Enteromyxum leei is a species of myxozoan, histozoic parasite that infects the intestinal tract and sometimes associated organs, like gall bladder and liver, of several teleostean fish species. Myxozoans are microscopic metazoans, with an obligate parasitic life-style. The parasite stages of this species live in the paracellular space between fish enterocytes. It is the causative agent of enteromyxosis, or emaciative disease, also known as "razor blade syndrome" in sparid fish. E. leei has a wide host and geographical range within marine fish (at least 60 species from 22 different families, mainly Perciforms), and even freshwater fish have been infected experimentally. E. leei initially emerged in the Mediterranean in the late 1980s and it is believed to have been unintentionally introduced into the Red Sea.Diamant, A. (1992) A new pathogenic histozoic Myxidium (Myxosporea) in cultured gilt-head sea bream Sparus aurataL. Bulletin of the European Association of Fish Pathology 12, 64-66.Diamant, A. (1997). Fish-to-fish transmission of a marine myxosporean. Diseases of Aquatic Organisms 30, 99-105. Its pathogenicity and economic impact depend on the host species. In the gilt-head seabream, it is manifested as a chronic disease that provokes anorexia, delayed growth with weight loss, cachexia, reduced marketability and increased mortality. In other species, it has no clinical signs. In sharpsnout seabream, infection results in very high mortality rates, which have pushed fish farmers to abandon the culture of this fish species.
Taxonomy Enteromyxum leei was formerly described as Myxidium leei,Diamant, A., Lom, J., Dyková, I. (1994) Myxidium leei n. sp., a pathogenic myxosporean of cultured sea bream Sparus aurata. Diseases of Aquatic Organisms, 20, 137-141. and initially reported in cultured gilthead sea bream (GSB) (Sparus aurata) from southern Cyprus. The morphology of the myxospores of this parasite differ slightly from others of the family Myxiidae: the polar capsules are located terminally and are elongated rather than subspherical (as in Myxidium), but they open to one side and their foramina are not located in the sutural plane (as in Zschokkella); the sutural line does not bisect the spore but is quite wavy, and does not reach the spore extremities (as in many Zschokkella). Subsequently, a new combination was formed when the genus Enteromyxum was erected based on molecular biology data as well as morphology.Palenzuela, O., Redondo M.J., Alvarez-Pellitero, P. (2002). Description of Enteromyxum scophthalmi gen. nov., sp. nov. (Myxozoa), an intestinal parasite of turbot (Scophthalmus maximus L.) using morphological and ribosomal RNA sequence data. Parasitology 124, 369-79. Today, the genus consists of only three intestinal species from marine fish hosts: E. leei, E. scopththalmi and E. fugu.
Life cycle The life cycle of myxosporeans generally involves two alternating hosts: fish and annelids. Myxospores are ingested by annelids, in which actinospores are produced. The actinospores released from the annelid to the water reach a fish, penetrate and the developmental stages migrate until they reach the final site of infection and develop into myxospores. In contrast to this complex life cycle, spontaneous, direct fish-to-fish transmission has been demonstrated for E. leei and other species belonging to the genus Enteromyxum in various marine fish.Sitjà-Bobadilla, A., Palenzuela, O. (2012). Enteromyxum species. in: Woo, P.T.K, Buchmann K. (eds.), Parasites: Pathobiology and Protection. CAB Int., Oxfordshire, pp 163-176. Horizontal transmission also occurs via effluent, cohabitation, oral and anal routes.Diamant, A., Wajsbrot, N. (1997) Experimental transmission of Myxidium leei in gilthead sea bream Sparus aurata. Bulletin of the European Association of Fish Pathologists, 17, 99-103.Diamant, A. (1998). Red drum Sciaenops ocellatus (Sciaenidae), a recent introduction to Mediterranean mariculture, is susceptible to Myxidium leei (Myxosporea). Aquaculture 162, 33-39.Yasuda, H., Ooyama, T., Iwata, K. et al. (2002). Fish-to-fish transmission of Myxidium spp. (Myxozoa) in cultured tiger puffer suffering from emaciation disease. Fish Pathology 37, 29-33.Yasuda, H., Ooyama, T., Nakamura, A. et al. (2005). Occurrence of the myxosporean emaciation disease caused byEnteromyxum leei in cultured Japanese flounder Paralichthys olivaceus. Fish Pathology 40, 175-180.Golomazou, E., Athanassopoulou, F., Karagouni, E., et al. (2006) Experimental transmission of Enteromyxum leeiDiamant, Lom and Dyková, 1994 in sharpsnout sea bream, Diplodus puntazzo C. and the effect on some innate immune parameters. Aquaculture 260, 44-53.Sitjà-Bobadilla, A., Diamant, A., Palenzuela, O., et al. (2007). Effect of host factors and experimental conditions on the horizontal transmission of Enteromyxum leei (Myxozoa) to gilthead sea bream, Sparus aurata L., and European sea bass, Dicentrarchus labrax (L.). Journal of Fish Diseases 30, 243-250.Alvarez-Pellitero, P., Palenzuela, O., Sitjà-Bobadilla, A. (2008). Histopathology and cellular response in Enteromyxum leei (Myxozoa) infections of Diplodus puntazzo (Teleostei). Parasitology International 57, 110-120. All these trials depend on a source of infected fish, since continuous in vitro culture of this parasite, as with any other Myxozoa, has not been achieved.
Although it is possible that this myxosporean parasite also has an indirect life cycle involving an invertebrate host in the wild, such putative intermediate has never been found. Rangel et al.Rangel, L.F., Cech, G., Szekely, C. et al. (2011). A new actinospore type Unicapsulactinomyxon (Myxozoa), infecting the marine polychaete, Diopatra neapolitana (Polychaeta: Onuphidae) in the Aveiro Estuary (Portugal). Parasitology 138, 698-712. found an actinospore infecting the marine polychaete Diopatra neapolitana in the Aveiro Estuary (Portugal) with an 81% similarity with E. leei, but no gilthead sea bream has been found with E. leei in Portuguese waters thus far.
Pathology and clinical signs Common field observations include loss of appetite, poor food conversion rates and difficulties to reach commercial size. Clinical signs of enteromyxosis usually consist of severe emaciation with epaxial muscle atrophy. This emaciation can be noticed externally as a knife or razor-like aspect. The emaciation is best noticed in subchronic infections at mild temperatures, with dead fish usually appearing wasted (caquexic). Emaciation can be imperceptible in very susceptible species and/or at high temperatures (e.g. D. puntazzo infections with E. leei), because fish die before reaching a caquexic condition. At dissection, macroscopical signs include intestinal focal congestion and haemorrhages, and it can appear fragile and semi-transparent, often filled with mucous liquid with reduced perivisceral fat deposits, pale internal organs and occasionally green liver. Enlarged or abnormally coloured gall bladders are common in some hosts (e.g. D. puntazzo).
The histopathology shows the presence of myxozoan stages located between the enterocytes, or free in the lumen with debris in severe infections. Ribbons of epithelium containing parasite stages are detached. In advanced GSB infections with E. leei, the intestine displays hypertrophy of the lamina propria-submucosa and loss of the epithelial palisade structure, together with an intense local inflammatory response.Cuadrado, M., Marques, A., Diamant, A., Sitjà-Bobadilla, A., Palenzuela, O., Álvarez-Pellitero, P., Padrós, F., Crespo, S. (2008) Ultrastructure of Enteromyxum leei (Diamant, Lom, & Dykova, 1994) (Myxozoa), an enteric parasite infecting gilthead sea bream (Sparus aurata) and sharpsnout sea bream (Diplodus puntazzo). Journal of Eukaryotic Microbiology 55, 178-184.Fleurance, R., Sauvegrain, C., Marques, A., et al. (2008). Histopathological changes caused by Enteromyxum leeiinfection in farmed sea bream Sparus aurata. Diseases of Aquatic Organisms 79, 219-228. These intestinal changes heavily impair nutrient absorption. The inflammatory response varies depending on the host. In general, more susceptible species present more marked inflammatory response and detachment of epithelium occurs earlier in the infection.
Impact The impact of enteromyxosis depends on the fish species, water temperature and the type of facilities involved in the aquaculture settings. This parasite has provoked the abandonment of the culture of sharpsnout sea bream (the most susceptible host) in some locations in Italy and Greece.Fioravanti, M. L. (2005). Stato dell’arte sulle principally patologie parassitarie nella maricoltura nazionale. XII Convegno Nazionale Societa Italiana Patologia Ittica, Cesenatico, Italy, p. 35.Rigos, G., Katharios, P. (2010). Pathological obstacles of newly-introduced fish species in Mediterranean mariculture: a review. Reviews in Fish Biology and Fisheries 20, 47-70. E. leei constitutes a threat for many other cultured sparids, such as sharpsnout sea bream, Diplodus puntazzo;Athanassopoulou, F., Rodger, T., Prapas, H. (1999) Diseases of Puntazzo puntazzo Cuvier in marine aquaculture systems in Greece. Journal of Fish Diseases 22, 215-218. black spot sea bream, Pagellus bogaraveo,Mladineo, I. (2003). Myxosporidean infections in Adriatic cage-reared fish. Bulletin of the European Association of Fish Pathologists 23, 113-122. common sea bream, Pagrus pagrus,Diamant, A. (1995). Myxidium leei (Myxosporea) infections in sharpsnout sea bream Diplodus puntazzo (Cetti) and common sea bream Pagrus pagrus (L.) (Sparidae), 4th International Symposium of Fish Parasitology, Munich. Book of Abstracts, 8. and red sea bream, Pagrus major.Le Breton, A., Marques, A. (1995). Occurrence of an histozoic Myxidium infection in 2 marine cultured species:Puntazzo puntazzo C. and Pagrus major. Bulletin of the European Association of Fish Pathologists 15, 210–212. However, the economic impact on a global scale is unknown.
Water temperature is a critical risk factor in the transmission and onset of enteromyxosis. A clear relationship between infection and water temperature has been demonstrated.Yanagida, T., Sameshima, M., Nasu, H. et al. (2006). Temperature effects on the development of Enteromyxum spp. (Myxozoa) in experimentally infected tiger puffer, Takifugu rubripes (Temminck & Schlegel). Journal of Fish Diseases 29, 561–567.Estensoro, I., Redondo, M.J., Álvarez-Pellitero, P. et al. (2010). Novel horizontal transmission route for Enteromyxum leei (Myxozoa) by anal intubation of gilthead sea bream Sparus aurata. Diseases of Aquatic Organisms 92, 51-58.Picard-Sánchez, A., Estensoro, I., Del Pozo, R., Palenzuela, O., Piazzon, M.C., Sitjà-Bobadilla, A. (2020). Water temperature, time of exposure and population density are key parameters in Enteromyxum leei fish-to-fish experimental transmission. Journal of Fish Diseases (in press). The onset of the disease is largely delayed or even suppressed at low temperatures (below 15 °C). However, the infection can remain latent during the cooler period within the fish and re-emerge when water temperature increases. This has important epizootiological consequences, since false negatives (during winter) are a source of the parasite when water temperatures rise.