Pathology of Chronic Mycoplasma ovipneumoniae Carriers in a Declining Bighorn Sheep (Ovis canadensis) Population.

Bighorn sheep (Ovis canadensis) across North America commonly experience population-limiting epizootics of respiratory disease. Although many cases of bighorn sheep pneumonia are polymicrobial, Mycoplasma ovipneumoniae is most frequently associated with all-age mortality events followed by years of low recruitment. Chronic carriage of M. ovipneumoniae by adult females serves as a source of exposure of naïve juveniles; relatively few ewes may be responsible for maintenance of infection within a herd. Test-and-remove strategies focused on removal of adult females with evidence of persistent or intermittent shedding (hereafter chronic carriers) may reduce prevalence and mitigate mortality. Postmortem confirmation of pneumonia in chronic carriers has been inadequately reported and the pathology has not been thoroughly characterized, limiting our understanding of important processes shaping the epidemiology of pneumonia in bighorn sheep. Here we document postmortem findings and characterize the lesions of seven ewes removed from a declining bighorn sheep population in Wyoming, USA, following at least two antemortem detections of M. ovipneumoniae within a 14-mo period. We confirmed that 6/7 (85.7%) had variable degrees of chronic pneumonia. Mycoplasma ovipneumoniae was detected in the lung of 4/7 (57.1%) animals postmortem. Four (57.1%) had paranasal sinus masses, all of which were classified as inflammatory, hyperplastic lesions. Pasteurella multocida was detected in all seven (100%) animals, while Trueperella pyogenes was detected in 5/7 (71.4%). Our findings indicate that not all chronic carriers have pneumonia, nor do all have detectable M. ovipneumoniae in the lung. Further, paranasal sinus masses are a common but inconsistent finding, and whether sinus lesions predispose to persistence or result from chronic carriage remains unclear. Our findings indicate that disease is variable in chronic M. ovipneumoniae carriers, underscoring the need for further efforts to characterize pathologic processes and underlying mechanisms in this system to inform management.

SOURCE AND SEASONALITY OF EPIZOOTIC MYCOPLASMOSIS IN FREE-RANGING PRONGHORN (ANTILOCAPRA AMERICANA).

Mycoplasma bovis is an economically important bacterial pathogen of cattle (Bos taurus) and bison (Bison bison) that most commonly causes pneumonia, polyarthritis, and mastitis. It is prevalent in cattle and ranched bison; however, infections in other species are rare. In early 2019, we identified M. bovis in free-ranging pronghorn (Antilocapra americana) in northeastern Wyoming. Here, we report on additional pronghorn mortalities caused by M. bovis, in the same approximately 120-km2 geographic region 1 yr later. Genetic analysis by multilocus sequence typing revealed that the mortalities were caused by the same M. bovis sequence type, which is unique among all sequence types documented thus far in North America. To explore whether pronghorn maintain chronic infections and begin assessing M. bovis status in other sympatric species, we used PCR testing of nasal swabs to opportunistically survey select free-ranging ungulates. We found no evidence of subclinical infections in 13 pronghorn sampled from the outbreak area (upper 95% binomial confidence limit [bCL], ∼24.7%) or among 217 additional pronghorn (upper 95% bCL, ∼1.7%) sampled from eight additional counties in Wyoming and 10 in Montana. All mule deer (Odocoileus hemionus; n=231; upper 95% bCL, ∼1.6%) sampled from 11 counties in Wyoming also were PCR negative. To assess the potential for environmental transmission, we examined persistence of M. bovis in various substrates and conditions. Controlled experiments revealed that M. bovis can remain viable for 6 h in shaded water and 2 h in direct sunlight. Our results indicate that environmental transmission of M. bovis from livestock to pronghorn is possible and that seasonality of infection could be due to shared resources during late winter. Further investigations to better understand transmission dynamics, to assess population level impacts to pronghorn, and to determine disease risks among pronghorn and other ungulate taxa appear warranted.

Mycoplasma bovis Infections in Free-Ranging Pronghorn, Wyoming, USA.

Mycoplasma bovis is 1 of several bacterial pathogens associated with pneumonia in cattle. Its role in pneumonia of free-ranging ungulates has not been established. Over a 3-month period in early 2019, ¼60 free-ranging pronghorn with signs of respiratory disease died in northeast Wyoming, USA. A consistent finding in submitted carcasses was severe fibrinosuppurative pleuropneumonia and detection of M. bovis by PCR and immunohistochemical analysis. Multilocus sequence typing of isolates from 4 animals revealed that all have a deletion in 1 of the target genes, adh-1. A retrospective survey by PCR and immunohistochemical analysis of paraffin-embedded lung from 20 pronghorn that died with and without pneumonia during 2007-2018 yielded negative results. These findings indicate that a distinct strain of M. bovis was associated with fatal pneumonia in this group of pronghorn.

Discovery of a Gut-Restricted JAK Inhibitor for the Treatment of Inflammatory Bowel Disease.

To identify Janus kinase (JAK) inhibitors that selectively target gastrointestinal tissues with limited systemic exposures, a class of imidazopyrrolopyridines with a range of physical properties was prepared and evaluated. We identified compounds with low intrinsic permeability and determined a correlation between permeability and physicochemical properties, clogP and tPSA, for a subset of compounds. This low intrinsic permeability translated into compounds displaying high colonic exposure and low systemic exposure after oral dosing at 25 mg/kg in mouse. In a mouse PK/PD model, oral dosing of lead compound 2 demonstrated dose-dependent inhibition of pSTAT phosphorylation in colonic explants post-oral dose but low systemic exposure and no measurable systemic pharmacodynamic activity. We thus demonstrate the utility of JAK inhibitors with low intrinsic permeability as a feasible approach to develop gut-restricted, pharmacologically active molecules with a potential advantage over systemically available compounds that are limited by systemic on-target adverse events.

Rates of iatrogenic ventriculitis before and after the use of an alcohol-impregnated external ventricular drain port cap.

Iatrogenic ventriculitis is a potential complication of ventriculostomy drain placement. In this study, an alcohol-impregnated external ventricular drain port cap was added to a standardized ventriculostomy placement bundle. Rates of ventriculitis were reduced postintervention, but this finding did not reach statistical significance.