Cryptobia salmosifica is a haemoflagellate of salmon (Oncorhynchus spp.). Although it is a pathogen there is currently no drug effective against the parasite. The main objective of this thesis was to develop a chemotherapeutic strategy against this pathogen ( C. salmosifica).; A series of compounds, classified as triphenylmethanes, thiazines, xanthenes, benzidines, phenanthridiniums, napthalamines, and diamidines, were screened for in vitro toxicity against C. salmositica. The triphenylmethanes and the phenanthridiniums were toxic at low concentrations; two compounds (crystal violet and isometamidium) were examined further for therapeutic and prophylactic activity against the parasite in Oncorhynchus mykiss and Oncorhynchus tshawytscha.; In vitro exposure of C. salmosifica to crystal violet and isometamidium reduced its infectivity and caused a rapid decantenation of kinetoplast DNA. Despite significant in vitro effects, crystal violet had no in vivo effects.; An enzyme-linked immunosorbent assay was developed to monitor isometamidium in fish plasma. The drug levels peaked at two weeks after intramuscular injection; this was supported by the in vivo results which showed a significant reduction in parasitaemia at the same time.; In vitro exposure of C. salmosifica to isometamidium reduced its oxygen consumption. The parasite switched to glycolysis on exposure to the drug and this was possible because the glycolytic enzymes were compartmentalized in the glycosome.; An intramuscular injection of 1.0 mg/kg of isometamidium eliminated or reduced the infection in rainbow trout, except during acute disease; treatment at acute disease resulted in higher parasitaemias. Isometamidium did not interfere with antibody production or function, nor complement production, nor ions required to initiate and regulate activation of complement. Cryptobia salmositica maintained in isometamidium supplemented medium were not lysed by complement-fixing antibodies nor agglutinated by immune plasma. In infected chinook salmon, isometamidium was both therapeutic and prophylactic. In untreated fish there was 100% mortality.; The drug was conjugated to polyclonal and monoclonal anti-C. salmositica antibodies. Polyclonal conjugates lysed the parasite under in vitro conditions, neutralized its infectivity, and were more effective than free-isometamidium or cotreatment with unconjugated antibodies and drug. Administered polyclonal antibody-drug conjugates lowered parasitaemias in chinook salmon.
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