Summary
The rationale behind the methodology employed to investigate a new disease that appears in an area hitherto unaffected is fundamentally different from that applied in an endemic disease situation. Special consideration must also be given to disease agents that appear and reappear at cyclical intervals. The authors present three separate approaches applicable in three different epidemiological situations. Each one may be used initially to determine the identity of the causal agent and the nature of the disease. These approaches, although described in a stepwise (flowchart) manner, are not meant to be applied rigidly, but rather should serve as a guideline for investigators. Special consideration is given to situations in which disease appears intermittently, using a sentinel model. Although this latter approach is expensive and time-consuming, it can yield excellent and reliable results when applied correctly.

Keywords
Akabane virus, Arbovirus, Arthrogryposis, Diagnosis, Hydranencephaly, Israel, Nested polymerase chain reaction, Sentinel mode, Real-time polymerase chain reaction.