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1.
Med Mycol ; 62(1)2024 Jan 09.
Artículo en Inglés | MEDLINE | ID: mdl-38148116

RESUMEN

Coccidioidomycosis is a potentially fatal fungal disease of humans and animals that follows inhalation of Coccidioides spp. arthroconidia in the environment. The disease in dogs resembles that in people, and because dogs may be at increased risk of exposure due to their proximity to the ground and digging behavior, they are valuable models for the disease in humans. Dogs have been sentinels for identification of new regions of endemicity in Washington and Texas. Canine serosurveillance has also been used to predict variables associated with environmental presence of Coccidioides spp. Expansion of the endemic region of coccidioidomycosis with climate change-along with predicted population increases and increased development in the southwest United States-may result in 45.4 million additional people at risk of infection by 2090. Here we provide an overview of the value of dogs as sentinels for the disease and encourage the routine reporting of coccidioidomycosis cases in dogs to public health agencies. We also highlight the value of dogs as naturally occurring models for studying novel treatment options and preventatives, such as a novel live avirulent coccidioidomycosis vaccine.


Asunto(s)
Coccidioidomicosis , Enfermedades de los Perros , Animales , Perros , Coccidioides , Coccidioidomicosis/epidemiología , Coccidioidomicosis/veterinaria , Coccidioidomicosis/microbiología , Enfermedades de los Perros/epidemiología , Enfermedades de los Perros/microbiología , Modelos Animales , Sudoeste de Estados Unidos
2.
Med Mycol ; 62(1)2024 Jan 09.
Artículo en Inglés | MEDLINE | ID: mdl-38061838

RESUMEN

The incidence of coccidioidomycosis continues to increase. The diagnosis frequently relies on non-invasive diagnostic testing with immunodiffusion and complement fixation (CF) testing the current gold standard. A direct comparison of quantitative immunodiffusion and CF for IgG antibodies has not been previously reported. In a comparison of 368 samples, there was close concordance observed (360/368 = 97.8%) (P-value < .001). These tests can be considerably interchangeable in the reference laboratory setting.


There are several diagnostic methodologies available in coccidioidomycosis. Direct comparisons of these methods are limited. Prior studies have not compared quantitative immunodiffusion to complement fixation testing. Our results show these tests are highly concordant.


Asunto(s)
Coccidioides , Coccidioidomicosis , Animales , Pruebas de Fijación del Complemento/veterinaria , Anticuerpos Antifúngicos , Coccidioidomicosis/diagnóstico , Coccidioidomicosis/veterinaria , Inmunodifusión/veterinaria
3.
Med Mycol ; 61(11)2023 Nov 06.
Artículo en Inglés | MEDLINE | ID: mdl-37935009

RESUMEN

Coccidioidomycosis is a fungal disease in arid regions of the United States that is predicted to expand with climate change. Cases in military personnel and military working dogs (MWDs) impact personnel readiness and result in healthcare costs. To examine Coccidioides exposure among MWDs, 276 banked serum samples were retrieved from dogs housed in California, Texas, Arizona, New Mexico, Nevada, and Utah. Using gel immunodiffusion, six (2.1%) specimens were IgG-positive and three (1.1%) were equivocally IgM-positive. The IgG-positive samples were from Arizona (2 [prevalence 8.0%]) and California (4 [3.7%]). These data will guide future efforts to study MWDs as sentinels for human coccidioidomycosis.


This study aimed to determine the prevalence of exposure to coccidioidomycosis, the cause of Valley Fever in both humans and animals, among military working dogs (MWDs)located in endemic regions of the United States. The data will be used to guide efforts to study MWDs as sentinels for human disease.


Asunto(s)
Coccidioides , Coccidioidomicosis , Estados Unidos/epidemiología , Humanos , Animales , Perros , Coccidioidomicosis/epidemiología , Coccidioidomicosis/veterinaria , Coccidioidomicosis/microbiología , Perros de Trabajo , Arizona/epidemiología , Inmunoglobulina G
4.
J Cardiovasc Magn Reson ; 23(1): 88, 2021 07 15.
Artículo en Inglés | MEDLINE | ID: mdl-34261494

RESUMEN

BACKGROUND: Intramyocardial hemorrhage (IMH) within myocardial infarction (MI) is associated with major adverse cardiovascular events. Bright-blood T2*-based cardiovascular magnetic resonance (CMR) has emerged as the reference standard for non-invasive IMH detection. Despite this, the dark-blood T2*-based CMR is becoming interchangeably used with bright-blood T2*-weighted CMR in both clinical and preclinical settings for IMH detection. To date however, the relative merits of dark-blood T2*-weighted with respect to bright-blood T2*-weighted CMR for IMH characterization has not been studied. We investigated the diagnostic capacity of dark-blood T2*-weighted CMR against bright-blood T2*-weighted CMR for IMH characterization in clinical and preclinical settings. MATERIALS AND METHODS: Hemorrhagic MI patients (n = 20) and canines (n = 11) were imaged in the acute and chronic phases at 1.5 and 3 T with dark- and bright-blood T2*-weighted CMR. Imaging characteristics (Relative signal-to-noise (SNR), Relative contrast-to-noise (CNR), IMH Extent) and diagnostic performance (sensitivity, specificity, accuracy, area-under-the-curve, and inter-observer variability) of dark-blood T2*-weighted CMR for IMH characterization were assessed relative to bright-blood T2*-weighted CMR. RESULTS: At both clinical and preclinical settings, compared to bright-blood T2*-weighted CMR, dark-blood T2*-weighted images had significantly lower SNR, CNR and reduced IMH extent (all p < 0.05). Dark-blood T2*-weighted CMR also demonstrated weaker sensitivity, specificity, accuracy, and inter-observer variability compared to bright-blood T2*-weighted CMR (all p < 0.05). These observations were consistent across infarct age and imaging field strengths. CONCLUSION: While IMH can be visible on dark-blood T2*-weighted CMR, the overall conspicuity of IMH is significantly reduced compared to that observed in bright-blood T2*-weighted images, across infarct age in clinical and preclinical settings at 1.5 and 3 T. Hence, bright-blood T2*-weighted CMR would be preferable for clinical use since dark-blood T2*-weighted CMR carries the potential to misclassify hemorrhagic MIs as non-hemorrhagic MIs.


Asunto(s)
Hemorragia , Infarto del Miocardio , Animales , Perros , Hemorragia/diagnóstico por imagen , Hemorragia/etiología , Humanos , Imagen por Resonancia Magnética , Espectroscopía de Resonancia Magnética , Infarto del Miocardio/diagnóstico por imagen , Miocardio , Valor Predictivo de las Pruebas
5.
Radiology ; 295(1): 82-93, 2020 04.
Artículo en Inglés | MEDLINE | ID: mdl-32096705

RESUMEN

Background Despite advances, blood oxygen level-dependent (BOLD) cardiac MRI for myocardial perfusion is limited by inadequate spatial coverage, imaging speed, multiple breath holds, and imaging artifacts, particularly at 3.0 T. Purpose To develop and validate a robust, contrast agent-unenhanced, free-breathing three-dimensional (3D) cardiac MRI approach for reliably examining changes in myocardial perfusion between rest and adenosine stress. Materials and Methods A heart rate-independent, free-breathing 3D T2 mapping technique at 3.0 T that can be completed within the period of adenosine stress (≤4 minutes) was developed by using computer simulations, ex vivo heart preparations, and dogs. Studies in dogs were performed with and without coronary stenosis and validated with simultaneously acquired nitrogen 13 (13N) ammonia PET perfusion in a clinical PET/MRI system. The MRI approach was also prospectively evaluated in healthy human volunteers (from January 2017 to September 2017). Myocardial BOLD responses (MBRs) between normal and ischemic myocardium were compared with mixed model analysis. Results Dogs (n = 10; weight range, 20-25 kg; mongrel dogs) and healthy human volunteers (n = 10; age range, 22-53 years; seven men) were evaluated. In healthy dogs, T2 MRI at adenosine stress was greater than at rest (mean rest vs stress, 38.7 msec ± 2.5 [standard deviation] vs 45.4 msec ± 3.3, respectively; MBR, 1.19 ± 0.08; both, P < .001). At the same conditions, mean rest versus stress PET perfusion was 1.1 mL/mg/min ± 0.11 versus 2.3 mL/mg/min ± 0.82, respectively (P < .001); myocardial perfusion reserve (MPR) was 2.4 ± 0.82 (P < .001). The BOLD response and PET MPR were positively correlated (R = 0.67; P < .001). In dogs with coronary stenosis, perfusion anomalies were detected on the basis of MBR (normal vs ischemic, 1.09 ± 0.05 vs 1.00 ± 0.04, respectively; P < .001) and MPR (normal vs ischemic, 2.7 ± 0.08 vs 1.7 ± 1.1, respectively; P < .001). Human volunteers showed increased myocardial T2 at stress (rest vs stress, 44.5 msec ± 2.6 vs 49.0 msec ± 5.5, respectively; P = .004; MBR, 1.1 msec ± 8.08). Conclusion This three-dimensional cardiac blood oxygen level-dependent (BOLD) MRI approach overcame key limitations associated with conventional cardiac BOLD MRI by enabling whole-heart coverage within the standard duration of adenosine infusion, and increased the magnitude and reliability of BOLD contrast, which may be performed without requiring breath holds. © RSNA, 2020 Online supplemental material is available for this article. See also the editorial by Almeida in this issue.


Asunto(s)
Técnicas de Imagen Cardíaca/métodos , Frecuencia Cardíaca , Corazón/diagnóstico por imagen , Imagenología Tridimensional , Imagen por Resonancia Magnética/métodos , Oxígeno/sangre , Tomografía de Emisión de Positrones , Adenosina , Adulto , Amoníaco , Animales , Medios de Contraste , Estenosis Coronaria/diagnóstico por imagen , Estenosis Coronaria/fisiopatología , Perros , Prueba de Esfuerzo , Femenino , Humanos , Masculino , Persona de Mediana Edad , Miocardio , Radioisótopos de Nitrógeno , Tomografía de Emisión de Positrones/métodos , Estudios Prospectivos , Adulto Joven
6.
Am J Physiol Heart Circ Physiol ; 316(3): H586-H595, 2019 03 01.
Artículo en Inglés | MEDLINE | ID: mdl-30575441

RESUMEN

Radiotherapy for the treatment of left-sided breast cancer increases the long-term risk of cardiovascular disease. The purpose of the present study was to noninvasively image the progression of radiation-induced cardiac inflammation in a large animal model using a hybrid PET and MRI system. Five canines were imaged using [18F]fluorodeoxyglucose PET to assess changes in myocardial inflammation. All animals were imaged at baseline, 1 wk, and 1, 3, 6, and 12 mo after focused cardiac external beam irradiation with image guidance. Radiation was delivered in a single fraction. The linear quadratic model was used to convert a typical multifractionated heart dose to a corrected single-fraction biologically equivalent dose. Immunohistochemistry was performed on excised left ventricular tissue samples from all five irradiated canines and one nonirradiated control canine to confirm the presence of inflammation. The mean doses delivered to the entire heart, left ventricle, left anterior descending artery, and left circumflex artery were 1.7 ± 0.2, 2.7 ± 0.2, 5.5 ± 0.9, and 1.1 ± 0.4 Gy, respectively. FDG standard uptake values remained persistently elevated compared with baseline (1.1 ± 0.03 vs. 2.6 ± 0.19, P < 0.05). The presence of myocardial inflammation was confirmed histologically and correlated with myocardial dose. This study suggests a global inflammatory response that is persistent up to 12 mo postirradiation. Inflammation PET imaging should be considered in future clinical studies to monitor the early changes in cardiac function that may play a role in the ultimate development of radiation-induced cardiac toxicity. NEW & NOTEWORTHY Using advanced cardiac PET imaging, we have shown the spatial and quantitative relationship between radiation dose deposition and temporal changes in inflammation. We have shown that the progression of radiation-induced cardiac inflammation is immediate and does not subside for up to 1 yr after radiation. Results are presented in a large animal model that closely resembles the size and vessel architecture of humans. The proposed imaging protocol can be easily replicated for clinical use.


Asunto(s)
Neoplasias de la Mama/radioterapia , Enfermedades Cardiovasculares/diagnóstico por imagen , Tomografía de Emisión de Positrones , Traumatismos por Radiación/diagnóstico por imagen , Radioterapia/efectos adversos , Animales , Enfermedades Cardiovasculares/etiología , Enfermedades Cardiovasculares/patología , Perros , Femenino , Fluorodesoxiglucosa F18 , Imagen por Resonancia Magnética , Imagen Multimodal , Dosis de Radiación , Traumatismos por Radiación/etiología , Traumatismos por Radiación/patología , Radiofármacos
7.
Med Mycol ; 57(Supplement_1): S67-S75, 2019 Feb 01.
Artículo en Inglés | MEDLINE | ID: mdl-30690600

RESUMEN

Canine coccidioidomycosis, a systemic fungal infection endemic to arid and semiarid regions of North, Central, and South America, is commonly diagnosed in dogs living in or traveling through lower Sonoran life zones in the states of California and Arizona. Canine and human cases have geographic overlap. Similarities between clinical coccidioidomycosis in dogs and humans include asymptomatic infection, primary respiratory disease and disseminated disease. Differences include a high rate of dissemination in dogs, differences in predilection of dissemination sites, and a granulomatous or diffuse meningoencephalopathic form in the canine central nervous system (CNS) without the obstructive component seen in humans. Dogs presenting with CNS coccidioidomycosis most commonly experience seizures. Prior disease history and serology are unreliable indicators of CNS coccidioidomycosis. Magnetic resonance imaging (MRI) is advantageous for diagnosis of CNS coccidioidomycosis in dogs. Long-term administration of antifungal medication is promoted for treatment of both primary and disseminated coccidioidomycosis in dogs. Supportive treatment addressing pain, fever, inappetance, coughing, and other clinical signs improves patient care. Glucocorticoids and or anticonvulsants are also recommended for canine disseminated CNS disease. Protracted treatment times, lack of owner compliance, failure of the disease to respond to the first antifungal drug selected, and high cost are challenges of successfully treating dogs.


Asunto(s)
Coccidioidomicosis/veterinaria , Enfermedades de los Perros/microbiología , Perros/microbiología , Meningoencefalitis/tratamiento farmacológico , Animales , Anticonvulsivantes/uso terapéutico , Antifúngicos/economía , Antifúngicos/uso terapéutico , Encéfalo/diagnóstico por imagen , Coccidioides/efectos de los fármacos , Coccidioidomicosis/tratamiento farmacológico , Tos , Enfermedades de los Perros/tratamiento farmacológico , Femenino , Fiebre , Glucocorticoides/uso terapéutico , Imagen por Resonancia Magnética , Masculino , Meningoencefalitis/diagnóstico , Meningoencefalitis/microbiología , Convulsiones
9.
BMC Genet ; 19(1): 16, 2018 03 22.
Artículo en Inglés | MEDLINE | ID: mdl-29566674

RESUMEN

BACKGROUND: Syringomyelia (SM) is a common condition affecting brachycephalic toy breed dogs and is characterized by the development of fluid-filled cavities within the spinal cord. It is often concurrent with a complex developmental malformation of the skull and craniocervical vertebrae called Chiari-like malformation (CM) characterized by a conformational change and overcrowding of the brain and cervical spinal cord particularly at the craniocervical junction. CM and SM have a polygenic mode of inheritance with variable penetrance. RESULTS: We identified six cranial T1-weighted sagittal MRI measurements that were associated to maximum transverse diameter of the syrinx cavity. Increased syrinx transverse diameter has been correlated previously with increased likelihood of behavioral signs of pain. We next conducted a whole genome association study of these traits in 65 Cavalier King Charles Spaniel (CKCS) dogs (33 controls, 32 with extreme phenotypes). Two loci on CFA22 and CFA26 were found to be significantly associated to two traits associated with a reduced volume and altered orientation of the caudal cranial fossa. Their reconstructed haplotypes defined two associated regions that harbor only two genes: PCDH17 on CFA22 and ZWINT on CFA26. PCDH17 codes for a cell adhesion molecule expressed specifically in the brain and spinal cord. ZWINT plays a role in chromosome segregation and its expression is increased with the onset of neuropathic pain. Targeted genomic sequencing of these regions identified respectively 37 and 339 SNPs with significantly associated P values. Genotyping of tagSNPs selected from these 2 candidate loci in an extended cohort of 461 CKCS (187 unaffected, 274 SM affected) identified 2 SNPs on CFA22 that were significantly associated to SM strengthening the candidacy of this locus in SM development. CONCLUSIONS: We identified 2 loci on CFA22 and CFA26 that contained only 2 genes, PCDH17 and ZWINT, significantly associated to two traits associated with syrinx transverse diameter. The locus on CFA22 was significantly associated to SM secondary to CM in the CKCS dog breed strengthening its candidacy for this disease. This study will provide an entry point for identification of the genetic factors predisposing to this condition and its underlying pathogenic mechanisms.


Asunto(s)
Malformación de Arnold-Chiari/veterinaria , Enfermedades de los Perros/genética , Sitios Genéticos , Siringomielia/veterinaria , Animales , Malformación de Arnold-Chiari/genética , Fosa Craneal Posterior/patología , Perros , Estudio de Asociación del Genoma Completo/veterinaria , Haplotipos , Imagen por Resonancia Magnética/veterinaria , Dolor/genética , Dolor/veterinaria , Polimorfismo de Nucleótido Simple , Siringomielia/genética
10.
Med Mycol ; 56(7): 857-867, 2018 Oct 01.
Artículo en Inglés | MEDLINE | ID: mdl-29554336

RESUMEN

Cryptococcosis is an opportunistic fungal infection caused by members of the two sibling species complexes: Cryptococcus neoformans and Cryptococcus gattii. Flucytosine (5FC) is one of the most widely used antifungals against Cryptococcus spp., yet very few studies have looked at the molecular mechanisms responsible for 5FC resistance in this pathogen. In this study, we examined 11 C. gattii clinical isolates of the major molecular type VGIII based on differential 5FC susceptibility and asked whether there were genomic changes in the key genes involved in flucytosine metabolism. Susceptibility assays and sequencing analysis revealed an association between a point mutation in the cytosine deaminase gene (FCY1) and 5FC resistance in two of the studied 5FC resistant C. gattii VGIII clinical isolates, B9322 and JS5. This mutation results in the replacement of arginine for histidine at position 29 and occurs within a variable stretch of amino acids. Heterologous expression of FCY1 and spot sensitivity assays, however, demonstrated that this point mutation did not have any effect on FCY1 activities and was not responsible for 5FC resistance. Comparative sequence analysis further showed that no changes in the amino acid sequence and no genomic alterations were observed within 1 kb of the upstream and downstream sequences of either cytosine permeases (FCY2-4) or uracil phosphoribosyltransferase (FUR1) genes in 5FC resistant and 5FC susceptible C. gattii VGIII isolates. The herein obtained results suggest that the observed 5FC resistance in the isolates B9322 and JS5 is due to changes in unknown protein(s) or pathway(s) that regulate flucytosine metabolism.


Asunto(s)
Antifúngicos/farmacología , Cryptococcus gattii/efectos de los fármacos , Flucitosina/farmacología , Proteínas Fúngicas/metabolismo , Mapas de Interacción de Proteínas , Criptococosis/microbiología , Cryptococcus gattii/genética , Cryptococcus gattii/aislamiento & purificación , Cryptococcus gattii/metabolismo , Citosina Desaminasa/genética , Citosina Desaminasa/metabolismo , Análisis Mutacional de ADN , Proteínas Fúngicas/genética , Humanos , Masculino , Proteínas de Transporte de Membrana/genética , Proteínas de Transporte de Membrana/metabolismo , Pruebas de Sensibilidad Microbiana , Pentosiltransferasa/genética , Pentosiltransferasa/metabolismo , Análisis de Secuencia de ADN
11.
Med Mycol ; 55(4): 396-401, 2017 Jun 01.
Artículo en Inglés | MEDLINE | ID: mdl-28339594

RESUMEN

Elevated fluconazole minimum inhibitory concentrations (MICs) are more frequently observed in Cryptococcus gattii compared to C. neoformans isolates; however, the development of in vivo resistance and the molecular mechanisms responsible have not been reported for this species. We report a case of Cryptococcus gattii (molecular type VGIII) that developed reduced susceptibility to fluconazole during therapy and delineate the molecular mechanisms responsible. Multilocus sequence typing and quantitative DNA analysis of the pre- and post-treatment isolates was performed using well-characterized methods. Pre- and post-treatment clinical isolates were confirmed isogenic, and no differences in ERG11 or PDR11 sequences were found. qPCR found an overexpression of ERG11 and the efflux pump PDR11 in the resistant isolate compared to the isolate collected prior to initiation of antifungal therapy. Reversion to wild-type susceptibility was observed when maintained in antifungal-free media confirming the in vivo development of heteroresistance. The in vivo development of heteroresistance to fluconazole in our patient with C. gattii is secondary to overexpression of the efflux pump PDR11 and the drug target ERG11. Additional work in other clinical isolates with elevated fluconazole MICs is warranted to evaluate the frequency of heteroresistance versus point mutations as a cause of resistance.


Asunto(s)
Antifúngicos/farmacología , Antifúngicos/uso terapéutico , Criptococosis/veterinaria , Cryptococcus gattii/efectos de los fármacos , Farmacorresistencia Fúngica , Fluconazol/farmacología , Fluconazol/uso terapéutico , Animales , Gatos , Criptococosis/tratamiento farmacológico , Criptococosis/microbiología , Cryptococcus gattii/aislamiento & purificación , Femenino , Proteínas Fúngicas/genética , Perfilación de la Expresión Génica , Genotipo , Pruebas de Sensibilidad Microbiana , Tipificación Molecular , Técnicas de Tipificación Micológica , Reacción en Cadena en Tiempo Real de la Polimerasa
12.
J Eukaryot Microbiol ; 62(3): 307-17, 2015.
Artículo en Inglés | MEDLINE | ID: mdl-25256157

RESUMEN

There are several reports of Sarcocystis sarcocysts in muscles of dogs, but these species have not been named. Additionally, there are two reports of Sarcocystis neurona in dogs. Here, we propose two new names, Sarcocystis caninum, and Sarcocystis svanai for sarcocysts associated with clinical muscular sarcocystosis in four domestic dogs (Canis familiaris), one each from Montana and Colorado in the USA, and two from British Columbia, Canada. Only the sarcocyst stage was identified. Most of the sarcocysts identified were S. caninum. Sarcocysts were studied using light microscopy, transmission electron microscopy (TEM), and polymerase chain reaction. Based on collective results two new species, S. caninum and S. svanai were designated. Sarcocystis caninum and S. svanai were structurally distinct. Sarcocystis caninum sarcocysts were up to 1.2 mm long and up to 75 µm wide. By light microscopy, the sarcocyst wall was relatively thin and smooth. By TEM, the sarcocyst wall was "type 9", 1-2 µm thick, and contained villar protrusions that lacked microtubules. Bradyzoites in sections were 7-9 µm long. Sarcocysts of S. svanai were few and were identified by TEM. Sarcocystis svanai sarcocysts were "type 1", thin walled (< 0.5 µm), and the wall lacked villar protrusions but had tiny blebs that did not invaginate. DNA was extracted either from infected frozen muscle biopsies or formalin-fixed paraffin-embedded sections. Dogs were either singly infected with S. caninum or multiply co-infected with S. caninum and S. svanai (the result of a mixed infection) based on multilocus DNA sequencing and morphology. BLASTn analysis established that the sarcocysts identified in these dogs were similar to, but not identical to Sarcocystis canis or Sarcocystis arctosi, parasites found to infect polar bears (Ursus maritimus) or brown bears (Ursus arctosi), respectively. However, the S. caninum sequence showed 100% identify over the 18S rRNA region sequenced to that of S. arctica, a parasite known to infect Arctic foxes (Vulpes lagopus).


Asunto(s)
Enfermedades de los Perros/patología , Enfermedades de los Perros/parasitología , Hepatitis Animal/patología , Miositis/veterinaria , Sarcocystis/clasificación , Sarcocystis/aislamiento & purificación , Sarcocistosis/veterinaria , Animales , Colombia Británica , Análisis por Conglomerados , Colorado , ADN Ribosómico/química , ADN Ribosómico/genética , Perros , Hepatitis Animal/parasitología , Microscopía , Datos de Secuencia Molecular , Montana , Tipificación de Secuencias Multilocus , Miositis/parasitología , Miositis/patología , Filogenia , Reacción en Cadena de la Polimerasa , ARN Ribosómico 18S/genética , Sarcocystis/citología , Sarcocystis/genética , Sarcocistosis/parasitología , Sarcocistosis/patología
13.
Mycopathologia ; 179(1-2): 1-9, 2015 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-25318989

RESUMEN

Coccidioidomycosis ('Valley Fever'), caused by the inhalation of the fungus Coccidioides, remains a recalcitrant health problem in large parts of California. The incidence and severity of the disease continues to rise in many parts of the state. In this manuscript, we highlight unanswered questions about the disease. Specifically, the extent of disease burden, genetic determinants of host susceptibility, diagnostic and treatment guidelines, natural reservoirs of the pathogens, antifungal drug resistance, and fungal determinants of mild or severe disease are all areas awaiting in depth investigations. We also recommend establishment of a California Coccidioidomycosis Registry to improve clinical care and translational research.


Asunto(s)
Coccidioides/efectos de los fármacos , Coccidioidomicosis/tratamiento farmacológico , Coccidioidomicosis/epidemiología , Reservorios de Enfermedades/microbiología , California/epidemiología , Coccidioides/genética , Coccidioides/patogenicidad , Coccidioidomicosis/diagnóstico , Farmacorresistencia Fúngica/genética , Humanos
14.
Infect Immun ; 82(7): 3058-65, 2014 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-24799631

RESUMEN

Compared to Cryptococcus neoformans, little is known about the virulence of the molecular types in Cryptococcus gattii. We compared in vitro virulence factor production and survival data using a Drosophila model of infection to further characterize the phenotypic features of different cryptococcal molecular types. Forty-nine different isolates were inoculated into wild-type flies and followed for survival. In vitro, isolates were assessed for growth at 30 and 37°C, melanin production, capsule size, resistance to H(2)O(2), and antifungal susceptibility. A mediator model was used to assess molecular type and virulence characteristics as predictors of survival in the fly model. VGIII was the most virulent molecular type in flies (P < 0.001). At 30°C, VGIII isolates grew most rapidly; at 37°C, VNI isolates grew best. C. gattii capsules were larger than those of C. neoformans (P < 0.001). Mediator model analysis found a strong correlation of Drosophila survival with molecular type and with growth at 30°C. We found molecular-type-specific differences in C. gattii in growth at different temperatures, melanin production, capsule size, ability to resist hydrogen peroxide, and antifungal susceptibility, while growth at 30°C and the VGIII molecular type were strongly associated with virulence in a Drosophila model of infection.


Asunto(s)
Cryptococcus gattii/genética , Cryptococcus gattii/patogenicidad , Drosophila melanogaster/microbiología , Animales , Antifúngicos/uso terapéutico , Cryptococcus gattii/citología , Cryptococcus gattii/efectos de los fármacos , Cryptococcus gattii/fisiología , Farmacorresistencia Fúngica , Regulación Bacteriana de la Expresión Génica , Melaninas/metabolismo , Virulencia
15.
J Clin Microbiol ; 52(6): 2061-70, 2014 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-24696030

RESUMEN

Molecular types of the Cryptococcus neoformans/Cryptococcus gattii species complex that infect dogs and cats differ regionally and with host species. Antifungal drug susceptibility can vary with molecular type, but the susceptibility of Cryptococcus isolates from dogs and cats is largely unknown. Cryptococcus isolates from 15 dogs and 27 cats were typed using URA5 restriction fragment length polymorphism analysis (RFLP), PCR fingerprinting, and multilocus sequence typing (MLST). Susceptibility was determined using a microdilution assay (Sensititre YeastOne; Trek Diagnostic Systems). MICs were compared among groups. The 42 isolates studied comprised molecular types VGI (7%), VGIIa (7%), VGIIb (5%), VGIIc (5%), VGIII (38%), VGIV (2%), VNI (33%), and VNII (2%), as determined by URA5 RFLP. The VGIV isolate was more closely related to VGIII according to MLST. All VGIII isolates were from cats. All sequence types identified from veterinary isolates clustered with isolates from humans. VGIII isolates showed considerable genetic diversity compared with other Cryptococcus molecular types and could be divided into two major subgroups. Compared with C. neoformans MICs, C. gattii MICs were lower for flucytosine, and VGIII MICs were lower for flucytosine and itraconazole. For all drugs except itraconazole, C. gattii isolates exhibited a wider range of MICs than C. neoformans. MICs varied with Cryptococcus species and molecular type in dogs and cats, and MICs of VGIII isolates were most variable and may reflect phylogenetic diversity in this group. Because sequence types of dogs and cats reflect those infecting humans, these observations may also have implications for treatment of human cryptococcosis.


Asunto(s)
Antifúngicos/farmacología , Enfermedades de los Gatos/microbiología , Criptococosis/veterinaria , Cryptococcus/clasificación , Cryptococcus/efectos de los fármacos , Enfermedades de los Perros/microbiología , Filogenia , Animales , Gatos , Análisis por Conglomerados , Criptococosis/microbiología , Cryptococcus/genética , Cryptococcus/aislamiento & purificación , Dermatoglifia del ADN , Perros , Femenino , Variación Genética , Genotipo , Humanos , Masculino , Pruebas de Sensibilidad Microbiana , Datos de Secuencia Molecular , Tipificación de Secuencias Multilocus , Técnicas de Tipificación Micológica , América del Norte , Polimorfismo de Longitud del Fragmento de Restricción , Análisis de Secuencia de ADN
16.
Vet Dermatol ; 25(3): 163-e43, 2014 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-24720433

RESUMEN

BACKGROUND: Superficial bacterial folliculitis (SBF) is usually caused by Staphylococcus pseudintermedius and routinely treated with systemic antimicrobial agents. Infection is a consequence of reduced immunity associated with alterations of the skin barrier and underlying diseases that may be difficult to diagnose and resolve; thus, SBF is frequently recurrent and repeated treatment is necessary. The emergence of multiresistant bacteria, particularly meticillin-resistant S. pseudintermedius (MRSP), has focused attention on the need for optimal management of SBF. OBJECTIVES: Provision of an internationally available resource guiding practitioners in the diagnosis, treatment and prevention of SBF. DEVELOPMENT OF THE GUIDELINES: The guidelines were developed by the Antimicrobial Guidelines Working Group of the International Society for Companion Animal Infectious Diseases, with consultation and advice from diplomates of the American and European Colleges of Veterinary Dermatology. They describe optimal methods for the diagnosis and management of SBF, including isolation of the causative organism, antimicrobial susceptibility testing, selection of antimicrobial drugs, therapeutic protocols and advice on infection control. Guidance is given for topical and systemic modalities, including approaches suitable for MRSP. Systemic drugs are classified in three tiers. Tier one drugs are used when diagnosis is clear cut and risk factors for antimicrobial drug resistance are not present. Otherwise, tier two drugs are used and antimicrobial susceptibility tests are mandatory. Tier three includes drugs reserved for highly resistant infections; their use is strongly discouraged and, when necessary, they should be used in consultation with specialists. CONCLUSIONS AND CLINICAL IMPORTANCE: Optimal management of SBF will improve antimicrobial use and reduce selection of MRSP and other multidrug-resistant bacteria affecting animal and human health.


Asunto(s)
Antibacterianos/uso terapéutico , Enfermedades de los Perros/diagnóstico , Foliculitis/veterinaria , Enfermedades Cutáneas Bacterianas/veterinaria , Animales , Antibacterianos/administración & dosificación , Enfermedades de los Perros/tratamiento farmacológico , Perros , Foliculitis/diagnóstico , Foliculitis/tratamiento farmacológico , Enfermedades Cutáneas Bacterianas/diagnóstico , Enfermedades Cutáneas Bacterianas/tratamiento farmacológico
17.
J Vet Intern Med ; 38(1): 375-380, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-37975704

RESUMEN

In response to concerns regarding numerous complex issues facing the veterinary specialty profession, several organizations, including the American College of Veterinary Internal Medicine, have made a clarion call to the American Veterinary Medical Association to begin discussions surrounding the formation of an accrediting body for internships, residencies, and fellowships. A proposed name for such a body is the Accreditation Council on Graduate Veterinary Medical Education, in alignment with the Accreditation Council on Graduate Medical Education (ACGME); the term "graduate" refers to specialty education that occurs after the first 4 years of the MD or DVM degree. Although the structure and financing of graduate education differ between the human medical and veterinary professions, we can nevertheless learn much from the history of evolution of human medical specialization as we navigate the path ahead.


Asunto(s)
Educación de Postgrado en Medicina , Internado y Residencia , Animales , Estados Unidos , Humanos , Acreditación
18.
J Am Vet Med Assoc ; 262(8): 1124-1128, 2024 Aug 01.
Artículo en Inglés | MEDLINE | ID: mdl-38810662

RESUMEN

A potential emerging shortage of veterinary medical educators requires the profession to acknowledge and understand the factors leading to this outcome. Expanding class sizes within existing schools and colleges of veterinary medicine and the expected expansion of new programs seeking AVMA-Council of Education accreditation have heightened the need to address an impending shortage of veterinary medical educators. A solution-oriented approach that accurately projects educator workforce needs and identifies factors contributing to the shortage requires effective collaboration across various partnering organizations to develop innovations in pedagogy and educational delivery methods. The veterinary profession must also identify and reduce disincentives that deter students and post-DVM trainees from pursuing careers in education. Finally, efforts at the state and federal level are critical to advocate for financial support and incentives for expansion of the veterinary medical educator workforce. Through these collective approaches and partnerships, the veterinary medical educator workforce can be strengthened to overcome obstacles for educating the next generation of veterinarians to meet societal needs.


Asunto(s)
Educación en Veterinaria , Veterinarios , Veterinarios/provisión & distribución , Estados Unidos , Humanos , Facultades de Medicina Veterinaria
19.
Vet Dermatol ; 24(1): 154-61.e34, 2013 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-23331692

RESUMEN

BACKGROUND: Canine pyodermas associated with meticillin-resistant Staphylococcus spp. (MRS) have increased in prevalence over the past decade. HYPOTHESIS/OBJECTIVES: To compare the prevalence of MRS isolation from dogs with superficial pyoderma at a primary care clinic (PCC) and those at a tertiary care facility (VMTH) in California, USA, and identify associated risk factors. ANIMALS: Client-owned dogs from the VMTH (80 dogs) and the PCC (30 dogs). METHODS: Aerobic bacterial culture and antibiotic susceptibility were performed on swab specimens collected from dogs, and meticillin resistance was determined using microdilution methods according to Clinical and Laboratory Standards Institute guidelines. A mecA gene PCR assay was used to confirm meticillin resistance when possible. RESULTS: Of 89 staphylococcal isolates from the VMTH, 34 (38.2%) were meticillin resistant. In 31 dogs, pyoderma persisted, and one or more follow-up isolates were obtained. The species isolated and drug susceptibility changed unpredictably during treatment. Of 33 PCC isolates, nine (27.3%) were meticillin resistant. Multiple drug resistance was identified in 41 of 53 (77.3%) MRS isolates from the VMTH and five of nine from the PCC. The sensitivity and specificity of PCR for the detection of meticillin resistance was 34 of 39 (87%) and 86 of 87 (99%), respectively. Risk factors for meticillin resistance for both sites were antibiotic treatment within the last year (P = 0.001), and for VMTH, hospitalization of dogs within the last year (P = 0.001). CONCLUSIONS AND CLINICAL IMPORTANCE: The prevalence of meticillin resistance was not different between VMTH and PCC isolates (P = 0.29). Previous antimicrobial therapy was an important risk factor for the isolation of MRS at both sites.


Asunto(s)
Enfermedades de los Perros/microbiología , Resistencia a la Meticilina , Piodermia/veterinaria , Infecciones Cutáneas Estafilocócicas/veterinaria , Staphylococcus/efectos de los fármacos , Animales , Proteínas Bacterianas/genética , Proteínas Bacterianas/metabolismo , California/epidemiología , Enfermedades de los Perros/epidemiología , Perros , Femenino , Masculino , Prevalencia , Piodermia/epidemiología , Piodermia/microbiología , Factores de Riesgo , Infecciones Cutáneas Estafilocócicas/epidemiología , Infecciones Cutáneas Estafilocócicas/microbiología , Staphylococcus/aislamiento & purificación
20.
Vet Clin North Am Small Anim Pract ; 53(1): 141-154, 2023 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-36400471

RESUMEN

Many tick-borne infections are increasing in geographic range as a result of activities such as reforestation and climate change. A history of outdoor activity in tick-endemic regions, together with consistent clinical signs (such as fever, splenomegaly, polyarthritis, thrombocytopenia), should raise suspicion for tick-borne infectious disease. Diseases with short incubation periods are best diagnosed with organism-detection assays. When the incubation period is long and organism numbers are low, diagnosis often relies on antibody testing, but it may be difficult to associate positive tests with infection. Positive antibody tests in healthy animals should prompt veterinarians to discuss prevention approaches with owners.


Asunto(s)
Enfermedades por Picaduras de Garrapatas , Garrapatas , Animales , Enfermedades por Picaduras de Garrapatas/diagnóstico , Enfermedades por Picaduras de Garrapatas/prevención & control , Enfermedades por Picaduras de Garrapatas/veterinaria
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