Salmonella enterica subspecies houtenae as an opportunistic pathogen in a case of meningoencephalomyelitis and bacteriuria in a dog.

BACKGROUND: We report the first case of canine Salmonella meningoencephalomyelitis and second case of canine Salmonella bacteriuria, as well as the first reported case of Salmonella enterica subspecies houtenae in a dog. CASE PRESENTATION: Immunosuppressive treatment in a dog for a relapse of steroid-responsive meningitis and arteritis (SRMA) allowed for the opportunistic establishment of a bacteremia with Salmonella enterica subsp. houtenae, ultimately causing meningoencephalomyelitis and subclinical bacteriuria. The bacterial infections were treated with a four-month course of amoxicillin; clinical treatment success was determined by serial negative urine cultures and lack of clinical signs correlated to the meningoencephalomyelitis. CONCLUSIONS: Both the bacteriuria and meningoencephalomyelitis represented opportunistic infections in a dog immunosuppressed for SRMA. The clinical course of this infectious meningoencephalitis emphasizes the importance of differentiating relapse of initial disease from opportunistic infection occurring in a compromised central nervous system. The novel Salmonella species identified in this case acts as a reminder that infectious disease diagnostics should not be curbed by anecdotal prediction of routine pathogenic suspects.

Gastric Ulceration and Immune Suppression in Weaned Piglets Associated with Feed-Borne Bacillus cereus and Aspergillus fumigatus.

As a multifactorial cause, gastric ulceration-mediated diarrhea is widely prevalent in the weaned piglets, impairing pig health and economic benefits. With full implementation of antibiotic stewardship programs in China, Bacillus cereus (B. cereus) and Aspergillus fumigatus (A. fumigatus) were identified frequently in porcine feedstuffs and feeds of the animal industry. Association between feed-borne B. cereus and frequent diarrhea remains unclear. In the present study, we conducted a survey of B. cereus and A. fumigatus from feeds and feedstuffs in pig farms during hot season. Interestingly, B. cereus, B. subtilis, B. licheniformis and B. thuringinesis were isolated and identified from piglets' starter meals to sow feeds, accounting for 56.1%, 23.7%, 13.7% and 6.5%, respectively. Obviously, both B. cereus and B. subtili were dominant contaminants in the survey. In an in vitro study, Deoxynivalenol (DON) contents were determined in a dose-dependent manner post fermentation with B. cereus (405 and DawuC). Subsequently, 36 weaned piglets were randomly assigned to four groups and the piglets simultaneously received the combination of virulent B. cereus (Dawu C) and A. fumigatus while animals were inoculated with B. cereus (Dawu C), A. fumigatus or PBS as the control group. Clinically, piglets developed yellow diarrhea on day 5 and significant reductions of relative body weight were observed in the B. cereus group, and co-infection group. More importantly, IgG titers against Classical swine fever virus (CSFV) and Porcine epidemic diarrhea (PED) were reduced dramatically during 14-day observation in co-infection group, the B. cereus (Dawu C) group or the A. fumigatus group. However, lower Foot and mouth disease (FMD) -specific antibodies were reduced on day 7 compared to those of the control group. Additionally, lower lymphocyte proliferations were found in the B. cereus group and the co-infection group compared to the control group. Postmortem, higher lesions of gastric ulceration were observed in the B. cereus group and the co-infection group from day 7 to day 14 compared with those of the A. fumigatus group and the control group. Compared to the A. fumigatus group, higher DON contents were detected in the stomach inoculated with B. cereus and the co-infection with A. fumigatus. In conclusion, our data support the hypothesis that B. cereus might be associated with severe diarrhea by inducing gastric ulcerations and A. fumigatus might aggravate immune suppression, threating a sustainable swine industry. It is urgently needed to control feed-borne B. cereus contamination.

Sarocladium and Acremonium infections: New faces of an old opportunistic fungus.

The genera Acremonium and Sarocladium comprise a high diversity of morphologically and genetically related fungi generally found in the environment, although a few species, mainly Sarocladium kiliense and Acremonium egyptiacum, can also be involved in many human infections. Clinical management of opportunistic infections caused by these fungi is very complex, since their correct identification is unreliable, and they generally show poor antifungal response. More than 300 clinical cases involving a broad range of Acremonium/Sarocladium infections have so far been published, and with this review we aim to compile and provide a detailed overview of the current knowledge on Acremonium/Sarocladium human infections in terms of presentation, diagnosis, treatments and prognoses. We also aim to summarise and discuss the data currently available on their antifungal susceptibility, emphasising the promising results obtained with voriconazole as well as their impact in terms of animal infections.

Cutaneous and Pulmonary Mucormycosis in Rag1- and Il2rg-deficient Rats.

Immunodeficient rats are valuable in transplantation studies, but are vulnerable to infection from opportunistic organisms such as fungi. Immunodeficient Rag1- and Il2rg-deficient (RRG) rats housed at our institution presented with dark, proliferative, keratinized dermal growths. Histologic and PCR results indicated that the predominant organism associated with these lesions was fungus from the family Mucoraceae, mostly of the genus Rhizopus. The Mucoraceae family of fungi are environmental saprophytes and are often found in rodent bedding. These fungi can cause invasive opportunistic infections in immunosuppressed humans and animals. We discuss husbandry practices for immunosuppressed rodents with a focus on controlling fungal contaminants.

High Prevalence of Cryptococcus neoformans and Isolation of Other Opportunistic Fungi From Pigeon (Columba livia) Droppings in Northeast Iran.

Cryptococcus neoformans is an opportunistic human pathogen that causes cryptococcosis, a life-threatening infection that usually manifests as meningoencephalitis in immunocompromised patients. Pigeon (Columba livia) droppings can spread pathogenic yeasts and mold fungi, such as C neoformans, in the environment. The objective of this study was to isolate C neoformans and other opportunistic fungi from feral pigeon droppings. One hundred twenty samples of feral pigeon droppings were suspended 1:10 in saline solution and then cultured. The fungi were identified by standard mycological techniques. Fungal contamination was detected in all examined samples. Yeast and mold fungi were isolated from 114 samples (95%) and 103 samples (85.8%), respectively, out of 120 samples. The highest frequency of yeast and mold fungi isolated from collected samples was C neoformans 77.5% and Rhizopus species 38.3%, respectively. Several types of fungi exist in pigeon droppings that can be spread in the environment and transmitted to children and elderly, as well as immunocompromised patients who are at increased risk of contracting opportunistic diseases.

Effects of Regulatory T Cell Depletion on NK Cell Responses against Listeria monocytogenes in Feline Immunodeficiency Virus Infected Cats.

Regulatory T cells (Treg) are key players in the maintenance of peripheral tolerance, preventing autoimmune diseases and restraining chronic inflammatory diseases. Evidence suggests Treg cells and NK cells have important roles in feline immunodeficiency virus (FIV) pathogenesis; however, in vivo studies investigating the interplay between these two cell populations are lacking. We previously described innate immune defects in FIV-infected cats characterized by cytokine deficits and impaired natural killer cell (NK) and NK T cell (NKT) functions. In this study, we investigated whether in vivo Treg depletion by treatment with an anti-feline CD25 monoclonal antibody would improve the innate immune response against subcutaneous challenge with Listeria monocytogenes (Lm). Treg depletion resulted in an increased overall number of cells in Lm-draining lymph nodes and increased proliferation of NK and NKT cells in FIV-infected cats. Treg depletion did not normalize expression of perforin or granzyme A by NK and NKT cells, nor did Treg depletion result in improved clearance of Lm. Thus, despite the quantitative improvements in the NK and NKT cell responses to Lm, there was no functional improvement in the early control of Lm. CD1a+ dendritic cell percentages in the lymph nodes of FIV-infected cats were lower than in specific-pathogen-free control cats and failed to upregulate CD80 even when Treg were depleted. Taken together, Treg depletion failed to improve the innate immune response of FIV-infected cats against Lm and this may be due to dendritic cell dysfunction.

Isolation of Arcobacter species and other neglected opportunistic agents from aborted bovine and caprine fetuses.

BACKGROUND: Infectious abortion in ruminants is a problem in animal husbandry worldwide. It is important to obtain a diagnosis, to make sure that proper control measures can be instituted, but most abortion cases remain without an etiologic diagnosis. This report describes the presence of Arcobacter species and several neglected opportunistic abortifacient agents in ruminant abortion cases showing or not co-infections among at least one of the major recognized protozoal, fungal, bacterial and viral abortifacient agents. RESULTS: A total of 67 fetuses (55 cattle and 12 goats) and just one placenta (cattle) were considered. Among the most common abortive agents, Neospora caninum (19,4%), followed by Chlamydophila abortus (4,5%), Listeria monocytogenes 1/2a (2,98%), Bovine Viral Diarrhea Virus type 1b (2,98%), Bovine herpesvirus 4 (2,98%), and Aspergillus spp. (2,98%) were detected. The isolated neglected opportunistic bacteria include Escherichia coli, Acinetobacter lwoffii, Staphylococcus spp., Streptococcus spp., Streptococcus uberis, Streptococcus suis, Trueperella pyogenes, Mannheimia haemolytica, Bacillus cereus and Nocardia spp. Other bacterial species, not associated with abortion by literature, but described as causes of diseases occurring sporadically both in humans and animals, were also detected. Three Arcobacter strains, namely two A. skirrowii and one A. cryaerophilus, were isolated from 3 bovine aborted fetuses, and A. butzleri was isolated from the placenta. CONCLUSIONS: A not negligible isolation of Arcobacter species and other neglected abortifacient agents has to be mentioned, with prevalences that seem to be emerging and replacing or co-placing the major infectious players in bovine and caprine reproductive failure due to abortion disease, even if further studies investigating the aetiological power and transmission routes are needed in order to define the role of these microrganisms in ruminant abortion.

Economic and epidemiological impact of different intervention strategies for subclinical and clinical mastitis.

The objective of this study was to evaluate and compare different combinations of intervention strategies for contagious or opportunistic subclinical and clinical intramammary infections (IMI). We simulated two different Danish dairy cattle herds with ten different intervention strategies focusing on cow-specific treatment or culling, including three baseline strategies without subclinical interventions. In one herd, the main causative pathogen of IMI was Staphylococcus (S.) aureus. In the other herd, Streptococcus (St.) agalactiae was the main causative agent. For both herds, we investigated costs and effectiveness of all ten intervention strategies. Intervention strategies consisted of measures against clinical and subclinical IMI, with baselines given by purely clinical intervention strategies. Our results showed that strategies including subclinical interventions were more cost-effective than the respective baseline strategies. Increase in income and reduction of IMI cases came at the cost of increased antibiotic usage and an increased culling rate in relation to IMI. However, there were differences between the herds. In the St. agalactiae herd, the clinical intervention strategy did not seem to have a big impact on income and number of cases. However, intervention strategies which included cow-specific clinical interventions led to a higher income and lower number of cases in the S. aureus herd. The results show that intervention strategies including interventions against contagious or opportunistic clinical and subclinical IMI can be highly cost-effective, but should be herd-specific.

PCR Prevalence of Murine Opportunistic Microbes and their Mitigation by Using Vaporized Hydrogen Peroxide.

Exposing immunodeficient mice to opportunistic microbes introduces risks of data variability, morbidity, mortality, and the invalidation of studies involving unique human reagents, including the loss of primary human hematopoietic cells, patient-derived xenografts, and experimental therapeutics. The prevalence of 15 opportunistic microbes in a murine research facility was determined by yearlong PCR-based murine and IVC equipment surveillance comprising 1738 specimens. Of the 8 microbes detected, 3 organisms- Staphylococcus xylosus, Proteus mirabilis, and Pasteurella pneumotropica biotype Heyl-were most prevalent in both murine and IVC exhaust plenum specimens. Overall, the 8 detectable microbes were more readily PCR-detectable in IVC exhaust airways than in murine specimens, supporting the utility of PCR testing of IVC exhaust airways as a component of immunodeficient murine health surveillance. Vaporized hydrogen peroxide (VHP) exposure of IVC equipment left unassembled (that is, in a 'static-open' configuration) did not eliminate PCR detectable evidence of microbes. In contrast, VHP exposure of IVC equipment assembled 'active-closed' eliminated PCR-detectable evidence of all microbes. Ensuring data integrity and maintaining a topographically complex immunodeficient murine research environment is facilitated by knowing the prevalent opportunistic microbes to be monitored and by implementing a PCR-validated method of facility decontamination that mitigates opportunistic microbes and the risk of invalidation of studies involving immunodeficient mice.

Genotypic differences between strains of the opportunistic pathogen Corynebacterium bovis isolated from humans, cows, and rodents.

Corynebacterium bovis is an opportunistic bacterial pathogen shown to cause eye and prosthetic joint infections as well as abscesses in humans, mastitis in dairy cattle, and skin disease in laboratory mice and rats. Little is known about the genetic characteristics and genomic diversity of C. bovis because only a single draft genome is available for the species. The overall aim of this study was to sequence and compare the genome of C. bovis isolates obtained from different species, locations, and time points. Whole-genome sequencing was conducted on 20 C. bovis isolates (six human, four bovine, nine mouse and one rat) using the Illumina MiSeq platform and submitted to various comparative analysis tools. Sequencing generated high-quality contigs (over 2.53 Mbp) that were comparable to the only reported assembly using C. bovis DSM 20582T (97.8 ± 0.36% completeness). The number of protein-coding DNA sequences (2,174 ± 12.4) was similar among all isolates. A Corynebacterium genus neighbor-joining tree was created, which revealed Corynebacterium falsenii as the nearest neighbor to C. bovis (95.87% similarity), although the reciprocal comparison shows Corynebacterium jeikeium as closest neighbor to C. falsenii. Interestingly, the average nucleotide identity demonstrated that the C. bovis isolates clustered by host, with human and bovine isolates clustering together, and the mouse and rat isolates forming a separate group. The average number of genomic islands and putative virulence factors were significantly higher (p<0.001) in the mouse and rat isolates as compared to human/bovine isolates. Corynebacterium bovis' pan-genome contained a total of 3,067 genes of which 1,354 represented core genes. The known core genes of all isolates were primarily related to ''metabolism" and ''information storage/processing." However, most genes were classified as ''function unknown" or "unclassified". Surprisingly, no intact prophages were found in any isolate; however, almost all isolates had at least one complete CRISPR-Cas system.

Opportunistic Fungal Infections in Small Animals.

Opportunistic fungal infections have long been recognized as rare causes of disease in immunocompetent dogs and cats. Recently, the escalating use of multiagent immunosuppression protocols (especially those that include cyclosporine) has resulted in an increased number of patients with opportunistic fungal infection encountered by small animal practitioners and has altered the typical case phenotype. Based on histologic and cytologic features such as pigmentation, hyphal diameter, and distribution in tissue, these opportunistic mycoses can be placed into categories such as phaeohyphomycosis, hyalohyphomycosis, and eumycotic mycetoma. This review aims to summarize the clinical presentations, methods for diagnosis, treatment recommendations, and prognosis for both immunocompetent and immunosuppressed patients with opportunistic fungal infections. An example case description is included to illustrate the most common current clinical presentation.

The determination of the infectious status and prevalence of motile Aeromonas species isolated from disease cases in rainbow trout (Oncorhynchus mykiss) and aquarium fish.

The aims of this study were to determine the prevalence and phylogenetic relationship of motile Aeromonas spp. that might be pathogenic species for rainbow trout in infected/mix infection cases (based upon different outbreaks on fish farms). A total of 99 motile Aeromonas isolates (and three reference strains) were analysed that were isolated from four different fish species in different sizes of fish (0.1-3,000 g), different months and water temperatures (6.1-21.2°C). The biochemical characteristics of the isolates were determined using conventional tests and a rapid test kit. Additionally, molecular identification was performed using the gyrB housekeeping gene region and with glycerophospholipid-cholesterol acyltransferase polymerase chain reaction (GCAT-PCR). The sequencing results obtained from the gyrB gene region were deposited in the GenBank database, and phylogenetic relationships were determined with the BioNumerics 7.6 database. Nearly half of the Aeromonas isolates that were isolated from rainbow trout showing signs of disease were determined to be possible infectious agents. Aeromonas species exhibit biochemical variability for many characters, so some Aeromonas species tested negative for GCAT-PCR despite that this test was created especially for Aeromonas identification. The phylogenetic tree based upon gyrB contained 10 different phylogroups that were based on 96% cut-off value in gyrB gene region.

Outbreak of Opportunistic Ascending Pyelonephritis with Numerous Yeast after Experimental Humanization Surgery in NOD.Cg-Prkdcscid Il2rgtm1Wjl/SzJ and NOD.Cg-Rag1tm1Mom Il2rgtm1Wjl/SzJ Immunodeficient Mice.

Unexpected mortality occurred in a group of 12 NOD.Cg-NOD.Cg-PrkdcscidIl2rgtm1Wjl/SzJ (NSG) and 12 NOD.Cg-Rag1tm1Mom Il2rgtm1Wjl/SzJ (NRG) immunodeficient mice. At 10 d after routine bone marrow-liver-thymus humanization surgery, 9 mice were found dead without observation of initiating clinical signs; 1 d later (day 11), 3 additional mice showed signs of morbidity, including severe hunching, lateral recumbency, slow movement, shallow respiration, and decreased response to external stimulus. All remaining mice rapidly decompensated and were found dead or were euthanized within 4 d after the first death. Histopathology revealed severe ascending pyelonephritis with numerous yeast. Cultures in some mice were positive for Enterococcus faecalis or Staphylococcus xylosus, 2 bacteria considered commensals in rodents. In addition, Candida albicans was cultured from some animals. Further investigation revealed that a restraining device used for tail vein injections was the likely fomite harboring Candida organisms. These findings indicate that ascending pyelonephritis, with Candida as the etiologic agent, can cause significant mortality in NSG and NRG immunodeficient mice.

Fungal infections in animals: a patchwork of different situations.

The importance of fungal infections in both human and animals has increased over the last decades. This article represents an overview of the different categories of fungal infections that can be encountered in animals originating from environmental sources without transmission to humans. In addition, the endemic infections with indirect transmission from the environment, the zoophilic fungal pathogens with near-direct transmission, the zoonotic fungi that can be directly transmitted from animals to humans, mycotoxicoses and antifungal resistance in animals will also be discussed. Opportunistic mycoses are responsible for a wide range of diseases from localized infections to fatal disseminated diseases, such as aspergillosis, mucormycosis, candidiasis, cryptococcosis and infections caused by melanized fungi. The amphibian fungal disease chytridiomycosis and the Bat White-nose syndrome are due to obligatory fungal pathogens. Zoonotic agents are naturally transmitted from vertebrate animals to humans and vice versa. The list of zoonotic fungal agents is limited but some species, like Microsporum canis and Sporothrix brasiliensis from cats, have a strong public health impact. Mycotoxins are defined as the chemicals of fungal origin being toxic for warm-blooded vertebrates. Intoxications by aflatoxins and ochratoxins represent a threat for both human and animal health. Resistance to antifungals can occur in different animal species that receive these drugs, although the true epidemiology of resistance in animals is unknown, and options to treat infections caused by resistant infections are limited.

Talaromycosis (Penicilliosis) in a Cynomolgus Macaque.

A sexually mature Chinese-origin female Macaca fascicularis assigned to the high-dose group in a 26-week toxicology study with an experimental immunomodulatory therapeutic antibody (a CD40 L antagonist fusion protein) was euthanized at the scheduled terminal sacrifice on study day 192. The animal was healthy at study initiation and remained clinically normal throughout the study. On study day 141, abnormal clinical pathology changes were found during a scheduled evaluation; splenomegaly was detected on study day 149 and supported by ultrasound examination. At the scheduled necropsy, there was marked splenomegaly with a nodular and discolored appearance. Cytologic examination of a splenic impression smear revealed yeast-like organisms within macrophages. Histologically, there was disseminated systemic granulomatous inflammation with 2- to 3-µm oval, intracytoplasmic yeast-like organisms in multiple organs identified as Talaromyces (Penicillium) marneffei. This organism, not previously reported as a pathogen in macaques, causes an important opportunistic infection in immunosuppressed humans in specific global geographic locations.

Características epidemiológicas, clínico-patológicas e morfotintoriais de quatorze casos de nocardiose em cães / Epidemiological, clinical, pathological and morphotinctorial features of fourteen cases of nocardiosis in dogs

Este artigo descreve os aspectos epidemiológicos, clínicos, patológicos e características morfotintoriais em quatorze casos de nocardiose em cães. Para isso foi realizado um estudo retrospectivo durante o período de janeiro de 2005 a dezembro de 2015 e selecionados os casos sugestivos de nocardiose. A identificação e caracterização do agente foi realizada através de técnicas histoquímicas especiais de Metenamina nitrato de prata de Grocott (GMS), Ziehl-Neelsen modificado, coloração de Gram do tipo Brown-Brenn modificado e Giemsa. Foram afetados predominantemente filhotes e em doze casos havia associação com o vírus da cinomose canina (VCC). Os sinais clínicos variaram de alterações respiratórias, neurológicas e cutâneas, relacionadas principalmente à infecção concomitante pelo VCC. Macroscopicamente haviam áreas multifocais a coalescentes, branco-amareladas, firmes, elevadas na superfície e que se aprofundavam ao corte, por vezes com material purulento, entremeadas por áreas avermelhadas irregulares afetando principalmente pulmões, linfonodos, fígado, rins e encéfalo. As lesões cutâneas foram observadas predominantemente nas regiões cervical e inguinal e variaram de supurativas a piogranulomatosas. No exame histopatológico a lesão era caracterizada principalmente por inflamação piogranulomatosa, porém em algumas áreas havia predomínio de inflamação necrossupurativa, e frequentemente eram observados macrófagos epitelioides, formando aglomerados de forma radiada, muitas vezes lembrando pseudorosetas. Nas técnicas histoquímicas foram observadas estruturas filamentosas, ramificadas, não septadas, medindo aproximadamente 1µm de espessura, impregnadas na coloração de prata, coradas em vermelho no Ziehl-Neelsen modificado, em azul na coloração de Gram do tipo Brown-Brenn modificado e fracamente rósea pálido no Giemsa. A nocardiose deve ser considerada em animais jovens que apresentam sinais respiratórios e neurológicos progressivos, bem como em lesões cutâneas com envolvimento do subcutâneo e linfonodos regionais. Deve ser investigado ainda um provável fator predisponente, como a infecção pelo vírus da cinomose canina e hemoparasitoses. O diagnóstico foi estabelecido através do exame histopatológico baseando-se na morfologia da bactéria e suas características histoquímicas, distinguindo principalmente de outros agentes bacterianos e fúngicos, constituindo uma importante ferramenta para o diagnóstico, quando não é possível a coleta do material para cultivo e isolamento do agente.(AU)

This paper describes the epidemiological, clinical, pathological and morphotinctorial characteristics in fourteen cases of nocardiosis in dogs. A retrospective study for the period of January 2005 to December 2015 was made and selected suggestive cases of nocardiosis. The identification and characterization of the agent was performed by special histochemical techniques Methenamine silver nitrate Grocott (GMS), modified Ziehl-Neelsen, Gram stain type modified Brown-Brenn and Giemsa. Were affected predominantly young and in twelve cases were associated with canine distemper virus (CDV). Clinical signs vary from respiratory, neurological and skin changes, mainly related to concomitant infection by CDV. Macroscopically had multifocal areas coalescing, yellowish-white, firm, elevated in surface and deepened the court, sometimes with purulent material, intermixed by irregular reddened areas affecting mainly lungs, lymph nodes, liver, kidneys, and brain. The cutaneous lesions were predominantly observed in cervical and inguinal and ranged from suppurative well as pyogranulomatous. In the histopathologic examination the injury was mainly characterized by inflammation pyogranulomatous, but in some areas there was a predominance of necrossupurativa inflammation, epithelioid macrophages and were frequently observed, forming clusters radiated form, often reminding rosettes. In the histochemical techniques were observed filamentous structures, branched, non-septate, measuring approximately 1µm thick, impregnated on silver staining, stained in red on the modified Ziehl-Neelsen, in blue on Gram stain type modified Brown-Brenn and weakly pale pink in Giemsa. The nocardiosis should be considered in young animals with progressive respiratory and neurological signs, as well as skin lesions involving the subcutaneous tissue and regional lymph nodes. It should be further investigated a possible predisposing factor, such as infection by canine distemper virus and hemoparasites. The diagnosis was established by histopathological examination based on the morphology of the bacteria and their histochemical characteristics, distinguishing mainly from other bacterial and fungal agents and is an important tool for the diagnosis, when the collection of material for cultivation and isolation of the agent is not possible.(AU)

Opportunistic Invasive Cutaneous Fungal Infections Associated with Administration of Cyclosporine to Dogs with Immune-mediated Disease.

BACKGROUND: Opportunistic invasive fungal infections (OIFIs) occur in dogs administered immunosuppressive medications. However, the epidemiology of OIFIs among dogs undergoing immunosuppressive treatment is poorly understood. The aims of this study were to (1) estimate the incidence of OIFIs among dogs diagnosed with certain immune-mediated diseases and treated with immunosuppressive drugs, and (2) determine if administration of particular drug(s) was a risk factor for OIFIs. HYPOTHESIS: Dogs receiving cyclosporine treatment (alone or as part of a multidrug protocol) are at higher risk of developing OIFIs. ANIMALS: One hundred and thirteen client-owned dogs diagnosed with select immune-mediated diseases: 42 with IMHA, 29 with ITP, 34 with IMPA, and 8 with Evans syndrome. METHODS: Retrospective cohort study. Medical records of dogs presenting to the Texas A&M University, Veterinary Medical Teaching Hospital between January 2008 and December 2015, and treated for 1 or more of IMHA, IMPA, ITP, or Evans syndrome were retrospectively reviewed. Dogs that did not develop an OIFI were excluded if they died, were euthanized, or were lost to follow-up within 120 days of initiation of immunosuppressive treatment. RESULTS: Fifteen dogs of 113 (13%) were diagnosed with an OIFI based on 1 or more of cytology, culture, or histopathology. The odds of developing an OIFI were greater among dogs that were treated with cyclosporine (OR = 7.1, P = 0.017; 95% CI, 1.5-34.4) and among male dogs (OR = 5.1, P = 0.018; 95% CI, 1.4-17.9). CONCLUSIONS AND CLINICAL IMPORTANCE: OIFIs were significantly more likely in male dogs and those receiving cyclosporine. It is important to consider OIFIs as a potential complication of immunosuppressive treatment, particularly cyclosporine.

Characterization of Demodex musculi Infestation, Associated Comorbidities, and Topographic Distribution in a Mouse Strain with Defective Adaptive Immunity.

A colony of B6.Cg-Rag1tm1Mom Tyrp1B-w Tg(Tcra,Tcrb)9Rest (TRP1/TCR) mice presented with ocular lesions and ulcerative dermatitis. Histopathology, skin scrapes, and fur plucks confirmed the presence of Demodex spp. in all clinically affected and subclinical TRP1/TCR mice examined (n = 48). Pasteurella pneumotropica and Corynebacterium bovis, both opportunistic pathogens, were cultured from the ocular lesions and skin, respectively, and bacteria were observed microscopically in abscesses at various anatomic locations (including retroorbital sites, tympanic bullae, lymph nodes, and reproductive organs) as well as the affected epidermis. The mites were identified as Demodex musculi using the skin fragment digestion technique. Topographic analysis of the skin revealed mites in almost all areas of densely haired skin, indicating a generalized demodecosis. The percentage of infested follicles in 8- to 10-wk-old mice ranged from 0% to 21%, and the number of mites per millimeter of skin ranged from 0 to 3.7. The head, interscapular region, and middorsum had the highest proportions of infested follicles, ranging from 2.3% to 21.1% (median, 4.9%), 2.0% to 16.6% (8.1%), and 0% to 17% (7.6%), respectively. The pinnae and tail skin had few or no mites, with the proportion of follicles infested ranging from 0% to 3.3% (0%) and 0% to 1.4% (0%), respectively. The number of mites per millimeter was strongly correlated with the percentage of infested follicles. After administration of amoxicillin-impregnated feed (0.12%), suppurative infections were eliminated, and the incidence of ulcerative dermatitis was dramatically reduced. We hypothesize that the Rag1-null component of the genotype makes TRP1/TCR mice susceptible to various opportunistic infestations and infections, including Demodex mites, P. pneumotropica, and C. bovis. Therefore, Rag1-null mice may serve as a useful model to study human and canine demodecosis. D. musculi should be ruled out as a contributing factor in immunocompromised mouse strains with dermatologic manifestations.

Severe Dermatitis Associated with Spontaneous Staphylococcus xylosus Infection in Rag-/-Tpl2-/- Mice.

Staphylococcus xylosus is a commensal bacterium found on the skin and mucosal surfaces of SPF mice. S. xylosus is rarely pathogenic, most often causing skin lesions and dermatitis in immunocompromised mice, particularly those with impaired NADPH oxidase function. Here we report spontaneous infection with S. xylosus in Rag1-/-Tpl2-/- mice. Infection was characterized by the presence of alopecia, crusts, and scaly skin. S. xylosus was detected in the feces, skin, lymph nodes, and lungs of Rag1-/-Tpl2-/- mice and led to mortality or euthanasia due to humane endpoints. C57BL/6 mice were culture-positive for S. xylosus on the skin, and Rag1-/- and Tpl2-/- mice were culture-positive on the skin and occasionally in the feces. However, S. xylosus did not cause clinical symptoms in C57BL/6, Rag1-/-, or Tpl2-/- mice. Compared with those in Rag1-/- mice, relative concentrations of circulating monocytes, but not neutrophils or lymphocytes, were increased in Rag1-/-Tpl2-/- mice, consistent with their increased incidence of clinical symptoms. Overall, this case study suggests a novel role for Tpl2 in T-cell-independent host resistance to the otherwise commensal organism S. xylosus.