The present invention provides methods and compositions designed for the treatment, management, and/or amelioration of an infection, in particular an intracellular pathogen infection, such as a viral, bacterial, protozoa or fungal infection. In particular, the present invention provides methods for treating, managing, preventing and/or ameliorating an infection where the expression of EphA2 is upregulated in infected cells (e.g., infected epithelial cells), said methods comprising administering to a subject an effective amount of one or more EphA2/EphrinA1 Modulators. In accordance with the present invention, such methods may also comprise the administration of one or more therapies other than an EphA2/EphrinA1 Modulator. The present invention also provides pharmaceutical compositions comprising EphA2/EphrinA1 Modulators, and optionally, one or more prophylactic or therapeutic agents other than an EphA2/EphrinA1 Modulator, and the use of such compositions in the treating, management, prevention and/or amelioration of an infection. Further provided by the invention are articles of manufacture and kits comprising an EphA2/EphrinA1 Modulator of the invention, and, optionally, other prophylactic or therapeutic agents (e.g., immunomodulatory agents, anti-viral agents, anti-inflammatory agents, anti-bacterial agents, anti-fungal agents, etc.).