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Leptospirosis is an archetypal One Health problem as described in the companion Currents in One Health article in the October 2022 issue of the Journal of the American Veterinary Medical Association by Sykes et al. A thorough understanding of leptospirosis requires a detailed analysis of the elaborate interplay among pathogenic leptospiral strains, host species, and the environment. Such an understanding is required to inform appropriate preventative measures including vaccine design, prophylaxis efforts, educational programs that help to reduce exposure to pathogenic spirochetes, as well as policy development. Because of the complex epidemiology of leptospirosis, a One Health approach as defined by the One Health Initiative Task Force is critical—an approach that calls for “the collaborative efforts of multiple disciplines working locally, nationally, and globally, to attain optimal health for people, animals and our environment.” Over the last three decades, progressive advances in cutting-edge molecular typing techniques, as well as our ability to rapidly generate and share large amounts of sequence data through establishment and growth of databases, have been central to accelerating a One Health understanding of the epidemiology of leptospirosis. Nevertheless, our dependence on serotype information because of the serovar-specific nature of current vaccines means that laborious serotyping efforts continue. With the advent of new approaches such as mRNA vaccines that are based on lipopolysaccharide immunogens, sequence- and/or proteomics-based typing methods may replace these methods.

OBJECTIVE To determine pharmacokinetics and adverse effects after voriconazole administration to cats and identify an oral dose of voriconazole for cats that maintains plasma drug concentrations within a safe and effective range. ANIMALS 6 healthy cats. PROCEDURES Voriconazole (1 mg/kg, IV) was administered to each cat (phase 1). Serial plasma voriconazole concentrations were measured for 24 hours after administration. Voriconazole suspension or tablets were administered orally at 4, 5, or 6 mg/kg (phase 2). Plasma voriconazole concentrations were measured for 24 hours after administration. Pharmacokinetics of tablet and suspension preparations was compared. Finally, an induction dose of 25 mg/cat (4.1 to 5.4 mg/kg, tablet formulation), PO, was administered followed by 12.5 mg/cat (2.05 to 2.7 mg/kg), PO, every 48 hours for 14 days (phase 3). Plasma voriconazole concentration was measured on days 2, 4, 8, and 15. RESULTS Voriconazole half-life after IV administration was approximately 12 hours. Maximal plasma concentration was reached within 60 minutes after oral administration. A dose of 4 mg/kg resulted in plasma concentrations within the target range (1 to 4 μg/mL). Adverse effects included hypersalivation and miosis. During long-term administration, plasma concentrations remained in the target range but increased, which suggested drug accumulation. CONCLUSIONS AND CLINICAL RELEVANCE Voriconazole had excellent oral bioavailability and a long half-life in cats. Oral administration of a dose of 12.5 mg/cat every 72 hours should be investigated. Miosis occurred when plasma concentrations reached the high end of the target range. Therefore, therapeutic drug monitoring should be considered to minimize adverse effects.

Objective—To determine within a cat shelter effects of dietary lysine supplementation on nasal and ocular disease and detection of nucleic acids of Chlamydophila felis, feline calicivirus (FCV), and feline herpesvirus (FHV-1). Animals—261 adult cats. Procedures—Cats were fed a diet containing 1.7% (basal diet; control cats) or 5.7% (supplemented diet; treated cats) lysine for 4 weeks. Plasma concentrations of lysine and arginine were assessed at the beginning (baseline) and end of the study. Three times a week, cats were assigned a clinical score based on evidence of nasal and ocular disease. Conjunctival and oropharyngeal swab specimens were tested for FHV-1, FCV, and C felis nucleic acids once a week. Results—Data were collected from 123, 74, 59, and 47 cats during study weeks 1, 2, 3, and 4, respectively. By study end, plasma lysine concentration in treated cats was greater than that in control cats and had increased from baseline. There was no difference between dietary groups in the proportion of cats developing mild disease. However, more treated cats than control cats developed moderate to severe disease during week 4. During week 2, FHV-1 DNA was detected more commonly in swab specimens from treated versus control cats. Conclusions and Clinical Relevance—Dietary lysine supplementation in the amount used in our study was not a successful means of controlling infectious upper respiratory disease within a cat shelter. Rather, it led to increases in disease severity and the incidence of detection of FHV-1 DNA in oropharyngeal or conjunctival mucosal swab specimens at certain time points.

Objective—To correlate gene transcription of cytokines and chemokines with histologic inflammation in nasal biopsy specimens of cats. Animals—25 study cats and 4 specific pathogen–free cats. Procedure—One nasal biopsy specimen from each cat was submitted for routine histologic evaluation; a second was submitted for evaluation by use of a quantitative real-time polymerase chain reaction analysis with a fluorogenic probe (ie, TaqMan) for detection of cytokines and chemokines (interleukin [IL]-4, IL-5, IL-6, IL-10, IL-12 p40, IL-16, IL-18, interferon [IFN]-γ, tumor necrosis factor [TNF]-α, and the regulated on activation normal T cell expressed and secreted [RANTES] protein). Specimens were grouped histologically by degree of inflammation (none, mild, moderate, or severe). Linearized TaqMan signals for each gene were compared among histologic groups. Results—Nasal biopsy specimens from specific pathogen–free cats were histologically normal, and cytokine transcription was low in these samples. As nasal inflammation in study cats worsened from absent (n = 3) to mild (4) to moderate (8) or severe (10), progressively and significantly increasing transcription of IL-6, IL-10, IL-12 p40, IFN-γ, TNF-α, and the RANTES protein was detected. Transcription of IL-4, IL- 5, IL-16, and IL-18 did not correlate with worsened histologic inflammation. Conclusions and Clinical Relevance—Transcription of specific cytokines and chemokines in nasal tissue of cats progressively increased with severity of histologic evidence of inflammation, and IL-6, IL-10, IL-12 p40, IFN-γ, TNF-α, and the RANTES protein were markers of inflammation. Our data suggest that the nasal cavity of cats is biased toward a Th1 cytokine profile that is augmented by inflammation. (Am J Vet Res 2005;66:996–1001)

Objective—To determine whether the active metabolite of leflunomide, A77 1726 (A77), inhibits replication of feline herpesvirus-1 (FHV-1) in cell culture. Study Population—Crandell Rees feline kidney (CRFK) cell cultures. Procedures—Cell cultures were inoculated with FHV-1 and treated simultaneously with concentrations of A77 ranging from 0 to 200μM. The antiviral effect of A77 was determined by use of conventional plaque reduction assays. The effect of A77 on viral load was determined via real-time PCR analysis, and transmission electron microscopy was used to evaluate the effect of A77 on viral morphology. To determine whether the antiviral effect was attributable to alterations in CRFK cell viability and number, CRFK cells were treated with various concentrations of A77 and stained with Annexin V and propidium iodide to assess apoptosis and a mitochondrial function assay was used to determine cell viability. Results—Concentrations of A77 ≥ 20μM were associated with substantial reduction in plaque number and viral load. Concentrations ≥ 100μM were associated with complete suppression of plaque formation. At low concentrations of A77, clusters of intracytoplasmic virus particles that appeared to lack tegument and an external membrane were detected. Treatment of uninfected CRFK cell monolayers with A77 was associated with reduction in mitochondrial function with minimal evidence of apoptosis. Conclusions and Clinical Relevance—Leflunomide may be an alternative to current calcineurin-based immunosuppressive protocols used in feline organ transplantation because of its antiherpesviral activity.