ABSTRACT
BACKGROUND: In humans, scleromyxoedema is a chronic progressive skin condition traditionally characterized by deposits of mucin, increased number of fibroblasts and fibrosis in the skin, and by systemic disease. Thyroid disease is typically absent. A monoclonal gammopathy is usually present, as are other comorbidities. Descriptions of scleromyxoedema in the veterinary literature are limited to a single feline case. One dog, previously reported as having papular mucinosis, exhibited features that matched the more current diagnostic criteria of scleromyxoedema. OBJECTIVES: To describe generalized papular mucinosis in a dog with systemic illness and to compare the signs with those of human lichen myxoedematosus conditions, specifically scleromyxoedema. RESULTS: A nine-year-old female, spayed English springer spaniel dog presented with generalized papules and nodules (0.5-5 cm) on the body and proximal fore and hind limbs, sparing the face and distal limbs distal to carpi/tarsi. Larger nodules were erythematous. Nodules occurred in proximal limb muscles. The dog had concurrent osteoarthritis of the elbows and coxofemoral joints, developed generalized weakness, declined in health and was euthanized. Thyroid disease was lacking and a monoclonal gammopathy was not present. Histopathological evaluation revealed the classic triad of mucin, fibroblast proliferation and fibrosis with very mild inflammation, as described for humans. CONCLUSION AND CLINICAL IMPORTANCE: We document scleromyxoedema in a dog with significant morbidity and features of the human disease. Recognizing the typical histopathology is important for identifying cases and to establish a diagnosis. Systemic evaluation is important to identify evidence of internal disease and associated comorbidities, which are common, variable, and impact classification and prognosis in humans.
Subject(s)
Dog Diseases/diagnosis , Scleromyxedema/veterinary , Skin Diseases/veterinary , Animals , Dog Diseases/pathology , Dogs , Female , Scleromyxedema/diagnosis , Scleromyxedema/pathology , Skin/pathology , Skin Diseases/diagnosis , Skin Diseases/pathologyABSTRACT
To describe the diagnosis and successful treatment of systemic francisellosis in a dog. An 11-year-old female spayed Labrador retriever presented for progressive lethargy, hyporexia, and cough. The dog was febrile with a neutrophilia, nonregenerative anemia, thrombocytopenia, and had increased activity in serum of liver-derived enzymes. Francisella philomiragia was isolated from aerobic blood culture. The dog was treated for 6 weeks with enrofloxacin orally. Repeated aerobic blood cultures after 2 and 6 weeks of antibiotic therapy were negative. The dog was clinically normal 7 months after diagnosis with no evidence of relapse.
Subject(s)
Anti-Bacterial Agents , Bacteremia , Dog Diseases , Enrofloxacin , Francisella , Gram-Negative Bacterial Infections , Animals , Dogs , Female , Dog Diseases/drug therapy , Dog Diseases/microbiology , Enrofloxacin/therapeutic use , Anti-Bacterial Agents/therapeutic use , Bacteremia/veterinary , Bacteremia/drug therapy , Bacteremia/microbiology , Gram-Negative Bacterial Infections/veterinary , Gram-Negative Bacterial Infections/drug therapy , Gram-Negative Bacterial Infections/microbiologyABSTRACT
BACKGROUND: Feline-associated hemotropic Mycoplasma (hemoplasmas) are believed to be transmitted by two primary mechanisms: (1) direct transmission via fighting and (2) vector-borne transmission by the cat flea (Ctenocephalides felis). While the efficiency of transmission by C. felis appears low, most manuscripts focus on the prevalence of hemoplasmas in wild-caught fleas and report either a very low (< 3%) or a high (> 26%) prevalence. Therefore, we aimed to assess the influence of sample processing and PCR methods on C. felis hemoplasma infection prevalence. METHODS: A systemic review of PubMed articles identified 13 manuscripts (1,531 fleas/flea pools) that met the inclusion criteria (performed PCR for >1 hemoplasma on C. felis collected from cats). Risk of bias was assessed utilizing the ROBINS-E tool. Meta-analysis performed in R of these manuscripts found that not washing samples and a common set of 16S rRNA primers first published in Jensen et al. 2001 were associated with increased hemoplasma prevalence. To evaluate the influence of washing on newly collected fleas, we assessed the hemoplasma status of 20 pools of 5 C. felis each, half of which were washed and half not washed. RESULTS: Flea washing did not influence the detection of hemoplasma but instead amplified Spiroplasma. To assess non-specific amplification with the Jensen et al. 2001 primers, 67 C. felis samples (34% previously reported hemoplasma infected) were subject to PCR and sequencing. By this method, hemoplasma was detected in only 3% of samples. In the remaining "hemoplasma infected" fleas, PCR amplified Spiroplasma or other bacteria. CONCLUSIONS: Therefore, we concluded that hemoplasma infection in C. felis is rare, and future flea prevalence studies should sequence all positive amplicons to validate PCR specificity. Further investigation of alternative methods of feline-associated hemoplasma transmission and the ability of C. felis to maintain hemoplasma infection is necessary.
Subject(s)
Cat Diseases , Ctenocephalides , Mycoplasma Infections , Mycoplasma , Animals , Mycoplasma/isolation & purification , Mycoplasma/genetics , Mycoplasma/classification , Ctenocephalides/microbiology , Cats , Cat Diseases/parasitology , Cat Diseases/microbiology , Cat Diseases/diagnosis , Cat Diseases/transmission , Cat Diseases/epidemiology , Mycoplasma Infections/veterinary , Mycoplasma Infections/diagnosis , Mycoplasma Infections/epidemiology , Mycoplasma Infections/transmission , Mycoplasma Infections/microbiology , Flea Infestations/veterinary , Flea Infestations/parasitology , Flea Infestations/epidemiology , Polymerase Chain Reaction , Prevalence , RNA, Ribosomal, 16S/geneticsABSTRACT
An 11-year-old female spayed German Wirehaired Pointer with a 1-week history of lethargy, hyporexia, diarrhea, and coughing presented with pericardial effusion causing cardiac tamponade. An echocardiogram revealed no structural cause for pericardial effusion. The pericardial effusion was an exudate with mixed macrophagic and neutrophilic inflammation. Morulae occasionally were found within neutrophils. The pericardial fluid and blood were qPCR and cPCR positive for Anaplasma phagocytophilum (NC State University, Vector-borne Disease Diagnostic Laboratory, Raleigh, NC). The dog's blood was negative by ELISA (Vetscan Flex4 Rapid Test, Zoetis, Parsippany, NJ) for A. phagocytophilum antibodies at initial presentation and subsequently positive (SNAP4DxPlus, IDEXX, Westbrook, ME) 7 days later. After pericardiocentesis and administration of doxycycline (5 mg/kg PO q12h for 14 days), a repeat echocardiogram performed 1 month later showed no recurrence of pericardial effusion.
Subject(s)
Anaplasma phagocytophilum , Dog Diseases , Doxycycline , Ehrlichiosis , Pericardial Effusion , Animals , Female , Pericardial Effusion/veterinary , Pericardial Effusion/microbiology , Dog Diseases/diagnosis , Dog Diseases/microbiology , Anaplasma phagocytophilum/isolation & purification , Dogs , Ehrlichiosis/veterinary , Ehrlichiosis/complications , Ehrlichiosis/diagnosis , Doxycycline/therapeutic use , Anti-Bacterial Agents/therapeutic use , Echocardiography/veterinary , Pericardiocentesis/veterinaryABSTRACT
Vector-borne infections may underlie some rheumatic diseases, particularly in people with joint effusions. This study aimed to compare serum and synovial fluid antibodies to B. burgdorferi and Bartonella spp. in patients with rheumatic diseases. This observational, cross-sectional study examined paired synovial fluid and serum specimens collected from 110 patients with joint effusion between October 2017 and January 2022. Testing for antibodies to B. burgdorferi (using CDC criteria) and Bartonella spp. via two indirect fluorescent antibody (IFA) assays was performed as part of routine patient care at the Institute for Specialized Medicine (San Diego, CA, USA). There were 30 participants (27%) with positive two-tier B. burgdorferi serology and 26 participants (24%) with IFA seroreactivity (≥1:256) to B. henselae and/or B. quintana. Both B. burgdorferi IgM and IgG were detected more frequently in synovial fluid than serum: 27% of patients were either IgM or IgG positive in synovial fluid, compared to 15.5% in serum (P = 0.048). Conversely, B. henselae and B. quintana antibodies were detected more frequently in serum than synovial fluid; overall only 2% of patients had positive IFA titers in synovial fluid, compared to 24% who had positive IFA titers in serum (P < 0.001). There were no significant associations between B. burgdorferi or Bartonella spp. seroreactivity with any of the clinical rheumatological diagnoses. This study provides preliminary support for the importance of synovial fluid antibody testing for documenting exposure to B. burgdorferi but not for documenting exposure to Bartonella spp. IMPORTANCE: This study focuses on diagnostic testing for two common vector-borne diseases in an affected patient population. In it, we provide data showing that antibodies to B. burgdorferi, but not Bartonella spp., are more commonly found in synovial fluid than serum of patients with joint effusion. Since Lyme arthritis is a common-and sometimes difficult to diagnose-rheumatic disease, improving diagnostic capabilities is of utmost importance. While our findings are certainly not definitive for changes to practice, they do suggest that synovial fluid could be a useful sample for the clinical diagnosis of Lyme disease, and future prospective studies evaluating this claim are warranted.
Subject(s)
Bartonella , Borrelia burgdorferi , Lyme Disease , Rheumatic Diseases , Humans , Antibodies, Bacterial , Cross-Sectional Studies , Immunoglobulin G , Immunoglobulin M , Lyme Disease/diagnosis , Synovial FluidABSTRACT
Introduction: The potential role of pathogens, particularly vector-transmitted infectious agents, as a cause of psychosis has not been intensively investigated. We have reported a potential link between Bartonella spp. bacteremia and neuropsychiatric symptoms, including pediatric acute onset neuropsychiatric syndrome and schizophrenia. The purpose of this study was to further assess whether Bartonella spp. exposure or infection are associated with psychosis. Methods: In a blinded manner, we assessed the presence of anti-Bartonella antibodies by indirect immunofluorescence assays (IFA), and infection by amplification of bacterial DNA from blood by quantitative polymerase chain reaction (qPCR), digital PCR (dPCR), and droplet digital PCR (ddPCR) in 116 participants. Participants were categorized into one of five groups: 1) controls unaffected by psychosis (n = 29); 2) prodromal participants (n = 16); 3) children or adolescents with psychosis (n = 7); 4) adults with psychosis (n = 44); and 5) relatives of a participant with psychosis (n = 20). Results: There was no significant difference in Bartonella spp. IFA seroreactivity between adults with psychosis and adult controls unaffected by psychosis. There was a higher proportion of adults with psychosis who had Bartonella spp. DNA in the bloodstream (43.2%) compared to adult controls unaffected by psychosis (14.3%, p = 0.021). The Bartonella species was determined for 18 of the 31 bacteremic participants, including infection or co-infection with Bartonella henselae (11/18), Bartonella vinsonii subsp. berkhoffii (6/18), Bartonella quintana (2/18), Bartonella alsatica (1/18), and Bartonella rochalimae (1/18). Discussion: In conjunction with other recent research, the results of this study provide justification for a large national or international multi-center study to determine if Bartonella spp. bacteremia is more prevalent in adults with psychosis compared to adults unaffected by psychosis. Expanding the investigation to include a range of vector-borne and other microbial infections with potential CNS effects would enhance knowledge on the relationship between psychosis and infection.
ABSTRACT
Immune thrombocytopenia (ITP) is the most common acquired primary hemostatic disorder in dogs. Immune thrombocytopenia less commonly affects cats but is an important cause of mortality and treatment-associated morbidity in both species. Immune thrombocytopenia remains a diagnosis of exclusion for which diagnostic guidelines are lacking. Primary, or non-associative, ITP refers to autoimmune platelet destruction. Secondary, or associative, ITP arises in response to an underlying disease trigger. However, evidence for which comorbidities serve as ITP triggers has not been systematically evaluated. To identify key diagnostic steps for ITP and important comorbidities associated with secondary ITP, we developed 12 Population Evaluation/Exposure Comparison Outcome (PECO) format questions. These questions were addressed by evidence evaluators utilizing a literature pool of 287 articles identified by the panelists using a structured search strategy. Evidence evaluators, using panel-designed templates and data extraction tools, summarized evidence and created guideline recommendations that then were integrated by diagnosis and comorbidity domain chairs. The revised PECO responses underwent a Delphi survey process to reach consensus on final guidelines. A combination of panel expertise and PECO responses were employed to develop algorithms for diagnosis of ITP in dogs and cats, which also underwent 4 iterations of Delphi review. Comorbidity evidence evaluators employed an integrated measure of evidence (IME) tool to determine evidence quality for each comorbidity; IME values combined with evidence summaries for each comorbidity were integrated to develop ITP screening recommendations, which also were subjected to Delphi review. Commentary was solicited from multiple relevant professional organizations before finalizing the consensus. The final consensus statement provides clinical guidelines for the diagnosis of, and underlying disease screening for, ITP in dogs and cats. The systematic consensus process identified numerous knowledge gaps that should guide future studies. This statement is a companion manuscript to the ACVIM Consensus Statement on the Treatment of Immune Thrombocytopenia.
Subject(s)
Cat Diseases , Dog Diseases , Purpura, Thrombocytopenic, Idiopathic , Dogs , Animals , Cats , Dog Diseases/diagnosis , Cat Diseases/diagnosis , Purpura, Thrombocytopenic, Idiopathic/veterinary , Purpura, Thrombocytopenic, Idiopathic/diagnosis , ConsensusABSTRACT
Recirculation of fluid and cells through lymphatic vessels plays a key role in normal tissue homeostasis, inflammatory diseases, and cancer. Despite recent advances in understanding lymphatic function (Alitalo, K., T. Tammela, and T.V. Petrova. 2005. Nature. 438:946-953), the cellular features responsible for entry of fluid and cells into lymphatics are incompletely understood. We report the presence of novel junctions between endothelial cells of initial lymphatics at likely sites of fluid entry. Overlapping flaps at borders of oak leaf-shaped endothelial cells of initial lymphatics lacked junctions at the tip but were anchored on the sides by discontinuous button-like junctions (buttons) that differed from conventional, continuous, zipper-like junctions (zippers) in collecting lymphatics and blood vessels. However, both buttons and zippers were composed of vascular endothelial cadherin (VE-cadherin) and tight junction-associated proteins, including occludin, claudin-5, zonula occludens-1, junctional adhesion molecule-A, and endothelial cell-selective adhesion molecule. In C57BL/6 mice, VE-cadherin was required for maintenance of junctional integrity, but platelet/endothelial cell adhesion molecule-1 was not. Growing tips of lymphatic sprouts had zippers, not buttons, suggesting that buttons are specialized junctions rather than immature ones. Our findings suggest that fluid enters throughout initial lymphatics via openings between buttons, which open and close without disrupting junctional integrity, but most leukocytes enter the proximal half of initial lymphatics.
Subject(s)
Endothelial Cells/cytology , Endothelial Cells/immunology , Lymphatic Vessels/cytology , Lymphatic Vessels/immunology , Animals , Cadherins/metabolism , Cell Movement , Endothelial Cells/metabolism , Lymphatic Vessels/metabolism , Lymphocytes/cytology , Lymphocytes/immunology , Mice , Mice, Inbred C57BL , Platelet Endothelial Cell Adhesion Molecule-1/genetics , Platelet Endothelial Cell Adhesion Molecule-1/metabolismABSTRACT
Bacteria of the genus Bartonella, a member of the Alphaproteobacteria, are fastidious, Gram-negative, aerobic bacilli that comprise numerous species, subspecies, and genotypes. Bartonella henselae, with a worldwide distribution, infects cats, dogs, horses, humans, and other mammals. Diagnostically, direct detection of Bartonella henselae in patient blood specimens by culture or molecular methods is required to confirm infection with this bacterium. Enrichment blood culture combined with quantitative PCR (qPCR) or ddPCR enhances the sensitivity of direct detection. The addition of sheep blood to liquid culture media increased the Bartonella henselae DNA concentration compared to controls, additionally improving PCR direct detection sensitivity. IMPORTANCE This study aims to improve diagnostic detection of Bartonella henselae. Patient samples are combined with enriched bacterial cultures aimed at growing Bartonella henselae for the best possible chance at detection. However, current Bartonella growth methods could be improved. The DNA extraction method used by most laboratories should also be optimized. Sheep blood was added to increase the growth of Bartonella henselae and multiple DNA extraction methods were to be compared to each other.
Subject(s)
Bartonella Infections , Bartonella henselae , Bartonella , Humans , Animals , Horses/genetics , Dogs , Sheep , Bartonella henselae/genetics , DNA, Bacterial/genetics , DNA, Bacterial/analysis , Bartonella Infections/diagnosis , Bartonella Infections/microbiology , Bartonella Infections/veterinary , Bartonella/genetics , Dietary Supplements , MammalsABSTRACT
Surveillance of the fleas and flea-borne pathogens infecting cats is important for both human and animal health. Multiple zoonotic Bartonella and Rickettsia species are known to infect the most common flea infesting cats and dogs worldwide: Ctenocephalides felis, the cat flea. The ability of other flea species to transmit pathogens is relatively unexplored. We aimed to determine cat host and flea factors independently associated with flea Bartonella and Rickettsia infection. We also assessed flea and cat infection by flea-host pair and location. To accomplish these aims, we performed qPCR for the detection of Bartonella, hemotropic Mycoplasma, Rickettsia, and Wolbachia DNA using paired cat and flea samples obtained from free-roaming cats presenting for spay or neuter across four locations in the United States. A logistic regression model was employed to identify the effect of cat (sex, body weight, geographic location, and Bartonella, hemotropic Mycoplasma, and Rickettsia spp., infection) and flea (clade and Rickettsia and Wolbachia infection) factors on C. felis Bartonella clarridgeiae infection. From 189 free roaming cats, we collected 84 fleas: Ctenocephalides felis (78/84), Cediopsylla simplex (4/84), Orchopeas howardi (1/84), and Nosopsyllus fasciatus (1/84). Ctenocephalides felis were phylogenetically assigned to Clades 1, 4, and 6 by cox1 gene amplification. Rickettsia asembonensis (52/84) and B. clarridgeiae (16/84) were the most common pathogenic bacteria detected in fleas. Our model identified host cat sex and weight as independently associated with B. clarridgeiae infection in fleas. Rickettsia asembonensis (52/84), Rickettsia felis (7/84) and Bartonella henselae (7/84) were detected in specific clades: R. felis was detected only in Clades 1 and 6 while B. henselae and R. asembonensis were detected only in Clade 4. Wolbachia spp., also displayed clade specificity with strains other than Wolbachia wCfeT only infecting fleas from Clade 6. There was poor flea and host agreement for Bartonella spp., infection; however, there was agreement in the Bartonella species detected in cats and fleas by geographic location. These findings reinforce the importance of considering reservoir host attributes and vector phylogenetic diversity in epidemiological studies of flea-borne pathogens. Widespread sampling is necessary to identify the factors driving flea-borne pathogen presence and transmission.
ABSTRACT
The effect of Bartonella henselae on the microbiome of its vector, Ctenocephalides felis (the cat flea) is largely unknown, as the majority of C. felis microbiome studies have utilized wild-caught pooled fleas. We surveyed the microbiome of laboratory-origin C. felis fed on B. henselae-infected cats for 24 h or 9 days to identify changes to microbiome diversity and microbe prevalence compared to unfed fleas, and fleas fed on uninfected cats. Utilizing Next Generation Sequencing (NGS) on the Illumina platform, we documented an increase in microbial diversity in C. felis fed on Bartonella-infected cats for 24 h. These changes returned to baseline (unfed fleas or fleas fed on uninfected cats) after 9 days on the host. Increased diversity in the C. felis microbiome when fed on B. henselae-infected cats may be related to the mammalian, flea, or endosymbiont response. Poor B. henselae acquisition was documented with only one of four infected flea pools having B. henselae detected by NGS. We hypothesize this is due to the use of adult fleas, flea genetic variation, or lack of co-feeding with B. henselae-infected fleas. Future studies are necessary to fully characterize the effect of endosymbionts and C. felis diversity on B. henselae acquisition.
ABSTRACT
We collected oral and/or rectal swabs and serum from dogs and cats living in homes with SARS-CoV-2-PCR-positive persons for SARS-CoV-2 PCR and serology testing. Pre-COVID-19 serum samples from dogs and cats were used as negative controls, and samples were tested in duplicate at different timepoints. Raw ELISA results scrutinized relative to known negative samples suggested that cut-offs for IgG seropositivity may require adjustment relative to previously proposed values, while proposed cut-offs for IgM require more extensive validation. A small number of pet dogs (2/43, 4.7%) and one cat (1/21, 4.8%) were positive for SARS-CoV-2 RNA, and 28.6 and 37.5% of cats and dogs were positive for anti-SARS-CoV-2 IgG, respectively.
Subject(s)
COVID-19 , Cat Diseases , Dog Diseases , Animals , Cats , Dogs , SARS-CoV-2/genetics , COVID-19/diagnosis , Pets , North Carolina/epidemiology , RNA, Viral/genetics , Dog Diseases/diagnosis , Immunoglobulin GABSTRACT
Blood vessel leakiness is an early, transient event in acute inflammation but can also persist as vessels undergo remodeling in sustained inflammation. Angiopoietin/Tie2 signaling can reduce the leakiness through changes in endothelial cells. The role of pericytes in this action has been unknown. We used the selective PDGF-B-blocking oligonucleotide aptamer AX102 to determine whether disruption of pericyte-endothelial crosstalk alters vascular leakiness or remodeling in the airways of mice under four different conditions: i) baseline, ii) acute inflammation induced by bradykinin, iii) sustained inflammation after 7-day infection by the respiratory pathogen Mycoplasma pulmonis, or iv) leakage after bradykinin challenge in the presence of vascular stabilization by the angiopoietin-1 (Ang1) mimic COMP-Ang1 for 7 days. AX102 reduced pericyte coverage but did not alter the leakage of microspheres from tracheal blood vessels at baseline or after bradykinin; however, AX102 exaggerated leakage at 7 days after M. pulmonis infection and increased vascular remodeling and disease severity at 14 days. AX102 also abolished the antileakage effect of COMP-Ang1 at 7 days. Together, these findings show that pericyte contributions to endothelial stability have greater dependence on PDGF-B during the development of sustained inflammation, when pericyte dynamics accompany vascular remodeling, than under baseline conditions or in acute inflammation. The findings also show that the antileakage action of Ang1 requires PDGF-dependent actions of pericytes in maintaining endothelial stability.
Subject(s)
Angiopoietin-1/metabolism , Inflammation/pathology , Pericytes/pathology , Trachea/blood supply , Trachea/pathology , Actins/metabolism , Animals , Aptamers, Nucleotide/pharmacology , Bradykinin/pharmacology , Cell Count , Cell Shape/drug effects , Desmin/metabolism , Inflammation/complications , Mice , Mice, Inbred C57BL , Microspheres , Mycoplasma Infections/complications , Mycoplasma Infections/pathology , Mycoplasma pulmonis/drug effects , Mycoplasma pulmonis/physiology , Pericytes/drug effects , Pericytes/microbiology , Proto-Oncogene Proteins c-sis/antagonists & inhibitors , Proto-Oncogene Proteins c-sis/metabolism , Receptor, Platelet-Derived Growth Factor beta/metabolism , Recombinant Fusion Proteins/pharmacology , Trachea/microbiologyABSTRACT
Bartonella spp. comprise a genus of Gram-negative alphaproteobacteria that are slow growing, fastidious, and facultative intracellular pathogens with zoonotic potential. Immunofluorescent antibody assays (IFAs), Western blot (WB), and enzyme-linked immunosorbent assays (ELISAs), the frequently used modalities for the serological diagnosis of canine and human Bartonelloses, generate numerous false negative results. Therefore, the development of a reliable serodiagnostic assay for Bartonelloses is of clinical and epidemiological importance. Pap31, a heme binding surface protein of B. henselae, is associated with bacterial adhesion and related to bacterial colonization. To our knowledge, B. henselae Pap31 and its fragments (N-terminal (NTD), middle (MD), and C-terminal (CTD) domains) have not been investigated for the serodiagnosis of canine and human Bartonelloses. In this study, we evaluate the diagnostic utility of B. henselae recombinant whole Pap31 (rPap31) and Pap31 fragments by ELISA using sera from 70 dogs (36 Bartonella spp. IFA-positive (naturally infected), and 34 Bartonella spp. IFA- and PCR-negative (control dogs)) and 36 humans (18 Bartonella spp. IFA-positive (naturally infected) and 18 controls)). In the dogs, the area under the curve (AUC) score of recombinant whole Pap31 was 0.714 with a sensitivity of 42% and specificity of 94% at an OD cutoff value of 0.8955. Among the evaluated recombinant Pap31 proteins for the diagnosis of canine Bartonelloses, rPap31-NTD yielded the highest AUC score of 0.792 (95% CI 0.688-0.895) with a sensitivity of 44% and specificity of 100% at a cutoff value of 1.198. In concordance with this finding, rPap31-NTD also had the highest AUC score of 0.747 (95% CI 0.581-0.913) among the Pap31 recombinant proteins for the diagnosis of human Bartonelloses, with 39% sensitivity and 94% specificity at a cutoff value of 1.366. Recombinant whole Pap31 (rPap31) resulted in 72% sensitivity and 61% specificity at a cutoff value of 0.215 for human Bartonelloses. Due to either low sensitivity or questionable specificity, our findings indicate that recombinant Pap31 and the selected fragments may not be appropriate diagnostic targets in detecting anti-Bartonella antibodies in Bartonella-infected dogs and humans. The findings from this study can be used to further assess the antigenicity and immunogenicity of B. henselae Pap31 as a diagnostic target.
ABSTRACT
The unique virulence factors of Bartonella spp make them stealth pathogens that evade the immune system and cause persistent infections that are often difficult to diagnose and treat. Understanding these pathogenic mechanisms allows clinicians to recognize when to pursue diagnostics, how to optimize diagnostic testing and treatment, and ultimately can lead to improved outcomes.
Subject(s)
Bartonella Infections , Cat Diseases , Dog Diseases , Animals , Cats , Dogs , Bartonella , Bartonella Infections/diagnosis , Bartonella Infections/veterinary , Cat Diseases/diagnosis , Cat Diseases/therapy , Dog Diseases/diagnosis , Dog Diseases/therapyABSTRACT
BACKGROUND: Ctenocephalides felis, the cat flea, is the most common ectoparasite of cats and dogs worldwide. As a cause of flea allergy dermatitis and a vector for two genera of zoonotic pathogens (Bartonella and Rickettsia spp.), the effect of the C. felis microbiome on pathogen transmission and vector survival is of substantial medical importance to both human and veterinary medicine. The aim of this study was to assay the pathogenic and commensal eubacterial microbial communities of individual C. felis from multiple geographic locations and analyze these findings by location, qPCR pathogen prevalence, and flea genetic diversity. METHODS: 16S Next Generation Sequencing (NGS) was utilized to sequence the microbiome of fleas collected from free-roaming cats, and the cox1 gene was used for flea phylogenetic analysis. NGS data were analyzed for 168 individual fleas from seven locations within the US and UK. Given inconsistency in the genera historically reported to constitute the C. felis microbiome, we utilized the decontam prevalence method followed by literature review to separate contaminants from true microbiome members. RESULTS: NGS identified a single dominant and cosmopolitan amplicon sequence variant (ASV) from Rickettsia and Wolbachia while identifying one dominant Bartonella clarridgeiae and one dominant Bartonella henselae/Bartonella koehlerae ASV. Multiple less common ASVs from these genera were detected within restricted geographical ranges. Co-detection of two or more genera (Bartonella, Rickettsia, and/or Wolbachia) or multiple ASVs from a single genus in a single flea was common. Achromobacter, Peptoniphilus, and Rhodococcus were identified as additional candidate members of the C. felis microbiome on the basis of decontam analysis and literature review. Ctenocephalides felis phylogenetic diversity as assessed by the cox1 gene fell within currently characterized clades while identifying seven novel haplotypes. NGS sensitivity and specificity for Bartonella and Rickettsia spp. DNA detection were compared to targeted qPCR. CONCLUSIONS: Our findings confirm the widespread coinfection of fleas with multiple bacterial genera and strains, proposing three additional microbiome members. The presence of minor Bartonella, Rickettsia, and Wolbachia ASVs was found to vary by location and flea haplotype. These findings have important implications for flea-borne pathogen transmission and control.
Subject(s)
Bartonella , Coinfection , Ctenocephalides , Rickettsia , Animals , Cats , Bartonella/genetics , Cat Diseases/parasitology , Ctenocephalides/microbiology , Flea Infestations/epidemiology , Flea Infestations/veterinary , Phylogeny , Rickettsia/geneticsABSTRACT
BACKGROUND: Bone foreign bodies are commonly encountered in small animal practice. Esophageal bone foreign bodies (E-bFBs) warrant removal, whereas gastric bone foreign bodies might not. OBJECTIVES: Describe management and outcomes for dogs with esophageal or gastric bone foreign bodies. ANIMALS: One hundred twenty-nine dogs with esophageal (n = 45) or gastric (n = 84) bone foreign bodies. METHODS: Retrospective review of medical records. RESULTS: Dogs with E-bFBs were younger than dogs with gastric bone foreign bodies (median age esophageal, 4 years [IQR 2-8]; median age gastric, 6 years [IQR 3-10]; P = .03), and had a higher bone cross-sectional area relative to body weight (median esophageal, 98.21 mm2 /kg [IQR 48.25-142.6]; median gastric, 28.6 mm2 /kg [IQR 17.25-64.28]; P < .001). Forty-two of 45 esophageal foreign bodies were resolved non-surgically and 3 by esophagotomy. Esophageal erosions were more likely with distal entrapment (OR 12.88, [95% CI 31.95-129.29], P = .01) and longer duration (OR 18.82 [95% CI 2.22-273.97], P = .01). Sixty-two of 84 bone gastric foreign bodies were left in situ. Endoscopic removal was successful in 20 of 22 (91%; 95% CI 70-99) attempts. CONCLUSIONS AND CLINICAL IMPORTANCE: While all E-bFBs were dislodged either by advancement into the stomach, endoscopic removal, or esophagotomy, the majority of gastric bone foreign bodies were left in situ for dissolution, with no reported complications. Gastric advancement of E-bFBs should be considered when oral removal is not feasible, and dissolution can be considered even with large bones.
Subject(s)
Dog Diseases , Esophageal Diseases , Foreign Bodies , Animals , Dog Diseases/diagnostic imaging , Dog Diseases/surgery , Dogs , Endoscopy/veterinary , Esophageal Diseases/veterinary , Foreign Bodies/complications , Foreign Bodies/surgery , Foreign Bodies/veterinary , Retrospective Studies , StomachABSTRACT
BACKGROUND: Improved understanding of Bartonella spp. serology in dogs may aid clinical decision making. OBJECTIVE: Describe demographic and geographic patterns of Bartonella spp. seroreactivity in dogs, and describe hematologic and serum biochemical abnormalities in Bartonella spp. seroreactive and nonseroreactive dogs. ANIMALS: Serum samples from 5957 dogs in the United States, previously submitted to IDEXX Reference Laboratories. METHODS: Serum was tested using 3 indirect ELISAs for B. henselae, B. vinsonii subsp. berkhoffii, and B. koehlerae. Complete blood count and serum biochemistry panel results were reviewed retrospectively. RESULTS: Overall, 6.1% of dogs were Bartonella spp. seroreactive. Toy breeds were less likely to be seroreactive (3.9%) than mixed breeds (7.5%; adjusted odds ratio [aOR], 0.48; 95% confidence interval [CI], 0.32-0.72), and dogs <1 year old were less likely to be seroreactive (3.4%) than dogs 1 to 5.5 years of age (7.3%; aOR, 0.42; 95% CI, 0.23-0.72). Dogs in the West South Central (9.8%) and South Atlantic (8.8%) regions were more likely than dogs elsewhere in the United States to be seroreactive (aOR, 2.22; 95% CI, 1.31-3.87; aOR, 2.44; 95% CI, 1.38-4.36). CONCLUSIONS AND CLINICAL IMPORTANCE: Demographic and geographic findings for Bartonella spp. exposure were broadly comparable to previously reported patterns.
Subject(s)
Bartonella Infections , Bartonella , Dog Diseases , Animals , Bartonella Infections/epidemiology , Bartonella Infections/veterinary , Dog Diseases/epidemiology , Dogs , Retrospective Studies , Seroepidemiologic Studies , United States/epidemiologyABSTRACT
Vascular endothelial growth factor (VEGF) is a key angiogenic factor in tumors, but less is known about what drives vascular remodeling in inflammation, where plasma leakage and leukocyte influx are prominent features. In chronic airway inflammation in mice infected by the bacterium Mycoplasma pulmonis (M. pulmonis), the segment of the microvasculature that supports leukocyte adhesion and migration expands through remodeling of capillaries into vessels with features of venules. Here, we report that the angiopoietin/Tie2 pathway is an essential driving force for capillary remodeling into venules in M. pulmonis-infected mouse airways. Similar to M. pulmonis infection, systemic overexpression of angiopoietin-1 (Ang1) resulted in remodeling of airway capillaries into venular-like vessels that expressed venous markers like P-selectin, ICAM-1, and EphB4 and were sites of leukocyte adhesion during lipopolysaccharide-induced acute inflammation. Ang1 and Ang2 protein increased in M. pulmonis-infected mouse airways but came from different cellular sources: Ang1 was expressed in infiltrating neutrophils and Ang2 in endothelial cells. Indeed, systemic administration of soluble Tie2 inhibited capillary remodeling, induction of venous markers, and leukocyte influx in M. pulmonis-infected mouse airways. Together, these findings suggest that blockade of the Ang/Tie2 pathway may represent a therapeutic approach in airway inflammation.
Subject(s)
Angiopoietin-1/metabolism , Capillaries/metabolism , Inflammation , Leukocytes/cytology , Receptor, TIE-2/metabolism , Signal Transduction , Vascular Endothelial Growth Factor A/metabolism , Adenoviridae/metabolism , Animals , Biological Transport , Intercellular Adhesion Molecule-1/biosynthesis , Mice , Mice, Inbred C57BL , Mycoplasma pulmonis/metabolism , Venules/metabolismABSTRACT
Recent advances have documented the development of lung vasculature before and after birth, but less is known of the growth and maturation of airway vasculature. We sought to determine whether airway vasculature changes during the perinatal period and when the typical adult pattern develops. On embryonic day 16.5 mouse tracheas had a primitive vascular plexus unlike the adult airway vasculature, but instead resembling the yolk sac vasculature. Soon after birth (P0), the primitive vascular plexus underwent abrupt and extensive remodeling. Blood vessels overlying tracheal cartilage rings regressed from P1 to P3 but regrew from P4 to P7 to form the hierarchical, segmented, ladder-like adult pattern. Hypoxia and HIF-1α were present in tracheal epithelium over vessels that survived but not where they regressed. These findings reveal the plasticity of airway vasculature after birth and show that these vessels can be used to elucidate factors that promote postnatal vascular remodeling and maturation.