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  Discussion on Research Summary: Post Deworming Inflammation
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Moderator:
DrO

Posted on Sunday, Oct 4, 2015 - 11:46 am:

The surprise here is not that the moxidectin had a small and perhaps clinically insignificant reaction but that the fenbendazole (5 day treatment) did not induce this reaction. We have always assumed that killing of the strongyle larvae within the tissues would cause a mild inflammatory response. Maybe the slower kill rate or is this an effect of the dewormer itself? I hope to get hold of this paper and get a better idea.
DrO

Vet Immunol Immunopathol. 2015 Sep 25.
Local and systemic inflammatory and immunologic reactions to cyathostomin larvicidal therapy in horses.
Nielsen MK1, Loynachan AT2, Jacobsen S3, Stewart JC4, Reinemeyer CR5, Horohov DW4.

Abstract
Encysted cyathostomin larvae are ubiquitous in grazing horses. Arrested development occurs in this population and can lead to an accumulation of encysted larvae. Large numbers of tissue larvae place the horse at risk for developing larval cyathostominosis. This disease complex is caused by mass emergence of these larvae and is characterized by a generalized acute typhlocolitis and manifests itself as a profuse protein-losing watery diarrhea with a reported case-fatality rate of about 50%. Two anthelmintic formulations have a label claim for larvicidal therapy of these encysted stages; moxidectin and a five-day regimen of fenbendazole. There is limited knowledge about inflammatory and immunologic reactions to larvicidal therapy. This study was designed to evaluate blood acute phase reactants as well as gene expression of pro-inflammatory cytokines, both locally in the large intestinal walls and systemically. Further, mucosal tissue samples were evaluated histopathologically as well as analyzed for gene expression of pro- and anti-inflammatory cytokines, cluster of differentiation (CD) cell surface proteins, and select transcription factors. Eighteen juvenile horses with naturally acquired cyathostomin infections were randomly assigned to three treatment groups; one group served as untreated controls (Group 1), one received a five-day regimen of fenbendazole (10mg/kg) (Group 2), and one group received moxidectin (0.4mg/kg) (Group 3). Horses were treated on day 0 and euthanatized on days 18-20. Serum and whole blood samples were collected on days 0, 5, and 18. All horses underwent necropsy with collection of tissue samples from the ventral colon and cecum. Acute phase reactants measured included serum amyloid A, iron and fibrinogen, and the cytokines evaluated included interferon γ, tumor necrosis factor α, transforming growth factor (TGF)-β, and interleukins 1β, 4, 5, 6, and 10. Transcription factors evaluated were FoxP3, GATA3 and tBet, and CD markers included CD163, CD3z, CD4, CD40, and CD8b. Histopathology revealed an inflammatory reaction with higher levels of lymphocytes, T cells, B cells, eosinophils and fibrous tissue in the moxidectin-treated group compared to controls or horses treated with fenbendazole. No apparent systemic reactions were observed. Expression of IL-5 and TGF-β in intestinal tissues was significantly lower in Group 3 compared to Group 1. This study revealed a subtle inflammatory reaction to moxidectin, which is unlikely to cause clinical issues.
Member:
rtrotter

Posted on Sunday, Oct 4, 2015 - 1:10 pm:

Dr.O,

On another discussion group we discussed the efficiency of both types of wormer. Research showed that the Moxidectin was proven to be the better choice for the removal of encysted strongyles the results of the deworming lasted longer than the 5 day Panacur powerpack. With the additional results from this current study. It would seem the 1 day moxidectin treatment in a single dose, would be the better choice.
Moderator:
DrO

Posted on Sunday, Oct 4, 2015 - 5:39 pm:

Hello rtrotter,
The problem with your point is that it does not take into account preexisting local resistance factors and future development of resistance patterns. For nearly a decade there have been decreasing prepatent periods from administration of moxidectin in areas where it is used widely. Fenbendazole has been used widely and frequently for decades and in many places there is a high level of resistance. The "power pack" dosing helps to overcome this but it would not be surprising if there is such resistance in some areas. Predeworming checks and then 30 day post deworming fecal checks in our area suggest it is effective here but I have not used benzimadazoles since the 80's until 5 years ago. It is best to use a post deworming fecal checks to determine which treatments are effective and which ones are not on your farm and then base deworming decisions on the results and remember, if you just use the one that works best, it will not be too long that it will not work well at all. The article associated with this discussion has a detailed discussion on this.
DrO
PS I have found a research summary that has the exact opposite conclusion from the one I published above:
Vet Parasitol. 2006 Jun 30;139(1-3):115-31. Epub 2006 May 3.

Small strongyle infection: consequences of larvicidal treatment of horses with fenbendazole and moxidectin.

Steinbach T1, Bauer C, Sasse H, Baumgärtner W, Rey-Moreno C, Hermosilla C, Damriyasa IM, Zahner H.
Abstract

The study was undertaken to evaluate adverse effects of larvicidal treatment in horses naturally infected with cyathostomins. Out of 24 ponies kept on pasture, four animals were housed in September and anthelmintically cured to serve as worm-free controls (group C-0). The others were housed in December. Eight animals each were treated 8 weeks later with 5 x 7.5mg/kg fenbendazole (FBZ) or 1 x 0.4 mg/kg moxidectin (MOX). Four animals remained untreated (group C-i). Two, 4, 6 and 14 days after the end of treatment two animals of each of the treated groups were necropsied together with group C-0 and C-i animals. Infected animals before treatment showed weight loss, eosinophilia, increased plasma protein and globulin contents. Treatment was followed by weight gain and temporal plasma protein and globulin increase. Proportions of CD4+ and CD8+ T lymphocytes in the peripheral blood did not differ between the groups before treatment but DrOpped significantly temporally after FBZ treatment. Group C-0 was worm-free at necropsy. Group C-i animals contained variable numbers of luminal and tissue cyathostomins. Histological sections showed larval stages in the lamina propria und submucosa surrounded by macrophages. Either treatment was effective against luminal parasites and reduced the number of larvae in the bowel wall beginning 4-6 days after FBZ and 6-14 days after MOX treatment. Histologically, as a first reaction after FBZ application T lymphocytes accumulated around morphologically intact L4 in the submucosa. Subsequently T lymphocytes associated with eosinophils infiltrated the submucosa. Parasites became enclosed by granulomas with eosinophils adhering to and invading the larvae which started to disintegrate on day 4. Later on, particularly on day 14 inflammation extended into the mucosa and was frequently associated with ulcerations. Third stage larvae in general and L4 in the lamina propria, however, seemed not to be affected until day 14 and even then, parasites did usually not generate extensive inflammation. After MOX treatment severe morphologically detectable alterations of tissue larvae could not be observed earlier than day 14. Different from FBZ treatment, larvae disintegrated and were obviously resorbed without causing severe inflammation in the gut wall. In conclusion treatment with either drug was efficacious against tissue larvae of cyathostomins but there may be different clinical consequences: in contrast to MOX effects, killing of larvae due to FBZ was associated with severe tissue damage, which clinically may correspond to reactions caused by synchronous mass emergence of fourth stage larvae, i.e., may mimic larval cyathostominosis.
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