# A Review on Food Safety: The Case of _Citrobacter_ sp., Fish and Fish Products
## 4 _Citrobacter_ sp.
### Citrobacter, Fish, and Animal Health  
_Citrobacter_ species are generally known as opportunistic pathogens in human and veterinary medicine, including aquaculture activities, due to the presence of immunosuppressive factors (stress and pollution, among others) that favor the appearance of diseases [39; 42; 47]. Clinical manifestations have been reported in patients who handled Nile tilapia (_Oreochromis niloticus_), leading to necrotizing fascitis and osteomyelitisitis [39].  
Intensive fish aquaculture activities are a profitable means to produce animal protein. The main condition to achieve this task is to maintain the vital and productive functions of the fish in adequate physiological conditions. However, changes in abiotic environmental factors, such as decreased oxygen, frequent changes in water temperature and pH, increased concentration of ammonia and carbon dioxide, and high stocking density, can favor animal stress and susceptibility to bacterial infections, which represent economic losses in aquaculture around the world [39; 48].  
_Citrobacter_ sp. have been isolated from apparently healthy fish [39; 42; 49; 50]. However, its negative effects on animal health in aquaculture activities have been reported, indicating most of the time its presence, along with the _Aeromonas_, _Acinetobacter_, _Bacteroides_, _Flavobacterium_, and _Pseudomonas_ species in the intestine of fish, where the intestinal tract of fish seems to be involved in _Citrobacter_ infection, being the first to become infected when exposed to contaminated water [50].  
Regarding the animal health field, species such as _C. freundii_ are common in eutrophic freshwater, from where it is possible to spread to fish [51], also causing infections in crustaceans, amphibians, reptiles, birds, and mammals, resulting in gastrointestinal diseases [39]. In fish, _C. freundii_ has been predominantly isolated in mixed infections and, in some cases, it is pointed out as a secondary and opportunistic pathogen causing damage and high mortality [50; 52]. Among the _Citrobacter_ species reported as causing diseases in fish are _Citrobacter braakii_ and _C. freundii_[47; 50; 52], the latter being associated with diseases in fish with episodes of hemorrhagic sepitemia, severe enteritis, severe kidney disease, and gill lesions of catfish (_Pseudoplatystoma_ spp.) [39; 52]. In silver catfish (_Rhamdia quelen_), the infection presents anemia degenerative disease, protein loss, leukopenia with neutropenia, lymphocytes and leucoblastosis, liver degeneration, a decrease in the amount of renal hematopoietic tissue, and the presence of melanomacrophage centers (MMCs) in the spleen and cephalic kidney of infected fish, contributing to the high mortality of affected fish [52]. In zebrafish (_Danio rerio_), the infection is associated with an increase in fish culture's temperature [50; 52]. In tilapia (_Oreochromis massambicus_), tail necrosis, sepitemia, hemorrhage, and reddening of the body have been reported. In Nile tilapia (_O. niloticus_), high mortality is present. In rainbow trout (_Oncorhynchus mykiss_), infection can produce gastroenteritis, dark pigmentation, incoordination, bilateral exophthalmia, lack of response to external stimuli, pale spleen, petechial hemorrhage in the intestine, and mortality [39; 47; 48; 52]. In cypirinds or carp, such as _Cyprinus carpio_, infection produces hemorrhagic gastroenteritis, systemic infection [39; 48; 52], and for angelfish (_Pter ophyllum scalare_), eels (_Anguilla japonica_), ornamental fish, pacu (_Piaractus mesopotanicus_), shrimp (_Litopenaeus vannamei_), and freshwater rays (_Potamotrygon motoro_), its effects are bleeding and hepatic and splenic granulomas [52].