Recombinant Paraprobiotics as a New Paradigm for Treating Gastrointestinal Nematode Parasites of Humans.

Gastrointestinal nematodes (GINs) of humans, e.g., hookworms, negatively impact childhood growth, cognition, nutrition, educational attainment, income, productivity, and pregnancy. Hundreds of millions of people are targeted with mass drug administration (MDA) of donated benzimidazole anthelmintics. However, benzimidazole efficacy against GINs is suboptimal, and reduced/low efficacy has been seen. Developing an anthelmintic for human MDA is daunting: it must be safe, effective, inexpensive, stable without a cold chain, and massively scalable. Bacillus thuringiensis crystal protein 5B (Cry5B) has anthelmintic properties that could fill this void. Here, we developed an active pharmaceutical ingredient (API) containing B. thuringiensis Cry5B compatible with MDA. We expressed Cry5B in asporogenous B. thuringiensis during vegetative phase, forming cytosolic crystals. These bacteria with cytosolic crystals (BaCC) were rendered inviable (inactivated BaCC [IBaCC]) with food-grade essential oils. IBaCC potency was validated in vitro against nematodes. IBaCC was also potent in vivo against human hookworm infections in hamsters. IBaCC production was successfully scaled to 350 liters at a contract manufacturing facility. A simple fit-for-purpose formulation to protect against stomach digestion and powdered IBaCC were successfully made and used against GINs in hamsters and mice. A pilot histopathology study and blood chemistry workup showed that five daily consecutive doses of 200 mg/kg body weight Cry5B IBaCC (the curative single dose is 40 mg/kg) was nontoxic to hamsters and completely safe. IBaCC is a safe, inexpensive, highly effective, easy-to-manufacture, and scalable anthelmintic that is practical for MDA and represents a new paradigm for treating human GINs.

Interpretation of canine and feline blood smears by emergency room personnel.

BACKGROUND: Interpretation of blood smears is commonly used to provide rapid laboratory evaluation of animals in veterinary emergency practice, but the accuracy of results of blood smear interpretation by emergency room personnel (ERP) compared with evaluation by trained veterinary clinical pathology personnel is unknown. OBJECTIVE: The goal of this study was to compare blood smear evaluation by ERP with that of clinical pathology personnel. METHODS: All animals that had a CBC determined by a diagnostic laboratory and had blood smears evaluated by personnel at the Foster Hospital for Small Animals Emergency Room between September 2008 and July 2009 were eligible for study inclusion. ERP who evaluated blood smears completed standardized forms with estimates of the WBC and platelet counts and evaluation of RBC and WBC morphology. Results from point-of-care assessment were compared with automated or manual results reported by the veterinary diagnostic laboratory. RESULTS: One hundred and fifty-five blood smears were evaluated. There was moderate agreement (κ value, 0.63; 95% confidence interval [CI]: 0.52, 0.74) between estimated platelet counts by ERP and automated counts. Poor agreement was found between estimated WBC counts by ERP and automated counts (κ value, 0.48; 95% CI: 0.37, 0.60). Specific abnormalities with a high likelihood of clinical significance, eg, toxic change, nucleated RBCs, spherocytes, hemoparasites, and lymphoblasts, were not predictably identified by ERP. CONCLUSIONS: ERP interpretation of canine and feline blood smears should be used cautiously and should not replace evaluation by a veterinary diagnostic laboratory.

Neurologic signs and hyperammonemia in a horse with colic.

A 23-year-old Thoroughbred gelding was referred for the evaluation of acute onset of ataxia and depression, and a 2-day history of fever. On physical examination, the gelding was profoundly depressed and 10-12% dehydrated. The horse appeared very unstable, with a wide-based stance in the hind limbs, severe symmetric ataxia in all 4 limbs, and proprioceptive deficits in both hind limbs. Nasogastric intubation produced 4 L of brown, fetid reflux, and rectal examination revealed mild small intestinal and cecal distention. Hematologic abnormalities included neutropenia with toxic change, compatible with acute inflammation and endotoxemia, and prolonged coagulation times. Serum biochemical abnormalities included prerenal azotemia. metabolic acidosis, and electrolyte abnormalities consistent with enteritis. Blood ammonia concentration was markedly increased (406 micromol/L; reference interval 4-49 micromol/L), however, serum bile acids concentration and hepatic enzyme activities were within reference intervals. Histopathologic examination of a liver biopsy revealed no abnormalities and results of tests for several infectious agents were negative. Clinical signs resolved with correction of the dehydration and electrolyte abnormalities and with antibiotic therapy. The horse was diagnosed with hyperammonemic neuropathy associated with gastrointestinal disease. In such cases, hyperammonemia is caused by increased production of ammonia by organisms in the gastrointestinal tract in combination with increased gut permeability that facilitates ammonia absorption.