Halofuginone lactate (HL) is registered in several countries for the prevention of calf cryptosporidiosis, but the compound's utility in the presence of co-infection with other enteropathogens is not well understood. We performed a randomized controlled field trial of the efficacy of HL for the prevention of natural calf cryptosporidiosis, in the presence of co-infection with rotavirus and Salmonella Typhimurium. Newborn calves on one farm were sequentially enrolled and allocated to a full dose (n=15), half dose (n=15), or a placebo control group (n=15), using a randomized block design. The Cryptosporidium oocysts in fecal specimens collected on Days 6, 8, 10, 14 and 20 were counted and the severity of the diarrhea was assessed using fecal consistency scores (solid, semisolid, or liquid). The oocyst numbers and fecal consistency scores were statistically compared between the groups. Ninety one percent of the calves shed Cryptosporidium parvum oocysts during the trial. The full dose group had a longer prepatent period than the control group, but no statistical difference in the number of oocysts was identified between the groups after controlling for the effects of sex and breed. The fecal consistency scores and mortality rates did not differ between the groups. These results indicated that the anti-Cryptosporidium activity and clinical benefit of HL were limited. It is concluded that in order to maximize the clinical efficacy of HL in the field, diagnostic efforts should aim to rule out the presence of other enteropathogens.

The protozoal pathogen Tritrichomonas foetus infects the colon of domestic cats and is a major cause of chronic colitis and diarrhea. Treatment failure is common, but antibiotics may improve clinical signs in a subset of cats, leading researchers to question involvement of the colonic microbiota in disease pathogenesis. Studies performed in women with venereal Trichomonas vaginalis infections have revealed that dysbiosis of host microbiota contributes to pathogenicity with similar findings also found in mice with intestinal Tritrichomonas musculis The aim of this study was to characterize differences in the fecal microbiota of cats with and without naturally occurring T. foetus infection and in a group of kittens prior to and after experimentally induced infection. Archived fecal DNA from cats undergoing testing for T. foetus infection (n = 89) and experimentally infected kittens (n = 4; at pre-, 2 weeks, and 9 weeks post-infection) were analyzed by sequencing of 16S rRNA genes. Amongst the naturally infected population, the genera Megamonas and Helicobacter were significantly increased in prevalence and abundance in cats testing positive for T. foetus infection. In the group of four experimentally infected kittens, fecal samples post-infection had significantly lower abundance of genus Dialister and Megamonas and greater abundance of the class Betaproteobacteria and family Succinivibrionaceae. We hypothesize that T. foetus promotes dysbiosis by competition for fermentable substrates used by these bacteria and that metabolic byproducts may contribute to the pathogenesis of colonic inflammation and diarrhea. Future studies are warranted for the measurement of fecal concentrations of microbial and protozoal metabolites in cats with T. foetus infection for the identification of potential therapeutic targets.

Background: Allergic diseases are triggered by signaling through the high-affinity IgE receptor, FcεRI. In both mast cells (MCs) and basophils, FcεRI is a tetrameric receptor complex comprising a ligand-binding α subunit (FcεRIα), a tetraspan β subunit (FcεRIβ, MS4A2) responsible for trafficking and signal amplification, and a signal transducing dimer of single transmembrane γ subunits (FcεRIγ). However, FcεRI also exists as presumed trimeric complexes that lack FcεRIβ and are expressed on several cell types outside the MC and basophil lineages. Despite known differences between humans and mice in the presence of the trimeric FcεRI complex, questions remain as to how it traffics and whether it signals in the absence of FcεRIβ. We have previously reported that targeting FcεRIβ with exon-skipping oligonucleotides eliminates IgE-mediated degranulation in mouse MCs, but equivalent targeting in human MCs was not effective at reducing degranulation.Results: Here, we report that the FcεRIβ-like protein MS4A6A exists in human MCs and compensates for FcεRIβ in FcεRI trafficking and signaling. Human MS4A6A promotes surface expression of FcεRI complexes and facilitates degranulation. MS4A6A and FcεRIβ are encoded by highly related genes within the MS4A gene family that cluster within the human gene loci 11q12-q13, a region linked to allergy and asthma susceptibility.Conclusions: Our data suggest the presence of either FcεRIβ or MS4A6A is sufficient for degranulation, indicating that MS4A6A could be an elusive FcεRIβ-like protein in human MCs that performs compensatory functions in allergic disease.

A long-term study was undertaken to monitor immune responses, faecal cultures and clinical disease in sheep experimentally infected with Mycobacterium avium subspecies paratuberculosis (Map) strain Telford. New Zealand Merino lambs (N=56) were challenged with three oral doses of Map suspension. The lambs were weighed and faecal and blood samples obtained at different time-points. At 63 weeks post-challenge, surviving sheep were euthanised and samples of liver, ileo-caecal valve and mesenteric lymph node were collected for histopathology and Map culture. High IFN-γ and antibody responses were evident as early as 8 weeks post-C1 which persisted until the end of the trial. Approximately 92% of the sheep shed Map in faeces at 36 weeks post-challenge, with the prevalence decreasing to around 40% at the end of the trial. Thirteen sheep progressively lost weight and were euthanised between weeks 32 and 58 post-challenge. Nearly 58% of surviving sheep exhibited histo-pathological lesions in at least one of the three tissues sampled, while 42% showed acid-fast bacilli in at least one tissue. A positive Map culture in at least one tissue was obtained from approximately 85% of sheep. These results indicate that the three doses of Map challenge were highly effective in establishing Johne's disease in NZ Merino lambs.