Background: School environments are thought to play an important role in the community spread of infectious diseases such as influenza because of the high mixing rates of school children. The closure of schools has therefore been proposed as an efficient mitigation strategy. Such measures come however with high associated social and economic costs, making alternative, less disruptive interventions highly desirable. The recent availability of high-resolution contact network data from school environments provides an opportunity to design models of micro-interventions and compare the outcomes of alternative mitigation measures. Methods and results: We model mitigation measures that involve the targeted closure of school classes or grades based on readily available information such as the number of symptomatic infectious children in a class. We focus on the specific case of a primary school for which we have high-resolution data on the close-range interactions of children and teachers. We simulate the spread of an influenza-like illness in this population by using an SEIR model with asymptomatics, and compare the outcomes of different mitigation strategies. We find that targeted class closure affords strong mitigation effects: closing a class for a fixed period of time – equal to the sum of the average infectious and latent durations – whenever two infectious individuals are detected in that class decreases the attack rate by almost 70% and significantly decreases the probability of a severe outbreak. The closure of all classes of the same grade mitigates the spread almost as much as closing the whole school. Conclusions: Our model of targeted class closure strategies based on readily available information on symptomatic subjects and on limited information on mixing patterns, such as the grade structure of the school, shows that these strategies might be almost as effective as whole-school closure, at a much lower cost. This may inform public health policies for the management and mitigation of influenza-like outbreaks in the community.