Clinical Signs And Pathology Associated With ESC: A Review     Andrew E. Goodwin   Aquaculture/Fisheries Center, University of Arkansas at Pine Bluff, 1200 N. University Drive, Mail Slot 4912, Pine Bluff, AR 71601          Edwardsiella ictaluri, the causative agent of ESC, is able to live for extended periods in pond mud.  There is good evidence for nasal, intestinal, and respiratory routes of infection. Entry through the nasal epithelium is likely to be the route leading to severe meningitis (responsible for “hole in the head), and the neurological signs sometimes associated with this disease.  Intestinal routes involve uptake by intestinal epithelia and transfer to phagocytic cells that carry E. ictaluri to other organs.  This organism is able to survive for extended periods in macrophages and infected fish may serve as carriers and reservoirs for future outbreaks.  Edwardsiella ictaluri also establishes acute infections and septicemia that are frequently associated with high rates of mortality.  The mortality and clinical signs of the infections are dependent on water temperature, feed consumption, fish age, and fish health (stress has been shown to play a major role).  Based on gross external clinical signs, ESC occurs in several different forms from peracute to chronic: 1.Ascites and exophthalmia with no other grossly visible lesions, 2. Ascites with red fin bases, 3.         Numerous petechial hemorrhages on the jaw and ventrum – the “rash” form, 4. Large (2-5 mm) hemorrhages or ulcers randomly scattered over the fish – the “buckshot” form, 5. Reddening over the cranial foramen or necrosis of the foramenal structures exposing the brain – the “hole in the head” form, 6.          Spectacular necrosis of skin and the underlying musculature in fish from which E. ictaluri can be obtained under anaerobic conditions (E. ictaluri may not be causative).  In addition to gross external signs, granulomatous inflammation and focal congestion of the liver accompany several of the forms of ESC.  These lesions are visible grossly as “mottled liver” and microscopically as massive aggregates of epitheliod macrophages.  Other histological lesions are present, but the liver lesion is pathognomonic.  Transmission of ESC occurs through the exposure to waterborne bacteria or through the consumption of other infected fish or bacteria-laden mud.  Viable E. ictaluri have also been recovered from the intestines of fish-eating birds.