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1.
Clin Infect Dis ; 78(5): 1214-1221, 2024 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-38381586

RESUMO

BACKGROUND: Nontoxigenic Corynebacterium diphtheriae, often associated with wounds, can rarely cause infective endocarditis (IE). Five patients with C. diphtheriae IE were identified within 12 months at a Seattle-based hospital system. We reviewed prior C. diphtheriae-positive cultures to determine if detections had increased over time and evaluated epidemiologic trends. METHODS: We conducted a formal electronic health record search to identify all patients aged ≥18 years with C. diphtheriae detected in a clinical specimen (ie, wound, blood, sputum) between 1 September 2020 and 1 April 2023. We collected patient demographics, housing status, comorbidities, substance-use history, and level of medical care required at detection. We extracted laboratory data on susceptibilities of C. diphtheriae isolates and on other pathogens detected at the time of C. diphtheriae identification. RESULTS: Between 1 September 2020 and 1 April 2023, 44 patients (median age, 44 years) had a C. diphtheriae-positive clinical culture, with most detections occurring after March 2022. Patients were predominantly male (75%), White (66%), unstably housed (77%), and had a lifetime history of injecting drugs (75%). Most C. diphtheriae-positive cultures were polymicrobial, including wound cultures from 36 (82%) patients and blood cultures from 6 (14%) patients, not mutually exclusive. Thirty-four patients (77%), including all 5 patients with C. diphtheriae IE, required hospital admission for C. diphtheriae or a related condition. Of the 5 patients with IE, 3 died of IE and 1 from COVID-19. CONCLUSIONS: Findings suggest a high-morbidity outbreak disproportionately affecting patients who use substances and are unstably housed.


Assuntos
Corynebacterium diphtheriae , Difteria , Humanos , Masculino , Adulto , Feminino , Washington/epidemiologia , Pessoa de Meia-Idade , Corynebacterium diphtheriae/isolamento & purificação , Difteria/epidemiologia , Difteria/microbiologia , Endocardite Bacteriana/epidemiologia , Endocardite Bacteriana/microbiologia , Adulto Jovem , Idoso , Antibacterianos/uso terapêutico , Endocardite/microbiologia , Endocardite/epidemiologia
2.
Clin Infect Dis ; 73(6): 1046-1054, 2021 09 15.
Artigo em Inglês | MEDLINE | ID: mdl-33822010

RESUMO

BACKGROUND: Following the 2013-2016 West African Ebola outbreak, distinct, persistent health complaints were recognized in Ebola virus disease (EVD) survivors. Here we provide an in-depth characterization of post-Ebola syndrome >2.5 years after resolution of disease. Additionally, we report subphenotypes of post-Ebola syndrome with overlapping symptom clusters in survivors from Eastern Sierra Leone. METHODS: Participants in Eastern Sierra Leone were identified by the Sierra Leone Association of Ebola survivors. Survivors and their contacts were administered a questionnaire assessing self-reported symptoms and a physical examination. Comparisons between survivors and contacts were conducted using conditional logistic regression. Symptom groupings were identified using hierarchical clustering approaches. Simplified presentation of incredibly complex evaluations (SPICE), correlation analysis, logistic regression, and principal component analysis (PCA) were performed to explore the relationships between symptom clusters. RESULTS: Three hundred seventy-five EVD survivors and 1040 contacts were enrolled into the study. At enrollment, EVD survivors reported significantly more symptoms than their contacts in all categories (P < .001). Symptom clusters representing distinct organ systems were identified. Correlation and logistic regression analysis identified relationships between symptom clusters, including stronger relationships between clusters including musculoskeletal symptoms (r = 0.63, P < .001; and P < .001 for correlation and logistic regression, respectively). SPICE and PCA further highlighted subphenotypes with or without musculoskeletal symptoms. CONCLUSIONS: This study presents an in-depth characterization of post-Ebola syndrome in Sierra Leonean survivors >2.5 years after disease. The interrelationship between symptom clusters indicates that post-Ebola syndrome is a heterogeneous disease. The distinct musculoskeletal and non-musculoskeletal phenotypes identified likely require targeted therapies to optimize long-term treatment for EVD survivors.


Assuntos
Ebolavirus , Doença pelo Vírus Ebola , Estudos de Coortes , Surtos de Doenças , Doença pelo Vírus Ebola/complicações , Doença pelo Vírus Ebola/epidemiologia , Humanos , Serra Leoa/epidemiologia , Síndrome
3.
Nature ; 520(7545): 104-8, 2015 Apr 02.
Artigo em Inglês | MEDLINE | ID: mdl-25539086

RESUMO

The skin represents the primary interface between the host and the environment. This organ is also home to trillions of microorganisms that play an important role in tissue homeostasis and local immunity. Skin microbial communities are highly diverse and can be remodelled over time or in response to environmental challenges. How, in the context of this complexity, individual commensal microorganisms may differentially modulate skin immunity and the consequences of these responses for tissue physiology remains unclear. Here we show that defined commensals dominantly affect skin immunity and identify the cellular mediators involved in this specification. In particular, colonization with Staphylococcus epidermidis induces IL-17A(+) CD8(+) T cells that home to the epidermis, enhance innate barrier immunity and limit pathogen invasion. Commensal-specific T-cell responses result from the coordinated action of skin-resident dendritic cell subsets and are not associated with inflammation, revealing that tissue-resident cells are poised to sense and respond to alterations in microbial communities. This interaction may represent an evolutionary means by which the skin immune system uses fluctuating commensal signals to calibrate barrier immunity and provide heterologous protection against invasive pathogens. These findings reveal that the skin immune landscape is a highly dynamic environment that can be rapidly and specifically remodelled by encounters with defined commensals, findings that have profound implications for our understanding of tissue-specific immunity and pathologies.


Assuntos
Linfócitos T CD8-Positivos/imunologia , Células Dendríticas/imunologia , Pele/imunologia , Pele/microbiologia , Simbiose/imunologia , Animais , Antígenos de Bactérias/imunologia , Linfócitos T CD8-Positivos/citologia , Células Dendríticas/citologia , Humanos , Imunidade Inata/imunologia , Interleucina-17/imunologia , Células de Langerhans/citologia , Células de Langerhans/imunologia , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Endogâmicos C57BL , Primatas , Pele/citologia , Staphylococcus epidermidis/imunologia
4.
J Clin Virol Plus ; 1(4): 100047, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-35262027

RESUMO

Serologic testing of residual blood samples from 812 children from a hospital in New Orleans, LA, between March and May 2020, demonstrated a SARS-CoV-2 seroprevalence of 6.8% based on S and N protein IgG; Black and Hispanic children, and children living in zip codes with lower household incomes were over-represented.

5.
J Virol ; 83(20): 10694-709, 2009 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-19656890

RESUMO

Epstein-Barr virus (EBV) can be reactivated from latency into the lytic cycle by many stimuli believed to operate by different mechanisms. Cell lines containing EBV differ in their responses to inducing stimuli, yet all stimuli require de novo protein synthesis (44). A crucial step preliminary to identifying these proteins and determining when they are required is to measure the duration of stimulus and response time needed for activation of expression of EBV BRLF1 and BZLF1, the earliest viral indicators of reactivation. Here we show, with four EBV-containing cell lines that respond to different inducing agents, that stimuli that are effective at reactivating EBV can be divided into two main groups. The histone deacetylase inhibitors sodium butyrate and trichostatin A require a relatively long period of exposure, from 2 to 4 h or longer. Phorbol esters, anti-immunoglobulin G (anti-IgG), and, surprisingly, 5-aza-2'-deoxycytidine require short exposures of 15 min or less. The cell/virus background influences the response time. Expression of the EBV BZLF1 and BRLF1 genes can be detected before 2 h in Akata cells treated with anti-IgG, but both long- and short-duration stimuli required 4 or more hr to activate BZLF1 and BRLF1 expression in HH514-16, Raji, or B95-8 cells. Thus, stimulus duration and response time are independent variables. Neither stimulus duration nor response time can be predicted by the number of cells activated into the lytic cycle. These experiments shed new light on the earliest events leading to lytic cycle reactivation of EBV.


Assuntos
Anticorpos Anti-Idiotípicos/farmacologia , Inibidores Enzimáticos/farmacologia , Herpesvirus Humano 4/fisiologia , Inibidores de Histona Desacetilases , Linfócitos/virologia , Ésteres de Forbol/farmacologia , Ativação Viral/efeitos dos fármacos , Linhagem Celular , Herpesvirus Humano 4/metabolismo , Histona Desacetilases/farmacologia , Humanos , Proteínas Imediatamente Precoces/genética , Proteínas Imediatamente Precoces/metabolismo , Fatores de Tempo , Transativadores/genética , Transativadores/metabolismo , Proteínas Virais/genética , Proteínas Virais/metabolismo
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