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1.
Emerg Infect Dis ; 25(2): 290-298, 2019 02.
Artigo em Inglês | MEDLINE | ID: mdl-30666927

RESUMO

Ebola virus disease (EVD) is associated with elevated cytokine levels, and hypercytokinemia is more pronounced in fatal cases. This type of hyperinflammatory state is reminiscent of 2 rheumatologic disorders known as macrophage activation syndrome and hemophagocytic lymphohistiocytosis, which are characterized by macrophage and T-cell activation. An evaluation of 2 cohorts of patients with EVD revealed that a marker of macrophage activation (sCD163) but not T-cell activation (sCD25) was associated with severe and fatal EVD. Furthermore, substantial immunoreactivity of host tissues to a CD163-specific antibody, predominantly in areas of extensive immunostaining for Ebola virus antigens, was observed in fatal cases. These data suggest that host macrophage activation contributes to EVD pathogenesis and that directed antiinflammatory therapies could be beneficial in the treatment of EVD.


Assuntos
Antígenos CD/sangue , Antígenos de Diferenciação Mielomonocítica/sangue , Ebolavirus/imunologia , Doença pelo Vírus Ebola/sangue , Doença pelo Vírus Ebola/imunologia , Ativação de Macrófagos/imunologia , Macrófagos/imunologia , Receptores de Superfície Celular/sangue , Biomarcadores , Doença pelo Vírus Ebola/diagnóstico , Doença pelo Vírus Ebola/virologia , Humanos , Imunoensaio , Células Matadoras Naturais/imunologia , Células Matadoras Naturais/metabolismo , Fígado/imunologia , Fígado/metabolismo , Fígado/patologia , Macrófagos/metabolismo
3.
N Engl J Med ; 372(25): 2423-7, 2015 Jun 18.
Artigo em Inglês | MEDLINE | ID: mdl-25950269

RESUMO

Among the survivors of Ebola virus disease (EVD), complications that include uveitis can develop during convalescence, although the incidence and pathogenesis of EVD-associated uveitis are unknown. We describe a patient who recovered from EVD and was subsequently found to have severe unilateral uveitis during convalescence. Viable Zaire ebolavirus (EBOV) was detected in aqueous humor 14 weeks after the onset of EVD and 9 weeks after the clearance of viremia.


Assuntos
Humor Aquoso/virologia , Ebolavirus/isolamento & purificação , Doença pelo Vírus Ebola/complicações , Pan-Uveíte/virologia , Transtornos da Visão/virologia , Adulto , Convalescença , Fundo de Olho , Humanos , Masculino
4.
J Infect Dis ; 215(12): 1862-1872, 2017 06 15.
Artigo em Inglês | MEDLINE | ID: mdl-28863472

RESUMO

A nurse who acquired Lassa virus infection in Togo in the spring of 2016 was repatriated to the United States for care at Emory University Hospital. Serial sampling from this patient permitted the characterization of several aspects of the innate and cellular immune responses to Lassa virus. Although most of the immune responses correlated with the kinetics of viremia resolution, the CD8 T-cell response was of surprisingly high magnitude and prolonged duration, implying prolonged presentation of viral antigens. Indeed, long after viremia resolution, there was persistent viral RNA detected in the semen of the patient, accompanied by epididymitis, suggesting the male reproductive tract as 1 site of antigen persistence. Consistent with the magnitude of acute T-cell responses, the patient ultimately developed long-term, polyfunctional memory T-cell responses to Lassa virus.


Assuntos
Anticorpos Antivirais/sangue , Linfócitos T CD8-Positivos/imunologia , Imunidade Celular , Febre Lassa/imunologia , Vírus Lassa/imunologia , Vírus Lassa/isolamento & purificação , Adulto , Amidas/uso terapêutico , Antígenos Virais/imunologia , Antivirais/uso terapêutico , Ensaio de Imunoadsorção Enzimática , Humanos , Switching de Imunoglobulina/genética , Febre Lassa/sangue , Ativação Linfocitária , Masculino , Pirazinas/uso terapêutico , Ribavirina/uso terapêutico , Viremia/sangue
6.
N Engl J Med ; 371(25): 2402-9, 2014 Dec 18.
Artigo em Inglês | MEDLINE | ID: mdl-25390460

RESUMO

West Africa is currently experiencing the largest outbreak of Ebola virus disease (EVD) in history. Two patients with EVD were transferred from Liberia to our hospital in the United States for ongoing care. Malaria had also been diagnosed in one patient, who was treated for it early in the course of EVD. The two patients had substantial intravascular volume depletion and marked electrolyte abnormalities. We undertook aggressive supportive measures of hydration (typically, 3 to 5 liters of intravenous fluids per day early in the course of care) and electrolyte correction. As the patients' condition improved clinically, there was a concomitant decline in the amount of virus detected in plasma.


Assuntos
Anticorpos Monoclonais/uso terapêutico , Anticorpos Antivirais/uso terapêutico , Drogas em Investigação/uso terapêutico , Ebolavirus/imunologia , Doença pelo Vírus Ebola/terapia , Adulto , Surtos de Doenças , Feminino , Doença pelo Vírus Ebola/tratamento farmacológico , Doença pelo Vírus Ebola/epidemiologia , Humanos , Libéria , Masculino , Pessoa de Meia-Idade , Estados Unidos
7.
Clin Infect Dis ; 63(4): 460-7, 2016 08 15.
Artigo em Inglês | MEDLINE | ID: mdl-27353663

RESUMO

BACKGROUND: Ebola virus (EBOV) infection causes a severe and often fatal disease. Despite the fact that more than 30 000 individuals have acquired Ebola virus disease (EVD), the medical and scientific community still does not have a clear understanding of the mechanisms by which EBOV causes such severe disease. METHODS: In this study, 54 biomarkers in plasma samples serially collected from 7 patients with EVD were analyzed in an attempt to define the kinetics of inflammatory modulators. Two clinical disease groups were defined (moderate and severe) based on the need for clinical support. Biomarkers were evaluated for correlation with viremia and clinical disease in an effort to identify pathways that could be useful targets of therapeutic intervention. RESULTS: Patients with severe disease had higher viremia than those with moderate disease. Several biomarkers of immune activation and control were significantly elevated in patients with moderate disease. A series of pro-inflammatory cytokines and chemokines were significantly elevated in patients with severe disease. CONCLUSIONS: Biomarkers that were associated with severe EVD were proinflammatory and indicative of endothelial or coagulation cascade dysfunction, as has been seen historically in patients with fatal outcomes. In contrast, biomarkers that were associated with moderate EVD were suggestive of a strong interferon response and control of both innate and adaptive responses. Therefore, clinical interventions that modulate the phenotype and magnitude of immune activation may be beneficial in treating EVD.


Assuntos
Quimiocinas/sangue , Citocinas/sangue , Ebolavirus/imunologia , Doença pelo Vírus Ebola/imunologia , Imunidade Humoral , Adulto , Biomarcadores/sangue , Coagulação Sanguínea , Estudos de Coortes , Células Endoteliais/imunologia , Feminino , Doença pelo Vírus Ebola/fisiopatologia , Doença pelo Vírus Ebola/terapia , Humanos , Inflamação , Cinética , Masculino , Pessoa de Meia-Idade , Índice de Gravidade de Doença , Viremia
8.
Clin Infect Dis ; 62(12): 1552-1555, 2016 06 15.
Artigo em Inglês | MEDLINE | ID: mdl-27045122

RESUMO

We investigated the duration of Ebola virus (EBOV) RNA and infectious EBOV in semen specimens of 5 Ebola virus disease (EVD) survivors. EBOV RNA and infectious EBOV was detected by real-time RT-PCR and virus culture out to 290 days and 70 days, respectively, after EVD onset.


Assuntos
Ebolavirus/isolamento & purificação , Doença pelo Vírus Ebola/virologia , Sêmen/virologia , Adulto , Estudos de Coortes , Ebolavirus/patogenicidade , Humanos , Masculino , Sobreviventes
9.
Ann Intern Med ; 163(2): 81-90, 2015 Jul 21.
Artigo em Inglês | MEDLINE | ID: mdl-25961438

RESUMO

BACKGROUND: More than 26,000 cases of Ebola virus disease (EVD) have been reported in western Africa, with high mortality. Several patients have been medically evacuated to hospitals in the United States and Europe. Detailed clinical data are limited on the clinical course and management of patients with EVD outside western Africa. OBJECTIVE: To describe the clinical characteristics and management of a cluster of patients with EVD, including the first cases of Ebola virus (EBOV) infection acquired in the United States. DESIGN: Retrospective clinical case series. SETTING: Three U.S. hospitals in September and October 2014. PATIENTS: First imported EVD case identified in the United States and 2 secondary EVD cases acquired in the United States in critical care nurses who cared for the index case patient. MEASUREMENTS: Clinical recovery, EBOV RNA level, resolution of Ebola viremia, survival with discharge from hospital, or death. RESULTS: The index patient had high EBOV RNA levels, developed respiratory and renal failure requiring critical care support, and died. Both patients with secondary EBOV infection had nonspecific signs and symptoms and developed moderate illness; EBOV RNA levels were moderate, and both patients recovered. LIMITATION: Both surviving patients received uncontrolled treatment with multiple investigational agents, including convalescent plasma, which limits generalizability of the results. CONCLUSION: Early diagnosis, prompt initiation of supportive medical care, and moderate clinical illness likely contributed to successful outcomes in both survivors. The inability to determine the potential benefit of investigational therapies and the effect of patient-specific factors that may have contributed to less severe illness highlight the need for controlled clinical studies of these interventions, especially in the setting of a high level of supportive medical care. PRIMARY FUNDING SOURCE: None.


Assuntos
Cuidados Críticos/métodos , Doença pelo Vírus Ebola/diagnóstico , Doença pelo Vírus Ebola/terapia , Adulto , Diagnóstico Precoce , Ebolavirus/genética , Ebolavirus/metabolismo , Evolução Fatal , Feminino , Doença pelo Vírus Ebola/virologia , Humanos , Masculino , RNA Viral/sangue , Insuficiência Renal/etiologia , Insuficiência Respiratória/etiologia , Estudos Retrospectivos , Texas , Viremia/diagnóstico , Viremia/terapia
10.
J Am Soc Nephrol ; 26(1): 31-7, 2015 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-25398785

RESUMO

AKI has been observed in cases of Ebola virus disease. We describe the protocol for the first known successful delivery of RRT with subsequent renal recovery in a patient with Ebola virus disease treated at Emory University Hospital, in Atlanta, Georgia. Providing RRT in Ebola virus disease is complex and requires meticulous attention to safety for the patient, healthcare workers, and the community. We specifically describe measures to decrease the risk of transmission of Ebola virus disease and report pilot data demonstrating no detectable Ebola virus genetic material in the spent RRT effluent waste. This article also proposes clinical practice guidelines for acute RRT in Ebola virus disease.


Assuntos
Injúria Renal Aguda/terapia , Controle de Doenças Transmissíveis/métodos , Doença pelo Vírus Ebola/terapia , Isolamento de Pacientes/métodos , Terapia de Substituição Renal/métodos , Injúria Renal Aguda/complicações , Pessoal de Saúde , Doença pelo Vírus Ebola/complicações , Humanos , Exposição Ocupacional , Segurança do Paciente , Projetos Piloto , Guias de Prática Clínica como Assunto , Reação em Cadeia da Polimerase em Tempo Real , Resultado do Tratamento
11.
Clin Infect Dis ; 61(4): 496-502, 2015 Aug 15.
Artigo em Inglês | MEDLINE | ID: mdl-25904375

RESUMO

BACKGROUND: The current West Africa Ebola virus disease (EVD) outbreak has resulted in multiple individuals being medically evacuated to other countries for clinical management. METHODS: We report two patients who were transported from West Africa to the United States for treatment of EVD. Both patients received aggressive supportive care measures, as well as an investigational therapeutic (TKM-100802) and convalescent plasma. RESULTS: While one patient experienced critical illness with multi-organ failure requiring mechanical ventilation and renal replacement therapy, both patients recovered without serious long-term sequelae to date. CONCLUSIONS: It is unclear what role the experimental drug and convalescent plasma had in the recovery of these patients. Prospective clinical trials are needed to delineate the role of investigational therapies in the care of patients with EVD.


Assuntos
Anticorpos Antivirais/uso terapêutico , Doença pelo Vírus Ebola/terapia , RNA Interferente Pequeno/uso terapêutico , Adulto , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Resultado do Tratamento , Estados Unidos
12.
J Clin Microbiol ; 53(9): 2956-60, 2015 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-26157148

RESUMO

Rapid, reliable, and easy-to-use diagnostic assays for detection of Zaire ebolavirus (ZEBOV) are urgently needed. The goal of this study was to examine the agreement among emergency use authorization (EUA) tests for the detection of ZEBOV nucleic acids, including the BioFire FilmArray BioThreat (BT) panel, the FilmArray BT-E panel, and the NP2 and VP40 quantitative real-time reverse transcriptase (qRT) PCR assays from the Centers for Disease Control and Prevention (CDC). Specimens used in this study included whole blood spiked with inactivated ZEBOV at known titers and whole-blood, plasma, and urine clinical specimens collected from persons diagnosed with Ebola virus disease (EVD). The agreement for FilmArray and qRT-PCR results using contrived whole-blood specimens was 100% (6/6 specimens) for each ZEBOV dilution from 4 × 10(7) to 4 × 10(2) 50% tissue culture infective dose (TCID50)/ml, as well as the no-virus negative-control sample. The limit of detection for FilmArray and qRT-PCR assays with inactivated ZEBOV, based on duplicate positive results, was determined to be 4 × 10(2) TCID50/ml. Rates of agreement between FilmArray and qRT-PCR results for clinical specimens from patients with EVD were 85% (23/27 specimens) for whole-blood specimens, 90% (18/20 specimens) for whole-blood specimens tested by FilmArray testing and matched plasma specimens tested by qRT-PCR testing, and 85% (11/13 specimens) for urine specimens. Among 60 specimens, eight discordant results were noted, with ZEBOV nucleic acids being detected only by FilmArray testing in four specimens and only by qRT-PCR testing in the remaining four specimens. These findings demonstrate that the rapid and easy-to-use FilmArray panels are effective tests for evaluating patients with EVD.


Assuntos
Ebolavirus/isolamento & purificação , Doença pelo Vírus Ebola/diagnóstico , Técnicas de Diagnóstico Molecular/métodos , Reação em Cadeia da Polimerase/métodos , Reação em Cadeia da Polimerase em Tempo Real/métodos , Reação em Cadeia da Polimerase Via Transcriptase Reversa/métodos , Humanos , Plasma/virologia , Sensibilidade e Especificidade , Urina/virologia
13.
Curr Opin Infect Dis ; 28(4): 343-8, 2015 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-26098504

RESUMO

PURPOSE OF REVIEW: This review details infection control issues encountered in the management of patients with Ebola virus disease (EVD), with emphasis on how these issues were confronted in two biocontainment patient care units in the United States. RECENT FINDINGS: There is a notable paucity of medical literature to guide infection control policies and procedures when caring for patients with EVD. Thus, the experience of the Serious Communicable Diseases Unit at Emory University Hospital and the Nebraska Biocontainment Unit at the University of Nebraska Medical Center serves as the basis for this review. Facility issues, staffing, transportation logistics, and appropriate use of personal protective equipment are detailed. Other topics addressed include the evaluation of patients under investigation and ethical issues concerning the safe utilization of advanced life support. SUMMARY: This review intends to serve as a reference for facilities that are in the process of creating protocols for managing patients with EVD. Given the lack of literature to support many of the recommendations discussed, it is important to utilize the available referenced guidelines, along with the practical experiences of biocontainment units, to optimize the care provided to patients with EVD while strictly adhering to infection control principles.


Assuntos
Defesa Civil/métodos , Doença pelo Vírus Ebola/prevenção & controle , Doença pelo Vírus Ebola/transmissão , Controle de Infecções/métodos , Georgia , Humanos , Nebraska
14.
PLoS Genet ; 7(8): e1002234, 2011 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-21901105

RESUMO

Exposure to influenza viruses is necessary, but not sufficient, for healthy human hosts to develop symptomatic illness. The host response is an important determinant of disease progression. In order to delineate host molecular responses that differentiate symptomatic and asymptomatic Influenza A infection, we inoculated 17 healthy adults with live influenza (H3N2/Wisconsin) and examined changes in host peripheral blood gene expression at 16 timepoints over 132 hours. Here we present distinct transcriptional dynamics of host responses unique to asymptomatic and symptomatic infections. We show that symptomatic hosts invoke, simultaneously, multiple pattern recognition receptors-mediated antiviral and inflammatory responses that may relate to virus-induced oxidative stress. In contrast, asymptomatic subjects tightly regulate these responses and exhibit elevated expression of genes that function in antioxidant responses and cell-mediated responses. We reveal an ab initio molecular signature that strongly correlates to symptomatic clinical disease and biomarkers whose expression patterns best discriminate early from late phases of infection. Our results establish a temporal pattern of host molecular responses that differentiates symptomatic from asymptomatic infections and reveals an asymptomatic host-unique non-passive response signature, suggesting novel putative molecular targets for both prognostic assessment and ameliorative therapeutic intervention in seasonal and pandemic influenza.


Assuntos
Infecções Assintomáticas , Interações Hospedeiro-Patógeno , Vírus da Influenza A Subtipo H3N2 , Influenza Humana/metabolismo , Adolescente , Adulto , Citocinas/biossíntese , Citocinas/metabolismo , Perfilação da Expressão Gênica , Humanos , Influenza Humana/genética , Influenza Humana/virologia , Pessoa de Meia-Idade , Estresse Oxidativo/genética , Proteínas Ribossômicas/genética , Proteínas Ribossômicas/metabolismo , Estresse Fisiológico
15.
Am J Infect Control ; 52(3): 344-348, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-37604209

RESUMO

To provide a safe environment, behavioral health settings must adhere to "ligature-resistant" protocols for patients at risk of harm to themselves or others. However, certain bathroom ligature-resistant fixtures alter environmental controls, such as sinks and showerheads, and increase the risk of water-borne pathogens due to low water output settings, highlighting the importance of an interdisciplinary water management program. We describe how ligature-resistant water fixtures may have been associated with a possible case of hospital-associated Legionellosis.


Assuntos
Legionella , Legionelose , Humanos , Abastecimento de Água , Água , Banheiros , Microbiologia da Água
16.
Infect Control Hosp Epidemiol ; : 1-7, 2024 May 06.
Artigo em Inglês | MEDLINE | ID: mdl-38706211

RESUMO

OBJECTIVE: To determine if the high-level personal protective equipment used in the treatment of high-consequence infectious diseases is effective at stopping the spread of pathogens to healthcare personnel (HCP) while doffing. BACKGROUND: Personal protective equipment (PPE) is fundamental to the safety of HCPs. HCPs treating patients with high-consequence infectious diseases use several layers of PPE, forming complex protective ensembles. With high-containment PPE, step-by-step procedures are often used for donning and doffing to minimize contamination risk to the HCP, but these procedures are rarely empirically validated and instead rely on following infection prevention best practices. METHODS: A doffing protocol video for a high-containment PPE ensemble was evaluated to determine potential contamination pathways. These potential pathways were tested using fluorescence and genetically marked bacteriophages. RESULTS: The experiments revealed existing protocols permit contamination pathways allowing for transmission of bacteriophages to HCPs. Updates to the doffing protocols were generated based on the discovered contamination pathways. This updated doffing protocol eliminated the movement of viable bacteriophages from the outside of the PPE to the skin of the HCP. CONCLUSIONS: Our results illustrate the need for quantitative, scientific investigations of infection prevention practices, such as doffing PPE.

19.
Infect Control Hosp Epidemiol ; 43(7): 935-938, 2022 07.
Artigo em Inglês | MEDLINE | ID: mdl-34236019

RESUMO

In total, 13 facilities changed C. difficile testing to reflexive testing by enzyme immunoassay (EIA) only after a positive nucleic acid-amplification test (NAAT); the standardized infection ratio (SIR) decreased by 46% (range, -12% to -71% per hospital). Changing testing practice greatly influenced a performance metric without changing C. difficile infection prevention practice.


Assuntos
Toxinas Bacterianas , Clostridioides difficile , Infecções por Clostridium , Clostridioides , Atenção à Saúde , Hospitais , Humanos , Técnicas Imunoenzimáticas , Reflexo
20.
Ophthalmology ; 123(12): 2626-2628.e2, 2016 12.
Artigo em Inglês | MEDLINE | ID: mdl-27594198
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