The routes of entry for the natural spread of disease are:
- Inhalation results in the deposition of infectious or toxic particles within alveoli and provides a direct pathway to the systemic circulation. The natural process of breathing causes a continuous influx of the agent to exposed individuals.
- Ingestion of contaminated food or water
- Percutaneous inoculation via breaks in the skin, including insect bites.
- Mucous membrane penetration
- Contact with infected blood and body fluids

Person-to person spread is the simplest method of transmission.