Understanding how populations respond to selective pressures is an active area of research, of particular relevance for pathogens, which often adapt after the implementation of epidemic control strategies. Yet attempts to anticipate how and when these populations will evolve, are challenging. By looking at population diversity of rotavirus and Streptococcus pneumoniae, we have explored the impact of negative-frequency dependent selection, which tends to confer an advantage to the rare and a disadvantage to the common, in the response to intervention. Our results emphasize the resilience to control measures, and thus low vaccine effectiveness, in pathogens for which frequency-dependent selection is a key driving force.