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2.
Vet Dermatol ; 2024 Apr 23.
Article in English | MEDLINE | ID: mdl-38654610

ABSTRACT

A dog presented with deep pyoderma on the paw, following treatment with ciclosporin and prednisone for immune-mediated haemolytic anaemia. Cytological evaluation, skin biopsy, aerobic culture, next-generation DNA sequencing and PCR were used to detect the first reported case of Burkholderia gladioli in a dog.

3.
J Zoo Wildl Med ; 54(1): 102-110, 2023 Mar.
Article in English | MEDLINE | ID: mdl-36971634

ABSTRACT

Over a span of 6 yr, six adult eastern bongo antelope (Tragelaphus eurycerus isaaci) from a single institution died due to systemic mycotic infections. All animals were of the same genetic lineage and in good body condition at the time of death. Gross findings in all cases included multifocal white-to-tan nodules up to 10 cm in diameter that were most numerous in the heart, lung, and kidney. Histologic examination identified these nodules as foci of granulomatous inflammation containing branching, septate, broad, undulating fungal elements. Identification of the fungal species was pursued using PCR with sequencing, immunohistochemistry, and culture. Multiple fungal species were identified using the various modalities, and commonality of species identification was limited to Cladosporium sp. in four of the cases. The clinical and postmortem findings in these cases were identical and were considered to be the same infectious disease. The Cladosporium sp. was considered a candidate as an emerging fatal infectious agent in this population of bongo antelopes. In all of these cases, death was attributed to conduction abnormalities associated with the cardiac lesions or euthanasia.


Subject(s)
Antelopes , Mycoses , Animals , Mycoses/veterinary
4.
Vet Dermatol ; 33(6): 559-567, 2022 Dec.
Article in English | MEDLINE | ID: mdl-35876313

ABSTRACT

BACKGROUND: Canine epitheliotropic cutaneous T-cell lymphoma (eCTCL) is thought to represent a disease homologue to human mycosis fungoides (MF). In human MF, neoplastic cells are phenotypically consistent with resident effector memory T cells, a population that remains for an extended period within tissue without circulating. Dogs with eCTCL often present with lesions in multiple locations, raising the question of whether the neoplasm is of the same T-cell subpopulation or not. OBJECTIVES: To characterize the antigen receptor gene rearrangements of lymphocytes from skin and blood of dogs with eCTCL to determine if neoplastic clones are identical. ANIMALS: Fourteen dogs with eCTCL. MATERIALS AND METHODS: Histological and immunohistochemical examination, and PCR for antigen receptor rearrangement (PARR) for T-cell receptor gamma (TRG) performed on multiple cutaneous biopsy samples and blood. RESULTS: All skin biopsies contained cluster of differentiation (CD)3-positive neoplastic lymphocytes. Within individual dogs, all skin biopsies revealed identical TRG clonality profiles, suggesting that the same neoplastic clone was present in all sites. In the blood, a matching clone was found in six of 14 dogs, a unique clone was observed in nine of 14 dogs, and no clone was detected in two of 14 dogs. CONCLUSIONS: These findings show that canine eCTCL lesions in multiple locations harbour the same neoplastic clone, neoplastic lymphocytes do not remain fixed to the skin and instead can circulate via blood, differing clones can be identified in skin versus blood, and circulating neoplastic cells can be detected without lymphocytosis.


Contexte - On pense que le lymphome T cutané épithéliotrope canin (eCTCL) représente une maladie homologue au mycosis fongoïde (MF) humain. Dans le MF humain, les cellules néoplasiques sont phénotypiquement compatibles avec les cellules T mémoire effectrices résidentes, une population qui reste pendant une période prolongée dans les tissus sans circuler. Les chiens atteints d'eCTCL présentent souvent des lésions à plusieurs endroits, ce qui soulève la question de savoir si le néoplasme appartient ou non à la même sous-population de lymphocytes T. Objectifs - Caractériser les réarrangements du gène du récepteur antigénique des lymphocytes de la peau et du sang des chiens atteints d'eCTCL afin de déterminer si les clones néoplasiques sont identiques. Animaux - Quatorze chiens avec eCTCL. Matériels et méthodes - Examen histologique et immunohistochimique, et PCR pour le réarrangement des récepteurs antigéniques (PARR) pour le récepteur gamma des lymphocytes T (TRG) effectués sur plusieurs échantillons de biopsie cutanée et de sang. Résultats - Toutes les biopsies cutanées contenaient des amas de lymphocytes néoplasiques positifs à la différenciation (CD)3. Chez les chiens individuels, toutes les biopsies cutanées ont révélé des profils de clonalité TRG identiques, suggérant que le même clone néoplasique était présent dans tous les sites. Dans le sang, un clone correspondant a été trouvé chez six des 14 chiens, un clone unique a été observé chez neuf des 14 chiens et aucun clone n'a été détecté chez deux des 14 chiens. Conclusions - Ces résultats montrent que les lésions eCTCL canines à plusieurs endroits abritent le même clone néoplasique, les lymphocytes néoplasiques ne restent pas fixés à la peau et peuvent plutôt circuler par le sang, différents clones peuvent être identifiés dans la peau par rapport au sang, et les cellules néoplasiques circulantes peuvent être détecté sans lymphocytose.


Introducción- se cree que el linfoma epiteliotrópico cutáneo de células T canino (eCTCL) representa una enfermedad homóloga a la micosis fungoide (MF) humana. En la MF humana, las células neoplásicas son fenotípicamente consistentes con las células T de memoria efectoras residentes, una población que permanece durante un período prolongado dentro del tejido sin circular. Los perros con eCTCL a menudo presentan lesiones en múltiples ubicaciones, lo que plantea la cuestión de si la neoplasia es de la misma subpoblación de células T o no. Objetivos- caracterizar los reordenamientos del gen del receptor de antígeno de los linfocitos de la piel y la sangre de perros con eCTCL para determinar si los clones neoplásicos son idénticos. Animales- catorce perros con eCTCL. Materiales y métodos - Examen histológico e inmunohistoquímico, y PCR para el reordenamiento del receptor de antígeno (PARR) para el receptor de células T gamma (TRG) realizado en múltiples muestras de biopsia cutánea y sangre. Resultados- todas las biopsias de piel contenían linfocitos neoplásicos positivos para grupos de diferenciación (CD)3. Dentro de perros individuales, todas las biopsias de piel revelaron perfiles de clonalidad de TRG idénticos, lo que sugiere que el mismo clon neoplásico estaba presente en todos los sitios. En la sangre, se encontró un clon compatible en seis de 14 perros, se observó un clon único en nueve de 14 perros y no se detectó ningún clon en dos de 14 perros. Conclusiones- estos hallazgos muestran que las lesiones de eCTCL canino en múltiples ubicaciones albergan el mismo clon neoplásico, los linfocitos neoplásicos no permanecen fijados a la piel y, en cambio, pueden circular a través de la sangre, se pueden identificar diferentes clones en la piel versus la sangre y las células neoplásicas circulantes pueden ser identificadas sin presencia de linfocitosis.


Contexto - Acredita-se que o linfoma epiteliotrópico cutâneo de células T canino (eCTCL) representa uma doença análoga à micose fungoide (MF) humana. Na MF humana, as células neoplásicas são fenotipicamente consistentes com células T efetoras de memória residentes, uma população que permanece por um período extenso no tecido sem entrar na circulação. Os cães com eCTCL frequentemente apresentam lesões em múltiplos locais, levantando a questão de se a neoplasia é da mesma subpopulação de células T ou não. Objetivos - Caracterizar os rearranjos dos genes receptores de antígenos dos linfócitos da pele e do sangue de cães com eCTCL para determinar se os clones neoplásicos são idênticos. Animais - Quatorze cães com eCTCL. Materiais e métodos - Exame histológico e imunohistoquímico, e PCR para rearranjo de receptor de antígeno (PARR) para o receptor Gama de células T (TRG) realizado em múltiplas amostras de biópsia cutânea e sangue. Resultados - Todas as biópsias cutâneas continham clusters de diferenciação linfócitos T (CD)3- positivos. Entre os indivíduos, todas as biópsias cutâneas revelaram perfis de clonalidade de TGR idênticos em seis dos 14 cães, sugerindo que a mesma célula neoplásica estava presente em todos os locais. No sangue, um clone correspondente foi encontrado em seis dos 14 cães, um clone único foi observado em nove dos 14 cães e nenhum clone foi detectado em dois dos 14 cães. Conclusões - Estes achados demonstraram que as lesões de eCTCL em múltiplos locais possuem o mesmo clone neoplásico, linfócitos neoplásicos não permanecem fixos na pele e podem circular por via sistêmica , diversos tipos de clones podem ser identificados na pele versus sangue, e as células neoplásicas circulantes podem ser detectadas sem linfocitose.


Subject(s)
Dog Diseases , Lymphoma, T-Cell, Cutaneous , Mycosis Fungoides , Skin Neoplasms , Dogs , Animals , Humans , Skin Neoplasms/diagnosis , Skin Neoplasms/veterinary , Mycosis Fungoides/pathology , Mycosis Fungoides/veterinary , Lymphoma, T-Cell, Cutaneous/veterinary , Lymphoma, T-Cell, Cutaneous/pathology , Skin/pathology , Biopsy/veterinary , Dog Diseases/pathology
5.
J Am Vet Med Assoc ; 259(S2): 1-3, 2022 05 18.
Article in English | MEDLINE | ID: mdl-35576181

ABSTRACT

In collaboration with the American College of Veterinary Pathologists.


Subject(s)
Pathology, Veterinary , Veterinarians , Animals , Humans , United States
6.
J Am Vet Med Assoc ; 259(S2): 1-3, 2022 04 08.
Article in English | MEDLINE | ID: mdl-35394933

ABSTRACT

In collaboration with the American College of Veterinary Pathologists.


Subject(s)
Pathology, Veterinary , Veterinarians , Animals , Humans , United States
7.
J Am Vet Med Assoc ; 260(13): 1-3, 2022 04 06.
Article in English | MEDLINE | ID: mdl-35389881
8.
Vet Dermatol ; 32(5): 448-e122, 2021 Oct.
Article in English | MEDLINE | ID: mdl-34351013

ABSTRACT

BACKGROUND: Micro-organisms associated with canine otitis externa (OE) may cause biofilm-associated infections (BAI). A key component of biofilm is microbial aggregate and extracellular polymeric substance (EPS). Periodic acid Schiff (PAS) can stain polysaccharide EPS in human otitis media with effusion, but this has not been tested in canine OE. There is no cytological definition for microbial aggregate, and definitive methods for identifying BAI in a clinical setting in canine OE have not been defined. OBJECTIVES: To establish whether PAS stain can identify polysaccharide matrix on cytological smears; and to determine the reproducibility of identification of microbial aggregates within a discrete area of stained matrix, using paired modified Wright's and PAS-stained smears. ANIMALS: Forty privately-owned dogs presenting to a dermatological referral practice. METHODS AND MATERIALS: In this prospective, cross-sectional study, three investigators independently and blindly classified 40 paired modified Wright's-PAS slide sets into groups: aggregate-associated infection (AAI) and non-AAI (n = 27); and control (n = 13). Agreement between investigators for presence of AAI was measured using Fleiss' kappa statistic (FK). Agreement between investigators and dermatologists for presence of AAI upon cytological evaluation, and suspected BAI based on clinical examination, was measured using Cohen's kappa statistic. RESULTS: The matrix was confirmed to stain PAS-positive. Interinvestigator agreement for AAI was very good using PAS (0.82 FK) and fair using modified-Wright's (MW) (0.33 FK). Reproducible cytological features associated with AAI were the presence of: three or more distinct aggregates (0.76 FK); discrete areas of PAS-positive matrix (0.70 FK); and the presence of high-density material (0.70 FK) using PAS stain. CONCLUSION: PAS can stain the extracellular matrix on otic smears, and a novel protocol for reproducible identification of cytological features such as microbial aggregates has been established.


Subject(s)
Dog Diseases , Otitis Externa , Animals , Biofilms , Coloring Agents , Cross-Sectional Studies , Dog Diseases/diagnosis , Dogs , Extracellular Polymeric Substance Matrix , Otitis Externa/diagnosis , Otitis Externa/veterinary , Periodic Acid , Prospective Studies , Reproducibility of Results
9.
Pediatr Infect Dis J ; 40(8): 715-722, 2021 08 01.
Article in English | MEDLINE | ID: mdl-33967229

ABSTRACT

BACKGROUND: In resource-limited settings, acute respiratory infections continue to be the leading cause of death in young children. We conducted postmortem investigations in children <5 years hospitalized with a clinical diagnosis of respiratory disease at Kenya's largest referral hospital. METHODS: We collected respiratory and other tissues postmortem to examine pathologic processes using histology, molecular and immunohistochemistry assays. Nasopharyngeal, trachea, bronchi and lung specimens were tested using 21-target respiratory pathogen real-time reverse transcription polymerase chain reaction assays deployed on Taqman Array Cards. Expert panels reviewed all findings to determine causes of death and associated pathogens. RESULTS: From 2014 to 2015, we investigated 64 pediatric deaths (median age 7 months). Pneumonia was determined as cause of death in 70% (42/52) of cases where death was associated with an infectious disease process. The main etiologies of pneumonia deaths were respiratory syncytial virus (RSV) (n = 7, 19%), Pneumocystis jirovecii (n = 7, 19%), influenza A (n = 5, 14%) and Streptococcus pneumoniae (n = 5, 14%)-10% of cases had multi-pathogen involvement. Among the other 10 deaths associated with a nonpneumonia infectious process, 4 did not have an etiology assigned, the others were associated with miliary tuberculosis (2), cerebral thrombosis due to HIV (1), Enterobacteriaceae (1), rotavirus (1), and 1 case of respiratory infection with severe hypokalemia associated with RSV. CONCLUSIONS: In spite of well-established vaccination programs in Kenya, some deaths were still vaccine preventable. Accelerated development of RSV monoclonal antibodies and vaccines, introduction of seasonal influenza vaccination, and maintenance or improved uptake of existing vaccines can contribute to further reductions in childhood mortality.


Subject(s)
Child, Hospitalized , Pneumonia/epidemiology , Pneumonia/microbiology , Pneumonia/mortality , Respiratory Tract Infections/epidemiology , Respiratory Tract Infections/microbiology , Respiratory Tract Infections/mortality , Autopsy , Cause of Death , Child, Preschool , Diagnosis , Female , Humans , Infant , Kenya/epidemiology , Male
10.
Clin Infect Dis ; 73(2): e345-e354, 2021 07 15.
Article in English | MEDLINE | ID: mdl-32615591

ABSTRACT

BACKGROUND: Death in patients with chikungunya is rare and has been associated with encephalitis, hemorrhage, and septic shock. We describe clinical, histologic, and immunohistochemical findings in individuals who died following chikungunya virus (CHIKV) infection. METHODS: We identified individuals who died in Puerto Rico during 2014 following an acute illness and had CHIKV RNA detected by reverse transcriptase-polymerase chain reaction in a pre- or postmortem blood or tissue specimen. We performed histopathology and immunohistochemistry (IHC) for CHIKV antigen on tissue specimens and collected medical data via record review and family interviews. RESULTS: Thirty CHIKV-infected fatal cases were identified (0.8/100 000 population). The median age was 61 years (range: 6 days-86 years), and 19 (63%) were male. Death occurred a median of 4 days (range: 1-29) after illness onset. Nearly all (93%) had at least 1 comorbidity, most frequently hypertension, diabetes, or obesity. Nine had severe comorbidities (eg, chronic heart or kidney disease, sickle cell anemia) or coinfection (eg, leptospirosis). Among 24 fatal cases with tissue specimens, 11 (46%) were positive by IHC. CHIKV antigen was most frequently detected in mesenchymal tissues and mononuclear cells including tissue macrophages, blood mononuclear cells, splenic follicular dendritic cells, and Kupffer cells. Common histopathologic findings were intra-alveolar hemorrhage and edema in the lung, chronic or acute tenosynovitis, and increased immunoblasts in the spleen. CHIKV infection likely caused fatal septic shock in 2 patients. CONCLUSIONS: Evaluation of tissue specimens provided insights into the pathogenesis of CHIKV, which may rarely result in septic shock and other severe manifestations.


Subject(s)
Chikungunya Fever , Chikungunya virus , Diabetes Mellitus , Chikungunya Fever/complications , Chikungunya Fever/epidemiology , Comorbidity , Humans , Male , Middle Aged , Puerto Rico
11.
Leukemia ; 34(5): 1394-1406, 2020 05.
Article in English | MEDLINE | ID: mdl-31811236

ABSTRACT

The frailty index (FI) is based on the principle that the more deficits an individual has, the greater their risk of adverse outcomes. It is expressed as a ratio of the number of deficits present to the total number of deficits considered. We developed an MDS-specific FI using a prospective MDS registry and assessed its ability to add prognostic power to conventional prognostic scores in MDS. The 42 deficits included in this FI included measurements of physical performance, comorbidities, laboratory values, instrumental activities of daily living, quality of life and performance status. Of 644 patients, 440 were eligible for FI calculation. The median FI score was 0.25 (range 0.05-0.67), correlated with age and IPSS/IPSS-R risk scores and discriminated overall survival. With a follow-up of 20 months, survival was 27 months (95% CI 24-30.4). By multivariate analysis, age >70, FI, transfusion dependence, and IPSS were significant covariates associated with OS. The incremental discrimination improvement of the frailty index was 37%. We derived a prognostic score with five risk groups and distinct survivals ranging from 7.4 months to not yet reached. If externally validated, the MDS-FI could be used as a tool to refine the risk stratification of current clinical prognostication models.


Subject(s)
Frailty/mortality , Frailty/pathology , Myelodysplastic Syndromes/mortality , Myelodysplastic Syndromes/pathology , Quality of Life , Registries/statistics & numerical data , Risk Assessment/methods , Activities of Daily Living , Aged , Aged, 80 and over , Comorbidity , Female , Follow-Up Studies , Humans , Male , Middle Aged , Prognosis , Prospective Studies , Risk Factors , Survival Rate
12.
Am J Clin Pathol ; 152(1): 36-49, 2019 06 05.
Article in English | MEDLINE | ID: mdl-31006817

ABSTRACT

OBJECTIVES: We compared minimally invasive tissue sampling (MITS) with conventional autopsy (CA) in detection of respiratory pathology/pathogens among Kenyan children younger than 5 years who were hospitalized with respiratory disease and died during hospitalization. METHODS: Pulmonary MITS guided by anatomic landmarks was followed by CA. Lung tissues were triaged for histology and molecular testing using TaqMan Array Cards (TACs). MITS and CA results were compared for adequacy and concordance. RESULTS: Adequate pulmonary tissue was obtained by MITS from 54 (84%) of 64 respiratory deaths. Comparing MITS to CA, full histologic diagnostic concordance was present in 23 (36%) cases and partial concordance in 19 (30%), an overall 66% concordance rate. Pathogen detection using TACs had full concordance in 27 (42%) and partial concordance in 24 (38%) cases investigated, an overall 80% concordance rate. CONCLUSIONS: MITS is a viable alternative to CA in respiratory deaths in resource-limited settings, especially if combined with ancillary tests to optimize diagnostic accuracy.


Subject(s)
Lung Diseases/pathology , Lung/pathology , Autopsy , Cause of Death , Female , Humans , Infant , Kenya , Male , Specimen Handling
13.
JMIR Res Protoc ; 8(1): e10854, 2019 Jan 10.
Article in English | MEDLINE | ID: mdl-30632968

ABSTRACT

BACKGROUND: In sub-Saharan Africa, where the burden of respiratory disease-related deaths is the highest, information on the cause of death remains inadequate because of poor access to health care and limited availability of diagnostic tools. Postmortem examination can aid in the ascertainment of causes of death. This manuscript describes the study protocol for the Pediatric Respiratory Etiology Surveillance Study (PRESS). OBJECTIVE: This study protocol aims to identify causes and etiologies associated with respiratory disease-related deaths among children (age 1-59 months) with respiratory illness admitted to the Kenyatta National Hospital (KNH), the largest public hospital in Kenya, through postmortem examination coupled with innovative approaches to laboratory investigation. METHODS: We prospectively followed children hospitalized with respiratory illness until the end of clinical care or death. In case of death, parents or guardians were offered grief counseling, and postmortem examination was offered. Lung tissue specimens were collected using minimally invasive tissue sampling and conventional autopsy where other tissues were collected. Tissues were tested using histopathology, immunohistochemistry, and multipathogen molecular-based assays to identify pathogens. For each case, clinical and laboratory data were reviewed by a team of pathologists, clinicians, laboratorians, and epidemiologists to assign a cause of and etiology associated with death. RESULTS: We have enrolled pediatric cases of respiratory illness hospitalized at the KNH at the time of this submission; of those, 14.8% (140/945) died while in the hospital. Both analysis and interpretation of laboratory results and writing up of findings are expected in 2019-2020. CONCLUSIONS: Postmortem studies can help identify major pathogens contributing to respiratory-associated deaths in children. This information is needed to develop evidence-based prevention and treatment policies that target important causes of pediatric respiratory mortality and assist with the prioritization of local resources. Furthermore, PRESS can provide insights into the interpretation of results using multipathogen testing platforms in resource-limited settings. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/10854.

14.
Clin Infect Dis ; 69(6): 949-955, 2019 08 30.
Article in English | MEDLINE | ID: mdl-30452604

ABSTRACT

BACKGROUND: On 29 April 2015, the Florida Department of Health in Miami-Dade County (DOH Miami-Dade) was notified by a local dermatologist of 3 patients with suspected nontuberculous mycobacterial (NTM) infection after receiving tattoos at a local tattoo studio. METHODS: DOH Miami-Dade conducted interviews and offered testing, described below, to tattoo studio clients reporting rashes. Culture of clinical isolates and identification were performed at the Florida Bureau of Public Health Laboratories. Characterization of NTM was performed by the Centers for Disease Control and Prevention and the US Food and Drug Administration (FDA), respectively. Whole-genome sequencing (WGS) and single-nucleotide polymorphism (SNP) analyses were used to construct a phylogeny among 21 Mycobacterium isolates at the FDA. RESULTS: Thirty-eight of 226 interviewed clients were identified as outbreak-associated cases. Multivariate logistic regression revealed that individuals who reported gray tattoo ink in their tattoos were 8.2 times as likely to report a rash (95% confidence interval, 3.1-22.1). Multiple NTM species were identified in clinical and environmental specimens. Phylogenetic results from environmental samples and skin biopsies indicated that 2 Mycobacterium fortuitum isolates (graywash ink and a skin biopsy) and 11 Mycobacterium abscessus isolates (5 from the implicated bottle of graywash tattoo ink, 2 from tap water, and 4 from skin biopsies) were indistinguishable. In addition, Mycobacterium chelonae was isolated from 5 unopened bottles of graywash ink provided by 2 other tattoo studios in Miami-Dade County. CONCLUSIONS: WGS and SNP analyses identified the tap water and the bottle of graywash tattoo ink as the sources of the NTM infections.


Subject(s)
Disease Outbreaks , Mycobacterium Infections, Nontuberculous/epidemiology , Mycobacterium Infections, Nontuberculous/transmission , Nontuberculous Mycobacteria , Skin Diseases, Bacterial/epidemiology , Skin Diseases, Bacterial/transmission , Tattooing/adverse effects , Adult , Environment , Female , Florida/epidemiology , Genome, Bacterial , Humans , Male , Middle Aged , Mycobacterium Infections, Nontuberculous/microbiology , Nontuberculous Mycobacteria/classification , Nontuberculous Mycobacteria/genetics , Phylogeny , Public Health Surveillance , Skin/pathology , Skin Diseases, Bacterial/microbiology , Whole Genome Sequencing , Young Adult
16.
Mycopathologia ; 183(5): 853-858, 2018 Oct.
Article in English | MEDLINE | ID: mdl-29872935

ABSTRACT

Protothecosis is a rare disease caused by environmental algae of the genus Prototheca. These are saprophytic, non-photosynthetic, aerobic, colorless algae that belong to the Chlorellaceae family. Seven different species have been described. Prototheca zopfii genotype 2 and P. wickerhamii are most commonly involved in pathogenic infections in humans and animals. The objective of this work is to describe, for the first time, a case of protothecosis caused by P. zopfii genotype 1 in a dog. The dog, a 4-year-old mix bred male, was presented to a veterinary clinic in Montevideo, Uruguay, with multiple skin nodules, one of which was excised by surgical biopsy. The sample was examined histologically and processed by PCR, DNA sequencing, and restriction fragments length polymorphisms for the detection and genotyping of P. zopfii. In addition, transmission electron microscopy and scanning electron microscopy were performed. Histology showed severe ulcerative granulomatous dermatitis and panniculitis with myriads of pleomorphic algae. Algal cells were 4-17 µm in size, with an amphophilic, 2-4-µm-thick wall frequently surrounded by a clear halo, contained flocculant material and a deeply basophilic nucleus, and internal septae with daughter cells (endospores) consistent with endosporulation. Ultrastructurally, algal cells/endospores at different stages of development were found within parasitophorous vacuoles in macrophages. Prototheca zopfii genotype 1 was identified by molecular testing, confirming the etiologic diagnosis of protothecosis.


Subject(s)
Dog Diseases/diagnosis , Dog Diseases/pathology , Infections/veterinary , Prototheca/isolation & purification , Animals , Biopsy , DNA, Algal/chemistry , DNA, Algal/genetics , Dog Diseases/microbiology , Dogs , Genotype , Histocytochemistry , Infections/diagnosis , Infections/microbiology , Infections/pathology , Male , Microscopy, Electron, Scanning , Microscopy, Electron, Transmission , Polymerase Chain Reaction , Polymorphism, Restriction Fragment Length , Prototheca/classification , Prototheca/genetics , Sequence Analysis, DNA , Skin/pathology , Uruguay
17.
J Infect Dis ; 218(3): 485-489, 2018 07 02.
Article in English | MEDLINE | ID: mdl-29659908

ABSTRACT

Human protothecosis is a rare microalgae infection, and its dissemination typically occurs in immunocompromised individuals, but no specific immune defect has been reported. Here, we describe an 8-year-old daughter of a consanguineous union with abdominal pain and bloody diarrhea for 3 months who was found to have pancolitis with numerous microalgae identified as Prototheca zopfii. In the absence of a known immunodeficiency, exome sequencing was performed, which uncovered a novel recessive frameshift mutation in CARD9 (p.V261fs). This report highlights that CARD9 deficiency should be investigated in patients with unexplained systemic/visceral protothecosis and suggests a new mechanistic insight into anti-Prototheca immunity.


Subject(s)
CARD Signaling Adaptor Proteins/genetics , Candidiasis, Chronic Mucocutaneous/complications , Colitis/genetics , Colitis/pathology , Prototheca/isolation & purification , Child , Female , Frameshift Mutation , Humans
18.
J Pediatric Infect Dis Soc ; 7(3): e169-e171, 2018 Aug 17.
Article in English | MEDLINE | ID: mdl-29522137

ABSTRACT

An 11-year-old immunocompetent girl presented with two and a half months of progressive right orbital cellulitis, which did not respond to multiple courses of antibiotics or prednisone. A panfungal polymerase chain reaction primer was positive for Saksenaea vasiformis, and she completed 5 months of oral posaconazole therapy after debridement. Saksenaea vasiformis is a rare cause of zygomycosis, and it typically causes skin and soft tissue infection in immunocompetent hosts, particularly after a traumatic injury. The diagnosis should be considered in cases with a protracted course that fail to respond to typical antibiotic therapy. Treatment includes surgical debridement, in additional to antifungal therapy with amphotericin B or posaconazole.


Subject(s)
Antifungal Agents/therapeutic use , Mucorales/isolation & purification , Mucormycosis/drug therapy , Mucormycosis/microbiology , Orbital Cellulitis/drug therapy , Orbital Cellulitis/microbiology , Triazoles/therapeutic use , Child , Combined Modality Therapy , Debridement , Female , Humans , Immunocompetence , Mucormycosis/immunology , Orbital Cellulitis/immunology
19.
Medicine (Baltimore) ; 97(2): e9650, 2018 Jan.
Article in English | MEDLINE | ID: mdl-29480879

ABSTRACT

BACKGROUND: Candida is frequently isolated from the respiratory tract and usually reflects airway colonization. True Candida pneumonia is rare. Our aim is to document a case of Candida pneumonia confirmed by cultures, molecular techniques, and surgical lung biopsy, and to highlight a previously unreported pathologic manifestation of this infection. CASE SUMMARY: A 59-year-old man with a history of chronic obstructive pulmonary disease (COPD) presented with dry cough, low-grade fever, and progressive dyspnea. He was eventually diagnosed with sarcoidosis based on bilateral lung infiltrates and granulomas in a transbronchial biopsy. His condition worsened after immunosuppression, prompting surgical lung biopsy, which revealed suppurative granulomas containing Candida albicans, confirmed by cultures and polymerase chain reaction. Despite multiple episodes of respiratory failure and a prolonged course in intensive care, he recovered fully after antifungal therapy and is currently alive with COPD-related dyspnea 3 years after his initial presentation. CONCLUSION: Candida can rarely cause clinically significant pneumonia in adults, and should be considered in the differential diagnosis of suppurative granulomas in the lung.


Subject(s)
Antifungal Agents/therapeutic use , Candida albicans , Candidiasis/drug therapy , Candidiasis/pathology , Pneumonia/drug therapy , Pneumonia/pathology , Candidiasis/physiopathology , Critical Care , Diagnosis, Differential , Humans , Male , Middle Aged , Pneumonia/microbiology , Pneumonia/physiopathology
20.
Leukemia ; 32(4): 920-930, 2018 04.
Article in English | MEDLINE | ID: mdl-29099493

ABSTRACT

Acalabrutinib, a highly selective Bruton's tyrosine kinase inhibitor, is associated with high overall response rates and durable remission in previously treated chronic lymphocytic leukemia (CLL); however, complete remissions were limited. To elucidate on-target and pharmacodynamic effects of acalabrutinib, we evaluated several laboratory endpoints, including proteomic changes, chemokine modulation and impact on cell migration. Pharmacological profiling of samples from acalabrutinib-treated CLL patients was used to identify strategies for achieving deeper responses, and to identify additive/synergistic combination regimens. Peripheral blood samples from 21 patients with relapsed/refractory CLL in acalabrutinib phase I (100-400 mg/day) and II (100 mg BID) clinical trials were collected prior to and on days 8 and 28 after treatment initiation and evaluated for plasma chemokines, reverse phase protein array, immunoblotting and pseudoemperipolesis. The on-target pharmacodynamic profile of acalabrutinib in CLL lymphocytes was comparable to ibrutinib in measures of acalabrutinib-mediated changes in CCL3/CCL4 chemokine production, migration assays and changes in B-cell receptor signaling pathway proteins and other downstream survival proteins. Among several CLL-targeted agents, venetoclax, when combined with acalabrutinib, showed optimal complementary activity in vitro, ex vivo and in vivo in TCL-1 adoptive transfer mouse model system of CLL. These findings support selective targeting and combinatorial potential of acalabrutinib.


Subject(s)
Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Leukemia, Lymphocytic, Chronic, B-Cell/drug therapy , Leukemia, Lymphocytic, Chronic, B-Cell/metabolism , Adenine/analogs & derivatives , Adoptive Transfer/methods , Animals , B-Lymphocytes/drug effects , B-Lymphocytes/metabolism , Benzamides/administration & dosage , Bridged Bicyclo Compounds, Heterocyclic/administration & dosage , Cell Movement/drug effects , Chemokine CCL3/metabolism , Chemokine CCL4/metabolism , Clinical Trials, Phase I as Topic , Clinical Trials, Phase II as Topic , Combined Modality Therapy/methods , Drug Resistance, Neoplasm/drug effects , Humans , Mice , Piperidines , Protein Kinase Inhibitors/administration & dosage , Protein-Tyrosine Kinases/metabolism , Proteomics , Pyrazines/administration & dosage , Pyrazoles/administration & dosage , Pyrimidines/administration & dosage , Signal Transduction/drug effects , Sulfonamides/administration & dosage
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