Failure of a common disease to respond to usual therapy/prophylaxis • Unusually short median/mean incubation period for a known disease • Higher rates of person-to-person transmission than previously observed • Higher attack and case fatality rates than previously observed • Differential attack rates or clustering likely to indicate potential unusual exposures • An unusual increase in the number of people seeking health care, especially if presenting with fever, respiratory, neurological or gastrointestinal syndromes • Confirmed atypical, genetically engineered, or antiquated strain of an agent • Laboratory-confirmed case/cluster of specific bioterrorism agent (in a case/cases with no known risk factors for a natural infection).