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Title: Chemotherapy of African bovine trypanosomiasis : aspects of resistance of Trypanosoma congolense to Isometamidium
Author: Sones, Keith Robert
Awarding Body: University of Glasgow
Current Institution: University of Glasgow
Date of Award: 1988
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The control of African bovine trypanosomiasis is likely to depend, to a large extent, on the use of trypanocidal drugs for the foreseeable future. Within the limited armoury of drugs currently available, Isometamidium occupies a position of prominence, and is probably the most widely used trypanocide. Drug resistance is commonly considered to be the major problem associated with the use of trypanocides, and therefore a number of aspects of resistance of Trypanosoma congolense to Isometamidium were investigated in the present study. Three basic approaches to the assessment of Isometamidium sensitivity of strains of T. congolense were explored; tests conducted using mice or cattle as hosts, and tests carried out using an in vitro system. The mouse sensitivity test was shown to have limitations in the degree of correlation between mouse and cattle results, while the in vitro approach had the major disadvantage that most strains of T. congolense had to undergo a period of adaptation to in vitro culture conditions, before any in vitro assessment of sensitivity could be made. It was concluded that the method of choice was sensitivity tests performed in the definitive host, ie cattle, and it was also noted that tests to assess the duration of prophylaxis should be carried out in addition to those to test therapeutic activity. An investigation of the apparent aparasitaemic interval following subcurative treatment with Isometamidium of T. congolense infections/ infections in a mouse model suggested that trypanosomes survived in the bloodstream in low numbers, rather than in cryptic foci, such as has been described for T. b. brucei. Two aspects of resistance to Isometamidium, studied as part of this thesis, were of particular interest. First, deliberate attempts to induce changes in sensitivity by repeated subcurative treatment, failed to alter significantly the Is etamidium sensitivities of strains of T. congolense, both in mice and goats. Secondly, a relatively Isometamidium resistant strain of T. congolense was apparently unable to establish an infection in the face of an existing infection of a sensitive strain, although in the reverse situation the sensitive strain established an infection and suppressed the resistant strain. These findings may help to explain the apparent scarcity of reported incidences of Isometamidium resistance arising in the field.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available