Examples of protocols for suspected serious infectious disease with signs and symptoms classified as high risk (e.g., skin rash or skin involvement and high fever); high fever prodrome (early symptom), as in possible smallpox (classic lesions); yellow fever (jaundice); and plague (buboes, which is a swelling of the lymph nodes) are stated as follows: when any of these other serious infectious diseases cannot be ruled out and there is uncertain diagnosis or no diagnosis, the patient is classified as high risk. Institute airborne and contact precautions, report immediately, and notify the appropriate health department. If rash is present, obtain a dermatology consult and collect specimens by specially trained personnel. Testing is done at the CDC.

Some of these diseases may be the result of possible bioterrorism and can only be diagnosed by the febrile stage and classic signs. A diagnosis of smallpox (a serious disease that kills 30% of infected people) is based on tests for variola virus and recognition of the febrile stage, classic smallpox lesions, and lesions in same stage of development.