Dose Titration of Oral and Injectable Moxidectin and Oral Morantel Tartrate in Camelids

Principal investigators:

Lisa Williamson DVM, MS and Ray Kaplan DVM, PhD

The primary purpose of this study was to identify optimal dosing regimens for moxidectin (oral and injectable preparations), and for oral morantel tartrate,in camelids. Dose titration studies were performed on 1 llama (Llama Farm C) and 3 alpaca farms (Alpaca M, P and D Farms) where natural infections with the nematode internal parasites, Haemonchuscontortus and Trichostrongyluscolubriformis, were recognized. Three morantel tartrate dose titration trials, and three moxidectin dose titration trials were completed, as planned. The owners of these 4 herds participated in a previous Morris Animal Foundation anthelmintic resistance study, and the anthelmintic resistance profile of these herds resident Haemonchuscontortus communities had been identified as moxidectin and levamisole sensitive, based on larval developmental assays. Both the morantel tartrate and moxidectin trials were performed on the Alpaca P and Llama C Farms. Moxidectin resistance was identified (based on the most recent larval developmental assay) on Alpaca M Farm, so only the morantel tartrate trial was performed. The Alpaca D Farm was used for the final moxidectin trial.

Alpacas and llamas are the primary benefactors of this research. Haemonchuscontortus is a virulent blood feeding internal parasite that causes tremendous debility and death in llamas and alpacas. Based on larval developmental assays, ivermectin and benzimidazole resistance is widespread, but many camelidH. contortus populations are still sensitive to moxidectin and levamisole. Although the larval developmental assay does not specifically test morantel tartrate, it has a similar mechanism of action to levamisole. Morantel tartrate has a much wider safety margin and is more commercially available than levamisole. This research will help producers make informed decisions on the use of morantel tartrate and moxidectin in camelids.

This research will enable owners and veterinarians to make more informed decisions on treatment of haemonchosis in camelids with moxidectin. Further, this research highlights the limitations of morantel tartrate as a sole therapeutic agent. Anthelmintic dosing protocols for camelids have been extrapolated from doses used in other species, and these doses are suspected to be sub-optimal for camelids. This research indicates that a higher dose of oral moxidectin (0.4 mg/kg) should be used for camelids than is recommended for cattle and sheep (0.2 mg/kg). Further, injectable moxidectin is less suitable for treatment of camelid haemonchosis than oral moxidectin. Since insufficient dosing with anthelmintics promotes parasite resistance, this information will contribute to efforts to decrease the rate at which anthelmintic resistance is developing in camelidH. contortus.

Studies conducted under field conditions on privately owned animals have predictable challenges, particularly owner availability and compliance. The owners that allowed us to use their animals for this study were incredibly gracious and hospitable. They were generous with their time, their medical records, and use of their herds. Further, they were flexible enough with their traditional anthelmintic protocols that we were able to conduct these dose titration trials. Weather factors were also an issue, but mainly with regards to human discomfort, ie collecting fecal samples on wet alpacas in the rain! Fortunately, there was enough precipitation in Georgia in 2010 to support parasitic life cycles.

This studys main challenge involved timing of data collection. Specifically, there needed to be a sufficient level of parasitism to do the dose titration and larval developmental tests, but this need had to be balanced with the more important need of maintaining health of the camelids in each herd. Multiple composite fecal egg counts were performed on each farm prior to starting each of the 6 trials, in order to ascertain if the parasitic load was adequate. Once composite fecal egg counts were 150 eggs per gram (EPG) or higher, the first visit was scheduled to collect individual fecal samples and weights. The 150 EPG baseline was selected based on the fact that H. contortus is a high egg shedder, and that fecal egg counts are highly correlated with the degree of anemia that the infection provokes in the host. Camelids with clinical haemonchosis generally have fecal egg counts exceeding 1,000 eggs per gram. However, composite fecal samples have limitations. They are not good indicators of individual fecal egg counts in the herd, as parasites are unevenly distributed among the animals. This disaggregate distribution of parasites generally manifests as 20 percent of the animals harboring 80% of the parasites in the herd. As a result, a composite (10 animals) fecal egg count of 150 EPG could arise from mixing feces from 1 high egg shedder with 9 very low shedders. So, it was possible that only a small portion of the herd would have qualifying fecal egg counts of 25 EPG (or greater) despite meeting the criteria set for composite fecal egg counts. This situation was encountered on several farms. For example, on one alpaca farm, only 32 out of 91 alpacas had fecal egg of 25 EPG or greater! We elected to maintain sufficient numbers of animals in each treatment group, and reduce the number of treatment groups, when this issue arose. This approach would ensure that there would be enough statistical power to make meaningful conclusions from the data.

The llamas and alpacas were individually screened with body condition scores and FAMACHA scores during the first farm visit, to make sure they were healthy enough to participate in the study. On several farms, 1 or 2 animals were excluded from the study because the researchers noted that the animals appeared to be dangerously pale and thin. These animals were immediately treated for suspected haemonchosis with an effective anthelmintic (based on previous larval developmental assay results), and were followed up with post-treatment fecal egg counts to check treatment efficacy. The owners and farm veterinarians were directly involved in the management of the unhealthy animals. On one farm, Mycoplasmahaemolama was documented as a contributing factor to the anemia in several alpacas, necessitating oxytetracycline treatments.

This project was not part of a Fellowship Training Grant. However, veterinary students and interns were engaged in the data collection and treatment phases of the study. The Southeastern Alpaca Association sponsored a summer research scholarship position for a second year veterinary student. The recipient worked over the summer break on this project.

Summary:

Three morantel tartratedose titration trials were performed on llama and alpaca farms. None of the dosages studied achieved a satisfactory fecal egg count reduction. Morantel tartrate appears to have limited benefit to treat haemonchosis in camelids.Further research to determine if a higher dose, or if consecutive day dosing of moranteltartrate would be more effective in llamas and alpacas.

Moxidectin dose titration trials were conducted on 3 alpaca and llama farms. On one alpaca farm (Alpaca P), oral moxidectin at 0.2 and 0.4 mg/kg, and injectablemoxidectin at 0.4 mg/kg failed to achieve a 95% or greater reduction in the fecal egg count. We suspect that the H. contortus community on Alpaca Farm P became resistant during the course of the study, either through whole herd treatment with moxidectin or through introduction of alpacas from a herd that the owner assimilated.

Moxidectin dose titration testing was performed on another alpaca farm, referred to as Alpaca Farm D. Oral moxidectin at 0.2 and 0.4 mg/kg resulted in fecal egg count reductions of 96%, and 98%, respectively. Both doses were efficacious based on WAAVP guidelines, but the 0.4 mg/kg dose appears to be superior.

Moxidectin dose titration was also performed on a farm referred to as Llama Farm C. Oral moxidectin at 0.2, 0.3, and 0.4 mg/kg resulted in fecal egg count reductions of 86, 88, and 100%, respectively. This trial indicated that the 0.4 mg/kg oral moxidectin dosage was the most effective dose. Moxidectin injectable preparations were also studied. Moxidectin given subcutaneously at 0.2, 0.3, and 0.4 mg/kg on Llama Farm C resulted in fecal egg count reductions of 81, 76, and 72%, all of which are well below the 95% threshold for efficacy established by WWVP. These results indicate that the injectable moxidectin products are not as efficacious as the orally administered products in camelids.