Investigation on gallium maltolate pharmacokinetics and efficacy, as antimicrobial alternative in an equine proliferative enteropathy infection model.
Lawsonia intracellularis causes proliferative enteropathies in juvenile mammals. The porcine (PPE) and equine (EPE) diseases are worldwide. Rabbits and hamsters are naturally susceptible, the latter being a classic modeling-host for PPE. None is known for EPE, besides foals. An in vitro evaluation of antimicrobial efficacy against L. intracellularis is difficult. This study aimed to validate a laboratory animal EPE model and to investigate pharmacokinetics (PK) and efficacy of gallium maltolate (GaM) as an alternative antimicrobial therapy. Infected animals were inoculated with cell-cultured L. intracellularis and infection was verified with clinically utilized diagnostic tests. Initially, 2 groups of EPE-infected rabbits were compared to 1 uninfected group. After inoculation (PI), EPE-infected rabbits showed mild clinical signs; detectable seroconversion, fecal shedding, gross lesions in intestinal tissues (IT), and early immuno-histochemistry labeling of L. intracellularis antigen. Thus, a humane EPE-rabbit model was achieved. Subsequently, EPE-infected hamsters were compared to uninfected and PPE-infected hamsters; whereas, PPE-infected rabbits were compared to EPE-infected rabbits. EPE-hamsters did not develop infection, unlike PPE-infected controls; and PPE-rabbits did not develop IT lesions or seroconversion comparable to EPE-rabbits. Therefore rabbits were chosen as the EPE modeling-host for the GaM studies. First, GaM PK and IT concentrations of Ga and Fe were measured. Then, GaM efficacy was compared to a current EPE antimicrobial treatment. During sampling, the intra-arterial catheters in the rabbits’ ears were protected with a novel moleskin-cover, allowing repeated sampling while minimally restrained. The PK study was based on the comparison of EPE-infected and uninfected rabbits, after a single treatment with GaM, collection of serial blood samples and IT samples. The only differing PK parameter, between groups, was a decrease in the terminal phase rate constant of the EPE-rabbits, so a 48h dosing interval was chosen for the efficacy study. In the efficacy study, 3 groups of EPE-infected rabbits were treated with GaM, doxycycline and a placebo, respectively. No differences were noted between treatments, in terms of lesions and fecal shedding. GaM appears no more efficacious than doxycycline in EPE- rabbits. In conclusion, albeit GaM tolerance appeared adequate in rabbits, results do not support its use in EPE-infected animals.
DegreeDoctor of Philosophy (Ph.D.)
DepartmentVeterinary Biomedical Sciences
ProgramVeterinary Biomedical Sciences
SupervisorHamilton, Don L.; Thompson, Julie -.
CommitteeAlcorn, Jane; Clark, Chris R.; Dowling, Patricia M.
Copyright DateApril 2013
equine proliferative enteropathy