<div><p>Background</p><p>Influenza A (H1N1) outbreaks have become common at schools in China since 2009. However, the effects of common countermeasures for school influenza outbreak have not been quantified so far, including isolation, vaccination, antivirus and school closure. We conducted a mathematically modeling study to address this unsolved issue.</p><p>Methods</p><p>We collected data of all small-scale school outbreaks caused by influenza A that occurred in Changsha city between January 2009 and December 2013. Two outbreaks (one was in 2009 and the other one was in 2013) were used for simulating the effects of single and combined use of common measures, including isolation (Iso), therapeutics (T), prophylactics (P), vaccinating 70% of susceptible individuals prior to the outbreak (V<sub>P70</sub>), vaccinating 70% of susceptible individuals every day during the outbreak (V<sub>D70</sub>) and school closure of one week (S1w). A susceptible—exposed—infectious/asymptomatic—recovered (SEIR) model was developed to implement the simulations based on the natural history of influenza A.</p><p>Results</p><p>When no control measures are taken, the influenza is expected to spread quickly at school for the selected outbreak in 2013; the outbreak would last 56 days, and the total attack rate (TAR) would reach up to 46.32% (95% CI: 46.12–46.52). Of all single control measures, V<sub>P70</sub> is most effective to control the epidemic (TAR = 8.68%), followed by V<sub>P50</sub>, V<sub>D70</sub>, V<sub>D50</sub> and Iso. The use of V<sub>P70</sub> with any other measure can reduce TAR to 3.37–14.04% and showed better effects than any other combination of two kinds of measures. The best two-measure combination is ‘S1w+V<sub>P70</sub>’ (TAR = 3.37%, DO = 41 days). All combinations of three kinds of measures were not satisfactory when V<sub>p70</sub> and V<sub>D70</sub> were excluded. The most effective three-intervention combination was ‘Iso+S1w+V<sub>P70</sub>’ (with TAR = 3.23%). When V<sub>P70</sub> or V<sub>D70</sub> is included, the combinations of four or five kinds of interventions are very effective, reducing TAR to lower than 5%. But the TAR of combination of ‘T+P+Iso+S1w’ is 23.20%. Similar simulation results were observed for the selected outbreak in 2009.</p><p>Conclusion</p><p>Vaccinating no less than 70% of individuals prior to the outbreak and isolation are recommended as single measures to control H1N1outbreak at school. The combination of V<sub>P70</sub>+S1w can achieve very good control for school outbreak.</p></div