The catheterized bladder environment promotes Efg1- and Als1-dependent Candida albicans infection.

Catheter-associated urinary tract infections (CAUTIs) account for 40% of hospital-acquired infections (HAIs). As 20 to 50% of hospitalized patients receive catheters, CAUTIs are one of the most common HAIs, resulting in increased morbidity, mortality, and health care costs. Candida albicans is the second most common CAUTI uropathogen, yet relative to its bacterial counterparts, little is known about how fungal CAUTIs are established. Here, we show that the catheterized bladder environment induces Efg1- and fibrinogen (Fg)-dependent biofilm formation that results in CAUTI. In addition, we identify the adhesin Als1 as the critical fungal factor for C. albicans Fg-urine biofilm formation. Furthermore, we show that in the catheterized bladder, a dynamic and open system, both filamentation and attachment are required, but each by themselves are not sufficient for infection. Our study unveils the mechanisms required for fungal CAUTI establishment, which may aid in the development of future therapies to prevent these infections.

Myocardial Iba1, MHC class II, and CD3 are diffusely increased in canine myocarditis: A step toward antemortem myocarditis diagnostics.

Canine myocarditis is a rare but serious health concern, potentially causing heart failure and death. Antemortem diagnosis is hampered by the numerous causes, nonspecific course, and dearth of diagnostic criteria. Currently, definitive diagnosis can only be made after death. The current human diagnostic gold standard is endomyocardial biopsy pairing cardiac histopathology with immunohistology to enhance detection of often-multifocal disease. We evaluated immune response markers in the canine heart to establish similar immunohistologic criteria. We hypothesized that myocardial major histocompatibility complex class II (MHCII), cluster of differentiation 3 (CD3), and ionized calcium binding adapter molecule 1 (Iba1), markers increased in human myocarditis, would be increased in canine myocarditis cases. Archived paraffin-embedded myocardial tissue from 22 histopathologically confirmed cases of adult and juvenile myocarditis and 23 controls was analyzed by immunohistochemistry for MHCII, CD3, and Iba1, and the fraction of myocardium with labeling was determined. All 3 markers were significantly increased compared with controls across the entire section: Iba1, 10.1× (P < .0001, Mann-Whitney U test); MHCII, 3.04× (P = .0019); and CD3, 4.4× (P = .0104). To mimic off-target biopsy, samples from 2 mm2 outside of inflammatory foci were analyzed, and these showed significant increases in Iba1 by 3.2× (P = .0036, Mann-Whitney U test) and CD3 by 1.2× (P = .0026). These data show diffusely increased immune response markers with canine myocarditis, with detection potentially independent of tissue sampling. Thus, endomyocardial biopsy and immunohistochemical detection of MHCII, CD3, and Iba1 may permit sensitive antemortem diagnosis of canine myocarditis.

Inhibiting host-protein deposition on urinary catheters reduces associated urinary tract infections.

Microbial adhesion to medical devices is common for hospital-acquired infections, particularly for urinary catheters. If not properly treated these infections cause complications and exacerbate antimicrobial resistance. Catheter use elicits bladder inflammation, releasing host serum proteins, including fibrinogen (Fg), into the bladder, which deposit on the urinary catheter. Enterococcus faecalis uses Fg as a scaffold to bind and persist in the bladder despite antibiotic treatments. Inhibition of Fg-pathogen interaction significantly reduces infection. Here, we show deposited Fg is advantageous for uropathogens E. faecalis, Escherichia coli, Pseudomonas aeruginosa, K. pneumoniae, A. baumannii, and C. albicans, suggesting that targeting catheter protein deposition may reduce colonization creating an effective intervention for catheter-associated urinary tract infections (CAUTIs). In a mouse model of CAUTI, host-protein deposition was reduced, using liquid-infused silicone catheters, resulting in decreased colonization on catheters, in bladders, and dissemination in vivo. Furthermore, proteomics revealed a significant decrease in deposition of host-secreted proteins on liquid-infused catheter surfaces. Our findings suggest targeting microbial-binding scaffolds may be an effective antibiotic-sparing intervention for use against CAUTIs and other medical device infections.

The Causes of Canine Myocarditis and Myocardial Fibrosis Are Elusive by Targeted Molecular Testing: Retrospective Analysis and Literature Review.

Myocarditis can cause death or permanent heart damage. As epidemiologic and etiopathologic data for canine myocarditis are lacking, we performed a retrospective study using nucleic acid extracted from archived (2007 to 2015) tissues from myocarditis cases and control dogs without myocardial lesions. Heart tissue from pediatric/juvenile and adult dogs was tested with a comprehensive panel of conventional and real-time polymerase chain reaction (PCR) assays targeting recognized agents of canine myocarditis based on a literature review and informed by the comparative epidemiology of human myocarditis. The PCR screen, which included canine parvovirus 2 (CPV-2), canine distemper virus, canine herpesvirus, Borrelia spp, West Nile virus, adenovirus, parainfluenza virus, pneumovirus, respiratory coronavirus, influenza virus, Bartonella spp, Rickettsia spp, Mycoplasma spp, and Neospora caninum, did not detect agents in 35 of 66 cases (53%; 95% confidence interval [CI], 41%-65%) and was frequently negative in adults (21/26); by comparison, agents were not detected in 27 of 57 controls (47%; 95% CI, 35%-60%). Canine distemper virus, herpesvirus, adenovirus, coronavirus, parainfluenza virus, Mycoplasma haemocanis, and N. caninum were occasionally detected in both cases and controls; thus, PCR detection was not considered to indicate causation. We previously reported that CPV-2 continues to be associated with myocarditis in young dogs despite widespread vaccination; in adults, CPV-2 was detected in 2 of 26 cases and 4 of 22 controls. As several agents were similarly detected in cases and controls, it is unclear if these are cardiopathogenic, incidental, or latent. West Nile virus was detected at the analytic limit in 1 adult case. We did not detect Borrelia spp, Bartonella spp, Rickettsia spp, or influenza A virus in the myocarditis cases. These data demonstrate the limitations of current targeted diagnostic tests and the need for additional research to identify unknown agents and develop testing strategies for canine myocarditis.

Lymphoplasmacytic Meningoencephalitis and Neuronal Necrosis Associated With Parvoviral Infection in Cats.

Neurologic manifestations other than cerebellar hypoplasia are rarely associated with feline panleukopenia virus (FPV) infection in cats. Here the authors describe lymphoplasmacytic meningoencephalitis and neuronal necrosis in 2 cats autopsied after exhibiting ataxia and nystagmus. Gross changes consisted of cerebellar herniation through the foramen magnum, with flattening of cerebrocortical gyri and narrowing of sulci. Histologically, lymphoplasmacytic meningoencephalitis, extensive neuronal necrosis, and neuroaxonal degeneration with digestion chambers were present in the telencephalon and brain stem in both cats. Frozen brain tissue of both cats was positive for parvoviral antigen via fluorescent antibody testing, and formalin-fixed, paraffin-embedded tissue sections of brain were immunoreactive for parvovirus antigen and positive for parvoviral DNA on in situ hybridization. Frozen brain tissue from 1 case was positive for parvovirus NS1 and VP2 genes using conventional polymerase chain reaction, and subsequent DNA sequencing and phylogenetic analysis revealed that the viral strain was a FPV. Reverse transcription quantitative polymerase chain reaction on formalin-fixed, paraffin-embedded brain tissue revealed high levels of parvovirus in both cases, supporting an acute and active viral infection. Although rare, FPV infection should be considered in cases of lymphoplasmacytic meningoencephalitis and neuronal necrosis in cats.

Cardiac Pathology and Genomics of Sudden Death in Racehorses From New York and Maryland Racetracks.

Postmortem evaluation of racehorses has focused primarily on musculoskeletal injuries; however, horses also die suddenly on the track (sudden death [SD]). Although cardiac conditions are frequently suspected as a cause of death, SD racehorses are often autopsy negative; however, previous studies have been limited due to inconsistent or insufficient cardiac sampling and lack of controls. SD in New York (NY) and Maryland (MD) racehorses was evaluated in an observational case vs control study comparing clinical information, postmortem evaluation including cardiac dissection, and cardiac conduction system histopathology. In the study period, there were 40 cases of SD. In NY, SD occurred in 12% (37/316) of submissions, and 36 (11%) cases of SD were exercise associated (EASD); 3 EASD cases occurred in MD. In NY/MD EASD cases with histologic examination of the heart, 11 of 36 (31%) had significant lesions, including mesenteric artery rupture (1), axial trauma (2), systemic inflammation (2), pulmonary hemorrhage (1), and cardiac disease (5). Mild myocardial fibrosis, mild inflammation, coronary arteriosclerosis, and variation in cardiac nodal connective tissue were present in both SD cases and controls and thus were not considered to be causes of SD. While not excluding a genetic basis for SD, analysis of the genotypes (GGP Equine 70 K Array) of cases and controls did not reveal significant differences in allele frequencies at any locus. Most SD racehorses were autopsy negative; further research using standardized protocols and controls is needed to understand the underlying causes of SD, which is crucial to protecting the viability of racing.

Parvovirus Infection Is Associated With Myocarditis and Myocardial Fibrosis in Young Dogs.

Perinatal parvoviral infection causes necrotizing myocarditis in puppies, which results in acute high mortality or progressive cardiac injury. While widespread vaccination has dramatically curtailed the epidemic of canine parvoviral myocarditis, we hypothesized that canine parvovirus 2 (CPV-2) myocardial infection is an underrecognized cause of myocarditis, cardiac damage, and/or repair by fibrosis in young dogs. In this retrospective study, DNA was extracted from formalin-fixed, paraffin-embedded tissues from 40 cases and 41 control dogs under 2 years of age from 2007 to 2015. Cases had a diagnosis of myocardial necrosis, inflammation, or fibrosis, while age-matched controls lacked myocardial lesions. Conventional polymerase chain reaction (PCR) and sequencing targeting the VP1 to VP2 region detected CPV-2 in 12 of 40 cases (30%; 95% confidence interval [CI], 18%-45%) and 2 of 41 controls (5%; 95% CI, 0.1%-16%). Detection of CPV-2 DNA in the myocardium was significantly associated with myocardial lesions ( P = .003). Reverse transcription quantitative PCR amplifying VP2 identified viral messenger RNA in 12 of 12 PCR-positive cases and 2 of 2 controls. PCR results were confirmed by in situ hybridization, which identified parvoviral DNA in cardiomyocytes and occasionally macrophages of juvenile and young adult dogs (median age 61 days). Myocardial CPV-2 was identified in juveniles with minimal myocarditis and CPV-2 enteritis, which may indicate a longer window of cardiac susceptibility to myocarditis than previously reported. CPV-2 was also detected in dogs with severe myocardial fibrosis with in situ hybridization signal localized to cardiomyocytes, suggesting prior myocardial damage by CPV-2. Despite the frequency of vaccination, these findings suggest that CPV-2 remains an important cause of myocardial damage in dogs.

Feline Panleukopenia Virus Is Not Associated With Myocarditis or Endomyocardial Restrictive Cardiomyopathy in Cats.

Canine parvovirus-2 (CPV-2) is nearly indistinguishable from feline panleukopenia virus (FPV) and is a well-known cause of viral myocarditis in young puppies; however, it is not known whether either FPV or CPV-2 naturally infects feline cardiomyocytes and causes myocarditis. Endomyocarditis (EMC) and left ventricular endomyocardial fibrosis (LVEF), clinically known as "endomyocardial restrictive cardiomyopathy," are important feline heart diseases suspected to have an infectious etiology. A continuum is suggested with EMC representing the acute reaction to an unknown infectious agent and LVEF the chronic manifestation of repair. The purpose of this study was to determine (1) whether there is natural parvovirus infection of the feline myocardium and (2) whether parvoviral infection is associated with feline EMC and/or LVEF. In a retrospective study, polymerase chain reaction and sequencing for the parvovirus VP1/2 gene was performed on archived heart tissue from cats with endomyocardial disease and controls. Similar methods were used prospectively on myocardial tissues from shelter-source kittens. Although 8 of 36 (22%; 95% confidence interval [CI], 11%-40%) shelter kittens had parvoviral DNA in myocardial tissue, VP1/2 DNA was not detected in 33 adult cases or 34 controls (95% CI, 0% to ∼11%). These findings were confirmed by in situ hybridization: adult cats did not have detectable parvovirus DNA, although rare intranuclear signal was confirmed in 7 of 8 shelter-source kittens. In kittens, parvovirus was not significantly associated with myocarditis, and in situ hybridization signal did not colocalize with inflammation. Although infection of cardiomyocytes was demonstrated in kittens, these data do not support a role for parvovirus in EMC-LVEF.