In this chapter, we discuss the diseases and related pathologic alterations that may be encountered in the gastrointestinal tract and associated organs of various species of laboratory animals, birds, fish, reptiles, and amphibians. Diseases of various segments of the gastrointestinal tract, the salivary glands, liver, and pancreas are discussed and categorized as inflammatory, parasitic, neoplastic, or miscellaneous. The latter category includes developmental anomalies and metabolic lesions. Due to space limitations, this presentation is not an all-inclusive review, but it does provide a rather extensive review of these lesions. We have also included a rather comprehensive literature review, with a list of references for those readers who want more detailed information with respect to specific diseases.

The Digestive System

The gnotobiotic animal as a tool in the study of host microbial relationships.

Salinomycin, an antibiotic potassium ionophore, has been reported recently to act as a selective breast cancer stem cell inhibitor, but the biochemical basis for its anticancer effects is not clear. The Wnt/β-catenin signal transduction pathway plays a central role in stem cell development, and its aberrant activation can cause cancer. In this study, we identified salinomycin as a potent inhibitor of the Wnt signaling cascade. In Wnt-transfected HEK293 cells, salinomycin blocked the phosphorylation of the Wnt coreceptor lipoprotein receptor related protein 6 (LRP6) and induced its degradation. Nigericin, another potassium ionophore with activity against cancer stem cells, exerted similar effects. In otherwise unmanipulated chronic lymphocytic leukemia cells with constitutive Wnt activation nanomolar concentrations of salinomycin down-regulated the expression of Wnt target genes such as LEF1, cyclin D1, and fibronectin, depressed LRP6 levels, and limited cell survival. Normal human peripheral blood lymphocytes resisted salinomycin toxicity. These results indicate that ionic changes induced by salinomycin and related drugs inhibit proximal Wnt signaling by interfering with LPR6 phosphorylation, and thus impair the survival of cells that depend on Wnt signaling at the plasma membrane.

https://www.pnas.org/content/pnas/108/32/13253.full.pdf

Salinomycin inhibits Wnt signaling and selectively induces apoptosis in chronic lymphocytic leukemia cells

Studies on the biology of the avian species of Eimeria are currently benefiting from the availability of a comprehensive sequence for the nuclear genome of Eimeria tenella. Allied to some recent advances in transgenic technologies and genetic approaches to identify protective antigens, some elements are now being assembled that should be helpful for the development of a new generation of vaccines. In the meantime, control of avian coccidiosis by vaccination represents a major success in the fight against infections caused by parasitic protozoa. Live vaccines that comprise defined populations of oocysts are used routinely and this form of vaccination is based upon the long-established fact that chickens infected with coccidial parasites rapidly develop protective immunity against challenge infections with the same species. Populations of wild-type Eimeria parasites were the basis of the first live vaccines introduced around 50 years ago and the more recent introduction of safer, live-attenuated, vaccines has had a significant impact on coccidiosis control in many areas of the world. In Europe the introduction of vaccination has coincided with declining drug efficacy (on account of drug resistance) and increasing concerns by consumers about the inclusion of in-feed medication and prospects for drug residues in meat. The use of attenuated vaccines throughout the world has also stimulated a greater interest in the vaccines that comprise wild-type parasites and, during the past 3 years worldwide, around 3x10(9) doses of each type of vaccine have been used. The need for only small numbers of live parasites to induce effective protective immunity and the recognition that Eimeria spp. are generally very potent immunogens has stimulated efforts to develop other types of vaccines. None has succeeded except for the licensing, within several countries in 2002, of a vaccine (CoxAbic vaccine; Abic, Israel) that protects via the maternal transfer of immunoglobulin to the young chick. Building on the success of viral vaccines that are delivered via the embryonating egg, an in ovo coccidiosis vaccine (Inovocox, Embrex Inc.) is currently in development. Following successful field trials in 2001, the product will be ready for Food and Drug Administration approval in 2005 and a manufacturing plant will begin production for sale in late 2005. Limited progress has been achieved towards the development of subunit or recombinant vaccines. No products are available and studies to identify potential antigens remain compromised by an absence of effective in vitro assays that correlate with the induction of protective immunity in the host. To date, only a relatively small portfolio of molecules has been evaluated for an ability to induce protection in vivo. Although Eimeria are effective immunogens, it is probable that to date none of the antigens that induce potent protective immune responses during the course of natural infection has been isolated.

The biology of avian Eimeria with an emphasis on their control by vaccination.

The use of live vaccines, either attenuated or non-attenuated, for the control of coccidiosis due to Eimeria infections in broiler breeder or layer chickens is well established. Use in broilers, however, has been slow to gain acceptance. This has been partly for economic reasons, but also because of perceived adverse effects on early chick growth, particularly with non-attenuated vaccines, and concerns about timely onset of protective immunity in such short-lived birds. This review describes advances in understanding of epidemiological factors and recent improvements of administration methods that have helped to allay these fears and to make the use of anticoccidial vaccines in broilers technically achievable. Topics discussed include: (1) types of commercially available vaccine, (2) vaccines in development, (3) vaccination methods and equipment, (4) basis of vaccine efficacy and immunogenic variation of parasites, (5) key factors in the survival, sporulation and dissemination of vaccinal oocysts, (6) descriptions and significance of patterns of litter oocyst accumulation and occurrence of intestinal lesions in vaccinated flocks, (7) rotation of anticoccidial vaccination and chemotherapy to restore drug sensitivity to resistant wild-type coccidia, (8) combinations of anticoccidial vaccination and chemotherapy, (9) interactions between coccidiosis and clostridiosis in broilers and compatibilities of potential control methods, (10) published performance data for live anticoccidial vaccines in broilers, (11) possible further developments of live vaccines.

https://www.tandfonline.com/doi/pdf/10.1080/03079450220148988

W. Malcolm Reid

Papers

Anticoccidial drugs: lesion scoring techniques in battery and floor-pen experiments with chickens.

Anticoccidial Activity of Salinomycin in Battery Raised Broiler Chickens

Histomonas meleagridis and several bacteria as agents of infectious enterohepatitis in gnotobiotic turkeys

Practical Immunization of Chickens against Coccidiosis Using an Attenuated Strain of Eimeria tenella

Anticoccidial Activity of Monensin in Floor-Pen Experiments