drugs

Trypanocides are essential in trypanosomosis management, but evidence regarding treatment efficacy in equids is scarce. The objective of this study was to establish the relative efficacy of three trypanocides (Diminasan® 3.5 mg/kg IM, Cymelarsan® 0.25 mg/kg IV and Samorin® 0.5 mg/kg IV) with respect to improvement of clinical parameters and parasitic burden and to evaluate adverse drug reactions. A prospective randomised clinical efficacy study was performed in ten villages in The Gambia. Owners were invited to present horses and donkeys for free examination (history, clinical examination and jugular blood sample for packed cell volume (PCV) and total serum protein). Horses and donkeys were enrolled if they fulfilled at least 2/5 inclusion criteria for trypanosomosis (anaemia (PCV<24%), poor body condition (≤1.5), limb or ventral oedema, abortion or pyrexia). Randomised trypanocide treatment was administered and the animals were observed for adverse reactions. Follow up evaluation was performed at one and two weeks to assess treatment effect. Blood samples for each animal collected at weeks 1, 2 and 3 underwent PCR analysis with validated specific primers1 for T. vivax west (TVW), T. congolense savannah (TCS) and T. brucei (TBR). 254/710 animals examined fulfilled study inclusion criteria with follow up data obtained for 243. Age, gender, species, median PCV (22%; range 8-26) and body condition score (median 1.5/5; range 0.5-2.5) were comparable between treatment groups (p>0.1). No immediate adverse reactions occurred following Cymelarsan® or Diminasan®. Immediate reactions occurred in 12/45 (27%) of donkeys treated with Samorin® ranging from neck scratching, lip smacking to tachycardia, cold extremities, sweating and hypothermia. Demeanour classifications improved following treatment with Samorin® or Diminasan® (p=0.002). PCV increased at 1 and 2 weeks post treatment for all treatment groups (p<0.001). On preliminary analysis of PCR results (n=65), animals representing four villages were positive before treatment (week 1) for TVW (55/65; 85%), TCS (44/65; 67%) and TBR (17/65; 26%) with mixed infection common (45/65; 69%). Trypanosome species profile varied between villages (p<0.05). Post treatment positives occurred in all groups for all Trypanosoma sp but with a marked decrease in prevalence (Fig 1). Positives were most common in the Cymelarsan® group, particularly for TCS (7/13; 54%). Two weeks post treatment Diminasan® (15/19; 79%) and Samorin® (19/23; 83%) had reduced parasitaemia below the threshold of detection in most cases. The data support the continuation of treatment with Diminasan® and Samorin® (with careful titration of dosing in donkeys). Further investigation to quantify parasitaemia in post treatment positives will aid differentiation between treatment failure, reduced parasitaemia, new infections and residual non-viable parasite DNA.

Acknowledgements

This work was funded by The Donkey Sanctuary.

Therapeutics are often administered to donkeys based on dosage and intervals recommended for horses because very few drugs have donkey-specific label indications. Yet differences between donkeys and horses in drug distribution, metabolism and elimination have been noted for most therapeutic agents studied. These differences can be partially explained by the donkey's unique physiology. Since their ancestors evolved in a desert environment, the modern donkey exhibits qualities that allow them to tolerate dehydration better than the horse and recover more quickly from its effects. Fluid balance and body water compartment partitioning differ from the horse and may have implications regarding drug distribution. Since donkeys are preferential browsers, differences in diet may have influenced evolutionary differences in metabolic disposition of drugs. It is important to acknowledge these differences when designing dose regimes for donkeys based on horse protocols in order to avoid either lack of efficacy or toxicity.