented per person treated with antiviral drugs for prophylaxis are shown in Table 4. For situations with a necessary tracing period of 2 days with 30% coverage, the mean number of total patients for 90 days would be decreased to 1.4% compared with the baseline. However, there were no significant differences in the number of patients for a necessary tracing period of 2, 4, and 6 days, respectively or for a coverage of 30, 50, and 70%, respectively. The ripple effect of the administration of antiviral drugs in STAP on the reduction of patient numbers was estimated to be 10.2- and 6.1-fold for a necessary tracing period of 6 days with 30% coverage and 2 days with 70%, respectively, which indicates that STAP intervention would have a weaker ripple effect than TAP.\nFig. 5 Comparison of the total number of patients (a) and the number treated with antiviral drugs (b) for 90 days with a tracing coverage of 30, 50, and 70%, respectively, and a necessary tracing period of 2, 4, and 6 days, respectively, for the STAP intervention. The squares show the mean value for 100-trial simulations with error bars showing the 95% CI. Grey, light grey, and white squares show the situations for necessary tracing periods of 2, 4, and 6 days, respectively\n\nSchool closure\nThe impact of school closure is shown in Fig. 6. School closure would, on average, delay the peak of infection for an average of 45 days compared to the baseline and decrease total and peak patients to 86 and 52% of the baseline scenario (Table 5).\nFig. 6 Comparison of epidemic curves for no intervention (baseline) (grey line) and school closure (black line)\nTable 5 Summary of results for school closure and restraint\nIntervention Total number of patients Total number of deaths\nMean (95% CI) Mean (95% CI)\nBaseline 1,087,165 (1,024,014, 1,150,316) 4,355 (4,102, 4,608)\nSchool closure 934,717 (876,811, 992,622) 3,772 (3,538, 4,006)\nRestraint (10%) 994,220 (936,468, 1,051,972) 3,985 (3,753, 4,217)\nRestraint (30%) 786,105 (737,405, 834,806) 3,159 (2,963, 3,355)\nRestraint (50%) 547,762 (506,031, 589,493) 2,191 (2,024, 2,358)\n\nRestraint\nThe impact of changes in the execution rate for restraint is shown in Fig. 7. With mean proportions of 10, 30, and 50% of total patients restraining their behavior, on average, the number of cases would decrease to 91, 72, and 50% of the baseline, and the peak would be delayed for 11, 43, and 96 days, respectively, compared with the baseline scenario (Table 5). At the same time, the epidemic period would be prolonged with respect to the baseline, which was similar to school closure.\nFig. 7 Comparison of epidemic curves between no intervention (baseline) (grey line) and restraint (black line). Solid, dashed, and dotted black lines show the situations at baseline and when restraint is practiced at execution rates of 10, 30, and 50%, respectively\n\nCombined intervention\nThe mean number of total patients, deaths, and persons treated with antiviral drugs with 95% CIs and the epidemic periods in scenarios 1–5 (Table 3) are shown in Table 6. In scenarios 1–3, which encompass the combination of the administration of antiviral drugs (TAP/STAP) with only school closure or restraint, the mean number of total patients would be decreased to 0.18, 0.15, and 0.23%, respectively, of the baseline scenario. Epidemic periods for scenarios 1–3 were assessed as 220, 193, and 226 days, on average, which indicates that these combined interventions would be effective in reducing the number of patients but not for shortening the epidemic period (Table 6). On the other hand, scenarios 4 and 5, which are two different combinations of three interventions [administration of antiviral drugs (TAP/STAP), school closure, and restraint] would have a greater effect on the suppression of infection in terms of the number of total patients, deaths, and persons treated with antiviral drugs and on shortening the epidemic period. In particular, the combination of TAP, school closure, and restraint in scenario 4 (Fig. 8) would decrease the total number of patients to 0.02% of that of the baseline scenario and shorten the epidemic period to 72 days (Table 6).\nTable 6 Summary of results for combined scenarios\nScenarios Total number of patients Total number of deaths Number of treated persons Epidemic period (days)\nBaseline 1,087,165 (1,024,014, 1,150,316) 4,354.89 (4,102, 4,608) 0 202.03\n1 1,987 (1,549, 2,425) 7.84 (5.98, 9.70) 2,471 (2,089, 2,854) 220.08\n2 1,657 (1,230, 2,084) 6.72 (4.95, 8.49) 2,044 (1,670, 2,418) 193.17\n3 2,453 (1,850, 3,055) 10.11 (7.54, 12.68) 2,943 (2,419, 3,467) 226.06\n4 171 (145, 196) 0.76 (0.53, 0.99) 132 (111, 152) 71.60\n5 191 (163, 219) 0.83 (0.57, 1.09) 148 (126, 171) 82.30\nValues in table are given as the mean, with the 95% CI in parenthesis\nFig. 8 Epidemic curves for scenario 4 in 100-trial simulations (grey lines) and in the profile of the average (black 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