Factors influencing the duration of isometamidium prophylaxis against bovine trypanosomiasis

Peregrine, Andrew Seaton (1987) Factors influencing the duration of isometamidium prophylaxis against bovine trypanosomiasis. PhD thesis, University of Glasgow.

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Experiments have been conducted with Boran (Bos indicus) cattle to determine the factors that influence the duration of isometamidium (Samorin) prophylaxis against experimental challenge with metacyclic forms of Trypanosoma conoglense and Trypanosoma vivax. The duration of a single isometamidium prophylactic treatment against T. congolense ILNat 3.1 and T. congolense IL 2642 was examined in 24 Boran steers with regard to (i) the dose of drug, (ii) the level of metacyclic challenge, and (iii) the influence of infection at the time of treatment with an unrelated serodeme. The cattle were repeatedly challenged at monthly intervals between 2 and 7 months following treatment, either by 5 infected Glossina morsitans central is or by intradermal inoculation of 5x10e3 or 5x10e5 in vitro-derived metacyclic trypanosomes. A dose of 1 mg kg-1 body weight afforded complete protection for 4 months and 0.5mg kg-1 for 3 months against the two T. conoolense serodemes examined, irrespective of the method or weight of challenge. In another group of cattle, which had an established infection at the time of treatment, the duration of chemoprophylaxis against an unrelated serodeme was the same as the other groups which had no previous experience of trypanosome infection. Antibodies to metacyclics did not appear in any of the cattle as long as the chemoprophylaxis was effective. An exception to this was the group challenged with 5x10 5 in vitro-derived metacyclic parasites, in which low antibody titres were detected. In all cases these proved to be non-protective. It was therefore concluded that under the experimental conditions employed, (i) there was a direct relationship betwen drug dosage and the duration of chemoprophylaxis, (ii) the weight of metacyclic challenge did not affect the duration of chemoprophylaxis, and (iii) when used to treat an existing infection, isometamidium exerted the same degree of chemoprophylactic activity. In experiments with T. vivax, twenty Boran steers were infected with T. vivax transmitted by G. m. central is; five with a T. vivax clone from Zaria, Nigeria (IL 2968), five with a T. vivax clone from Kilifi, Kenya (IL 2969), five with a T. vivax population from Galana, Kenya (IL 2982) and five with a T. vivax population from Likoni, Kenya (IL 2986). Eleven days after infection all 20 animals were treated with 0.5mg kg-1 isometamidium chloride. All steers except one infected with the Zaria T. vivax were completely cured. When twenty different Boran steers were administered a single prophylactic dose of 0.5mg kg-1 isometamidium chloride and subjected to monthly tsetse-transmitted challenge with the same T. vivax populations, complete protection was afforded for two months against challenge with the Zaria T. vivax. for one month against the Likoni T. vivax and for less than one month against the Kilifi and Galana T. vivax. The findings indicated that the level of sensitivity of a T. vivax population to the prophylactic activity of isometamidium cannot be concluded from sensitivity studies based on the therapeutic action of the drug. In a similar manner to studies with T. conqolense, acquisition of immunity to homologous T. vivax challenge did not appear to occur whilst animals were protected by isometamidium and did not contribute to the apparent prophylactic period. Using a T. congolense in vitro culture system, a qualitative technique was developed to detect trypanocidal activity in sera from drug-administered cattle: Trypanocidal activity, as detected by inhibition of infectivity and in vitro growth of T. congolense ILNat 3.1, was detected in sera, collected from cattle as long as 5 months after administration of lmg kg-1 isometamidium chloride; activity that correlated with susceptibility of cattle to challenge with T. conqolense ILNat 3.1. The same technique was used to confirm the high level of resistance expressed by the Kilifi T. vivax to the prophylactic activity of isometamidium. Trypanocidal activity, against T. conqolense ILNat 3.1, was detected in serum taken from cattle 1 and 2 months after administration of 0.5mg kg-1 isometamidium chloride, at a time when the cattle were susceptible to challenge with the Kilifi T. vivax. Similar studies were conducted with a T. vivax in vitro culture system: Freshly isolated bloodstream forms of T. vivax IL 2968 (Zaria) expressed a similar level of sensitivity as T. conqolense ILNat 3.1 bloodstream forms to trypanocidal activity in sera from drug-treated cattle. Freshly isolated murine bloodstream forms were found to be better suited to the detection of trypanocidal activity in sera from drug-treated cattle than freshly isolated bovine bloodstream forms. It was concluded from in vitro tests using T. conqolense ILNat 3.1 and T. vivax IL 2968 that there was in general a positive correlation between the expression of trypanocidal activity of serum in vitro and the susceptibility of cattle to challenge with the same trypanosome populations. However, the reliability of the in vitro test was diminished by the observation that sera from untreated cattle occasionally possessed trypanocidal activity. The reason for this latter observation is, at present, unknown.

Item Type: Thesis (PhD)
Qualification Level: Doctoral
Keywords: Veterinary science, Animal sciences, Animal diseases, Parasitology
Date of Award: 1987
Depositing User: Enlighten Team
Unique ID: glathesis:1987-76662
Copyright: Copyright of this thesis is held by the author.
Date Deposited: 19 Nov 2019 13:57
Last Modified: 19 Nov 2019 13:57
URI: https://theses.gla.ac.uk/id/eprint/76662

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