Revisiting Ophidiomycosis (Snake Fungal Disease) After a Decade of Targeted Research.

Emerging infectious diseases (EIDs) are typically characterized by novelty (recent detection) and by increasing incidence, distribution, and/or pathogenicity. Ophidiomycosis, also called snake fungal disease, is caused by the fungus Ophidiomyces ophidiicola (formerly "ophiodiicola"). Ophidiomycosis has been characterized as an EID and as a potential threat to populations of Nearctic snakes, sparking over a decade of targeted research. However, the severity of this threat is unclear. We reviewed the available literature to quantify incidence and effects of ophidiomycosis in Nearctic snakes, and to evaluate whether the evidence supports the ongoing characterization of ophidiomycosis as an EID. Data from Canada remain scarce, so we supplemented the literature review with surveys for O. ophidiicola in the Canadian Great Lakes region. Peer-reviewed reports of clinical signs consistent with ophidiomycosis in free-ranging, Nearctic snakes date back to at least 1998, and retrospective molecular testing of samples extend the earliest confirmed record to 1986. Diagnostic criteria varied among publications (n = 33), confounding quantitative comparisons. Ophidiomycosis was diagnosed or suspected in 36/121 captive snakes and was fatal in over half of cases (66.7%). This result may implicate captivity-related stress as a risk factor for mortality from ophidiomycosis, but could also reflect reporting bias (i.e., infections are more likely to be detected in captive snakes, and severe cases are more likely to be reported). In contrast, ophidiomycosis was diagnosed or suspected in 441/2,384 free-ranging snakes, with mortality observed in 43 (9.8 %). Ophidiomycosis was only speculatively linked to population declines, and we found no evidence that the prevalence of the pathogen or disease increased over the past decade of targeted research. Supplemental surveys and molecular (qPCR) testing in Ontario, Canada detected O. ophidiicola on 76 of 657 free-ranging snakes sampled across ~136,000 km2. The pathogen was detected at most sites despite limited and haphazard sampling. No large-scale mortality was observed. Current evidence supports previous suggestions that the pathogen is a widespread, previously unrecognized endemic, rather than a novel pathogen. Ophidiomycosis may not pose an imminent threat to Nearctic snakes, but further research should investigate potential sublethal effects of ophidiomycosis such as altered reproductive success that could impact population growth, and explore whether shifting environmental conditions may alter host susceptibility.

Mortality Rates in Transplant Recipients and Transplantation Candidates in a High-prevalence COVID-19 Environment.

BACKGROUND: The risk of COVID-19 infection in transplant recipients (TRs) is unknown. Patients on dialysis may be exposed to greater risk of infection due to an inability to isolate. Consideration of these competing risks is important before restarting suspended transplant programs. This study compared outcomes in kidney and kidney/pancreas TRs with those on the waiting list, following admission with COVID-19 in a high-prevalence region. METHODS: Audit data from all 6 London transplant centers were amalgamated. Demographic and laboratory data were collected and outcomes included mortality, intensive care (ITU) admission, and ventilation. Adult patients who had undergone a kidney or kidney/pancreas transplant, and those active on the transplant waiting list at the start of the pandemic were included. RESULTS: One hundred twenty-one TRs and 52 waiting list patients (WL) were admitted to hospital with COVID-19. Thirty-six TR died (30%), while 14 WL patients died (27% P = 0.71). There was no difference in rates of admission to ITU or ventilation. Twenty-four percent of TR required renal replacement therapy, and 12% lost their grafts. Lymphocyte nadir and D-dimer peak showed no difference in those who did and did not die. No other comorbidities or demographic factors were associated with mortality, except for age (odds ratio of 4.3 [95% CI 1.8-10.2] for mortality if aged over 60 y) in TR. CONCLUSIONS: TRs and waiting list patients have similar mortality rates after hospital admission with COVID-19. Mortality was higher in older TRs. These data should inform decisions about transplantation in the COVID era.

Effect of intravenous administration of dextrose on coagulation in healthy dogs.

OBJECTIVE: To investigate effects of IV administration of dextrose on coagulation in healthy dogs. ANIMALS: 7 dogs. PROCEDURES: Thromboelastography and coagulation panel analysis were used to assess coagulation. Samples (S1 through S9) were collected during the study phases: phase 0 (S1 [baseline]); phase 1 (S2 and S3), infusion of crystalloid fluid without dextrose; phase 2 (S4 and S5), high-rate dextrose infusion; phase 3 (S6, S7, and S8), moderate-rate dextrose infusion; and phase 4 (S9), discontinuation of fluids for 24 hours. In phase 3, dogs were allocated to 2 groups; 1 was administered dextrose at a rate comparable to total parental nutrition (40% of resting energy requirement; group A), and 1 was administered dextrose at rates equaling 70% to 90% of resting energy requirement (group B). Blood glucose concentration was measured every 2 hours. RESULTS: No dogs had clinically relevant sustained hyperglycemia. Maximum amplitude and elastic shear modulus were significantly lower at S6 than at S1 through S4. Concentration of D-dimer was significantly higher at S6 than at S1, S3, and S4 and significantly higher at S5 than at S3. Prothrombin time was significantly prolonged at S3, S5, S7, S8, and S9, compared with the value at S1. Activated partial thromboplastin time was significantly prolonged at S5 and S6, compared with values at S1, S2, S3, S4, and S9. CONCLUSIONS AND CLINICAL RELEVANCE: IV administration of dextrose to healthy dogs at rates comparable to or higher than those for conventional parenteral nutrition resulted in mild but clinically unimportant interference with coagulation.

Effect of nonsteroidal anti-inflammatory drugs with varied cyclooxygenase-2 selectivity on cyclooxygenase protein and prostanoid concentrations in pyloric and duodenal mucosa of dogs.

OBJECTIVE: To assess in vivo effects of short-term administration of NSAIDs with varied cyclooxygenase (COX)-2 selectivity on pyloric and duodenal mucosa. ANIMALS: 8 healthy dogs. PROCEDURES: Each dog received deracoxib (2 mg/kg, PO, q 24 h for 3 days), firocoxib (5 mg/kg, PO, q 24 h for 3 days), meloxicam (0.2 mg/kg, PO, q 24 h for 1 day followed by 0.1 mg/kg, PO, q 24 h for 2 days), or placebo orally for 3 days; there was a 4-week interval between successive treatments. Prior to and on day 3 of drug administration, pyloric and duodenal mucosae were assessed endoscopically and biopsy specimens obtained for histologic examination. Cyclooxygenase-1 and -2 protein expressions were assessed (western blotting) and prostanoid concentrations measured (ELISAs). Data were analyzed by use of an ANOVA. RESULTS: Drug administration did not significantly affect endoscopic mucosal scores, histologic scores, or COX-1 or -2 protein expression. The COX-1 protein expression was significantly higher in the pylorus than in the duodenum. Total prostaglandin and thromboxane B(2) (TXB(2)) concentrations were significantly greater in pyloric than in duodenal mucosa. Drug administration had no effect on prostaglandin or TXB(2) concentrations. CONCLUSIONS AND CLINICAL RELEVANCE: Prostanoid concentrations in gastric and duodenal tissues, and gross and histologic appearances, were not significantly affected by drugs with varied COX-2 selectivity. These findings suggested that, for these experimental conditions, there were no differences among the preferential and selective COX-2 inhibitors with regard to adverse effects on the gastric and duodenal portions of the gastrointestinal tract of dogs.

Cyclooxygenase expression and prostanoid production in pyloric and duodenal mucosae in dogs after administration of nonsteroidal anti-inflammatory drugs.

OBJECTIVE: To assess cyclooxygenase (COX) expression and prostanoid concentrations in pyloric and duodenal mucosae of dogs after administration of nonsteroidal anti-inflammatory drugs (NSAIDs). ANIMALS: 8 healthy dogs. PROCEDURES: Each dog received carprofen (4.4 mg/kg, q 24 h), deracoxib (2 mg/kg, q 24 h), aspirin (10 mg/kg, q 12 h), and placebo (1 dog treat, q 24 h) orally for 3 days (4-week interval between treatments). Before study commencement (baseline) and on day 3 of each treatment, pyloric and duodenal mucosal appearance was assessed endoscopically and biopsy specimens were obtained for histologic examination. Cyclooxygenase-1 and COX-2 protein expressions were assessed via western blotting, and prostanoid concentrations were measured via ELISAs. An ANOVA was used to analyze data. RESULTS: Treatments had no effect on mucosal appearance and ulceration was not evident histologically. In pyloric and duodenal mucosae, COX-1 expression was unaffected by treatments. Cyclooxygenase-2 expression remained unchanged in pyloric mucosa; in duodenal mucosa, aspirin significantly increased COX-2 expression, compared with effects of deracoxib and carprofen. At baseline, total prostaglandin and thromboxane B2 concentrations in pyloric mucosa were significantly greater than those in duodenal mucosa. Aspirin significantly decreased both prostanoid concentrations in both mucosal tissues, compared with other treatments. In pyloric mucosa, carprofen administration significantly decreased total prostaglandin and thromboxane B2 concentrations, compared with deracoxib administration. CONCLUSIONS AND CLINICAL RELEVANCE: In dogs, prostanoid synthesis was greater in pyloric mucosa than it was in duodenal mucosa. Nonselective NSAIDs significantly decreased prostanoid concentrations in these mucosae, compared with the effects of a selective COX-2 NSAID.