Pitfalls of salicylhydroxamic acid plus glycerol treatment of T. vivax infected goats.

A dosage regime of SHAM (260 to 355 mg/kg) plus glycerol (890 to 1216 mg/kg), cleared T. vivax from peripheral blood of infected goats. Relapses occurred on two occasions in one goat and death during infusion of the drug in two other goats. Pharmacokinetic studies showed that both SHAM and glycerol are rapidly eliminated, the elimination possibly being slower in infected than in uninfected goats. For this reason and also because of the poor solubility of SHAM, very large volumes (500-1000 ml) had to be infused intravenously to obtain therapeutic plasma concentrations. The difficulties of adjusting the pH, the large volumes to be injected combined with the narrow margin between therapeutic and lethal dose preclude practical application of this form of treatment. Toxicity became apparent as a marked increase in heart rate and cessation of the ruminal movements which lasted for about 6 hours. A Herxheimer reaction may play an additional role in infected goats. Relapses may be due either to the fact that the levels of the drugs in the tissue were too low, or to the presence of a sub-population of T. vivax which is not susceptible to the treatment with SHAM plus glycerol.