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1.
Emerg Infect Dis ; 25(2): 290-298, 2019 02.
Artículo en Inglés | MEDLINE | ID: mdl-30666927

RESUMEN

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.


Asunto(s)
Antígenos CD/sangre , Antígenos de Diferenciación Mielomonocítica/sangre , Ebolavirus/inmunología , Fiebre Hemorrágica Ebola/sangre , Fiebre Hemorrágica Ebola/inmunología , Activación de Macrófagos/inmunología , Macrófagos/inmunología , Receptores de Superficie Celular/sangre , Biomarcadores , Fiebre Hemorrágica Ebola/diagnóstico , Fiebre Hemorrágica Ebola/virología , Humanos , Inmunoensayo , Células Asesinas Naturales/inmunología , Células Asesinas Naturales/metabolismo , Hígado/inmunología , Hígado/metabolismo , Hígado/patología , Macrófagos/metabolismo
2.
Clin Obstet Gynecol ; 61(1): 186-196, 2018 03.
Artículo en Inglés | MEDLINE | ID: mdl-29351152

RESUMEN

The 2014 to 2016 Ebola outbreak, primarily based in 3 West African countries, had far-reaching global effects. Importantly, the crisis highlighted large gaps in reproductive health services in affected countries and inadequate health care system preparedness for obstetrical patients in the setting of highly contagious infectious diseases. We aim to review Ebola virus effects with a focus on the obstetrical implications in the context of this recent Ebola outbreak, discuss the lessons learned following this outbreak and propose current measures specific to obstetrics that should be considered in preparation for the next concerning emergent infectious disease.


Asunto(s)
Fiebre Hemorrágica Ebola/diagnóstico , Transmisión de Enfermedad Infecciosa de Paciente a Profesional/prevención & control , Transmisión Vertical de Enfermedad Infecciosa/prevención & control , Complicaciones Infecciosas del Embarazo/diagnóstico , Lactancia Materna , Parto Obstétrico , Brotes de Enfermedades , Femenino , Fiebre Hemorrágica Ebola/terapia , Fiebre Hemorrágica Ebola/transmisión , Humanos , Control de Infecciones , Embarazo , Complicaciones Infecciosas del Embarazo/terapia , Sobrevivientes
4.
J Infect Dis ; 215(12): 1862-1872, 2017 06 15.
Artículo en Inglés | MEDLINE | ID: mdl-28863472

RESUMEN

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.


Asunto(s)
Anticuerpos Antivirales/sangre , Linfocitos T CD8-positivos/inmunología , Inmunidad Celular , Fiebre de Lassa/inmunología , Virus Lassa/inmunología , Virus Lassa/aislamiento & purificación , Adulto , Amidas/uso terapéutico , Antígenos Virales/inmunología , Antivirales/uso terapéutico , Ensayo de Inmunoadsorción Enzimática , Humanos , Cambio de Clase de Inmunoglobulina/genética , Fiebre de Lassa/sangre , Activación de Linfocitos , Masculino , Pirazinas/uso terapéutico , Ribavirina/uso terapéutico , Viremia/sangre
5.
Health Secur ; 15(3): 253-260, 2017.
Artículo en Inglés | MEDLINE | ID: mdl-28636442

RESUMEN

The National Ebola Training and Education Center (NETEC) was established in 2015 in response to the 2014-2016 Ebola virus disease outbreak in West Africa. The US Department of Health and Human Services office of the Assistant Secretary for Preparedness and Response and the US Centers for Disease Control and Prevention sought to increase the competency of healthcare and public health workers, as well as the capability of healthcare facilities in the United States, to deliver safe, efficient, and effective care to patients infected with Ebola and other special pathogens nationwide. NYC Health + Hospitals/Bellevue, Emory University, and the University of Nebraska Medical Center/Nebraska Medicine were awarded this cooperative agreement, based in part on their experience in safely and successfully evaluating and treating patients with Ebola virus disease in the United States. In 2016, NETEC received a supplemental award to expand on 3 initial primary tasks: (1) develop metrics and conduct peer review assessments; (2) develop and provide educational materials, resources, and tools, including exercise design templates; (3) provide expert training and technical assistance; and, to add a fourth task, create a special pathogens clinical research network.


Asunto(s)
Fiebre Hemorrágica Ebola/prevención & control , Control de Infecciones/métodos , África Occidental , Prestación de Atención de Salud , Brotes de Enfermedades , Ebolavirus , Humanos , Nebraska , Estados Unidos
6.
Curr Top Microbiol Immunol ; 411: 115-137, 2017.
Artículo en Inglés | MEDLINE | ID: mdl-28601946

RESUMEN

Like most viral illnesses in humans, supportive care of the patient is the mainstay of clinical care for patients with Ebola virus disease (EVD). The goal is to maintain and sustain the patient until a specific immune response develops and clears the viral infection. Clearly, antiviral therapy may eventually help speed recovery, but supportive care will likely always be the centerpiece of care of the patient with EVD. While terrible in terms of human suffering and loss, the EVD outbreak of 2014-2016 provided an unheralded opportunity to advance our understanding in the care of patients (WHO 2016). Regardless of the care setting, resource-rich or resource-constrained, it is beneficial to have an established team of care providers. This team should consist of nurses and physicians who are familiar with clinical care of patients with EVD and have demonstrated competency using necessary personal protective equipment (PPE). Consideration should be given to having several physician specialties on the team, including critical care, infectious diseases, and anesthesiology. Additional individuals in other medical specialties should be identified in case needed during the course of caring for a patient. The National Ebola Training and Education Center (NETEC) has detailed guidance on preparations for developing a high-containment unit and care team (NETEC 2016).


Asunto(s)
Recursos en Salud/provisión & distribución , Fiebre Hemorrágica Ebola/terapia , Personal de Salud/estadística & datos numéricos , Recursos en Salud/economía , Fiebre Hemorrágica Ebola/economía , Humanos , Equipo de Protección Personal/provisión & distribución
7.
Ophthalmology ; 123(12): 2626-2628.e2, 2016 12.
Artículo en Inglés | MEDLINE | ID: mdl-27594198
8.
Microbiol Spectr ; 4(3)2016 06.
Artículo en Inglés | MEDLINE | ID: mdl-27337477

RESUMEN

Ending the West Africa Ebola virus disease (EVD) outbreak required an unprecedented international response. For the United States, participation in the international response to the West Africa EVD outbreak provided an opportunity to learn important lessons in four key domains critical to preparing for future outbreaks of EVD and other serious communicable diseases: (i) safe and effective patient care, (ii) the role of experimental therapeutics and vaccines, (iii) infection control, and (iv) hospital and community preparedness.


Asunto(s)
Enfermedades Transmisibles/epidemiología , Brotes de Enfermedades/prevención & control , Ebolavirus/patogenicidad , Fiebre Hemorrágica Ebola , Control de Infecciones/métodos , África Occidental/epidemiología , Anticuerpos Monoclonales/biosíntesis , Anticuerpos Monoclonales/uso terapéutico , Enfermedades Transmisibles/transmisión , Vacunas contra el Ebola/inmunología , Vacunas contra el Ebola/uso terapéutico , Fiebre Hemorrágica Ebola/epidemiología , Fiebre Hemorrágica Ebola/prevención & control , Fiebre Hemorrágica Ebola/terapia , Fiebre Hemorrágica Ebola/transmisión , Humanos , Terapias en Investigación/métodos , Estados Unidos/epidemiología , Uveítis/microbiología
9.
Clin Infect Dis ; 63(4): 460-7, 2016 08 15.
Artículo en Inglés | MEDLINE | ID: mdl-27353663

RESUMEN

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.


Asunto(s)
Quimiocinas/sangre , Citocinas/sangre , Ebolavirus/inmunología , Fiebre Hemorrágica Ebola/inmunología , Inmunidad Humoral , Adulto , Biomarcadores/sangre , Coagulación Sanguínea , Estudios de Cohortes , Células Endoteliales/inmunología , Femenino , Fiebre Hemorrágica Ebola/fisiopatología , Fiebre Hemorrágica Ebola/terapia , Humanos , Inflamación , Cinética , Masculino , Persona de Mediana Edad , Índice de Severidad de la Enfermedad , Viremia
10.
Clin Infect Dis ; 62(12): 1552-1555, 2016 06 15.
Artículo en Inglés | MEDLINE | ID: mdl-27045122

RESUMEN

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.


Asunto(s)
Ebolavirus/aislamiento & purificación , Fiebre Hemorrágica Ebola/virología , Semen/virología , Adulto , Estudios de Cohortes , Ebolavirus/patogenicidad , Humanos , Masculino , Sobrevivientes
12.
J Clin Microbiol ; 53(9): 2956-60, 2015 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-26157148

RESUMEN

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.


Asunto(s)
Ebolavirus/aislamiento & purificación , Fiebre Hemorrágica Ebola/diagnóstico , Técnicas de Diagnóstico Molecular/métodos , Reacción en Cadena de la Polimerasa/métodos , Reacción en Cadena en Tiempo Real de la Polimerasa/métodos , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa/métodos , Humanos , Plasma/virología , Sensibilidad y Especificidad , Orina/virología
13.
Curr Opin Infect Dis ; 28(4): 343-8, 2015 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-26098504

RESUMEN

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.


Asunto(s)
Defensa Civil/métodos , Fiebre Hemorrágica Ebola/prevención & control , Fiebre Hemorrágica Ebola/transmisión , Control de Infecciones/métodos , Georgia , Humanos , Nebraska
15.
Ann Intern Med ; 163(2): 81-90, 2015 Jul 21.
Artículo en Inglés | MEDLINE | ID: mdl-25961438

RESUMEN

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.


Asunto(s)
Cuidados Críticos/métodos , Fiebre Hemorrágica Ebola/diagnóstico , Fiebre Hemorrágica Ebola/terapia , Adulto , Diagnóstico Precoz , Ebolavirus/genética , Ebolavirus/metabolismo , Resultado Fatal , Femenino , Fiebre Hemorrágica Ebola/virología , Humanos , Masculino , ARN Viral/sangre , Insuficiencia Renal/etiología , Insuficiencia Respiratoria/etiología , Estudios Retrospectivos , Texas , Viremia/diagnóstico , Viremia/terapia
16.
N Engl J Med ; 372(25): 2423-7, 2015 Jun 18.
Artículo en Inglés | MEDLINE | ID: mdl-25950269

RESUMEN

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.


Asunto(s)
Humor Acuoso/virología , Ebolavirus/aislamiento & purificación , Fiebre Hemorrágica Ebola/complicaciones , Panuveítis/virología , Trastornos de la Visión/virología , Adulto , Convalecencia , Fondo de Ojo , Humanos , Masculino
17.
Clin Infect Dis ; 61(4): 496-502, 2015 Aug 15.
Artículo en Inglés | MEDLINE | ID: mdl-25904375

RESUMEN

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.


Asunto(s)
Anticuerpos Antivirales/uso terapéutico , Fiebre Hemorrágica Ebola/terapia , ARN Interferente Pequeño/uso terapéutico , Adulto , Humanos , Masculino , Persona de Mediana Edad , Estudios Prospectivos , Resultado del Tratamiento , Estados Unidos
18.
AJR Am J Roentgenol ; 204(6): 1157-9, 2015 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-25730332

RESUMEN

OBJECTIVE: Individuals with Ebola virus disease, a contagious and potentially lethal infection, are now being treated in specialized units in the United States. We describe Emory University's initial experience, current operating procedures, and ongoing planning with diagnostic ultrasound in the isolation unit. CONCLUSION: Ultrasound use has been limited to date. Future planning considerations include deciding what types of ultrasound studies will be performed, which personnel will acquire the images, and which ultrasound machine will be used.


Asunto(s)
Fiebre Hemorrágica Ebola/diagnóstico por imagen , Fiebre Hemorrágica Ebola/prevención & control , Hospitales de Aislamiento , Aislamiento de Pacientes/instrumentación , Aislamiento de Pacientes/métodos , Ultrasonografía/instrumentación , Ultrasonografía/métodos , Georgia , Humanos , Aisladores de Pacientes , Proyectos Piloto , Sistemas de Atención de Punto , Reproducibilidad de los Resultados , Sensibilidad y Especificidad
19.
Proc Natl Acad Sci U S A ; 112(15): 4719-24, 2015 Apr 14.
Artículo en Inglés | MEDLINE | ID: mdl-25775592

RESUMEN

Four Ebola patients received care at Emory University Hospital, presenting a unique opportunity to examine the cellular immune responses during acute Ebola virus infection. We found striking activation of both B and T cells in all four patients. Plasmablast frequencies were 10-50% of B cells, compared with less than 1% in healthy individuals. Many of these proliferating plasmablasts were IgG-positive, and this finding coincided with the presence of Ebola virus-specific IgG in the serum. Activated CD4 T cells ranged from 5 to 30%, compared with 1-2% in healthy controls. The most pronounced responses were seen in CD8 T cells, with over 50% of the CD8 T cells expressing markers of activation and proliferation. Taken together, these results suggest that all four patients developed robust immune responses during the acute phase of Ebola virus infection, a finding that would not have been predicted based on our current assumptions about the highly immunosuppressive nature of Ebola virus. Also, quite surprisingly, we found sustained immune activation after the virus was cleared from the plasma, observed most strikingly in the persistence of activated CD8 T cells, even 1 mo after the patients' discharge from the hospital. These results suggest continued antigen stimulation after resolution of the disease. From these convalescent time points, we identified CD4 and CD8 T-cell responses to several Ebola virus proteins, most notably the viral nucleoprotein. Knowledge of the viral proteins targeted by T cells during natural infection should be useful in designing vaccines against Ebola virus.


Asunto(s)
Linfocitos T CD4-Positivos/inmunología , Linfocitos T CD8-positivos/inmunología , Ebolavirus/inmunología , Fiebre Hemorrágica Ebola/inmunología , Inmunidad Celular/inmunología , Linfocitos T CD4-Positivos/metabolismo , Linfocitos T CD8-positivos/metabolismo , Ebolavirus/metabolismo , Ensayo de Inmunoadsorción Enzimática , Citometría de Flujo , Fiebre Hemorrágica Ebola/sangre , Fiebre Hemorrágica Ebola/virología , Humanos , Inmunidad Humoral/inmunología , Inmunoglobulina G/sangre , Inmunoglobulina G/inmunología , Inmunofenotipificación , Interferón gamma/inmunología , Interferón gamma/metabolismo , Activación de Linfocitos/inmunología , Células Precursoras de Linfocitos B/inmunología , Células Precursoras de Linfocitos B/metabolismo , Factor de Necrosis Tumoral alfa/inmunología , Factor de Necrosis Tumoral alfa/metabolismo , Proteínas Virales/inmunología , Proteínas Virales/metabolismo
20.
J Am Soc Nephrol ; 26(1): 31-7, 2015 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-25398785

RESUMEN

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.


Asunto(s)
Lesión Renal Aguda/terapia , Control de Enfermedades Transmisibles/métodos , Fiebre Hemorrágica Ebola/terapia , Aislamiento de Pacientes/métodos , Terapia de Reemplazo Renal/métodos , Lesión Renal Aguda/complicaciones , Personal de Salud , Fiebre Hemorrágica Ebola/complicaciones , Humanos , Exposición Profesional , Seguridad del Paciente , Proyectos Piloto , Guías de Práctica Clínica como Asunto , Reacción en Cadena en Tiempo Real de la Polimerasa , Resultado del Tratamiento
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